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Secondary Philadelphia chromosome after non-myeloablative peripheral blood stem cell transplantation for a myelodysplastic syndrome in transformation

Bone Marrow Transplantation volume 33, pages 247–249 (2004)Cite this article

A secondary Philadelphia chromosome (Ph) appearing during the late course of hematopoietic malignancies is exceptional,1,2 frequently therapy-related and associated with poor prognosis.3 In addition, Ph is very rarely observed in myelodysplastic syndromes, and is usually associated with a minor breakpoint (p190Bcr-Abl).4 Here, we report the first case of a secondary Ph with a minor breakpoint at relapse after a sibling-donor nonmyeloablative peripheral blood stem cell transplantation performed for a myelodysplastic syndrome in partial remission.

We describe here the first case of a secondary minor Bcr-Abl Ph occurring after non-myeloablative sibling-donor allogeneic hematopoietic stem cell transplantation, with poor prognosis. Secondary Ph occurring after conventional chemotherapy or autologous hematopoietic transplantations has already been reported a few times in the literature.1,3,4 In myelodysplastic syndromes, the Ph is an unusual finding (19 cases reported to date4,7,8), and mostly concomitant with acute transformation of the disease, as in our case. Since we could perform a retrospective analysis by FISH and RTRQ-PCR on the patient and donor's frozen cells along the course of the medical history, we could ensure that (1) the Ph has really been acquired after allogeneic transplantation and was not present at diagnosis, (2) this chromosomal abnormality was developed from recipient cells and not donor cells, and this was particularly important to point out as normal donors can harbor the Bcr-Abl+ translocation,10,11 (3) the Ph acquisition occurred shortly (3 months) after allogeneic transplantation and it is probably unlikely that conventional chemotherapy given initially (started 9 months earlier) could induce such genetic lesions, as it usually takes much longer time to occur,9 (4) a different cytological (polymorphic blasts, megakaryocytic dysplastic features), immunophenotypical (CD34negative), cytogenetical (Ph and 5q deletion) and molecular (p190Bcr-Abl transcript) phenotype than that was found from diagnosis. All these last features can be encountered in myelodysplastic syndromes,4,7 which illustrates here once again the genetic instability that characterizes myelodysplastic syndromes associated with the outgrowth of a new malignant Bcr-Abl+ leukemic subclone enhanced by post transplant immunosuppression. Unfortunately, imatinib mesylate, after an initial response, subsequently failed in long-term control of the disease as in blastic-phase CMLs.12

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Acknowledgements

This work was partially supported by a grant from the ‘Ligue Contre le Cancer de la Drôme’ (Valence, France).

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  1. Hematology Department, Edouard Herriot Hospital, 5, place d'Arsonval, Lyon, 69437, Cédex 03, France

    T Prebet, A-S Michallet, A Thiébaut, M Michallet & F E Nicolini

  2. Laboratory for Hematology, Edouard Herriot Hospital, 5, place d'Arsonval, Lyon, 69437, Cédex 03, France

    C Charrin, S Hayette & J-P Magaud

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  1. T Prebet
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Prebet, T., Michallet, AS., Charrin, C. et al. Secondary Philadelphia chromosome after non-myeloablative peripheral blood stem cell transplantation for a myelodysplastic syndrome in transformation. Bone Marrow Transplant 33, 247–249 (2004). https://doi.org/10.1038/sj.bmt.1704308

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