Welcome to the ESID 2022 Meeting Interactive Programme

Background and Aims

Hemophagocytic lymphohistiocytosis (HLH) is polygenetic disease caused by mutations in genes associated with granule-dependent lymphocyte-mediated cytotoxicity (PRF1, UNC13D, STX11, STXBP2, LYST, AP3B1, AP3D1 RAB27A, XIAP, SH2D1A).

Methods

We describe the clinical and immunological manifestations and mutation spectrum in HLH cohort (n=19) diagnosed in Belarus (n=15) and Ukraine (n=4) since 1991-2022.

Results

Enrolled patients were residents of Belarus (n=14), Ukraine (n=4) and Kazakhstan (n=1). Genetic diagnose of HLH was established in 12/19 patients, NK activity was checked in 5/19. UNC13D gene variants were revealed in 10 patients (4 patients from 2 families from Ukraine; 6-from 4 families, Belarus); 3 unrelated Belarusian and Ukrainian families had c.2346_2349delCTCC(p.R782fs in homozygous state, 4pts out of 2 families (Belarus)-in heterozygous compound. Also variants in XIAP(n=2) were detected.

One patient is alive after HSCT, one patient waiting for HSCT, 17 children died, 3 after HSCT, 8 were genetically diagnosed postmortem. 3/19pts had an "atypical" presentation, age of manifestation and death was 9m/2.5yr; 1.5yr/2.5yr, and 2yr/19yr (genetic diagnosis was established post-mortem in 3/3). "Atypical" manifestation was-lymphoproliferation (n=3), neurological presentation (brain cysts/epilepsy (n=1), disseminated encephalitis (n=1). Hemophagocytosis was not manifested biochemically during all period of observation; a small number of phagocytic macrophages were detected once in one patient’s bone marrow.

Conclusions

Our cohort of patients demonstrated a repeated mutation in the UNC13D gene- c.2346_2349delCTCC(p.R782fs), which may be associated with the “founder effect” in Slavic countries. Atypical manifestation causes difficulties in rapid diagnosis, fast sequencing of all PID genes are necessary for establishing correct diagnosis and start appropriate treatment.

Background and Aims

Primary immunodeficiencies (PIDs) are heterogeneous disorders, characterized by variable clinical and immunological features. We report on data collected from the Belarussian PID registry.

Methods

Clinical and laboratory data was collected from Belarusian patients with PIDs, treated at the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology in the Minsk Region and the Republican Research Center for Radiation Medicine and Human Ecology in Gomel.

Results

Collaboration with the J Project, the Jeffrey Modell Foundation significantly expands the possibilities of helping patients with PIDs in Belarus. The prevalence of PID in Belarus is 6.23 per 100,000 inhabitants. At the beginning of 2022, 621 cases of PIDs were registered, more than half of the patients were genetically confirmed diagnosed (62.8%, n=390). Based on the updated IUIS classification of 2019, PID distribution in Belarus showed that predominantly antibody deficiencies (32.53%, n=202) account for the majority of cases, followed by combined immunodeficiencies with associated or syndromic features (28.34%, n=176), complement deficiencies (14.98%, n=93), diseases of immune dysregulation (8.21%, n=51), immunodeficiencies affecting cellular and humoral immunity (7.25%, n=45) and congenital defects in phagocyte number or function (4.99%, n=31), autoinflammatory disorders (1.77%, n=11), bone marrow failure (1.13%, n=7), defects of innate immunity (0.81%, n=5). The distribution of patients with PID in the regions of Belarus is almost the same, however the prevalence of Ataxia-telangiectasia and Nijmegen syndrome is higher in Western Belarus.

Conclusions

Data from the PID Registry of Belarus contribute to the expansion of clinical knowledge about PID, help in the development of new diagnostic procedures and treatments.

Background and Aims

Wiskott-Aldrich syndrome (WAS) is a life-threatening primary immunodeficiency, associated with bleeding risk due to thrombocytopenia. We previously demonstrated that romiplostim is effective for thrombocytopenia treatment in 60% of WAS patients.

Methods

In this open-label prospective study WAS patients (0-18 years) were treated with romiplostim or eltrombopag. We assessed platelet response, proportion of patients additionally achieving platelet response by changing an arm of treatment, bleeding severity and adverse events. Criteria for switching were lack of efficacy, loss of long-term response and adverse events.

Results

21 patients underwent randomization. Mean age was 2.6 years [range 0.2-15.2]; mean platelet level, 23×10⁹/L [range 4-49]. The incidence of achieving platelet response did not differ between romiplostim (7/11 [64%]) and eltrombopag (5/10[50%]; 95% CI, 0.07-4.4; P=0.67) groups.

5/11 (45%) participants in romiplostim group and 6/10 (60%) in eltrombopag group required switch of therapy. Conversion to the alternative arm of treatment allowed to attain durable response in 1 non-responder in romiplostim group and in 2 non-responders in eltrombopag group. 1 eltrombopag responder was switched to romiplostim due to the severe adverse event (ALT/AST increase >3 norms) after 17 months of therapy and continued to have complete response.

The number of patients with grade 2-4 bleeding at baseline declined from 91% to 27% in romiplostim group and from 70% to 10% in eltrombopag group after 1 month of treatment (p=0.864).

Conclusions

Both romiplostim and eltrombopag are effective in WAS. We demonstrate that in cases of inefficiency switching to the another agonist is beneficial.