Rapid Donor Identification Improves Survival in High-Risk First-Remission Patients With Acute Myeloid Leukemia

Abstract

Purpose: Patients with acute myeloid leukemia with high-risk cytogenetics in first complete remission (CR1) achieve better outcomes if they undergo allogeneic hematopoietic cell transplantation (HCT) compared with consolidation chemotherapy alone. However, only approximately 40% of such patients typically proceed to HCT.

Methods: We used a prospective organized approach to rapidly identify donors to improve the allogeneic HCT rate in adults with high-risk acute myeloid leukemia in CR1. Newly diagnosed patients had cytogenetics obtained at enrollment, and those with high-risk cytogenetics underwent expedited HLA typing and were encouraged to be referred for consultation with a transplantation team with the goal of conducting an allogeneic HCT in CR1.

Results: Of 738 eligible patients (median age, 49 years; range, 18-60 years of age), 159 (22%) had high-risk cytogenetics and 107 of these patients (67%) achieved CR1. Seventy (65%) of the high-risk patients underwent transplantation in CR1 (P < .001 compared with the historical rate of 40%). Median time to HCT from CR1 was 77 days (range, 20-356 days). In landmark analysis, overall survival (OS) among patients who underwent transplantation was significantly better compared with that of patients who did not undergo transplantation (2-year OS, 48% v 35%, respectively [P = .031]). Median relapse-free survival after transplantation in the high-risk cohort who underwent transplantation in CR1 (n = 70) was 11.5 months (range, 4-47 months), and median OS after transplantation was 14 months (range, 4-44 months).

Conclusion: Early cytogenetic testing with an organized effort to identify a suitable allogeneic HCT donor led to a CR1 transplantation rate of 65% in the high-risk group, which, in turn, led to an improvement in OS when compared with the OS of patients who did not undergo transplantation.

Fig 1.

(A) Consort diagram displaying random assignment and distribution of patients. Diagram shows patient flow through the initial induction stage of the S1203 controlled trial (eligibility and random assignment) with depiction of those high-risk patients in each arm who achieved complete remission (CR) and subsequently underwent transplantation in first CR (CR1). Flow charts outlining (B) the method for patient assessment of high-risk cytogenetics at study entry and (C) the expedited donor identification and transplantation procedure for patients with high-risk acute myeloid leukemia (AML). Panel B shows the process of obtaining a buccal swab at time of diagnosis and study entry before random assignment to induction therapy, with expedited human leukocyte antigen (HLA) typing performed within 5 business days for patients with high-risk cytogenetics. Panel C depicts flow for determining appropriate donor identification for hematopoietic cell transplantation (HCT) of high-risk patients in CR1. 7+3, standard cytarabine plus daunorubicin; APL, acute promyelocytic leukemia; AraC, cytarabine; dUCB, double umbilical cord blood; IA, idarubicin with high-dose cytarabine; IA+V, IA with vorinostat; Ph+, Philadelphia chromosome positive; TB, tuberculosis; URD, unrelated donor.

Fig 2.

Cumulative incidence of transplantation among high-risk patients in first complete remission (CR1) and all high-risk patients. (A) Cumulative incidence of receiving a transplant (with relapse and death as competing events) among the 107 high-risk patients who had achieved CR1 was 13% by 3 months after CR1, 38% by 4 months, 54% by 5 months, 60% by 6 months, and 65% by 9 months. (B) Cumulative incidence of transplantation among all high-risk patients (n =159, death as the competing event) was 11% by 3 months after registration, 33% by month 4, 46% by month 5, 53% by month 6, 58% by month 9, and 60% by month 13.

Fig 3.

Survival outcomes for patients transplanted in CR1. (A) Landmark analysis for OS and (B) RFS among patients alive after 6 months after randomization. (C) RFS and (D) OS among CR1 high-risk patients who were treated using a matched related donor v a matched unrelated donor. CR1, first complete remission; OS, overall survival; RFS, relapse-free survival.