Immune and Hematological Reconstitution after Allogenic Bone Marrow Transplantation in Tunisian Pediatric Recipients: Prospective Study and Tunisian Experience Report
DOI:
https://doi.org/10.12974/2312-5411.2017.04.4Keywords:
Immune reconstitution, monitoring, lymphocyte T cell enumeration, CD4 /CD8 ratio, CMV infection, bone marrow transplantation, pediatric tunisian patients.Abstract
AIM: A regular monitoring of the immune reconstitution mainly based on the quantitative determination of lymphocyte T subpopulation. This is prospective analysis for 1 year in Tunisian children treated with allogenic intrafamilial bone marrow transplantation.
Methods: We conducted a prospective analysis for 1 year follow up enrolling 25 children treated with allogenic intrafamilial bone marrow transplantation among them two cases of Peripheral hematopoietic transplantation and placental cord blood transplantation including: aplastic anemia (6 cases), hemoglobinopathies (12 cases), myelodysplastic syndrome (1 case), 2 cases of Acute lymphocytic leukemia, a case of congenital amegacarycytosis and 3 cases of primary immunodeficiency with lack of expression of major MHC class II. All subjects received different conditioning regimens according to the indication. Our study consisted of a regular monitoring of the immune reconstitution mainly based on the quantitative determination of lymphocyte T subpopulation. So, these tests were routinely requested to 1 month, 2 months, 3 months, 6 months, 9 months and 12 months post- bone marrow transplantation.
Results: The average time of engraftment was 18 days corresponding to neutrophil recovery (12-24). For the T cell recovery, a rate of CD4 + T lymphocytes > 200/ mm3 was provided within an average of 2.5 months (1-7). The average time to obtain CD8+ T lymphocytes >200 /mm3 was 2 months (1-5). The humoral immune reconstitution was made within an average of 2 months (1-4). A ratio of CD4+ / CD8+ T lymphocytes (>1) was obtained within 10 months and a half (1-24). Univaried analysis showed a significant correlation between the bone marrow sex matched and the faster reorganization of CD8 + T cells (p = 0.042). Moreover, a quantity of CD34 +> 6x 106/ kg was significantly associated with the recapture of a formula lymphocyte T CD4+ / CD8+ (> 1) (p=0.03).
Conclusion: The immune recovery post bone marrow transplantation in children began with myeloid lineage then lymphoid B then lymphoid T. The inversion of the ratio CD4 +/CD8+ T lymphocytes, seemed to be influenced on the one hand by the high content of CD34 + cells in the graft as well as the type of conditioning on the other hand by the CMV infection since it accelerates significantly CD8+ T lymphocyte reconstitution.
References
Barbara C Godthelp, Maarten JD van Tol, Jaak M Yossen and Peter J van den Elsen. T Cell immune reconstitution in pediatric leukemia pat bone marrow transplantation with T cell depleted or unmanupelated grafts: evaluation of overall an antigen specific T cell repertoires. Blood 1999; 94: 4358- 4369.
Roberts MM, To LB, Gillis D, et al. Immune reconstitution following peripheral blood stem cell transplantation, autologous bone marrow transplantation and allogeneic bone marrow transplantation. Bone Marrow Transplant 1993; 12: 469-475. PMID: 7905331
Demirer T, Barkholt L, Blaise D, et al. Transplantation of allogeneic hematopoietic stem cells: an emerging treatment modality for solid tumors. Nat Clin Pract Oncol 2008; 5(5): 256-267. PMID:18398414 https://doi.org/10.1038/ncponc1104
Lum LG. The kinetics of immune reconstitution after human marrow grafting. Blood 1987; 63: 369. PMID:11498301
Janice M Brown*, Irving L Weissman† and Judith A Shizuru. Immunity to infections following hematopoietic cell transplantation. Current Opinion in Immunology 2001; 13: 451-457. PMID:11498301 https://doi.org/10.1016/S0952-7915(00)00240-5
Parkman R and Weinberg KI. Immunological reconstitution following bone marrow transplantation. Immunol Rev 1997; 157: 73. PMID: 9255623. https://doi.org/10.1111/j.1600-065X.1997.tb00975.x
Uchida N, Aguila HL, Fleming WH, Jerabek L and Weissman IL. Rapid and sustained hematopoietic recovery in lethally irradiated mice transplanted with purified Thy-1.1lo Lin-Sca- 1+ hematopoietic stem cells. Blood 1994; 83: 3758-3779. PMID: 7911343.
Storek J, Joseph A, Espino G, et al. Immunity of patients surviving 20 to 30 years after allogeneic or syngeneic bone marrow transplantation. Blood 2001; 98(13): 3505-3512. PMID: 11739150 https://doi.org/10.1182/blood.V98.13.3505
Atkinson K, Hansen JA, Storb R et al. T-cell subpopulations identified by monoclonal antibodies after human marrow transplantation. I. Helper-inducer and cytotoxic-suppressor subsets. Blood 1982; 59(6): 1292-1298. PMID: 6211202
Storek J, Dawson MA, Storer B, et al. Immune reconstitution after allogeneic marrow transplantation compared with blood stem cell transplantation. Blood 2001; 97(11): 3380-3389. PMID:11369627 https://doi.org/10.1182/blood.V97.11.3380
Glucksberg, H Storb, A Fefer, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors. Transplantation 1974; 18: 295- 304. PMID: 4153799 https://doi.org/10.1097/00007890-197410000-00001
Kelsey SM, Lowdell MW and Newland AC. IgG subclass levels and immune reconstitution after T cell-depleted allogeneic bone marrow transplantation. Clin Exp Immunol 1990; 80: 409–412. PMID:2372989 https://doi.org/10.1111/j.1365-2249.1990.tb03302.x
Symann M, Bosly A, Gisselbrecht C, et al. Immune reconstitution after bone marrow transplantation. Cancer Treat Rev 1989; 16(Suppl. A): 15-19. PMID:2670211 https://doi.org/10.1016/0305-7372(89)90018-2
Pignata C, Sanghera JS, Soiffer RJ, et al. Defective activation of mitogen-activated protein kinase after allogeneic bone marrow transplantation. Blood 1996; 88: 2334-2341. PMID:8822956
Moller J, Hofmann B, Jacobsen N, et al. Defective T-cell stimulatory pathways in patients after allogeneic bone marrow transplantation (BMT) in man. APMIS 1993; 101: 480-486. PMID:8363824 https://doi.org/10.1111/j.1699-0463.1993.tb00136.x
Parra C, Roldan E, Rodriguez C, et al. Immunologic reconstitution of peripheral blood lymphocytes in patients treated by bone marrow transplantation. Med Clin Barc 1996; 106: 169-173. PMID:8684015
Leino L, Lilius EM, Nikoskelainen J, et al. The reappearance of 10 differentiation antigens on peripheral blood lymphocytes after allogeneic bone marrow transplantation. Bone Marrow Transplant 1991; 8: 339-344. PMID:1768967
Foot AB, Potter MN, Donaldson C, et al. Immune reconstitution after BMT in children. Bone Marrow Transplant 1993; 11: 7-13. PMID:8431713
Lowdell MW, Craston R, Ray N, et al. The effect of T cell depletion with Campath-1M on immune reconstitution after chemotherapy and allogeneic bone marrow transplant as treatment for leukaemia. Bone Marrow Transplant 1998; 21: 679-686. PMID:9578307 https://doi.org/10.1038/sj.bmt.1701153
Chan EY, Chiu EK, So MK, et al. Peripheral blood lymphocyte subsets after allogeneic bone marrow transplantation: reconstitution and correlation with the occurrence of acute graft-versus-host disease. Asian Pac J Allergy Immunol 1994; 12: 117-123. PMID:7612104
Storek J. Immunological reconstitution after hematopoietic cell transplantation-its relation to the contents of the graft. Expert Opin Biol Ther 2008; 8(5): 583-597. PMID:18407763 https://doi.org/10.1517/14712598.8.5.583
Witherspoon RP, LG Lum and Strob R. Immunologic reconstitution after human marrow grafting. Semin Hematol 1984; 21: 2-10. PMID:6230723
Autran B, Malphettes M, Dhédin N, et al. Studies of T cell reconstitution after hematopoieticstem cell transplant. Hematol Cell Ther 1997; 39(5): 252-256. PMID:9395899 https://doi.org/10.1007/s00282-997-0252-8
Leino L, Lilius EM, Nikoskelainen J, et al. The reappearance of 10 differentiation antigens on peripheral blood lymphocytes after allogenic bone marrow transplantation. Bone Marrow Transplant 1991; 8: 339-344. PMID:1768967
Handgretinger R, Schumm M, Lang P, et al. Transplantation of megadoses of purified haploidentical stem cells, Ann. New York Acad Sc 1999; 872: 351-362. PMID:10372137 https://doi.org/10.1111/j.1749-6632.1999.tb08479.x
Schulenburg A, Fisher M, Kalhs P, et al. Immune recovery after conventional and nonmyeloablative allogenic stem cell transplantation. Leuk Lymphoma 2005; 46: 1755-1760. PMID:16263578 https://doi.org/10.1080/10428190500264496
Daniel C, Douek DC, Richard D, et al. Changes in thymic functions with age and during the treatment of HIV infection. NATURE 1998; 396: 690-695. PMID:9872319 https://doi.org/10.1038/25374
Gastermans E, Baron F, Willes E, et al. Evidence for neogeneration of T cells by the thymus after non-myeloablative conditioning. Haematologica 2008; 93(2): 240-247. PMID 18223286 https://doi.org/10.3324/haematol.11708
Weinberg K, Blazar BR, Wagner JE, et al. Factors affecting thymic function after allogenic hematopoietic stem cell transplantation. Blood 2001; 97(5): 1458-1466. PMID:11222394 https://doi.org/10.1182/blood.V97.5.145830
Bertrand Y. Thèse de Doctorat en Médecine, Université de Claude Bernard-Lyon1, N° d’ordre 3; 2002.
