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Comparison of immune recovery in recipients of unmanipulated vs T-cell-depleted grafts from unrelated donors in a multicenter randomized phase II–III trial (T-cell depletion trial)

Bone Marrow Transplantation volume 45, pages 587–589 (2010)Cite this article

The NHLBI (National Heart, Lung and Blood Institute) T-cell depletion (TCD) randomized phase II–III multicenter trial was conducted to examine the impact of TCD of unrelated BM grafts on specific outcomes. The major findings of the study have been reported earlier;1 however, an analysis of lymphocyte reconstitution for study patients has been recently performed and is presented in this report.

Patients received BM grafts from unrelated donors that were either infused unmanipulated, or were TCD using selective ex vivo depletion of αβ+ T cells (αβTCD) or a prescribed T-cell dose of 5 × 105 cells/kg after counterflow centrifugal elutriation. Those randomized to receive unmanipulated grafts were conditioned with 1320–1375 cGy fractional TBI over 4 days and CY 120 mg/kg over 2 days. MTX (15 mg/m2 on day 1 and 10 mg/m2 on days +3, +6 and +11) and CsA were used as GVHD prophylaxis. Patients who received αβTCD grafts received 1410 cGy fractionated TBI over 3 days and 100 mg/kg CY over 2 days. Patients who received elutriated grafts received 1320–1375 cGy fractional TBI over 4 days, CY 120 mg/kg over 2 days, and equine antithymocyte globulin over 2 days. All patients received post-BMT CsA sufficient to achieve trough levels of 200–400 ng/ml. Lymphocyte recovery was assessed at 1, 3, 6, 12, 18 and 24 months post-HSCT. To be included in this analysis, patients had to have survived at least 60 days and completed at least 2 of 3 initial post-BMT immunophenotyping assessments at the 30, 60 or 100-day post-BMT time point. Lymphocyte subsets were enumerated using dual platform flow cytometry with a whole blood lyse/wash procedure and staining with fluorochrome-conjugated MoAbs to CD3, CD4, CD8, CD19, CD20, CD45, CD45RA, CD16, CD56, CD57, HLA-DR, TCR αβ and TCR γδ (BD Biosciences, San Jose, CA, USA). Data were tabulated and analyzed using SAS. Published normal ranges for lymphocyte subsets were used to determine time to complete lymphocyte recovery.2, 3 The Wilcoxon's non-parametric test was used to compare recovery of absolute cell counts between groups at each measurement period. A mixed model estimated the rate of change in cell counts for each subject and its slope estimate for each cell subset was then used as a variable to assess disease-free survival. The Cox proportional hazards model was used to examine associations between recovery of individual cell subsets and disease-free survival.

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Acknowledgements

The trial was supported by a contract from the National Heart, Lung and Blood Institute N01-HB-47195 (JEW), N01-HB-47097 (JST), N01-HB-47094 (SLC) and N01-HB-47098 (NAK).

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Authors and Affiliations

  1. Blood and Marrow Transplant Program, Medical College of Wisconsin, Milwaukee, WI, USA

    C A Keever-Taylor

  2. Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

    J E Wagner

  3. Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    N A Kernan & T N Small

  4. EMMES Corporation, Rockville, MD, USA

    S L Carter

  5. Department of Medicine, University of Kentucky, Lexington, KY, USA

    J S Thompson

  6. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    G A Cloud & L S Lamb

  7. Department of Pediatrics, University of South Carolina, Columbia, SC, USA

    L S Lamb

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  1. C A Keever-Taylor
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Correspondence to L S Lamb.

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Keever-Taylor, C., Wagner, J., Kernan, N. et al. Comparison of immune recovery in recipients of unmanipulated vs T-cell-depleted grafts from unrelated donors in a multicenter randomized phase II–III trial (T-cell depletion trial). Bone Marrow Transplant 45, 587–589 (2010). https://doi.org/10.1038/bmt.2009.170

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