Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Marrow transplantation is now preferred treatment, if the patient has a suitable identical twin or HLA-identical sibling donor, for aplastic anemia, acute myelogenous or lymphoblastic leukemia that has relapsed once, and is commonly employed for the treatment of acute myelogenous leukemia in the first remission, for chronic myelogenous leukemia in the chronic phase, and for certain congenital disorders. The results of transplantation from HLA-nonidentical donors appears promising, but the follow-up is short at this time. The low incidence of relapse or nonrelapse mortality beyond the first 3-5 years with follow-up now to almost 20 years from transplantation signifies that surviving patients are cured of their disease and are likely to have survival similar to the normal population thereafter. They will probably lead normal productive lives in society. These data support applying criteria for insurance candidacy of patients who have survived more than 5 years from marrow transplantation which are similar to criteria applied to other normal individuals.
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PMID:Long-term results of bone marrow transplantation for leukemia or aplastic anemia. 235 90

In a multicenter study (seven University clinics) in the German Federal Republic bone marrow transplants from HLA-identical donors were performed in 177 patients (113 men, 64 women, mean age 32 [1.3-50] years) with Philadelphia chromosome-positive chronic myeloid leukaemia from 1982 to 1988. The survival rate among the 144 patients in whom the transplant had been carried out during the first chronic phase amounted to 58.4 +/- 11.4% after a median observation period of 3 years; survival rate among the 24 patients who underwent transplantation during the acceleration phase was 29.2 +/- 20.4%. All nine patients who received bone marrow transplants in the second chronic phase or during a blast crisis died during the period of observation (after median periods of 4 and 2 months, respectively). The most frequent causes of death among the group as a whole (82/177 patients) were interstitial pneumonia, acute and chronic graft versus host reactions (GVHD), recurrences and the toxic effects of previous treatment. The risk factors which significantly diminished survival rate were moderate to severe acute GVHD, chronic GVHD and age over 30 years.
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PMID:[Allogeneic bone marrow transplantation in chronic myeloid leukemia. The results of HLA-identical transplants in the Federal Republic of Germany]. 235 28

We present, to our knowledge, the first extensively studied case of lymphoid L2 blast crisis of chronic myelogenous leukemia with a hand mirror cell (HMC) variant. Special stains revealed the leukemic cells to be terminal deoxynucleotidyl transferase positive by immunofluorescence and cytochemically positive for alpha-naphthyl acetate esterase and acid phosphatase (diffuse granular). Immunophenotyping identified the major leukemic cell population as B-cells that expressed CD10+, CD19+, and HLA-DR+. It was not possible to separate the HMC and the non-HMC leukemic population by gating various cell populations, dual staining, cytochemistry, or by terminal deoxynucleotidyl transferase. Gene rearrangements were observed in both Ig heavy-chain alleles and one T-cell antigen receptor gamma-subunit allele. The rearrangements occupied all of the cells, indicating that the HMC and non-HMC were of a common clonal origin. The patient had a mosaic karyotype, with 90% of the cells having t(9;22), t(8;14), and t(9;15) translocations, an additional chromosome 8, and deleted chromosomes 9 and 15. Antibodies to simian sarcoma-associated virus and baboon endogenous virus were isolated in the patient's peripheral blood plasma.
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PMID:Lymphoblastic crisis of chronic myelogenous leukemia. Hand mirror variant. 236 26

A 32-year-old male patient with chronic myelocytic leukemia in accelerated phase received a bone marrow allograft from his 42-year-old HLA/MLC-identical sister. He recovered from acute graft-versus-host disease (GVHD) grade III-IV of skin, liver and gut, but chronic GVHD of progressive onset developed. On day 556 post-graft severe thrombocytopenia was resistant to prednisolone, cyclophosphamide and high dose immunoglobulin. Splenectomy was followed by a normalization of platelet counts. The subsequent clinical course was characterized by progressive muscular atrophy and weight loss. Dysphagia, dysarthria, cachexia and ultimately recurrent pneumonic episodes ensued. The cachectic patient developed a highly abnormal breathing pattern with hypoventilation and intermittent apnea requiring mechanical ventilation. Auditory evoked potentials revealed a considerable dysfunction of the brainstem. The patient died on day 1120 post-graft from pneumonia, aggravated by thoracic muscular insufficiency. Postmortem examination revealed diffuse predominantly lymphoid perivascular infiltration in meninges and CNS tissue; proliferation of activated microglial cells expressing the HLA-DR antigen was prominent in the brainstem. These histologic changes are similar to those observed in the CNS in experimental GVHD. We suggest that this case represents the first documentation of CNS involvement in chronic GVHD.
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PMID:Fatal encephalitis in a patient with chronic graft-versus-host disease. 239 Jun 33

We studied 2254 persons receiving HLA-identical sibling bone marrow transplants for acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) in first remission, or chronic myelogenous leukemia (CML) in first chronic phase to determine whether graft-versus-leukemia (GvL) reactions are important in preventing leukemia recurrence after bone marrow transplantation. Four groups were investigated; recipients of non-T-cell depleted allografts without graft-versus-host disease (GvHD), recipients of non-T-cell depleted allografts with GvHD, recipients of T-cell depleted allografts, and recipients of genetically identical twin transplants compared with recipients of non-T-cell depleted allografts without GvHD, Decreased relapse was observed in recipients of non-T-cell depleted allografts with acute (relative risk 0.68, P = 0.03), chronic (relative risk, 0.43, P = 0.01), and both acute and chronic GvHD (relative risk 0.33, P = 0.0001). These data support an anti-leukemia effect of GvHD. AML patients receiving identical twin transplants had an increased probability of relapse (relative risk 2.58, P = 0.008) compared to allograft recipients without GvHD supporting an anti-leukemia effect of allografts independent of GvHD. CML patients receiving T-cell depleted transplants without GvHD had a higher probability of relapse (relative risk 6.91, P = 0.0001) than recipients of non-T-cell depleted allografts without GvHD. These data support an antileukemia effect independent of GvHD altered by T-cell depletion. These results indicate that much of the anti-leukemia effect of bone marrow transplants is related to immune factors rather than high-dose chemotherapy and/or radiation.
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PMID:Graft-versus-leukemia in bone marrow transplantation. The Advisory Committee of the International Bone Marrow Transplant Registry. 239 Jun 46

The recognition of minor alloantigens by cytotoxic T lymphocytes (CTL) serves as a model for the recognition of tumor and viral antigens. Progress in this area has been limited, however, since CTL recognize minor alloantigens only in association with self-class I antigens. Thus, experiments designed to study minor alloantigens are limited to target cells that share HLA determinants with the CTL. We raised CTL lines that recognized human minor alloantigens. In order to circumvent the problem that only target cells which expressed the appropriate restriction determinants could be tested for minor antigens. Sendai virus mediated fusion was used to integrate appropriate HLA antigens into cells that did not express them naturally. The target cells were then tested in CML for their expression of minor antigens. The results of experiments demonstrated that, following class I implantation, the detection of minor antigens on certain restriction determinant negative cells was possible. Furthermore, the restriction determinant was able to associate with the minor antigen in a manner appropriate for recognition by the T-cell receptor.
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PMID:The detection of human minor alloantigens following restriction determinant implantation. 243 60

The indications and results of allogeneic bone marrow transplantation are well known by the analyses of European and International registries. In acute nonlymphoblastic leukemia in first CR, the disease-free survival (DFS) is 45% with a risk of relapse (RR) of 15%, in ALL in first CR the DFS is 60% with a RR of 15%, in ALL in second CR the DFS is 40% with a RR of 30%, and in CML in the chronic phase the DFS is 60%, with a RR of 20%. These results must be adjusted with other risk factors such as age, sex mismatch, disease status, CMV serology, and GvHD. The use of donors who differ from genotypically matched related donors is currently under investigation. Mismatched related transplants give disappointing results except in the case of 1 HLA mismatch. Unrelated HLA-matched donor panels have recently been established in various countries with 200 transplants performed with a DFS of approximately 40%. Researchers are currently trying to reduce the RR by intensifying the conditioning regimen or using the graft-versus-leukemia effect of allogeneic T cells, reducing GvHD by the use of monoclonal antibodies, and improving the engraftment by the use of growth factors. The recent use of cryopreserved cord blood cells for transplantation may improve the results of partially mismatched transplants in children.
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PMID:Recent trends in allogeneic bone marrow transplantation. 248 57

Utilization of bone marrow transplantation as a therapeutic modality continues to increase. More and more institutions are initiating bone marrow transplant programs. During the 33-year period between 1955 and 1987, more than 20,000 patients received allogeneic bone marrow transplants; more than 50% of these were performed in the 3 years, 1985-1987. Transplantation is an effective therapy for acute leukemia; in some instances it is the preferred treatment. In chronic myelogenous leukemia, severe aplastic anemia, and some genetic and immune deficiency diseases, bone marrow transplantation provides the only possibility for cure. Bone marrow transplantation is associated with serious problems such as graft-versus-host disease (GvHD), graft failure, interstitial pneumonitis and, until recently, the requirement for an HLA-identical sibling donor. In the past few years, an increasing number of transplants have been performed using HLA-partially matched related or unrelated donors with some success, the level of which is yet to be determined. The development of acute GvHD (8) and interstitial pneumonitis (9, 10) can often be predicted by risk factor assessment. Special precautions can then be taken for patients at high risk of these complications. In this report, current data from the International Bone Marrow Transplant Registry were summarized and several risk factors affecting outcome were identified.
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PMID:Current status of bone marrow transplantation. 248 30

ABO-mismatched bone marrow transplants have resulted in delayed red cell production in patients who have persistently elevated anti-ABO isohemagglutinin titers. We present a patient with chronic myelogenous leukemia who received an HLA-matched, ABO-incompatible bone marrow transplant from his sister. Post-transplant, he developed pure red cell aplasia with exuberant production of donor red cell precursors by in vitro BFU-E assay. Restriction fragment length polymorphism (RFLP) analysis of bone marrow, peripheral blood and BFU-E colonies demonstrated only donor type DNA post-transplant. However, the patient had persistently elevated isohemagglutinin titer and Ph1 chromosome-positive metaphases on chromosome analysis, indicating the presence of persistent host lymphocytes. With onset of acute graft vs. host disease (GVHD), the isohemagglutinin titer dropped, Ph1 chromosome-positive metaphases disappeared, and full hematopoietic recovery ensued. Longitudinal analysis of RFLP's, isohemagglutinin titers and chromosomes may be helpful in understanding the immunological interplay following allogeneic bone marrow transplantation.
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PMID:Red cell aplasia due to host type isohemagglutinins with exuberant red cell progenitor production of donor type in an ABO-mismatched allogeneic bone marrow transplant recipient. 250 37

A 26-year-old man, who presented with bilateral fundal haemorrhages, was found to have chronic myeloid leukaemia (CML). The Ph chromosome was not present but a clone with t(1;9) (p32;q34) was detected. On referral for bone marrow transplant (BMT) he was found to be in accelerated phase with clonal evolution in three cell lines inv(3)(q21q26); inv(3)(q),i(17q); inv(3q)+8. Molecular investigation revealed a breakpoint on chromosome 22 within the breakpoint cluster region (bcr) similar to that found in Ph+ cases. After BMT, from an HLA-identical sister, successful engraftment (46,XX) was accompanied by evidence of a residual host cell population with further evolution (del(7)(q22)) and persistence of the bcr+ clone. Acute myeloid leukaemia, detected 5 months later, was associated with predominance of the clone 46XY,t(1;9),inv(3q),del(7)(q22) which failed to respond to treatment and the patient died 6.5 months after BMT. This case indicates that BMT, after the acquisition of additional chromosomal change in accelerated phase, may fail owing to persistence of the leukaemic clone. In addition the BMT conditioning regimen may produce further abnormalities which confer drug resistance on the persisting clone, which can emerge as an intractable myeloid blast crisis.
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PMID:Clonal evolution in Ph-negative, bcr-positive chronic myeloid leukaemia before and after bone marrow transplantation. 251 23


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