A randomized comparison of cyclophosphamide vs. reduced dose cyclophosphamide
plus fludarabine for allogeneic hematopoietic cell transplantation in patients
with aplastic anemia and hypoplastic myelodysplastic syndrome.
Author(s): Kim H, Lee JH, Joo YD, Bae SH, Hyun MS, Lee JH, Kim DY, Lee WS, Ryoo HM, Kim MK,
Park JH, Lee KH; Cooperative Study Group A for Hematology (COSAH).
Affiliation(s): Division of Hematology-Oncology, Ulsan University Hospital University of Ulsan
College of Medicine, Ulsan, Republic of Korea.
Publication date & source: 2012, Ann Hematol. , 91(9):1459-69
Recently, a less toxic regimen comprising reduced cyclophosphamide (Cy),
fludarabine, and anti-thymocyte globulin (ATG) (Cy-Flu-ATG) was used to condition
high-risk patients scheduled for allogeneic hematopoietic cell transplantation
(alloHSCT) instead of standard Cy-ATG in patients with severe aplastic anemia
(AA). We performed a randomized phase III study to compare the regimen-related
toxicities (RRTs) of two different conditioning regimens: Cy-ATG vs. Cy-Flu-ATG.
Patients in the Cy-ATG arm received Cy at 200 mg/kg. Those in the Cy-Flu-ATG arm
received fludarabine (Flu) at 150 mg/m(2) and Cy at 100 mg/kg. A total of 83
patients (40 in the Cy-ATG and 43 in the Cy-Flu-ATG) were enrolled. Seventy-nine
patients had AA and four had MDS. All predefined RRTs were significantly lower in
patients of the Cy-Flu-ATG arm (23.3 vs. 55.0 %; p = 0.003). Infection with
identified causative organism and sinusoidal obstruction syndrome, hematuria,
febrile episodes, and death from any cause tended to be more frequent in Cy-ATG
arm but did not differ significantly between arms. There was no difference in
neutrophil engraftment failure (2.5 vs. 2.33 %; p = 0.959), acute
graft-versus-host disease (GvHD) (15.0 vs. 23.3 %; p = 0.388), and chronic GvHD
(16.7 vs. 16.2 %; p = 0.961) between Cy-ATG and Cy-Flu-ATG arms. The 4-year
survival rate did not differ between the Cy-ATG and Cy-Flu-ATG arms.
Preconditioning with Cy-Flu-ATG was superior to that afforded by Cy-ATG in terms
of reducing RRT levels without increasing engraftment failure.
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