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Allogeneic transplantation in primary refractory AML

Bone Marrow Transplantation volume 52, pages 950–951 (2017)Cite this article

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Acquisition of a morphological CR after induction chemotherapy was until recently considered a pre-requisite for allogeneic stem cell transplant (allo-SCT) in patients with AML. However, up to 30% of adults with newly diagnosed AML fail to achieve CR after two courses of intensive chemotherapy, and treatment options for this sizeable patient population have until recently been extremely limited.1 Consequently, the accumulating evidence that allo-SCT can deliver long-term disease-free survival in a proportion of patients with primary refractory (PREF) AML represents an important advance in the treatment of high-risk AML.2, 3 The paper by Rambaldi and colleagues4 in this edition of Bone Marrow Transplantation makes an important contribution to the field and raises fundamentally important questions concerning both the identification of patients with PREF AML likely to benefit from allo-SCT, and the development of strategies with the potential to reduce the risk of disease relapse following allo-SCT.

Although recognized as one of the most important causes of treatment failure in adult AML, there remains a lack of clarity concerning the definition of PREF AML.5 While the International Working Group and the European LeukaemiaNet, both define refractory disease as persistent leukaemic blasts following one course of intensive chemotherapy (IC) in either the peripheral blood or the bone marrow in a patient alive 7 days or more following treatment,6, 7 most transplant studies, in contrast, have defined refractoriness as the failure to achieve a morphological CR after two courses of induction chemotherapy.2, 3 There is however a striking paucity of data to inform the definition of PREF AML in either setting. A recent analysis from the UK NCRI study group compared outcomes after IC with or without subsequent allo-SCT receiving at least two courses of induction chemotherapy according to the residual bone marrow blast percentage after each course.8 This study analysed more than 8 000 patients with newly diagnosed AML and found that patients with greater than 15% residual blasts or a less than a 50% proportional reduction in blast count after course 1 demonstrated similar outcomes to patients who failed to achieve a morphological CR after two courses of induction chemotherapy. Importantly, while patients in both populations were essentially incurable if treated with IC alone (long-term survival rates less than 10%), allo-SCT demonstrated the capacity to deliver long-term survival in up to 30% of such patients. Consequently, utilization of these revised criteria permit early identification of refractoriness after one course of induction whose only curative therapy is an allograft. It will clearly be important to validate these data prospectively, particularly in patients receiving induction regimens containing high dose Ara-C.

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Authors and Affiliations

  1. Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, UK

    P Ferguson & C Craddock

  2. Cancer Research UK Clinical Trials Unit (CRCTU), Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK

    C Craddock

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Correspondence to C Craddock.

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Ferguson, P., Craddock, C. Allogeneic transplantation in primary refractory AML. Bone Marrow Transplant 52, 950–951 (2017). https://doi.org/10.1038/bmt.2017.61

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