ORLANDO, FL—Allogeneic stem cell transplantation (SCT) “represents a curative strategy”  in patients with refractory acute myeloid leukemia (AML) defined by specific criteria.1

That’s the conclusion of “the first study to assess the impact of allogeneic SCT on outcome in patients with primary refractory AML using differing definitions of refractoriness,” Paul Ferguson, MBChB, PhD, Centre for Clinical Haematology, Queen Elizabeth Hospital Birmingham NHS Foundation Trust in the United Kingdom, told 57th American Society of Hematology (ASH) Annual Meeting attendees on behalf of the NCRI AML Working Group.

“This definition of primary refractory AML is valid irrespective of whether patients are treated on induction chemotherapy protocols designed for older or younger patients,” Dr. Ferguson said. In addition, the ability to identify primary refractory AML using defined criteria “has the potential to improve transplant outcomes” in this population.

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To date, there has been no universally agreed upon definition of primarily refractory AML, he added, “nor has the role of allogeneic SCT been defined in this clinical setting in a large patient cohort.”

The Working Group identified patients with refractory AML after induction chemotherapy and examined overall survival and predictors of outcome using 4 criteria: (1) failure to achieve complete marrow remission (CR) after one cycle (REF1A; 2548 patients); (2) “minor response,” less than a 50% reduction in blast numbers with greater than 15% residual blasts after 1 cycle (REF1B; achieved by 808 of REF1A group); (3) “major response,” greater than 50% in blast numbers with less than 15% residual blasts after one cycle (REF1C; achieved by 1746 of REF1A group), and (4) failure to achieve a CR after 2 courses (REF2; 473 patients). Complete remission was defined using conventional criteria of less than 5% myeloblasts 14 days following induction chemotherapy in a non-hypocellular bone marrow.

A total of 581 patients identified using the four criteria of refractoriness proceeded to an allogeneic SCT.

When compared with patients achieving a complete remission following one cycle of induction chemotherapy, “overall survival was significantly reduced in patients fulfilling any of the criteria for refractory disease,” he said. Specifically, 5-year overall survival was 40%, compared with patients in each of the cohorts: 17% for REF1A, 9% for REF1B, 21% for REF1C, and 8% for REF2.

For patients younger than 60, the rates were 49% for those who achieved a complete remission following one cycle of induction therapy, compared with 25% for REF1A, 14% for REF1B, 291% for REF1C, and 12% for REF2.

Each cohort was analyzed as a whole and by age (youger than 50 and 50 or older) “to reflect changes in transplant practice with the advent of reduced intensity regimens,” he noted.

They found that overall survival in allografted patients was significantly improved compared with non-transplant patients in the REF1B cohort, in those both younger (28% vs 6%; P = .003) and older (22% vs 4%; P = .0006) than 50 as well as in the and REF 2 cohort in those younger (33% vs 7%; P = .004) and older (12% vs 2%; P = .003) than 50.

“Failure to achieve complete remission following 1 course of induction chemotherapy is associated with reduced survival compared to patients receiving complete remission,” Dr. Ferguson reported. Both “the REF1B and REF2 criteria identify patients with primary refractory AML whose survival is extremely poor with chemotherapy alone.”

“Adoption of REF1B criteria allows early identification of primary refractory AML patients and represents a novel, operational disease definition,” he concluded, adding that this definition requires validation in patients receiving induction chemotherapy with high-dose Ara C.


1. Ferguson P, Hills RK, Grech A, et al. An operational definition of primary refractory acute myeloid leukaemia which allows early identification of patients for whom allogeneic stem cell Transplantation Represents the Only Curative Therapy. Oral presentation at: 57th American Society of Hematology (ASH) Annual Meeting; December 7, 2015, Orlando, FL.