Immune reconstitution following autologous and allogeneic stem cell transplant

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

SUMMARY: The Preclinical Development and Clinical Monitoring Facility (PDCMF) projects have developed from transplantation protocols developed within ETIB. The PDCMF processes and preserves peripheral blood, marrow aspirates, and tumor and CGVHD tissue biopsies from all ongoing ETIB protocols. In close collaborative relationships with the Cell Processing Service of DTM, the ETIB Flow Cytometry Facility, the ETIB T Cell Facility, and the laboratory of Ronald Gress, we have evaluated lymphocyte subsets, cytokine content, T cell receptor repertoire diversity, and gene expression to support research studies of clinical protocols. All data are incorporated into protocol-specific spreadsheets, linking samples to protocol arms and transplant time points, and are accessible by Branch clinicians over secure NIH networks. These routine tasks describe the Facility's role in support of any ETIB protocol currently in the stages of long-term follow-up, including 11-C-0136 (PI: Chris Kanakry). The Facility provides additional services unique to other studies. Those transplant-related protocols can be categorized as: 1) myeloablative transplant for leukemias and lymphomas, and 2) transplantation for monogenic immune deficiencies. 19-C-0112 (PI: Christopher Kanakry) is currently the only ETIB transplant protocol to treat hematologic malignancies and tests the effects of varying dose levels and timing of post-transplant cyclophosphamide. To our past strategies to characterize immune reconstitution and graft-versus-host-disease (GVHD), we will add the assessment of changes in the gastrointestinal microbiome, based on the collection of stool samples pre- and post-transplant. Several protocols employing allogeneic transplants as a curative therapy for primary immunodeficiencies are conducted by ETIB. This Facility monitors the repopulation of deficient cell lineages, especially by preparing samples at post-transplant intervals for the ETIB Flow Cytometry Facility (William Telford) to then be assessed for subset-specific donor chimerism by the Hematology Service of the Department of Laboratory Medicine. 16-C-0003, 18-C-0135, and 19-C-0085 (PI: Jennifer Kanakry) enroll an array of patients with various defined mutations. The manuscript described in the 2019 Annual Report, encompassing an entire cohort of 16-C-0003, has been published. Similar studies are ongoing for 18-C-0135 and 19-C-0085, in addition to assaying residual anti-thymocyte globulin (ATG) levels and specificity in the plasma collected from patients enrolled in those protocols.