HLA immunization is a common complication of transfusion therapy in 30% to 60% of oncohematologic patients. Evidence shows that leukocytes present in cellular blood products are the main component involved in the occurrence of HLA immunization, and several studies showed that leukocyte-poor blood products are less able to induce it. However, leukocyte-poor platelet concentrates obtained by conventional techniques, ie, centrifugation, frequently have a high level of remaining leukocytes. Cotton wool filter Imugard IG 500 can be used to obtain leukocyte-poor cellular blood products. The technique is easy to perform, even in an emergency, and can be used with either packed RBCs or platelet concentrates. Means of 97%, 92%, and 76% elimination of leukocytes are obtained for packed RBCs, pooled standard platelet concentrates, and single-donor platelet concentrates, respectively. Patients were randomized to receive either standard (control group) or filtered (leukocyte-poor group) blood products. Of 112 randomized patients, 69 were evaluable, 35 in the control group and 34 in the leukocyte-poor group. Both groups are comparable according to age, diagnosis, sex ratio, previous transfusions, and pregnancies. There is a significant difference in regard to the HLA immunization rate (31.4% in the control v 11.7% in the leukocyte-poor group, P less than .05) and frequency of refractoriness to platelet transfusions (46.6% v 11.7%, P less than .05). We conclude that this filtration technique can be an efficient means to reduce the HLA immunization rate in polytransfused oncohematologic patients.
The IL route allowed reproducible administration of specified numbers of DCs. The IN route sometimes yielded fairly similar results, but not reproducibly. Lastly, we showed that DCs matured without PGE2 that have in vitro TH1 polarisation capacities can migrate to lymph nodes after ID injection.
This study compares the behavior of 2 commercially available polyriboinosinic-polyribocytidylic acids (poly I:C1 and poly I:C2) and the structural analog poly I:C12U in regard to dendritic cell (DC) maturation. When the Toll-like receptor 3 (TLR3) agonists are tested in combination with interferon-alpha, tumor necrosis factor-alpha, interleukin (IL)-1beta, and interferon-gamma (the so-called alpha-type-1 DC), the 3 different cocktails generate phenotypically mature DCs, but with different functional properties. Higher migratory capacity is observed with poly I:C1, the only poly I:C allowing spontaneous release of IL-12p70 by DCs. However, upon CD40 triggering, cocktails containing poly I:C2 or poly I:C12U allow a far higher production of IL-12p70 compared with those containing poly I:C1. Using a TLR signaling pathway reverse transcription profiler polymerase chain reaction to analyze changes in gene expression after treatment of DCs with the agonists alone, we show that 39% of the 84 tested genes are differentially regulated between the 3 conditions. Poly I:C12U induces far fewer regulated genes than the 2 other poly I:Cs. These different behaviors could be due to alternative ways of sensing double-stranded RNA, which do not rely solely on TLR3 but also on other types of receptors, depending on the size of poly I:Cs. As the 2 poly I:Cs tested here have very different molecular weights, this could partly explain the observed differences. In conclusion, neither the poly I:Cs nor their structural analog poly I:C12U have an equivalent behavior. This should be taken into an account not only when they are used in cocktails for DC maturation but also when analyzing signaling pathways with synthetic double-stranded RNA analogs.
Patients' autologous macrophages (AM) were used as antigen-presenting cells (APC) in a vaccination protocol against malignant melanoma. AM were administered by various routes, including intralymphatic, since these cells did not express CCR7, a molecule required for APC migration to lymph nodes. Seven HLA-A2 patients with metastatic melanoma-two classified as M1 and five as M3-were included in the study. AM were produced from leukapheresis-separated mononuclear cells by 7-day culture with granulocyte-macrophage colony-stimulating factor. After separation by elutriation, AM were frozen in aliquots and subsequently thawed at monthly intervals, exposed to MAGE-3(271-279) peptide and injected subcutaneously into lymph nodes or into one peripheral lymph vessel. Intradermal tests were performed before and after treatment to determine peptide reactivity. No acute toxicity was observed following injection. One M1 patient had a 7-mm induration intradermal reaction response and was stabilized for 64 weeks. The M3 patients did not show any immunological or clinical response. In 11 patients, the biodistribution of 111In-labeled AM was investigated. There was no clear evidence that AM injected intradermally or subcutaneously left the site of injection. After injection into a lymph vessel of the foot region, scintigraphs showed five to ten popliteal and inguinocrural lymph nodes. This appeared to be the most efficient way to administer rapidly and safely large amounts of peptide-loaded APC into lymph nodes.
A series of 11 investigations confirms the previously reported distribution pattern of intravenously injected AAM. It is possible that in patients treated with hematopoietic cell-mobilizing agents, granulocytes develop in cultures designed to produce monocyte-derived antigen-presenting cells.
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