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Biomedical subjects

R Champlin

Publications and source records attributed to R Champlin.

At least 217 records · Page 12Linked to original sources
PubMed1987

Bone marrow transplantation for acute leukemia: recent advances and comparison with alternative therapies.

Bone marrow transplantation is an effective therapy in patients with acute leukemia. High-dose chemotherapy with or without total body irradiation and allogeneic bone marrow transplantation is a more effective antileukemic treatment than chemotherapy. This approach is limited, however, by a relatively high risk of transplant-related complications, particularly graft rejection, GVHD, and interstitial pneumonitis. Autologous bone marrow transplantation avoids the problems of graft rejection and GVHD. It does, however, introduce a risk of reinfusing residual leukemia cells with the autologous bone marrow and absence of a possible graft-versus-leukemia effect associated with allogeneic transplants. Bone marrow transplantation is useful in AML. Syngeneic or allogeneic HLA-identical bone marrow transplantation is the preferred treatment for patients under age 45 to 50 who fail chemotherapy. Transplantation is also likely to be superior or comparable to chemotherapy for patients less than 20 to 30 years of age in first remission. Transplantation in older individuals in first remission is controversial; results are comparable to those achieved with postremission chemotherapy. Transplants from donors other than HLA-identical siblings must be considered investigational but may be a reasonable alternative in young individuals in first relapse or second remission. Autotransplants are difficult to evaluate critically but may be considered as investigational therapy for individuals in second or later remission for whom a suitable allogeneic donor is unavailable. Autotransplants in first remission should be restricted to controlled clinical trials because it is otherwise impossible to determine their efficacy. It is uncertain whether ex vivo treatment of the bone marrow to remove leukemia cells is necessary in the context of autotransplantation; again, controlled trials are required. Bone marrow transplantation from an HLA-identical sibling is effective in individuals with ALL who relapse despite chemotherapy. Patients undergoing transplantation while in second or later remission or in relapse have a survival rate superior to those treated with chemotherapy. One important and unresolved issue is whether patients with high-risk ALL should receive bone marrow transplants or intensive postremission chemotherapy while in first remission; controlled clinical trials are needed. Bone marrow transplants from donors other than HLA-identical siblings and autologous bone marrow transplants are investigational approaches that should be considered in selected young patients who fail despite chemotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Agents↗
PubMed1987

Acute myelogenous leukemia: recent advances in therapy.

Results of treatment of AML have improved over the last decade. With modern remission induction chemotherapy, most patients achieve complete remission. The median remission duration is now 1 to 2 years, and a substantial fraction of patients achieve long-term disease-free survival. Bone marrow transplantation provides an improved antileukemic effect compared with chemotherapy alone, and it is the treatment of choice for selected groups of patients. The major limitation is the risk of transplant-related mortality. Most patients are not currently eligible for bone marrow transplants because of advanced age or lack of a histocompatible donor. Autologous marrow transplantation may be effective in selected setting, but this remains investigational at present. Substantial improvement in results of treatment of AML requires the development of new and effective chemotherapeutic agents that are non-cross-resistant with available drugs. Results of bone marrow transplantation may substantially improve if innovative measures to prevent major complications are successful.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Myasthenia gravis and polymyositis in a dog following fetal hematopoietic cell transplantation.

Myasthenia gravis and focal polymyositis occurred in a dog following successful transplantation of DLA-identical fetal liver hematopoietic cells. There was no evidence of acute or chronic graft-versus-host disease. Antibodies to acetylcholinesterase receptor and immune complexes reactive with myoneural junctions were demonstrated, as well as focal inflammation with perifascicular and type 2 muscle atrophy. The dog responded to treatment with prednisolone and pyridostigmine.

Animals↗
PubMed1985

Oral mucositis in patients undergoing bone marrow transplantation.

Thirty patients who received bone marrow transplantation treatment from HLA identical sibling donors for immunologic and malignant diseases were studied. In essentially all of the patients oral changes developed during the first 30 days following transplant. Oral symptoms frequently constituted the major complaints of the patients during the follow-up period. The oral changes included mucositis, xerostomia, pain, and bleeding. Mucositis was more severe and of longer duration when associated with herpes simplex infections and when optimal oral hygiene was not maintained. Xerostomia which accompanies engraftment was an early sign of acute graft-versus-host disease. A nonbrushing method of oral hygiene was effective in reducing the severity and duration of mucositis. This technique offers a short-term alternative to brushing in pancytopenic patients who are susceptible to bleeding or trauma.

Adolescent↗
PubMed1985

Abnormalities of myeloid progenitor cells after "successful" bone marrow transplantation.

We studied recovery of peripheral blood- and bone marrow-derived myeloid progenitor cells (CFU-G,M) in 29 patients who received bone marrow transplants 2 mo to 8.5 yr previously. All patients had normal levels of peripheral blood neutrophils, normal bone marrow cellularity, and a normal myeloid-erythroid ratio. Both peripheral blood- and bone marrow-derived CFU-G,M were markedly reduced compared with normal controls and bone marrow donors [5 +/- 1/10(6) vs. 37 +/- 4/10(6) (P less than 0.001) and 23 +/- 5/2 x 10(5) vs. 170 +/- 21/2 x 10(5) (P less than 0.001)]. Five patients had no detectable CFU-G,M even when 10(6) bone marrow cels were plated. These abnormalities of CFU-G,M were unrelated to age, sex, diagnosis, conditioning regimen, dose of bone marrow cells transplanted, and presence or absence of graft-vs.-host disease. Patients who received either autotransplants or transplants from identical twins also had decreased or absent CFU-G,M indicating that allogeneic factors and posttransplant immune suppressor with methotrexate or corticosteroids were not major determinants of this abnormality. Co-culture of normal or donor peripheral blood or bone marrow mononuclear cells with recipients peripheral blood or bone marrow mononuclear cells, purified T cells, or serum failed to show any evidence of active CFU-G,M suppression. Furthermore, the abnormality of CFU-G,M could not be corrected by the addition of normal syngeneic (donor) hematopoietic cells or serum. Depletion of T-cells from recipient bone marrow by physical techniques resulted in marked increase in CFU-G,M (36 +/- 13 vs. 138 +/- 36; P less than 0.05). The abnormality could be reproduced in vitro by readdition of autologous T cells. In contrast to results with T cell depletion by physical techniques, T cell depletion with a monoclonal anti-T antibody (B7) and complement had no effect. These data indicate that most-transplant recipients have a marked abnormality in CFU-G,M when these cells are cultured in vitro. In at least some of these patients, the decreased cloning efficiency of CFU-G,M appears to be mediated by a suppressive effect of autologous T cells.

Adolescent↗
PubMed1985

Fetal liver cell transplantation in dogs: results with DLA-compatible and incompatible grafts.

We evaluated the ability of fetal liver hematopoietic cells to reconstitute hematopoiesis and immunity in lethally irradiated dogs. Nineteen consecutive dogs received transplants of fetal liver cells from donors identical or mismatched for DLA antigens. Six animals received 16 Gy fractionated total body irradiation (TBI) followed by transplantation of DLA-identical fetal liver. Three other dogs received transplants of fetal liver that was homozygous for a DLA haplotype shared by the recipient. No post-transplant immunosuppressive treatment was administered. All nine dogs had rapid and sustained restoration of hematopoiesis and none developed graft-versus-host disease. T and B-lymphocyte function recovered slowly over several months in all animals with sustained engraftment and they remained free of infection in open kennel conditions. These data indicate that a single DLA-identical fetal liver can reconstitute hematopoiesis in lethally irradiated dogs. This conditioning regimen was inadequate for transplantation of DLA-mismatched fetal liver cells; 6 of 6 dogs failed to engraft. We evaluated whether more intensive conditioning with 18 Gy fractionated TBI or 16 Gy TBI followed by post transplant treatment with methotrexate was feasible in 4 dogs. These regimens produced severe mucositis and gastrointestinal toxicity; 2 recipients of DLA-matched fetal liver transplants survived but 2 dogs receiving DLA-haploidentical fetal liver had engraftment but died of toxicity. Further studies are required to develop an effective, yet tolerable conditioning regimen in this setting. Fetal liver transplantation may ultimately be useful as a source of hematopoietic cells for transplantation in human patients if an effective conditioning regimen can be developed to allow engraftment of histoincompatible transplants.

Animals↗
PubMed1984

Prolonged survival in acute myelogenous leukaemia without maintenance chemotherapy.

46 adults with previously untreated acute myelogenous leukaemia who achieved complete remission with 6-thioguanine, cytarabine, and daunorubicin (TAD) received two courses of intensive consolidation chemotherapy. The first cycle consisted of 5-azacytidine and doxorubicin followed by a second consolidation cycle with TAD. Maintenance chemotherapy was not administered. Median remission duration was 14 months and 26% (95% confidence interval, 11%-41%) remained in continuous remission at 5 years. Actuarial 5 year survival was 31% (+/- 15%). Results were most favourable in patients who achieved complete remission within 60 days of chemotherapy being initiated. These data indicate that prolonged disease-free survival can be achieved in patients treated with intensive induction and consolidation treatment alone without maintenance chemotherapy.

Adolescent↗
PubMed1984

Allogeneic bone-marrow transplantation for chronic myelogenous leukaemia.

In 117 patients with chronic myelogenous leukaemia (CML) treatment with a combination of high-dose chemoradiotherapy plus transplantation of allogeneic bone-marrow from HLA-identical, mixed-lymphocyte-culture-identical siblings resulted in an actuarial probability of 3-year survival of 63 +/- 16% (95% confidence interval) for 39 patients transplanted in chronic phases; 36 +/- 14% for 56 transplanted in accelerated phase; and 12 +/- 15% for 22 transplanted during blast crisis. Irrespective of disease status at the time of transplantation, and in contrast to chemotherapy, a plateau-effect was observed in the survival curves starting 14 to 19 months after transplantation. The actuarial probability of recurrent or persistent leukaemia at 3 years was 7 +/- 9% for patients transplanted in chronic phase, 41 +/- 19% for accelerated phase, and 41 +/- 39% for blastic phase. All relapses occurred within 18 months of transplantation. This study demonstrates that long-term disease-free survival in CML can be achieved with bone-marrow transplantation. Best results were obtained in patients transplanted during chronic phase of the disease.

Adolescent↗
PubMed1984

Comparison between bone marrow transplantation and antithymocyte globulin in treatment of young patients with severe aplastic anemia.

Fifty-seven patients younger than 25 years with severe aplastic anemia underwent either bone marrow transplantation or antithymocyte globulin therapy (ATG) to ascertain which approach should be used in young patients. Thirty-five patients who had an HLA-identical sibling donor underwent bone marrow transplantation after conditioning with cyclophosphamide and low-dose total-body radiation. Twenty-two patients who did not have an HLA-identical donor received ATG. The 2-year actuarial survival of patients after transplant is 72% (95%, CI 64% to 80%), versus 45% (95%, CI 29% to 61%) in those given ATG therapy (P = 0.18). In those patients surviving 6 months after treatment, return of peripheral blood counts to normal values was more common in patients who received marrow transplant compared with those given ATG therapy (P less than 0.001). Furthermore, 24 of 26 transplant survivors had Karnofsky performance scores greater than 90%, compared with only five of 13 ATG survivors. These data suggest that bone marrow transplantation is the preferred therapy for severe aplastic anemia in young patients who have an HLA-identical sibling donor. ATG should be reversed for those young patients with severe aplastic anemia who do not have a histocompatible marrow donor.

Adolescent↗
PubMed1984

Immunologic defects in young male patients with hepatitis-associated aplastic anemia.

Extensive immunologic studies were done in 97 patients with severe aplastic anemia between 1973 and 1979. Sixteen young male patients with hepatitis-associated aplastic anemia appeared to constitute a unique subset. Compared with most patients with aplastic anemia from other causes, these 16 patients had significant reductions in the mean values of circulating T lymphocytes, serum IgG and IgM, mitogen reactivity, and decreased cutaneous hypersensitivity. The ratio of peripheral blood helper to suppressor T lymphocytes identified by monoclonal antibodies was within normal limits in 3 patients studied with hepatitis-associated aplastic anemia. Interestingly, the ratio was low (less than 1) in 3 of 7 patients studied with aplastic anemia from other causes, although the mean for these 7 patients was normal. These data suggest that patients in this subset with hepatitis-associated severe aplastic anemia have a severe immunodeficiency. Whether this immunodeficiency is the cause or result of the hepatitis or aplastic anemia, or both, is unknown.

Adolescent↗