Lymphodepleting effects and safety of pentostatin for nonmyeloablative allogeneic stem-cell transplantation

Steven Z. Pavletic; R. Gregory Bociek; James M. Foran; Ronald J. Rubocki; Charles A. Kuszynski; James L. Wisecarver; Lori Hatcher; David M. Lucas; John C. Byrd; Michael R. Grever; Shantaram S. Joshi; Penny Hardiman; Lynette M. Smith; Timothy R. McGuire; Philip J. Bierman; Julie M. Vose; James O. Armitage; James E. Talmadge

doi:10.1097/01.TP.0000084869.08639.A0

Lymphodepleting effects and safety of pentostatin for nonmyeloablative allogeneic stem-cell transplantation

Steven Z. Pavletic, R. Gregory Bociek, James M. Foran, Ronald J. Rubocki, Charles A. Kuszynski, James L. Wisecarver, Lori Hatcher, David M. Lucas, John C. Byrd, Michael R. Grever, Shantaram S. Joshi, Penny Hardiman, Lynette M. Smith, Timothy R. McGuire, Philip J. Bierman, Julie M. Vose, James O. Armitage, James E. Talmadge

Hematology / Oncology / Cancer Center / Breast Clinic

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

Nonmyeloablative allogeneic stem-cell transplantation (alloNST) is the focus of investigations searching for less-toxic transplantation regimens. We report studies on the kinetics of lymphodepletion and safety of pentostatin (PT) conditioning in alloNST. Patients with hematologic malignancy received mobilized blood from human leukocyte antigen-matched related (n=4) or unrelated (n=8) donors. PT 4 mg/m² was administered on days -21, -20, and -19 and 200 cGy of total-body irradiation was administered on day -1, followed by cyclosporine A and mycophenolate mofetil. Mononuclear cell adenosine deaminase after PT was inhibited 84%. The absolute CD3⁺ cells decreased significantly by day -7 (49%) and CD19⁺ cells declined 92% by day -1. CD4⁺ cells were depressed more than CD8⁺ cells. Neutrophils and monocytes were minimally affected by PT. Median posttransplant peripheral blood chimerism on day 70 showed 95% donor leukocytes and 82.5% donor CD3 lymphocytes. PT demonstrated lymphodepleting effects and promising safety, supporting alloNST as early as 7 days after initiation of PT.

Original language	English (US)
Pages (from-to)	877-881
Number of pages	5
Journal	Transplantation
Volume	76
Issue number	5
DOIs	https://doi.org/10.1097/01.TP.0000084869.08639.A0
State	Published - Sep 15 2003

ASJC Scopus subject areas

Transplantation

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Pavletic, S. Z., Gregory Bociek, R., Foran, J. M., Rubocki, R. J., Kuszynski, C. A., Wisecarver, J. L., Hatcher, L., Lucas, D. M., Byrd, J. C., Grever, M. R., Joshi, S. S., Hardiman, P., Smith, L. M., McGuire, T. R., Bierman, P. J., Vose, J. M., Armitage, J. O., & Talmadge, J. E. (2003). Lymphodepleting effects and safety of pentostatin for nonmyeloablative allogeneic stem-cell transplantation. Transplantation, 76(5), 877-881. https://doi.org/10.1097/01.TP.0000084869.08639.A0

Pavletic, SZ, Gregory Bociek, R, Foran, JM, Rubocki, RJ, Kuszynski, CA, Wisecarver, JL, Hatcher, L, Lucas, DM, Byrd, JC, Grever, MR, Joshi, SS, Hardiman, P, Smith, LM, McGuire, TR, Bierman, PJ, Vose, JM, Armitage, JO & Talmadge, JE 2003, 'Lymphodepleting effects and safety of pentostatin for nonmyeloablative allogeneic stem-cell transplantation', Transplantation, vol. 76, no. 5, pp. 877-881. https://doi.org/10.1097/01.TP.0000084869.08639.A0

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abstract = "Nonmyeloablative allogeneic stem-cell transplantation (alloNST) is the focus of investigations searching for less-toxic transplantation regimens. We report studies on the kinetics of lymphodepletion and safety of pentostatin (PT) conditioning in alloNST. Patients with hematologic malignancy received mobilized blood from human leukocyte antigen-matched related (n=4) or unrelated (n=8) donors. PT 4 mg/m2 was administered on days -21, -20, and -19 and 200 cGy of total-body irradiation was administered on day -1, followed by cyclosporine A and mycophenolate mofetil. Mononuclear cell adenosine deaminase after PT was inhibited 84%. The absolute CD3+ cells decreased significantly by day -7 (49%) and CD19+ cells declined 92% by day -1. CD4+ cells were depressed more than CD8+ cells. Neutrophils and monocytes were minimally affected by PT. Median posttransplant peripheral blood chimerism on day 70 showed 95% donor leukocytes and 82.5% donor CD3 lymphocytes. PT demonstrated lymphodepleting effects and promising safety, supporting alloNST as early as 7 days after initiation of PT.",

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AU - Rubocki, Ronald J.

AU - Kuszynski, Charles A.

AU - Wisecarver, James L.

AU - Hatcher, Lori

AU - Lucas, David M.

AU - Byrd, John C.

AU - Grever, Michael R.

AU - Joshi, Shantaram S.

AU - Hardiman, Penny

AU - Smith, Lynette M.

AU - McGuire, Timothy R.

AU - Bierman, Philip J.

AU - Vose, Julie M.

AU - Armitage, James O.

AU - Talmadge, James E.

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N2 - Nonmyeloablative allogeneic stem-cell transplantation (alloNST) is the focus of investigations searching for less-toxic transplantation regimens. We report studies on the kinetics of lymphodepletion and safety of pentostatin (PT) conditioning in alloNST. Patients with hematologic malignancy received mobilized blood from human leukocyte antigen-matched related (n=4) or unrelated (n=8) donors. PT 4 mg/m2 was administered on days -21, -20, and -19 and 200 cGy of total-body irradiation was administered on day -1, followed by cyclosporine A and mycophenolate mofetil. Mononuclear cell adenosine deaminase after PT was inhibited 84%. The absolute CD3+ cells decreased significantly by day -7 (49%) and CD19+ cells declined 92% by day -1. CD4+ cells were depressed more than CD8+ cells. Neutrophils and monocytes were minimally affected by PT. Median posttransplant peripheral blood chimerism on day 70 showed 95% donor leukocytes and 82.5% donor CD3 lymphocytes. PT demonstrated lymphodepleting effects and promising safety, supporting alloNST as early as 7 days after initiation of PT.

AB - Nonmyeloablative allogeneic stem-cell transplantation (alloNST) is the focus of investigations searching for less-toxic transplantation regimens. We report studies on the kinetics of lymphodepletion and safety of pentostatin (PT) conditioning in alloNST. Patients with hematologic malignancy received mobilized blood from human leukocyte antigen-matched related (n=4) or unrelated (n=8) donors. PT 4 mg/m2 was administered on days -21, -20, and -19 and 200 cGy of total-body irradiation was administered on day -1, followed by cyclosporine A and mycophenolate mofetil. Mononuclear cell adenosine deaminase after PT was inhibited 84%. The absolute CD3+ cells decreased significantly by day -7 (49%) and CD19+ cells declined 92% by day -1. CD4+ cells were depressed more than CD8+ cells. Neutrophils and monocytes were minimally affected by PT. Median posttransplant peripheral blood chimerism on day 70 showed 95% donor leukocytes and 82.5% donor CD3 lymphocytes. PT demonstrated lymphodepleting effects and promising safety, supporting alloNST as early as 7 days after initiation of PT.

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Lymphodepleting effects and safety of pentostatin for nonmyeloablative allogeneic stem-cell transplantation

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