Unmanipulated Haploidentical Reduced-Intensity Stem Cell Transplantation Using Fludarabine, Busulfan, Low-Dose Antithymocyte Globulin, and Steroids for Patients in Non-Complete Remission or at High Risk of Relapse: A Prospective Multicenter Phase I/II Study in Japan.
This prospective, multicenter phase I/II study of unmanipulated HLA-haploidentical reduced-intensity stem cell transplantation using a low dose of anti-T lymphocyte globulin (ATG) and steroid was conducted in 5 institutions in Japan. Thirty-four patients with hematologic malignancies who were in an advanced stage or at a high risk of relapse at the time of transplantation were enrolled. Among them, 7 patients underwent transplantation as a second transplantation because of relapse after the previous allogeneic stem cell transplantation. The conditioning regimen consisted of fludarabine, busulfan, and ATG (Fresenius, 8 mg/kg), and graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methylprednisolone (1 mg/kg). All patients except 1 (97.1%) achieved donor-type engraftment. Rapid hematopoietic engraftment was achieved, with neutrophils > .5 × 10(9)/L on day 11 and platelets > 20 × 10(9)/L on day 17.5. Treatment was started for ≥grade I GVHD, and the cumulative incidences of acute grade I and grade II to IV GVHD were 27.5% and 30.7%, respectively. The incidence of chronic GVHD (extensive type) was 20%. Fourteen patients (41.2%) had a relapse. The cumulative incidence of transplantation-related mortality at 1 year after transplantation was 26.5%. The survival rate at day 100 was 88.2%. The survival rates at 1 year for patients with complete remission (CR)/chronic phase (n = 8) and non-CR (n = 26) status before transplantation were 62.5% and 42.3%, respectively. In the multivariate analysis, non-CR status before transplantation was the only factor significant prognostic factor of increased relapse (P = .0424), which tended to be associated with a lower survival rate (P = .0524). This transplantation protocol is safe and feasible, if a suitable donor is not available in a timely manner. As the main cause of death was relapse and not GVHD, more intensified conditioning or attenuation of GVHD prophylaxis and/or donor lymphocyte infusion may be desirable for patients with non-CR status.
Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
Kazuhiro
K
Ikegame
Department of Internal Medicine, Toyama Prefectural Central Hospital, Toyama, Japan.
Takashi
T
Yoshida
Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
Satoshi
S
Yoshihara
Department of Biostatistics, Hyogo College of Medicine, Hyogo, Japan.
Takashi
T
Daimon
Leukemia Research Center, Saiseikai Maebashi Hospital, Maebashi, Japan.
Hiroaki
H
Shimizu
Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Yoshinobu
Y
Maeda
Department of Hematology/Oncology, Transfusion and Hemapheresis Center, Kurashiki Central Hospital, Kurashiki, Japan.
Yasunori
Y
Ueda
Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
Katsuji
K
Kaida
Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
Shinichi
S
Ishii
Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
Kyoko
K
Taniguchi
Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
Masaya
M
Okada
Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
Hiroya
H
Tamaki
Department of Internal Medicine, Toyama Prefectural Central Hospital, Toyama, Japan.
Hirokazu
H
Okumura
Department of Internal Medicine, Toyama Prefectural Central Hospital, Toyama, Japan.
Hiroyasu
H
Kaya
Department of Internal Medicine, Toyama Prefectural Central Hospital, Toyama, Japan.
Toshiro
T
Kurokawa
Department of Promotion for Blood and Marrow Transplantation, Aichi Medical University School of Medicine, Aichi, Japan.
Yoshihisa
Y
Kodera
Department of Haematology, Toranomon Hospital, Tokyo, Japan.
Shuichi
S
Taniguchi
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
Yoshinobu
Y
Kanda
Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan. Electronic address: ogawah@hyo-med.ac.jp.
Hiroyasu
H
Ogawa
D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002066:Busulfan / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D013256:Steroids / Q000009:adverse effects / Q000627:therapeutic use*; D019172:Transplantation Conditioning / Q000379:methods*; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000961:Antilymphocyte Serum; D013256:Steroids; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine
Anti–T lymphocyte globulin; Haploidentical stem cell transplantation; Reduced-intensity conditioning; Steroid