Adult patients with Ph+ ALL benefit from conditioning regimen of medium‐dose VP16 plus CY/TBI
The medium‐dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used in allogenic hematopoietic stem cell transplantation (allo‐HSCT) for acute lymphoblastic leukemia (ALL). However, the patient subgroups who...
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| Published in | Hematological oncology Vol. 40; no. 5; pp. 1041 - 1055 |
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| Main Authors | , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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England
Wiley Subscription Services, Inc
01.12.2022
John Wiley and Sons Inc |
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| Online Access | Get full text |
| ISSN | 0278-0232 1099-1069 1099-1069 |
| DOI | 10.1002/hon.3046 |
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| Abstract | The medium‐dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used in allogenic hematopoietic stem cell transplantation (allo‐HSCT) for acute lymphoblastic leukemia (ALL). However, the patient subgroups who can actually benefit from VP16/CY/TBI compared to CY/TBI have not been precisely defined. Therefore, we conducted a multi‐center retrospective study using the Japanese nationwide registry database to elucidate the efficacy of VP16/CY/TBI on post‐transplant prognosis. Biological and clinical distinct subtypes (i.e., Philadelphia chromosome‐positive (Ph+) and ‐negative (Ph−) ALL) were evaluated separately, which included 820 Ph+ and 1463 patients with Ph− ALL, respectively. Compared with the CY/TBI group, the VP16/CY/TBI group showed superior progression‐free survival (PFS) in patients with Ph+ ALL (65% vs. 57% at 3 years after HSCT; adjusted hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55–0.98; p = 0.03), along with significantly reduced incidence of relapse (adjusted HR, 0.58; 95% CI, 0.37–0.90; p = 0.02) without the increase of non‐relapse mortality (NRM). By contrast, in patients with Ph− ALL, VP16/CY/TBI did not improve PFS nor incidence of relapse; addition of VP16 reduced relapse (HR, 0.65; p = 0.06) in patients with Ph− ALL transplanted at CR1, while improved PFS was not observed (HR, 0.90; p = 0.52) due to increased NRM. This study demonstrated that VP16/CY/TBI is a more effective and well‐tolerated regimen in comparison with CY/TBI in patients with myeloablative allo‐HSCT for adult Ph+ ALL. Our findings can provide a novel algorithm for conditioning regimen selection in patients with adult ALL. |
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| AbstractList | The medium‐dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used in allogenic hematopoietic stem cell transplantation (allo‐HSCT) for acute lymphoblastic leukemia (ALL). However, the patient subgroups who can actually benefit from VP16/CY/TBI compared to CY/TBI have not been precisely defined. Therefore, we conducted a multi‐center retrospective study using the Japanese nationwide registry database to elucidate the efficacy of VP16/CY/TBI on post‐transplant prognosis. Biological and clinical distinct subtypes (i.e., Philadelphia chromosome‐positive (Ph+) and ‐negative (Ph−) ALL) were evaluated separately, which included 820 Ph+ and 1463 patients with Ph− ALL, respectively. Compared with the CY/TBI group, the VP16/CY/TBI group showed superior progression‐free survival (PFS) in patients with Ph+ ALL (65% vs. 57% at 3 years after HSCT; adjusted hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55–0.98;
p
= 0.03), along with significantly reduced incidence of relapse (adjusted HR, 0.58; 95% CI, 0.37–0.90;
p
= 0.02) without the increase of non‐relapse mortality (NRM). By contrast, in patients with Ph− ALL, VP16/CY/TBI did not improve PFS nor incidence of relapse; addition of VP16 reduced relapse (HR, 0.65;
p
= 0.06) in patients with Ph− ALL transplanted at CR1, while improved PFS was not observed (HR, 0.90;
p
= 0.52) due to increased NRM. This study demonstrated that VP16/CY/TBI is a more effective and well‐tolerated regimen in comparison with CY/TBI in patients with myeloablative allo‐HSCT for adult Ph+ ALL. Our findings can provide a novel algorithm for conditioning regimen selection in patients with adult ALL. The medium‐dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used in allogenic hematopoietic stem cell transplantation (allo‐HSCT) for acute lymphoblastic leukemia (ALL). However, the patient subgroups who can actually benefit from VP16/CY/TBI compared to CY/TBI have not been precisely defined. Therefore, we conducted a multi‐center retrospective study using the Japanese nationwide registry database to elucidate the efficacy of VP16/CY/TBI on post‐transplant prognosis. Biological and clinical distinct subtypes (i.e., Philadelphia chromosome‐positive (Ph+) and ‐negative (Ph−) ALL) were evaluated separately, which included 820 Ph+ and 1463 patients with Ph− ALL, respectively. Compared with the CY/TBI group, the VP16/CY/TBI group showed superior progression‐free survival (PFS) in patients with Ph+ ALL (65% vs. 57% at 3 years after HSCT; adjusted hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55–0.98; p = 0.03), along with significantly reduced incidence of relapse (adjusted HR, 0.58; 95% CI, 0.37–0.90; p = 0.02) without the increase of non‐relapse mortality (NRM). By contrast, in patients with Ph− ALL, VP16/CY/TBI did not improve PFS nor incidence of relapse; addition of VP16 reduced relapse (HR, 0.65; p = 0.06) in patients with Ph− ALL transplanted at CR1, while improved PFS was not observed (HR, 0.90; p = 0.52) due to increased NRM. This study demonstrated that VP16/CY/TBI is a more effective and well‐tolerated regimen in comparison with CY/TBI in patients with myeloablative allo‐HSCT for adult Ph+ ALL. Our findings can provide a novel algorithm for conditioning regimen selection in patients with adult ALL. The medium‐dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used in allogenic hematopoietic stem cell transplantation (allo‐HSCT) for acute lymphoblastic leukemia (ALL). However, the patient subgroups who can actually benefit from VP16/CY/TBI compared to CY/TBI have not been precisely defined. Therefore, we conducted a multi‐center retrospective study using the Japanese nationwide registry database to elucidate the efficacy of VP16/CY/TBI on post‐transplant prognosis. Biological and clinical distinct subtypes (i.e., Philadelphia chromosome‐positive (Ph+) and ‐negative (Ph−) ALL) were evaluated separately, which included 820 Ph+ and 1463 patients with Ph− ALL, respectively. Compared with the CY/TBI group, the VP16/CY/TBI group showed superior progression‐free survival (PFS) in patients with Ph+ ALL (65% vs. 57% at 3 years after HSCT; adjusted hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55–0.98; p = 0.03), along with significantly reduced incidence of relapse (adjusted HR, 0.58; 95% CI, 0.37–0.90; p = 0.02) without the increase of non‐relapse mortality (NRM). By contrast, in patients with Ph− ALL, VP16/CY/TBI did not improve PFS nor incidence of relapse; addition of VP16 reduced relapse (HR, 0.65; p = 0.06) in patients with Ph− ALL transplanted at CR1, while improved PFS was not observed (HR, 0.90; p = 0.52) due to increased NRM. This study demonstrated that VP16/CY/TBI is a more effective and well‐tolerated regimen in comparison with CY/TBI in patients with myeloablative allo‐HSCT for adult Ph+ ALL. Our findings can provide a novel algorithm for conditioning regimen selection in patients with adult ALL. The medium-dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used in allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL). However, the patient subgroups who can actually benefit from VP16/CY/TBI compared to CY/TBI have not been precisely defined. Therefore, we conducted a multi-center retrospective study using the Japanese nationwide registry database to elucidate the efficacy of VP16/CY/TBI on post-transplant prognosis. Biological and clinical distinct subtypes (i.e., Philadelphia chromosome-positive (Ph+) and -negative (Ph-) ALL) were evaluated separately, which included 820 Ph+ and 1463 patients with Ph- ALL, respectively. Compared with the CY/TBI group, the VP16/CY/TBI group showed superior progression-free survival (PFS) in patients with Ph+ ALL (65% vs. 57% at 3 years after HSCT; adjusted hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55-0.98; p = 0.03), along with significantly reduced incidence of relapse (adjusted HR, 0.58; 95% CI, 0.37-0.90; p = 0.02) without the increase of non-relapse mortality (NRM). By contrast, in patients with Ph- ALL, VP16/CY/TBI did not improve PFS nor incidence of relapse; addition of VP16 reduced relapse (HR, 0.65; p = 0.06) in patients with Ph- ALL transplanted at CR1, while improved PFS was not observed (HR, 0.90; p = 0.52) due to increased NRM. This study demonstrated that VP16/CY/TBI is a more effective and well-tolerated regimen in comparison with CY/TBI in patients with myeloablative allo-HSCT for adult Ph+ ALL. Our findings can provide a novel algorithm for conditioning regimen selection in patients with adult ALL.The medium-dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used in allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL). However, the patient subgroups who can actually benefit from VP16/CY/TBI compared to CY/TBI have not been precisely defined. Therefore, we conducted a multi-center retrospective study using the Japanese nationwide registry database to elucidate the efficacy of VP16/CY/TBI on post-transplant prognosis. Biological and clinical distinct subtypes (i.e., Philadelphia chromosome-positive (Ph+) and -negative (Ph-) ALL) were evaluated separately, which included 820 Ph+ and 1463 patients with Ph- ALL, respectively. Compared with the CY/TBI group, the VP16/CY/TBI group showed superior progression-free survival (PFS) in patients with Ph+ ALL (65% vs. 57% at 3 years after HSCT; adjusted hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55-0.98; p = 0.03), along with significantly reduced incidence of relapse (adjusted HR, 0.58; 95% CI, 0.37-0.90; p = 0.02) without the increase of non-relapse mortality (NRM). By contrast, in patients with Ph- ALL, VP16/CY/TBI did not improve PFS nor incidence of relapse; addition of VP16 reduced relapse (HR, 0.65; p = 0.06) in patients with Ph- ALL transplanted at CR1, while improved PFS was not observed (HR, 0.90; p = 0.52) due to increased NRM. This study demonstrated that VP16/CY/TBI is a more effective and well-tolerated regimen in comparison with CY/TBI in patients with myeloablative allo-HSCT for adult Ph+ ALL. Our findings can provide a novel algorithm for conditioning regimen selection in patients with adult ALL. The medium-dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used in allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL). However, the patient subgroups who can actually benefit from VP16/CY/TBI compared to CY/TBI have not been precisely defined. Therefore, we conducted a multi-center retrospective study using the Japanese nationwide registry database to elucidate the efficacy of VP16/CY/TBI on post-transplant prognosis. Biological and clinical distinct subtypes (i.e., Philadelphia chromosome-positive (Ph+) and -negative (Ph-) ALL) were evaluated separately, which included 820 Ph+ and 1463 patients with Ph- ALL, respectively. Compared with the CY/TBI group, the VP16/CY/TBI group showed superior progression-free survival (PFS) in patients with Ph+ ALL (65% vs. 57% at 3 years after HSCT; adjusted hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55-0.98; p = 0.03), along with significantly reduced incidence of relapse (adjusted HR, 0.58; 95% CI, 0.37-0.90; p = 0.02) without the increase of non-relapse mortality (NRM). By contrast, in patients with Ph- ALL, VP16/CY/TBI did not improve PFS nor incidence of relapse; addition of VP16 reduced relapse (HR, 0.65; p = 0.06) in patients with Ph- ALL transplanted at CR1, while improved PFS was not observed (HR, 0.90; p = 0.52) due to increased NRM. This study demonstrated that VP16/CY/TBI is a more effective and well-tolerated regimen in comparison with CY/TBI in patients with myeloablative allo-HSCT for adult Ph+ ALL. Our findings can provide a novel algorithm for conditioning regimen selection in patients with adult ALL. |
| Author | Morita‐Fujita, Mari Kondo, Tadakazu Ota, Shuichi Toya, Takashi Harada, Kaito Arai, Yasuyuki Ichinohe, Tatsuo Kimura, Takafumi Kako, Shinichi Atsuta, Yoshiko Ozawa, Yukiyasu Onizuka, Makoto Kanda, Yoshinobu Maruyama, Yumiko Ara, Takahide Uchida, Naoyuki Takada, Satoru Fukuda, Takahiro Kawakita, Toshiro |
| AuthorAffiliation | 14 Department of Hematology and Oncology Research Institute for Radiation Biology and Medicine Hiroshima University Hiroshima Japan 15 Preparation Department Japanese Red Cross Kinki Block Blood Center Osaka Japan 16 Japanese Data Center for Hematopoietic Cell Transplantation Nagakute Japan 6 Department of Hematology Japanese Red Cross Nagoya First Hospital Nagoya Japan 7 Department of Hematopoietic Stem Cell Transplantation National Cancer Center Hospital Tokyo Japan 17 Department of Registry Science for Transplant and Cellular Therapy Aichi Medical University School of Medicine Nagakute Japan 12 Department of Hematology National Hospital Organization Kumamoto Medical Center Kumamoto Japan 1 Department of Hematology and Oncology Graduate School of Medicine Kyoto University Kyoto Japan 9 Division of Hematology Jichi Medical University Saitama Medical Center Saitama Japan 11 Leukemia Research Center Saiseikai Maebashi Hospital Maebashi Japan 5 Hematology Division Tokyo Metropolitan Cancer and Inf |
| AuthorAffiliation_xml | – name: 2 Department of Clinical Laboratory Medicine Graduate School of Medicine Kyoto University Kyoto Japan – name: 17 Department of Registry Science for Transplant and Cellular Therapy Aichi Medical University School of Medicine Nagakute Japan – name: 5 Hematology Division Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Tokyo Japan – name: 15 Preparation Department Japanese Red Cross Kinki Block Blood Center Osaka Japan – name: 12 Department of Hematology National Hospital Organization Kumamoto Medical Center Kumamoto Japan – name: 4 Department of Hematology Toranomon Hospital Tokyo Japan – name: 9 Division of Hematology Jichi Medical University Saitama Medical Center Saitama Japan – name: 7 Department of Hematopoietic Stem Cell Transplantation National Cancer Center Hospital Tokyo Japan – name: 8 Department of Hematology Sapporo Hokuyu Hospital Sapporo Japan – name: 16 Japanese Data Center for Hematopoietic Cell Transplantation Nagakute Japan – name: 6 Department of Hematology Japanese Red Cross Nagoya First Hospital Nagoya Japan – name: 10 Department of Hematology University of Tsukuba Hospital Ibaraki Japan – name: 14 Department of Hematology and Oncology Research Institute for Radiation Biology and Medicine Hiroshima University Hiroshima Japan – name: 1 Department of Hematology and Oncology Graduate School of Medicine Kyoto University Kyoto Japan – name: 3 Department of Hematology and Oncology Tokai University School of Medicine Isehara Japan – name: 13 Department of Hematology Hokkaido University Hospital Sapporo Japan – name: 11 Leukemia Research Center Saiseikai Maebashi Hospital Maebashi Japan |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/35790020$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1016_j_jcyt_2023_07_008 crossref_primary_10_1038_s43856_024_00680_y crossref_primary_10_1016_j_jtct_2023_12_004 |
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| PublicationYear | 2022 |
| Publisher | Wiley Subscription Services, Inc John Wiley and Sons Inc |
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| Snippet | The medium‐dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used... The medium-dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used... |
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| SubjectTerms | Acute lymphoblastic leukemia Adult Algorithms Conditioning Cyclophosphamide Etoposide Hematopoietic stem cells Humans Irradiation Leukemia Lymphatic leukemia Medical prognosis Original Philadelphia chromosome Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Radiation Registries Retrospective Studies Stem cell transplantation Stem cells Subgroups Transplantation Transplants & implants VP16 protein VP16/CY/TBI Whole-Body Irradiation |
| Title | Adult patients with Ph+ ALL benefit from conditioning regimen of medium‐dose VP16 plus CY/TBI |
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