[Show abstract][Hide abstract] ABSTRACT: Donor cytomegalovirus seropositivity was reported to improve leukemia outcomes in HLA-A2 identical hematopoietic cell transplant (HCT) recipients, due to a possible cross-reactivity of donor HLA-A2-restricted CMV-specific T cells with minor histocompatibility (H) antigen of recipient cells. This study analyzed the role of donor CMV serostatus and HLA-A2 status on leukemia outcomes in a large population of HLA-identical HCT recipients.
Leukemia patients transplanted between 1992 and 2003 at the Fred Hutchinson Cancer Research Center were categorized as standard risk [leukemia first remission, chronic myeloid leukemia in chronic phase (CML-CP)] and high risk (advanced disease) patients. Time-to-event analysis was used to evaluate the risk of relapse and death associated with HLA-A2 status and donor CMV serostatus.
In standard risk patients, acute leukemia (p<0.001) and sex mismatch (female to male, p=0.004)) independently increased the risk of death, while acute leukemia increased the risk of relapse (p<0.001). In high risk patients acute leukemia (p=0.01), recipient age > or = 40 (p=0.005) and herpes simplex virus (HSV) seropositivity (p<0.001) significantly increased the risk death; HSV seropositivity (p=0.006) increased the risk of relapse. Donor CMV serostatus had no significant effect on mortality or relapse in any HLA group.
This epidemiological study did not confirm the previously reported effect of donor CMV serostatus on the outcomes of leukemia in HLA-A2-identical HCT recipients. Addressing the question of cross-reactivity of HLA-A2-restricted CMV-specific T cells with minor H antigens in a clinical study would require knowledge of the patient's minor H antigen genotype. However, because of the unbalanced distribution of HLA-A2-restricted minor H antigens in the population and their incomplete identification, this question might be more appropriately evaluated in in vitro experiments than in a clinical study.
[Show abstract][Hide abstract] ABSTRACT: The transplantation of bone marrow cells or isolated hematopoietic stem cells from the bone marrow or peripheral blood is a widely utilized form of therapy for patients with incurable diseases of the hematopoietic and immune systems. Successful engraftment of the transplanted stem cells in an adequately prepared recipient normally leads to bone marrow reconstitution over a period of several weeks, accompanied by more gradual reconstitution of the immune system. Since the recipient is profoundly ill during the initial treatment period, laboratory data is critical for monitoring engraftment, detecting residual/recurrent disease, and identifying problems that may delay bone marrow reconstitution or lead to other medical complications. Accurate blood cell counts are imperative, and most bone marrow transplantation patients undergo periodic monitoring with bone marrow aspirates and biopsies with cytogenetic, molecular, and multiparametric flow cytometric studies. The potential complications of bone marrow transplantation include engraftment failure and delayed engraftment, infection, residual bone marrow disease, acute and chronic graft versus host disease, myelofibrosis, therapy-related acute leukemia, post-transplant lympho-proliferative disorders, and toxic myelopathy.
[Show abstract][Hide abstract] ABSTRACT: Human cytomegalovirus is a large DNA virus that is well-equipped to evade both innate and adaptive host immune responses and to establish lifelong latency. It is a major opportunistic pathogen in immunocompromised hosts. Following allogeneic transplantation, immune responses are often inadequate to inhibit viral reactivation, resulting in progressive tissue damage, manifesting as overt human cytomegalovirus disease that usually presents as pneumonitis, colitis or hepatitis. Currently available antiviral pharmacotherapies are limited by toxicities if used prophylactically, and by a lack of efficacy in established human cytomegalovirus disease. Efforts have therefore focused on molecular diagnostic surveillance protocols that allow earlier intervention and the development of adoptive immunotherapeutic strategies to hasten host immune reconstitution.
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