Accepted Manuscript Donor Chimerism Early after Reduced-intensity Conditioning Hematopoietic Stem Cell Transplantation Predicts Relapse and Survival John Koreth , MBBS DPhil Haesook T. Kim , PhD Sarah Nikiforow , MD PhD Edgar L. Milford , MD Philippe Armand , MD PhD Corey Cutler , MD MPH Brett Glotzbecker , MD Vincent T. Ho , MD Joseph H. Antin , MD Robert J. Soiffer , MD Jerome Ritz , MD Edwin P. Alyea III, MD PII:

S1083-8791(14)00323-1

DOI:

10.1016/j.bbmt.2014.05.025

Reference:

YBBMT 53479

To appear in:

Biology of Blood and Marrow Transplantation

Received Date: 7 April 2014 Accepted Date: 22 May 2014

Please cite this article as: Koreth J, Kim HT, Nikiforow S, Milford EL, Armand P, Cutler C, Glotzbecker B, Ho VT, Antin JH, Soiffer RJ, Ritz J, Alyea EP III, Donor Chimerism Early after Reduced-intensity Conditioning Hematopoietic Stem Cell Transplantation Predicts Relapse and Survival, Biology of Blood and Marrow Transplantation (2014), doi: 10.1016/j.bbmt.2014.05.025. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

Donor Chimerism Early after Reduced-intensity Conditioning Hematopoietic Stem Cell Transplantation Predicts Relapse and Survival

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John Koreth, MBBS DPhil1*, Haesook T. Kim, PhD2, Sarah Nikiforow, MD PhD1, Edgar L. Milford, MD3, Philippe Armand, MD PhD1, Corey Cutler, MD MPH1, Brett Glotzbecker, MD1, Vincent T. Ho, MD1, Joseph H. Antin, MD1, Robert J. Soiffer, MD1, Jerome Ritz, MD1, Edwin P. Alyea III, MD1 1

Hematologic Malignancies Division, 2Division of Biostatistics & Computational Biology, Dana-Farber Cancer Institute; 3Tissue Typing Laboratory, Brigham & Women’s Hospital

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*Corresponding Author Dana-Farber Cancer Institute

Boston MA 02215 Ph: 617-632-3470 Fax: 617-632-5168

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Email: [email protected]

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450 Brookline Ave

Running Title: Early Donor Chimerism Predicts RIC HSCT Outcomes

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Keywords: Allogeneic transplantation, Reduced-intensity, Chimerism

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Word Count: Abstract 244; Manuscript 2838

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ACCEPTED MANUSCRIPT

Abstract The impact of early donor cell chimerism on outcomes of T-replete reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) is ill-defined. We

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evaluated day 30 (D30) and 100 (D100) total donor cell chimerism after RIC HSCT undertaken between 2002 and 2010 at our institution, excluding patients who died or relapsed before D30. When available, donor T-cell chimerism was also assessed. The

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primary outcome was overall survival (OS). Secondary outcomes included progressionfree survival (PFS), relapse and non-relapse mortality (NRM). 688 patients with

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hematologic malignancies (48% myeloid; 52% lymphoid) and a median age of 57 years (range, 18-74) undergoing RIC HSCT with T-replete donor grafts (97% peripheral blood; 92% HLA-matched) and median follow-up of 58.2 months (range, 12.6-120.7) were evaluated. In multivariable analysis total donor cell and T-cell chimerism at D30 and D100 each predicted RIC HSCT outcomes, with D100 total donor cell chimerism most

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predictive. D100 total donor cell chimerism