Optimization of high-dose methotrexate prophylaxis for central nervous system relapse in diffuse large B-cell lymphoma: a multicenter analysis.
Yu FangNing SuShuyun MaJun CaiLiye ZhongWenyu LiHuiqiang HuangZhiming LiHe HuangYi XiaPanpan LiuLinlang GuoZhihua LiYudan WuXiaopeng TianJinni WangYuchen ZhangQing-Qing CaiPublished in: Annals of hematology (2022)
Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is a rare but devastating event. Intravenous high-dose methotrexate (HD-MTX) is recommended as CNS prophylaxis, but the optimal timing and dose has not been elucidated. Here, we report a multicenter analysis of prophylactic HD-MTX administration for DLBCL. Two hundred eighty-four patients receiving HD-MTX either concurrent with each induction chemotherapy cycle (n = 221) or at the end of induction therapy (EOI, n = 63) were included. Patients with CNS-IPI scoring 4-6, and/or testicular involvement, and/or double/triple hit lymphoma, were stratified into the high-risk group and the others into the moderate-risk group. Concurrent HD-MTX was associated with increased risk of grade 3/4 treatment-related toxicity (OR,1.49; P = 0.006) and subsequent chemotherapy delays (OR, 1.87; P = 0.003) in multivariate analysis. With a median follow-up of 36.0 months, no significant difference in CNS relapse rate was identified between the concurrent and EOI groups (3.2% vs 4.8%, P = 0.34), even in the high-risk group. Analysis on systemic MTX dose suggested that high-dose MTX (≥ 2 g/m 2 ) was associated with better CNS relapse control only in the high-risk group, but not in the moderate-risk group. This study may elucidate the superiority of EOI HD-MTX to some extent. High MTX dose (≥ 2 g/m 2 ) may not be necessary for the moderate-risk patients.
Keyphrases
- diffuse large b cell lymphoma
- high dose
- epstein barr virus
- low dose
- blood brain barrier
- stem cell transplantation
- locally advanced
- end stage renal disease
- free survival
- high intensity
- oxidative stress
- newly diagnosed
- chronic kidney disease
- ejection fraction
- stem cells
- squamous cell carcinoma
- clinical trial
- peritoneal dialysis
- radiation therapy
- cross sectional
- replacement therapy
- drug induced