Immunity of patients surviving 20 to 30 years after allogeneic or syngeneic bone marrow transplantation

Abstract

IntroductionMore than 125 000 allogeneic and syngeneic hematopoietic cell transplantations (HCTs) have been performed worldwide for hematologic malignancies, aplastic anemia, and inborn errors of hematolymphopoietic cells. [1][2][3] Immunodeficiency follows HCT and lasts for more than 1 year. [4][5][6][7][8][9][10][11] Because HCT only came into general practice in the 1980s, there has been, up until now, no opportunity to observe the immunity of very long-term survivors. There are conflicting views about what might happen to the immunity of these patients. On the one hand, infection rates as well as laboratory parameters of immunity like CD4 T-cell counts gradually improve in the first 5 years after transplantation (reviewed in Parkman and Weinberg 4 and Storek and Witherspoon 5 ). Thus, by 20 years, one might expect relatively complete recovery. On the other hand, there is the possibility that the replicative potential of the transplanted immune cells and/or their precursors might be limited. 12 This possibility could result in late onset immune deficiency. We have undertaken a study of a unique cohort of patients, the first group surviving 20 to 30 years after transplantation. We have asked the following questions: (1) What are the counts of immune cells in this group of patients? CD4 T cells were of particular interest because low CD4 T-cell counts have been associated with high rates of postengraftment infections and because the duration of CD4 T lymphocytopenia in adult marrow transplant recipients is not known (CD4 T-cell counts remain low for at least 5 years after transplantation). 13-15 (2) What are the counts of T cells generated de novo (from hematolymphopoietic cells)? This question is important because concerns have been raised that the grafted hematolymphopoietic cells or the host thymus cannot sustain de novo T lymphopoiesis for more than 14 years after transplantation. 12 (3) What are the levels of immunoglobulin (Ig)G 2 and IgG against the capsular polysaccharides of commonly encountered encapsulated bacteria? Low levels have been associated with infections in HCT recipients, and the duration of this selective immunoglobulin deficiency is not known (levels remain low for at least 2 to 5 years after transplantation). [16][17][18][19][20] (4) How frequently do the very late survivors develop infections? Infections, the incidence of which is the most clinically relevant measure of immunity, have been described to cause significant morbidity and mortality even between 2 and 16 years after transplantation. 21,22 Patients, materials, and methods PatientsOf 389 patients undergoing allogeneic (361) or syngeneic (28) bone marrow grafting in Seattle before January 1, 1978, 72 patients survived for Reprints: Jan Storek, FHCRC, D1-100, 1100 Fairview Ave N, Seattle, WA 98109-1024; e-mail: jstorek@fhcrc.org.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 U.S...

Impact of different post-remission strategies on quality of life in patients with acute myeloid leukemia

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B-cell reconstitution after allogeneic SCT impairs minimal residual disease monitoring in children with ALL

“…Higher numbers of total B cells were also observed in a study of patients surviving 20-30 years after transplantation. 43 The problem of extensive regeneration causing unspecific primer binding could be theoretically overcome by using regenerating BM DNA instead of DNA from buffy coats as a negative control; however, the availability of such CsA, MP no IS n =44 n =18 P < 0.0001 material in practice is very limited. Our recommendation is to continue using PB buffy coats while carefully judging cases of not quantifiable post-SCT MRD positivity.…”

Lymphocyte reconstitution following allogeneic hematopoietic stem cell transplantation: a retrospective study including 148 patients

“…Therefore, determination of lymphocyte subsets by flow cytometry remains a valid and routinely practicable method to characterize the risk for infections in patients after allogeneic transplantation. Several studies have analyzed the role of defined parameters in lymphocyte reconstitution after alloHSCT [10][11][12][13][14][15] and immune reconstitution has been found to be influenced by the source of graft (peripheral blood stem cells (PBSC) vs bone marrow (BM)), [10][11][12][13] type of conditioning, 16 incidence or extent of GvHD, 17 cytomegalovirus (CMV) reactivation or the CMV serostatus before HSCT. 18 However, most of these studies are hampered, because the role of defined parameters was investigated in relatively small cohorts of patients, mostly with focus on the source and cellular composition of the graft.…”