HLA haploidentical peripheral blood stem cell transplantation using reduced dose of posttransplantation cyclophosphamide for poor-prognosis or refractory leukemia and myelodysplastic syndrome.
Nonmyeloablative, human leukocyte antigen (HLA) haploidentical, T-cell-replete bone marrow transplantation followed by high-dose posttransplantation cyclophosphamide (PT/Cy) has recently been developed. This transplantation milieu has resulted in favorable outcomes with low transplantation-related mortality, owing to a low incidence of graft-versus-host disease (GVHD), without increased infectious complications. However, the high relapse rate remains a major concern. We therefore performed a prospective pilot study of HLA haploidentical peripheral blood stem cell transplantation (PBSCT) with intensified conditioning, followed by two lower doses of PT/Cy. A total of 20 patients with refractory or poor-prognosis myelodysplastic syndrome (MDS) and leukemia were enrolled in the study. A trend toward a lower incidence of grade III-IV acute GVHD at day 100 in the group receiving 25 mg/kg × 2 doses of PT/Cy, compared with the group receiving 25 mg/kg of PT/Cy (9.1% vs. 33%, p = 0.20), was noted. However, the cumulative incidence of chronic GVHD was low, at 10% irrespective of PT/Cy dose. The number of infused CD34(+) cells significantly correlated with the grade of acute GVHD (p = 0.004). In addition, the occurrence of BK virus hemorrhagic cystitis was significantly more common in the double-dose PT/Cy group (25% vs. 0%, p = 0.043), especially when combined with busulfan. The probability of overall survival at 1 year in the double-dose group tended to be better compared with that in the single-dose group (64% vs. 44%, respectively; p = 0.20). In conclusion, HLA haploidentical, T-cell-replete PBSCT with 25 mg/kg × 2 doses of PT/Cy might be a feasible option for treating high-risk leukemia and MDS.
Department of Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan. Electronic address: hirohisa@msic.med.osaka-cu.ac.jp.
Hirohisa
H
Nakamae
Department of Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Hideo
H
Koh
Department of Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Takako
T
Katayama
Department of Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Mitsutaka
M
Nishimoto
Department of Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Yoshiki
Y
Hayashi
Department of Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Yasuhiro
Y
Nakashima
Department of Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Takahiko
T
Nakane
Department of Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Mika
M
Nakamae
Department of Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Asao
A
Hirose
Department of Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Masayuki
M
Hino
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002066:Busulfan / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D015994:Incidence; D007938:Leukemia / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality* / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation; D010865:Pilot Projects; D011446:Prospective Studies; D015996:Survival Rate
D003520:Cyclophosphamide; D002066:Busulfan