Conditioning Intensity for Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia Patients with Poor-Prognosis Cytogenetics in First Complete Remission

Konuma, Takaaki; Kondo, Tadakazu; Mizuno, Shohei; Doki, Noriko; Aoki, Jun; Fukuda, Takahiro; Tanaka, Masatsugu; Sawa, Masashi; Katayama, Yuta; Uchida, Naoyuki; Ozawa, Yukiyasu; Morishige, Satoshi; Matsuoka, Ken‐ichi; Ichinohe, Tatsuo; Onizuka, Makoto; Kanda, Junya; Atsuta, Yoshiko; Yanada, Masamitsu

doi:10.1016/j.bbmt.2019.09.025

Cited by 14 publications

(17 citation statements)

References 30 publications

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“…Additionally, the NRM was lower in all three cytogenetic risk groups, which was consistent with our findings in Figure 4 A. From another perspective, patients in CR1 with high-risk cytogenetics or with MRD positive in genomics or multi-parameter flow cytometry (MFC) can benefit more from the MAC regimens 45 - 47 .…”

Section: Discussionsupporting

confidence: 89%

Reduced-intensity versus Myeloablative Conditioning Regimens for Younger Adults with Acute Myeloid Leukemia and Myelodysplastic Syndrome: A systematic review and meta-analysis

Ma¹,

Shi²,

Li³

et al. 2020

J. Cancer

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Background: Historically, reduced-intensity conditioning (RIC) was recommended to be performed for older patients who were considered ineligible for myeloablative conditioning (MAC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the evidence regarding the optimal conditioning intensity in younger patients with AML or MDS is weak and contradictory. Methods: PubMed, Medline, Embase, and other online sources were searched from the initial period to February 25, 2020. Odds ratios and 95% confidence intervals were calculated to estimate pooling effects. Results: Four randomized controlled trials (RCTs) about conditioning intensity involving 633 patients were included. There were no significant differences of 1/2/4/5 years progression-free survival (PFS) and relapse incidence (RI) between two conditioning intensities. Overall survival (OS) was similar at 1/2/4 years, but patients receiving RIC had a higher OS at 5 years. Additionally, RIC were associated with lower non-relapse mortality, less grade II-IV and grade III-IV acute graft-versus-host disease (GVHD), and lower incidence of chronic GVHD compared with MAC regimens. Subgroup analysis showed similar OS and RI for AML patients, and there was a trend towards lower NRM and grade II-IV aGVHD in RIC group. Available data for MDS indicated that OS, PFS, and RI were comparable. For intermediate-risk patients, there was no evidence that RIC is inferior to MAC. However, for high-risk patients, MAC tends to perform better. Conclusions: Based on the above results, it might be concluded that RIC is a feasible treatment option for adults with AML or MDS younger than 66 years, particularly those with intermediate-risk disease. Future RCTs incorporating of risk stratifications are warranted to guide the optimal decision under certain conditions.

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Section: Discussionsupporting

confidence: 89%

Reduced-intensity versus Myeloablative Conditioning Regimens for Younger Adults with Acute Myeloid Leukemia and Myelodysplastic Syndrome: A systematic review and meta-analysis

Ma¹,

Shi²,

Li³

et al. 2020

J. Cancer

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“…An analysis of patients with poor-risk cytogenetics who underwent allogeneic HCT during CR1 revealed that MAC was associated with better OS than RIC because of the higher relapse incidence in patients receiving RIC. This study highlights the fact that there were better survival rates in patients who received the optimal conditioning intensity given their specific combination of disease features 27 .…”

Section: Conditioningmentioning

confidence: 66%

Hematopoietic cell transplantation in adults with acute myeloid leukemia: A review of the results from various nationwide registry studies in Japan

Arai

Konuma

Yanada

2021

BCT

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Hematopoietic cell transplantation (HCT) is an integral part of the treatment of acute myeloid leukemia (AML) . Although AML is the most common indication for allogeneic HCT, the relatively small number of patients and the highly complex nature of the procedure often render prospective studies on HCT unfeasible. Observational studies using registry data serve as important sources of information under such circumstances. Thus, the Japanese Society of Hematopoietic Cell Transplantation (JSHCT) has been conducting a nationwide survey of HCT since 1993, and this registration program now covers ＞99% of transplantation centers in Japan. A constant increase in the number of HCT procedures has been noted with recent annual registrations recording more than ＞1,000 new AML patients undergoing allogeneic or autologous HCT. Since its establishment in 2010, the Adult AML Working Group within the JSHCT has been using this registry data to complete several studies focusing on various aspects of HCT in adults with AML, with particular attention paid to patient-, disease-, and transplantation-related factors. This article comprehensively reviews the results obtained from these studies and discusses the strengths and limitations of these kinds of registry-based studies.

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“…The relapse rate is affected by many factors; for example, the cytogenetic and molecular biologic characteristics of diseases, minimal residual disease (MRD) before HSCT and immunosuppressant ajustment protocol, etc. [30][31][32][33] It was impossible that all factors before transplantation were similar in every study, hence the CIR was expected to be heterogeneous between studies. In a large observational analysis by the EBMT included 2974 middle-aged AML patients, relapse incidence was higher in intermediateor high-risk patients but not in low-risk patients in the RIC group.…”

Section: Discussionmentioning

confidence: 99%

Reduced Intensity Conditioning Before Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia in Complete Remission and Myelodysplastic Syndrome: A Meta-Analysis of Randomized Controlled Trials

Song¹,

Yin²,

Ding³

et al. 2021

Preprint

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BackgroundReduced intensity conditioning (RIC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) was reported had the same overall survival (OS) as myeloablative conditioning (MAC) for acute myeloid leukemia (AML) in complete remission (CR) and myelodysplastic syndrome (MDS) but results in different studies are contradictory. Therefore, we conducted a meta-analysis according to the PRISMA 2009 guidelines to confirm the efficacy and safety of RIC vs. MAC for AML in CR and for MDS.MethodsPubMed, Web of Science, Embase, Cochrane central, related websites, major conference proceedings were searched, and related journals were hand-searched from Jan 1, 1980 to July 1, 2020 for studies comparing RIC with MAC before the first allo-HSCT in patients with AML in CR or MDS. Only RCTs were included. OS was the primary endpoint and generic inverse variance method was used to combine hazard ratio (HR) and 95% CI.ResultsWe retrieved 7770 records. Six RCTs with 1413 participants (711 in RIC, 702 in MAC) were included. RIC had the same OS (HR = 0·95, 95% CI 0·64–1·4, P = 0·80) and cumulative incidence of relapse as MAC (HR = 1·18, 95% CI 0·88–1·59, P = 0·28). RIC reduced non-relapse mortality more than total body irradiation/busulfan based MAC (HR = 0·53, 95% CI 0·36–0·80, P = 0·002).ConclusionRIC also had similar long-term OS and graft failure as MAC. RIC is also a good choice for patients with AML in CR or MDS.

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Conditioning Intensity for Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia Patients with Poor-Prognosis Cytogenetics in First Complete Remission

Cited by 14 publications

References 30 publications

Reduced-intensity versus Myeloablative Conditioning Regimens for Younger Adults with Acute Myeloid Leukemia and Myelodysplastic Syndrome: A systematic review and meta-analysis

Reduced-intensity versus Myeloablative Conditioning Regimens for Younger Adults with Acute Myeloid Leukemia and Myelodysplastic Syndrome: A systematic review and meta-analysis

Hematopoietic cell transplantation in adults with acute myeloid leukemia: A review of the results from various nationwide registry studies in Japan

Reduced Intensity Conditioning Before Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia in Complete Remission and Myelodysplastic Syndrome: A Meta-Analysis of Randomized Controlled Trials

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