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

• Published in: Bone marrow transplantation (Basingstoke) 2022-01, Vol.57 (1), p.65-71
• Main Authors: Kharfan-Dabaja, Mohamed A., Reljic, Tea, Kumar, Arni, Yassine, Farah, Keller, Katelyn, Fernandez, Andre, Murthy, Hemant, Ayala, Ernesto, Aljurf, Mahmoud, Iqbal, Madiha
• Format: Article
• Language: English
• Subjects: 692/308; 692/308/2171; Bone marrow; Calcineurin; Calcineurin inhibitors; Cell Biology; Graft versus host disease; Graft vs Host Disease - etiology; Graft-versus-host reaction; Hematology; Hematopoietic Stem Cell Transplantation - methods; Humans; Impact damage; Internal Medicine; Medicine; Medicine & Public Health; Meta-analysis; Methotrexate; Methotrexate - therapeutic use; Morbidity; Mortality; Mucositis; Prophylaxis; Prospective Studies; Public Health; Recurrence; Stem cell transplantation; Stem Cells; Survival; Systematic review; Toxicity; Transplantation; Transplantation Conditioning - methods
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/s41409-021-01496-3

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.