Background and Aims

PIDs are characterized by recurrent infections and increased risk of malignancies because of the reduced immunological surveillance against cancer cells and oncogenic viruses.

Methods

We report the incidence and the characteristics of the treatment of tumors among 690 patients with PID, diagnosed from 1990 until 2017 in Brescia.

Results

Out of 690 patients, 25 patients(3.6%) developed 33 tumors.Of the 25 affected patients, 8 patients suffered from CVID, 5 from CID, 3 from AT, 2 from HSP2, 2 from XLA, 2 from WAS, 2 from HIES, 1 from SCID.The age at diagnosis ranged from 1 to 52 years, with a median age of 19.6 years. The time between diagnosis of PID and onset of tumor was short, often<1 year between diagnosis and appearance of cancer in case of CID.Moreover, in two cases of CID, the diagnosis of cancer was made before the diagnosis of PID, so cancer was the onset clinical manifestation.Hematological malignancies were prevalent(22/33,66.7%) with a minority of solid tumors(11/33,33.33%).In particular Non-Hodgkin lymphomas were the most frequent(16/33,48.48%).In total 13 patients survived(52%) and tumor was the main cause of death(7 cases).Two patients underwent BMT once the disease was in remission.

Conclusions

Malignancies in PID patients can be successful treated if a prompt diagnosis is posed.Moreover tailored treatment is often necessary.Our data suggest an encouraging survival rate(52%) in lymphomas.

ESID Subregistry on PID and Malignancies was created with aim to analyze more in depth the phenomenon and to understand how to improve the prognosis of these patients often considered at poor prognosis.

Background and Aims

ADA-SCID is a rare disease(10-15% of SCID) due to the mutations of the ADA-gene resulting in the accumulation of high systemic levels of ADA toxic metabolites.There are 3 treatment options:HSCT from matched sibling donor(the best therapeutic options), Enzyme Replacement Therapy(ERT) with PEG-ADA to manage disease in short term, autologous Gene Therapy(GT) or allogeneic HSCT from MUD/parents.Long term ERT is a therapeutic options although with time long-term immune reconstitution may be sub-optimal in some patients.

Methods

In our center 29 ADA patients were diagnosed,of which three were treated with ERT from diagnosis.

Results

The patients were diagnosed early:1 prenatal diagnosis, at 2 months and 3 months of age.They started immediately ERT.Median time of ERT follow up is 20 years.They are well detoxified(median value of %dAXP is 0.65%), but have very low level of lymphocytes.An approach to correct the immunological situation by GT with peripheral stem cells, considering the bone marrow stem cell exhaustion in these patients, was hypothesized but was inapplicable.At diagnosis, approximately 20 years ago, gene therapy wasn’t a consolidates therapy and ERT seemed the more solid therapeutic option.In the process of programming HSCT, unfortunately, one of these patients has developed plasmablastic lymphoma after 21 years of ERT.Last follow up shows 12/mm3 CD3+, 10/mm3 CD19+ and %dAXP 1.7%.

Conclusions

Our experience shows that ERT gives a good therapeutic option as bridge therapy for HSCT.For patients in long-term ERT, would be beneficial the use of the newly approved recombinant PEG-ADA.Nevertheless strict monitoring would be necessary to check the results of this new therapeutical approach.

Background and Aims

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.

Methods

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.

Results

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.

Conclusions

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.