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Immune Reconstitution of CD4+T Cells after Allogeneic Hematopoietic Stem Cell Transplantation and its Correlation with Invasive Fungal Infection in Patients with Hematological Malignancies

  • Peng, Xin-Guo (Laboratory Department, Binzhou Medical University Hospital) ;
  • Dong, Yan (Laboratory Department, Binzhou Medical University Hospital) ;
  • Zhang, Ting-Ting (Laboratory Department, Binzhou Medical University Hospital) ;
  • Wang, Kai (Laboratory Department, Binzhou Medical University Hospital) ;
  • Ma, Yin-Jian (Laboratory Department, Binzhou Medical University Hospital)
  • Published : 2015.04.29

Abstract

Objective: To explore the immune reconstitution of $CD4^+T$ cells after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and its relationship with invasive fungal infection (IFI) in patients with hematological malignancies. Materials and Methods: Forty-seven patients with hematological malignancies undergoing Allo-HSCT in Binzhou Medical University Hospital from February, 2010 to October, 2014 were selected. At 1, 2 and 3 months after transplantation, the immune subpopulations and concentration of cytokines were assessed respectively using flow cytometry (FCM) and enzyme linked immunosorbent assay (ELISA). The incidence of IFI after transplantation and its correlation with immune reconstitution of $CD4^+T$ cells were investigated. Results: The number of $CD4^+T$ cells and immune subpopulations increased progressively after transplantation as time went on, but the subpopulation cell count 3 months after transplantation was still significantly lower than in the control group (p<0.01). In comparison to the control group, the levels of interleukin-6 (IL-6) and IL-10 after transplantation rose evidently (p<0.01), while that of transforming growth factor-${beta}$ (TGF-${beta}$) was decreased (p<0.01). There was no statistically significant difference level of interferon-${\gamma}$ (IFN-${\gamma}$) (p>0.05). The incidence of IFI was 19.2% (9/47), and multivariate logistic regression revealed that IFI might be related to Th17 cell count (p<0.05), instead of Th1, Th2 and Treg cell counts as well as IL-6, IL-10, TGF-${beta}$ and IFN-${\gamma}$ levels (p>0.05). Conclusions: After Allo-HSCT, the immune reconstitution of $CD4^+T$ cells is delayed and Th17 cell count decreases obviously, which may be related to occurrence of IFI.

Keywords

Hematological malignancy;allogeneic hematopoietic stem cell transplantation;immune reconstitution

References

  1. Bastien JP, Roy J, Roy DC (2012). Selective T-cell depletion for haplotype-mismatched allogeneic stem cell transplantation. Semin Oncol, 39, 674-82. https://doi.org/10.1053/j.seminoncol.2012.09.004
  2. Dong WM, Cao XS, Wang B, et al (2014). Allogeneic hemopietic stem cell transplants for the treatment of B cell acute lymphocytic leukemia. Asian Pac J Cancer Prev, 15, 6127-30. https://doi.org/10.7314/APJCP.2014.15.15.6127
  3. Gu Z, Cai B, Yuan L, et al (2014). Successful treatment of polymorphic post-transplant lymphoproliferative disorder after allo-HSCT with reduction of immunosuppression. Int J Clin Exp Med, 7, 1904-9.
  4. Holtick U, Frenzel LP, Shimabukuro-Vornhagen A, et al (2014). CD4+ T cell counts reflect the immunosuppressive state of CD4 helper cells in patients after allogeneic stem cell transplantation. Ann Hematol, 94, 129-37.
  5. Lehrnbecher T, Schmidt S, Tramsen L, et al (2013). Immunotherapy of invasive fungal infection in hematopoietic stem cell transplant recipients. Front Oncol, 3, 17.
  6. Liu F, Wu T, Wang JB, et al (2013). Risk factors for recurrence of invasive fungal infection during secondary antifungal prophylaxis in allogeneic hematopoietic stem cell transplant recipients. Transpl Infect Dis, 15, 243-50. https://doi.org/10.1111/tid.12068
  7. Mensen A, Jöhrens K, Anagnostopoulos I, et al (2014). Bone marrow T-cell infiltration during acute GVHD is associated with delayed B-cell recovery and function after HSCT. Blood, 124, 963-72. https://doi.org/10.1182/blood-2013-11-539031
  8. Mohty B, Mohty M (2011). Long-term complications and side effects after allogeneic hematopoietic stem cell transplantation: an update. Blood Cancer J, 1, 16. https://doi.org/10.1038/bcj.2011.14
  9. Omer AK, Ziakas PD, Anagnostou T, et al (2013). Risk factors for invasive fungal disease after allogeneic hematopoietic stem cell transplantation: a single center experience. Biol Blood Marrow Transplant, 19, 1190-6. https://doi.org/10.1016/j.bbmt.2013.05.018
  10. Perales MA, Goldberg JD, Yuan J, et al (2012). Recombinant human interleukin-7 (CYT107) promotes T-cell recovery after allogeneic stem cell transplantation. Blood, 120, 4882-91. https://doi.org/10.1182/blood-2012-06-437236
  11. Perlingeiro Beltrame M, Malvezzi M, Bonfim C, et al (2014). Immune reconstitution in patients with Fanconi anemia after allogeneic bone marrow transplantation. Cytotherapy, 16, 976-89. https://doi.org/10.1016/j.jcyt.2014.02.015
  12. Qin LL, Wang QR, Wang Q, et al (2013).T-SPOT.TB for detection of tuberculosis infection among hematological malignancy patients and hematopoietic stem cell transplant recipients. Asian Pac J Cancer Prev, 14, 7415-9. https://doi.org/10.7314/APJCP.2013.14.12.7415
  13. Toubert A1, Glauzy S, Douay C, et al (2012). Thymus and immune reconstitution after allogeneic hematopoietic stem cell transplantation in humans: never say never again. Tissue Antigens, 79, 83-9. https://doi.org/10.1111/j.1399-0039.2011.01820.x
  14. Tacke D, Buchheidt D, Karthaus M, et al (2014). Primary prophylaxis of invasive fungal infections in patients with haematologic malignancies. 2014 update of the recommendations of the infectious diseases working party of the german society for haematology and oncology. Ann Hematol, 93, 1449-56. https://doi.org/10.1007/s00277-014-2108-y
  15. Wils EJ, van der Holt B, Broers AE, et al (2011). Insufficient recovery of thymopoiesis predicts for opportunistic infections in allogeneic hematopoietic stem cell transplant recipients. Haematologica, 96, 1846-54. https://doi.org/10.3324/haematol.2011.047696
  16. Yetisyigit T, Babacan N, Urun Y, et al (2014).Predictors of outcome in patients with advanced nonseminomatous germ cell testicular tumors. Asian Pac J Cancer Prev, 15, 831-5. https://doi.org/10.7314/APJCP.2014.15.2.831