RESUMO
PURPOSE: HLA (human leukocyte antigen)-class I genes are highly polymorphic, play many roles in organ and bone marrow transplantation. HLA-B is the most polymorphic class I locus with 414 alleles. HLA-class I typing, which is based on serologic method, has been used until recently. The development of molecular biological techniques make it possible to define the genotypes of HLA genes. METHODS: Analyses of HLA-B genotyping on 1,000 UCB (Umbilical Cord Blood) samples which were considered to be HLA-B homozygote or blank were performed by ARMS-PCR (Amplification Refractory Mutation System-PCR) method and direct sequencing. RESULTS: We could identify HLA-B*5001 which was known to be absent in Koreans. CONCLUSION: It is strongly suggested that HLA-B homozygote should be confirmed to the DNA level especially in cases of donor selection for the unrelated bone marrow transplantation.
Assuntos
Alelos , Transplante de Medula Óssea , DNA , Seleção do Doador , Sangue Fetal , Genótipo , Antígenos HLA-B , Homozigoto , LeucócitosRESUMO
No abstract available.
Assuntos
Medula Óssea , Quimerismo , Neoplasias Hematológicas , RecidivaRESUMO
BACKGROUND: The success of allogeneic bone marrow transplantation(allo-BMT) is affected by underlying disease relapse. Although mixed chimerism(MC) is not necessarily a poor prognostic factor, several groups have suggested that MC is associated with an increased risk of disease relapse. There is evidence that patients with MC benefit from additional immunotherapy if the treatment is started in minimal residual disease status(mixed chimerism status), not in frank hematological relapse. The purposes of this study are to evaluate 1) the risk for relapse or graft rejection in correlation to persistent MC status after allo-BMT, and 2) the possibility of preventing relapse by immune modulation treatments (withdrawal or rapid taper-off of post-transplant immuno-suppression, additional interferon treatment, or the administration of donor lymphocytes) in hematologic malignancies. PATIENTS AND METHODS: Of 337 allogeneic donor-recipient pairs between March 1996 and August 1998, 12 patients who showed persistent or progressive MC and who received immune modulation treatments were evaluated. Twelve patients, median age 31 years(range 9 to 39 years), received an allo-BMT for: acute myelogenous leukemia(AML, n = 5), chronic myelogenous leukemia(CML, n = 4), acute lymphocytic leukemia(ALL, n = 3). Serial polymerase chain reaction(PCR) analysis of YNZ 22-, 33.6-minisatellites or Y chromosome-specific PCR analysis at short term intervals(pre- and post-transplant 1, 3, 6, 9, ... months) was performed. Once MC was detected, immune modulation treatments on the basis of increasing MC in an early phase of recurrence of underlying disease were started. RESULTS: Nine of 12 patients converted to complete chimerism(CC) (AML 5/5, CML 3/4, ALL 1/3). Four of 9 CC patients developed graft-versus-host disease(GVHD) grade < or = 2 during immune modulation. All were treated successfully with steroids. Three patients who were not converted to CC showed relapse of underlying diseases or graft failure. CONCLUSION: The results demonstrate that, in patients with hematologic malignancies after allo-BMT, persistent MC is associated with relapse of underlying diseases or graft failure. Furthermore, when patients receive early immune modulation treatment, MC can be changed to complete donor pattern chimerism and ultimately prevent relapse.
Assuntos
Adulto , Criança , Feminino , Humanos , Masculino , Adolescente , Transplante de Medula Óssea/imunologia , Quimera , Doença Enxerto-Hospedeiro/etiologia , Teste de Histocompatibilidade , Leucemia/terapia , Leucemia/mortalidade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Recidiva , Transplante HomólogoRESUMO
PURPOSE: Multidrug resistance mediated by several drug resistant genes impedes the successful outcome of anti-cancer chemotherapy. In this study, we investigated the expressions of drug resistant genes encoding multidrug resistance (MDR1), multidrug resistance-associated protein (MRP), topoisomerase I (Topo I), topoisomerase II g (Topo II a) in narmal volunteers (n=12) in and patients with myeloid leukemia (n=34). Material and Method: We compared the levels of their transcripts in bone matrow mononuclear cells by semiquantitative RT-PCR. The amount of specific transcripts was represented as the optical density ratio of PCR product of target gene to that of B2- microglobulin (MG). Twenty patients of acute myelogenous leukemia (eight in remission state, twelve in refractory) and fourteen patients of chronic myelogenous leukemia (nine in chronic phase and five in blastic crisis) were examined. Twelve normal healthy persons were compared with leukemic patients. RESULTS: The expression levels of all resistant genes in normal volunteers were relatively high as those of AML patients. Regardless of the disease status including remission status of AML (complete remission versus refractory) and the phase of CML (chronic phase versus blastic phase), the expression levels of all resistant genes in patients with CML were significantly lower than in the patients with AML (p < 0.05). Of interest, the patients with refractary AML did not show any statistical difference in comparison with normal controls and even the patients with AML in complete remission. Among the four drug resistant genes, the optical density ratio of MDRl was significantly lower than that of any other genes (p<0.05). Using HL-60 cell line, we compared the changes of various resistant gene expressions before and after differentiation induced by dimethylsulfoxide. The expressions of resistant genes declined in paralle1 with granulocytic differentiation, suggesting that the induction of cell differentiation might make leukemic cells susceptible to chemotherapeutic agents. CONCLUSION: It is impossibble to explain the mechanism of drug resistance by comparing the level of drug resistant gene expression between nonnal subjects and patients with myeloid leukemias. Therefore, we suppose that longitudinal study of drug resistant gene expression is necessary to demonstrate the development of drug resistant during chemotherapy.