PMID- 17084371 OWN - NLM STAT- MEDLINE DCOM- 20070320 LR - 20131121 IS - 1083-8791 (Print) IS - 1083-8791 (Linking) VI - 12 IP - 10 DP - 2006 Oct TI - Unmanipulated HLA 2-3 antigen-mismatched (haploidentical) stem cell transplantation using nonmyeloablative conditioning. PG - 1073-84 AB - 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. FAU - Ogawa, Hiroyasu AU - Ogawa H AD - Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. ogawah@hyo-med.ac.jp FAU - Ikegame, Kazuhiro AU - Ikegame K FAU - Yoshihara, Satoshi AU - Yoshihara S FAU - Kawakami, Manabu AU - Kawakami M FAU - Fujioka, Tatsuya AU - Fujioka T FAU - Masuda, Tomoki AU - Masuda T FAU - Taniguchi, Yuki AU - Taniguchi Y FAU - Hasei, Hitomi AU - Hasei H FAU - Kaida, Katsuji AU - Kaida K FAU - Inoue, Takayuki AU - Inoue T FAU - Kim, Eui Ho AU - Kim EH FAU - Kawase, Ichiro AU - Kawase I LA - eng PT - Clinical Trial PT - Journal Article PL - United States TA - Biol Blood Marrow Transplant JT - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JID - 9600628 RN - 0 (Antilymphocyte Serum) RN - 0 (Cytokines) RN - 0 (HLA Antigens) RN - 0 (Immunosuppressive Agents) RN - FA2DM6879K (Vidarabine) RN - G1LN9045DK (Busulfan) RN - P2K93U8740 (fludarabine) RN - WM0HAQ4WNM (Tacrolimus) RN - X4W7ZR7023 (Methylprednisolone) SB - IM MH - Adult MH - Antilymphocyte Serum/administration & dosage MH - Bone Marrow/drug effects/immunology/radiation effects MH - Busulfan/administration & dosage MH - CD4 Lymphocyte Count MH - Combined Modality Therapy MH - Cytokines/physiology MH - Disease-Free Survival MH - Family MH - Female MH - Graft Survival MH - Graft vs Host Disease/epidemiology/etiology/*prevention & control MH - HLA Antigens/*analysis/genetics MH - Hematologic Neoplasms/drug therapy/mortality/*surgery MH - *Histocompatibility MH - Humans MH - Immunosuppressive Agents/therapeutic use MH - Incidence MH - Male MH - Methylprednisolone/therapeutic use MH - Middle Aged MH - Myelodysplastic Syndromes/drug therapy/mortality/surgery MH - Peripheral Blood Stem Cell Transplantation/mortality/*statistics & numerical data MH - Recurrence MH - Remission Induction MH - T-Lymphocytes MH - Tacrolimus/therapeutic use MH - Tissue Donors MH - *Transplantation Conditioning/mortality MH - Transplantation, Homologous/*immunology MH - Treatment Outcome MH - Vidarabine/administration & dosage/analogs & derivatives EDAT- 2006/11/07 09:00 MHDA- 2007/03/21 09:00 CRDT- 2006/11/07 09:00 PHST- 2006/03/19 00:00 [received] PHST- 2006/06/07 00:00 [accepted] PHST- 2006/11/07 09:00 [pubmed] PHST- 2007/03/21 09:00 [medline] PHST- 2006/11/07 09:00 [entrez] AID - S1083-8791(06)00419-8 [pii] AID - 10.1016/j.bbmt.2006.06.007 [doi] PST - ppublish SO - Biol Blood Marrow Transplant. 2006 Oct;12(10):1073-84. doi: 10.1016/j.bbmt.2006.06.007.