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ctt-journal > Maschan M.1 et al. (Abstract)

Maschan M.1 et al. (Abstract)

Cellular Therapy and Transplantation (CTT), Vol. 3, No. 12
doi: 10.3205/ctt-2011-No12-abstract31

© The Authors. This abstract is provided under the following license: Creative Commons Attribution 3.0 Unported

Abstract accepted for "5th Raisa Gorbacheva Memorial Meeting Hematopoietic Stem Cell Transplantation in Children and Adults", Saint Petersburg, Russia, September 18–20, 2011

Preliminary Program

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Primary hemophagocytic lymphohistiocytosis: molecular genetic analysis and results of therapy

Michael A. Maschan, Natalia V. Poltavets, Lili A. Khachatryan, Irina I. Kalinina, Dina D. Baidildina, Julia V. Skvortsova, Elena V. Suntsova, Pavel E. Trakhtman, Elena V. Skorobogatova, Galina A. Novichkova, Alexei A. Maschan

Federal Research Center for Pediatric Hematology, Oncology and Immunology, Medico-genetic scientific center of the Russian academy of medical sciences, Moscow, Russia

Correspondence: Michael A. Maschan, Federal Research Center for Pediatric Hematology, Oncology and Immunology, 117, Leninskii pr, 117997, Moscow, Russia, E-mail: mmaschan@spam is badyandex.ru

Abstract

Introduction: Familial hemophagocytic lymphohistiocytosis (FHL) is rare genetic immune deficiency caused by defects of cellular cytotoxicity mechanisms. Hematopoietic stem cell transplantation (HSCT) remains the only curative therapy.

Aims of study: To perform molecular analysis and retrospective analysis of therapy outcomes in a group of FHL patients.

Patients and methods: Thirty-four FHL patients were included. All exons of PRF1, UNC13D, STX, STXBP, SH2D1A and XIAP genes were sequenced. Immune suppressive therapy was delivered to 29 pts according to HLH-94\2004 protocol. Twelve patients were transplanted after myeloablative (n=8) or reduced-intensity (n=4) conditioning. Donors were matched siblings in 3 pts, matched unrelated in 7, and mismatched family in 2 cases.

Results: Germinal mutations in the studied genes were detected in 54% pts, UNC13D: 38%, PRF1: 4%, STX11: 4%, and SH2D1A: 7.5%. No relevant clinico-genetic correlations were discovered. Five-year survival (рOS) was 12±7%. The only factor affecting survival was HSCT, рOS=30±16% vs. 0%, log-rank p=0.0005. The major reason for treatment failure after HSCT was transplant-related mortality, TRM = 54 ± 15%.

Conclusion: Genetic defects in UNC13D gene are the most frequent cause of FHL in Russia. HSCT should be offered to all patients with FHL as the only curative therapy, irrespective of "perfect donor" availability.

Keywords: hematopoietic stem cell transplantation, familial hemophagocytic lymphohistiocytosis, molecular analysis, transplant-related mortality