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

Conditioning regimens for transplantation are important in determining transplant outcome. This review focuses on transplantation in aplastic anemia and leukemia using marrow from HLA-identical siblings. Results of conditioning with newer regimens such as busulfan plus cyclophosphamide and etoposide plus total body irradiation are reviewed and compared to results achieved with cyclophosphamide and total body irradiation. The potential for improved results using recent innovations such as dose adjustment of busulfan, agents which may decrease transplant-related toxicity, and directed radiation are discussed.
 ...
PMID:Conditioning regimens for allogeneic bone marrow transplantation. 148 92

Bone marrow transplantation from an HLA-identical sibling is increasingly used as a curative therapy for patients with hemopoietic stem cell disorders including acute leukemia, chronic myelogenous leukemia and severe aplastic anemia. Between March 1983 and March 1991, we performed 86 cases of allogeneic bone marrow transplantation (BMT) for the patients with hemopoietic stem cell disorders: 25 acute myelogenous leukemia (AML); 15 acute lymphoblastic leukemia (ALL); 20 chronic myelogenous leukemia (CML); and 26 severe aplastic anemia (SAA). Ten out of 25 AML are in disease free survival (DFS). The causes of death were recurrence of leukemia (12), acute GVHD (3), sepsis (1) and veno-occlusive disease (1). Nine of 15 ALL are in unmaintained remission. Thirteen out of 20 CML are in DFS. Among 26 SAA, 21 are enjoying DFS, but 1 died of engraftment failure, 3 of graft rejection followed by cytomegalovirus (1) and aspergillus pneumonia (1). Comparing the survival between standard [less than or equal to CR1: 9/14 (64%)] and high risk [greater than or equal to CR1: 1/11 (9%)] AML, our data suggest that preparative regimen for high risk AML was not potent enough to eradicate the minimal residual disease in advanced AML. Although our cases are limited and the follow-up period is short, our result of ALL [overall: CCR (60%), standard risk (adult less than or equal to CR1, children less than or equal to CR2; 8/11 (73%) and high risk; 1/4 (25%)] and CML [overall: 65%, CP; 9/10 (90%), AP; 4/6 (67%), BP; 0/4 (0%)] are optimistic. It is of our interest that the incidence of death related with IP (1/33: 3%) and with AGVHD 94/33: 12%) were much less than that of other's observation but the explanation for this still remains to be clear.
 ...
PMID:Allogeneic bone marrow transplantation for the patients with hemopoietic stem cell disorders: CUMC experience. 151 32

Fanconi's anemia is an autosomal recessive disorder with a high incidence (greater than 90%) of aplastic anemia and a premalignant component with a greater than 10% risk of leukemia or solid tumors. The diagnosis of Fanconi's anemia depends on increased chromosomal breakage in lymphocytes following treatment with a DNA cross-linking agent; patients have been identified who are clinically well and whose physical appearance is normal. Although bone marrow or cord blood transplants can be curative, treatment for the aplastic anemia usually depends on androgens. Close to 20 patients with Fanconi's anemia have delivered normal babies, and the mothers' hematologic status was not significantly adversely affected by the pregnancy. A few patients have clonal cytogenetic abnormalities in their bone marrow that do not necessarily indicate leukemic transformation, but further follow-up is important. Studies of in vitro erythropoiesis indicate a correlation between the clinical hematologic status and the presence of erythroid progenitors in the blood or bone marrow. Certain hematopoietic growth factors do increase growth in vitro, suggesting that new types of therapy may become available. Not every patient has a poor prognosis. There are now many adults with Fanconi's anemia, some with families of their own.
 ...
PMID:Fanconi's anemia. Current concepts. 153 Jan 23

This study was undertaken to ascertain the frequency of compatible sibling donors for individuals requiring bone marrow transplantation (BMT) in Ireland. During the study period 1984-89, a total of 392 patients were HLA typed. Of these, 218 (55.6%) had a compatible sibling donor. Among the latter there were 4 degrees of compatibility: 168 (42.9%) were HLA-A,B,DR identical MLC unreactive: three (0.8%) were HLA-A,B,DR identical MLC reactive: 12 (3.0%) were HLA-A,B,DR identical (no MLC performed) and 35 (8.9%) were HLA-A, B identical (no DR or MLC performed). The leukaemias and aplastic anaemia comprised 82.9% of all requests. The majority of patients with acute myeloid leukaemia (64.4%), acute lymphoblastic leukaemia (51.2%), chronic myeloid leukaemia (73.9%) and aplastic anaemia (77.3%) had a potential sibling donor. Subsequently 144 of these patients had an allogeneic BMT, 79.9% of which were for patients with leukaemia (acute and chronic). This study found that there was a higher probability of finding a donor within the family than reported in most series. A clear relationship was demonstrated between family size and the likelihood of obtaining a HLA-identical sibling donor.
 ...
PMID:Probability of finding a compatible sibling donor for bone marrow transplantation in Ireland. 153 37

The presence of two distinct T-cell receptors (TCR) alpha/beta and gamma/delta dimers as well as of the activated T cells was analysed in peripheral blood mononuclear cells from seventeen recipients of allogeneic bone marrow transplants for leukemia and for severe aplastic anemia. Nine of seventeen recipients expressed an elevated percentage of T cells bearing TCR gamma/delta receptors in their peripheral blood. Seven out of nine cases having elevated gamma/delta positive cells showed chronic graft-versus-host (GVH) disease; one patient was treated with Cyclosporin A, and one patient was asymptomatic. In the twelve patients with GVH or other clinical symptoms, activated T cells (CD3+/HLA-DR+) were elevated indicating an autoreactive or alloreactive cell population. Our results confirmed earlier in vitro data showing that TCR-gamma/delta-bearing lymphocytes may be an activated T-cell population, and this T cell subset might be involved in mediating GVH disease, or in prolonging immunodeficiency after transplantation.
Leukemia 1992
PMID:TCR gamma/delta bearing lymphocytes in peripheral blood of allogenic bone marrow transplanted patients. 153 60

Nineteen patients with leukaemia, preleukaemia, and aplastic anaemia were treated by marrow transplantation from HLA-identical siblings. All were given postgrafting immunosuppression with a combination of methotrexate (days 1, 3, 6 and 11) and cyclosporin (days--1 to 180). In an attempt at reducing cyclosporin-associated toxicity, we explored whether the cyclosporin dose during the first 2 weeks could be decreased by 50% (from 3.0 to 1.5 mg/kg/d intravenously) without adversely affecting the incidence, onset, and severity of acute graft-versus-host disease (GVHD) and overall survival. Results from this pilot study were compared to those of a matched cohort of 38 patients given a standard dose of 3.0 mg cyclosporin/kg/d starting on day--1. The cumulative incidence of grade II and III acute GVHD in the 'low dose' cyclosporin group was 42% compared to 51% in the 'standard dose' group (P = 0.60). Three-year survival was 63% and 54% respectively (P = 0.59). Patients receiving the reduced cyclosporin dose during the first 14 d appeared to have less hepatotoxicity, and the methotrexate and cyclosporin doses administered were closer to the doses intended per protocol. We suggest that 'low dose' cyclosporin from day--1 to day 15 postgrafting might be as effective as 'standard dose' cyclosporin during that time period for the prevention of acute GVHD.
 ...
PMID:A pilot study of low-dose cyclosporin for graft-versus-host prophylaxis in marrow transplantation. 153 9

Thymus humoral factor-gamma 2 (THF gamma 2), an octapeptide important for T-lymphocyte regulation, was assessed for its effect on the in vitro growth of human hematopoietic progenitor cells. This was achieved using a recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF)-stimulated myeloid cell colony formation (granulocyte-macrophage colony-forming cells, GM-CFC) assay as well as a recombinant erythropoietin (rEpo)-stimulated erythroid burst formation (erythroid burst-forming units, BFU-E) assay. Cells were obtained from bone marrow (BM) and peripheral blood (PB) of normal healthy donors and from patients with suppressed bone marrows. The latter group included aplastic anemia, leukemia, and lymphoma patients and patients with solid tumors who responded to intensive chemotherapy with significant pancytopenia. THF gamma 2 significantly enhanced normal BM and PB GM-CFC and PB BFU-E by 2- to 2.5-fold. This effect was totally dependent on the presence of the respective growth factors, that is, rGM-CSF or rEpo, and was specifically reversed by an anti-THF gamma 2 antiserum. Furthermore, although THF gamma 2-induced enhancement of GM-CFC colony formation was not affected by lymphocyte or monocyte depletion, the augmenting effect of the peptide on BFU-E was completely abrogated in the absence of lymphocytes. THF gamma 2-induced augmented growth of progenitor cells derived from severely suppressed marrows was minimal. However, cells from moderately neutropenic patients with leukemia in remission or with lymphoma under chemotherapy responded to the peptide similarly to cells from normal donors. These results suggest a stimulatory role for THF gamma 2 on human myeloid and erythroid hematopoietic progenitor cells. They also suggest the lymphocyte dependence of BFU-E enhancement and lymphocyte independence of GM-CFC stimulation by THF gamma 2. In the former case the thymus-derived peptide may act through the induction of certain erythroid-enhancing lymphokines.
 ...
PMID:Thymic humoral factor-gamma 2, an immunoregulatory peptide, enhances human hematopoietic progenitor cell growth. 154 85

The linear growth of 26 children with progressive and advanced neuroblastoma treated with high-dose chemotherapy, total body irradiation, and bone marrow transplantation between 1978 and 1988 at the Children's Hospital of Philadelphia was compared with the growth of 33 children who had transplants for leukemia and of 12 who had transplants for aplastic anemia. The mean growth velocity, expressed as a standard deviation score, for the children who underwent bone marrow transplantation for neuroblastoma was -2.83. This was significantly (p less than 0.005) less than the standard deviation scores for children with transplants for acute lymphoblastic leukemia, acute nonlymphocytic leukemia, and aplastic anemia, which were -0.98, -0.07, and -1.05, respectively. A 6-year follow-up study of 32 long-term survivors of cancer revealed that the 11 patients with neuroblastoma continued to grow poorly, whereas a comparison group of 21 survivors of bone marrow transplantation for leukemia had essentially normal growth 2 years after the procedure. Major therapeutic differences between the two groups included the doses of local radiotherapy and the type and number of cytotoxic agents used. In comparison with the relatively mild growth-inhibiting effects of preparative regimens for leukemia and aplastic anemia, the very intensive preparative regimens used in patients with neuroblastoma have significant negative effects on growth.
 ...
PMID:Growth in children after bone marrow transplantation for advanced neuroblastoma compared with growth after transplantation for leukemia or aplastic anemia. 157 7

Twenty-three patients with leukemia and ten patients with aplastic anemia who needed long-term platelet transfusion were regularly screened for platelet associated antibodies by a combination of platelet suspension immunofluorescence test (PSIFT) and lymphocytotoxicity test (LCT). Subsequently 13 of the patients (56.5%) with leukemia and 7 of the patients with aplastic anemia (70%) became alloimmunized. The overall incidence was 60.6% (20/33). The concordance of PSIFT and LCT was 100%, suggesting that all the platelet associated antibodies were of HLA specificity. The identified antibodies were anti-A2, A11, A24, B5, B40, B46, B57, B60 and B62. Most of them were antibodies against the high frequency HLA antigens in the Chinese population. There was no dose-response relationship in the development of alloimmunization. The interval between the initiation of platelet transfusion and the development of antibody varied from 10 to 192 days. The immunization is of all or none response. In our study group, about 40% of the patients who did not develop alloantibody within six months will never do so. We concluded that platelet transfusion should not be withheld for fear of alloimmunization and that HLA matched or lymphocytotoxic compatible platelet-donors may be helpful to alloimmunized patients.
 ...
PMID:Platelet antibody screening in patients with leukemia and aplastic anemia. 164 72

Feline leukemia virus is a naturally occurring, contagiously transmitted and oncogenic immunosuppressive retrovirus of cats. The effects of FeLV are paradoxical, causing cytoproliferative and cytosuppressive disease (eg, lymphoma and myeloproliferative disorders vs immunodeficiency and myelosuppressive disorders). In the first few weeks after virus exposure, interactions between FeLV and hemolymphatic system cells determine whether the virus or the cat will dominate in the host/virus relationship--persistent viremia and progressive infection or self limiting, regressive infection will develop. The outcome of these early host/virus interactions is revealed in the diagnostic assays for FeLV antigenemia and viremia. The latter, in turn, predict the outcome of FeLV infection in cats. Known host resistance factors include age and immune system functional status. Known virus virulence factors are magnitude of exposure and virus genotype. Molecular analysis of FeLV strains indicated that natural virus isolates exist as mixtures of closely related virus genotypes and that minor genetic variations among FeLV strains can impart major differences in pathogenicity. The genetic coding regions responsible for cell targeting and specific disease inducing capacity (eg, thymic lymphoma, acute immunosuppression, or aplastic anemia) have been mapped to the virus surface glycoprotein and/or long terminal repeat regions for several FeLV strains. Infection by specific FeLV strains leads to either malignant transformation or cytopathic deletion of specific lymphocyte and hemopoietic cell population, changes that prefigure the onset of clinical illness. Another notable feature of the biology of FeLV is that many cats are able to effectively contain and terminate viral replication, an important example of host immunologic control of a retrovirus infection and a process that can be selectively enhanced by vaccination. Thus, FeLV infection serves as a natural model of the multifaceted pathogenesis of retroviruses and as a paradigm for immunoprophylaxis against an immunosuppressive leukemogenic retrovirus.
 ...
PMID:Feline leukemia virus infection and diseases. 166 70


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>