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Allografting

Allogeneic bone marrow transplantation for juvenile myelomonocytic leukemia: a single center experience of 23 patients

Bone Marrow Transplantation volume 35, pages 455–461 (2005)Cite this article

Summary:

Juvenile myelomonocytic leukemia (JMML) is a childhood leukemia for which allogeneic BMT is the only curative therapy. At our pediatric stem cell transplantation unit, we performed 26 BMTs in 23 children (age 0.5–12.7 years). Conditioning was CY/TBI based (1980–1996, n=14) or BU/CY/melphalan based (1996–2001, n=9). Donors were HLA-identical siblings (n=11), unrelated volunteers (n=9) or mismatched family members (n=3). A total of 10 patients survive in CR (median follow-up 6.8 years, range 3.1–22.2 years). Relapse or persistent disease was observed in eight and two patients, respectively. Nine of these patients died, one achieved a second remission following acute nonlymphatic leukemia chemotherapy (duration to date 5.3 years). Transplant-related mortality occurred in four patients. Overall survival at 5 and 10 years was 43.5%. Using T-cell-depleted, one-antigen mismatched unrelated donors was the only significant adverse factor associated with relapse in multivariate analysis (P=0.039, hazard ratio 4.9). Together with a trend towards less relapse in patients with graft-versus-host-disease and in patients transplanted with matched unrelated donors, this suggests a graft-versus-leukemia effect of allogeneic BMT in JMML.

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References

  1. Bennett JM, Catovsky D, Daniel MT et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982; 51: 189–199.

    Article  CAS  PubMed  Google Scholar 

  2. Aricò M, Biondi A, Pui CH . Juvenile myelomonocytic leukemia. Blood 1997; 90: 479–488.

    PubMed  Google Scholar 

  3. Hasle H, Niemeyer CM, Chessels JM et al. A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. Leukemia 2003; 17: 277–282.

    Article  CAS  PubMed  Google Scholar 

  4. Side LE, Emanuel PD, Taylor B et al. Mutations of the NF1 gene in children with juvenile myelomonocytic leukemia without clinical evidence of neurofibromatosis, type 1. Blood 1998; 92: 267–272.

    CAS  PubMed  Google Scholar 

  5. Flotho C, Valcamonica S, Mach-Pascual S et al. RAS mutations and clonality analysis in children with juvenile myelomonocytic leukemia (JMML). Leukemia 1999; 13: 32–37.

    Article  CAS  PubMed  Google Scholar 

  6. Niemeyer CM, Tartaglia M, Büchner J et al. Clinical characteristics of children with JMML and germline or somatic PTPN11 mutations, RAS mutations or neurofibromatosis type 1. Leuk Res 2003; 27 (Suppl 1. add): 3 (abstr. 1-9-246).

    Google Scholar 

  7. Tartaglia M, Niemeyer CM, Fragale A et al. Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Nat Genet 2003; 34: 148–150.

    Article  CAS  PubMed  Google Scholar 

  8. Niemeyer CM, Arico M, Basso G et al. Chronic myelomonocytic leukemia in childhood: a retrospective analysis of 110 cases. Blood 1997; 89: 3534–3543.

    CAS  PubMed  Google Scholar 

  9. Chan HSL, Estrov Z, Weitzmann SS, Freedman MH . The value of intensive combination chemotherapy for juvenile chronic myelogenous leukemia. J Clin Oncol 1987; 5: 1960–1967.

    Article  CAS  PubMed  Google Scholar 

  10. Woods WG, Barnard DR, Alonzo TA et al. Prospective study of 90 children requiring treatment for juvenile myelomonocytic leukemia or myelodysplastic syndrome: a report from the Children's Cancer Group. J Clin Oncol 2002; 20: 434–440.

    PubMed  Google Scholar 

  11. Locatelli F, Niemeyer C, Angelucci E et al. Allogeneic bone marrow transplantation for chronic myelomonocytic leukemia in childhood: a report from the European Working Group on Myelodysplastic Syndrome in Childhood. J Clin Oncol 1997; 15: 566–573.

    Article  CAS  PubMed  Google Scholar 

  12. Novitzky N . Myelodysplastic syndromes in children. A critical review of the clinical manifestations and management. Am J Hematol 2000; 63: 212–222.

    Article  CAS  PubMed  Google Scholar 

  13. Maguire AM, Vowels MR, Russell S et al. Allogeneic bone marrow transplant improves outcome for juvenile myelomonocytic leukaemia. J Paediatr Child Health 2002; 38: 166–169.

    Article  CAS  PubMed  Google Scholar 

  14. Manabe A, Okamura J, Yumura-Yagi K et al. MDS Committee of the Japanese Society of Pediatric Hematology. Allogeneic hematopoietic stem cell transplantation for 27 children with juvenile myelomonocytic leukemia diagnosed based on the criteria of the International JMML Working Group. Leukemia. 2002; 16: 645–649.

    Article  CAS  PubMed  Google Scholar 

  15. Smith FO, King R, Nelson G et al. Unrelated donor bone marrow transplantation for children with juvenile myelomonocytic leukaemia. Br J Haematol 2002; 116: 716–724.

    Article  PubMed  Google Scholar 

  16. Van't Veer-Korthof ET . Myelodysplastic syndromes in childhood: description of 11 cases. In: Schmalz F, Mufti GF (eds). Myelodysplastic Syndromes. Proceedings of the First International Conference on Myelodysplastic Syndromes. Springer Verlag: Heidelberg, Germany, 1992, pp 38–42.

    Chapter  Google Scholar 

  17. Locatelli F, Pession A, Comoli P et al. Role of allogeneic bone marrow transplantation from an HLA-identical sibling or a matched unrelated donor in the treatment of children with juvenile chronic myeloid leukaemia. Br J Haematol 1996; 92: 49–54.

    Article  CAS  PubMed  Google Scholar 

  18. Slaper-Cortenbach ICM, Wijngaarden-du Bois MJGJ, Vries-van Rossen A de et al. The depletion of T cells from haematopoietic stem cell transplants. Rheumatology 1999; 38: 751–754.

    Article  CAS  PubMed  Google Scholar 

  19. Glucksberg H, Storb R, Fefer A et al. Clinical manifestation of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors. Transplantation 1974; 18: 295–304.

    Article  CAS  PubMed  Google Scholar 

  20. Shulman HM, Sullivan KM, Weiden PL et al. Chronic graft-versus-host syndrome in man. Am J Med 1980; 69: 204–217.

    Article  CAS  PubMed  Google Scholar 

  21. Vossen JM, Heidt PJ, Berg H van den et al. Prevention of infection and graft-versus-host disease by suppression of intestinal microflora in children treated with allogeneic bone marrow transplantation. Eur J Clin Microbiol Infect Dis 1990; 9: 14–22.

    Article  CAS  PubMed  Google Scholar 

  22. Matthes-Martin S, Mann G, Peters C et al. Allogeneic bone marrow transplantation for juvenile myelomonocytic leukaemia: a single centre experience and review of the literature. Bone Marrow Transplant 2000; 26: 377–382.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Mrs JDJ Bakker-Steeneveld for expert data managing, Dr R Wolterbeek for help with statistical analysis, Dutch pediatricians for referring patients for BMT, and the Dutch Childhood Leukemia Study Group for ANLL-chemotherapy protocols.

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Author notes

  1. P P Snijder

    Present address: Institute for Child Psychiatry, Oegstgeest, The Netherlands

Authors and Affiliations

  1. Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands

    E T Korthof, P P Snijder, A A de Graaff, A C Lankester, R G M Bredius, L M Ball, J M Vossen & R M Egeler

  2. Europdonor Foundation, Leiden, The Netherlands

    J L W T Lie

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  1. E T Korthof
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Correspondence to E T Korthof.

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Korthof, E., Snijder, P., de Graaff, A. et al. Allogeneic bone marrow transplantation for juvenile myelomonocytic leukemia: a single center experience of 23 patients. Bone Marrow Transplant 35, 455–461 (2005). https://doi.org/10.1038/sj.bmt.1704778

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