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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alloimmunization by platelet transfusions was studied in 154 patients with acute leukaemia. 17 patients had HLA antibodies at initial presentation induced by previous transfusions or pregnancies; one of these also had platelet-specific antibodies and one other patient had platelet-specific antibodies alone. A further 38 patients developed HLA antibodies during therapy; three also had platelet-specific antibodies and two patients developed platelet-specific antibodies alone. Of these, 37 patients with HLA antibodies including three with platelet-specific antibodies and one patient with platelet-specific antibodies alone survived their initial therapy and formed the basis of this study. Antibodies once detected persisted throughout the study in seven of the 37 patients with HLA antibodies including one patient with platelet-specific antibodies and in the patient with platelet-specific antibodies alone. HLA antibodies disappeared after discontinuation of transfusions in six patients, and after switching to HLA matched platelet transfusions and leucocyte-poor blood in eight patients; two of the latter patients also had platelet-specific antibodies which disappeared. The other 16 patients with HLA antibodies lost their antibodies despite continued transfusions.
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PMID:Disappearance of HLA and platelet-specific antibodies in acute leukaemia patients alloimmunized by multiple transfusions. 368 93

We have reported that immunization of H-2k mice with lymphoid cells from various allogeneic strains induced a population of cells that could eliminate first-passage spontaneous AKR leukemia from the spleens of immuno-suppressed AKR (H-2k) hosts. In the present study, we examined the nature of the cells responsible for this graft-vs-leukemia (GVL) reaction and compared them to cytolytic cells detected in vitro. Spleen cells from alloimmunized CBA/J (H-2k) mice were selectively depleted of various subpopulations by treatment with antibody and complement (C), then tested in vivo for GVL reactivity. Cell suspensions depleted of Thy-1.2+, Lyt-1+, or Lyt-2+ lymphocytes had no significant GVL reactivity, whereas suspensions depleted of NK-1.2+ cells retained GVL reactivity. The GVL-reactive cells persisted in H-2-compatible donor mice for up to 56 days. Lyt-1+2+ lymphocytes that were cytotoxic for cultured AKR leukemia cells in vitro could be detected in the spleens of alloimmunized H-2-compatible mice after expansion of the cells in T cell growth factor. Using quantitative limiting dilution cytotoxicity assays, we found that the frequency of leukemia-reactive cytotoxic lymphocytes (CL) in the spleen showed a direct correlation with the GVL efficacy of the cells in vivo. Alloimmunization was essential for induction of the GVL-reactive cell population. CL in alloimmunized mice consisted of heterogeneous cytotoxic specificities; i.e., some CL were leukemia-specific, others lysed only nonleukemic AKR target cells, and a third group mediated killing of both leukemic and nonleukemic target cells. The CL appeared to be H-2 restricted and specific for non-H-2 antigens shared by the AKR leukemia and the alloimmunizing cells.
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PMID:Characterization of alloimmunization-induced T lymphocytes reactive against AKR leukemia in vitro and correlation with graft-vs-leukemia activity in vivo. 619 24

Supportive care of the child with leukemia and solid tumors has improved dramatically due to advances in blood component preparation and use. Despite these advances, unsolved questions remain which will require research into better component preparation and randomized clinical trials. The prevention of post-transfusion graft-vs-host disease in the immunocompromised patient will require research into optimum radiation dosages for blood products and the appropriate choice of patients to receive these products. Alloimmunization to platelet concentrates will continue to be a problem as children receive more ablative cancer therapy. The use of leukocyte-poor platelets and allogeneic cryopreserved platelets may aid some of these patients, but the value of these products needs to be proven by more clinical trials. Finally, crossmatching of platelet products may become more readily available and may prove useful for more adequate selection of donors. If bone marrow transplantation becomes a therapeutic modality following remission induction for a large number of leukemic patients, the use of blood products pretransplantation will require intense investigation. Graft rejection in these children may be linked to the kind, number, and cytomegalovirus status of blood products given during their acute leukemic phase. The blood bank provides an important resource for procurement of blood products and for specialized product preparation. In addition, it should serve as a resource for new ideas and experimental blood products for use of the clinician caring for the child with cancer.
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PMID:Transfusion therapy with platelets and leukocytes. 634 81

Transplanted immunocompetent cells from CBA (H-2k) mice immunized against individual or pooled lymphoid cells from various allogeneic strains resulted in the elimination of widely disseminated leukemia cells in AKR (H-2k) host mice as measured in a GVL bioassay. In most cases, alloimmunization resulted in reactivity against AKR-L comparable to that observed when CBA donors were specifically immunized with irradiated AKR-L cells. Cells from unimmunized or isoimmunized CBA mice had no detectable GVL reactivity. Alloimmunization caused no increase in the mild GVH reactivity of unimmunized or isoimmunized CBA lymphoid cells transplanted into lethally irradiated nonleukemic AKR hosts; whereas, specific immunization with AKR-LX cells resulted in significantly increased GVH-related mortality.
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PMID:Alloimmunization: induction of antileukemic reactivity without modification of anti-host reactivity in H-2-compatible mice. 696 95

Advances in platelet transfusion have contributed to improved outcomes in the treatment of patients with cancer and leukemia. However, the optimal strategies to avoid some of the side effects that could result from platelet transfusions remain under investigation. These side effects include the development of refractoriness to transfusions, alloimmunization, transfusion reactions, the transmission of infectious agents, and transfusion-associated graft-versus-host disease. Leukodepletion by filtration is promising as a means of preventing the development of alloimmunization. Results of the Trial to Reduce Alloimmunization to Platelets will be reported shortly and will shed more light on that issue. Bedside filtration of cellular blood products also diminishes the transmission of cytomegalovirus infections by that route. Transfusion reactions are often mediated by cytokines in the plasma fraction of transfused platelet concentrates, and leukodepletion prior to storage reduces their incidence. Serious bacterial infections are sometimes transmitted by platelet transfusions and improved methods are needed for their detection and prevention. Photochemical methods that could inactivate bacteria and viruses in contaminated products deserve further study.
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PMID:Platelet transfusion support for patients with cancer and hematologic malignancies. 937

The two major methods of modifying donor blood products to prevent alloimmunization are leukocyte reduction or ultraviolet B (UVB) irradiation. Two studies have suggested that leukocyte reduction to levels <5 x 10(6) may be required to prevent alloantibody production. Three prospective, randomized transfusion trials demonstrated a statistically significant (P < 0.05) decrease in both platelet refractoriness and lymphocytotoxic antibody production in patients who received leukocyte-reduced blood components as compared to those who received standard unmodified blood products. The results of the Trial to Reduce Alloimmunization to Platelets (TRAP trial) further confirm the potential beneficial effects of leukocyte-reduced and UVB-irradiated blood products in preventing alloimmune platelet refractoriness. Five hundred thirty antibody-negative patients undergoing induction chemotherapy for acute myeloid leukemia were randomly assigned to receive either unmodified platelet concentrates, filtered leukocyte-reduced platelet concentrates, UVB-irradiated platelet concentrates, or filtered leukocyte-reduced platelets obtained by apheresis. Patients who received modified platelet components had statistically significantly lower rates of both alloimmune platelet refractoriness and lymphocytotoxic antibodies than did patients who received unmodified platelet components. There were no differences in any study endpoints among patients who received any of the three modified platelet components. The investigators concluded that leukocyte-reduced and UVB-irradiated platelet components were equally effective in preventing alloimmune-mediated platelet refractoriness; platelets obtained by apheresis provided no additional benefit.
Leukemia 1998 Sep
PMID:Platelet refractoriness and alloimmunization. 977 97

Most adverse blood transfusion (BT) events are immune-mediated and in the majority of severe reactions antibodies can be identified as causal factors. Alloimmunization not only causes symptomatic reactions, transfused cells can also be (silently) destroyed. Immunization by BT can contribute to hemolytic disease of the newborn as well as to allograft rejection after transplantation. Reversely, pregnancy and transplantation may evoke immunity hampering transfusion therapy. Besides causing mortality and morbidity, alloimmunization has a huge economic impact. Transfusion reactions prolong hospital stay, require diagnostic tests and complex donor selection procedures and create the need for typed donor registries. In the 1970s, Opeltz and colleagues described that pre-transplantation BT impaired rejection of renal transplants. Leukocytes were essential for this immunosuppressive BT effect that raised concern about negative effects on cancer growth and resistance against infections. Studies on the mechanism were however preliminary abandoned when calcineurin inhibitors for prevention of graft rejection became available and since all blood products underwent leukoreduction in most countries as precautionary measure against transmission of variant Creutzfeldt-Jacob disease. Whether current leukoreduced BT are immunosuppressive and for which patients or circumstances this may contribute to worse outcome, is unknown. The last decades of the previous century, leukoreduction of cellular blood products for leukemia patients significantly reduced the incidence of immunological platelet transfusion refractoriness. The first decade of this century the avoidance of plasma- and platelet-products from females, that may contain donor-derived leukocyte antibodies, decreased transfusion related acute lung injury (TRALI) by more than 30%. These were major achievements. Challenge for the near future is to further reduce alloimmunization in particular against red blood cells (RBC) as a cause of severe hemolytic transfusion reactions and problems to find compatible donors. This can be achieved by extended matching. Inventory limitations prevent to match all BT for clinically relevant RBC antigens. A (European-wide) registration of clinical and genetic risk factors associated with alloimmunization could support effective use of matched blood products.
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PMID:Immunological complications of blood transfusions. 2749 23

Red cell alloimmunization may induce severe hemolytic side effects. Identification of risk-modifying conditions will help tailor preventative strategies. This study aims to quantify the associations of hematologic malignancies and solid cancers with red cell alloimmunization in patients receiving red cell transfusions. We performed a nested multicenter case-control study in a source population of 24,063 patients receiving their first and subsequent red cell transfusions during an 8-year follow-up period. Cases (n=505), defined as patients developing a first transfusion-induced red cell alloantibody, were each compared with 2 non-alloimmunized controls (n=1010) who received a similar number of red cell units. Using multivariate logistic regression analyses, we evaluated the association of various malignancies and treatment regimens with alloimmunization during a delineated 5-week risk period. The incidence of alloimmunization among patients with acute (myeloid or lymphoid) leukemia and mature (B- or T-cell) lymphoma was significantly reduced compared to patients without these malignancies: adjusted relative risks (RR) with 95% confidence interval (CI) 0.36 (range 0.19-0.68) and 0.30 (range 0.12-0.81). Associations were primarily explained by immunosuppressive treatments [RR for (any type of) chemotherapy combined with immunotherapy 0.27 (95%CI: 0.09-0.83)]. Alloimmunization risks were similarly diminished in allogeneic or autologous stem cell transplanted patients (RR 0.34, 95%CI: 0.16-0.74), at least during the six months post transplant. Alloimmunization risks of patients with other hematologic diseases or solid cancers, and their associated treatment regimens were similar to risks in the general transfused population. Our findings suggest that, in contrast to malignancies in general, hemato-oncological patients treated with dose-intensive regimens have strongly diminished risk of red cell alloimmunization.
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PMID:Treatments for hematologic malignancies in contrast to those for solid cancers are associated with reduced red cell alloimmunization. 2763 4