PMID- 25267759 OWN - NLM STAT- MEDLINE DCOM- 20141229 LR - 20220321 IS - 1527-7755 (Electronic) IS - 0732-183X (Print) IS - 0732-183X (Linking) VI - 32 IP - 31 DP - 2014 Nov 1 TI - Multi-institutional study of post-transplantation cyclophosphamide as single-agent graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation using myeloablative busulfan and fludarabine conditioning. PG - 3497-505 LID - 10.1200/JCO.2013.54.0625 [doi] AB - PURPOSE: The clinical safety and efficacy of intravenous busulfan and fludarabine (IV Bu/Flu) myeloablative conditioning as well as graft-versus-host disease (GVHD) prophylaxis with high-dose, post-transplantation cyclophosphamide (PTCy) have been demonstrated independently in several single-institutional studies. We hypothesized that combining these two promising approaches in a multi-institutional study of human leukocyte antigen (HLA) -matched bone marrow transplantation would provide low rates of severe acute and chronic GVHD, low toxicity, and effective disease control. PATIENTS AND METHODS: Ninety-two adult patients (median age, 49 years; range, 21 to 65 years) with high-risk hematologic malignancies were enrolled at three centers (clinical trial No. NCT00809276). Forty-five patients received related allografts, and 47 received unrelated allografts. GVHD prophylaxis was solely with PTCy at 50 mg/kg/day on post-transplantation days +3 and +4. RESULTS: The cumulative incidences of grades 2 to 4 acute, grades 3 to 4 acute, and chronic GVHD were 51%, 15%, and 14%, respectively. Nonrelapse mortality (NRM) at 100 days and 1 year were 9% and 16%, respectively. With a median follow-up period of 2.2 years, the 2-year disease-free survival (DFS) and overall survival (OS) rates were 62% and 67%, respectively. Donor relatedness did not affect NRM, DFS, or OS. Patients in complete remission (CR) without evidence of minimal residual disease (MRD) had markedly better DFS (80%) and OS (80%) than patients in CR with MRD or with active disease at the time of transplantation (DFS, P = .0005; OS, P = .019). CONCLUSION: This multi-institutional study demonstrates that PTCy can be safely and effectively combined with IV Bu/Flu myeloablative conditioning and confirms PTCy's efficacy as single-agent, short-course GVHD prophylaxis for both acute and chronic GVHD after bone marrow transplantation from HLA-matched donors. CI - (c) 2014 by American Society of Clinical Oncology. FAU - Kanakry, Christopher G AU - Kanakry CG AD - Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - O'Donnell, Paul V AU - O'Donnell PV AD - Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Furlong, Terry AU - Furlong T AD - Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - de Lima, Marcos J AU - de Lima MJ AD - Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Wei, Wei AU - Wei W AD - Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Medeot, Marta AU - Medeot M AD - Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Mielcarek, Marco AU - Mielcarek M AD - Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Champlin, Richard E AU - Champlin RE AD - Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Jones, Richard J AU - Jones RJ AD - Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Thall, Peter F AU - Thall PF AD - Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Andersson, Borje S AU - Andersson BS AD - Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Luznik, Leo AU - Luznik L AD - Christopher G. Kanakry, Marta Medeot, Richard J. Jones, Leo Luznik, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Paul V. O'Donnell, Terry Furlong, Marco Mielcarek, Fred Hutchinson Cancer Research Center, Seattle, WA; Marcos J. de Lima, Wei Wei, Richard E. Champlin, Peter F. Thall, Borje S. Andersson, The University of Texas MD Anderson Cancer Center, Houston, TX. luznile@jhmi.edu. LA - eng SI - ClinicalTrials.gov/NCT00809276 GR - P30 CA016672/CA/NCI NIH HHS/United States GR - P01 CA015396/CA/NCI NIH HHS/United States GR - T32 HL007525/HL/NHLBI NIH HHS/United States GR - R01 HL108307/HL/NHLBI NIH HHS/United States GR - P01-CA015396/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140929 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Immunosuppressive Agents) RN - 0 (Myeloablative Agonists) RN - 8N3DW7272P (Cyclophosphamide) RN - FA2DM6879K (Vidarabine) RN - G1LN9045DK (Busulfan) RN - P2K93U8740 (fludarabine) SB - IM MH - Adult MH - Aged MH - Bayes Theorem MH - Busulfan/therapeutic use MH - Cyclophosphamide/*therapeutic use MH - Female MH - Graft vs Host Disease/epidemiology/*prevention & control MH - *Hematopoietic Stem Cell Transplantation MH - Humans MH - Immunosuppressive Agents/*therapeutic use MH - Incidence MH - Male MH - Middle Aged MH - Myeloablative Agonists/therapeutic use MH - Transplantation Conditioning/*methods MH - Treatment Outcome MH - Vidarabine/analogs & derivatives/therapeutic use PMC - PMC4209101 COIS- Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article. EDAT- 2014/10/01 06:00 MHDA- 2014/12/30 06:00 PMCR- 2015/11/01 CRDT- 2014/10/01 06:00 PHST- 2014/10/01 06:00 [entrez] PHST- 2014/10/01 06:00 [pubmed] PHST- 2014/12/30 06:00 [medline] PHST- 2015/11/01 00:00 [pmc-release] AID - JCO.2013.54.0625 [pii] AID - 40625 [pii] AID - 10.1200/JCO.2013.54.0625 [doi] PST - ppublish SO - J Clin Oncol. 2014 Nov 1;32(31):3497-505. doi: 10.1200/JCO.2013.54.0625. Epub 2014 Sep 29.