Allogeneic stem cell transplantation (allo-SCT) for de novo Ph+ AML: a study from the French Society of Bone Marrow Transplantation and Cell Therapy

Philadelphia chromosome incidence in primary AML (Ph+ AML) is 0.5–3%.1, 2 The reality of Ph+ AML remains controversial and to date is not described in the 2008 revision of the WHO (World

Health Organization) classification as a separate entity.3 CML in myeloid blast crisis (MBC-CML) and mixed phenotype acute leukemia (MPAL) with t(9;22)(q34;q11) are differential diagnoses.

Unlike CML, cases of Ph+ AML do not have a history of abnormal hemograms, lack an argument for a previous chronic phase of CML and lack basophilia or splenomegaly.4 In addition, cytogenetic

and molecular abnormalities may be useful to distinguish CML from Ph+ AML5 as much as trisomy 8, trisomy 19 or isochromosome 17q, besides t(9;22) and ABL1 mutations are common additional

abnormalities in MBC-CML,4, 6, 7 while Ph+ AML generally exhibits gene mutations suppressing cell differentiation (Core Binding Factor AML, NPM1) or mutations increasing cell proliferation

(FLT3, RAS).3, 6, 8 Primary Ph+ AML has recently been described as a distinct AML subtype with a specific genome signature compared with CML.9 Although allogeneic stem cell transplantation

(Allo-SCT) is often proposed as the curative option, the outcome of Ph+ AML treated with Allo-SCT remains unknown in the literature. The objective of the study was to compared primary Ph+

AML with others Ph+ acute leukemia (MPAL and MBC-CML). Here we wanted to present the result of a retrospective, multi-center study assessing the results of allo-HSCT in Ph+ acute leukemia

patients that reported to the SFGM-TC registry between 2000 and 2012 (though ProMISe, a Project Manager Internet Server). Nineteen patients with Ph+ AML were identified in France and

compared with 21 patients with Ph+ MPAL and 52 patients with MBC-CML. For AML, MPAL and MBC-CML patients, the median age per group was, respectively, 46 (range: 18–67), 36 (range: 18–52) and

36 (range: 18–63) years. Ph+ de novo AML was defined in patients with AML who do not have a history of abnormal hemograms, lack evidence of a previous chronic phase of CML and lack

basophilia or splenomegaly.4 MBC-CML was defined by CML history or AML with CML features such as splenomegaly, basophilia or cytogenetic additional abnormality known to be associated with

CML-MBC (as trisomy 8, trisomy 19 or isochromosome 17q).

As previously described in AML,10 patients in this study developing a chronic graft versus host disease (GvHD) have both improved overall survival and better relapse free survival. However,

the present study has some limits. The retrospective nature of the study may have induced selection biases. On the other hand, it is possible to criticize the other two groups (MBC-CML and

MPAL) taken for comparison. Indeed, these two groups must be differentiated from Ph+ AML in terms of treatment choice and/or response to chemotherapy. The majority of MPAL patients received

lymphoblastic like therapy in contrast to patients with Ph+ AML or MBC-CML. Nevertheless, whatever the comparator arms, the present study has the merit to describe the survival of Ph+ AML

patients treated with allo-SCT, which has never been done. In conclusion, our study enriches the knowledge of primary Ph+ AML, describing a promising 68% 2-years overall survival.

Supplementary Information accompanies this paper on Bone Marrow Transplantation website

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