PMID- 26305035 OWN - NLM STAT- MEDLINE DCOM- 20160425 LR - 20220330 IS - 1759-4782 (Electronic) IS - 1759-4774 (Print) IS - 1759-4774 (Linking) VI - 13 IP - 1 DP - 2016 Jan TI - Modern approaches to HLA-haploidentical blood or marrow transplantation. PG - 10-24 LID - 10.1038/nrclinonc.2015.128 [doi] AB - Allogeneic blood or bone-marrow transplantation (alloBMT) is a potentially curative treatment for a variety of haematological malignancies and nonmalignant diseases. Historically, human leukocyte antigen (HLA)-matched siblings have been the preferred source of donor cells owing to superior outcomes compared with alloBMT using other donors. Although only approximately one-third of patients have an HLA-matched sibling, nearly all patients have HLA-haploidentical related donors. Early studies using HLA-haploidentical alloBMT resulted in unacceptably high rates of graft rejection and graft-versus-host disease (GVHD), leading to high nonrelapse mortality and consequently poor survival. Several novel approaches to HLA-haploidentical alloBMT have yielded encouraging results with high rates of successful engraftment, effective GVHD control and favourable outcomes. In fact, outcomes of several retrospective comparative studies seem similar to those seen using other allograft sources, including those of HLA-matched-sibling alloBMT. In this Review, we provide an overview of the three most-developed approaches to HLA-haploidentical alloBMT: T-cell depletion with 'megadose' CD34(+) cells; granulocyte colony-stimulating factor-primed allografts combined with intensive pharmacological immunosuppression, including antithymocyte globulin; and high-dose, post-transplantation cyclophosphamide. We review the preclinical and biological data supporting each approach, results from major clinical studies, and completed or ongoing clinical studies comparing these approaches with other alloBMT platforms. FAU - Kanakry, Christopher G AU - Kanakry CG AD - Sidney Kimmel Comprehensive Cancer Center, 1650 Orleans Street, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. FAU - Fuchs, Ephraim J AU - Fuchs EJ AD - Sidney Kimmel Comprehensive Cancer Center, 1650 Orleans Street, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. FAU - Luznik, Leo AU - Luznik L AD - Sidney Kimmel Comprehensive Cancer Center, 1650 Orleans Street, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. LA - eng GR - P01 CA015396/CA/NCI NIH HHS/United States GR - P30 CA006973/CA/NCI NIH HHS/United States PT - Journal Article PT - Review DEP - 20150825 PL - England TA - Nat Rev Clin Oncol JT - Nature reviews. Clinical oncology JID - 101500077 RN - 0 (Antigens, CD34) RN - 0 (Antilymphocyte Serum) RN - 0 (HLA Antigens) RN - 0 (Immunosuppressive Agents) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) RN - 8N3DW7272P (Cyclophosphamide) SB - IM EIN - Nat Rev Clin Oncol. 2016 Feb;13(2):132. PMID: 26718103 MH - Antigens, CD34/immunology MH - Antilymphocyte Serum/administration & dosage MH - *Bone Marrow Transplantation/methods MH - Cyclophosphamide/administration & dosage MH - Evidence-Based Medicine MH - Graft vs Host Disease/*prevention & control MH - Granulocyte Colony-Stimulating Factor/administration & dosage MH - HLA Antigens/*blood MH - Haploidy MH - Hematologic Neoplasms/*therapy MH - *Histocompatibility Testing MH - Humans MH - *Immunomodulation/immunology MH - Immunosuppressive Agents/administration & dosage MH - Lymphocyte Depletion/methods MH - T-Lymphocytes MH - *Transplantation, Homologous MH - Treatment Outcome PMC - PMC4695979 MID - NIHMS737885 EDAT- 2015/08/26 06:00 MHDA- 2016/04/26 06:00 PMCR- 2016/01/01 CRDT- 2015/08/26 06:00 PHST- 2015/08/26 06:00 [entrez] PHST- 2015/08/26 06:00 [pubmed] PHST- 2016/04/26 06:00 [medline] PHST- 2016/01/01 00:00 [pmc-release] AID - nrclinonc.2015.128 [pii] AID - 10.1038/nrclinonc.2015.128 [doi] PST - ppublish SO - Nat Rev Clin Oncol. 2016 Jan;13(1):10-24. doi: 10.1038/nrclinonc.2015.128. Epub 2015 Aug 25.