ABSTRACT
Outcomes with conventional allogeneic hematopoietic cell transplantation (HCT) after failed HCT are typically poor. To reduce transplantation-related mortality (TRM), 55 patients (median age, 43 years; range, 18-69 years) who had failed conventional autologous (n = 49), allogeneic (n = 4), or syngeneic (n = 2) HCT received human leukocyte antigen-matched related (n = 31) or unrelated (n = 24) donor allografts after nonmyeloablative conditioning with 2 Gy of total body irradiation or 2 Gy of total body irradiation and 90 mg/m(2) of fludarabine. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. One rejection occurred. 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% (95% confidence interval [CI], 9% to 31%). The median follow-up among the 22 survivors is 368 days (range, 173-796 days). Seventeen of 22 survivors are progression-free. One-year estimates of overall and progression-free survival rates are 49% (95% CI, 35% to 62%) and 28% (95% CI, 16% to 41%), respectively. Untreated disease at the time of allografting after nonmyeloablative conditioning increased the risk of death (hazard ratio = 2.4; P =.04). Although the length of follow-up is still short, it appears that encouraging outcomes can be achieved with nonmyeloablative conditioning in patients expected to have poor outcomes with conventional allografting.
Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Mycophenolic Acid/analogs & derivatives , Salvage Therapy , Transplantation Conditioning/methods , Vidarabine/analogs & derivatives , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/toxicity , Cyclosporine/administration & dosage , Graft Survival , Hematologic Neoplasms/complications , Hematologic Neoplasms/mortality , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/mortality , Humans , Immunosuppression Therapy/methods , Middle Aged , Mycophenolic Acid/administration & dosage , Survival Analysis , Transplantation, Autologous , Transplantation, Homologous , Treatment Failure , Treatment Outcome , Vidarabine/administration & dosage , Whole-Body IrradiationABSTRACT
Many patients with acute myeloid leukaemia (AML) in first complete remission (CR1) are ineligible for allogeneic transplantation as a result of age or medical problems other than leukaemia. Eighteen patients (median age 59 years, range 36-73 years) with de novo (n = 13) and secondary (n = 5) AML in morphological CR1, who were not candidates for conventional allografting, received non-myeloablative peripheral blood stem cell transplants from human leucocyte antigen identical sibling donors after conditioning with 2 Gy total body irradiation (TBI; n = 10) or 2 Gy TBI and 90 mg/m2 of fludarabine (n = 8). Postgrafting immunosuppression was with cyclosporine and mycophenolate mofetil. Two rejections were observed in patients not given fludarabine and one died with relapse. Overall, 10 patients died between 77 and 841 d, seven from relapse and three from non-relapse mortality (NRM). Day +100 NRM was 0% with a 1-year estimated NRM of 17%[95% confidence interval (CI) 0-35%]. The median follow-up among the eight survivors was 766 d (range, 188-1141 d). Seven of these eight survivors remain in complete remission (CR). One-year estimates of overall and progression-free survivals were 54% (95% CI 31-78%) and 42% (95% CI 19-66%) respectively. While follow-up is short, this analysis demonstrates that the procedure is sufficiently safe to be studied in a wider group of patients.
