Reduced-Intensity Conditioning with Busulfan, Fludarabine, and Antithymocyte Globulin for Hematopoietic Cell Transplantation from Unrelated or Haploidentical Family Donors in Patients with Acute Myeloid Leukemia in Remission.
To investigate the role of antithymocyte globulin (ATG)-containing reduced-intensity conditioning (RIC) in hematopoietic cell transplantation (HCT) from unrelated (UD) or haploidentical family donors (HFD), we conducted a phase 2 trial of 237 patients (age range, 16 to 69 years) with acute myeloid leukemia (AML) in remission. Patients undergoing UD-HCT (n = 93) or HFD-HCT (n = 59) received RIC comprising busulfan, fludarabine, and ATG, 9 mg/kg, whereas those undergoing HCT from matched sibling donors (MSD, n = 85) received myeloablative busulfan and cyclophosphamide conditioning or aforementioned RIC with ATG, 4.5 mg/kg. For graft-versus-host disease (GVHD) prophylaxis, cyclosporine and methotrexate were administered. The median follow-up period was 44.7 months after HCT for 161 survivors. For UD-HCT versus HFD-HCT, there were no significant differences in leukemia recurrence, nonrelapse mortality, relapse-free survival, grades 2 to 4 acute GVHD, and moderate-to-severe chronic GVHD. Furthermore, when the outcomes of UD-HCT and HFD-HCT were combined and compared with those of MSD-HCT, there were no significant differences in leukemia recurrence (3-year cumulative incidence, 30% versus 29%), nonrelapse mortality (3-year cumulative incidence, 7% versus 8%), relapse-free survival (3-year estimate, 63% versus 63%), and grades 2 to 4 acute GVHD (120-day cumulative incidence, 16% versus 13%). Moderate-to-severe chronic GVHD, however, occurred less frequently in UD/HFD-HCT (2-year cumulative incidence, 22% versus 40%; P = .006). The addition of ATG to conditioning regimen was a significant predictor for less chronic GVHD (subdistribution hazard ratio, .59). In AML in remission, UD/HFD-HCT after ATG-containing RIC achieved leukemia control equivalent to that of MSD-HCT. Despite HLA disparity in UD/HFD-HCT, chronic GVHD occurred less frequently after ATG-containing RIC, suggesting a strong GVHD-modulating effect of ATG.
Lee KH
，Lee JH
，Lee JH
，Kim DY
，Park HS
，Choi EJ
，Ko SH
，Seol M
，Lee YS
，Kang YA
，Jeon M
，Baek S
，Kang YL
，Kim SH
，Yun SC
，Kim H
，Jo JC
，Choi Y
，Joo YD
，Lim SN
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Incidence and risk factor of hemorrhagic cystitis after allogeneic transplantation with fludarabine, busulfan, and anti-thymocyte globulin myeloablative conditioning.
Hemorrhagic cystitis (HC) is a complication of allogeneic stem cell transplantation (SCT), associated with factors such as BK polyomavirus reactivation, age, conditioning regimen, and presence of graft-versus-host disease (GVHD). The incidence and impact of HC in patients receiving fludarabine (Flu), busulfan (Bu), and anti-thymocyte globulin (ATG) conditioning is unknown.
We conducted a case-control study of patients undergoing SCT at our center between January 1, 2003 and Dec 31, 2012, to determine the incidence of HC and its effect on patient outcomes including overall survival (OS), relapse, non-relapse mortality (NRM), GVHD, and healthcare resource use.
In total, 94 cases of HC were identified and matched to controls based on age, donor type, disease type, and disease status at transplantation. The total incidence of HC was 17.7% (117 of 661 patients). Cases had a higher rate (43.6% vs 27.1%, P=.0394) of acute GVHD (Grade II-IV), and chronic GVHD requiring systemic steroids (34.9% vs 18.6%, P=.004). Male gender was found to be a risk factor (hazard ratio [HR]=1.725, P=.017). OS and progression-free survival did not differ between cases and controls (OS HR=1.128, 95% confidence interval [CI] 0.7807-1.639; progression-free survival HR=0.8809, 95% CI 0.6320-1.234), however the rate of NRM was higher in cases (HR=1.632, 95% CI 1.007-2.830). Median length of hospitalization was longer for patients with HC than matched controls (65.5 days vs 40.5 days, P<.0001).
HC is common in patients undergoing allogeneic SCT with FluBuATG conditioning, and affects the duration of hospitalization. Rate of GVHD is higher among patients with HC. While OS is not affected, an association was seen with higher NRM in our study. Improvement in treatment for HC may lead to reductions in morbidity and healthcare resource utilization.
Lam W
，Storek J
，Li H
，Geddes M
，Daly A
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