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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1560-1563.
Prepublished online as a Blood First Edition Paper on October 9, 2003; DOI 10.1182/blood-2003-04-1170.

Submitted April 16, 2003
Accepted September 22, 2003
Prior chemotherapy and allograft CD34+ dose impact donor engraftment following nonmyeloablative allogeneic stem cell transplantation in solid tumor patients
Cristian Carvallo, Nancy Geller, Roger Kurlander, Ramaprasad Srinivasan, Othon Mena, Takehito Igarashi, Linda M Griffith, W Marston Linehan, and Richard W Childs*
Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
Department of Laboratory Medicine, Warren Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, USA
Department of Transfusion Medicine, Warren Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, USA
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
* Corresponding author; email: childsr{at}nhlbi.nih.gov.
Significant engraftment variability occurs among patients following nonmyeloablative hematopoietic cell transplantation. We analyzed the impact of multiple factors on donor myeloid and T-cell engraftment in 36 patients with metastatic tumors undergoing cyclophosphamide/fludarabine-based conditioning. Higher
CD34+ doses facilitated donor myeloid engraftment while prior chemotherapy exposure facilitated both donor myeloid and T-cell engraftment. At day 30, median donor T-cell and myeloid chimerism was 98% and 76% respectively in those with prior chemotherapy versus 88% (p=0.008) and 26% (p<0.0001) in chemotherapy-naive patients. Donor myeloid chimerism at day 45 was predicted by prior chemotherapy exposure and the log10 of the CD34+ dose (adjusted R2=.47, p< 0.0001), while chemotherapy alone impacted donor T-cell engraftment. Patients with prior chemotherapy were more likely to develop acute grade II-IV GVHD (8/18) compared to chemotherapy-naive patients (2/18; p=0.031). Thus, tailoring the intensity of nonmyeloablative conditioning based on prior chemotherapy exposure is an important consideration in trial design.

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