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Biomedical subjects

R E Champlin

Publications and source records attributed to R E Champlin.

At least 199 records · Page 11Linked to original sources

Abnormal T-lymphocyte colonies (CFU-TL) following bone marrow transplantation.

We studied the presence of peripheral-blood- and bone-marrow-derived T-lymphocyte colony formation (CFU-TL) in 28 bone marrow transplant recipients from 1 month to six years after transplantation. Peripheral blood leukocyte and lymphocyte counts were generally normal, and all had morphologic evidence of engraftment without leukemia at the time of study. Both peripheral-blood- and bone-marrow-derived CFU-TL were markedly reduced after transplantation as compared to normal controls, which included bone marrow donors (14.2 +/- 5/4 X 10(4) vs 313 +/- 100/4 X 10(4) [p less than 0.001] and 26 +/- 4/2 X 10(5) vs 1004 +/- 60/2 X 10(5) [p less than 0.001]). Among the patients, four had no detectable bone-marrow-derived CFU-TL when tested less than six months after transplantation. Peripheral blood CFU-TL, while present in all patients, was markedly decreased for more than 12 months after transplantation. After two years, the number of CFU-TL returned to normal in several patients. The abnormalities in CFU-TL were unrelated to diagnosis, age, sex, graft-versus-host disease (GVHD), pretransplant conditioning, or posttransplant immunosuppressive treatment. Patients receiving autologous bone marrow transplants also had decreased CFU-TL. Cocultures of normal peripheral-blood- or bone-marrow-derived mononuclear cells with recipients' mononuclear cells or sera did not inhibit normal CFU-TL growth. Furthermore, the addition of mononuclear cells or sera from normal individuals, or of exogenous interleukin 1 or interleukin 2, did not correct the deficiency of CFU-TL growth by recipient cells. Depletion of T-lymphocytes from bone marrow or peripheral blood in transplant recipients by physical techniques or with a monoclonal antibody (CT-2) and complement had no effect on CFU-TL recovery. Similarly, addition of recipients' T cells to normal peripheral blood or bone marrow mononuclear cells did not suppress CFU-TL. These data indicate that most transplant recipients have a marked reduction in CFU-TL which persists for up to two years after transplantation. This reduction in the growth of T-cell colonies appears to be due to deficient numbers of these cells or an intrinsic defect in their responsiveness to T-cell lymphokines, rather than a result of growth suppression by inhibitory cells or serum factors. This observed defect in CFU-TL may have implications for therapeutic attempts to facilitate immune reconstitution after bone marrow transplantation.

Adolescent↗

Pure red cell aplasia characterized by erythropoietic maturation arrest. Response to anti-thymocyte globulin.

Pure red cell aplasia is a syndrome characterized by markedly decreased erythropoiesis. On bone marrow examination, there are typically less than 0.5 percent erythroblasts, but sometimes a picture of maturation arrest can be seen. This report describes a patient with maturation arrest of erythropoiesis at the basophilic normoblast stage who had a response to an eight-day course of anti-thymocyte globulin with a return of normal erythropoiesis.

Adult↗

Molecular epidemiology of cytomegalovirus infections associated with bone marrow transplantation.

Restriction endonuclease analysis of purified viral DNA was used to study the molecular epidemiologic characteristics of cytomegalovirus infection in 18 patients having bone marrow transplantation. Four patients who had had asymptomatic excretion of cytomegalovirus in urine before transplantation subsequently developed a cytomegalovirus infection after transplantation (pneumonia in 2 patients, fever and viremia in 1 patient, and asymptomatic viruria in 1 patient). In each patient, the infection that developed after transplantation was caused by a cytomegalovirus strain genetically identical to the isolate detected in urine before transplantation. Cytomegalovirus isolates from different sites (buffy coat, lung, and urine) of the same patient were also identical, but cytomegalovirus isolates from different patients were never identical. Our results suggest that some cytomegalovirus infections after bone marrow transplantation may be caused by strains present before transplantation. The great structural and genetic variability of cytomegalovirus isolates must be considered in the development of effective diagnostic and immunoprophylactic measures for infection after marrow transplantation.

Adolescent↗

Treatment of acute myelogenous leukemia. A prospective controlled trial of bone marrow transplantation versus consolidation chemotherapy.

In a prospective controlled trial, the relative effectiveness of allogeneic bone marrow transplantation and postremission chemotherapy was assessed for adult patients with acute myelogenous leukemia in first complete remission. Twenty-three patients, 15 to 45 years of age, who had an HLA-identical sibling donor were designated to receive bone marrow transplantation. Forty-four patients who either lacked an HLA-identical sibling or were over 45 years of age were designated to receive intensive consolidation chemotherapy. The actuarial rate of leukemia relapse was significantly lower in the transplantation group than in the chemotherapy group (40 +/- 25% [95% confidence interval] compared with 71 +/- 14%, p = 0.01). Actuarial survival at greater than 4 years was not significantly different (40 +/- 21% compared with 27 +/- 14%, p greater than 0.4). These data show that bone marrow transplantation is more effective than consolidation chemotherapy in preventing leukemia relapse, but overall survival was not improved in this study.

Adolescent↗

[Use of a polyvalent intravenous immunoglobulin or specific cytomegalovirus hyperimmunoglobulin for modification of cytomegalovirus infections and prevention of interstitial pneumonias following bone marrow transplantation].

The effects of prophylactic, polyvalent intravenous immune globulin on cytomegalovirus infection and interstitial pneumonia in allogenic marrow transplants were evaluated in an ongoing, randomized controlled trial. Thirty-eight patients were given weekly doses (20 cc/kg) of polyvalent intravenous immune globulin before and after transplantation, and 37 patients were controls. Both symptomatic cytomegalovirus infection (17 of 37 or 46% vs. 8 of 38 or 21%, p = 0.04) and interstitial pneumonia (17 of 37 or 46% vs. 7 of 38 or 18%, p = 0.02) occurred less frequently in the recipients of polyvalent intravenous immune globulin. In separate kinetic studies, a 5 cc/kg dose of a cytomegalovirus-specific hyperimmune globulin produced cytomegalovirus antibody titers in patients equivalent to those achieved after the 20 cc/kg dose of polyvalent intravenous immune globulin. All immune globulin preparations were well-tolerated. These preliminary results suggest that intravenous immune globulin can modify the severity of cytomegalovirus infection and prevent interstitial pneumonia in marrow transplants. Additional trials are now needed to define the minimal effective dose of intravenous immune globulin and to compare the effectiveness of different intravenous immune globulin formulations.

Anemia, Aplastic↗

Recombinant alpha-2-interferon for hairy cell leukemia.

Twenty-two patients with hairy cell leukemia were treated with biosynthetic (recombinant) alpha-2-interferon in an open-label, single-arm efficacy study. Patients received 2 X 10(6) U/m2 recombinant alpha-2-interferon three times weekly. Therapy was well tolerated subjectively with minimal short-term hematologic toxicity. Two patients had bacterial infections during the period of study, and one patient experienced a short-lived readily reversible rejection of a corneal transplant. Statistical comparison of the mean hematologic indices at study entry and after three to six months of therapy with recombinant alpha-2-interferon indicates a significant improvement in hemoglobin, granulocyte, and platelet counts. Bone marrow biopsies in six of 14 patients after six months of therapy showed a greater than 50% decrease in the infiltration of leukemia cells. We conclude that recombinant alpha-2-interferon is highly effective therapy for hairy cell leukemia.

Adult↗

Do androgens enhance the response to antithymocyte globulin in patients with aplastic anemia? A prospective randomized trial.

We analyzed the effect of antithymocyte globulin (ATG) with or without androgens in 121 patients with aplastic anemia. Fifty-three patients with moderate to severe aplastic anemia were prospectively randomized to receive ATG with or without oral androgens. Eleven of 26 patients (42%) receiving ATG plus androgen responded, including three complete and eight partial responses. Twelve of 27 patients (44%) receiving ATG plus placebo responded, including five complete and seven partial responses. The difference in response rates was not significant (P greater than .9). Survival was also comparable in the two groups; for patients with severe aplastic anemia, actuarial survival at two years was 55% +/- 24% (95% confidence interval) in patients receiving ATG plus androgen compared with 50% +/- 24% in the ATG plus placebo group (P = .65). Furthermore, results in both groups were indistinguishable from those obtained in 68 historical controls receiving ATG without androgens. These data indicate that androgens are not required in order to respond to antithymocyte globulin and the addition of androgens, as used in this trial, did not significantly improve response rates to ATG treatment.

Adolescent↗

How does bone-marrow transplantation cure leukaemia?

Bone-marrow transplantation from an HLA-identical sibling is effective in eradicating leukaemia in most patients with acute myelogenous leukaemia (AML) in first remission. The efficacy is widely assumed to be related to the high doses of drugs and radiation administered before transplantation. Relapse rates in 31 transplants from monozygotic twins were compared with those in 339 transplants from HLA-identical siblings managed with similar chemoradiotherapy. The actuarial relapse rate in the twins was 59% (95% confidence interval +/- 20%) compared with 18 +/- 4% in the non-twin siblings. The high relapse rate in identical twins may be related to the absence of graft-versus-host disease after transplantation. If success depends substantially on the immunotherapeutic effect of allogeneic bone-marrow, only limited benefit can be expected from autotransplantation and intensification chemotherapy for AML.

Bone Marrow Transplantation↗

Intravenous immunoglobulin for modification of cytomegalovirus infections associated with bone marrow transplantation. Preliminary results of a controlled trial.

The effects of immune globulin intravenous, 5 percent in 10 percent maltose, on cytomegalovirus infection and interstitial pneumonia in bone marrow transplants were evaluated in a randomized controlled trial. Eighteen patients were given weekly doses (20 cc/kg) of intravenous immunoglobulin before and after transplantation, and 18 patients were controls. The incidence of cytomegalovirus infection was similar in the control and intravenous immunoglobulin-treated groups, but symptomatic cytomegalovirus infection (eight of 18 versus three of 18, p = 0.14) and interstitial pneumonia (10 of 18 versus four of 18, p = 0.08) occurred less frequently in the group receiving intravenous immunoglobulin. Cytomegalovirus pneumonia developed in eight control patients and in three patients receiving intravenous immunoglobulin (p = 0.14), whereas two control patients and one patient receiving intravenous immunoglobulin experienced idiopathic interstitial pneumonia. These preliminary results suggest that intravenous immunoglobulin can modify the severity of cytomegalovirus infection and prevent interstitial pneumonia in bone marrow transplant recipients.

Adolescent↗

Moxalactam plus piperacillin versus moxalactam plus amikacin in febrile granulocytopenic patients.

In a prospective randomized trial, febrile granulocytopenic patients received either moxalactam plus piperacillin or moxalactam plus amikacin as initial empiric antimicrobial therapy. Most patients were also given prophylactic vitamin K. The overall response rates for the two regimens were similar (105 of 136, or 77 percent, for moxalactam plus piperacillin versus 107 of 136, or 79 percent, for moxalactam plus amikacin). For Pseudomonas aeruginosa infections, the response rate was better in patients receiving moxalactam plus amikacin (seven of nine versus one of five, p = 0.06); two patients treated with moxalactam plus piperacillin experienced relapse of P. aeruginosa bacteremia in association with the emergence of beta-lactam-resistant P. aeruginosa isolates. On the other hand, bacteremic enterococcal superinfections occurred in seven patients receiving moxalactam plus amikacin but in none given moxalactam plus piperacillin (p = 0.02). Serious side-effects were minimal with both regimens, and nephrotoxicity was less common in patients receiving moxalactam plus piperacillin (two of 136 versus six of 136, p = 0.28). There was no antibiotic-related hemorrhage. These results suggest that the overall efficacy and toxicity of moxalactam plus piperacillin and moxalactam plus amikacin are similar. Moxalactam/piperacillin therapy may be limited in certain patients by the emergence of beta-lactam-resistant P. aeruginosa, whereas enterococcal superinfections may complicate moxalactam/amikacin therapy.

Adolescent↗

Bone marrow transplantation from identical twins in the treatment of aplastic anaemia: implication for the pathogenesis of the disease.

Treatment of aplastic anaemia by bone marrow transplantation from a syngeneic (identical twin) donor has provided insights into the pathophysiology of the disease. We report from patients with severe anaemia who were treated by syngeneic bone marrow transplantation. None of the patients had sustained recovery of peripheral blood counts. All four received second transplants from the same twin donor after immunosuppressive conditioning treatment. Each had prompt recovery of haematopoiesis. A review of the literature indicates that failure of syngeneic bone marrow transplantation in patients with aplastic anaemia is not uncommon. These data indicate that aplastic anaemia may be caused by a mechanism other than an absence or intrinsic abnormality of haematopoietic stem cells in many patients.

Adolescent↗

Role of bone marrow transplantation in the treatment of hematologic malignancies and solid tumors: critical review of syngeneic, autologous, and allogeneic transplants.

Intensive chemoradiotherapy and bone marrow transplantation is effective for selected patients with acute or chronic leukemia, lymphoma, or solid tumors. This paper will summarize the results of treatment utilizing syngeneic transplants from identical twins, allogeneic transplants from HLA identical and nonidentical donors, and the use of the patient's own bone marrow cells in autologous bone marrow transplantation. The potential complications of marrow transplantation are described and the current results of bone marrow transplantation are compared with recent advances in alternative forms of treatment for these malignancies.

Bone Marrow Transplantation↗