Influence of Pretransplant Platinum-Based Chemotherapy on Renal Function and Outcomes after Allogeneic Hematopoietic Cell Transplantation for Lymphoma

Background: Platinum derivatives play important roles in salvage chemotherapy of malignant lymphoma, but may cause renal dysfunction. We examined the influence of pretransplant platinum-based chemotherapy on renal function and outcomes after allogeneic hematopoietic cell transplantation (HCT) for lymphoma. Methods: This retrospective study cohort included 229 adult patients with malignant lymphoma who had a first allogeneic HCT between 2000 and 2014 at our center. We collected cumulative doses of cisplatin (CDDP) and carboplatin (CBDCA) before allogeneic HCT, and daily renal function (eGFR) during the first 100 days after HCT. Risk factors for renal injury (eGFR <75 ml/min/1.73 m2) are examined using logistic models. Changes in renal function between the groups were conducted by the repeated measures ANOVA. Non-relapse mortality rates were compared with the Gray test. Results: 145 patients were males and 84 females. The median patient age was 49 years (range, 19-67). Patients were divided into three groups according to the cumulative dose of each platinum agent: no CDDP (n = 129), CDDP ≤275 mg/m2 (n = 50) and >275 mg/m2 (n = 50); and no CBDCA (n = 111), CBDCA ≤1200 mg/m2 (n = 77) and CBDCA >1200 mg/m2 (n = 41). Proportions of patients with pretransplant renal injury were 32% in no CDDP group, 36% in CDDP ≤275 mg/m2 group, and 70% in CDDP >275 mg/m2 group (P < .01). Proportions did not differ statistically according to cumulative CBDCA doses. Multivariate analysis showed that cumulative CDDP doses >275 mg/m2, aggressive and highly aggressive B cell lymphoma, and patient age ≥50 years were associated with pretransplant renal injury. Changes in eGFR across time after HCT are shown in Figure 1. Repeated measures ANOVA showed significant differences in between–subject factor and within-subject factor between no CDDP group and CDDP >275 mg/m2 group. Between no CDDP group and CDDP ≤275 mg/m2 group, there was a significant difference in within-subject factor and interaction. Pretransplant renal injury was associated with a trend for higher 2-year nonrelapse mortality rates (17% versus 10%, P = .12). Proportions of renal-related causes of death were higher among patients with pretransplant renal injury than those with normal renal function (34% versus 13%, P = .02). Conclusion: We should pay attention to pretransplant cumulative CDDP doses in patients with malignant lymphoma who are eligible for allogeneic HCT. Our results may support avoidance of CDDP use for these patients. CBDCA could have less influence on renal injury than CDDP.