Jean Donadieu, France

Hopital Trousseau Pediatric hemato Oncology
Pediatrician and epidemiologist. Coordinator of the French Chronic neutropenia registry and reference center and of the French Histiocytosis registry and reference center for pediatric histiocytosis. Full time pratictionner in Trousseau Hospital, one the paris pediatric hospitals.

Presenter Of 4 Presentations

Oral Communications Malignancy and PID

WHIM SYNDROME IS ASSOCIATED WITH A HIGH INCIDENCE MALIGNANCIES MAINLY RELATED TO HPV- AND EBV- INFECTIONS

Lecture Time
11:10 - 11:20
Room
Copper
Date
19.09.2019, Thursday
Session Time
11:00 - 12:30
Presentation Topic
Malignancy and PID

Abstract

Background and Aims

Warts, hypogammaglobulinemia, infections, and myelokathexis syndrome (WHIMS) is a rare combined primary immunodeficiency caused by gain-of-function mutations in the chemokine receptor CXCR4 gene. While the susceptibility to human papillomavirus (HPV) induced malignancy is established, the overall malignancy risk is less well characterized. We present here an update on the global incidence of malignancy in WHIMS based on a literature review and data from the French Severe Chronic Neutropenia Registry.

Methods

We analyzed retrospective cohort data from 14 patients diagnosed with WHIMS from the French Severe Chronic Neutropenia Registry and conducted a literature review in PubMed to identify all cases of WHIMS associated with malignancy.

Results

Five Registry patients developed malignancy at median age of 37 years. The 40-years rate of malignancy was 46% (95% CI 17-88%). We observed two HPV-induced vulvar cancers (one lethal), 2 lymphomas (one bone, one skin lymphoma) and one basal cell carcinoma. In the literature, malignancy was reported in 12 reports (excluding our data) mainly in the 3 rd and 4 th decades. Malignancies included Epstein–Barr Virus (EBV) associated lymphoproliferative disorders, cutaneous B-cell lymphoma, melanoma, HPV oral squamous cell carcinoma, and multiple cases of HPV-related genital and anal cancers. In total, 8 cases of malignancy were linked to HPV and 3 to EBV. The CXCR4 variant Ser338* (c.1013C>G) was present in 6 WHIMS patients with malignancy reported in the literature.

Conclusions

Immunocompromised WHIMS patients are at high risk of malignancy, mainly HPV induced followed by lymphoma which is frequently EBV related.

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Meet the Expert Malignancy and PID

HEMATOPOIETIC STEM CELL TRANSPLANTATION MAY LOWER THE RISK OF LEUKEMIA IN ELANE NEUTROPENIA: HISTORICAL TRENDS FROM FRENCH SEVERE CHRONIC NEUTROPENIA REGISTRY (FSCNR) COHORT

Lecture Time
08:15 - 08:25
Room
Copper
Date
20.09.2019, Friday
Session Time
07:45 - 08:45
Presentation Topic
Malignancy and PID

Abstract

Background and Aims

ELANE neutropenia (EN) is associated with myelodysplasia/acute-leukemia (MDS-AL) as well as severe infections. As the risk of MDS-AL has been shown to be associated with the exposure to GCSF, since 2005, in France, patients that receive a high daily dose of GCSF (>15 μg/kg/day), are eligible for hematopoietic stem cell transplantation (HSCT), in addition to classic indications of HSCT (MDS-AL, or GCSF refractoriness). We analyzed the effect of this policy

Methods

Among 144 patients with ELANE neutropenia enrolled in the French Severe Chronic Neutropenia Registry (FSCNR), prospectively followed, we defined 2 groups according to the period of follow up. The first group called “before 2005” included patients born before 2005 and followed till 31/12/2004 (1588 person-years). The second one designed by “after 2005” comprised patients born after 2005 or patients born before 2005 but followed after 2005 till 31/03/2019 (1327 person-years).

Results

16 HSCT has been performed in our cohort (14 with long term survival) and 6 MDS-AL has been observed. 6 leukemic transformations occurred in the group “before 2005” and no “after 2005”. (Incidence 3.8 x 10-3 “before 2005” vs. 0 “after 2005”; p< 0.01) while 4 HSCT has been performed before 2005 and 12 since 2005 (incidence of HSCTs increased 2.5 x 10-3“before 2005” vs. 9 x 10-3 “after 2005”; p< 0.01).

Conclusions

Our results supported early HSCT in patients with ELANE mutations that received high GCSF doses (>15 μg/kg/day but not considered as refractory to GCSF) might lower the risk of leukemic transformation.

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Meet the Expert Malignancy and PID

DYNAMIC AND IMPACT OF ACQUIRED TP53 MUTATIONS IN THE HEMATOLOGICAL COMPLICATIONS OF SHWACHMAN-DIAMOND SYNDROME

Lecture Time
08:25 - 08:35
Room
Copper
Date
20.09.2019, Friday
Session Time
07:45 - 08:45
Presentation Topic
Malignancy and PID

Abstract

Background and Aims

Shwachman-Diamond Syndrome (SDS) due to SBDS mutations is associated with a high rate of leukemic transformation. Mutational somatic profile was evaluated on a cohort of patients from the french SCN registry

Methods

Hematological data were correlated with targeted NGS performed in SDS cohort of 57 patients.

Results

We detect the presence of an acquired TP 53 mutation in 32/57 SDS patients (56%) with VAF (Variant Allele Frequency) ranging from 0.5% to 82.6%. Five patients had more than one mutation either concomitantly or at different times of evolution. The other mutations detected affect the DNMT3A (2 patients), IDH1, SF3B1, PHF6, SMC1A, ASXL2, FLT3 and KRAS genes. The longitudinal follow-up of 13 patients shows that the VAFs of TP53 mutations can grow or decrease and that clones can become detectable or undetectable over time in the same patient. In 11 patients we detected TP53 mutations with VAFs greater than 10% (affecting more than 20% of the cells analyzed). Of these, 5 patients were in fatal leukemic transformation with complex karyotype, 1 were at the SMD stage with excess blasts, 2 were in severe cytopenia without SMD, and 3 had no severe cytopenia with stable or decreased VAF over time. In the rest of the cohort, we observe that patients who do not have mutated TP53 clone clones or clones with low VAF (<10%) have few severe hematologic complications.

Conclusions

Mutations of TP53 are detected in half of the SDS and constitute a somatic event essential in the evolution in SMD or LAM, detectable early.

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Parallel Session No Topic Needed

BRAF INHIBITORS AND LCH

Lecture Time
11:25 - 11:50
Room
Copper
Date
20.09.2019, Friday
Session Time
11:00 - 12:30
Presentation Topic
No Topic Needed