Mei Guo1, Nelson J Chao2, Jian-Yong Li3, David A Rizzieri2, Qi-Yun Sun1, Ann Mohrbacher4, Elizabeth F Krakow5, Wan-Jun Sun6, Xu-Liang Shen7, Xin-Rong Zhan8, De-Pei Wu9, Li Liu10, Juan Wang11, Min Zhou12, Lin-Hua Yang13, Yang-Yi Bao14, Zheng Dong1, Bo Cai1, Kai-Xun Hu1, Chang-Lin Yu1, Jian-Hui Qiao1, Hong-Li Zuo1, Ya-Jing Huang1, Anthony D Sung2, Jun-Xiao Qiao6, Zhi-Qing Liu1, Tie-Qiang Liu1, Bo Yao1, Hong-Xia Zhao6, Si-Xuan Qian3, Wei-Wei Liu15, Rafael Forés16, Rafael F Duarte16, Hui-Sheng Ai1. 1. Department of Hematology and Transplantation, Affiliated Hospital of The Academy of Military Medical Sciences, Beijing, China. 2. Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University, Duke Cancer Institute, Durham, North Carolina. 3. Department of Hematology, Jiangsu Province People's Hospital, Nanjing, China. 4. Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, Keck School of Medicine of University of Southern California, Los Angeles. 5. Division of Medical Oncology, University of Washington, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle. 6. Department of Hematology, The Second Artillery General Hospital, Beijing, China. 7. Department of Hematology, He Ping Central Hospital of the Changzhi Medical College, Changzhi, China. 8. Department of Hematology, Central Hospital of Xinxiang City, Xinxiang, China. 9. Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China. 10. Department of Hematology, The Fourth Military Medical University, Xi'an, China. 11. Department of Hematology, Central Hospital of Cangzhou City, Cangzhou, China. 12. Department of Hematology, The Second People's Hospital of Changzhou City, Changzhou, China. 13. Department of Hematology, The Second Affiliated Hospital of Shanxi University, Taiyuan, China. 14. Department of Hematology, Central Hospital of Hefei City, Hefei, China. 15. Statistics Department, The Academy of Military Medical Sciences, Beijing, China. 16. Department of Hematology, Hospital Universitario Puerta de Hierro, Majadahonda, Comunidad de Madrid, Spain.
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.
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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