TY - JOUR
T1 - Allogeneic Hematopoietic Stem Cell Transplantation for Adult Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia in Second Complete Remission
AU - Adult Acute Lymphoblastic Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation
AU - Kaito, Satoshi
AU - Kurosawa, Shuhei
AU - Najima, Yuho
AU - Sakaida, Emiko
AU - Shingai, Naoki
AU - Fukuda, Takahiro
AU - Tachibana, Takayoshi
AU - Uchida, Naoyuki
AU - Ozawa, Yukiyasu
AU - Sawa, Masashi
AU - Nakazawa, Hideyuki
AU - Ota, Shuichi
AU - Kato, Jun
AU - Nakamae, Hirohisa
AU - Katayama, Yuta
AU - Eto, Tetsuya
AU - Tanaka, Junji
AU - Kanda, Yoshinobu
AU - Atsuta, Yoshiko
AU - Arai, Yasuyuki
AU - Kako, Shinichi
N1 - Funding Information:
The authors thank all physicians and staff at the transplant centers who provided clinical data to the Transplant Registry Unified Management Program of the Japan Society of Hematopoietic Cell Transplantation. We also thank the staff at the Japan Society of Hematopoietic Cell Transplantation and the Japanese Data Center for Hematopoietic Cell Transplantation for their dedication to the organization and management of the data. Financial disclosure: None to report. Conflict of interest statement: There are no conflicts of interest to report. Authorship statement: S. Kaito designed the study, analyzed data, and wrote the manuscript. S. Kurosawa, Y.N. and E.S. advised on methods and wrote the manuscript. N.S. T.F. T.T. N.U. Y.O. M.S. H. Nakazawa, S.O. J.K. H. Nakamae, Y. Katayama, and T.E. collected data and revised the manuscript. J.T. and Y. Kanda collected data, revised the manuscript, and were responsible for data management. Y.A. managed the unified registry database and revised the manuscript. Y.A. and S. Kako designed the study, advised on the methods, revised the manuscript, and was responsible for the project of Adult Acute Lymphoblastic Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation. Financial disclosure: See Acknowledgments on page 326.e9.
Publisher Copyright:
© 2022 The American Society for Transplantation and Cellular Therapy
PY - 2022/6
Y1 - 2022/6
N2 - Even in the era of high-intensity chemotherapy, disease recurrence remains a major cause of treatment failure in adult patients with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (Ph-negative B-ALL). For patients who achieved second complete remission (CR2) with salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) could be the best curative treatment. However, limited data are available on the outcomes of allo-HSCT for adult Ph-negative B-ALL in CR2 in the high-intensity chemotherapy era. We evaluated the transplantation outcomes of adult patients with Ph-negative B-ALL in CR2 compared with those in CR1. We also clarified the prognostic factors among adult allo-HSCT recipients with Ph-negative B-ALL in CR2. We conducted a nationwide retrospective study using the data form Japanese transplant registry database. Patients aged ≥16 years and underwent their first allo-HSCT between 2003 and 2017 were included. The 3-year overall survival (OS) rate of the patients in CR2 (n = 382) was significantly lower than that in first complete remission (n = 1375) (51.8% versus 68.1%; P < .001), accompanied by a higher relapse rate (34.2% versus 17.6% at 3 years; P < .001). In a multivariate analysis among CR2 patients, time from diagnosis to allo-HSCT (≤2 years) was a significant factor for OS (hazard ratio [HR] 1.87; P < .001) and relapse (HR = 1.88; P < .001), whereas age at allo-HSCT (≥30 years) was a significant factor for OS (HR = 2.10, P < .001) and nonrelapse mortality (HR = 2.68; P < .001). By assigning a score of 1 to each factor, the 3-year OS rate of CR2 patients significantly stratified: 70.7% in patients with score 0, 56.4% with score 1, and 28.4% with score 2 (P < .001). The survival outcomes of allo-HSCT in adult Ph-negative B-ALL patients in CR2 were inferior to those in CR1 in the high-intensity chemotherapy era, mainly because of the higher relapse rate. Among the CR2 patients, the short time between diagnosis and allo-HSCT was a significant risk factor for disease recurrence and overall mortality. Better disease control with novel treatment strategies may be needed for early relapse. In addition, the nonrelapse mortality rate in patients over 30 years of age was particularly high among CR2 patients, suggesting the need for improved supportive care for these patients. Further studies are warranted on the outcomes of allo-HSCT after achieving CR2 with novel drugs, such as inotuzumab ozogamicin and blinatumomab.
AB - Even in the era of high-intensity chemotherapy, disease recurrence remains a major cause of treatment failure in adult patients with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (Ph-negative B-ALL). For patients who achieved second complete remission (CR2) with salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) could be the best curative treatment. However, limited data are available on the outcomes of allo-HSCT for adult Ph-negative B-ALL in CR2 in the high-intensity chemotherapy era. We evaluated the transplantation outcomes of adult patients with Ph-negative B-ALL in CR2 compared with those in CR1. We also clarified the prognostic factors among adult allo-HSCT recipients with Ph-negative B-ALL in CR2. We conducted a nationwide retrospective study using the data form Japanese transplant registry database. Patients aged ≥16 years and underwent their first allo-HSCT between 2003 and 2017 were included. The 3-year overall survival (OS) rate of the patients in CR2 (n = 382) was significantly lower than that in first complete remission (n = 1375) (51.8% versus 68.1%; P < .001), accompanied by a higher relapse rate (34.2% versus 17.6% at 3 years; P < .001). In a multivariate analysis among CR2 patients, time from diagnosis to allo-HSCT (≤2 years) was a significant factor for OS (hazard ratio [HR] 1.87; P < .001) and relapse (HR = 1.88; P < .001), whereas age at allo-HSCT (≥30 years) was a significant factor for OS (HR = 2.10, P < .001) and nonrelapse mortality (HR = 2.68; P < .001). By assigning a score of 1 to each factor, the 3-year OS rate of CR2 patients significantly stratified: 70.7% in patients with score 0, 56.4% with score 1, and 28.4% with score 2 (P < .001). The survival outcomes of allo-HSCT in adult Ph-negative B-ALL patients in CR2 were inferior to those in CR1 in the high-intensity chemotherapy era, mainly because of the higher relapse rate. Among the CR2 patients, the short time between diagnosis and allo-HSCT was a significant risk factor for disease recurrence and overall mortality. Better disease control with novel treatment strategies may be needed for early relapse. In addition, the nonrelapse mortality rate in patients over 30 years of age was particularly high among CR2 patients, suggesting the need for improved supportive care for these patients. Further studies are warranted on the outcomes of allo-HSCT after achieving CR2 with novel drugs, such as inotuzumab ozogamicin and blinatumomab.
KW - Allogeneic hematopoietic stem cell transplantation
KW - B-cell acute lymphoblastic leukemia
KW - Philadelphia chromosome-negative
KW - Second complete remission
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U2 - 10.1016/j.jtct.2022.03.017
DO - 10.1016/j.jtct.2022.03.017
M3 - Article
C2 - 35306218
AN - SCOPUS:85128436878
SN - 2666-6367
VL - 28
SP - 326.e1-326.e10
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
IS - 6
ER -