Allogeneic Transplantation for Advanced Acute Myeloid Leukemia: The Value of Complete Remission

• Type of Material: Article
• Authors: Daniel Weisdorf, University of Minnesota; Heather R. Millard, Medical College of Wisconsin; Mary M. Horowitz, Medical College of Wisconsin; Parvinder S. Hyare, Sunesis Pharmaceuticals; Richard Champlin, University of Texas MD Anderson Cancer Center; Vincent Ho, Dana-Farber Cancer Institute; Marco Mielcarek, Seattle Cancer Care Alliance; Andrew Rezvani, Stanford Health Care; Keith Stockerl-Goldstein, Barnes Jewish Hospital; H Jean Khoury, Emory University; Marcos De Lima, Seidman Cancer Center; Wael Saber, Medical College of Wisconsin; Brenda Sandmaier, University of Washington; Mei Jie Zhang, Medical College of Wisconsin; Mary Eapen, Medical College of Wisconsin
• Language: English
• Date: 2017-06-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 American Cancer Society.
• Final Published Version (URL): http://dx.doi.org/10.1002/cncr.30536
• Title of Journal or Parent Work: Cancer
• ISSN: 0008-543X
• Volume: 123
• Issue: 11
• Start Page: 2025
• End Page: 2034
• Grant/Funding Information: The study was performed at the CIBMTR with partial financial support from Sunesis who had no independent part in the data collection, analysis or publication.; The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement 5U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-15-1-0848 and N00014-16-1-2020 from the Office of Naval Research; and grants from Alexion; *Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; AstraZeneca; Be the Match Foundation; *Bluebird Bio, Inc.; *Bristol Myers Squibb Oncology; *Celgene Corporation; Cellular Dynamics International, Inc.; *Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Genentech, Inc.; Genzyme Corporation; *Gilead Sciences, Inc.; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Janssen Scientific Affairs, LLC; *Jazz Pharmaceuticals, Inc.; Jeff Gordon Children's Foundation; The Leukemia & Lymphoma Society; Medac, GmbH; MedImmune; The Medical College of Wisconsin; *Merck & Co, Inc.; Mesoblast; MesoScale Diagnostics, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Neovii Biotech NA, Inc.; Novartis Pharmaceuticals Corporation; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Otsuka Pharmaceutical Co, Ltd. – Japan; PCORI; Perkin Elmer, Inc.; Pfizer, Inc; *Sanofi US; *Seattle Genetics; *Spectrum Pharmaceuticals, Inc.; St. Baldrick's Foundation; *Sunesis Pharmaceuticals, Inc.; Swedish Orphan Biovitrum, Inc.; Takeda Oncology; Telomere Diagnostics, Inc.; University of Minnesota; and *Wellpoint, Inc.
• Keywords: CHEMOTHERAPY; BONE-MARROW-TRANSPLANTATION; REFRACTORY ACUTE-LEUKEMIA; RELAPSE; SURVIVAL; relapse; ACUTE MYELOGENOUS LEUKEMIA; complete remission; Oncology; PRIMARY INDUCTION FAILURE; Science & Technology; allogeneic transplantation; acute myeloid leukemia; STEM-CELL TRANSPLANTATION; THERAPY; primary induction failure; Life Sciences & Biomedicine; DONOR
• Research Categories: Health Sciences, Oncology; Health Sciences, General

Abstract

BACKGROUND: Patients with acute myeloid leukemia (AML) without complete remission (CR) or in first relapse (Rel1) can have extended leukemia control and survival after allogeneic hematopoietic cell transplantation (HCT). For patients in Rel1 or primary induction failure (PIF), transplantation versus treatment to achieve a second CR (CR2) and subsequent HCT might yield similar outcomes, but available comparative data are scarce. METHODS: Survival was analyzed in 4682 HCT recipients according to disease status: PIF (N = 1440), Rel1 (failing ≥1 reinduction; N = 1256), and CR2 (N = 1986). RESULTS: Patient, disease, and transplantation characteristics were similar, except that patients in CR2 more often had performance scores of 90% to 100%, de novo AML, and longer CR1 duration. Adverse cytogenetics were more common in patients who experienced PIF. The 5-year survival rate adjusted for performance score, cytogenetic risk, and donor type for CR2 was 39% (95% confidence interval [CI], 37%-41%) compared with 18% (95% CI, 16%-20%) for HCT in Rel1 and 21% (95% CI, 19%-23%) in PIF (P <.0001). CONCLUSIONS: Although survival is superior for patients who undergo HCT in CR2, transplantation for selected patients in Rel1 or PIF may still be valuable. These data can guide decision making about additional salvage therapy versus prompt HCT for patients not in CR, but they also highlight that AML is intrinsically more treatable in patients who have favorable-risk cytogenetics, those with longer CR1 duration, and younger patients with better performance status. Cancer 2017;123:2025–2034.