Abstract

Reduced-intensity stem cell transplantation (RIST) with a purine analog most often involves fludarabine (Flu). The alternative drug, 2CdA, is rarely used partly because of a potential risk of renal toxicity. We retrospectively reviewed the medical records of 282 patients (median age, 54 y; range, 21-68) with various hematological malignancies who underwent RIST between 1999 and 2007 with a conditioning regimen that consisted of busulfan (po 8 mg/kg or iv 6.4 mg/kg) in combination with either 2CdA (0.66 mg/kg, n=71, C-group) or Flu (180 mg/m2, n=211, F-group). Seventy-four patients also received 2-4 Gy of TBI. The donor was related (BM 8, PB 177) in 185 patients, and unrelated in 97 (BM 79, PB 1, CB 17). GVHD prophylaxis consisted of cyclosporine (CSP, starting dose 3 mg/kg/day civ, target whole blood conc. 250-350 ng/ml, n=232) or tacrolimus (starting dose 0.03 mg/kg/day civ, target whole blood conc. 10-20 ng/ml, n=50), with (n=131) or without (n=151) MTX. Sixty-nine patients also received anti-human T- lymphocyte immunoglobulin (ATG, 5-10 mg/kg). Except for the stem cell sources, there were no significant differences between the C- and F-groups. Acute renal failure (ARF) within 100 days was defined as there was a greater than two-fold rise in the serum creatinine concentration compared to the baseline. The median follow-up in surviving patients was 1589 days (50-3291). The 275 patients who survived more than 30 days (except for one patient who died of relapse) all achieved neutrophil engraftment in a median 13 days (range, 5-42 days). No significant difference was observed between C- and F-group with regard to OS (59% vs 48% at 3 y, p=0.20), relapse rate (42% vs 35% at 3 y, p=0.42), NRM (7% vs 6% on d100, 22% vs 32% at 3 y, p=0.15), or the cumulative incidences of ARF (34% vs 27% on d 100, p=0.26), grade II-IV acute GVHD (46% vs 47%, p=0.40), and extensive chronic GVHD (62% vs 54% at 3 y, p=0.21). Multivariate analyses showed that TBI [HR 2.96 (1.86-4.72), p<0.001] for NRM, TBI [HR 1.75 (1.23-2.49), p=0.002] and high-risk disease [HR 2.39 (1.62-3.55), p<0.001] for OS, and TBI [HR 1.98 (1.25-3.14), p=0.004] and CSP [HR 2.10 (1.06-4.17), p=0.03] for ARF were significant factors for poor outcomes. However, 2CdA was not significantly associated with NRM, OS or ARF. Our study suggested that a relatively low dose of 2CdA was tolerable and feasible as part of a reduced-intensity regimen, and was not associated with any significant nephrotoxicities.

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