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Room
Poster Area
Date
19.09.2019, Thursday
Session Time
10:00 - 17:00
Poster Display Malignancy and PID

THE ASSOCIATION OF LYMPHOMA WITH PRIMARY IMMUNODEFICIENCIES

Lecture Time
10:00 - 10:01
Room
Poster Area
Date
19.09.2019, Thursday
Session Time
10:00 - 17:00
Board Number
170
Presentation Topic
Malignancy and PID

Abstract

Background and Aims

Patients with primary immunodeficiency disorder(PID) have a markedly increased risk of lymphomas. Here, we report twelve patients with PID diagnosed as lymphoma. Our aim was to evaluate the characteristics of the patients with PID who were diagnosed with lymphoma.

Methods

Clinical, immunophenotypic and genetic analysis of 12 patients with PID were obtained from medical records of Hacettepe University Ihsan Dogramaci Children Hospital, Department of Pediatric Immunology from 2016 to 2019.

Results

Twelve patients (female/male:6/6) was diagnosed as lymphoma and PID. The consanguinity ratio was 66%. Nine patients(75%) were diagnosed with lymphoma before PID. PID cases included combined immune deficiency(n:11) and ataxia telangiectasia(n:1). Three patients had defects in LRBA, while two patients and one patient had PI3KCD and STK4 defects, respectively.

Recurrent repiratory tract infections(83%) and chronic lung disease(66%) occurred in patients. Immune thrombocytopenic purpura(n:2), autoimmune hemolytic anemia(n:2), Celiac disease(n:1), amiloidosis(n:1), optic neuritis(n:1), psoriasis(n:1) and lymphoproliferation (lymphadenopathy(100%) and splenomegaly(83%)) were also reported.

The lymphoma was associated with Epstein-Barr virus (EBV) in 7 patients. Five of twelve patients (41%) are in remission, two patients(18%) are receving chemotherapy and five patients(41%) suffered from relapse within two year. Of the five patients who experienced relapse, three patients are in the second remission, and one patient is receiving chemotherapy. One patient with STK4 deficiency died from pneumonia during relapse chemotherapy.

Conclusions

Malignancies may be the first or only sign of an underlying PID. Patients diagnosed with lymphoma should be considered to have a PID, if there is parental consanguinity, EBV assosiation, recurrent and severe infections, autoimmunity and lymphoproliferation.

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Poster Display Other

A MYELODYSPLASTIC SYNDROME THAT HIDES A CHRONIC GRANULOMATOUS DISEASE :

Lecture Time
10:01 - 10:02
Room
Poster Area
Date
19.09.2019, Thursday
Session Time
10:00 - 17:00
Board Number
173
Presentation Topic
Other

Abstract

Background and Aims

Chronic granulomatous disease ( CGD) is a rare primary immunodeficiency caused by defects in any of the five subnits of the NADPH oxidase complex responsible for the respiratory burst in phagocytic leukocytes.

Methods

We report here the case of a 3 year 6/12 old boy , diagnosed with a myelodysplastic syndrome at the age of 18 months.

He presented several infections such a renal abcess, anal abcess that was not explained by his MDS .An exploration of the immunity was done and a flow cytometric dihydrorhodamine (DHR) neutrophil respiratory burst assay concludes to a CGD.

Results

CGD is a rare PID and the probability to be associated to an other disease is very weak.

The case of this young boy is interesting because he presented first a MDS wich required an hematological disease.

The abscesses were the initial presentation of the CGD in our patient and occur at the age of 36 months

Conclusions

CGD is a rare PID that usually established in life before 5 years old.

The association with an other chronic disease is exceptionnel. A genetic study would have been desirable to see if there is any relationship between CGD and MDS.

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Poster Display Therapy

A SYSTEMATIC LITERATURE REVIEW ON THE DISEASE BURDEN OF SECONDARY IMMUNODEFICIENCY DISEASE (SID)

Lecture Time
10:02 - 10:03
Room
Poster Area
Date
19.09.2019, Thursday
Session Time
10:00 - 17:00
Board Number
174
Presentation Topic
Therapy

Abstract

Background and Aims

Secondary immunodeficiency disease (SID) is a broad group of diseases characterized by hypogammaglobulinemia and caused by heterogenous etiologies such as hematological malignancies (HMs) and stem cell transplantation (SCT). This study summarized the scientific literature on disease burden of SID in patients with HMs or SCT.

Methods

Systematic searches were conducted through Medline, EMBASE, the Cochrane Library, and other databases to identify English-language articles from 1994 to 2018 reporting on the clinical, humanistic, and economic burden of SID due to HMs or SCT.

Results

Of 906 unique publications, 21 (RCTs, n=6; observational studies, n=15) met eligibility criteria. In most (n=13) studies, patients received intravenous immunoglobulin replacement therapy (IGRT). Several studies indicated significant reductions in the number of serious bacterial infections (n=2), hospitalizations (n=2), and hospital lengths of stay (n=1) with IGRT. Two studies reported reduced usage of antibiotic therapy with IGRT; however, 1 study found no statistically significant difference. Only 3 studies reported on quality of life (all used SF-36 or a derivative measure). No economic studies were identified. Overall, the findings suggested some beneficial effects of IGRT on clinical outcomes and quality of life; however, disparate definitions of SID and serum IgG thresholds, infrequent reporting of statistical significance, and scarcity of clinical trial data post-1990s present potential areas for further investigation.

Conclusions

The paucity of available data indicates a clear unmet need for healthcare professionals to have current evidence available for assessing the efficacy and potential humanistic and economic benefits of IGRT in patients with SID.

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Poster Display Malignancy and PID

GENOTYPE-PHENOTYPE VARIATIONS AND SPECTRUM OF MALIGNANCIES IN PATIENTS WITH NOONAN SYNDROME: A REVIEW OF LITERATURE

Lecture Time
10:03 - 10:04
Room
Poster Area
Date
19.09.2019, Thursday
Session Time
10:00 - 17:00
Board Number
179
Presentation Topic
Malignancy and PID

Abstract

Background and Aims

Noonan syndrome (NS)the commonest RASopathy, autosomal dominant trait, characterized by short stature, craniofacial dysmorphism, congenital heart defects and susceptibility to cancer. A relationship is suggested between the underlying genotype and the apparent phenotype. The aim of this review is to examine NS’s genotype-phenotype variations and the spectrum of malignancies.

Methods

A review of previously published literature through PubMed database. Articles were chosen if they characterized NS, were available in English and were peer reviewed.

Results

Ninety-three articles met the inclusion criteria. NS was described as the commonest of an inherited overlapping group of disorders collectively known as “RASopathies”. Heterozygous mutations in PTPN11, SOS1, KRAS, NRAS, BRAF, SHOC2, CBL, and others were identified as leading etiologies through abnormal activation of the RAS-MAPK signaling that's also incriminated in oncogenesis. Forty-seven articles described abnormal myelopoiesis, particularly Juvenile Myelo-Monocytic Leukemia (JMML) as the commonest malignancies followed by CNS tumors. Solid tumors as neuroblastoma, chondroma and rhabdomyosarcoma were limited to case reports. The clinical features of NS were described in 21 articles and another 7 detailed its genotypic variations. Genotype-phenotype variabilities were described by many authors. Germline CBL mutations had increased risk of neurological disorders, JMML but lower risk for cardiac defects, growth retardation, and cryptorchidism. NRAS positive NS linked to hyperpigmentation. Neurofibromatosis-Noonan (NFNS) harbor both PTPN11 and neurofibromin mutations were described distinctly.

Conclusions

Available research suggests the relationship between the underlying genotype and the variably expressed phenotype in NS.Mutations in the RAS-MAPK pathway that are potential therapeutic targets,drive oncogenesis and should be molecularly identified in every patient.

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Poster Display T Cell Biology

UNUSUAL PRESENTATIONS OF HODGKIN LYMPHOMA

Lecture Time
10:04 - 10:05
Room
Poster Area
Date
19.09.2019, Thursday
Session Time
10:00 - 17:00
Board Number
180
Presentation Topic
T Cell Biology

Abstract

Background and Aims

Paraneoplastic syndrome(s)(PNSs); A rare phenomenon charcterizes HL occurring months/years before diagnosis-typically an advanced stage with B symptoms-or preceding relapse.Aims:To evaluate the available evidence regarding PNSs in HL.

Methods

A systematic review of literature on paraneoplastic syndromes in HL according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The online database PubMed was searched using wth key words “paraneoplastic syndromes and Hodgkin lymphoma”, “vanishing bile duct syndrome in Hodgkin lymphoma” and “neurological manifestations in Hodgkin lymphoma”. Studies done on humans, published in the last 10 years were included.

Results

112 studies met the inclusion criteria. 23 review articles and 83 case reports were identified. The most common PNSs are the neurologic manifestations including paraneoplastic cerebellar degeneration (PCD),limbic encephalitis,Guillain-Barré syndrome,autonomic neuropathy and motor neuron disease.An immune related phenomenon is the proposed pathogenesis of PNSs supported by the presence of anti-Tr antibodies against Purkinje cells and anti-mGluR5 antibodies in the case of PCD and in HL and limbic encephalopathy (Ophelia syndrome) respectively. The most serious hepatic affection:Vanishing Bile Duct syndrome (VBDS) .Reported cases of toxic epidermal necrolysis, Stevens Johnson syndrome and angiokeratoma corpora diffusum were the most severe dermatologic manifestations. Early initiation of chemotherapy with high dose steroids and IVIG is the mainstay of tratment. Prognosis is unfavorable sometimes fatal as in VBDS progressing to liver cell failure.

Conclusions

The management of PNSs is challenging. Most available evidence is centered on the use of steroids, IVIG concomitantly with chemotherapy based on case reports and case series. Establishing evidence-based guidelines is mandatory to improve outcome.

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Poster Display Other

MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASES (MSMD) IN IL12RB1 DEFICIENT CHILD

Lecture Time
10:05 - 10:06
Room
Poster Area
Date
19.09.2019, Thursday
Session Time
10:00 - 17:00
Board Number
181
Presentation Topic
Other

Abstract

Background and Aims

Introduction:
MSMD is caused by genetic defects in the mononuclear phagocyte/T helper cell type1 (Th1) pathway. Common to all the infections seen in MSMD are defects in the interferon gamma (IFN-gamma)-interleukin 12(IL-12) pathway and/or supporting accessory pathways.
Purpose: case report of a girl with MSMD by default expression of IL-12RB1

Methods

Observation:
This is a 07-year-old girl.She presented a disseminated BCG infection at age of 7 months, a cutaneous and ganglionic tuberculosis at the age of 13 months. Treated with antituberculosis,. A salmonella cervical adenitis at the age of 5 years. She received second-line anti-tuberculosis.The IFN gamma assay is negative with no secretion after mitogen stimulation and tuberculous antigens.The genetic study has found a mutation in the gene encoding the IL-12 receptor beta1 (IL-12RB1).The child presented for one year a tubulo-interstitial nephritis secondary to anti tuberculosis treatment currently in end-stage renal failure under dialysis.

Results

Discussion:
IL-12Rbeta1 deficiency may present with disseminated tuberculosis or nontuberculous mycobacterial and Salmonella infections in the setting of IL-12 unresponsiveness.
The treatment consists of a suitable and prolonged antibiotherapy, especially in the case of disseminated infections with non-typhoid salmonella as in our patient. IFNγ is sometimes useful when the well-managed anti-mycobacterial treatment does not allow eradication of infectious foci.

Conclusions

It is a disease of good prognosis. In our patient the prognosis was clouded by toxic tubulointerstitial nephritis secondary to prolonged antibiotic therapy.

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Poster Display Malignancy and PID

SOMATIC STAT3 GOF MUTATION

Lecture Time
10:06 - 10:07
Room
Poster Area
Date
19.09.2019, Thursday
Session Time
10:00 - 17:00
Board Number
182
Presentation Topic
Malignancy and PID

Abstract

Background and Aims

STAT3 proteins are critical transcription factors which regulates transcription of the genes that play roles in prolifration, apoptosis, differentiation, inflammation and

survival. STAT3 genes can be affected by mutations related to the both Los of Function (LOS) and Gain of Function (GOF). STAT3 GOF have a wide range of phenotype consisting of recurrent infection, lymphoprolifration, autoimmunity, short stature and malignancy.

In this article we describe an 8 years old patient which his first presentation was an autoimmune anemia at age 3. he was referred to our immunolgy office at age 5 with previous history of hyper reactive airway disease, coombs positive autoimmune hemolytic anemia, refractory seizure, Pneumocystis Carinii Pnemonia (PCP) infection, recurrent sinopulmonary infections and otitis media, intermittent fever and neutropenia.His immunologic evaluation showed inadequate increase in IgG level despite of receiving IVIG due to hemolytic anemia, low levels of IgA and IgE and normal level of IgM wich were suggestive Hyper IgM Syndrome (HIGM). at age 8 his biopsy of mediastinum showed large B-cell lymphoma (CD20 positive).furthur evaluations showed decreased level of CD4 T cells in peripheral blood flow cytometry with decreased antibody titers to tetanus toxin.

Methods

Patient was referred to our office, he provided us with his dossier wich is involving all his ducuments since he was only 3 years old.

Results

Screening of primary immunodeficiency related genes showed Somatic STAT3 GOF mutation.what is patricular is mutation was found within somatic cells.

Conclusions

Contrary to our patient,all cases which were reported in three previous studies carried germline STAT3 GOF mutation.

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Poster Display Malignancy and PID

IMMUNE DYSREGULATION WITH LYMPHOPROLIFERATION PROGRESSING TO A RARE T-CELL NON-HODGKIN LYMPHOMA

Lecture Time
10:07 - 10:08
Room
Poster Area
Date
19.09.2019, Thursday
Session Time
10:00 - 17:00
Board Number
183
Presentation Topic
Malignancy and PID

Abstract

Background and Aims

Primary immunodeficiencies and immune dysregulation disorders have an increased susceptibility to develop lymphomas. The vast majority are B cell lymphomas, whereas T cell lymphomas (TCL) are extremely rare and carry a poor prognosis, similar as in the general population. Most cases of TCL were observed in patients with antibody deficiency or combined immunodeficiencies with associated or syndromic features.

Methods

We describe the case of a 46-year-old male patient.

Results

The patient presented in 2017 with recurrent skin abscesses and severe transient neutropenia. In addition, he developed diffuse lymphadenopathies and splenomegaly with reduced serum immunoglobulin levels (IgG and IgM) and peripheral blood analysis showed an atypical monoclonal CD4+CD7-lymphocytosis.

Lymph node biopsy showed atypical paracortical hypertrophy, suggestive of a reactive hyperplasia in the context of an underlying immunodeficiency. Two years later, the patient presented with B symptoms, generalized adenopathy and splenic infarction. Histologic examination of the spleen showed nodular white-pulp hyperplasia with periarteriolar T-zone hyperplasia and granulomas, as was observed in a cohort of CVID patients. A repeat lymph node biopsy revealed progression of the clonal lymphoid hyperplasia to a peripheral PTCL-NOS (peripheral T cell non-Hodgkin lymphoma, not otherwise specified).

Conclusions

Immunodeficiency-associated lymphoid hyperplasia is challenging. Isolated evidence of clonality in biopsy material can precede the diagnosis of lymphoma. Currently, further investigations are ongoing in this patient, to define a genetic cause for the underlying immunodeficiency by analysis for germline-encoded mutations in patient’s fibroblasts and somatic mutational analysis of the tumor sample.

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