Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ethnic background of human T-lymphotropic virus types I and II (HTLV-I/II) infections and associated diseases was investigated in association with human leukocyte antigens (HLA) (alleles) and haplotypes. Japanese HTLV-I carriers were characterized by two categories of HLA class I antigens (A24, A26, B7, B61, Cw1, and Cw7) and class II alleles (DRB1 *0101, 0803, 1403, 1501, and 1502 and DQB1 *0303, 0501, and 0601); one category was associated with adult T-cell leukemia (ATL) patients and the other with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients. The ATL-associated haplotypes had unique DRB1-DQB1 alleles (0901-0303, 1501-0602, 1401-0503), which were correlated with a low immune responsiveness to HTLV-I, while the HAM/TSP haplotypes had different DRB1-DQB1 alleles (0101-0501, 0803-0601, 1502-0601), which were correlated with a high immune responsiveness to HTLV-I. Both ATL- and HAM/TSP-associated haplotypes were found among HTLV-I carriers and the patients from other ethnic groups (Jamaican blacks, Andes natives, South American mestizos, and Mashhadi Jews). HLA haplotypes of HTLV-II carriers were different from those of HTLV-I carriers among South American natives. These results suggested that HTLV-I/II infections and the associated diseases might be determined by immunogenetic factors segregated with HLA alleles and haplotypes.
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PMID:Immunogenetics of HTLV-I/II and associated diseases. 879 14

Use of 2-D gel and imaging plate analysis enabled biosynthetically radiolabeled immunoprecipitates to be quantitated at the very low level of gene products during processing from RER inside cells to cell surface. We used this efficient and sensitive measurement to analyse expression of HLA-DR molecules in human eosinophilic leukaemia cell lines. We found that they synthesized a constitutive amount of DRA gene products and differential amounts of DRB1 gene products. Thus, the incompletely inducible expression of DRB1 gene products was responsible for the limited accumulation of normally assembled molecules for cell surface expression and the lack of serological determination.
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PMID:Differential and constitutive expression of the DRB1 and DRA gene products controls the surface HLA-DR expression level in human eosinophilic leukaemia cell lines. 911 85

Between January 1989 and July 1995 the search for an unrelated donor (UD) was started for 379 consecutive Italian patients with Philadelphia positive (Ph+) chronic myelogenous leukaemia (CML). 89 (23%) were transplanted. The overall probability of transplant before and after December 1991 was 16% and 49%, respectively (P=0.0001), and average interval between search activation and graft was 23 months and 13 months, respectively (P=0.0001). Disease-free survival (DFS) following 60 consecutive transplants performed before February 1996 was 41.5% at 48 months and was 64% for patients grafted after January 1993. In univariate analysis, five variables had a favourable effect on DFS: year of bone marrow transplantation (BMT) after 1993 (P=0.0002), HLA-DRB1 donor/recipient (D/R) match (P=0.0006), total body irradiation (TBI) containing regimen (P=0.0006), graft-versus-host disease (GvHD) prophylaxis including 'early' cyclosporin before the transplant, and a marrow cell dose > 3 x 10(8)/kg of recipient body weight (P=0.04). Multivariate analysis confirmed that HLA identity (P=0.006), TBI-containing regimen (P=0.0001) and 'early cyclosporin' (P=0.04) were associated with higher DFS. Transplant-related mortality (TRM) was 67% in patients grafted before January 1993 and 30% in patients grafted subsequently (P=0.002). Multivariate analysis confirmed DRB1 identity (P=0.03) and TBI-containing regimen (P=0.0005) to be independent factors predictive of low TRM. This suggests that the outcome of patients transplanted from an HLA DRB1 matched donor, after a TBI-containing preparative regimen, is similar to results recently reported in patients transplanted from geno-identical siblings. These results indicate that the search should be initiated at diagnosis for patients < 45 years of age and UD BMT should be considered early in the disease course for those with an available DRB1-matched unrelated donor.
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PMID:Unrelated donor marrow transplantation for chronic myelogenous leukaemia. 969 72

Patients with advanced acute leukemia (AL) have a poor prognosis with death due to disease or complications of therapy. High-dose chemoradiotherapy followed by allogeneic marrow transplantation (BMT) has been used to overcome resistance of the leukemic clone resulting in long-term survival of up to 20%. Due to lack of suitable related donors BMT from an HLA-compatible unrelated donor (MUD) has been increasingly applied in these patients during the last years. Between January 1991 and August 1997 twenty five patients with advanced acute myeloid (n=19) or lymphoid (n=6) leukemia, 11 males and 14 females, age 22 to 41 (median 32) years received MUD (n=22) or 1-antigen mismatched unrelated donor (n=3) grafts. In four patients an autologous BMT had been performed previously. For conditioning all patients were given total body irradiation containing regimens. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (CSA) and methotrexate (n=24) or CSA and methylprednisone (n=1). In 23 patients (92%) class II region compatibility was assessed by DRB1, DRB3, DRB5, and DQB1 allele typing by hybridization of amplified DNA with ligation based typing. In 2 patients HLA-DR typing was performed by two colour fluorescence cytotoxicity test and mixed lymphocyte cultures. As of November 1997 10/25 patients (40%) are surviving leukemia-free after a median observation time of 17 (range, 3 to 38) months. Transplant-related mortality was an overall of 36% and 28% in patients receiving their first BMT. In 6/25 patients (24%) relapse occurred 2 to 26 months after BMT. Incidence of acute GVHD grade I to IV was 85%. The probability of relapse projected at 3 years was 35%. High-dose chemoradiotherapy followed by MUD marrow infusion has a curative potential for patients with advanced acute leukemia and offers the chance of long-term leukemia-free survival. Currently, up to 80% of patients with acute myelogenous leukemia (AML) and acute lymphoid leukemia (ALL) under the age of 50 years achieve complete hematological remission (CR) with conventional dose chemotherapy. However, in patients who are refractory to induction chemotherapy or relapse prognosis is still poor. There, high-dose chemoradiotherapy followed by allogeneic marrow infusion has been used to overcome resistance of the refractory leukemic clone and has resulted in long-term survival. For selected patients lacking a human leukocyte antigen (HLA) compatible family donor marrow transplantation (BMT) with a suitable unrelated marrow donor (MUD) has become a feasible and effective treatment. Here, we report our experience in patients with advanced acute leukemia given marrow grafts from unrelated donors.
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PMID:Matched unrelated donor marrow transplantation in patients with advanced acute leukemia. 991 36

Transplants from related donors who share one HLA haplotype and are variably matched with the recipient for HLA-A, B, or DRB1 loci on the unshared haplotype are associated with increased risks of graft failure and graft-versus-host disease (GVHD) that correlate with the degree of HLA mismatch. Survival, however, is not necessarily inferior if recipient incompatibility is limited to one HLA locus. Available methods for post-transplant immunosuppression have not allowed similar success with transplants incompatible for two or three HLA loci. GVHD incidence and severity can be decreased by depletion of donor T cells from the marrow inoculum. However, the potential benefit is offset by increased graft failure and leukemia relapse with no improvement in survival. Since fewer than 30% of the patients in North America or Europe have an HLA-matched sibling and less than 5% have a one HLA-locus mismatched relative, most candidates for an allogeneic marrow transplant are in need of an unrelated donor. As of October 1993, the National Marrow Donor Program (NMDP) has accrued more than 1 million volunteers typed for HLA-A and B, including 200,000 typed for HLA-DR, and has provided donors for more than 2000 transplants. The probability of finding an HLA-A, B, DR match at the initial search has increased from 10-15% in 1987, to 50-55% in 1992. An additional 12% of patients will find a match when available HLA-A and B matched donors are typed for DR, and 20% of patients have a one HLA-locus incompatible unrelated donor. Through an international network of regional registries a search for an unrelated donor can now be conducted among 1.7 million volunteers worldwide. Unrelated donor transplants have allowed long-term disease-free survival of patients with a variety of hematological disorders. When compared to HLA-matched sibling transplants, unrelated donor transplants are associated with an increase in the incidence of graft failure and GVHD. Such an increase may be due to undetected HLA disparities or to non-HLA-linked histocompatibility genes. At our center patients with CML in chronic phase, the most common indication for unrelated donor transplantation, have a 50-55% probability of survival 2-6 years after an unrelated donor transplant, whereas patients with aplastic or refractory anemia have a 25-35% probability of survival.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of HLA incompatibility in marrow transplantation from unrelated and HLA-mismatched related donors. 1015 43

To improve the clinical outcome of allogeneic hematopoietic stem cell transplantation from an unrelated donor, the identification of human leukocyte antigen (HLA) alleles responsible for immunologic events such as graft-versus-host disease (GVHD), engraftment failure, and graft-versus-leukemia effect is essential. Genomic typing of HLA-A, -B, -C, -DRB1, and -DQB1 was retrospectively performed in 1298 donor-patient pairs in cases where marrow was donated from serologically HLA-A, -B, and -DR compatible donors. Single disparities of the HLA-A, -B, -C, or -DRB1 allele were independent risk factors for acute GVHD, and the synergistic effect of the HLA-C allele mismatch with other HLA allele mismatches on acute GVHD was remarkable. HLA-A and/or HLA-B allele mismatch was found to be a significant factor for the occurrence of chronic GVHD. HLA class I (A, B, and/or C) allele mismatch caused a significantly higher incidence of engraftment failure than HLA match. Significant association of HLA-C allele mismatch with leukemia relapse was not observed. As the result of these events, HLA-A and/or HLA-B allele mismatch reduced overall survival remarkably in both standard-risk and high-risk leukemia cases, whereas the HLA-C mismatch or HLA-class II (DRB1 and/or DQB1) mismatch did not. Furthermore, multiple mismatch of the HLA locus was found to reduce survival in leukemia cases. Thus, the role of the HLA class I allele in unrelated bone marrow transplantation was elucidated. Notably, HLA-C alleles had a different mode from HLA-A or -B alleles for acute GVHD and survival.
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PMID:The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors. 1201 Aug 26

Unrelated donor (URD) bone marrow transplantation (BMT) in adults can be associated with high non-relapse mortality (NRM). Therefore, factors determining survival in 136 human leucocyte antigen (HLA)-A, B, DRB1-matched adult BMT recipients were reviewed. Fifty-four per cent of patients had chronic myelogenous leukaemia (CML) and 36% had acute leukaemia or myelodysplasia. Graft-versus-host disease (GvHD) prophylaxis was either cyclosporin A (CSA)/methotrexate (64%) or T-cell depletion and CSA/corticosteroids (34%). The probability of donor engraftment by d 45 was 97% (95% CI: 94-100). Incidence of grades III-IV acute GvHD was 18% (95% CI: 12-24) at 100 d, and chronic GvHD was 42% (95% CI: 32-52) at 2 years. At 2 years, 14% (95% CI: 8-20) had relapsed. Multiple regression analysis showed that adverse risk factors for survival were non-CML diagnosis, age > 35 years, diagnosis to transplant time of > 18 months [chronic-phase CML (CML-CP) only]; and grades III-IV acute GvHD. Patients <or= 35 years with early CML-CP had a 2 year survival of 77% (95% CI: 54-100), which compared with a survival in advanced CML patients <or=35 years of 67% (95% CI: 37-97) and 37% (95% CI: 20-54) in non-CML patients. Two year survival for patients > 35 years with early CML-CP was 55% (95% CI: 33-77), 40% (95% CI: 19-61) in advanced CML and 14% (95% CI:1-27) in non-CML. Future efforts should focus on improving the outcome for older BMT recipients, especially those with diagnoses other than CML.
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PMID:Determinants of survival after human leucocyte antigen-matched unrelated donor bone marrow transplantation in adults. 1210 Jan 32

An 8-month-old girl had acute myelogenous leukemia (EAB M2) that relapsed 5 months after diagnosis during intensive consolidation chemotherapy. She underwent bone marrow transplantation (BMT) from an HLA-A, -B, -C and -DR phenotypically matched, but one locus DRB1 genotypically mismatched unrelated donor, but rejection occurred.Subsequently, she received reduced-intensity transplant (fludarabine/cytosine arabinoside/cyclophosphamide) from one locus HLA-A-mismatched, but DRB1 genotypically matched unrelated cord blood stem cells and remission was induced by acute GVHD (grade II) that progressed to chronic GVHD with involvement of the skin, liver, and gastrointestinal tract. In this case, it seems that remission was induced by an adequate graft-versus-leukemia effect and mild chronic graft-versus-disease due to the HLA-A difference more than DRB1 matched between the patient and the cord blood stem cells.
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PMID:Successful reduced-intensity stem cell transplant from one-locus HLA-mismatched unrelated cord blood after rejection of unrelated bone marrow in an infant with myelogenous leukemia. 1218 99

Aims of this study were to verify whether reduction in transplant-related mortality (TRM) of children with acute lymphoblastic leukemia (ALL) in second complete remission (CR) given allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated volunteers has occurred over time and to investigate the role of other variables on the probabilities of relapse, TRM and event-free survival (EFS). We compared results obtained in 26 children given HSCT before January 1998 with those of 37 patients transplanted beyond that date. In all donor-recipient pairs, histocompatibility was determined by serology for HLA-A and -B antigens and by high-resolution DNA typing for DRB1 antigen. High-resolution molecular typing of HLA class I antigens was employed in 20 of the 37 children transplanted more recently. Probability of both acute and chronic GVHD was comparable in the two groups of patients. In multivariate analysis, children transplanted before January 1998, those with T-lineage ALL and those experiencing grade II-IV acute GVHD had a higher relative risk of TRM at 6 months after transplantation. Relapse rate was unfavorably affected by a time interval between diagnosis and relapse <30 months. The 2-year probability of EFS for children transplanted before and after 1 January 1998 was 27% (10-44) and 58% (42-75), respectively (P = 0.02), this difference remaining significant in multivariate analysis. EFS of unrelated donor HSCT in children with ALL in second CR has improved in the last few years, mainly due to a decreased TRM. This information is of value for counseling of patients with relapsed ALL.
Leukemia 2002 Nov
PMID:Improvement over time in outcome for children with acute lymphoblastic leukemia in second remission given hematopoietic stem cell transplantation from unrelated donors. 1239 66

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


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