Is immunological recovery clinically relevant at 100 days after allogeneic transplantation?
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Background/Aims: Immune reconstitution following allogeneic hematopoietic stem cell transplantation (HSCT) is affected by multiple variables during the transplantation. Methods: We assessed the clinical factors contributing to immune function reconstitution at 100 days post-allogeneic HSCT in 114 patients receiving fludarabine- based conditioning. Immunophenotypic analysis using flow cytometry was performed to evaluate the percentage and the absolute numbers of T-cell subsets, natural killer cells, and B-cells as clinical outcomes. Results: Tacrolimus-based graft-versus-host disease (GVHD) prophylaxis, T-cell depletion, and acute GVHD were significantly associated with delayed immune reconstitution of T-cell subsets. The incidence of chronic GVHD was significantly increased in the normal recovery group compared to the abnormal group (p = 0.01). Epstein-Barr virus reactivation was more frequently observed in the abnormal group of T-cell subsets (p = 0.045). All viral reactivation events including cytomegalovirus reactivation appeared to be more frequent in the abnormal group of T-cell subsets. Conclusions: The immune recovery status post-allogeneic HSCT was affected by GVHD prophylactic regimens, especially in cases receiving tacrolimus-based GVHD prophylaxis, T-cell depletion, and possibly those manifesting acute GVHD. Delayed immune reconstitution might increase the morbidity due to viral reactivation. Treatment strategies are needed to prevent infectious complications and enhance immune reconstitution based on the immune recovery status following allogeneic HSCT with fludarabine-based conditioning.
Abstract
Background/Aims: Immune reconstitution following allogeneic hematopoietic stem cell transplantation (HSCT) is affected by multiple variables during the transplantation. Methods: We assessed the clinical factors contributing to immune function reconstitution at 100 days post-allogeneic HSCT in 114 patients receiving fludarabine- based conditioning. Immunophenotypic analysis using flow cytometry was performed to evaluate the percentage and the absolute numbers of T-cell subsets, natural killer cells, and B-cells as clinical outcomes. Results: Tacrolimus-based graft-versus-host disease (GVHD) prophylaxis, T-cell depletion, and acute GVHD were significantly associated with delayed immune reconstitution of T-cell subsets. The incidence of chronic GVHD was significantly increased in the normal recovery group compared to the abnormal group (p = 0.01). Epstein-Barr virus reactivation was more frequently observed in the abnormal group of T-cell subsets (p = 0.045). All viral reactivation events including cytomegalovirus reactivation appeared to be more frequent in the abnormal group of T-cell subsets. Conclusions: The immune recovery status post-allogeneic HSCT was affected by GVHD prophylactic regimens, especially in cases receiving tacrolimus-based GVHD prophylaxis, T-cell depletion, and possibly those manifesting acute GVHD. Delayed immune reconstitution might increase the morbidity due to viral reactivation. Treatment strategies are needed to prevent infectious complications and enhance immune reconstitution based on the immune recovery status following allogeneic HSCT with fludarabine-based conditioning.
참고문헌 (22)
- Ogonek J, "Immune reconstitution after allogeneic hematopoietic stem cell transplantation", Front Immunol, 7, pp.507~ (2016)
- Neven B, "Long-term outcome after hematopoietic stem cell transplantation of a single-center cohort of 90 patients with severe combined immunodeficiency", Blood, 113, pp.4114~4124 (2009)
- Wingard JR, "Hematopoietic stem cell transplantation: an overview of infection risks and epidemiology", Infect Dis Clin North Am, 24, pp.257~272 (2010)
- Krenger W, "The immunopathology of thymic GVHD", Semin Immunopathol, 30, pp.439~456 (2008)
- Seggewiss R, "Immune reconstitution after allogeneic transplantation and expanding options for immunomodulation:an update", Blood, 115, pp.3861~3868 (2010)
- Sorror ML, "Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT", Blood, 106, pp.2912~2919 (2005)
- Filipovich AH, "National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report", Biol Blood Marrow Transplant, 11, pp.945~956 (2005)
- Rowlings PA, "IBMTR severity index for grading acute graft-versus-host disease:retrospective comparison with Glucksberg grade", Br J Haematol, 97, pp.855~864 (1997)
- Storek J, "Reconstitution of the immune system after hematopoietic stem cell transplantation in humans", Semin Immunopathol, 30, pp.425~437 (2008)
- Bergmann L, "Immunosuppressive effects and clinical response of fludarabine in refractory chronic lymphocytic leukemia", Ann Oncol, 4, pp.371~375 (1993)
- Lee JH, "Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine", J Clin Oncol, 31, pp.701~709 (2013)
- Dumont-Girard F, "Reconstitution of the T-cell compartment after bone marrow transplantation: restoration of the repertoire by thymic emigrants", Blood, 92, pp.4464~4471 (1998)
- Chaudhry MS, "Immune Reconstitution after allogeneic hematopoietic stem cell transplantation: time to T up the thymus", J Immunol, 198, pp.40~46 (2017)
- Palmer DB, "The effect of age on thymic function", Front Immunol, 4, pp.316~ (2013)
- Fagnoni FF, "T-cell dynamics after high-dose chemotherapy in adults: elucidation of the elusive CD8+ subset reveals multiple homeostatic T-cell compartments with distinct implications for immune competence", Immunology, 106, pp.27~37 (2002)
- Mackall CL, "Distinctions between CD8+ and CD4+ T-cell regenerative pathways result in prolonged T-cell subset imbalance after intensive chemotherapy", Blood, 89, pp.3700~3707 (1997)
- Chatzidimitriou D, "Hematopoietic cell transplantation and emerging viral infections", J Med Virol, 82, pp.528~538 (2010)
- Gennery AR, "Infection following haematopoietic stem cell transplantation", Paediatr Child Health, 24, pp.236~241 (2014)
- 민창기, "The pathophysiology of chronic graft-versus-host disease: the unveiling of an enigma", Blood Research, 46(2), pp.80~87 (2011), 대한혈액학회
- Fry TJ, "Immune reconstitution following hematopoietic progenitor cell transplantation: challenges for the future", Bone Marrow Transplant, 35(Suppl 1), pp.S53~S57 (2005)
- Sullivan KM, "A controlled trial of long-term administration of intravenous immunoglobulin to prevent late infection and chronic graft-vs.-host disease after marrow transplantation: clinical outcome and effect on subsequent immune recovery", Biol Blood Marrow Transplant, 2, pp.44~53 (1996)
- Mehta RS, "Immune reconstitution post allogeneic transplant and the impact of immune recovery on the risk of infection", Virulence, 7, pp.901~916 (2016)
