TY - JOUR
T1 - 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
T2 - A Prospective Multicenter Phase I/II Study in Japan
AU - Ikegame, Kazuhiro
AU - Yoshida, Takashi
AU - Yoshihara, Satoshi
AU - Daimon, Takashi
AU - Shimizu, Hiroaki
AU - Maeda, Yoshinobu
AU - Ueda, Yasunori
AU - Kaida, Katsuji
AU - Ishii, Shinichi
AU - Taniguchi, Kyoko
AU - Okada, Masaya
AU - Tamaki, Hiroya
AU - Okumura, Hirokazu
AU - Kaya, Hiroyasu
AU - Kurokawa, Toshiro
AU - Kodera, Yoshihisa
AU - Taniguchi, Shuichi
AU - Kanda, Yoshinobu
AU - Ogawa, Hiroyasu
N1 - Funding Information:
Financial disclosure: This work was supported in part by a grant for Allergic Disease and Immunology ( H20-016 , H23-009 ) from the Health and Labour Sciences Research Grants for Clinical Cancer Research from the Ministry of Health, Labour and Welfare, Japan.
Publisher Copyright:
© 2015 American Society for Blood and Marrow Transplantation.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - This prospective, multicenter phase I/II study of unmanipulated HLA-haploidentical reduced-intensity stem celltransplantation 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× 109/L on day 11 and platelets > 20× 109/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%. Thesurvival 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.
AB - This prospective, multicenter phase I/II study of unmanipulated HLA-haploidentical reduced-intensity stem celltransplantation 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× 109/L on day 11 and platelets > 20× 109/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%. Thesurvival 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.
KW - Anti-T lymphocyte globulin
KW - Haploidentical stem cell transplantation
KW - Reduced-intensity conditioning
KW - Steroid
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U2 - 10.1016/j.bbmt.2015.04.012
DO - 10.1016/j.bbmt.2015.04.012
M3 - Article
C2 - 25921715
AN - SCOPUS:84937725503
SN - 1083-8791
VL - 21
SP - 1495
EP - 1505
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 8
ER -