There are limited data in second HSCT outcomes in PID. Conditioning regimen, stem cell source and GVHD prophylaxis (either with graft processing, or immunosuppression) are serious issues to consider before re-transplantation following severe graft failure (GF). We share our experience of second HSCT in PID patients.
Between 2012 and 2018 238 patients with various PID underwent HSCT in our center. 34 patients developed GF (non-engraftment, n=5; graft rejection, n=29) after HSCT from MUD (n=22), MRD (n=2) and MMRD (n=10); graft rejection occurred within 1,0-14,7 months (median 3,1).
Second HSCT was performed in 31 patients in 2,1-23,0 months (median 6) after first HSCT. The source of stem cells was PB (n=23) or BM (n=8) from MUD (n=21) or MMRD (n =10). 12 patients received predominantly immunoablative conditioning with TLI, fludarabin, cyclophosphamide and melphalan, 19 - different treosulfan/busulfan based myeloablative regimens. All but one patients received serotherapy. TCRab+/CD19+ graft depletion was performed in 23 cases, 8 patients had non-manipulated graft; 5 of them with posttransplant cyclophosphamide d+3,+4.
Acute GVHD grade II-IV was observed in 3 patients, GF in 7. Overall survival was 66%+8,8. Causes of death were bacterial sepsis (n=5), viral infections (n=2), cGVHD (n=1), TMA/MOF (n=2). Immuno- or myeloablative conditioning did not influence HSCT outcomes.
Second HSCT after severe GF is a feasible option for PID patients. Infections are still the leading cause of TRM. Patient’s clinical status, time and type of GF after first HSCT has to be considered for individualized conditioning regimen and GVHD prophylaxis strategy.
Rituximab is a chimeric anti-CD20 monoclonal antibody used for a variety of clinical indications. Many patients with primary immunodeficiency (PID) require rituximab for autoimmune and/or lymphoproliferative disease. The prevalence and indications for rituximab use not well-characterized. We sought to better understand the use and effect of rituximab in PID patients.
The United States Immunodeficiency Network (USIDNET) Database was queried for patients receiving rituximab. Patient demographics, underlying primary immunodeficiency, indication for rituximab, infectious complications, effectiveness and adverse effects were evaluated.
We identified 200 patients who had received rituximab in the USIDNET Database. Most were male (62%), with a median age of 24. The majority of patients were Caucasian (74%). The most common underlying immunodeficiencies included common variable immunodeficiency (n=78), hemophagocytic lymphohistiocytosis (n=22), immune dysregulation (n=18), and severe combined immunodeficiency (n=18). The primary indications for rituximab included idiopathic thrombocytopenic purpura (n=36), EBV infection (n=24), lymphoma (n=23), interstitial lung disease (n=22), and autoimmune hemolytic anemia (n=14). Infectious complications were reported in 130/200 (65%) of the patients. Rituximab was physician reported as being effective in 84/98 (86%) patients. Rituximab was well tolerated, with no adverse reactions described by physician report in 34/49 (69%) of patients.
Many PID patients require biologics including rituximab for autoimmune and lymphoproliferative disease including autoimmune cytopenias, viral infections, and malignancy. While many PID patients require repeated courses of rituximab or other immunomodulators for immune dysregulation including autoimmunity and lymphoproliferation, rituximab was reported as being well tolerated and effective.
Autologous reconstitution of myeloid cells after allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in patients with primary immunodeficiencies (PID) is associated with incomplete immunological reconstitution or recurrence of the primary disease. T cells can remain -at least in part- of donor origin. Conditioning before a second HSCT from the same donor in this situation is supposed to preserve established donor T-cell function, cause limited toxicity but to allow stable myeloid engraftment.
In a retrospective analysis we reviewed data of seven consecutive pediatric patients with different PIDs (SCID n=3, CGD, Griscelli syndrome, Reticular Dysgenesis, Leukocyte Adhesion Deficiency I), who underwent allogenic stem cell transplantation between 2005 and 2016. After initial myeloid engraftment, all patients experienced partial or complete autologous reconstitution of myeloid cells with remaining donor t-cells.
Second stem cell grafts were administered at 5 to 38 months after the initial transplantation. Patients received a conditioning regimen containing predominantly myelosuppressive drugs or radioimmunotherapy avoiding immunosuppression or serotherapy before the administration of T-cell replete (n=2) or T-cell depleted (n=5) grafts from the same donor. Limited toxicity and neutrophil engraftment between day +13 to +22 was noted. No acute (>II°) or chronic GvHD occurred. All patients survived with a follow up of 6 to 118 months, with complete (n=5) or stable mixed (n=2) chimerism.
In summary these data demonstrate that a selective myelosuppressive conditioning regimen for retransplantation from the same donor after autologous myeloid reconsititution is a feasible approach to achieve stable myeloid engraftment with low toxicity or treatment related mortality.
Primary Immune Deficiencies (PID) are increasingly being recognized in several parts of India. Despite being diagnosed, many patients fail to receive optimal care due to financial and social constraints.
Analyze the outcomes of patients diagnosed with PIDs at Aster CMI Hospital, Bangalore.
Case records of patients diagnosed and treated (including hematopoietic stem cell transplants) for PID diseases during Feb 2017 – March 2019 were analyzed. Factors leading to deferred or suboptimal care were assessed in detail.
74 patients with various PIDs were diagnosed during the study period (Table). 43 of them warranted a hematopoietic stem cell transplant (HSCT) as definitive curative treatment. A total of 10 children received 12 HSCT. 3 of them died while 7 of them are alive and well. 20 children died before an HSCT could be carried out. 14 of them were critically ill at presentation, while 6 were stable but deferred further treatment citing financial and social constraints. Only 23% of children warranting HSCT could be transplanted in our cohort. Among those where HSCT is potentially curative 46% of children died before HSCT could be offered.
We present our experience from a developing country and discuss non-medical factors leading to suboptimal care in children with PID. Transplants in developing countries pose unique challenges due to the absence of government funding and/or universal insurance coverage. In addition to the delay in diagnosis and critical state of patients at admission, financial and social factors significantly contributed to a poor outcome.
In a multicenter randomized clinical trial we evaluated the efficacy of an intravenous immunoglobulin (IVIG) protocol to decrease the rate of re-infection in solid organ recipients with severe infections and secondary antibody deficiency.
Distribution: Heart 19, Lung 9, Kidney 5, Liver transplantation 3. Patients with post transplant severe infections and secondary antibody deficiency (IgG levels < 600 mg/dL) were included. IVIG protocol: Two doses of 15 grams (interval between doses 7-15 days) followed by another 3 doses of 20 grams (interval between doses 15-30 days) of a 5% IVIG product. 36 patients were randomized to receive IVIG in combination with conventional antimicrobial therapy (n=17) or conventional antimicrobial therapy alone (n=19). Specific antibodies were tested at inclusion in the clinical trial and 30-45 days after last IVIG dose (last-visit) in a subgroup of patients to assess the kinetics of humoral immunity reconstitution.
The primary outcome measure (rate of re-infection) was significantly lower in patients randomized to receive IVIG as compared with patients receiving only conventional antimicrobial therapy (37.5 vs 76.5%, chi-square test, p=0.024). Time to reach normal IgG (IgG > 750 mg/dL) was shorter in IVIG group (55±44 vs 93±42 days, p=0.06). Significantly higher levels of specific anti-cytomegalovirus, anti-clostridium difficile toxins A and B was demonstrated at last-visit in patients who received IVIG as compared with patient that were treated with antimicrobial therapy alone.
In a multicenter randomized clinical trial we have preliminarily demonstrated that IVIG is associated with a lower rate of re-infection in solid organ transplantation with severe infection and secondary antibody deficiency.
Children with primary immunodeficiencies (PIDs) constitute life-threatening medical emergencies. Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) has been shown to be curative for children with PIDs. We analyzed the outcome of allo-HSCT in Taiwanese children with PIDs at a single pediatric transplantation center using both related and unrelated donors.
Eighteen children with the diagnosis of PIDs treated at Chang Gung Memorial Hospital between 2004 and 2018 were identified and analyzed. The medical records including the diagnosis of PIDs, transplant protocol, engraftment, adverse events, and treatment outcome retrospectively reviewed.
There were 8 patients with severe combined immunodeficiency, 6 with chronic granulomatous disease, 3 with Wiskott-Aldrich syndrome, and 1 with congenital neutropenia. The median age of transplant was 8 months (range: 2 – 143 months). Conditioning regimens were myeloablative conditioning in 13 (72.2%) patients and reduced-intensity conditioning in 3 (16.7%). The stem cell sources were unrelated cord blood in 15 (83.3%), and peripheral blood progenitor cells in 3 (16.7%). Three patients required a second HSCT (cord blood transplantation) owing to graft failure or rejection. Grade III acute graft-versus-host disease occurred in 2 patients. Three patients had limited chronic GVHD involving the skin. The overall survival at 5 years for the entire cohort was 76.4%. In all surviving patients, either stable mixed chimerism or full donor chimerism were observed.
Allo-HSCT is safe and effective in Taiwanese children with PID. Unrelated cord blood can serve as an ideal donor source for children with PID if a matched sibling donor is not available.
In this study (NCT 01888484) the efficacy, safety and tolerability of a 16.5% IgG preparation for subcutaneous administration (cutaquig®, Octapharma/Switzerland) were evaluated in adult and pediatric PID patients. This sub-analysis focused specifically on pediatric patients. Primary outcome was to assess efficacy in preventing serious bacterial infections. Secondary endpoints included tolerability, safety and rate of other infections.
Prospective, open-label, single-arm phase 3 study conducted in North America and Europe. PID patients stable on IVIG treatment for at least six infusions (with IgG trough levels ≥5.0 g/L) underwent a 12-week wash-in/wash-out period, followed by a 52-week efficacy period. In both periods patients received weekly SCIG doses.
Twenty-four children (age: 2-16 years; 25% female) received a total of 1,350 SCIG infusions. No serious bacterial infections were recorded. Among the 77 other infections during the efficacy period only one infection (RSV bronchiolitis) was graded as severe. All other infections were either mild (86%) or moderate (13%) in intensity. Infection rate per person-year was 3.6. Of the 115 reported adverse events, 5 were assessed as being related to the study drug (all non-serious). Rate of related adverse events per infusion: 0.0037. The majority of infusions (82%) did not trigger an infusion site reaction. Serum IgG trough levels were relatively constant and higher at the end of the study than after IVIG treatment.
Results demonstrate that treatment with the subcutaneous 16.5% human normal immunoglobulin preparation (cutaquig®) in pediatric patients with PID is effective, safe, and well tolerated.
For advances in donor selection,graft manipulation, conditioning regimens and treatment of complications, HSCT is an established curative treatment.Sometime HSCT cannot guarantee definitive cure but good control and life quality to patient.
We present 2 pediatric cases with LRBA deficiency and SMARCD2 defect,with recurrent invasive bacterial and fungal infections.Because of the seriousness of the conditions,despite a debated indication to HSCT,it was decided to graft them.
LRBAdeficiency should be considered as high risk disease,especially in children with early-onset hypogammaglobulinemia,severe autoimmune manifestations,enteropathy,multifocal liver cirrhosis, lymphoproliferation,recurrent respiratory tract infections.SMARCD2 patients are characterized by neutropenia and specific granule deficiency.HSCTs were given after Treosulfan oriented protocol conditioning in LRBA child and i.v. Busulphan myeloablative agent in SMARCD2 child and both received prophylaxis for GvHD.The high number of MUDCD34+cells(>10x106/Kg) infused with a controlled number of CD3+cells(30x106/Kg) were the key of rapid engraftment with minimal GvHD in LRBA,while the SMARCD2 child had a matched family donor.Neutrophil and platelet engraftments were at 12 and 17days,respectively.There wasn’t episode of serious conditioning-related toxicity.
The HSCT benefits,namely control of infections,normal growth and improvement in quality of life with drastic reduction of medications were our major achievement.In contrast the non-transplanted patients remain on lifelong antimicrobial and antifungal prophylaxis,with a consistent risk of infections due to resistant strains that in most cases require hospitalization.Moreover in both pathologies autoimmune phenomena are frequent.For critically patients,transplantation is risky. Often,HSCT is postponed until the patient ends up in clinical conditions that contraindicate HSCT.If transplantation is delayed,the risk of severe infections,GvHD and other serious transplant related complications significantly increase.
Widespread vaccination against the measles virus (MV) has reduced disease incidence and led to a progressive decline of MV antibody (MVAb) levels in human plasma, thereby decreasing MVAb levels in individual lots of immunoglobulin (IG). Although IG lot release from the United States (US) requires a minimum MVAb titer, equivalent information is unavailable for other geographies. This analysis assessed regional differences in MVAb titers in IG preparations prepared from plasma collected from the US and European Union (EU).
MVAb titers were determined in 1739 IG lots fractionated from US (n=1466) and EU (Austria, Germany, and the Czech Republic; n=273) plasma between 2013-2018. Plasma was collected by plasmapheresis (source plasma) or by whole blood donations (recovered plasma). Titers were determined as the reciprocal dilution resulting in 50% MV neutralization (NT50[1:X]) using a fully validated neutralization assay.
Mean (SEM) neutralizing MVAb titers were significantly higher in IG lots from the EU than from the US (1521  vs 1373 ; P<0.0001). MVAb titers for IG fractionated from recovered plasma were significantly higher than titers from source plasma (2000  vs 1245 ; P<0.0001); this difference was evident in IG from the US and the EU (Figure).
Neutralizing MVAb titer levels in IG lots from the EU are functionally similar but slightly higher than levels in IG lots from the US, supportive of equivalent protection against MV infection. Thus, dosage in the EU could be aligned with US Food and Drug Administration recommendations for IG use as post-exposure MV prophylaxis.
fSCIG (HyQvia®) is a recombinant human hyaluronidase (rHuPH20)-facilitated subcutaneous immunoglobulin 10% replacement therapy approved in the European Union for patients with primary immunodeficiency disease (PID). This study is acquiring additional data on the long-term safety of fSCIG and assessing the prescribed treatment regimens and administration in routine clinical practice.
This ongoing prospective, non-interventional, open-label, uncontrolled, multicenter study initiated in July 2014 in Europe, includes patients aged ≥18 years with PID currently receiving or prescribed fSCIG (EUPAS5812). The treatment regimens are prescribed at the discretion of the attending physician in accordance with standard clinical practice. Assessments of anti-rHuPH20 antibodies are performed on a voluntary basis.
As of January 10, 2019, out of 111 enrolled patients, 103 patients had received ≥1 dose of fSCIG and were included in the safety analysis population; the mean (SD) fSCIG exposure duration was 2.26 (1.19) years. Incidence of treatment emergent non-serious (non-infectious) adverse events/treatment emergent serious adverse events in the safety population (n=103) was 2.37/0.24 events per person-year; 553/57 events were observed in 83/28 patients. 2 of 78 patients with immunogenicity data developed positive binding antibodies (defined as titer ≥160) to rHuPH20. There were no neutralizing antibodies to rHuPH20. The average annualized per-patient rates for both hospitalizations and emergency room visits were <0.25. Most treatments were administered at home during the first (91.2%), second (93.2%), third (93.2%), and fourth year (85.2%).
This interim analysis of prospectively-collected data of fSCIG use suggests that fSCIG is well tolerated in a real-word study population.
HyQvia (facilitated subcutaneous immunoglobulin [fSCIG]) is a dual-vial unit of recombinant human hyaluronidase (rHuPH20) and 10% normal immunoglobulin (IgG) solution. In the registration study, fSCIG was effective, safe, and bioequivalent to intravenous IgG at the same administration intervals, with fewer systemic reactions. FIGARO will provide real-world data about fSCIG usage in routine administration.
In this multicenter, prospective, observational study in Europe under the auspices of ESID (NCT03054181), patients are eligible for documentation if they receive treatment for primary or secondary immunodeficiency disease and provide informed consent. Planned enrolment is 100 patients. The cut-off for this interim analysis was February 18, 2019.
Patient characteristics (n=85) are shown in the Table. For most patients, average time between infusions was every 4 (68.3%) or every 3 (22.0%) weeks. Median dose of the last fSCIG infusion was 30g (interquartile range: 20–35g), median maximum infusion rate was 300 ml/hr, and thus, median volume infused was 300 ml; most patients used one application site (91.9%; most commonly abdomen) and an infusion pump (97.4%). The most recent fSCIG administration was most commonly given at home (80.5%), followed by doctor’s office (12.2%) and hospital (7.3%) by self-administration (84.0%) or by nurse/physician (16.0%). Technical problems occurred twice. In all cases, the full planned dose of fSCIG was administered.
fSCIG offers the flexibility of infusions performed at home by the patient or in the hospital. Dosing schedule allows variability; however, most infusions are administered every 4 weeks into 1 site. The study is recruiting, and patient observation continues.
To report interim data from an ongoing non-interventional, 2-arm, prospective, uncontrolled, open-label, multicenter, post-authorization registry study in Europe and North America to evaluate the safety of women who become pregnant during or after treatment with facilitated subcutaneous immunoglobulin (fSCIG), and to assess fetal and infant growth/development (NCT02556775).
Women who became pregnant during or after fSCIG exposure were encouraged to participate. During the study, patients either continued to receive fSCIG treatment or an alternate treatment (with a licensed human immunoglobulin product other than fSCIG or an alternative treatment as determined by the physician) in countries where fSCIG treatment during pregnancy is restricted. Assessments were performed per standard of care and data were obtained from medical records during the pregnancy. Data were also assessed on fetal development, and the growth and development of the infant for 2 years post-delivery. The study duration is ~6 years from initiation. Enrollment completed in 2017; however, the study is ongoing.
A total of 16 patients (9 pregnant women and 7 infants) were enrolled. Seven pregnant women were included in the fSCIG-treatment arm and 2 in the alternate-treatment arm. As of February 28, 2019, 7 adverse events were reported for mothers receiving fSCIG; none were assessed as related to fSCIG. All 7 infants were live births and had normal Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) scores.
To date, there were no adverse events related to fSCIG in patients who became pregnant during or after fSCIG treatment and all infants born were normal according to APGAR scores.
The highly concentrated immunoglobulin (IG) formulation—immune globulin subcutaneous (human) 20% solution (Ig20Gly/Cuvitru)—was designed to allow for subcutaneous (SC) infusion of IG in small infusion volumes and to reduce infusion times compared with less-concentrated products. The CORE study will collect representative real-world information about the utilisation, safety, tolerability, and patient experience of Ig20Gly.
CORE is a noninterventional, prospective, longitudinal study being conducted in Germany and Switzerland (DRKS00014562). Patients of all ages are eligible for participation if they provide written informed consent, have primary humoral immunodeficiency disease requiring gamma globulin replacement, received any SCIG therapy (for at least 3 months at a stable dose) prior to Ig20Gly, received Ig20Gly according to drug-label specifications, and are expected to continue treatment with Ig20Gly. Planned enrolment size is 150 patients at 30 sites who will be followed for 1 year (3 visits). Patient and usage data including maximum infusion rate and volume, number of infusion sites, infusion duration, dose and dosing schedule, number and reason for discontinued, slowed, or interrupted infusions, patient experience including satisfaction, and healthcare utilization will be collected during respective visits. Adverse drug reactions will be recorded according to regulatory requirements.
13 patients have started the study to date, and enrolment is ongoing. The first patient was enrolled on 26 November 2018 and study completion is expected in March 2021.
The CORE study is expected to provide a detailed and complete description of Ig20Gly usage under real-life conditions and to describe the patient experience after switching from other SCIG therapies.
Subcutaneous immune globulin 20% (Ig20Gly) is indicated in primary immunodeficiency disease (PID). We evaluated baseline medical history events, ongoing medical conditions, concomitant medication use, adverse events (AEs), tolerability, and infusion parameters by age in data pooled from 2 phase 2/3 studies of Ig20Gly in PID.
Data were pooled from North American (NCT01218438) and European (NCT01412385) Ig20Gly phase 2/3 studies in PID and assessed by age (advanced-age [≥60 years], adult [16–<60 years], and pediatric/adolescent [<16 years]).
Baseline medical history events were more common in advanced-age (n=19; 24.2 events/patient) versus adult (n=64; 12.8 events/patient) and pediatric/adolescent patients (n=39; 5.7 events/patient). Of these, ongoing medical conditions at baseline (comorbid events) were also higher in advanced-age (17.0 events/patient) versus adult (8.9 events/patient) and pediatric/adolescent patients (2.7 events/patient). All advanced-age patients needed concomitant medications to treat preexisting conditions (247 medications for 19 patients). Despite more comorbid conditions, median maximum infusion rates and infusion volumes/site were comparable in advanced-age (60.0 mL/h/site; 40.8 mL/site) and adult (55.0 mL/h/site; 36.3 mL/site) patients; as expected, lower infusion rates and volumes/site were reported in pediatric/adolescent patients (24.0 mL/h/site; 15.7 mL/site). Infusions were tolerated in patients of all ages and infusions associated with causally related AEs were low in advanced-age (local: 0.3%; systemic: 0.7%), adult (local: 1.8%; systemic: 3.4%), and pediatric/adolescent (local: 5.4%; systemic: 0.8%) patients.
Despite the higher prevalence of comorbidities in advanced-age patients, Ig20Gly was infused at relatively high rates and volumes. In this study, Ig20Gly was well tolerated in patients of all ages with PID.
Patients with primary immunodeficiency disease (PID) who require immunoglobulin (IG) replacement (IGRT) receive either intravenous IG (IVIG) or subcutaneous IG (SCIG), which provide equivalent efficacy. Using the Spanish National Health system and societal perspectives, this study developed a cost-minimization analysis to evaluate costs of SCIG versus IVIG.
The base case modeled the annual cost/mg of IVIG and SCIG for the mean doses (established by clinical consensus) over a 1-year time horizon in terms of direct (drug and administration) and indirect (lost productivity for adults [45% assumed working] and parents of pediatric patients [64% assumed working]) costs. Adults (≥19 years) comprised 52.5% of the model population. IVIG was assumed to be administered in a day hospital, whereas SCIG was predominantly (95%) administered at home. Drug costs were calculated from ex-factory prices obtained from local databases minus the mandatory deduction. Costs were valued on 2018 euros.
The annual modeled costs were €4,338/mg lower for patients with PID who received SCIG (total: €14,394/mg) compared with those who received IVIG (total: €18,732/mg). Annual modeled costs were lower for both adult (–€1,773/mg) and pediatric (–€2,565/mg) patients. The two largest contributors were differences in annual immunoglobulin costs and dosage (–€1,927/mg) and annual hospital administration costs (–€2,688). However, SCIG incurred training costs for home administration (€695/year). Costs of pre-medication, dispensing, and indirect costs were also included in the model.
Our model suggests that SCIG may represent a cost-saving alternative to IVIG for patients with PID in Spain.
Spironolactone was identified as inhibiting a step subsequent to viral DNA replication in EBV, a new mechanism of action. The objective of this study was to describe the adjuvant use of spirololactone in the treatment of active chronic EBV in the Immunology Service of the Hospital das Clínicas of the Federal University of Minas Gerais.
We retrospectively reviewed three patients hospital records. Their parents signed the written informed consent for this description.
Patient 1, 10 years old, male. At 7 years, he evolved Hemophagocytic Lymphohistiocytosis (HLH) secondary to EBV (HLHEBV), and was treated with dexamethasone, etoposide, rituximab and human immunoglobulin. Bone marrow transplantation (BMT) was indicated, but no donor was available. Spironolactone was prescribed in june 2018. He persistes with recurrent episodes of fever with oropharyngeal plaques.
Patient 2, 11-year-old male had recurrent fever with the diagnosis of HLHEBV, treated with immunoglobulin and dexamethasone. While waiting BMT, spironolactone has been in used for eight months.
Patient 3, 2 years, male, persistent fever, demonstrated HLHEBV, received intravenous immunoglobulin and dexamethasone, supplemented with etoposide and cyclosporine. Spironolactone was initiated after increased levels of PCR for EBV, despite therapy.
These three cases show that the use of spironolactone in patients with active chronic EBV, still with very variable results between them, requiring longer follow-up time and a longer series of cases for greater definitions. However, it is known that its limited toxicity is one of the most important factors to be considered if promising results occur.
There is no data describing the usage of ECMO in PubMed, MEDLINE in patients suffering from CVID and respiratory failure, as as a complication, who underwent ECMO-technik support. One of the main contradictions of ECMO use is immunosuppression. We share a clinical case with severe comorbidity complications of CVID followed with acute respiratory failure and depressed cardial function successfully managed using ECMO. The main reason of developing disease severe manifestation was 2 years-long break in replacement therapy with immunoglobulin and such unprecedented incompliance was explained by “religion” family views.
Multidiciplinary comission's concluded that the AV- ECMO treatment was the only option to be used in life-threatening condition in a patinet with CVID, despite the contraindications, when all less invasive methods of treatment failed. Individualised titration of the replacement therary with Ig has been taking place in all the time points of procedure, due to unpredicted Ig- level varaibility.
13 days on ECMO was an option for saving time for complex antibacterial effort to succseed. A 26-year patient overcame the septick shok and afterwords sucsessfuly decanulated. The serum level of IgG was ruined at the initiative staged of swiching to ECMO , and was corrected by flexible high dose replacement scheme, individualy adapted to the demands of the condition.
We describe the first adult case with bilateral pneumonia, pansinusitis, and myocarditis in the frame of CVID complications. . The outcome was a healthy patient without sequelaes. This case underlines the necessity of a close interdisciplinary cooperation.
Immunoglobulin replacement therapy (IRT) via intravenous (IVIG) or subcutaneous (SCIG) administration routes is the standard treatment for patients with humoral immunodeficiencies. The aim of our work is to describe and compare the clinical characteristics, the treatment regime and the impact on the quality of life of patients with IGIV and IGSC in a Hospital Unit of Minority Diseases.
For this purpose, we retrospectively analysed the data of 61 patients receiving IRT for 12 months. Clinical and therapeutical variables were recorded and statistically processed with SPSS 20 software.
The mean age of the participants was 45 years-old and 59.6% (34) were women. The most frequent diagnoses were common variable immunodeficiency (62.2%) and secondary immunodeficiencies. Bronchiectasis was present in 36.7% of the patients, followed by enteropathy (31.7%) and dermopathies (28.3%).
Patients treated with IVIG were significantly older than those on SCIG. No significant sex differences were observed. 84.2% of the patients switched the administration route, mainly from IGIV to IGSC (91.4%). Adverse reactions were more frequently seen with IVIG (18.2%) with respect to SCIG (10.8%), and they were predominantly systemic in the first group. There were no significant differences in the posology, the through levels or in the average days lost.
This study shows that IRT with SCIG is safer and equally effective compared to IVIG, as suggested by previous evidence. The SCIG route is preferred among younger patients, probably due to greater ease in training and the need to preserve their work or school activity versus older and more inactive adults.
It was aimed to determine the effect of home-based treatment with immunoglobulin on the quality of life of the children with primary immunodeficiencies (PID) and the caregiving burden in their families.
The patient population consisted of 34 patients who were receiving subcutaneous immunoglobulin (SCIG). Three patients were excluded and nine patients returned to intravenous route in follow-up. “Pediatric Quality of Life Inventory” was applied during intravenous immunoglobulin (IVIG) and SCIG therapy phases to the patients and their parents and “Zarit Caregiver Burden Questionnaire” was applied to the parents of the twenty-two patients who continued with SCIG treatment.
Fourteen boys and 8 girls, with a mean age of 150.0 ± 59.5 months completed the study. The most common diagnosis (50%) was common variable immunodeficiency. When the quality of life scores were evaluated, it was seen that the emotional, school and psychosocial total scores on parent reports were significantly higher and the emotional, psychosocial total and general total scores on patient self reports were significantly higher in SCIG phase than in IVIG period. The total Zarit Caregiver Burden Questionnaire score was found to be lower in SCIG phase than in IVIG period (34.9±9.1 vs 42.8±15.7, p=0.009).
The home-based SCIG treatment option provides better quality of life in patients with PID and reduces the care burden of caregivers. In particular, SCIG treatment is a good alternative for cases with systemic side effects, vascular access problems and for families who have difficulties with transportation to the hospital.
We aimed to characterize the pharmacokinetics (PK) of serum immunoglobulin G (IgG) following 3- or 4-weekly administration of IgPro10 (Privigen®, CSL Behring) in Japanese patients with primary immunodeficiencies, and compare with non-Japanese patients. A previously-developed population PK (PPK) model (Landersdorfer CB et al., Postgrad Med 2013;125:53‒61) was validated, and predicted parameters compared with clinical study results.
The previously-developed PPK model, containing IgG concentration data from 5 non-Japanese studies, was supplemented with data from 3 Japanese studies (IgPro10 or IgPro20 [Hizentra®, CSL Behring]). The model was externally validated by simulating IgG concentration-time profiles in Japanese patients to predict serum IgG PK characteristics and compare with observed Japanese PK data in Study IgPro10_3004 (EudraCT: 2016-001631-12).
The analysis included 4,502 serum IgG concentration values (34 Japanese/168 non-Japanese patients). PPK estimates from the current analysis were consistent with the previously-published PPK model (including clearance [%inter-individual variability, IIV], 0.139 [24%] vs 0.142 L/day; central volume, 4.01 [92.1%] vs 3.94 L, respectively), with similar bootstrap mean and 95% confidence intervals (CI). Prediction-corrected visual predictive checks confirmed a good description of data for SCIG and IVIG. PK parameters were equivalent between Japanese/non-Japanese patients. Simulated and observed area under concentration-time curve, and maximum and minimum serum IgG concentrations were similar (Figure), with 90% CI overlapping between simulated and observed values.
PK parameter estimates of serum IgG were similar between Japanese and non-Japanese patients. The PPK model, updated with Japanese data, could accurately predict both individual and population serum IgG concentration-time profiles following 3-weekly and 4-weekly IgPro10.
Immunoglobulin G (IgG) replacement therapy is the standard of care for patients with primary immunodeficiency (PID). Intravenous (IVIG) requires less frequent infusions and is beneficial for highly symptomatic patients, due to an immediate rise in serum IgG concentration post-infusion. IVIG is favorable for elderly and patients with aversion to self-administration. This study assessed the safety of Privigen® (IgPro10, CSL Behring, King of Prussia, PA, USA) in Japanese PID patients.
This was a prospective, Phase 3, open-label, single-arm study. Privigen® was administered at pre-study doses of 138–556 mg/kg body weight per dosing cycle (3- or 4-weekly) for up to 4 months including a 12-week wash-in/wash-out period. Frequency and intensity of adverse events (AEs), relationship to study drug and AE rate per infusion (AERI) were assessed.
Ten patients completed the study. The median (range) total duration of exposure was 16.14 (4.1–16.3) weeks. A total of 19 AEs, most of which mild (45.5%), were reported in 8 patients, giving an AERI of 0.442. One AE was deemed related to Privigen® treatment (infusion site discomfort, resolved). Three patients experienced temporally associated AEs (within 72 h post-infusion). No serious AEs or deaths were reported. Most patients (90%) tolerated flow rates of ≥8 mg/kg/min, of which 5 (50%) tolerated 12 mg/kg/min. This translated into a 3-fold decrease in mean (SD) infusion time, from 173.4 (53.65) min for the first to 58.5 (14.24) min during the fourth infusion.
Privigen® was well tolerated at flow rates of up to 12 mg/kg/min.
The pharmacokinetic (PK) properties of IgPro10 (Privigen®, CSL Behring, King of Prussia, PA, USA), a 10% liquid intravenous immunoglobulin (IVIG), are well-established in non-Japanese patients with primary immunodeficiency (PID). This study evaluated PK parameters of IgPro10 in Japanese patients with PID.
This was a prospective, Phase 3, open-label, single-arm study of IgPro10 in Japanese patients with PID. IgPro10 (138–554 mg/kg body weight, as per patient’s last steady-state dose) was administered in 3- or 4-weekly dosing regimens for up to 4 months. Serum samples for PK analysis were collected during the last IgPro10 dosing cycle (beginning from Week 13). PK parameters including area under the concentration-time curve from time point zero to the last quantifiable time point (AUC0–last), dose-adjusted AUC0–last (dAUC), lowest/highest observed immunoglobulin G levels (Cmin/Cmax), time to reach Cmax (Tmax), and total clearance (CL) were analyzed for both dosing regimens.
Ten patients were included in this analysis (3-weekly/4-weekly: n=2/n=8); the small number of patients in the 3-weekly regimen limits the interpretation. Cmax was observed approximately 1 h after the start of the infusion in both treatment groups. Mean (SD [not applicable for 3-weekly infusion parameters]) PK parameters were: Cmax, 16.60 and 14.20 (5.53) g/L; Cmin, 10.60 and 8.53 (3.89) g/L; AUC0–last, 5971 and 6591 (2633) g*h/L; dAUC, 0.41 and 0.46 (0.19) g*h/L; CL, 2.53 and 2.53 (0.99) mL/h and median Tmax was 1.19 and 1.14 h, for 3-weekly/4-weekly dosing regimens, respectively.
PK parameters of IgPro10 in Japanese patients were similar between 3- and 4-weekly dosing regimens.
Intravenous immunoglobulin (IVIG) replacement therapy, has been standard treatment in patients with Primary Immunodeficiency Diseases (PID). Several studies have shown that subcutaneous immunoglobulin (SCIG) infusions demonstrate similar efficacy and are safe and well tolerated in this population.
The objective of this study was to describe the clinical evolution, side effects and tolerability of SCIG in PID patients in reference hospitals in Guanajuato Sate.
An observational, retrospective and transversal study was conducted. A total of 11 patients with PID, who received SCIG (200MG/KG bi-weekle) at any time of their treatment, were included. The intensity of the pain was measured by Analogical Visual Scale (AVS).
Spectrum of PID was: Specific Antobody Deficiency (54%), hypogammaglobulinemia (27%) and IgG1 deficiency (18%). SCIG was the first option therapy in 2 patients, and as IVIG alternative in 9 These patients were switched to 20% SCIG because persistent infections (44%), IVIG high cost (22%), no secure venous acces (22%) and their own confort (11%). A total of 173 SCIG infusions were analized: These were administrated in abdomen, lumbar area, interescapulovertebral zone and back side of arms. Side effects were reported in 8 patients (5 local reactions and 3 systemic effects). No patients suffered infections and no visits to emergency room were reported. AVS average score was 2.11.
This data confirm that SCIG is a safe (no several side effects) and a well tolerated alternative to IVIG. In our patients, the most tolerated area for the SCIG administration was back side of arms.
Disseminated BCG disease is often fatal and results from impaired immunity. The aim of our study is to describe the outcome of BCG disease in immune-compromised (PIDs) children receiving haematopoietic stem cell transplantation (HSCT).
We included all patients how underwent HSCT for PIDs in whom BCG infection occurred before or after HSCT. Isoniazide and rifampycine were discontinued before conditioning to ovoid drug interactions and switched to ethambutol and ciprofloxacin.
Eleven included patients received HSCT for CMH class II deficiency (n= 2), Wiskott Aldrich syndrome (n= 2), chronic granulomatous disease (n=1), Interferon-gamma receptor deficiency (n=1) and severe combined immunodeficiency (n= 5). BCG disease onset was prior to HSCT in 10 patients and after HSCT in one patient. Before HSCT, BCG disease was loco-regional in four patients and disseminated in six patients. Five patients had a sustained response to treatment, two patients relapsed and three patients had persistent disease. After HSCT, one patient developed regional BCG disease at one month. One patient showed persistent disseminated BCGite requiring splenectomy at 12 months post HSCT. BCG disease treatment was continued for at least 6 months in all patients with improvement in clinical signs and progressive regression of lymphadenitis. Good immune reconstitution was acheived in 10 patients without recurrence of BCG disease. One patient died from severe graft versus host disease one month after HSCT.
BCG disease is lethal in severe PIDs if not treated. Combined with prolonged medical therapy, HSCT has significantly improved survival once immune reconstitution was achieved.
Infectious complications in patients with CLL represent the main cause of their morbidity and mortality with 50-60 % of all disease-related deaths. The aim of our study was to identify potential risk factors such as cytogenetic aberrations, immunoglobulin heavy chain variable region (IGVH) mutational status, and hypogammaglobulinaemia with emphasis on anti-pneumococcal capsular polysaccharide (anti-PCP) and natural anti-galactosyl (anti-Gal) antibodies.
Study participants comprised 96 CLL patients (67 ± 9 years) and 76 age-matched healthy individuals. The CLL patients were newly diagnosed, not exposed to any antipneumococcal vaccine. Each blood sample was tested for total IgG, IgA, and IgM; anti-Gal IgG, IgA, and IgM; and anti-PCP IgG, IgG2 and IgA. Patients were sorted according to Rai stage, cytogenetic aberrations, IGVH mutational status and experience of severe bacterial infections during the last year.
All measured humoral parameters (excluding anti-Gal IgG) negatively correlated with Rai stage. The IgG level less than 4 g/L were observed in 9 % and unprotective anti-PCP IgG levels in 22 % of CLL patients. 30 patients developed severe bacterial infection. Despite the fact that almost all measured parameters (except anti-PCP IgG2) were significantly lower in CLL group compared to healthy controls, no significant difference between patients with and without history of severe bacterial infection in relation to all followed factors were observed.
Characteristics such as genetic abberations, IGVH status, immunoglobulin level, anti-PCP or anti-Gal antibodies do not seem to predict severe bacterial infection risk in newly diagnosed CLL patients. Therefore preemptive immunoglobulin substitution is not indicated in this group.
Thymus transplantation (TT) can correct athymia with severe T-cell immunodeficiency secondary to FOXN1 deficiency. In presence of CMV infection, TT has previously never achieved thymopoeisis.
We describe the first patient with thymopoeisis and CMV clearance after TT.
The patient displayed alopecia totalis at birth and at two months developed a desquamating erythematous rash followed by pneumonitis with CMV viraemia (viral load: 12xE6 copies/ml), which responded to anti-viral treatment. Additionally she suffered from BCGitis, improving after quadruple anti-mycobacterial treatment. Immunological assessment revealed lymphopaenia with oligoclonal T-cells, impaired mitogen proliferation, few naïve T-cells and low TREC levels. A homozygous FOXN1 mutation was identified, resulting in a premature stop codon (R114X). Upon referral to London, CMV viral load (VL) was low in serum (25xE3 copies/ml, CT33), but high in the CSF (CT26) with minimally raised protein, but no leukocytes. Except for a bulging fontanelle, she was neurologically asymptomatic. She underwent TT without anti-thymocyte globulin, but with cyclosporine to control Omenn-like features. With continuing anti-viral treatment, whole blood VL remained relatively low (maximum 34x10E3 copies/ml). At four months post-transplantation, she deteriorated neurologically, displaying features of mild encephalopathy and absence-like seizures after reduction in anti-viral treatment. After re-introduction of full treatment, her neurological status improved. At six months VL became undetectable in whole blood and CSF. Thymopoiesis was confirmed on transplant biopsy with simultaneous appearance of circulating naïve CD4 T-cells and recent thymic emigrants.
TT can be successful despite CMV disease, possibly because of low viraemia in our patient. Antiviral treatment did not impair thymopoeisis.
There are only a few cases who underwent hematopoietic stem cell transplantatişon (HSCT) for PRKDC defect in the literature. Here we report a patient with PRKDC defect who underwent HSCT after myeloablative conditioning.
Clinical and transplantation characteristics of the patient was recorded.
A two years old girl was admitted to our hospital for oral moniliais, recurrent pulmonary infections, intermittent diarrhea episodes and skin lesions and diagnosed with combined immunodefciency. During the follow-up PRKDC mutation was shown with molecular analysis. At the age of 4.8 years the patient undewent HSCT from his HLA 9/10 identical relative. The myeloablative conditioning regimen included busulfan (20.4 mg/kg) and fludarabine (160 mg/kg) and anti-thymocyte globulin (30 mg/kg). Cyclosporine A and methotrexate were used as graft versus host disease (GVHD) prophylaxis. Bone marrow (BM) was used as a stem cell source and number of CD34+ cells was 8.2x106/kg. Neutrophil and platelet engraftment were achieved on day +15 and +19 respectively. During the posttransplant period the patient developed steroid resistant grade III acute GVHD and treated with calcinuerin inbitors, mycophenolate mofetil, etanercept, mesenchymal stem cells and extracorporeal photopheresis. Chimerism analysis showed 99% donor profile at the first month and 98% at the first year of HSCT. 15 months after HSCT the patient has no clinical findings associated with CD40 deficiency and GVHD is improved.
HSCT with myeloablative conditioning is effective in PRKDC defect even from an HLA 9/10 matched relative donor although more experience is required to assess clinical outcome.
Haematopoietic stem cell transplantation (HSCT) has been shown to be a curative option in patient with CD40 deficiency, however, few reported cases of successful HSCT have been published in the medical literature. Here we report a patient with CD40 deficiency who underwent HSCT after myeloablative conditioning.
Clinical and transplantation charactersitics of the patient was recorded.
3.8 years old boy referred to our hospital with the history of recurrent pulmonary infection for the investigation of immunodefciency and diagnosis of Hyper-IgM syndrome was made with molecular testing. At the age of 6.3 years patient undewent HSCT from his unaffected HLA-genotypeidentical sibling selected using preimplantation genetic diagnosis. The conditioning regimen included busulfan (19.6 mg/kg) and fludarabine (160 mg/m2). Cyclosporine A and methotrexate (day +1, day +3, day +6) were used as graft versus host disease (GVHD) prophylaxis. Bone marrow and cord blood were used as a stem cell source. Neutrophil and platelet engraftment were achieved on day +19 and +22, respectively. During posttransplant period acute/chronic GVHD, venoocclusive disease were not observed. CMV reactivation developed and treated with gancyclovir. Chimerism analysis showed %98 donor profile at the third month and 95% at the sixth month of HSCT. Eights months after HSCT patient in good clinical condition and had no clinical finding associated with CD40 deficiency.
HSCT with myeloablative conditioning in the early stage of the disease and an HLA-matched sibling donor is effective at curing the disease with fewer complications although more experience is required to assess clinical outcome.
Intravenous immunoglobulin (IVIG) is recommended for children with primary and secondary antibody deficiencies.
Chylothorax (CL) has been associated with T-lymphocyte loss and hypogammaglobulinaemia. The aim of this systematic review is to summarize the evidence concerning the potential protective role of IVIG in children with chylothorax.
Medline was systematically inquired using relevant keywords and articles were retrieved for full-text review. Data were collected, analyzed and then summarized in a qualitative analysis in order to examine the evidence of IVIG use in children with CL and its potential beneficial effect on them.
A total of five retrospective, descriptive cohort studies and case series were retrieved; no prospective randomized control trial was identified. Use of IVIG as adjunct to conservative treatment was reported in 29 patients aged 5 days to 5 years. All cases were diagnosed with CL after cardiac surgery. Hypogammaglobulinemia, lymphopenia and septicaemia were the most common indications for IVIG treatment (13/29). IVIG doses varied from 0.1 to 1 gr/kg/day. Administration of IVIG did not prevent recurrent infections or serious complications in the majority of patients (51.7%, 15/29). Blood stream infections were seen after IVIG therapy in 13 cases (44.8%). Mortality was high and affected 24.1% of the treated patients (7/29). Only one study (N: 37) provided comparative data between treated and untreated patients and did not manage to show significant differences in outcome.
Limited evidence exists to support treatment with IVIG in children with CL. Large, well designed prospective studies on IVIG administration are required.
Autosomal dominant form of the hyper-IgE syndrome is caused by STAT3 dominant-negative mutations, whereas autosomal recessive form is caused by loss-of-function mutations in ZNF341, which transcriptionally governs STAT3 activation. These patients present with severe allergy, including a severe form of eczema, which is thought to be caused by increased Th2 immunity. No effective treatment of their atopy is available besides topical steroids.
We treated a patient with ZNF341 deficiency and severe eczema with Dupilumab, blocking the alpha chain of the interleukin-4 receptor. Dupilumab was administered subcutaneously every 2 weeks for a year at 300 mg per dose. Every month, patient filled the DLQI and SCORAD standardized questionnaires to monitor the response. IgE levels and adverse events were monitored.
At Dupilumab initiation, patient used steroids class I, DLQI was 22/30, and SCORAD was 85,5/100, defining a severe form of eczema. IgE were highly elevated at 16,689 kU/L. We observed a rapid improvement with a DLQI at 2, and a SCORAD at 9 after 2 months. Steroids were tapered and stopped after 3 months. After 1 year, the response was sustainable. Physical examination noted a remarkable improvement. Patient no longer suffered from scratching lesions. Nodular lesions disappeared, and epithelialization occurred in depigmented areas. No adverse effects were noted. IgE progressively decreased, up to 6022 kU/L.
Dupilumab is a safe and efficient therapy in patients with genetically driven severe eczema. Moreover, this observation furnishes a rational for the use of Dupilumab in other patients with inborn error of immunity and Th2-mediated severe allergy.
Rotavirus vaccines have been reported to cause enteropathy in infants who received vaccine prior to a diagnosis of SCID.
We studied the impact of rotavirus vaccine on transplant outcome in 24 infants with SCID transplanted at the Great North Children’s Hospital between 2013 and 2018.
7 patients diagnosed at birth did not receive rotavirus vaccine. Rotavirus vaccine was associated with increased incidence of acute GvHD (p=0.03), increased need of PN (p=0.01) and increased need for ICU (p=0.03).
|No rotavirus vaccine||rotavirus vaccine||p-value|
|Median age at diagnosis (range), months||0.6(birth–13.6)||4.6(2.8-7.1)||0.005|
|Median age at transplant (range), months||2.4(1.0 – 15.4)||7.4(3.4-9.4)||0.005|
|Median interval transplant to diagnosis (range), months||1.9(0.24– 2.6)||1.6(0.6-4.1)||0.64|
|BCG vaccination, n||4||1||0.16|
|Growth failure, n||3||6||0.4|
|Conditioned transplant, n (%)||11(92)||10(83)||0.5|
|TCR ab/CD19 PBSC||2||3|
|Median TNC (range), 108/kg||11.5(0.93-40.0)||9.65(0.21-53.0)||0.45|
|Median CD34 (range), 106/kg||11.3(1.9-96.0)||0.4(0.5-26.6)||0.98|
|Median days of PN (range)||36(26-125)||87(21-196)||0.31|
|PICU admission, n||1||6||0.03|
|Median days of PICU stay (range)||0(0-39)||16(0-25)||0.05|
|Median days of total inpatient stay (range)||83.5(0-168)||129.5(26-341)||0.13|
Rotavirus vaccine is associated with significant transplant morbidity for infants with SCID
Severe combined immunodeficiency (SCID) is a paediatric emergency and early haematopoeitic cell transplantation is the only curative therapy
We studyed transplant outcomes in 35 infants with SCID who were transplanted at Great North Children’s Hospital from 2013 to 2018.
Stem cell sources were: Haploidentical donor (HID) (TCR ab/CD19, 9), matched family donor (MFD) (marrow, 7; PBSC 4), matched unrelated donor (MUD) (marrow, 3; cord, 8; PBSC, 4). Fludarabine and Treosulfan were used for patients who received conditioni ng. 2-year OS was 100% for HID, 79% for MSD and 84% for MUD. CD4 recovery at 6 months post-HCT was comparable between stem cell sources.
|Median age at diagnosis (range), months|| |
|Median age at transplant (range), months||6.0(1.7-9.7)||4.3(1.0-7.1)||5.3(0.8-16.3)||0.31|
|Median interval between diagnosis and transpant (range), months||2.3(0.6-9.7)||1.6(1.0-2.8)||2.0(0.3-14.3)||0.33|
|Pre-transplant gut viraemia||6||5||7||0.57|
|Median TNC (range), 108/kg||12 (3.7-40.0)||9.7 (5.7-21.0)||3.4 (0.93-20.4)||0.03|
|Median CD34 (range), 106/kg||20.7 (4.0-53.0)||11.7 (5.0-25.7)||1.5 (0.21-24.2)||0.02|
|Median day of neutrophil engraftment (range)|| |
|Median days of inpatient stay (range)||87(38-260)||88(36-190)||105(43-263)||0.29|
HID is a safe alternative donor source for infants with SCID
Hospitalizations are often required in patients with Primary immunodeficiencies (PID), especially before the diagnosis. Immunoglobulin replacement therapy (IgRT) is standard treatment in majority cases.
Aim: To compare the frequency of hospitalization in children with PID previous to intravenous IgRT at Children´s Hospital of Brasilia–Brazil (pre- IgRT) with one-year period after initial IgRT (post-IgRT).
Medical reports during a 7-year period were reviewed. Comparisons between the groups were carried out using the Wilcoxon test.
Thirty-eight children were studied, aged 1-16yo, of whom 24 (63%) were males. Specific antibody deficiency and unclassified hypogammaglobulinemia were the predominant diagnosis (30% and 20%, respectively). X-linked agammaglobulinemia, Hyper IgE syndrome, Class-Switchrecombination defects , transient hypogammaglobulinemia of infancy, and Common Variable Immunodeficiency (CVID ) were also reported, in a low frequency. Mean ages at onset symptoms were 9mo, first consultation was at 63mo and the initial IgRT at 70mo. Thirty-six (97%) patients were hospitalized before IgRT, and 10 patients (27%) after. The hospitalization total for all the 38 patients was 211 (pre-IgRT) and 29 (post-IgRT) (p<0.0001). The length of stay at hospital for all the 38 patients pre-IgRT was 3102 days, of which 856 days were at PICU; at post-IgRT, 399 days at hospital was the number of days children spent at hospital of which, and 15 days at PICU (p<0.001).
One-year IgRT had a significantly decreased the number of hospitalizations, length of stay at hospital, as well as at PICU, in our cohort . Social and economic impacts would be required.
Background: Vaccines are important to prevent life-threatening infectious diseases. This is also, and particularly, true for children with primary and secondary immunodeficiency who have an increased risk of complications and hospitalizations upon exposure to vaccine-preventable diseases. We aimed to measure vaccination coverage and seroprotection in children with primary immunodeficiencies (PID) and solid organ transplantation (SOT) in a university hospital in Flanders, Belgium.
Methods: Serological testing was performed on blood samples of 123 patients aged 2-16 years. Antibody titers were determined by ELISA (MMR) and multiplex assays (DTP) and were considered seropositive if above cut-off value. Vaccination status was assessed retrospectively by parental questionnaire. In particular, vaccination data were copied from relevant documents, verified against the Flemish vaccination register and missing data were requested from the general practitioner. Patients were considered fully vaccinated if they were correctly vaccinated according to the Flemish immunisation programme.
Results: protection against vaccine-preventable diseases measles mumps rubella, diphteria, pertussis but not tetanus, is signficiantly lower in immunocompromised children, compared to historical data found in literature. This is true even in fully vaccinated children and in children on immunoglobulin substitution. Detailes follow at presentation.
Conclusion: Immunocompromised children remain at risk for vaccine preventable diseases. This is due to the nature of their disease and due to the immunosuppressive medication in SOT. Increasing the vaccination status of not only immunocompromised children, but also of healthy children to prevent circulation of vaccine-preventable diseases remains extremely important. The protective under IG substitution should be examined more in depth.
DOCK8 deficiency is a combined immunodeficiency characterised by susceptibility to viral, bacterial infections, malignancies and immunodysregulation. Haematopoietic stem cell transplant (HSCT) offers a cure but data on long term immune reconstitution and post-HSCT inflammatory complications are limited.
Retrospective case notes audit of patients treated at Great Ormond Street Hospital, London.
Ten children from 8 families underwent HSCT for DOCK8 deficiency from 2000-2018. Median age at HSCT was 9.4 years. Reduced intensity conditioning(RIC) with busulphan or melphalan with fludarabine and serotherapy was used. Four patients underwent matched sibling donor and 6 patients underwent 9/10 (n=3) or 10/10 (n=3) matched unrelated donor HSCT with bone marrow and peripheral blood stem cells respectively. Median follow-up post-HSCT was 71 months (3-191 months) and overall survival was 90%. One child died at day+98 due to rubella encephalitis. 5/9 surviving patients had 100% donor chimerism. The other 4 had >80% CD3-donor chimerism with myeloid engraftment of 0-54%. Of 9 surviving patients, three developed de novo immunodysregulation (inflammatory bowel disease, autoimmune thyroiditis, inflammatory skin lesions) 12 months post-HSCT. Two of these three had full donor chimerism. All evaluable patients had excellent immune reconstitution with age appropriate thymopoiesis post-HSCT. Two patients (with low class switch memory B-cells post-HSCT) developed early loss of serotype specific pneumococcal antibodies following revaccination.
RIC-HSCT offers a cure from the serious complications of DOCK8 deficiency. Mixed chimerism with high donor T-cell engraftment appears sufficient to ameliorate the major manifestations of this disorder however post-HSCT immunodysregulation may persist despite full donor chimerism.
In common variable immunodeficiency disorders (CVID), splenectomy has been used mainly in refractory autoimmune cytopenia. The aim of the study is to explore circumstances and outcomes after therapeutic splenectomy in CVID.
We retrospectively reviewed two cases of CVID patients who underwent splenectomy.
Case 1: A 19-year-old boy born to non-consanguineous parents, followed for CVID revealed at 16 years of age, with chronic respiratory symptoms, interstitial lung disease, lymphoproliferative syndrome, and recurrent infections. Respiratory pathology has been attributed to a granulomatous lymphocytic interstitial lung disease. He had heterogeneous splenomegaly exceeding 20 cm leading to hypersplenism and refractory cytopenia. Splenectomy was done at the age of 19 years; The pathological study showed granulomatosis. The short-term evolution was favorable.
Case2: A 42-year-old woman, followed for CVID, diagnosed at age 26, in front of the family history of CVID, episodes of recurrent skin infections, ORL (sinusitis and otitis) and respiratory (recurrent pneumopathies with obliterant bronchopathy), as well as autoimmune thrombocytopenia. Biology has shown a low level of different immunoglobulins and low B-memory-lymphocytes. The patient was splenectomized for corticosteroid-dependent autoimmune thrombocytopenia. The intervention was followed by a long-term normalization of platelet count but without a significant reduction in infections after a 20-year follow-up.
Splenectomy is recommended as a therapeutic option for patients with refractory cytopenias and/or autoimmunity, even though CVID patients undergoing splenectomy may be at increased risk for infection given their intrinsic immunological defects. Future trials are needed to provide clearer guidance on the second-line management.
Haplo-haploidentical HSCT with post-transplant cyclophosphamide (PT-Cy) is an emerging alternative in primary immune deficiency patients without sibling matched donor (MSD). There are very few reports of haplo-haploidentical HSCT with PT-Cy in WAS patients. The aim of the study is to report the results of this technique in a WAS patient.
We report the case of a 3-year-old boy followed for a WAS. His maternal cousin received HSCT for the same disease from MSD. He presented repetitive hemorrhagic syndrome with thrombocytopenia, eczema, autoimmune anemia, and locoregional becegitis. The detection of a WASp gene mutation confirmed the diagnosis. He has no MSD, so haplo-identical HSCT was performed from his mother.
Pre-transplant conditioning regimen included thymoglobulin, Busilvex, and Fludarabine. He received PT-Cy (day 3 and 4), in addition to Cyclosporine and Mycophenolate Mofetil. Graft CD34 were 3.75 106/kg. Neutrophile engraftment was achieved at day 20 post-HSCT. Chimerism showed donor cells at day 30. At day 30, he presented a severe cutaneous and digestive GVHD confirmed by biopsies. No sufficient improvement was noted after three first-line immunosuppressors. Cutaneous and digestive remission was obtained after treatment with rabbit thyroglobulin. CMV reactivation responsive to preemptive treatment occurred at day 45. Four months after HSCT, He is alive, infection free, no GVHD sign, but immune reconstitution is not yet achieved.
Haploidentical HSCT with PT-Cy is a new therapeutic alternative in WAS patients who do not have a MSD. However viral infections and GVHD could delay immune reconstitution and make management difficult.
Enterovirus encephalitis has been described in patients with agammaglobulinemia since 1961.It can occur even with adequate immunoglobulin replacement as there can be great variation in antibody titres against circulating enterovirus serotypes.Lack of specific therapy and delay in diagnosis contribute to the poor outcome. We present two patients managed at our centre in collaboration with Great Ormond Street Hospital with near complete recovery.
Aims- Retrospective analysis of clinical manifestations, management and outcome in two agammaglobulinemic patients diagnosed with enterovirus encephalitis.
2 patients from 2 different families with enterovirus encephalitis while on immunoglobulin replacement therapy were retrospectively analysed.
Patient 1- 3 ½ year old girl on ivig for agammaglobulinemia developed subacute onset of drowsiness.CSF showed pleocytosis, enterovirus detected by PCR and MRI was suggestive of meningoencephalitis.She had persistence of enterovirus in CSF, developed status epilepticus 6 months later with rapid neurological deterioration. A trial of ribavirin and fluoxetine with high dose ivig resulted in clinical improvement within a month.She regained most of her milestones with improvement in MRI changes and CSF pleocytosis but developed orthostatic tremors during a year of follow up.Patient 2- 5 year old boy diagnosed as XLA, on immunoglobulin replacement therapy presented with acute onset encephalopathy with CSF pleocytosis and enterovirus detected by PCR.He was started on fluoxetine and ivig at first presentation.Within 3 months of treatment all symptoms had resolved except left arm paresis.
Fluoxetine and ribavirin have antiviral activity against enterovirus and are easily available. Early treatment with high dose ivig and antivirals may have better outcomes.
Autoimmunity in CVID patients is frequently described, with an estimated prevalence of 30% of all CVID patients. Among these complications, autoimmune thrombocytopenia (ITP) are the most commonly reported. The aim of our work was to evaluate the safety of the facilitated subcutaneous administration of immunoglobulin (f-SCIg) in patients with ITP CVID-related.
We described three women with CVID, diagnosed according to ESID criteria. All of the patients presented symptomatic ITP. In one of them ITP was the onset manifestation of the related immune disorder. The others two cases had a long-history of refractory ITP in course of CVID, treated with steroids and intravenous immunoglobulin with relapses. One patient presented residual splenic tissue after splenectomy performed many years before.
All patients were treated with Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase (Hyqvia ®, Shire Pharmaceuticals) at the initial dosage of 20 g every 2 weeks. All patients achieved remission of the thrombocytopenia without relapse during the follow-up period (respectively 52 months for two patients, 28 months for the latter). No hemorrhagic complications due to the subcutaneous infusions were reported. Nor hemolytic nor thrombotic events were observed. Patients did not report systemic adverse events related to the infusions, but only mild local reactions in the infusion site. Once remission was obtained, we gradually increased the interval between infusions to 4 weeks, maintaining a stable remission, with platelets values persistently > 90.000/mmc.
f-SCIg is an effective and safe option of treatment in CVID related ITP.
CTLA-4 deficiency is a widely known cause of immunodeficiency and autoimmunity, determining an immune dysregulation syndrome. We here present the case of a young woman with a severe inflammatory bowel disease (IBD) secondary to CTLA4 deficiency, successfully treated with abatacept.
We describe the case of a 41-year-old woman affected by CVID-associated IBD determining chronic diarrhea and severe malabsorption. Her medical history included psoriatic arthritis, idiopathic thrombocytopenic purpura and multifactorial anemia. Replacement therapy was based on subcutaneous Ig (Hizentra ®, CSL Behring) at 8 g/week. The first time she came to our attention, her weight was 33 kg and she was in parenteral nutrition by a central venous catheter (CVC). She was firstly treated with steroids and anti-TNF alfa (adalimumab), with initial partial clinical response. Anyway, six months after we had to definitely stop adalimumab because of several serious infective complications (including CVC infection). Considering the comorbidities and the suboptimal therapeutic response, we decided to asses a genetic test in order to find out an underlying monogenic cause of immunodeficiency.
The genetic examination documented a CTLA4 gene heterozygous mutation, with consequent deficiency. Thus we decided to administer her abatacept, a CTLA4-immunoglobulin fusion protein, at the dose of 125 mg/week subcutaneously in association with oral topical steroid (budesonide). At one year follow-up the patient has gained weight and diarrhea is in remission.
CTLA-4 mutations determine an immune dysregulation syndrome potentially associated to severe enteropathy. Abatacept can be effective in inducing and maintaining remission in these patients.
We assessed the health-related quality of life (HRQoL) in CVID adults receiving different schedules of immunoglobulin replacement therapy (IgRT) by intravenous (IVIG), subcutaneous (SCIG), and facilitated (fSCIG) preparations. For these patients, IgRT schedule was chosen after a period focused on identifying the most suitable individual option.
327 participants were enrolled in a prospective, observational, 18-month study. Participants received IgRT for at least 2 years. The first 6-months were devoted to the educational process during which the choices related to IgRT were regularly re-assessed, and the shift to alternative regimen was permitted. During the following 12 months, clinical data were prospectively collected, and only patients who did not further modify their IgRT schedule were included in the analysis of HRQoL measured by CVID_QoL, a specific instrument, and by GHQ-12, a tool to assess minor psychiatric nonpsychotic disorders (Fig.1).
304 patients were included in the analysis. CVID_QoL global score and its dimensions (emotional functioning, relational functioning, gastrointestinal symptoms) were similar in IVIG, SCIG, and fSCIG recipients. Patients receiving IgRT by different routes of administration reported similar capacity to make long-term plans, discomfort due to therapy, and concern to run out of medications (Fig2). Multivariate analysis revealed the GHQ-12 status, but not the IgRT mode of administration, as the major factor impacting on treatment-related QoL items, and a significant impact of age on discomfort related to IgRT.
IgRT schedules do not impact the HRQoL in CVID if the treatment is established after an extensive educational period focused on individualizing the best therapeutic regimen
Stem cell transplantation is the only cure for most of the PIDs. As an newly established transplant unit we have transplanted 18 patients with primary immunodeficiencies between 2013-2019.
Eighteen patients were transplanted between 2013-2019. Three of them were Syrian refugees.There were 14 boys 6 girls. The median age was 5 years (min 1 max 12 years) There were 11 MSD, 4 matched MUD, 4 one allele mismatch MUD and one haploidentical transplants. Two patients were transplanted twice due to graft failure. Their diagnoses were as follows; 3 CGD, 2 MHC Class II deficiency, 1 WAS, 1 LAD I deficiency, 1 Kostman syndrome, 8 SCIDs, 1 cartilage hair dysplasia with immunodeficiency, 1 Dock 8 deficiency.
12 patients are engrafted and alive. Of the 6 patients who died,one had graft failure and went for second transplant. All patients died due to interfering infections and respiratory distress posttransplant.
There has been a great improvement in treating PID with SCT with a greater understanding of the genetics and immunobiology of these diseases and also facilitating the matching of donor type and conditioning regimens.
The IPEX syndrome is the X-linked immunodysregulation syndrome, with poliendocrynopathy, and enteropathy caused by the FOXP3 mutation. Clinical hallmarks are enteropathy, endocrinopathy and dermatitis.
We report the patient with classical IPEX syndrome who developed insulin-dependent diabetes, autoimmune thyroiditis, nephrotic syndrome and coeliac disease. The patient was transplanted with an unrelated 8/10 HLA matched umbilical cord blood (UCBT) after conditioning regimen with treosulfan 36 g/m2, fludarabine 150 mg/m2, thiotepa 10 mg/kg, and Thymoglobulin at a dose of 7.5 mg/kg. Due to rapid and complete rejection of the UCBT, a second transplantation from a 6/10 HLA matched mother was performed.
The second conditioning regimen consisted of busulfan 16 mg/kg, fludarabine 150 mg/m2, cyclophosphamide 1g/m2, Grafalon at a cumulative dose of 30mg/kg, and rituximab at a dose of 375 mg/m2. The donor underwent stem cell apheresis on day -1, and alpha-beta T-cell depletion was performed using the CliniMacs Prodigy. The graft product contained 15.06 x 106 CD34+ cells/kg BW and 4.19 x 105 alpha-beta T-lymphocytes/kg BW. From day +15 to +18, due to acute graft rejection the boy was treated with Thymoglobulin and the full donor chimerism was achieved. Around day +40 after transplantation, the boy developed symptoms of stage 1 skin graft versus host disease and was treated with topical steroids and mycophenolate mofetil. Three years after SCT, the patient remains free from GVHD and immunosuppression.
Haploidentical SCT in IPEX syndrome is feasible and well tolerated, but chimerism monitoring and aggressive graft rejection therapy are warranted due to hyperreactivity of autologous T-lymphocytes.
Killer immunoglobulin-like receptors (KIR) play a role in regulation of NK-lymphocyte reactivity and affect immunological response in stem cell transplantation (SCT) recipients.
Patients were transplanted for malignant (89) or non-malignant diseases (113) from matched sibling donors (MSD, 35), matched donors (MD, 133) or partially matched donors (MMD/HAPLO, 33). The donor samples were tested for KIR genotype using KIR typing kit (Miltenyi, DE). The effects of diagnosis, degree of HLA-match, pre-transplant conditioning, and KIR-genotyping results on survival were analyzed.
Neither differences in single KIR loci, nor the KIR B-content score affected patients’ OS/EFS/TRM/DFS. The graft-versus-host (GVH) KIR-ligand mismatch was observed in 13 patients and host-versus-graft (HVG) in 9 cases. The probability of OS was superior in non-malignant entities 83.96 % vs 60.5% (p=0.0004). Better donor choice (MSD vs MUD vs MMD/HAPLO) was associated with higher probability of OS (94.3% vs 80% vs 31.2%, p=0.00001) and EFS (88.6% vs 77% vs 28.8%, p=0.00001). The probability of OS was decreased in the presence of any HLA mismatch (61.02% vs 88.99%, p=0.00008), and GVH KIR mismatch (41.6% vs 81.5%, p=0.002). The multivariate analysis using the Cox regression model revealed GVH KIR mismatch as the factor relevant for OS, EFS, HVG mismatch for TRM, and in non-malignant entities degree of donor’s HLA B match was significant for OS.
KIR associated mechanisms affect patients outcome after SCT. In case of partially matched donors, the optimal donor choice algorithm should eliminate the presence of KIR ligand GVH mismatch.
Introduction : Patients suffering from diseases associated with poor immunoglobulins levels or function can be helped with an immunoglobulin replacement therapy. These are often life-long therapies. Headaches are the most common adverse events of intravenous immunoglobulins. Multiple manufacturers make IV immunoglobulins, each having a proper manufacturing proces. This leads to a difference in tolerability.
Purpose : To investigate if the new IVIG Privigen causes more headaches in pediatric patients than other IVIG such as Nanogam, Multigam and Kiovig.
Material and methods : This is a retrospective study : in the first part, the data of the children treated with IVIG since 2008 will be studied. We will look for the incidence of headaches in relation to the used product. The second part of the study is a survey data collection. It will aim to evaluate their headaches during/before/after the treatment. Other adverse events such as fatigue, nausea and fever will also be evaluated.
Results : 21.9% suffered from headaches with Privigen, 20.4% with non-Privigen IVIG. Only in 56.3% of the Privigen group and in 63.3% of the other group was there use of precautionary measures. There tend to be less headaches in patients getting higher dosis (p:0.045). Fatigue is the most common AE with 80.6% experiencing it. This was also the most invalidating AE, i.e. school absenteeism.
Conclusions : Privigen didn’t cause more headaches than the alternative IVIG products. On the other hand, fatigue is an important cause of morbidity in IVIG therapy. Precautionary measures should be used more.
Intravenous Immunoglobulin (IVIG) has been established for the treatment of various autoimmune and systemic inflammatory conditions. Several modes of action including the modulation Fc receptor function, interference with complement activation and cytokine network, and provision of anti-idiotypic antibodies have been proposed. We show here that anti-RAGE (receptor for advanced glycosylation endproducts) IgGs, contained in the IVIG preparation KIOVIG, are predominantly from the IgG2 subclass.
A synthetic N-terminal human RAGE peptide was used to set up an ELISA and after immobilization to purify anti-RAGE IgG from KIOVIG. IgG subclasses were measured with ELISAs; α2,6-bound sialic acid levels were determined with a lectin binding assay using Sambucus nigra agglutinin.
Uniform anti-RAGE IgG titer were found in 14 lots of KIOVIG. Affinity purification provided a fraction counting for 0.07% of the loaded IgG with an anti-RAGE IgG concentration 300-times higher than that of the starting material. IgG2 counted for 88% of the total IgG which was more than twice as high as that measured for the starting material. The content of α2,6-bound sialic acid was reduced and made up only 63% of that measured for the starting material.
Naturally occurring anti-RAGE IgGs predominantly belong to the IgG2 subclass. IgG2 antibodies have low affinities to all Fcg-receptors and activate complement less effectively than IgG3 or IgG1. Binding of naturally occurring anti-RAGE IgG to cell surface expressed RAGE could inhibit activating downstream signaling and due to the low effector functions of these IgG2 antibodies not results in destruction of the RAGE-expressing cell.
Activating PIK3CD mutations confer increased lifetime risk of EBV-associated lymphoma, recurrent infections, and immune cytopenias. Allogeneic HCT is curative, but risk of graft failure is high across transplantation platforms, and comorbidities may preclude myeloablative conditioning (MAC). We compare the outcomes of 3 PIK3CD patients transplanted using a serotherapy-free reduced-intensity-conditioning (RIC) platform including sirolimus for graft-versus-host disease (GVHD) prophylaxis and 3 subsequent patients who received a modified RIC platform designed to reduce graft failure.
Six PIK3CD patients received one of two HCT platforms (Figure 1).
All patients are alive (Figure 2). P1 has phenotype reversal despite ongoing mixed donor chimerism. P2 has full donor chimerism and resolution of pre-HCT chronic infections, but a course complicated by CMV pneumonitis and focal segmental glomerulosclerosis requiring ongoing immunosuppression. P3 had primary graft failure requiring a second, alemtuzumab-containing RIC HCT, with threatened secondary graft failure but increased donor chimerism upon withdrawal of sirolimus. He developed Grade III acute GVHD following donor lymphocyte infusion but is currently clinically well, off immunosuppression. P4, P5, and P6 are engrafted, with early signs of phenotype reversal and no GVHD in P4 and P5.
Our experience suggests that enhancing host lymphodepletion pre-HCT and avoiding post-HCT exposure to sirolimus, which may provide survival advantage to host cells, improves engraftment outcomes in PIK3CD patients. While follow up is short for the patients receiving our modified platform, their robust donor chimerism and lack of GVHD to date are encouraging and show MAC is not necessary to ensure engraftment in this high-risk population.
Interferon-γ receptor 1 (INFGR1) deficiency is a severe form of Mendelian susceptibility to mycobacterial disease (MSMD) that characterized by predisposition to infections caused by weakly virulent Mycobacteria and Salmonella. INFGR1deficiency leads to loss of the cellular responsiveness to type II Interferon (INF-γ) which plays a major role in controlling viruses and intracellular bacteria. On the other hand, type I interferons like INF-α and β are critical for defense against viruses. In this report, we examined the response of IFN–β therapy against invasive mycobacterial infection in a patient with INFGR1 deficiency.
A 16-year-old girl presented with disseminated BCGitis early in life that was treated successfully with antimycobacterial medications. Subsequently, she presented with recurrent pneumonia and lymphadenopathy. Her lung biopsy grew multidrug resistant Mycobacterium abscesses. Multiple antimycobacterial medications were tried without improvement. Her genetic testing revealed heterozygous frameshift mutation in INFGR1 (c.819-822delTAAT). By 14 years of age, she started to have persistent headache and brain imaging showed diffuse infiltrative process involving right side of skull base and deep neck spaces with intracranial extension (Fig-1a).Biopsy of extended nasopharyngeal lesion part grew the same Mycobacterium abscesses.
She was started on IFN–β therapy in addition to her previous antimicrobial medications that leads to dramatic response (Fig-1b).
IFN–β might be a useful therapy for invasive CNS mycobacterial infections in INFGR1-deficient patients. While antimicrobial therapies are the definitive curative therapy for mycobacterial infections, the availability of adjunct therapies like IFN- β should enable management of persistent infections especially for those with complete INFGR1 deficiency.
Immunoglobulin replacement therapy (IgGRT) in CVID aims to reduce recurrent infections and increased mortality. We aimed to build a CVID health-economic model and to evaluate the cost-utility (CU) of IgGRT (intervention) compared to no IgGRT (comparator).
Based on a literature review, we built a Markov chain model with seven distinct health states (cycle length 1 month), simulating progression from a ‘controlled state’ to minor infections, major infections, bronchiectasis, auto-immune disease, cancer and death. Time horizon was set at 50 years. The outcomes included Quality-Adjusted Life Years (QALYs) and healthcare costs, both were extracted from publically available sources. Annual discounting was set at 3% for QALYs and 6% for costs. Monthly probabilities were converted from rates using the followingformula: rate=−ln(1-p)/t.
Cumulative 50-years-mortality was 98% in the no IgGRT group and 45% in case of IgGRT. The discounted cost and QALY results were as follows:
Healthcare cost total
The incremental cost-utility ratio (ICUR) was €29,454/QALY after discounting.
Without IgGRT, healthcare costs are limited because of the lack of associated treatment costs and high patient mortality. IgGRT increases survival and QoL with an incremental benefit per patient estimated at 10.4 QALYs. The ICUR is ~ €29,500/QALY which is illustrating the efficiency of optimal IgG-treatment.
) A one-year-old girl with immune deficiency with necrotic ulcer in the left axillary region of the autolytic debridement and infection control, and using advanced dressings during a one-month period completely healing .
A 2 years girl old I1 10 R deficiency that caused digestive problems and caused ileostomy and prolapsed , separation which was completely repaired during 15 days by managing defecation and using colostomy bags and appropriate powder and rings.
A 9-month-old boy suffered from necrotic and protogenos ulcers due to insect bites caused wounds in each of the eight regions of both heath and abdomen, and the left and right legs caused immunodeficiency disorder. Healing wound with advance dressing include : honey D and hydrofiber and alginate dressings and honey jel and hydroclean plus control the infection within 45 completely closed wounds.
Primary immunodeficiency are growing of disorders that presented with infections autoimmune and malignancy .These patients are prone with skin ulcers, sometimes associated with morbidity and mortality.
Here we want to report three case of PID that wound healing is accelerated by advanced dressing and helped to improve the quality of life of these patients and their parents
Three case PID that was referred to mofid children hospital with wound and ulcer around ileostomy were studied
Protocols that use advanced ways of management wound healing in PID good help to improvement quality of life .
Repair wounds, and improve the quality of life of children and parents andcontrol the complications of the disease.
Mycophenolate mofetil (MMF) is an immunosuppressive agent that exerts relatively selective antiproliferative effects on T and B lymphocytes.
The side effect profile of mycophenolate mofetil is generally at least as good as those of most immunomodulatory agents used in autoinmmune diseases.
Gastrointestinal symptoms and dose-related bone marrow suppression are the most commonly observed adverse effects, but these usually resolve with dose adjustments.
CASE REPORT :
A case of a 65 year old patient with a history of Raynaud’s phenomenon and overlap syndrome (1/1200 FAN, antiKU+) with pulmonary involvement NSIP initiates drug treatment with 40 mg of prednisone and 2000 mg/day MMF. After 7 months of treatment, the patient comes to the guard for presenting febrile syndrome of 2 days of evolution, diarrhea and marked weight loss.
The admission laboratory: Hypogammaglobulinemia 0.15.Lymphopenia.IgA: 10- IgG <200, IgM 20.Absolute value of CD 4 70, CD8 107.HBV, HIV,HCV- CMV IgM +IgG. Charge CMV: 5353.
A diagnosis of CMV colitis was made and which was confirmed by endoscopic biopsy.
She was treated with 3 weeks course of Valganciclovir with excellent response.It evolves with a good response, recovering the deficit in cellular immunity, requiring Gg EV after 3 months.
DISCUSSION:Is mycophenolate a drug capable of generating alteration of cellular and humoral immunity?
The reported cases of alteration of cellular and humoral immunity by mycophenolate were very low.Only 3 cases were reported (Boddana 2011; Keven 2003; Robertson 2009).It is a very rare adverse effect. The purpose of this report is to highlight a potentially significant immune dysfunction following Mycophenolate therapy.