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Unmanipulated HLA 2-3 antigen-mismatched (haploidentical) stem cell transplantation using nonmyeloablative conditioning.
Biol Blood Marrow Transplant. 2006 Oct; 12(10):1073-84.BB

Abstract

The major problems in human leukocyte antigen (HLA)-mismatched stem cell transplantation (SCT) are graft failure and graft-versus-host disease (GVHD). Less-intensive regimens should be associated with a lower release of inflammatory cytokines and possibly less GVHD. The objective of this study was to investigate whether HLA-haploidentical SCT can be performed using nonmyeloablative conditioning and pharmacologic GVHD prophylaxis, including glucocorticoids. Using conditioning consisting of fludarabine, busulfan, and anti-T-lymphocyte globulin and GVHD prophylaxis consisting of tacrolimus and methylprednisolone (1 mg/kg/day), 26 patients who had hematologic malignancies in an advanced stage or with a poor prognosis underwent transplantation using peripheral blood stem cells from an HLA-haploidentical donor (2-3 antigen mismatches in the graft-versus-host [GVH] direction) without T-cell depletion. All patients except for 1 achieved donor-type engraftment. Rapid hematologic engraftment was achieved (neutrophils > 0.5 x 10(9)/L on day 12 and platelets > 20 x 10(9)/L on day 12), with full donor chimerism achieved by day 14. Fifteen patients did not develop acute GVHD clinically, and only 5 patients developed grade II GVHD. The recovery of CD4+ T cells was delayed compared with that of CD8+ T cells. Sixteen of the 26 patients are alive in complete remission. Four died of transplantation-related causes, and 6 died of progressive disease. These data suggest that nonmyeloablative conditioning, GVHD prophylaxis consisting of tacrolimus and methylprednisolone, and early therapeutic intervention for the GVH reaction allow stable engraftment and effectively suppress GVHD in HLA 2-3 antigen-mismatched SCT.

Authors+Show Affiliations

Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. ogawah@hyo-med.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

17084371

Citation

Ogawa, Hiroyasu, et al. "Unmanipulated HLA 2-3 Antigen-mismatched (haploidentical) Stem Cell Transplantation Using Nonmyeloablative Conditioning." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 12, no. 10, 2006, pp. 1073-84.
Ogawa H, Ikegame K, Yoshihara S, et al. Unmanipulated HLA 2-3 antigen-mismatched (haploidentical) stem cell transplantation using nonmyeloablative conditioning. Biol Blood Marrow Transplant. 2006;12(10):1073-84.
Ogawa, H., Ikegame, K., Yoshihara, S., Kawakami, M., Fujioka, T., Masuda, T., Taniguchi, Y., Hasei, H., Kaida, K., Inoue, T., Kim, E. H., & Kawase, I. (2006). Unmanipulated HLA 2-3 antigen-mismatched (haploidentical) stem cell transplantation using nonmyeloablative conditioning. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 12(10), 1073-84.
Ogawa H, et al. Unmanipulated HLA 2-3 Antigen-mismatched (haploidentical) Stem Cell Transplantation Using Nonmyeloablative Conditioning. Biol Blood Marrow Transplant. 2006;12(10):1073-84. PubMed PMID: 17084371.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Unmanipulated HLA 2-3 antigen-mismatched (haploidentical) stem cell transplantation using nonmyeloablative conditioning. AU - Ogawa,Hiroyasu, AU - Ikegame,Kazuhiro, AU - Yoshihara,Satoshi, AU - Kawakami,Manabu, AU - Fujioka,Tatsuya, AU - Masuda,Tomoki, AU - Taniguchi,Yuki, AU - Hasei,Hitomi, AU - Kaida,Katsuji, AU - Inoue,Takayuki, AU - Kim,Eui Ho, AU - Kawase,Ichiro, PY - 2006/03/19/received PY - 2006/06/07/accepted PY - 2006/11/7/pubmed PY - 2007/3/21/medline PY - 2006/11/7/entrez SP - 1073 EP - 84 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol Blood Marrow Transplant VL - 12 IS - 10 N2 - The major problems in human leukocyte antigen (HLA)-mismatched stem cell transplantation (SCT) are graft failure and graft-versus-host disease (GVHD). Less-intensive regimens should be associated with a lower release of inflammatory cytokines and possibly less GVHD. The objective of this study was to investigate whether HLA-haploidentical SCT can be performed using nonmyeloablative conditioning and pharmacologic GVHD prophylaxis, including glucocorticoids. Using conditioning consisting of fludarabine, busulfan, and anti-T-lymphocyte globulin and GVHD prophylaxis consisting of tacrolimus and methylprednisolone (1 mg/kg/day), 26 patients who had hematologic malignancies in an advanced stage or with a poor prognosis underwent transplantation using peripheral blood stem cells from an HLA-haploidentical donor (2-3 antigen mismatches in the graft-versus-host [GVH] direction) without T-cell depletion. All patients except for 1 achieved donor-type engraftment. Rapid hematologic engraftment was achieved (neutrophils > 0.5 x 10(9)/L on day 12 and platelets > 20 x 10(9)/L on day 12), with full donor chimerism achieved by day 14. Fifteen patients did not develop acute GVHD clinically, and only 5 patients developed grade II GVHD. The recovery of CD4+ T cells was delayed compared with that of CD8+ T cells. Sixteen of the 26 patients are alive in complete remission. Four died of transplantation-related causes, and 6 died of progressive disease. These data suggest that nonmyeloablative conditioning, GVHD prophylaxis consisting of tacrolimus and methylprednisolone, and early therapeutic intervention for the GVH reaction allow stable engraftment and effectively suppress GVHD in HLA 2-3 antigen-mismatched SCT. SN - 1083-8791 UR - https://www.unboundmedicine.com/medline/citation/17084371/Unmanipulated_HLA_2_3_antigen_mismatched__haploidentical__stem_cell_transplantation_using_nonmyeloablative_conditioning_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(06)00419-8 DB - PRIME DP - Unbound Medicine ER -