Renal Dysfunction in Pediatric Acute Leukemia Patients after Allogeneic Hematopoietic Cell Transplantation with Total Body Irradiation-Containing Conditioning Regimen

Abstract

<h3>Purpose/Objective(s)</h3> Renal dysfunction after hematopoietic cell transplantation (HCT) is a multi-factorial disorder. Studies have linked dose and fractionation with the incidence of late renal dysfunction in patients who underwent total body irradiation (TBI)-based myeloablative conditioning, but the effect of dose rate remains under studied. We conducted a single-institution retrospective study to elucidate the effect of TBI parameters and peri-HCT factors on late renal dysfunction among pediatric patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) after allogeneic HCT. <h3>Materials/Methods</h3> 123 patients (age 1-22) with acute leukemia (38 AML, 85 ALL) underwent HCT using a TBI-based regimen at our institution from 2006-2019. HCT conditioning regimen included cyclophosphamide with or without fludarabine followed by TBI (13.2 Gy in 8 twice-daily fractions over 4 days). TBI dose rate was limited to < 20 cGy/min but ranged from 8.7-19.2 cGy/min depending on Linac availability. TBI parameters and peri-HCT factors were recorded and stratified by recipient of high-dose-rate (HDR; > 15 cGy/min; 35%) or low-dose-rate (LDR; ≤15 cGy/min; 65%) TBI. All patients received a calcineurin inhibitor to prevent graft-versus-host disease (GVHD). Serum creatinine (Cr) was recorded at baseline and trended post-HCT. Late renal dysfunction was defined as persistent increase of Cr > 1.2 mg/dL or ≥ 1.25 times the upper limit of age-dependent normal, onset ≥ 3 months after HCT. Using a statistical software, dichotomous variables were tested using Chi-square or Fisher's exact test; and continuous variables using Wilcoxon rank-sum test. Univariate and multivariate analyses were used to examine the association of these variables with late renal dysfunction. <h3>Results</h3> A total of 14 patients developed late renal dysfunction (11%): 6/38 patients in HDR group (14%) vs. 8/79 patients in LDR group (10%, <i>P</i> = 0.03). Comparison between HDR and LDR groups found no difference in age, sex, remission status, HCT comorbidity index (HCT-CI, predictive of late organ dysfunctions, factoring in baseline Cr) or baseline Cr. More patients in the HDR group were cord blood recipients taking cyclosporine/mycophenolate mofetil (37% vs. 19% in LDR, <i>P</i> < 0.01), and fewer were sibling recipients taking tacrolimus/methotrexate (0% vs. 10%, <i>P</i> < 0.01). More patients in HDR group developed acute GVHD (35% vs. 27%, <i>P</i> = 0.05). In univariate analysis, incidence of late renal dysfunction was associated with patient's age ≤12 at HCT (22% vs. 5% > 12), intermediate-high HCT-CI (22% vs. 6% low HCT-CI) and HDR (24% vs. 8% in LDR). On multivariate regression, late renal dysfunction remained associated with age, HCT-CI, and HDR (<i>P</i> = 0.01, 0.02, and < 0.01 respectively). <h3>Conclusion</h3> Patient's age ≤12 at HCT, intermediate-high HCT-CI, and HDR were associated with late renal dysfunction post-HCT. Since dose rate is the only modifiable factor, adoption of LDR TBI is recommended.