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Omission of day +11 methotrexate dose and allogeneic hematopoietic cell transplantation outcomes: results of a systematic review/meta-analysis

Bone Marrow Transplantation volume 57, pages 65–71 (2022)Cite this article

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Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for patients with malignant and benign hematologic conditions. Graft-versus-host disease (GVHD) is a known complication of allo-HCT that results in significant morbidity and mortality. A common GVHD prophylaxis strategy combines a calcineurin inhibitor with methotrexate. When mucositis and organ toxicity develop, the day +11 dose is frequently omitted to limit further organ damage. The potential impact of this practice on allo-HCT outcomes is unclear as published data show conflicting results. Thus, we performed a systematic review/meta-analysis of the available literature to assess the impact of omitting day +11 methotrexate on allo-HCT recipients. Data were extracted in relation to benefits (overall survival [OS], progression-free survival [PFS]) and harms (acute and chronic GVHD, non-relapse mortality [NRM], and relapse). Pooled OS rate favored those who received day +11 methotrexate vs. those who did not (HR = 1.21; 95% CI = 1.02–1.43; p = 0.03). There was no significant difference in pooled rates of PFS (HR = 0.96; 95% CI = 0.60–1.52; p = 0.85), acute GVHD (HR = 1.03; 95% CI = 0.35–2.98; p = 0.96), chronic GVHD (HR = 0.83; 95% CI = 0.44–1.57; p = 0.57), NRM (HR = 0.86; 95% CI = 0.67–1.11; p = 0.25), and relapse (HR = 0.97; 95% CI = 0.75–1.26; p = 0.83) between the two groups. Large prospective multicenter studies are needed to better define the significance of day +11 methotrexate omission.

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Fig. 1: Study selection flow diagram.
Fig. 2: Pooled overall survival rate.
Fig. 3: Pooled progression-free survival rate.
Fig. 4: Pooled acute GVHD rate.
Fig. 5: Pooled chronic GVHD rate.
Fig. 6: Pooled non-relapse mortality rate.

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Authors and Affiliations

  1. Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Programs, Mayo Clinic, Jacksonville, FL, USA

    Mohamed A. Kharfan-Dabaja, Farah Yassine, Katelyn Keller, Andre Fernandez, Hemant Murthy, Ernesto Ayala & Madiha Iqbal

  2. Research Methodology and Biostatistics Core, Office of Research, Morsani College of Medicine, University of South Florida, Tampa, FL, USA

    Tea Reljic

  3. Largo High School, IB Program, Largo, FL, USA

    Arni Kumar

  4. Department of Adult Hematology and Stem Cell Transplantation, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

    Mahmoud Aljurf

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  1. Mohamed A. Kharfan-Dabaja
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Contributions

MAK-D: developed the concept, obtained the data, analyzed the data, interpreted the results, and wrote the manuscript. TR: obtained the data, analyzed the data, interpreted the results, and wrote the manuscript. AK: obtained the data, analyzed the data, and interpreted the results. FY: obtained the data, analyzed the data, interpreted the results, and edited the manuscript. KK: obtained the data, analyzed the data, and interpreted the results. AF: obtained the data, analyzed the data, and interpreted the results. HM: interpreted the results and edited the manuscript. EA: interpreted the results and edited the manuscript. MA: interpreted the results and edited the manuscript. MI: analyzed the data, interpreted the results, and edited the manuscript.

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Correspondence to Mohamed A. Kharfan-Dabaja.

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MAK-D reports consultancy for Daiichi Sankyo in the past 36 months. All other authors declare no relevant conflicts of interest.

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Kharfan-Dabaja, M.A., Reljic, T., Kumar, A. et al. Omission of day +11 methotrexate dose and allogeneic hematopoietic cell transplantation outcomes: results of a systematic review/meta-analysis. Bone Marrow Transplant 57, 65–71 (2022). https://doi.org/10.1038/s41409-021-01496-3

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