Omission of day +11 methotrexate dose and allogeneic hematopoietic cell transplantation outcomes: results of a systematic review/meta-analysis.
Mohamed A Kharfan-DabajaTea ReljicArni KumarFarah YassineKatelyn KellerAndre FernandezHemant MurthyErnesto AyalaMahmoud AljurfMadiha IqbalPublished in: Bone marrow transplantation (2021)
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.
Keyphrases
- free survival
- high dose
- allogeneic hematopoietic stem cell transplantation
- stem cell transplantation
- systematic review
- liver failure
- drug induced
- bone marrow
- cell cycle arrest
- oxidative stress
- respiratory failure
- electronic health record
- primary care
- case control
- randomized controlled trial
- meta analyses
- big data
- risk factors
- acute myeloid leukemia
- cell death
- aortic dissection
- radiation therapy
- clinical trial
- cardiovascular disease
- type diabetes
- hematopoietic stem cell
- radiation induced
- cross sectional
- intensive care unit
- kidney transplantation
- signaling pathway
- cell proliferation
- climate change