Hematopoietic stem cell transplantation for de novo acute megakaryocytic leukemia in first complete remission: a retrospective study of the European Group for Blood and Marrow Transplantation (EBMT).
ABSTRACT Acute megakaryoblastic leukemia (M7 AML) is a highly aggressive disease. We evaluated outcomes in 57 children (11 with Down syndrome) and 69 adults with M7 AML after first complete remission (CR1) following autologous or HLA-identical allogeneic transplantation. Characteristics of the recipients of autologous transplants (38 children, 37 adults) were, respectively: median age, 1.7 and 46 years; non-total body irradiation (non-TBI) conditioning regimen, 97% and 70%; bone marrow as stem cell source, 74% and 43%. Characteristics of the recipients of allogeneic transplants (19 children, 32 adults) were, respectively: median age, 2.8 and 37 years; non-TBI regimen, 63% and 42%; bone marrow as stem cell source, 95% and 69%. Autologous transplantation benefited children more; the relapse rate was high in adults. Results for autologous transplantation were (children and adults, respectively): engraftment, 90% and 100%; 3-year treatment-related mortality (TRM) rate, 3% and 8%; relapse rate, 45% and 64%; leukemia-free survival (LFS) rate, 52% and 27%; overall survival (OS) rate, 61% and 30%. After allogeneic transplantation, TRM was fairly low in children and adults, and relapse rates were lower than after autologous transplantation. Results for allogeneic transplantation were, respectively: engraftment, 95% and 90%; TRM, 0% and 26%; relapse rate, 34% and 28%; LFS, 66% and 46%; OS, 82% and 43%). We conclude that M7 AML patients in CR1 (except children with Down syndrome, who already have better outcomes) can benefit from transplantation.
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ABSTRACT: Acute erythro- and megakaryoblastic leukaemias are associated with very poor prognoses and the mechanism of blastic transformation is insufficiently elucidated. The murine Graffi leukaemia retrovirus induces erythro- and megakaryoblastic leukaemias when inoculated into NFS mice and represents a good model to study these leukaemias. To expand our understanding of genes specific to these leukaemias, we compared gene expression profiles, measured by microarray and RT-PCR, of all leukaemia types induced by this virus. The transcriptome level changes, present between the different leukaemias, led to the identification of specific cancerous signatures. We reported numerous genes that may be potential oncogenes, may have a function related to erythropoiesis or megakaryopoiesis or have a poorly elucidated physiological role. The expression pattern of these genes has been further tested by RT-PCR in different samples, in a Friend erythroleukaemic model and in human leukaemic cell lines.We also screened the megakaryoblastic leukaemias for viral integrations and identified genes targeted by these integrations and potentially implicated in the onset of the disease. Taken as a whole, the data obtained from this global gene profiling experiment have provided a detailed characterization of Graffi virus induced erythro- and megakaryoblastic leukaemias with many genes reported specific to the transcriptome of these leukaemias for the first time.BMC Medical Genomics 01/2010; 3:2. · 3.47 Impact Factor
- Pathology 08/2011; 43(5):517-9. · 2.66 Impact Factor
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ABSTRACT: Acute myeloid leukemia (AML) is a very heterogeneous disease. Prognosis is related not only to intrinsic characteristics such as cytogenetics and molecular markers, but also the patient's ability to tolerate therapy, and treatment response. Allogeneic stem cell transplantation (allo-HCT) has been traditionally indicated for poor-risk disease in first complete remission (CR1) or for treatment of relapsed or refractory AML. 'Poor-risk' disease is now better defined due to genetic subtyping, particularly in chromosomally normal AML. In addition, the presence of comorbid conditions should be included in the decision-making process. Improvements in supportive care and the use of modern conditioning regimens have been associated with improved outcomes, mostly due to a reduction in treatment-related mortality. Therefore, a significant proportion of patients with AML-CR1 can potentially benefit from allo-HCT. We give general guidelines on how to incorporate cytogenetic and molecular risk factors, donor selection, and patient characteristics in order to determine when allo-HCT should be indicated in CR1.Current Hematologic Malignancy Reports 03/2014;