Regulatory T-cell recovery in recipients of haploidentical nonmyeloablative hematopoietic cell transplantation with a humanized anti-CD2 mAb, MEDI-507, with or without fludarabine.

Regulatory T-cell recovery in recipients of haploidentical nonmyeloablative hematopoietic cell transplantation with a humanized anti-CD2 mAb, MEDI-507, with or without fludarabine. Research Abstract Details 

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Regulatory T-cell recovery in recipients of haploidentical nonmyeloablative hematopoietic cell transplantation with a humanized anti-CD2 mAb, MEDI-507, with or without fludarabine. Abstract Text:

Juanita Shaffer,Jean Villard,Terry K Means,Stephen Alexander,David Dombkowski,Bimalangshu R Dey,Steven McAfee,Karen K Ballen,Susan Saidman,Frederic I Preffer,David H Sachs,Thomas R Spitzer,Megan Sykes,

OBJECTIVE: We have evaluated T-cell reconstitution and reactivity in patients receiving nonmyeloablative haploidentical hematopoietic cell transplantation (HCT) protocols involving an anti-CD2 monoclonal antibody (MEDI 507) to treat chemorefractory hematopoietic malignancies. METHODS: Three cohorts of four patients each and one cohort of six patients received one of four Medi-507-based regimens, all of which included cyclophosphamide, thymic irradiation, and a short posttransplantation course of cyclosporine. RESULTS: Following marked T-cell depletion, initially recovering CD4 and CD8 T cells were mainly memory-type cells. A high percentage of CD4 T cells expressed high levels of CD25 in recipients of all protocols, except the only protocol to include fludarabine, early post-HCT. CD25 expression varied inversely with T-cell concentrations in blood. CD25(high) CD4 T cells expressed Foxp3 and cytotoxic T-lymphocyte-associated protein 4, indicating that they were regulatory T cells (Treg). CONCLUSIONS: Fludarabine treatment prevents Treg enrichment after haploidentical nonmyeloablative stem cell transplantation, presumably by depleting recipient Tregs. In vitro analyses of allorecognition were consistent with a cytokine-mediated rejection process in one case and in another provided proof of principle that mixed chimerism achieved without graft-vs-host disease induces donor- and recipient-specific tolerance. More reliable achievement of this outcome could provide a promising strategy for organ allograft tolerance induction.

Regulatory T-cell recovery in recipients of haploidentical nonmyeloablative hematopoietic cell transplantation with a humanized anti-CD2 mAb, MEDI-507, with or without fludarabine. Publishing Authors By Initials

J Shaffer,J Villard,TK Means,S Alexander,D Dombkowski,BR Dey,S McAfee,KK Ballen,S Saidman,FI Preffer,DH Sachs,TR Spitzer,M Sykes,

For similar heterocyclic compounds: heterocyclic compounds, 2-ring: purines: purine nucleosides: adenosine: vidarabine research abstracts see: heterocyclic compounds: heterocyclic compounds, 2-ring: purines: purine nucleosides: adenosine: vidarabine research

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Regulatory T-cell recovery in recipients of haploidentical nonmyeloablative hematopoietic cell transplantation with a humanized anti-CD2 mAb, MEDI-507, with or without fludarabine. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Experimental hematology

VOLUME: 35

Page Numbers: 1140-52

Journal Abbreviation: Exp. Hematol.

ISSN: 0301-472X

DAY: 3

MONTH: Jul

YEAR: 2007

Regulatory T-cell recovery in recipients of haploidentical nonmyeloablative hematopoietic cell transplantation with a humanized anti-CD2 mAb, MEDI-507, with or without fludarabine. Information

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LANGUAGE: eng

NlmUniqueID: 402313

Regulatory T-cell recovery in recipients of haploidentical nonmyeloablative hematopoietic cell transplantation with a humanized anti-CD2 mAb, MEDI-507, with or without fludarabine. Keywords Mesh Terms:

KEYWORDS: Vidarabine

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Regulatory T-cell recovery in recipients of haploidentical nonmyeloablative hematopoietic cell transplantation with a humanized anti-CD2 mAb, MEDI-507, with or without fludarabine. Information

Substance Name: Interferon Type II

Registry Number: 82115-62-6

Grant and Affiliation Information for Regulatory T-cell recovery in recipients of haploidentical nonmyeloablative hematopoietic cell transplantation with a humanized anti-CD2 mAb, MEDI-507, with or without fludarabine.

AFFILIATION: Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA.

Country: Netherlands

AGENCY: United States NHLBI

GRANT: R01 HL63474

ACRONYM: HL

MEDLINETA: Exp Hematol

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