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Original Investigation
January 2018

HLA-Mismatched Microtransplant in Older Patients Newly Diagnosed With Acute Myeloid Leukemia: Results From the Microtransplantation Interest Group

Author Affiliations
  • 1Department of Hematology and Transplantation, Affiliated Hospital of The Academy of Military Medical Sciences, Beijing, China
  • 2Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University, Duke Cancer Institute, Durham, North Carolina
  • 3Department of Hematology, Jiangsu Province People’s Hospital, Nanjing, China
  • 4Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, Keck School of Medicine of University of Southern California, Los Angeles
  • 5Division of Medical Oncology, University of Washington, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle
  • 6Department of Hematology, The Second Artillery General Hospital, Beijing, China
  • 7Department of Hematology, He Ping Central Hospital of the Changzhi Medical College, Changzhi, China
  • 8Department of Hematology, Central Hospital of Xinxiang City, Xinxiang, China
  • 9Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
  • 10Department of Hematology, The Fourth Military Medical University, Xi’an, China
  • 11Department of Hematology, Central Hospital of Cangzhou City, Cangzhou, China
  • 12Department of Hematology, The Second People’s Hospital of Changzhou City, Changzhou, China
  • 13Department of Hematology, The Second Affiliated Hospital of Shanxi University, Taiyuan, China
  • 14Department of Hematology, Central Hospital of Hefei City, Hefei, China
  • 15Statistics Department, The Academy of Military Medical Sciences, Beijing, China
  • 16Department of Hematology, Hospital Universitario Puerta de Hierro, Majadahonda, Comunidad de Madrid, Spain
JAMA Oncol. 2018;4(1):54-62. doi:10.1001/jamaoncol.2017.2656
Key Points

Question  Can microtransplant improve outcomes in older patients with acute myeloid leukemia?

Findings  In a multicenter clinical study among 185 patients with de novo acute myeloid leukemia at 12 centers in China, the United States, and Spain, the overall complete remission rate was 74.6% among patients aged 60 to 85 years; the 1-year overall survival rates were 77.8% to 87.7% among patients grouped in 5-year age increments between 60 and 74 years, which were much higher than the rate among patients aged 75 to 85 years (51.7%). The nonrelapse mortality and graft-vs-host disease rates were 10.1% and 1.1%, respectively, among the entire cohort aged 60 to 85 years.

Meaning  As a novel transplantation technique, microtransplant provides an effective and safe therapy for older patients with acute myeloid leukemia.

Abstract

Importance  The outcome of older patients with acute myeloid leukemia (AML) remains unsatisfactory. Recent studies have shown that HLA-mismatched microtransplant could improve outcomes in such patients.

Objective  To evaluate outcomes in different age groups among older patients with newly diagnosed AML who receive HLA-mismatched microtransplant.

Design, Setting, and Participants  This multicenter clinical study included 185 patients with de novo AML at 12 centers in China, the United States, and Spain in the Microtransplantation Interest Group. Patients were divided into the following 4 age groups: 60 to 64 years, 65 to 69 years, 70 to 74 years, and 75 to 85 years. The study period was May 1, 2006, to July 31, 2015.

Exposures  Induction chemotherapy and postremission therapy with cytarabine hydrochloride with or without anthracycline, followed by highly HLA-mismatched related or fully mismatched unrelated donor cell infusion. No graft-vs-host disease prophylaxis was used.

Main Outcomes and Measures  The primary end point of the study was to evaluate the complete remission rates, leukemia-free survival, and overall survival in different age groups. Additional end points of the study included hematopoietic recovery, graft-vs-host disease, relapse rate, nonrelapse mortality, and other treatment-related toxicities.

Results  Among 185 patients, the median age was 67 years (range, 60-85 years), and 75 (40.5%) were female. The denominators in adjusted percentages in overall survival, leukemia-free survival, relapse, and nonrelapse mortality are not the sample proportions of observations. The overall complete remission rate was not significantly different among the 4 age groups (75.4% [52 of 69], 70.2% [33 of 47], 79.1% [34 of 43], and 73.1% [19 of 26). The 1-year overall survival rates were 87.7%, 85.8%, and 77.8% in the first 3 age groups, which were much higher than the rate in the fourth age group (51.7%) (P = .004, P = .008, and P = .04, respectively). The 2-year overall survival rates were 63.7% and 66.8% in the first 2 age groups, which were higher than the rates in the last 2 age groups (34.2% and 14.8%) (P = .02, P = .03, P < .001, and P < .001, respectively). The 1-year cumulative incidences of nonrelapse mortality were 10.2%, 0%, 3.4%, and 26.0% in the 4 age groups and 8.1% in all patients. The median times to neutrophil and platelet recovery were 12 days and 14 days after induction chemotherapy, respectively. Five patients had full or mixed donor engraftment, and 30.8% (8 of 26) of patients demonstrated donor microchimerism. Two patients (1.1%) developed severe acute graft-vs-host disease.

Conclusions and Relevance  Microtransplant achieved a high complete remission rate in AML patients aged 60 to 85 years and higher 1-year overall survival in those aged 60 to 74 years.

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