Increased non‐relapse mortality due to high‐dose cytarabine plus <scp>CY</scp>/<scp>TBI</scp> in <scp>BMT</scp>/<scp>PBSCT</scp> for acute lymphoblastic leukaemia in adults

Arai, Yasuyuki; Kondo, Tadakazu; Shigematsu, Akio; Tanaka, Junji; Ohashi, Kazuteru; Fukuda, Takahiro; Kawakita, Toshiro; Mori, Takehiko; Hoshino, Takumi; Onizuka, Makoto; Ozawa, Yukiyasu; Yoshida, Shuro; Ueda, Yasunori; Mizuno, Ishikazu; Atsuta, Yoshiko; Mizuta, Shuichi

doi:10.1111/bjh.14652

Cited by 11 publications

(12 citation statements)

References 12 publications

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“…Retrospective analysis of Japanese registry data showed that HDCA/CY/TBI improved prognosis in CBT, but had no effectiveness due to increased NRM in BMT/PBSCT. 28,29 In this study, the benefit of VP16/CY/TBI was less apparent in CBT than in BMT/PBSCT, although the number of cases was smaller in CBT.…”

Section: No Survival Advantage With Vp16/cy/tbi Observed In Patients ...mentioning

confidence: 58%

Adult patients with Ph+ ALL benefit from conditioning regimen of medium‐dose VP16 plus CY/TBI

Morita-Fujita

Arai

Kondo

et al. 2022

Hematological Oncology

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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,This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Section: No Survival Advantage With Vp16/cy/tbi Observed In Patients ...mentioning

confidence: 58%

Adult patients with Ph+ ALL benefit from conditioning regimen of medium‐dose VP16 plus CY/TBI

Morita-Fujita

Arai

Kondo

et al. 2022

Hematological Oncology

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“…It is well recognised that simple conditioning intensification by the additional use of chemotherapeutic agents usually results in the reduction of relapse and increase of NRM simultaneously; ultimately, OS after intensified conditioning is similar to that after standard regimen. 38–40 However, superior OS is observed in some retrospective studies if the clinical study is conducted by inclusion of mainly young and fit patients. 17 41 In BM transplantation and peripheral blood stem cell transplantation, intensified conditioning is more likely to be associated with the increase of severe GVHD triggered by mucosal injury due to the adverse effect of drugs; such severe GVHD often results in mortality.…”

Section: Discussionmentioning

confidence: 99%

Randomised controlled trial of conditioning regimen for cord blood transplantation for adult myeloid malignancies comparing high-dose cytarabine/cyclophosphamide/total body irradiation with versus without G-CSF priming: G-CONCORD study protocol

et al. 2020

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IntroductionA better long-term quality of life after umbilical cord blood transplantation (CBT) is observed compared with transplants from other alternative donors, whereas graft failure and relapses after CBT are still major issues. To minimise graft failure and relapse after CBT, intensification of conditioning by the addition of high-dose cytosine arabinoside (CA) and concomitant continuous use of granulocyte-colony stimulating factor (G-CSF) are reported to convey a significantly better survival after CBT in some retrospective studies. To confirm the effect of G-CSF plus CA combination, in addition to the standard conditioning regimen, cyclophosphamide (CY)/total body irradiation (TBI), we design a randomised controlled study comparing CA/CY/TBI with versus without G-CSF priming (G-CSF combined conditioned cord blood transplantation [G-CONCORD] study).Methods and analysisThis is a multicentre, open-label, randomised phase III study that aimed to compare G-CSF+CA/CY/TBI as a conditioning regimen for CBT with CA/CY/TBI. Patients with acute myeloid leukaemia or myelodysplastic syndrome, aged 16–55 years, are eligible. The target sample size is 160 and the registration period is 4 years. The primary endpoint is the 2-year disease-free survival rate after CBT. The secondary endpoints are overall survival, relapse, non-relapse mortality, acute and chronic graft-versus-host disease, engraftment rate, time to neutrophil recovery, short-term adverse events, incidence of infections and causes of death.This study employs a single one-to-one web-based randomisation between the with-G-CSF versus without-G-CSF groups after patient registration. Combination of high-dose CA and CY/TBI in both groups is used for conditioning.Ethics and disseminationThe study protocol was approved by the central review board, Nagoya University Certified Review Board, after the enforcement of the Clinical Trials Act in Japan. The manuscripts presenting data from this study will be submitted for publication in quality peer-reviewed medical journals. Study findings will be disseminated via presentations at national/international conferences and peer-reviewed journals.Trial registration numbersUMIN000029947 and jRCTs041180059.

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“…The HO-1 rs2071746 SNP was analyzed in 593 HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 allele-matched, unrelated BMT donor-transplant recipient pairs (Table 1). Based on the disease status and other risk factors that influence post-transplant outcomes, as previously reported [22,[27][28][29], standard-risk disease was defined as acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or multiple myeloma (MM) in the first complete remission; malignant lymphoma (ML) in any complete remission; or myelodysplastic syndrome (MDS) or chronic myeloid leukemia (CML) in the chronic phase. Both ALL and AML, which were in the second complete remission, were included in the high-risk group, according to recent reports [27,29] indicating that patients with AML and ALL in the second complete remission have worse post-transplant outcomes than those in the first complete remission.…”

Section: The Frequencies Of Ho-1 Genotypesmentioning

confidence: 99%

Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients

Horio

Morishita

Mizuno

et al. 2020

Cancers

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Heme oxygenase-1 (HO-1), an intracellular enzyme that catalyzes the degradation of heme into biliverdin, free iron, and carbon monoxide, exerts anti-inflammatory and cytoprotective effects against endothelial cell injury. The HO-1 promoter gene has one important single-nucleotide polymorphism (SNP) rs2071746 (-413A>T) that is functional, and the A allele has been reported to be associated with higher HO-1 expression levels than the T allele. We investigated the influence of the HO-1 rs2071746 SNP on the transplant outcomes in 593 patients with hematological malignancies undergoing unrelated, human leukocyte antigen (HLA)-matched, T-cell-replete bone marrow transplantation (BMT) through the Japan Donor Marrow Program. In patients with high-risk diseases, the donor A/A or A/T genotype was associated with better 5 year overall survival (35% vs. 25%; p = 0.03) and 5 year disease-free survival (35% vs. 22%; p = 0.0072), compared to the donor T/T genotype. These effects were not observed in patients with low-risk diseases. The current findings therefore indicate that HO-1 rs2071746 genotyping could be useful for selecting donors and tailoring transplant strategies for patients with high-risk hematologic malignancies.

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Increased non‐relapse mortality due to high‐dose cytarabine plus CY/TBI in BMT/PBSCT for acute lymphoblastic leukaemia in adults

Cited by 11 publications

References 12 publications

Adult patients with Ph+ ALL benefit from conditioning regimen of medium‐dose VP16 plus CY/TBI

Adult patients with Ph+ ALL benefit from conditioning regimen of medium‐dose VP16 plus CY/TBI

Randomised controlled trial of conditioning regimen for cord blood transplantation for adult myeloid malignancies comparing high-dose cytarabine/cyclophosphamide/total body irradiation with versus without G-CSF priming: G-CONCORD study protocol

Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients

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