Hct With Nonmyeloablative Conditioning After Failure Of Previous

Given that TRM after a second myeloablative allo-geneic HCT in adults ranges from 50 to 80%,57 several authors have investigated the use of nonmyeloabla-tive or reduced-intensity conditioning regimens in this setting. Nagler et al. described 12 high-risk, heavily treated patients with a median age of 33 (range 8-63) years who received HLA-identical sibling (n = 9) or unrelated (n = 3) HCT58 for acute leukemias or lymphomas. Patients were conditioned with a reduced-intensity regimen consisting of fludarabine (180 mg/m2), busulfan (8 mg/kg/day), and ATG (40 mg/kg). Three-year TRM and progression-free survival rates were 10 and 50%, respectively. Branson et al. reported on 38 patients with refractory, progressive, or relapsed lymphoproliferative diseases after autologous HCT.59 The median age was 44 (range 25-64) years. The conditioning regimen consisted of Campath-1H (100 mg), fludarabine (150 mg/m2), and melphalan (140 mg/m2). Fourteen-month TRM and progressionfree survival rates were 20 and 50%, respectively. Feinstein et al. studied 55 patients with a median age of 43 (range 18-69) years who failed previous mye-loablative autologous (n = 49), allogeneic (n = 4), or syngeneic (n = 2) HCT.60 All patients were considered ineligible for conventional allografts because of age (older than 30 years), medical infirmity, or high-risk of TRM (prior high-dose TBI or dose-limiting organ irradiation). Twelve patients had disease that remained untreated after they failed conventional HCT, and 13 others had treatment-refractory disease at the time of the nonmyeloablative HCT. The non-myeloablative conditioning regimen consisted of 2 Gy TBI alone (n = 7), or 2 Gy TBI and 90 mg/m2 flu-darabine (n = 48). Donors were HLA-identical siblings (n = 31) or HLA-matched unrelated donors (n = 24). Thirty-three patients died a median of 127 days (range 7-834 days) after HCT: 21 of relapse, 11 of TRM, and 1 of suicide. The TRM rate on day 100 was 11%, with an estimated 1-year TRM rate of 20%. One-year progression-free survival was 28%, and untreated disease at the time of the nonmyeloablative HCT increased the risk of death.

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