RENAL TOXICITY AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION - THE COMBINED EFFECTS OF TOTAL-BODY IRRADIATION AND GRAFT-VERSUS-HOST DISEASE

Purpose: To evaluate retrospectively the cumulative risk probability a nd factors correlated with renal dysfunction after allogeneic bone mar row transplantation (BMT). Patients and Methods: From October 1984 to July 1994, 84 patients with malignant hematopoietic diseases received allogeneic BMT after conditioning with high-dose chemotherapy and tota l-body irradiation (TBI). Seventy-nine patients with normal renal func tion before conditioning are included in this study. Conditioning incl uded high-dose cyclophosphamide without (n = 46) or with (n = 33) othe r agents (daunorubicin, busulfan, cytarabine, and thiotepa) followed b y TBI. The TBI dose prescribed to the center of the abdomen was 10 Gy for 24 patients, 12 Gy for 32, and 13.5 Gy for 23. In vitro T-cell dep letion was undertaken in 48 cases. The post-BMT nephrotoxicity of amin oglycosides, vancomycin, amphotericin, and cyclosporine was assessed. Time to renal dysfunction was defined as the time to a persistent incr ease of serum creatinine (SCr) level greater than 110 mu mol/L. The po tential influence of sex, age, diagnosis, chimerism, and graft-versus- host disease (GVHD) on renal dysfunction was also assessed. Results: T he 18-month probability of renal dysfunction-free survival (RDFS) for the whole group was 77%.Only TBI dose and presence of GvHD were signif icantly correlated with renal dysfunction by multivariate analysis. Th e 18-month probabilities of RDFS were 95%, 74%, and 55% for the patien ts conditioned with 10, 12, and 13.5 Gy, respectively. The 18-month RD FS probabilities were 88% and 61% for patients without and with GvHD, respectively. Combining both variables, we have defined two risk categ ories: low-risk (ie, 10 Gy TBI with/without GVHD and 12 Gy TBI without GVHD) and highrisk (ie, 12 Gy TBI with GVHD and 13.5 Gy TBI with/with out GVHD). The predicted 18-month RDFS rates were 93% and 52% for the low- and high-risk groups, respectively. Conclusion: Renal dysfunction after allogeneic BMT is strongly related to the delivered TBI dose (a nd dose per fraction) and to the presence of GVHD. Renal shielding sho uld be recommended if a TBI dose greater than 12 Gy (fractionated twic e daily over 3 days) is to be prescribed. Furthermore, in those cases with a high risk of developing GvHD (eg, unrelated allogeneic BMT, abs ence of T-cell depletion), these data suggest that kidney doses greate r than 10 Gy should be avoided. (C) 1996 by American Society of Clinic al Oncology.