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ctt-journal > Maschan M.2 et al. (Abstract)

Maschan M.2 et al. (Abstract)

Cellular Therapy and Transplantation (CTT), Vol. 3, No. 12
doi: 10.3205/ctt-2011-No12-abstract32

© 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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Juvenile myelomonocytic leukemia: molecular genetic analysis and results of therapy

Michael A. Maschan, Vlasta O. Bobrynina, Lili A. Khachatryan, Dina D. Baidildina, Julia V. Skvortsova, Elena Yu. Osipova, Dmitri N. Balashov, Elena V. Skorobogatova, Galina A. Novichkova, Alexei A. Maschan

Federal Research Center for Pediatric Hematology, Oncology and Immunology, 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: Juvenile myelomonocytic leukemia (JMML) is a rare childhood hematological malignancy, with features of myelodysplasia and myeloproliferation. 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 JMML patients.

Patients and methods: Sixty-one JMML patients were included. Exons 3 and 13 of PTPN11, 2 and 3 NRAS, and KRAS, 8 and 9 CBL were sequenced directly. First-line therapy included 13-cis retinoic acid and cytosine arabinoside (differentiation therapy, DT) in 32 pts, and high-dose chemotherapy in 18 pts. HSCT was performed in 20 pts. The conditioning regimen was myeloablative in all cases with busulfan (n=15) and treosulfan (n=2) (3=unknown). Donors were matched sibling (n=5), matched unrelated (n=10) (with cord blood in 2 cases), and mismatched related (n=5).

Results: Somatic mutations in the studied genes were detected in 70% of patients, PTPN11-35%, NRAS: 14%, KRAS: 11%, and CBL: 13%. NRAS and KRAS mutations were associated with ages <1 year, HbF <1%, and good response to DT. Five-year survival (pOS) was 28±7%. In the whole group HSCT did not improve pOS (26±12 vs. 31±8%, p=ns), but when those with a good response to DT were excluded from analysis HSCT provided a significantly improved survival rate (35±13 vs. 0±0%, p = 0.0019).  

Conclusion: JMML is a biologically and clinically heterogeneous disease. It requires in-depth molecular analysis and a tailored approach to therapy.

Keywords: hematopoietic stem cell transplantation, juvenile myelomonocytic leukemia, molecular analysis, differentiation therapy