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Biomedical subjects

R E Champlin

Publications and source records attributed to R E Champlin.

At least 163 records · Page 9Linked to original sources
PubMed1989

B-cell dysfunction following human bone marrow transplantation: functional-phenotypic dissociation in the early posttransplant period.

We investigated the defect in humoral immunity that occurs following bone marrow transplantation (BMT). B cells from BMT recipients were tested for their ability to undergo the sequential steps of activation (RNA synthesis on stimulation with anti-mu or PMA), proliferation (DNA synthesis on stimulation with anti-mu plus B cell growth factor [BCGF], phorbol myristate acetate [PMA], or Staphylococcus aureus Cowan I [SAC] strain bacteria) and differentiation (Ig synthesis stimulated by T cell replacing factor [TRF]). B-cell maturation-associated cell surface markers were simultaneously investigated. "Early" (less than 10 months) posttransplant patients demonstrated defective B-cell activation and also failed to undergo normal proliferation and differentiation. Despite their functional impairment, the early patients' B cells displayed an "activated" phenotype with increased proportions of B cells displaying CD23 (a BCGF receptor) and decreased proportions of Leu 8+ B cells. Furthermore, these patients were uniquely distinguished by the fact that their B cells only weakly (if at all) expressed the CD19 antigen. In contrast, B cells from "late" patients (greater than or equal to 10 months post-BMT) activated and proliferated normally and displayed a normal cell surface phenotype, yet were unable to differentiate to high rate Ig secretion with TRF. Our results suggest a phenotype/function dissociation in early posttransplant period. With time, B cells in BMT patients acquire a normal surface phenotype and can activate and proliferate normally, yet still demonstrate a block in terminal differentiation.

Adolescent↗
PubMed1989

Bone marrow transplantation after the Chernobyl nuclear accident.

On April 26, 1986, an accident at the Chernobyl nuclear power station in the Soviet Union exposed about 200 people to large doses of total-body radiation. Thirteen persons exposed to estimated total-body doses of 5.6 to 13.4 Gy received bone marrow transplants. Two transplant recipients, who received estimated doses of radiation of 5.6 and 8.7 Gy, are alive more than three years after the accident. The others died of various causes, including burns (the cause of death in five), interstitial pneumonitis (three), graft-versus-host disease (two), and acute renal failure and adult respiratory distress syndrome (one). There was hematopoietic (granulocytic) recovery in nine transplant recipients who could be evaluated, six of whom had transient partial engraftment before the recovery of their own marrow. Graft-versus-host disease was diagnosed clinically in four persons and suspected in two others. Although the recovery of endogenous hematopoiesis may occur after exposure to radiation doses of 5.6 to 13.4 Gy, we do not know whether it is more likely after the transient engraftment of transplanted stem cells. Because large doses of radiation affect multiple systems, bone marrow recovery does not necessarily ensure survival. Furthermore, the risk of graft-versus-host disease must be considered when the benefits of this treatment are being weighed.

Accidents↗
PubMed1989

Treatment of refractory aplastic anemia with recombinant human granulocyte-macrophage-colony-stimulating factor.

Fifteen patients with refractory aplastic anemia or agranulocytosis received treatment with recombinant human granulocyte-macrophage-colony-stimulating factor (rhGM-CSF) in doses from 4 to 64 micrograms/kg/d by continuous intravenous (IV) infusion. Ten of 11 evaluable patients with aplastic anemia had substantial increments in granulocytes, monocytes, and eosinophils associated with myeloid and eosinophilic hyperplasia in the bone marrow. Patients with pretreatment granulocytes greater than 0.3 x 10(9)/L had greater increments in circulating myeloid cells than patients with more severe granulocytopenia. Only one patient had improvement in erythrocytes and platelets. Blood counts fell to baseline after rhGM-CSF treatment was discontinued. Doses up to 16 micrograms/kg/d were relatively well tolerated in the absence of extreme leukocytosis. Fatigue and myalgia were common. Three patients developed pulmonary infiltrates that resolved with discontinuation of treatment. Patients tended to have recurrent inflammation in previously diseased tissues. These data indicate that rhGM-CSF will increase circulating granulocytes, monocytes, and eosinophils in patients with refractory aplastic anemia. Further studies are necessary to determine if rhGM-CSF treatment will reduce morbidity or improve survival.

Anemia, Refractory↗
PubMed1989

Bone marrow aplasia associated with proliferation of large granular lymphocytes and subsequent transformation to acute lymphoblastic leukemia.

Proliferation of large granular lymphocytes may be associated with neutropenia and, less frequently, thrombocytopenia. In this report, we describe a patient with severe aplastic anemia in the setting of a proliferation of cells with natural killer (NK) phenotype. We demonstrated evolution to acute lymphoblastic leukemia by cells of identical phenotype.

Anemia, Aplastic↗
PubMed1989

Anaphylaxis to infusion of autologous bone marrow: an apparent reaction to self, mediated by IgE antibody to bovine serum albumin.

A case of anaphylaxis during autologous bone marrow infusion is reported. The patient was demonstrated to be skin test positive to fetal calf serum used in the cryopreservation of his bone marrow cells. The patient's serum was demonstrated to contain IgE antibody directed against bovine serum albumin. A second aliquot of the patient's bone marrow preparation was depleted of contaminating bovine proteins, and the patient successfully received a transplant and was engrafted. Clinicians need to be aware that the increasing use of biologic response modifiers, both as whole cells and effector molecules manipulated or produced in vitro, may lead to cryptic reactions to xenogeneic proteins.

Adult↗
PubMed1989

Efficacy of intensive chemotherapy for acute myelogenous leukemia associated with a preleukemic syndrome.

One hundred ninety-six patients with acute myelogenous leukemia (AML) were treated with intensive induction chemotherapy using similar daunorubicin/cytarabine/thioguanine regimens. Treatment results of 44 patients who had a documented preleukemic syndrome or cytopenia present for more than 2 months before developing over AML were compared with 152 patients with de novo AML. Eighteen (41%) patients with preleukemia evolving into AML achieved complete remission compared with 111 (73%) patients with de novo AML (P less than .01). Patients with preleukemia-AML had a significantly longer period to recovery of granulocytes. Multivariate analysis indicated that presence of a previous preleukemic syndrome and advancing age were independent poor prognostic indicators for achieving remission. For patients who achieved remission, disease-free survival and overall survival were also inferior for patients with previous preleukemia; disease-free survival was 17 +/- 17% at 3 years compared with 29 +/- 10% in patients with de novo AML (P = .02). These data indicate that intensive chemotherapy has limited efficacy in patients with AML following a preleukemic syndrome. Durable remissions may be achieved in some patients.

Age Factors↗
PubMed1989

Long-term complete chimerism and stable hematopoiesis in beagles after fetal liver hematopoietic stem cell transplantation.

Karyotype analysis of bone marrow cells was performed from 6 Beagles that had received sex-mismatched fetal liver hematopoietic stem cell grafts 2.4 to 6.5 years earlier. Two dogs received dog leukocyte antigen-matched fetal liver cells and 4 received dog leukocyte antigen-mismatched cells. In each dog, all 25 evaluated metaphase spreads were of donor genotype. All dogs had normal hemograms and repopulation of bone marrow and no dog developed graft-vs-host disease.

Animals↗
PubMed1989

Graft failure following bone marrow transplantation for severe aplastic anemia: risk factors and treatment results.

Graft failure was analyzed in 625 patients receiving allogeneic bone marrow transplants from HLA-identical sibling donors as treatment for severe aplastic anemia. Sixty-eight (11%) had no or only transient engraftment. Second bone marrow transplants were successful in achieving extended survival in 16 of 27 patients with transient initial engraftment but in none of ten patients with no sign of engraftment after the first transplant. The major factors associated with a reduced risk of graft failure were use of radiation for pretransplant immunosuppression and use of cyclosporine rather than methotrexate or T-cell depletion of the donor bone marrow for prophylaxis against graft-v-host disease (GVHD). Among 266 patients prepared for transplantation with cyclophosphamide alone, the risk of graft failure was increased in patients who received previous transfusions and reduced in those who received corticosteroids for previous therapy. Neither cell dose nor administration of donor buffy coat cells affected the probability of engraftment. Although use of radiation in conditioning reduced graft failure, survival was not improved. Posttransplant treatment with cyclosporine and avoidance of pretransplant blood transfusions were associated with improved survival.

Actuarial Analysis↗
PubMed1989

Treatment of acute myelogenous leukemia in the elderly.

Current data indicate that most elderly patients with acute myelogenous leukemia should be treated with intensive chemotherapy. Most should receive remission induction chemotherapy using cytarabine 100 to 200 mg/m2/d by constant intravenous infusion for five to seven days plus daunorubicin greater than or equal to 30 mg/m2/d for three days. Patients in good overall condition with a near-normal performance status may benefit from a more intensive regimen. Patients achieving remission should receive one to three courses of consolidation chemotherapy. Highly debilitated patients have poor results with any form of therapy, and there has been no apparent advantage for low-dose chemotherapy compared to standard treatment regimens. The intensity of chemotherapy treatment must be individualized to the requirements of the patient.

Aged↗
PubMed1989

Current approaches to management of infections in bone marrow transplants.

Infections continue to be common complications of bone marrow transplantation, but recent advances have improved their outcome. Oral chemoprophylaxis with the fluoroquinolones has reduced gram-negative infections during periods of granulocytopenia, while new triazole drugs show promise for improving antifungal prophylaxis. Similarly, recombinant hematopoietic growth factors may reduce infections by shortening the period of post-transplant granulocytopenia. The efficacy of double beta-lactam antibiotic therapy or monotherapy with imipenem has obviated the need to use aminoglycosides in the empiric treatment of febrile patients receiving cyclosporine or other nephrotoxic agents. Treatment of post-transplant interstitial pneumonia associated with cytomegalovirus (CMV) remains problematic, but recent results using the combination of ganciclovir plus intravenous immune globulin have been favorable. In CMV-seronegative patients, CMV infections and pneumonia can be prevented or modified by using CMV-seronegative blood products and intravenous immune globulin. Intravenous immune globulin also has the additional benefits of modifying graft versus host disease and preventing late bacterial infections after marrow engraftment. In CMV-seropositive patients, prophylactic ganciclovir may prevent CMV reactivation and pneumonia and is the subject of an ongoing controlled clinical trial.

Bone Marrow Transplantation↗
PubMed1988

Serum cholesterol-lowering activity of granulocyte-macrophage colony-stimulating factor.

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) is a glycoprotein hormone that stimulates the growth of hematopoietic progenitor cells and enhances the functional activity of mature myeloid effector cells. Granulocyte-macrophage colony-stimulating factor was administered to eight patients with severe aplastic anemia in an attempt to restore adequate hematopoiesis. Profound decreases in serum cholesterol concentrations were observed during GM-CSF therapy that were not dependent on changes in the patients' peripheral blood cell counts. Serum cholesterol levels decreased by an average of 37% during treatment, reaching levels of less than 4.40 mmol/L in all patients. Serum cholesterol concentrations returned to baseline in all patients after discontinuation of GM-CSF therapy. Treatment with GM-CSF prominently alters cholesterol homeostasis in vivo, although the mechanism of this effect is unknown. Our results suggest that GM-CSF may be potentially useful in the treatment of hypercholesterolemia and, possibly, in the prevention and treatment of atherosclerosis.

Adolescent↗
PubMed1988

Radiation accidents and nuclear energy: medical consequences and therapy.

After the accidents at Chernobyl, the Soviet Union, and in Goiania, Brazil, there is increasing concern about the medical risks from radiation accidents. This overview summarizes the principles of nuclear energy, the biologic effects of accidental radiation exposure, the emergency response to nuclear accidents, and approaches to treating radiation injuries. Also discussed are the related issues of reactor safety, the disposal of radioactive waste, and the proliferation of nuclear weapons. With the increasing use of radioactive materials for power, weapons, and medical diagnostics, the medical community needs to understand the health consequences of radiation exposure.

Accidents↗
PubMed1988

Controlled trials of double beta-lactam therapy with cefoperazone plus piperacillin in febrile granulocytopenic patients.

The efficacy and safety of double beta-lactam therapy with cefoperazone plus piperacillin in febrile granulocytopenic patients were compared with moxalactam plus piperacillin, ceftazidime plus piperacillin, and imipenem alone in two separate clinical trials. All patients also received prophylactic vitamin K. When National Committee for Clinical Laboratory Standards breakpoints for susceptibility were used, a greater proportion of pretherapy isolates of gram-negative aerobic bacilli and gram-positive organisms were found to be susceptible to cefoperazone (94 percent) and imipenem (91 percent) than to moxalactam (84 percent), ceftazidime (85 percent), or piperacillin (85 percent). In trial I, the overall response rates for documented or possible infections were 78 percent (76 of 97 patients) for cefoperazone/piperacillin and 80 percent (72 of 90 patients) for moxalactam/piperacillin. In trial II, the overall response rates were 86 percent (25 of 29 patients) for cefoperazone/piperacillin, 74 percent (20 of 27 patients) for ceftazidime/piperacillin, and 72 percent (21 of 29 patients) for imipenem alone. There was no nephrotoxicity or hemorrhage related to the study drugs. Diarrhea was more frequent with each of the double beta-lactam regimens, whereas nausea and seizures were more common with imipenem given at a dosage of 1.0 g intravenously every six hours. Seizures occurred in three of 29 imipenem-treated patients but in none of 243 patients treated with the double beta-lactam regimens (p less than 0.001). These results suggest that cefoperazone plus piperacillin provides adequate coverage for most common bacterial pathogens and is safe and effective therapy for febrile granulocytopenic patients.

Adolescent↗
PubMed1988

Recombinant interferon alpha-2a for treatment of herpes zoster in immunosuppressed patients with cancer.

PURPOSE: Acyclovir and high doses of intramuscular leukocyte interferon have been shown to prevent dissemination of herpes zoster in cancer patients with localized herpes zoster. With the availability of recombinant interferon, we decided to conduct a multicenter, placebo-controlled, double-blind trial of intramuscular recombinant interferon alpha-2a to assess its efficacy and safety in the treatment of localized herpes zoster in immunosuppressed patients with cancer. PATIENTS AND METHODS: Immunosuppressed cancer patients with localized herpes zoster were randomly assigned to receive placebo, 36 X 10(6) units of recombinant interferon alpha-2a per day, or 68 X 10(6) units of recombinant interferon alpha-2a per day. Due to frequent adverse effects, the 68 X 10(6) unit dose of interferon was discontinued prior to conclusion of the trial. RESULTS: Dissemination of herpes zoster occurred in 14 of the 24 patients (58 percent) who received placebo but in only four of 24 recipients (17 percent) of 36 X 10(6) units of interferon per day (p = 0.003). Adverse effects (fever, chills, headaches, gastrointestinal irritability, fatigue, and myalgias) were more common or severe in interferon-treated patients. CONCLUSION: These results suggest that interferon modifies the severity of herpes zoster in immunosuppressed patients with cancer but is associated with frequent side effects.

Adult↗
PubMed1988

Bone marrow transplantation for chronic myelogenous leukemia in chronic phase. Increased risk for relapse associated with T-cell depletion.

Data on 405 patients with chronic myelogenous leukemia who received bone marrow transplants in chronic phase were analyzed for factors predictive of outcome. The 4-year actuarial probability of relapse was 19% (95% confidence interval [CI], 12% to 28%) and of survival, 55%. In multivariate analyses the probability of relapse was higher for recipients of T-cell-depleted bone marrow compared with recipients of non-T-cell-depleted bone marrow (relative risk, 5.4; P less than 0.0001) and for patients who did not develop chronic graft-versus-host disease (95% CI, 50% to 60%) with patients who did (relative risk, 3.1; P less than 0.01). The probability of survival was lower for patients who developed moderate to severe acute graft-versus-host disease than for patients with no or mild acute graft-versus-host disease (relative risk, 3.7; P less than 0.0001), and in patients aged 20 or older than in younger patients (relative risk, 2.6; P less than 0.0002). Duration of disease before transplant was not associated with outcome. Bone marrow transplantation done in the chronic phase of chronic myelogenous leukemia offers some patients prolonged leukemia-free survival. The T-cell-depleted grafts are associated with an increased probability of relapse.

Acute Disease↗
PubMed1988

Immunomodulating effects in vitro of interleukin-2 and interferon-gamma on human blood and bone marrow mononuclear cells.

Mononuclear cells (MNC) derived from peripheral blood (PBMNC) of 23 normal donors and 4 AIDS patients, and from bone marrow (BMMNC) of 15 normal donors were incubated at 37 degrees C in culture medium alone or in the presence of either natural or recombinant human interleukin-2 (IL-2) or recombinant human interferon-gamma (IFN-gamma; 1-1,000 U/ml). The cultured cells were washed on days 1, 4 or 7 and tested for various immune functions in vitro and for cell surface phenotype. IL-2, but not IFN-gamma, was found mitogenic for both PBMNC and BMMNC. The natural killer (NK) activity of both PBMNC and BMMNC was the only function tested that was markedly augmented (over 100-fold compared to medium control) by both lymphokines. Pretreatment of PBMNC with IL-2 at greater than or equal to 10 U/ml profoundly suppressed (up to 90%) various functions, such as mitogenic responses (phytohemmagglutinin, concanavalin A, pokeweed mitogen), allogeneic mixed leukocyte reaction, antibody production and T cell colony formation in agar. In contrast, some BMMNC functions were elevated at low doses of IL-2 and IFN-gamma, and significant suppression of BMMNC was seen only with high doses of IL-2 (greater than or equal to 100 U/ml) and IFN-gamma (1,000 U/ml). IL-2 was by far more effective than IFN-gamma in both the amplification of NK activity and the suppression of most of the other functions. IL-2, but not IFN-gamma, was found to activate/induce suppressor cells and increased the proportion of Leu-2+ (CD8) cells in PBMNC; the suppressive effect was time- and dose-dependent. The IL-2-induced suppression could be diminished by inclusion of anti-IL-2 antibody during the pretreatment phase. Similar suppressive effects were noted in PBMNC from AIDS patients. These findings suggest that: (a) high-dose IL-2 may elicit immunosuppression which can be mediated by nondiscriminative highly cytotoxic cells (i.e. lymphokine-activated killer cells) and/or by noncytotoxic, nonspecific suppressor cells, and (b) that PBMNC respond differently to the lymphokines than do BMMNC.

Acquired Immunodeficiency Syndrome↗