Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Imatinib or STI 571 is a phenylaminopyrimidine derivative and a member of a new class of drugs known as signal transduction inhibitors. These compounds specifically inhibit the proliferation of v-abl- and bcr-abl-expressing cells and have recently been approved as treatment for chronic myeloid leukaemia (CML). Results have been promising, and imatinib may well be the best single agent for the treatment of CML in the near future. Here we report an erosive oral lichenoid eruption confined to the buccal mucosa and dorsum of the tongue which appeared 12 weeks after commencement of imatinib in a 72-year-old woman with CML. The histology was consistent with a lichenoid drug eruption. The lesions resolved upon withdrawal of the drug. To our knowledge, this is the first reported lichenoid reaction to imatinib, and in the setting of CML it must be differentiated from idiopathic lichen planus, paraneoplastic pemphigus and graft-versus-host disease.
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PMID:Oral lichenoid reaction to imatinib (STI 571, Gleevec). 1221 35

We describe a patient with bcr/abl-positive acute mixed lineage leukemia who successfully underwent transplantation in primary induction failure, using unmanipulated bone marrow from a human leukocyte antigen (HLA)-haploidentical cousin. The tumor burden was successfully reduced by the administration of imatinib mesylate (STI571) before transplantation. As graft-versus-host disease (GVHD) prophylaxis, a combination of tacrolimus and a short course of methotrexate, methylprednisolone, and mycophenolate mofetil was used. Hematopoietic reconstitution was rapid, and acute GVHD was limited to the skin (grade I). The patient is still in complete remission past day +400. This successful case suggests that HLA-haploidentical transplantation using unmanipulated marrow from a distantly related relative can be considered for patients in urgent situations who do not have HLA-identical donors.
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PMID:Successful treatment of bcr/abl-positive acute mixed lineage leukemia by unmanipulated bone marrow transplantation from an HLA-haploidentical (3-antigen-mismatched) cousin. 1279 97

To explore the hematopoietic reconstitution and transplantation-related complications of two units of unrelated umbilical cord blood combined transplantation for the treatment of adult hematologic malignancies, one adult patient with chronic myelogenous leukemia received two units of unrelated umbilical cord blood combined transplantation. The conditioning regimen was busulfan and cyclophosphamide (Bu-Cy). GVHD prophylaxis regimen consisted of mycophenolate mofetil (MMF), cyclosporine A (CsA) and methotrexate (MTX). The patient received total nucleated cells 4.63 x 10(7)/kg with CD34+ cells 8.34 x 10(5)/kg. Engraftment was documented by the analysis of short tandem repeat with polymerase chain reaction (STR-PCR). The results showed that the STR-PCR analysis for peripheral blood at day 31, 46 and 71 after transplantation suggested that one of two units of cord blood were completely engrafted. The ANC > 0.5 x 10(9)/L in the patient occurred at day 23, blood platelet counts > 20 x 10(9)/L at day 33 and > 50 x 10(9)/L at day 47. The Philadelphia chromosome and bcr/abl fusion gene of the patient also turned to negative after engraftment. Acute GVHD grade II occurred at day 13 and cured after treatment. It is concluded that umbilical cord blood can be used in adult hematopoietic stem cell transplantation. Two or more units umbilical cord blood combined transplantation might be the way to solve the problem of the low counts of nucleated cells when be used for adult.
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PMID:[Treatment of one case of adult chronic myelogenous leukemia by two units of unrelated umbilical cord blood transplantation]. 1457 47

Immunocompetent alloreactive donor lymphocytes directed against minor histocompatibility antigens are supposed to be responsible for graft-versus-host disease (GvHD) and graft-versus-leukemia (GvL) activity after allogeneic stem cell transplantation. The authors describe the detection of HA-1-specific T cells by peptide-loaded dimers and flow cytometry in the peripheral blood of a patient in complete remission but without GvHD after donor lymphocyte infusion for chemotherapy-resistant Philadelphia chromosome-positive acute lymphoblastic leukemia. The HA-1-specific T cells were sorted and an alloreactive, polyclonal T-cell line with specific lytic activity against HA-1-positive target cells, including leukemic cells, was established. Although P190 bcr/abl peptide-specific CD8positive T cells were detected in the peripheral blood at the same time, these T cells could not be expanded. Furthermore, no P190 bcr/abl peptide-specific T-cell response could be induced in vitro, even when peptide-loaded dendritic cells were used as stimulator cells. The authors conclude that in the absence of GvHD, HA-1-specific rather than P190 bcr/abl-specific T cells are responsible for ongoing GvL activity.
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PMID:Hematopoietic lineage-restricted minor histocompatibility antigen HA-1 in graft-versus-leukemia activity after donor lymphocyte infusion. 1477 87

Evaluation of minimal residual disease (MRD) provides prognostic information on various hematological malignancies. We describe here the prognostic efficacy of real-time quantitative polymerase chain reaction (RQ-PCR)-based analysis of major bcr/abl mRNA in cases of Philadelphia chromosome-positive leukemia (Ph-leukemia). Twenty-one patients with Ph-leukemia were enrolled as subjects to determine the usefulness of RQ-PCR-based measurement of bcr-abl/abl ratios. Imatinib mesylate (imatinib) was administered to seven of the 21 patients before allogeneic stem cell transplantation (SCT). Hematological relapse or failure of treatment with SCT was observed in 2 of those patients who showed bcr-abl/abl ratios of more than 0.002%, and 5 of the 7 patients showed both RQ-PCR and RT-PCR negativity immediately after SCT. All of the 5 patients who did not receive imatinib before allogeneic SCT showed RQ-PCR negativity immediately after SCT, but the results of RT-PCR were positive in 3 patients at the same time points, and those became negative after donor lymphocyte infusion or the appearance of graft-versus-host disease. Administration of imatinib before SCT was thought to induce an early remission. On the other hand, 8 patients who received imatinib without SCT showed a remarkable decrease in bcr-abl/abl ratios. The ratio gradually rose in one patient with Ph+ALL, enabling prediction of the hematological relapse preceding detection by fluorescence in situ hybridization (FISH) analysis. Standardization of RQ-PCR analysis of bcr-abl mRNA will help to predict early hematological relapse in patients with MRD. In conclusion, it is thought that measurement of RQ-PCR-based major bcr/abl mRNA in patients who were given imatinib and were treated with SCT is useful for the evaluation of MRD and in deciding additional treatment.
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PMID:[Prognostic efficacy for measurement of real-time quantitative PCR-based major bcr/abl mRNA in patients with Philadelphia chromosome-positive leukemia]. 1567 15

The purpose of this study was to investigate the efficacy of non-myeloablative allogeneic stem cell transplantation (allo-NST) and its related technologies in hematological malignancies. 26 patients with hematological malignancies (acute leukemia 10, chronic myeloid leukemia 14, multiple myeloma 2) received allo-NST following conditioning regimens with fludarabine/cyclophosphamide/ATG in 14 cases or busulfan or melphalan/cyclophosphamide/ATG in 12 cases prior to infusion of 2 or 3 collections of G-CSF (600 microg/d) or G-CSF (300 microg/d) plus GM-CSF (300 microg/d) mobilized blood stem cell on the fifth day. A combination of cyclosporine A (CsA) and methotrexate (MTX) was administered for GVHD prophylaxis. Patients were eligible for donor lymphocyte infusion (DLI) (or donor stem cell infusion (DSI)) given in graded increments according to the chimeric formation and clinical feature. Generally, the dose of the first infusion was 1 x 10(7)/kg in 4th week post-transplantation. The engraftment analyses included the detection of microsatellite short tandem repeats (STRs), bcr/abl fusion gene, Philadelphia chromosome, HLA-locus analysis, sex chromosome and ABO blood type or blood subtype. The results showed that out of 26 patients, 22 (84.62%) were engrafted, 18/22 were full donor chimerism (FDC) up to now. Acute GVHD occurred in 3/26 (11.54%), while chronic GVHD was diagnosed in 6 out of 26 (23.07%) patients. The incidence and degree of infection and hemorrhage were low and slight. It is concluded that NST is a safe and effective therapy for hematological malignancies, whereas related technologies such as adaptation selected, conditioning regimen and transplantation immunotherapy should be studied further.
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PMID:Nonmyeloablative allogeneic hematopoietic stem cell transplantation in 26 cases of hematological malignancies. 1692 19

The purpose of study was to evaluate the effect of stopping use of cyclosporine A (CsA) in reversion of donor chimeras of chronic myeloid leukemia (CML) patients relapsed after transplantation. Two CML patients were transplanted with allogeneic peripheral blood stem cells, and relapsed after transplantation, their bcr/abl gene and/or ph1 chromosome showed positive, donor chimeras decreased. For these two CML patients relapsed after transplantation, the use of CsA was stopped immediately, and the patient's body temperature, skin rash, blood picture, liver function and chimeras were planed to observe carefully. The results indicated that acute graft versus host disease (aGVHD) appeared in both patients. A hundred percent (100%) of donor chimeras were then found with bcr/abl gene and/or ph1 chromosome turning to negative in both patients. In conclusion, to stop using of CsA might be effective in the treatment of some CML patients relapsed after transplantation by reversing of donor chimeras and inducing graft-versus-leukemia (GVL) effect accompanied by GVHD.
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PMID:[Reversing of donor chimeras by stopping use of CsA in 2 CML patients relapsed after transplantation]. 1760 84

CBSCT with low incidence of GVHD is associated with higher rates of delayed engraftment and relapse compared with other stem cells transplants. The immune-mediated effect of NK and cytotoxic T cells against residual tumor cells was shown to prevent relapse and reinduce remission after bone marrow transplantation. We expanded CD34+ and T and NK cells ex vivo in cord blood with different cytokines combination and transplanted into leukemic BALB/C nude mouse. The results showed significant expansion of MNCs and CD34+ cells. The CD3+ T cells increased in the groups containing cytokines cocktail, especially in the group with IL-7 or IL-2. CD56+ NK cells number increased significantly only in a medium containing IL-2. Of the 20 engrafted BALB/C nude mice, 14 survived after 6 weeks transplantation, and the numbers in each group were from 3 to 4. Human CD3+ cells in the bone marrow of the survived mice were analyzed by flow cytometry and showed existing evidences. RT-PCR was used to detect leukemic fusion bcr/abl gene; all mice that experienced expanded cord blood transplantation could not be found to have expression of fusion bcr/abl gene. These suggest that T, NK cells as well as CD34+ cells could be expanded from CB MNCs in the same medium with the combination of cytokines. The expanded CB MNCs could reconstitute hematopoiesis and eliminate minimal residue leukemia disease in transplanted mice.
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PMID:Ex vivo expansion of CD34+ and T and NK cells from umbilical cord blood for leukemic BALB/C nude mouse transplantation. 1825 86

A 23-year-old man with Philadelphia-chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) underwent myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) from his HLA-identical brother in first hematological remission following induction chemotherapy which included imatinib. He had no acute graft-versus-host disease (GVHD), and 4.5 months after HSCT, he had a molecular relapse (180,000 copies/mug RNA of minor bcr/abl transcripts (m-bcr/abl) without mutation in 22 sites including the p-loop region). Following discontinuation of cyclosporine A, imatinib (600 mg daily) was restarted and 4 days later donor lymphocyte infusion (DLI) (5 x 10(7)/kg of CD3(+) cells) was given. In 2 weeks, the marrow m-bcr/abl became undetectable. He received two further DLIs and imatinib was continued at a reduced dose of 400 mg a day. At the time of this report, he remains in complete hematological remission more than 33 months after allo-HSCT and persists in the second molecular remission for longer than 24 months. During this clinical course, he became positive for anti-nuclear antibody after second DLI, without any other manifestations of GVHD. The standard treatment for Ph(+) ALL relapsing after allo-HSCT still remains to be established. Imatinib in combination with DLI for early molecular relapse may be a promising option.
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PMID:Case of a patient with Philadelphia-chromosome-positive acute lymphoblastic leukemia relapsed after myeloablative allogeneic hematopoietic stem cell transplantation treated successfully with imatinib and sequential donor lymphocyte infusions. 1869 83

This study was aimed to investigate the chimerism and fusion gene expression in patients with CML after allo-HSCT, to analyse engraftment and minimal residual disease by using STR-PCR combined with RT-PCR qualitative and quantitative assays, and to evaluate their clinical value for predicting disease relapse. 4 relapsed patients with CML after allo-HSCT were dynamically investigated. Qualitative analysis of donor chimerism was performed by multiplex PCR amplification of STR markers and capillary electrophoresis with fluorescence detection, qualitative detection of bcr/abl transcripts was performed by RT-PCR. The results showed that the 100% donor chimerism appeared in 4 patients on day 28 after transplantation and bcr/abl expression was negative, but the 4 patients were in status of unstable mixed chimerism (DC: 0% - 80.4%) at the different time points during the following up with bcr/abl gene positive. 2 patients of them were continuously mixed chimerism after relapse of CML, the other 2 changed from MC to CC by intervention of clinical treatment. Decreasing values of donor chimerism were detected prior to the occurrence of graft rejection and CML relapse, and bcr/abl gene expression was positive. It is concluded that the results of STR-PCR in the range of its sensitivity fully correspond with bcr/abl tests in patients. The combination of STR-PCR with RT-PCR will provide a highly sensitive and valuable tool for evaluating engraftment, graft rejection, and relapse and predicting GVHD. Furthermore, it can provide a basis for early intervention of clinical treatment, and can identify these high risk patients with molecular or cytogenetic relapse after allo-HSCT.
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PMID:[Dynamic detection of chimerism and fusion gene in chronic myeloid leukemia patients relapsed after allogeneic hematopoietic stem cell transplantation]. 1871 71


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