Comparable long‐term outcomes after reduced‐intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high‐risk acute lymphoblastic leukemia in complete remission

The role of reduced‐intensity conditioning (RIC) in adult acute lymphoblastic leukemia (ALL) remains unclear because of the small sample size, short follow‐up duration, various regimens for conditioning and graft‐versus‐host disease (GVHD) prophylaxis, and the heterogeneity of selection criteria for...

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Published inAmerican journal of hematology Vol. 88; no. 8; pp. 634 - 641
Main Authors Eom, Ki‐Seong, Shin, Seung‐Hwan, Yoon, Jae‐Ho, Yahng, Seung‐Ah, Lee, Sung‐Eun, Cho, Byung‐Sik, Kim, Yoo‐Jin, Kim, Hee‐Je, Min, Chang‐Ki, Kim, Dong‐Wook, Lee, Jong‐Wook, Min, Woo‐Sung, Park, Chong‐Won, Lee, Seok
Format Journal Article
LanguageEnglish
Published United States Wiley Subscription Services, Inc 01.08.2013
Subjects
Adolescent
Adult
Cyclophosphamide - administration & dosage
Disease-Free Survival
Female
Follow-Up Studies
Graft vs Host Disease - mortality
Graft vs Host Disease - prevention & control
Graft vs Host Disease - therapy
Hematology
Humans
Male
Middle Aged
Myeloablative Agonists - administration & dosage
Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality
Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy
Remission Induction
Retrospective Studies
Risk Factors
Stem Cell Transplantation
Survival Rate
Transplantation Conditioning - methods
Transplantation, Homologous
Whole-Body Irradiation - methods
Online AccessGet full text
ISSN0361-8609
1096-8652
1096-8652
DOI10.1002/ajh.23465

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Abstract The role of reduced‐intensity conditioning (RIC) in adult acute lymphoblastic leukemia (ALL) remains unclear because of the small sample size, short follow‐up duration, various regimens for conditioning and graft‐versus‐host disease (GVHD) prophylaxis, and the heterogeneity of selection criteria for transplantation. We compared long‐term outcomes of 60 consecutive RIC transplants (fludarabine plus melphalan) with 120 myeloablative conditioning (MAC) transplants (total body irradiation plus cyclophosphamide) for adult high‐risk ALL in first or second complete remission. All transplants received a uniform strategy of pretransplant chemotherapy and GVHD prophylaxis. Compared to MAC transplants, RIC transplants had older age (46 years vs. 33 years, P < 0.001) and higher proportions of transplantation using peripheral blood (93.3% vs. 13.3%; P < 0.001) but otherwise showed similar characteristics. After a median follow‐up of 67 months, RIC transplants showed comparable nonrelapse mortality (21.2% vs. 24.3%) and disease‐free survival (50.8% vs. 54.9%) to MAC transplants, although relapse risk was higher (34.2% vs. 26.4%; HR, 2.07; P = 0.019) in multivariate analysis. Other independent factors associated with better outcomes were the presence of chronic GVHD and transplantation in first complete remission. Interestingly, the negative impact of RIC on relapse risk was seen only for Philadelphia‐positive ALL transplants (32.7% vs. 19.6%; HR, 3.46; P = 0.020), while no difference was found between RIC and MAC for Philadelphia‐negative ALL transplants (35.0% vs. 32.1%; HR, 1.39; P = 0.429). RIC can be considered as a reasonable choice for providing a sufficient long‐term graft‐versus‐leukemia effect for adult high‐risk ALL patients ineligible for MAC. Am. J. Hematol. 88:634–641, 2013. © 2013 Wiley Periodicals, Inc.
AbstractList The role of reduced‐intensity conditioning (RIC) in adult acute lymphoblastic leukemia (ALL) remains unclear because of the small sample size, short follow‐up duration, various regimens for conditioning and graft‐versus‐host disease (GVHD) prophylaxis, and the heterogeneity of selection criteria for transplantation. We compared long‐term outcomes of 60 consecutive RIC transplants (fludarabine plus melphalan) with 120 myeloablative conditioning (MAC) transplants (total body irradiation plus cyclophosphamide) for adult high‐risk ALL in first or second complete remission. All transplants received a uniform strategy of pretransplant chemotherapy and GVHD prophylaxis. Compared to MAC transplants, RIC transplants had older age (46 years vs. 33 years, P  < 0.001) and higher proportions of transplantation using peripheral blood (93.3% vs. 13.3%; P  < 0.001) but otherwise showed similar characteristics. After a median follow‐up of 67 months, RIC transplants showed comparable nonrelapse mortality (21.2% vs. 24.3%) and disease‐free survival (50.8% vs. 54.9%) to MAC transplants, although relapse risk was higher (34.2% vs. 26.4%; HR, 2.07; P  = 0.019) in multivariate analysis. Other independent factors associated with better outcomes were the presence of chronic GVHD and transplantation in first complete remission. Interestingly, the negative impact of RIC on relapse risk was seen only for Philadelphia‐positive ALL transplants (32.7% vs. 19.6%; HR, 3.46; P  = 0.020), while no difference was found between RIC and MAC for Philadelphia‐negative ALL transplants (35.0% vs. 32.1%; HR, 1.39; P  = 0.429). RIC can be considered as a reasonable choice for providing a sufficient long‐term graft‐versus‐leukemia effect for adult high‐risk ALL patients ineligible for MAC. Am. J. Hematol. 88:634–641, 2013. © 2013 Wiley Periodicals, Inc.
The role of reduced-intensity conditioning (RIC) in adult acute lymphoblastic leukemia (ALL) remains unclear because of the small sample size, short follow-up duration, various regimens for conditioning and graft-versus-host disease (GVHD) prophylaxis, and the heterogeneity of selection criteria for transplantation. We compared long-term outcomes of 60 consecutive RIC transplants (fludarabine plus melphalan) with 120 myeloablative conditioning (MAC) transplants (total body irradiation plus cyclophosphamide) for adult high-risk ALL in first or second complete remission. All transplants received a uniform strategy of pretransplant chemotherapy and GVHD prophylaxis. Compared to MAC transplants, RIC transplants had older age (46 years vs. 33 years, P<0.001) and higher proportions of transplantation using peripheral blood (93.3% vs. 13.3%; P<0.001) but otherwise showed similar characteristics. After a median follow-up of 67 months, RIC transplants showed comparable nonrelapse mortality (21.2% vs. 24.3%) and disease-free survival (50.8% vs. 54.9%) to MAC transplants, although relapse risk was higher (34.2% vs. 26.4%; HR, 2.07; P=0.019) in multivariate analysis. Other independent factors associated with better outcomes were the presence of chronic GVHD and transplantation in first complete remission. Interestingly, the negative impact of RIC on relapse risk was seen only for Philadelphia-positive ALL transplants (32.7% vs. 19.6%; HR, 3.46; P=0.020), while no difference was found between RIC and MAC for Philadelphia-negative ALL transplants (35.0% vs. 32.1%; HR, 1.39; P=0.429). RIC can be considered as a reasonable choice for providing a sufficient long-term graft-versus-leukemia effect for adult high-risk ALL patients ineligible for MAC. Am. J. Hematol. 88:634-641, 2013. © 2013 Wiley Periodicals, Inc [PUBLICATION ABSTRACT].
The role of reduced‐intensity conditioning (RIC) in adult acute lymphoblastic leukemia (ALL) remains unclear because of the small sample size, short follow‐up duration, various regimens for conditioning and graft‐versus‐host disease (GVHD) prophylaxis, and the heterogeneity of selection criteria for transplantation. We compared long‐term outcomes of 60 consecutive RIC transplants (fludarabine plus melphalan) with 120 myeloablative conditioning (MAC) transplants (total body irradiation plus cyclophosphamide) for adult high‐risk ALL in first or second complete remission. All transplants received a uniform strategy of pretransplant chemotherapy and GVHD prophylaxis. Compared to MAC transplants, RIC transplants had older age (46 years vs. 33 years, P < 0.001) and higher proportions of transplantation using peripheral blood (93.3% vs. 13.3%; P < 0.001) but otherwise showed similar characteristics. After a median follow‐up of 67 months, RIC transplants showed comparable nonrelapse mortality (21.2% vs. 24.3%) and disease‐free survival (50.8% vs. 54.9%) to MAC transplants, although relapse risk was higher (34.2% vs. 26.4%; HR, 2.07; P = 0.019) in multivariate analysis. Other independent factors associated with better outcomes were the presence of chronic GVHD and transplantation in first complete remission. Interestingly, the negative impact of RIC on relapse risk was seen only for Philadelphia‐positive ALL transplants (32.7% vs. 19.6%; HR, 3.46; P = 0.020), while no difference was found between RIC and MAC for Philadelphia‐negative ALL transplants (35.0% vs. 32.1%; HR, 1.39; P = 0.429). RIC can be considered as a reasonable choice for providing a sufficient long‐term graft‐versus‐leukemia effect for adult high‐risk ALL patients ineligible for MAC. Am. J. Hematol. 88:634–641, 2013. © 2013 Wiley Periodicals, Inc.
The role of reduced-intensity conditioning (RIC) in adult acute lymphoblastic leukemia (ALL) remains unclear because of the small sample size, short follow-up duration, various regimens for conditioning and graft-versus-host disease (GVHD) prophylaxis, and the heterogeneity of selection criteria for transplantation. We compared long-term outcomes of 60 consecutive RIC transplants (fludarabine plus melphalan) with 120 myeloablative conditioning (MAC) transplants (total body irradiation plus cyclophosphamide) for adult high-risk ALL in first or second complete remission. All transplants received a uniform strategy of pretransplant chemotherapy and GVHD prophylaxis. Compared to MAC transplants, RIC transplants had older age (46 years vs. 33 years, P < 0.001) and higher proportions of transplantation using peripheral blood (93.3% vs. 13.3%; P < 0.001) but otherwise showed similar characteristics. After a median follow-up of 67 months, RIC transplants showed comparable nonrelapse mortality (21.2% vs. 24.3%) and disease-free survival (50.8% vs. 54.9%) to MAC transplants, although relapse risk was higher (34.2% vs. 26.4%; HR, 2.07; P = 0.019) in multivariate analysis. Other independent factors associated with better outcomes were the presence of chronic GVHD and transplantation in first complete remission. Interestingly, the negative impact of RIC on relapse risk was seen only for Philadelphia-positive ALL transplants (32.7% vs. 19.6%; HR, 3.46; P = 0.020), while no difference was found between RIC and MAC for Philadelphia-negative ALL transplants (35.0% vs. 32.1%; HR, 1.39; P = 0.429). RIC can be considered as a reasonable choice for providing a sufficient long-term graft-versus-leukemia effect for adult high-risk ALL patients ineligible for MAC.
The role of reduced-intensity conditioning (RIC) in adult acute lymphoblastic leukemia (ALL) remains unclear because of the small sample size, short follow-up duration, various regimens for conditioning and graft-versus-host disease (GVHD) prophylaxis, and the heterogeneity of selection criteria for transplantation. We compared long-term outcomes of 60 consecutive RIC transplants (fludarabine plus melphalan) with 120 myeloablative conditioning (MAC) transplants (total body irradiation plus cyclophosphamide) for adult high-risk ALL in first or second complete remission. All transplants received a uniform strategy of pretransplant chemotherapy and GVHD prophylaxis. Compared to MAC transplants, RIC transplants had older age (46 years vs. 33 years, P < 0.001) and higher proportions of transplantation using peripheral blood (93.3% vs. 13.3%; P < 0.001) but otherwise showed similar characteristics. After a median follow-up of 67 months, RIC transplants showed comparable nonrelapse mortality (21.2% vs. 24.3%) and disease-free survival (50.8% vs. 54.9%) to MAC transplants, although relapse risk was higher (34.2% vs. 26.4%; HR, 2.07; P = 0.019) in multivariate analysis. Other independent factors associated with better outcomes were the presence of chronic GVHD and transplantation in first complete remission. Interestingly, the negative impact of RIC on relapse risk was seen only for Philadelphia-positive ALL transplants (32.7% vs. 19.6%; HR, 3.46; P = 0.020), while no difference was found between RIC and MAC for Philadelphia-negative ALL transplants (35.0% vs. 32.1%; HR, 1.39; P = 0.429). RIC can be considered as a reasonable choice for providing a sufficient long-term graft-versus-leukemia effect for adult high-risk ALL patients ineligible for MAC.The role of reduced-intensity conditioning (RIC) in adult acute lymphoblastic leukemia (ALL) remains unclear because of the small sample size, short follow-up duration, various regimens for conditioning and graft-versus-host disease (GVHD) prophylaxis, and the heterogeneity of selection criteria for transplantation. We compared long-term outcomes of 60 consecutive RIC transplants (fludarabine plus melphalan) with 120 myeloablative conditioning (MAC) transplants (total body irradiation plus cyclophosphamide) for adult high-risk ALL in first or second complete remission. All transplants received a uniform strategy of pretransplant chemotherapy and GVHD prophylaxis. Compared to MAC transplants, RIC transplants had older age (46 years vs. 33 years, P < 0.001) and higher proportions of transplantation using peripheral blood (93.3% vs. 13.3%; P < 0.001) but otherwise showed similar characteristics. After a median follow-up of 67 months, RIC transplants showed comparable nonrelapse mortality (21.2% vs. 24.3%) and disease-free survival (50.8% vs. 54.9%) to MAC transplants, although relapse risk was higher (34.2% vs. 26.4%; HR, 2.07; P = 0.019) in multivariate analysis. Other independent factors associated with better outcomes were the presence of chronic GVHD and transplantation in first complete remission. Interestingly, the negative impact of RIC on relapse risk was seen only for Philadelphia-positive ALL transplants (32.7% vs. 19.6%; HR, 3.46; P = 0.020), while no difference was found between RIC and MAC for Philadelphia-negative ALL transplants (35.0% vs. 32.1%; HR, 1.39; P = 0.429). RIC can be considered as a reasonable choice for providing a sufficient long-term graft-versus-leukemia effect for adult high-risk ALL patients ineligible for MAC.
Author Yahng, Seung‐Ah
Kim, Dong‐Wook
Min, Woo‐Sung
Shin, Seung‐Hwan
Lee, Seok
Cho, Byung‐Sik
Lee, Jong‐Wook
Min, Chang‐Ki
Eom, Ki‐Seong
Kim, Hee‐Je
Park, Chong‐Won
Yoon, Jae‐Ho
Lee, Sung‐Eun
Kim, Yoo‐Jin
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/23620000$$D View this record in MEDLINE/PubMed
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Snippet The role of reduced‐intensity conditioning (RIC) in adult acute lymphoblastic leukemia (ALL) remains unclear because of the small sample size, short follow‐up...
The role of reduced-intensity conditioning (RIC) in adult acute lymphoblastic leukemia (ALL) remains unclear because of the small sample size, short follow-up...
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SubjectTerms Adolescent
Adult
Cyclophosphamide - administration & dosage
Disease-Free Survival
Female
Follow-Up Studies
Graft vs Host Disease - mortality
Graft vs Host Disease - prevention & control
Graft vs Host Disease - therapy
Hematology
Humans
Male
Middle Aged
Myeloablative Agonists - administration & dosage
Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality
Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy
Remission Induction
Retrospective Studies
Risk Factors
Stem Cell Transplantation
Survival Rate
Transplantation Conditioning - methods
Transplantation, Homologous
Whole-Body Irradiation - methods
Title Comparable long‐term outcomes after reduced‐intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high‐risk acute lymphoblastic leukemia in complete remission
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fajh.23465
https://www.ncbi.nlm.nih.gov/pubmed/23620000
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Volume 88
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