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dc.contributorSonis, Stephen-
dc.contributorArmand, Philippe-
dc.contributorKawai, Toshihisa-
dc.creatorAboalela, Ali Anwar-
dc.date2015-07-14T19:09:04Z-
dc.date2015-05-
dc.date2015-07-02-
dc.date2015-
dc.date2015-07-14T19:09:04Z-
dc.date.accessioned2023-04-10T04:30:35Z-
dc.date.available2023-04-10T04:30:35Z-
dc.identifierAboalela, Ali Anwar. 2015. Immune Reconstitution of B Cells Following Allogeneic Hematopoietic Cell Transplantation. Doctoral dissertation, Harvard School of Dental Medicine.-
dc.identifierhttp://nrs.harvard.edu/urn-3:HUL.InstRepos:17331949-
dc.identifier.urihttp://lib.yhn.edu.vn/handle/YHN/173-
dc.descriptionObjectives: Graft versus host disease (GVHD), infections and disease relapse continue to be major complications of allogeneic hematopoietic cell transplantation (HCT). B cell abnormalities have been associated with these complications, and the objective of these studies was to identify and quantify abnormalities of B cell recovery after allogeneic HCT. Methods: Flow cytometry was used to analyze peripheral blood from healthy donors (HD) and samples obtained at 1, 2, 3, 6, 9, 12, 18, 24, 30, and 36 months post HCT. A panel of 8 fluorophore-conjugated monoclonal antibodies specific for B cell surface markers was used to identify levels of total B cells, antigen naïve, antigen experienced, transitional B cells, naïve B cells, IgD memory, pre germinal, post germinal, and plasmablasts. Results: 224 male patients and 175 female patients (total N=399) with a median age of 58 years (range 19-74) were included in this study. 308 patients received reduced intensity and 91 received myeloablative conditioning for allogeneic HCT in the management of various hematological malignancies. The 2-year overall survival was 65% and progression free survival was 55%. The absolute number of total B cells in patients compared to HD remained low for 9 months (118.8 x 106/L vs 204 x 106/L, P < 0.02) and normal levels were reached by month 12. Recovering cells were primarily antigen naïve B cells and the frequency of antigen experienced B cells remained below normal when compared to HD for all time points post HCT (P < 0.0001). Within the antigen naïve compartment, the frequency of transitional B cells remained elevated and naïve B cells remained below normal until normal levels were reached by month 9. Within the antigen experienced compartment, the frequency of pre germinal cells was elevated compared to HD from 6 months (4.8% vs 0.70%; P < 0.0002) post HCT. Plasmablast frequencies were elevated compared to HD from 6 months (7.3% vs 1.1%; P < 0.0009) post HCT. IgD memory cells did not reach normal frequency for most time points. Post germinal cells did not reach normal frequencies from 6 to 12 months post HCT. Conclusion: Disturbances in B cell maturation after HCT persist for prolonged periods despite recovery of normal numbers of circulating B cells. Naïve and transitional B cells that predominate have low affinity BCRs and have been implicated in cGVHD. Reduced numbers of high affinity antigen experienced B cells likely predispose patients to infectious complications post HCT.-
dc.descriptionHematopoietic Cell Transplantation; B cells; Immune reconstitution-
dc.formatapplication/pdf-
dc.formatapplication/pdf-
dc.languageen-
dc.subjectHealth Sciences, Immunology-
dc.subjectHealth Sciences, Oncology-
dc.subjectBiology, Cell-
dc.titleImmune Reconstitution of B Cells Following Allogeneic Hematopoietic Cell Transplantation-
dc.typeThesis or Dissertation-
dc.typetext-
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