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Spitzer, Thomas

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Spitzer

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Spitzer, Thomas
Author's Publications: search.filters.isAuthorOfPublication.233c2705-4a92-499a-a00c-96616bc2b359Subject: search.filters.subject.Bone marrow transplantation

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    Mixed Chimerism, Lymphocyte Recovery, and Evidence for Early Donor-Specific Unresponsiveness in Patients Receiving Combined Kidney and Bone Marrow Transplantation to Induce Tolerance

    (Ovid Technologies (Wolters Kluwer Health), 2010) LoCascio, Samuel A.; Morokata, Tatsuaki; Chittenden, Meredith; Preffer, Frederic; Dombkowski, David M.; Andreola, Giovanna; Crisalli, Kerry; Kawai, Tatsuo; Saidman, Susan; Spitzer, Thomas; Tolkoff-Rubin, Nina; Cosimi, A.; Sachs, David; Sykes, Megan

    Background

    We have previously reported operational tolerance in patients receiving HLA-mismatched combined kidney and bone marrow transplantation (CKBMT). We now report on transient multilineage hematopoietic chimerism and lymphocyte recovery in five patients receiving a modified CKBMT protocol, and evidence for early donor-specific unresponsiveness in one of these patients.

    Methods

    Five patients with end-stage renal disease received CKBMT from HLA-mismatched, haploidentical living related donors following modified non-myeloablative conditioning. Polychromatic flow cytometry (FCM) was used to assess multilineage chimerism where evaluable and lymphocyte recovery post-transplant. Limiting dilution analysis was used to assess helper-T-lymphocyte reactivity to donor antigens.

    Results

    Transient multilineage mixed chimerism was observed in all patients but chimerism became undetectable by 2 weeks post-CKBMT. A marked decrease in T and B lymphocyte counts immediately following transplant was followed by gradual recovery. Initially recovering T cells were depleted of CD45RA+/CD45RO− “naïve-like” cells, which have shown strong recovery in two patients and CD4/CD8 ratios increased immediately following transplant but then declined markedly. NK cells were enriched in the peripheral blood of all patients following transplant.

    For Subject 2, a pre-transplant limiting dilution assay revealed T helper cells recognizing both donor and third-party PBMCs. However, the anti-donor response was completely undetectable by Day 24, while third-party reactivity persisted.

    Conclusion

    These results characterize the transient multilineage mixed hematopoietic chimerism and recovery of lymphocyte subsets in patients receiving a modified CKBMT protocol. The observations are relevant to the mechanisms of donor-specific tolerance in this patient group.