13Immune reconstitution following hematopoietic stem-cell transplantation
Section snippets
Barrier immunity
Within the respiratory, gastrointestinal and urogenital tracts and on the skin, intact epithelium provides a physical barrier preventing translocation of bacteria and infection. Secretions like tears or saliva that contain antimicrobial molecules (including lysozyme) further facilitate this barrier function.14 Chemotherapy, radiation therapy and GVHD cause mucosal damage and skin damage. Mucosal damage is typically repaired within several weeks, except in the presence of GVHD which is
T-lymphocyte number and function
T-lymphocyte function is essential for cell-mediated immunity protective against fungal, viral, and protozoan infections, and for control of B-lymphocyte responses to encapsulated bacteria. The number of mature T cells infused during transplantation is 1 to 1.5 log higher when allogeneic stem cells are obtained from blood than marrow.*21, 40, 41 Cord blood contains fewer T cells than a typical adult marrow graft, and has a high naïve:memory/effector T-cell ratio.42, 43
CD8 cell counts recover
Non-myeloablative transplantation
Non-myeloablative transplants use non-intensive chemoradiation, relying on graft antineoplastic activity to treat the underlying disease. Some non-myeloablative conditioning regimens include anti-T-cell antibodies. Non-myeloablative transplants are increasingly used in patients with comorbidities or increased age in an attempt to reduce treatment-related mortality, and result in decreased damage to mucosal and dermal barriers. In comparison to myeloablative transplantation, reduced-intensity
Pathogen avoidance
During the neutropenic period regular hand-washing, isolation of hospitalized patients with resistant organisms to prevent spread, and the use of high-efficiency particulate air (HEPA) filters on hospital units as well as avoidance of ill contacts are important in avoiding infection.90, 91 A diet avoiding unwashed fruits and vegetables, uncooked meats and unpasteurized dairy products may prevent exposure to environmental and food-borne pathogens; the impact on infection rates of strict
Summary
Immune reconstitution following allogeneic transplant involves all aspects of innate and adaptive immunity. Breakdown of barrier immunity due to chemoradiation or GVHD is repaired, and donor cells rapidly replace phagocytes. With myeloablative transplants, there is rapid reconstitution of B lymphocytes and CD8 T lymphocytes over months, with recapitulation of B-cell ontogeny, but CD8 T cells adopt a phenotype consistent with antigen-primed rather than naïve cells. CD4 T-lymphocyte recovery is
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Cited by (65)
Immune reconstitution after allogenic stem cell transplantation: An observational study in pediatric patients
2023, Hematology, Transfusion and Cell TherapyCitation Excerpt :Over this 6-month period, the lymphocyte reconstitution was gradual and each subtype showed different reconstitution rates on D+100. Our study reiterates that the lymphocyte count after the HSCT impacts patient survival and is associated with pre-transplant factors, such as age, source of stem cells, donor, serotherapy, conditioning, disease and clinical outcomes, such as the CMV and aGvHD.10-13 In the first three months after the HSCT, natural killer (NK) lymphocytes and the CD3+CD8+ clonal expansion propel the lymphocyte reconstitution.10,14
Safety and Tolerability of SARS-CoV2 Emergency-Use Authorized Vaccines for Allogeneic Hematopoietic Stem Cell Transplant Recipients
2021, Transplantation and Cellular TherapyCitation Excerpt :Another potential explanation of lower incidence rates of adverse events could be an impaired immune response to the vaccine in the HCT population, as a significant proportion of vaccine recipients had active chronic GVHD. The required uptake of mRNA from BNT162b2 or mRNA-1273 by dendritic cells to encode for the necessary spike protein and ability to mobilize adaptive immunity via T cells and B cell lymphocytes toward COVID-19 might be suboptimal in HCT patients, as immune function might not normalize until a year after HCT and might further be delayed by GVHD and its treatment [19,20]. Approximately 12% of patients in our study had worsening of baseline chronic GVHD or development of new-onset chronic GVHD after vaccination.
Splenomegaly Negatively Impacts Neutrophil Engraftment in Cord Blood Transplantation
2020, Biology of Blood and Marrow TransplantationAltered thymic CD4<sup>+</sup> T-cell recovery after allogeneic hematopoietic stem cell transplantation is critical for nocardiosis
2019, Current Research in Translational MedicineCitation Excerpt :As same as NTE, RTE count was significantly lower in nocardiosis cohort than control cohort and continued over time. Delay for NTE and RTE repopulation until “normal” level [51,52] was described as a key point that infection risk and mortality risk decreased after AHCT [29,57,58]. Peripheral naïve T-CD4+ cells RTE or not (CD31+ or not) [59] may have equal function but RTE presented a broader polyclonal TCR repertoire compared to non-thymic naïve T-CD4+ cells [60].
Comprehensive viromewide antibody responses by systematic epitope scanning after hematopoietic cell transplantation
2019, BloodCitation Excerpt :Human viral pathogens number in the hundreds, with thousands of possible strains, and clinically used proxies for risk of viral infection, such as absolute lymphocyte count (ALC) or total immunoglobulin levels (immunoglobulin G [IgG]), do not strongly predict protection against specific viral pathogens. Following HCT, preformed antibodies from the recipient continue to circulate, with an average half-life of ∼26 days, and are thought to be slowly replaced by donor IgG following establishment of the donor B cell and plasma cell population much later.3-6 Much is known about how cytomegalovirus (CMV) impacts clinical outcomes, including death, following HCT, and recent data demonstrate the importance of humoral immunity and far-reaching immunologic effects of this virus.7-11