UMLS:C0023418 - FACTA Search

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

An 11-year-old boy with acute lymphoblastic leukemia received unrelated cord blood transplantation at the second remission. Because of early graft failure, he was given a second non-T-cell depleted bone marrow transplant from his HLA 2 loci (HLA-A and -DRB1)-mismatched mother 36 days after the first transplantation. Feto-maternal microchimerism was verified before transplantation. The second transplantation was performed with fludarabine/melphalan as a conditioning regimen, and tacrolimus/short-course methotrexate as graft-versus-host disease (GVHD) prophylaxis. Engraftment was prompt with a recovery of neutrophils (> 0.5 x 10(9)/1) by day +10, reticulocytes (> 1%) by day +17 and platelets (> 50 x 10(9)/l) by day +18. Mild regimen-related toxicities (grade I gastrointestinal, grade II hepatic) were observed and acute GVHD was grade I (skin: stage 2). No severe complication was noted. At 6 months post-transplantation, he had no chronic GVHD or leukemia relapse. This experience indicates the future feasibility of a back-up non-T-cell depleted transplantation from HLA 2 loci-mismatched and feto-maternal microchimerism-positive mothers in cases with primary graft failure.
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PMID:[Acute lymphoblastic leukemia in childhood treated with non-T-cell depleted bone marrow transplantation from an HLA 2 loci (HLA-A and-DRB1)-mismatched mother after early graft failure of cord blood transplantation]. 1468 75

The aim of this study was to identify significant prognostic factors by using unrelated genomically HLA-A, -B and -DRB1-identical donors. Such data could help to choose the best donor. We studied 136 consecutive patients with hematologic malignancies and a median age of 32 years (range, 0-55 years) who received hematopoietic stem cell transplantation. Bone marrow grafts were given to 83 and peripheral blood stem cells to 53 patients. The cumulative incidence of grade II to IV acute graft-versus-host disease (GVHD) was 30% and of chronic GVHD was 54%. At 5 years, the overall transplant-related mortality (TRM) was 34%, and patient survival was 50%. In Cox multivariate analysis, 32 potential risk factors were analyzed. Monoclonal antibody OKT-3 during conditioning was correlated with grade II to IV acute GVHD, chronic GVHD, and TRM. HLA-DP mismatch was associated with poor TRM and poor survival. Cytomegalovirus-seropositive patients with a seronegative donor had a decreased leukemia-free survival. Five-year TRM was 14% with no risk factor, 38% with 1 risk factor, and 87% with 2 risk factors. The 5-year survival was 72%, 48%, and 30% with 0, 1, and 2 risk factors, respectively. We concluded that unrelated hematopoietic stem cell transplantation may be improved if an optimal donor and immunosuppression are chosen.
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PMID:Which donor should be chosen for hematopoietic stem cell transplantation among unrelated HLA-A, -B, and -DRB1 genomically identical volunteers? 1475 78

In order to determine whether matching/mismatching for microsatellite polymorphism provides useful information on acute graft-vs-host disease (GVHD), survival, and leukemia relapse in hematopoietic stem cell (HSC) transplantation, we genotyped for polymorphisms at 13 microsatellite loci within the major histocompatibility complex (MHC) of 100 unrelated HSC transplant donor-recipient pairs who were matched at five classical human leukocyte antigen (HLA) loci. A high percentage of allele matching was obtained for five microsatellite loci, DQCARII (96%), MICA (93%), MIB (89%), C1-3-1 (93%), and D6S510 (97%), that are localized within 100 kb of the HLA-DR, HLA-DQ, HLA-B, HLA-C, or HLA-A locus. In contrast, the other eight microsatellites are located farther away from the HLA classical loci and have much lower percentages of allele matching [e.g. tumor necrosis factor a (TNFa) (73%), TNFd (74%), D6S273 (64%), C3-2-11 (46%), C5-3-1 (50%), C5-4-5 (63%), C5-2-7 (68%), and D6S265 (81%)]. Therefore, there were at least eight microsatellite markers with relatively high percentages of mismatches in the donor/recipient pairs with acute or chronic GVHD, poor graft survival, and leukemia relapse. However, there were no statistically significant associations between mismatched donor-recipient pairs at the 13 microsatellite loci and acute or chronic GVHD, graft survival, and leukemia relapse. Nevertheless, allele matching at the microsatellite TNFd locus near the TNFa gene was found by the Fisher's exact double-sided test to be significantly associated with decreased survival in the grade III/IV acute GVHD group. Overall, these results suggest that the matching of microsatellite polymorphisms within the HLA region, especially the ones farthest from the classical HLA loci, was not useful indicator for the outcome of HSC transplantation from unrelated donors. In this regard, the future determination of the genome-wide microsatellite genotypes in HLA-matched donor-recipient pairs, outside the MHC, may be a better possibility for identifying minor histocompatibility genes in linkage disequilibria with microsatellites as potential predictive markers for the occurrence of acute GVHD and survival rate in HSC transplantation.
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PMID:Association of polymorphic MHC microsatellites with GVHD, survival, and leukemia relapse in unrelated hematopoietic stem cell transplant donor/recipient pairs matched at five HLA loci. 1500 8

Human leukocyte antigen (HLA) class I antigen defects may have a negative impact on the growing application of T-cell-based immunotherapeutic strategies for treatment of leukemia. Therefore in the present study, taking advantage of a large panel of HLA class I allele-specific human monoclonal antibodies, we have compared HLA class I antigen expression on leukemic cells with that on autologous and allogeneic normal cells. Down-regulation of HLA-A and/or -B allospecificities was present in the majority of the patients studied. However, down-regulation did not affect all HLA class I alleles uniformly, but was almost exclusively restricted to HLA-A allospecificities and to HLA-B allospecificities which belong to the HLA-Bw6 group. The latter allospecificities, at variance from those that belong to the HLA-Bw4 group, do not modulate the interactions of leukemic cells with natural killer (NK) cells. Therefore, our results suggest that the selective down-regulation of HLA-A and HLA-Bw6 allospecificities associated with HLA-Bw4 preservation provides leukemic cells with an escape mechanism not only from cytotoxic T lymphocytes (CTLs), but also from NK cells. As a result T-cell-based immunotherapeutic strategies for leukemia should utilize HLA-Bw4 alloantigens as restricting elements since a selective HLA-Bw4 allele loss would provide leukemic cells with an escape mechanism from CTLs, but would increase their susceptibility to NK cell-mediated lysis.
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PMID:Down-regulation of HLA-A and HLA-Bw6, but not HLA-Bw4, allospecificities in leukemic cells: an escape mechanism from CTL and NK attack? 1507 Jun 94

Recurrent cytogenetic abnormalities in leukemic blasts make these an attractive source for dendritic cells (DC) to induce a leukemia-specific immune response. In this study, three leukemic cell lines were investigated: Kasumi-1 and SKNO-1 (two acute myeloid leukemia (AML) cell lines carrying the (8;21)-chromosomal translocation, resulting in the expression of the leukemia-specific fusion protein AML1-eight-twenty-one) and REH, an acute lymphoblastic leukemia cell line with the (12;21)-chromosomal translocation and expression of translocation ETS-like leukemia-AML1. These fusion proteins are implicated in the pathogenesis of the leukemic state by recruiting corepressors and histone deacetylases (HDAC), which interfere with normal cell differentiation. In vitro generation of DC was achieved using a cytokine cocktail containing tumor necrosis factor alpha, granulocyte macrophage-colony stimulating factor, c-kit ligand, and soluble CD40 ligand; yet, addition of the HDAC inhibitor (Hdi) trichostatin A enhanced DC differentiation with retention of the fusion transcripts. These leukemic DC showed high-level CD83 and human leukocyte antigen (HLA)-DR expression and had a high allostimulatory potential. Only DC generated from these cell lines after Hdi induced blast-specific cytotoxic T cell responses in HLA-A-matched T cells with a cytotoxicity of 42% in parental Kasumi-1 and 83% in parental REH cells, respectively. This model system suggests that the Hdi supports the in vitro differentiation of DC from leukemic blasts with AML1-containing fusion proteins.
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PMID:Histone deacetylase inhibition improves dendritic cell differentiation of leukemic blasts with AML1-containing fusion proteins. 1519 37

This study was aimed to observe the efficacy and side effects of allogeneic peripheral blood stem cell transplantation (Allo-PBSCT) in patients with leukemia. The donors were siblings matched with t HLA-A, B, DR loci of recipient. After mobilization with 250 microg/day rhG-CSF for 5 days, peripheral blood stem cells were collected 1 to 2 times. 4 patients with leukemia received 6.78 x 10(8)/kg +/- 1.96 x 10(8)/kg (5 x 10(8)/kg-8.67 x 10(8)/kg) peripheral blood mononuclear cells, which contained 15.02 x 10(6)/kg +/- 8.93 x 10(6)/kg (5.3 x 10(6)/kg-24.23 x 10(6)/kg) CD34(+) cells after modified Bu/Cy conditioning regimen and MTX + CsA + MMF were given for prophylaxis of aGVHD. The results showed that the leukocyte was reduced to the lowest at pretransplantation 2 days-posttransplantation 2 days. Neutrophil amount >0.5 x 10(9)/L was found at 11 - 17 day after transplantation, platelet >50 x 10(9)/L-at 11 - 55 days after transplantation. Out of 4 patients, aGVHD, cGVHD and infection took place in 2,2 and 2 cases, respectively. Bone marrow displayed hematopoietic recovery at 28 day after transplantation, examination of STR in DNA revealed proliferation of donor cells in patients. In conclusion, Allo-PBSCT in combination with modified Bu/Cy conditioning regimen and MTX + CsA + MMF prophylaxis of aGVHD is safety and reliable for treatment of leukemia.
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PMID:[Treatment of leukemia by allogeneic peripheral blood stem cell transplantation from sibling donors]. 1563 69

Cord blood transplants are now widely used for allogeneic hematopoietic stem cell transplants (HSCT) in patients with various hematologic disorders. One advantage of this source of stem cells is the decrease of graft-versus-host disease (GVHD) because of the immaturity of lymphocytes at birth. The role of human leukocyte antigen (HLA) for donor search and post-transplant outcomes is not very well described. The Eurocord Registry has analyzed more than 1,000 cases of unrelated cord blood transplants (UCBT). Results show that HLA matching is important for engraftment and graft versus leukemia but not for survival and GVHD. Allelic matching for HLA-A, -B, -C, -DRB1, and -DQB1 shows that the number of mismatches is very high and does not allow identification of prognostic factors. Contrary to the criteria of donor choice for an unrelated bone marrow transplant where HLA allelic matching is important, in the case of cord blood transplants the number of nucleated cells infused is the most important predictor of success.
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PMID:Human leukocyte antigen matching in cord blood transplantation. 1584 74

A non-total body irradiation-containing preparative regimen was studied in young children (<4 years old) undergoing unrelated donor cord blood transplantation as part of the Cord Blood Transplantation trial for the treatment of acute lymphoblastic leukemia (n = 14), acute myeloid leukemia (n = 13), undifferentiated leukemia (n = 1), juvenile myelomonocytic leukemia (n = 2), and myelodysplastic syndromes (n = 2). Donor/recipient HLA matching based on low-/intermediate-resolution molecular typing for HLA-A and -B and high-resolution HLA-DRB1 typing was 5/6 or 6/6 (n = 21) or 4/6 (n = 11). The preparative therapy consisted of busulfan, melphalan, and antithymocyte globulin, with cyclosporine and corticosteroids for graft-versus-host disease (GVHD) prophylaxis. The median age was 1.6 years (range, 0.5-3.9 years), and the median weight was 10.5 kg (range, 5.8-19.5 kg). Cord blood grafts contained a median of 10.7 x 10 7 nucleated cells per kilogram (range, 4.6-29.2) and 2.6 x 10(5) CD34+ cells per kilogram (range, 0.7-8.3). The cumulative incidence (CINC) of neutrophil recovery (absolute neutrophil count >500/microL) at day 42 was 0.59 (95% confidence interval [CI], 0.44-0.78) at a median of 31 days (range, 23-55 days). The CINC and Kaplan-Meier estimates of platelet engraftment at day 180 were 0.53 (95% CI, 0.34-0.69) and 0.82 (95% CI, 0.61-1.00), respectively. CINC estimates of grade III/IV acute GVHD at day 100 and chronic GVHD at 1 year were 0.25 (95% CI, 0.09-0.41) and 0.26 (95% CI, 0.09-0.44), respectively. The CINC estimate of relapse was 0.31 (95% CI, 0.16-0.47) at 2 years. With a median follow-up of 27.8 months (range, 23.4-46.7 months), the probability of survival at 1 year was 0.47 (95% CI, 0.30-0.64). A preparative regimen containing a busulfan/melphalan/antithymocyte globulin preparative regimen is well tolerated in the setting of unrelated donor cord blood transplantation for childhood leukemia and can serve as a platform preparative regimen for intensifying host immunosuppression and antileukemic therapy to allow for improved engraftment and improved relapse-free survival.
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PMID:Busulfan/melphalan/antithymocyte globulin followed by unrelated donor cord blood transplantation for treatment of infant leukemia and leukemia in young children: the Cord Blood Transplantation study (COBLT) experience. 1604 14

This study was aimed to investigate the corelation between the HLA (human leukocyte antigen) genes and susceptibility of leukeamia. 605 patients with leukeamia including 189 ALL, 184 AML and 232 CML were selected for this investigation. 900 normal umbilical cord blood samples from umbilical cord blood bank were used as control population compared to the leukemia patients. HLA-A, B, C typing was done by polymerase chain reaction with sequence-specific primers (SSP-PCR). The results showed that frequencies of HLA-A*26, A*68, B*56 in ALL patients were higher (4.46%, 2.65%, 1.17%), as compared with controls (2.31%, 0.95%, 0.22%), HLA-CW*06 in ALL patients was lower (3.64%), as compared with control (11.65%). In AML patients HLA-A*01 (9.41%), B*37 (3.60%) was higher and A*33 (3.60%), B*51 (4.73%) were lower than those in controls (3.57%, 1.75% and 7.64%, 7.93%). HLA-A*32, B*27, B*44, B*54, B*55 (2.18%, 3.96%, 5.06%, 4.63%, 2.84%) in CML patients were higher than those in control (0.84%, 2.04%, 3.07%, 2.44%, 1.29%). These results suggested that positive association may exist between certain HLA-class I genes and leukemias. These preliminary data may be useful for further study on the mechanisms of leukemia pathogenesis.
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PMID:[Association of gene HLA-class I with leukemia]. 1612 34

Several leukaemia-specific antigens have been discovered in the recent past, which raised the possibility for T-cell-based immunotherapy for leukaemia. However, failure of such approaches involving interleukin-2 and/or T-cell-based immunotherapy indicated the importance of investigation of the human leucocyte antigen (HLA) status of the haematopoietic malignant cells. Considerable number of reports indicate that both HLA class I and class II are down-regulated in different cases of leukaemias, enabling them to evade immuno-surveillance. However, locus-specific down-regulation in leukaemia has not been widely investigated, although majority of cytotoxic T lymphocyte (CTL) responses are modulated by HLA-A and HLA-B, whereas expression of only HLA-C is unable to block natural killer (NK)-cell-mediated cytotolysis. Therefore, using RT-PCR, we have investigated the HLA class I transcriptional expression in a locus-specific manner, along with HLA-associated accessory molecules beta2-microglobulin and transporter-associated antigen processing molecule (TAP1). Our data suggest that in several newly diagnosed untreated leukaemic patients, HLA-C and beta2-microglobulin are expressed, but not the locus HLA-A or -B. Moreover, TAP1 and beta2-microglobulin were observed to be down-regulated in a number of cases of leukaemia. Our flow cytometric analysis of HLA-ABC also indicates a decrease in mean fluorescent intensity but no complete loss in surface expression of HLA class Ia on the leukaemic cells. Therefore, the observed low surface expression of HLA-ABC may be due to the down-regulation of transcription of HLA-A or -B itself and/or transcriptional suppression of the accessory molecules.
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PMID:Analysis of HLA class Ia transcripts in human leukaemias. 1613 50

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