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Biomedical subjects

R E Champlin

Publications and source records attributed to R E Champlin.

At least 145 records · Page 8Linked to original sources
PubMed1992

Second HLA-identical sibling transplants for leukemia recurrence.

We analysed data from 114 recipients of HLA-identical sibling transplants who relapsed and received a second transplant between 1978 and 1989. Twenty-nine patients had acute lymphoblastic leukemia, 46 acute myeloid leukemia and 39 chronic myelogenous leukemia. Median (range) interval between first and second transplants was 15 (1-80) months. Following the second transplant, graft failure occurred in 2%, acute graft-versus-host disease (GVHD) in 27% and chronic GVHD in 21% of patients at risk. Risks of interstitial pneumonia and hepatic veno-occlusive disease were higher after the second than the first transplant. Two-year probabilities (95% confidence interval) of treatment-related mortality, relapse and leukemia-free survival were 41% (30-53%), 65% (53-75%) and 21% (14-30%), respectively. Leukemia-free survival was 7% (2-19%) among patients relapsing less than 6 months after their first transplant, with high rates of both relapse, 77% (49-92%), and treatment-related mortality 69% (46-85%). In contrast, leukemia-free survival was 28% (19-41%) in those relapsing more than 6 months after the first transplant; in this group the probability of relapse was 59% (45-72%) and treatment-related mortality 30% (20-43%). Factors correlated with better outcome included a diagnosis of chronic myelogenous leukemia, relapse more than 6 months after the first transplant, acute leukemia in remission prior to the second transplant and good performance status.

Adolescent↗
PubMed1991

Beta-lactam antibiotic therapy in febrile granulocytopenic patients. A randomized trial comparing cefoperazone plus piperacillin, ceftazidime plus piperacillin, and imipenem alone.

OBJECTIVE: To compare the efficacy, toxicity, and cost-effectiveness of double beta-lactam therapy with monotherapy. DESIGN: A randomized, controlled trial. PATIENTS: Febrile, granulocytopenic patients (429). INTERVENTIONS: Patients were randomly assigned to receive iv cefoperazone (3 g every 12 hours) plus piperacillin (75 mg/kg body weight every 6 hours), ceftazidime (2 g every 8 hours) plus piperacillin (75 mg/kg every 6 hours), or imipenem alone (1.0 g or 0.5 g every 6 hours). Patients also received prophylactic vitamin K. MEASUREMENTS: Clinical improvement, eradication of the infecting organism, and toxicity in 403 evaluable patients with one or more infections. MAIN RESULTS: Cefoperazone and ceftazidime, when given in combination with piperacillin, were equally effective (response rates of 75% (104 of 138 patients) and 74% (101 of 137 patients), respectively). Monotherapy with imipenem had a response rate of 82% (111 of 136 patients) and was as effective as double beta-lactam therapy. Overall antibiotic-related toxicity was minimal, although seizures were associated with high doses of imipenem. Seizures occurred in 3 of 29 patients (10.3%) who were receiving 4 g/d of imipenem, in 3 of 136 patients (2.2%) who were receiving cefoperazone plus piperacillin, in 0 of the 132 patients who were receiving ceftazidime plus piperacillin, and in 1 of 106 patients (0.9%) who were receiving 2 g/d of imipenem (P less than 0.005). The 2-g daily dose of imipenem was as effective as the 4-g daily dose. Diarrhea was more frequent in patients receiving cefoperazone, whereas nausea occurred more often with imipenem. No antibiotic-related hemorrhage or nephrotoxicity was observed. Superinfections caused by beta-lactam-resistant, gram-negative bacilli were uncommon but occurred more frequently with double beta-lactam therapy than with imipenem monotherapy (11 of 268 patients compared with 1 of 135 patients; P = 0.06). Xanthomonas maltophilia superinfections occurred only in patients receiving imipenem (3 of 135 patients compared with 0 of 268 patients; P = 0.03). Imipenem monotherapy was the least expensive therapy. CONCLUSIONS: Cefoperazone and ceftazidime were equally effective when used in combination antibiotic therapy with piperacillin. Twice-daily cefoperazone is less expensive than ceftazidime given three times daily. Monotherapy with imipenem, at a daily dose of 2 g, is as efficacious as double beta-lactam therapy and costs less than combination therapy.

Adolescent↗
PubMed1991

T-cell depletion of HLA-identical transplants in leukemia.

We analyzed the effects of T-cell depletion on the outcome of HLA-identical sibling bone marrow transplants for leukemia by comparing 731 T-cell-depleted transplants with 2,480 non-T-cell-depleted transplants. T-cell depletion decreased acute graft-versus-host disease (GVHD) (relative risk [RR] 0.45; P less than .0001) and chronic (GVHD) (RR 0.56; P less than .0001). However, it increased graft failure (RR 9.29; P less than .0001). Leukemia relapse also was increased. In first remission acute leukemia or chronic phase chronic myelogenous leukemia, leukemia relapse was 2.75 times more likely after T-cell-depleted transplants (P less than .0001). T-cell depletion increased the risk of treatment failure (RR 1.35; P less than .0003) and decreased leukemia-free survival. We also studied controllable variables associated with outcome of T-cell-depleted transplants. The unique findings were that among recipients of T-cell-depleted transplants for early leukemia, radiation doses greater than or equal to 11 Gy (RR 0.54; P less than .01), dose rates greater than 14 cGy/min (RR 0.56; P less than .002), and additional posttransplant immune suppression with cyclosporine alone (RR 0.53; P less than .0006) or cyclosporine plus methotrexate (RR 0.36; P less than .01) were associated with fewer treatment failures. Use of monoclonal antibodies rather than physical techniques for T-cell depletion (RR 2.01; P less than .03) and fractionated radiation (RR 1.69; P less than .05) were associated with increased treatment failure and lower leukemia-free survival. These data may be useful in designing strategies to improve results of T-cell-depleted transplants.

Adolescent↗
PubMed1991

Amplification by the polymerase chain reaction of hypervariable regions of the human genome for evaluation of chimerism after bone marrow transplantation.

We combined the polymerase chain reaction (PCR) with oligonucleotide hybridization as a novel and sensitive technique to evaluate posttransplant chimerism. Specific oligonucleotides for hybridization were synthesized homologous to tandemly repetitive core sequences of regions with a variable number of tandem repeats (VNTRs). Polymorphisms at such loci result from allelic differences in the number of repeats. Primers flanking the repeat region of each of the corresponding VNTRs were used for amplification. Recipient and donor pretransplant DNA and recipient posttransplant DNA were amplified. The resultant fragments were analyzed after gel electrophoresis either by hybridization in-gel or after Southern transfer. To confirm our findings, we also performed standard assays of restriction fragment length polymorphisms (RFLPs). Evaluation of 13 selected cases indicated mixed chimerism (4), complete chimerism (5), recurrence of leukemia (2), and endogenous repopulation of hematopoiesis (2) after marrow transplantation. Sensitivity of the method was determined by mixing various proportions of recipient and donor DNA; the limit of detection of the minor component in a mixture was 0.1%. PCR data correlated with RFLP data in all cases except two in which PCR proved more sensitive than RFLP. PCR amplification of VNTRs combined with oligonucleotide hybridization is a novel technique for documenting posttransplant chimerism and has advantages over RFLP analysis: high sensitivity, use of small amounts of DNA (250 ng), ease of preparation of DNA, elimination of need for restriction enzymes, and the ability to complete studies in 2 days.

Base Sequence↗
PubMed1991

Bone marrow transplantation for severe aplastic anemia.

Allogeneic marrow transplantation from an HLA-identical sibling has proven to be an effective treatment for severe aplastic anemia with restoration of normal hematopoiesis and long-term survival in 70-80% of recipients. Results are related to patient age, with improved survival in younger patients. Marrow transplantation from HLA nonidentical family and unrelated donors has been less successful and is the focus of ongoing clinical research. Graft rejection and graft-versus-host disease (GVHD) remain major problems. A number of pre- and post-transplant immunosuppressive regimens to prevent these complications continue to be studied. The risk of graft rejection is increased in patients who have been transfused before transplant, whereas the risk is decreased with the infusion of larger numbers of transplanted marrow cells. The incidence of graft rejection is 10-32% when cyclophosphamide is used alone as the pretransplant conditioning regimen. The addition of donor buffy coat cells and whole body or limited field radiation have reduced the rate of graft rejection, but increased the incidence of complications such as chronic GVHD and secondary malignancies. GVHD is an immune disorder caused by incompatibility between donor and recipient for histocompatibility antigens. Approximately 18-40% of patients experience moderate to severe acute GVHD. Previous pregnancy in female donors and increasing age of the patient are factors predictive of its development. Methotrexate and cyclosporin have been used most frequently as prophylactic immunosuppressive agents; various combinations of these drugs and prednisone are being evaluated. Symptomatic chronic GVHD occurs in approximately 25% of recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Aplastic↗
PubMed1990

T-cell depletion for bone marrow transplantation: effects on graft rejection, graft-versus-host disease, graft-versus-leukemia, and survival.

T-cell depletion of the donor bone marrow offers the most effective approach yet reported to prevent graft-versus-host disease and its associated mortality. This approach has allowed histoincompatible bone marrow transplants for children with immunodeficiency states. It has been more difficult to apply T-cell depletion to bone marrow transplants for leukemia. Failure of engraftment and leukemia relapse are more frequent than with transplants of unmodified bone marrow. Hopefully more effective immunosuppressive and antileukemic preparative regimens can be developed to allow successful application of T-cell-depleted transplants and effective prevention of graft-versus-host disease.

Bone Marrow Cells↗
PubMed1990

Ofloxacin versus vancomycin/polymyxin for prevention of infections in granulocytopenic patients.

INTRODUCTION: The efficacy and safety of oral ofloxacin were compared with those of vancomycin/polymyxin for prophylaxis of bacterial infections in granulocytopenic patients undergoing chemotherapy for hematologic malignancy. PATIENTS AND METHODS: Antimicrobial prophylaxis was begun at the time of initiation of chemotherapy. Thirty patients received ofloxacin tablets (300 mg orally every 12 hours) plus a nystatin suspension. Thirty-two patients received vancomycin capsules (500 mg orally every eight hours) and polymyxin capsules (100 mg orally every eight hours) plus a nystatin suspension. RESULTS: In the group of patients receiving ofloxacin, there were a lower number of acquired gram-negative bacillary organisms per patient (0.13 versus 1.37, p less than 0.00005), fewer patients with documented infection (11 of 30 versus 21 of 32, p = 0.04), and fewer cases of gram-negative septicemia (zero of 30 versus five of 32, p = 0.05). Ofloxacin was also better tolerated (24 of 30 versus 10 of 32 patients highly compliant, p = 0.01) and associated with fewer gastrointestinal side effects (one of 30 versus nine of 32 patients with gastrointestinal side effects, p = 0.01) than vancomycin/polymyxin. However, except for a reduction of Staphylococcus aureus colonization and infection by ofloxacin, neither ofloxacin nor vancomycin/polymyxin was effective in eliminating colonization or infection with viridans group streptococci, coagulase-negative staphylococci, or other gram-positive organisms. Only three isolates of ofloxacin-resistant gram-negative bacteria (Pseudomonas fluorescens, Pseudomonas putida, and Enterobacter aerogenes) were isolated from surveillance cultures, but none caused infection. CONCLUSION: These results suggest that oral ofloxacin is a more tolerable and efficacious alternative to vancomycin/polymyxin for prevention of serious gram-negative bacillary infections in granulocytopenic patients. More effective prophylaxis of gram-positive infections, however, is still needed.

Adolescent↗
PubMed1990

Bone marrow transplantation using unrelated donors for patients with advanced leukemia or bone marrow failure.

Thirty-four patients received bone marrow transplants from unrelated donors. Donors and recipients were phenotypically matched for 6 of 6 HLA-A, B, and DR antigens in 27 cases and at 5 of 6 antigens in 7 cases. Twenty-three patients had leukemia, six had myelodysplasia, and five had aplastic anemia. Twenty-four patients had durable engraftment. Five died of sepsis prior to engraftment. Five patients failed to engraft; 2 of these patients had autologous bone marrow recovery. Seventeen patients developed grade greater than or equal to II acute graft-versus-host disease for an actuarial probability of 67 +/- 20%. The severity of acute graft-versus-host disease and its mortality appeared increased for recipients matched for 5 of 6 HLA-A, B, and DR antigens. Of the 34 patients, 13 (38%) are alive; actuarial survival beyond 6 months is 44 +/- 17%. None of the 25 leukemia and myelodysplasia patients achieving engraftment have relapsed. For leukemia and myelodysplasia recipients of 6 of 6 HLA-matched grafts, actuarial survival at 6 months was 55 +/- 21% compared with 14 +/- 26% for recipients matched for 5 of 6 HLA loci (P = 0.19). Infection and acute graft-versus-host disease were the primary causes of death in the engrafted patients. Survival for aplastic anemia patients was 20%. Late deaths due to pneumonia and bronchiolitis obliterans occurred after one year in 2 patients. Closely matched unrelated donor bone marrow transplants are associated with a higher incidence of graft failure and graft-versus-host disease than typically reported for transplants from HLA-identical siblings, but these preliminary data suggest a lower rate of relapse.

Acute Disease↗
PubMed1990

Bone marrow transplantation for severe aplastic anemia. Effect of a preparative regimen of cyclophosphamide-low-dose total-lymphoid irradiation and posttransplant cyclosporine-methotrexate therapy.

Twenty-nine patients with severe aplastic anemia were entered into a study of pre- and posttransplant immunosuppressive therapy for bone marrow transplantation. Four of twenty-five previously transfused recipients prepared with cyclophosphamide 200 mg/kg and total-lymphoid irradiation 3 Gy experienced graft failure, indicating that this regimen was inadequate to ensure sustained engraftment. Posttransplant treatment with cyclosporine and methotrexate resulted in an actuarial incidence for grade greater than or equal to 2 graft-versus-host disease of 22 +/- 16%. Actuarial survival was 78 +/- 15%. These data indicate that more effective treatment is necessary to prevent graft failure, but since many patients can be successfully retransplanted, overall survival is comparable to other recent studies.

Adolescent↗
PubMed1990

Thyroid function tests in patients undergoing bone marrow transplantation.

Thyroid function was studied prospectively in 27 patients receiving bone marrow transplants to determine the effect of this procedure and its sequelae on serum thyroid hormone levels and thyrotropin secretion. Serum triiodothyronine and free triiodothyronine concentrations declined to subnormal levels in nearly all of the patients; free thyroxine concentration became subnormal in 15 patients. At the time of the nadir of the serum T3 concentration, serum thyrotropin concentration, measured by a sensitive immunoradiometric assay, declined significantly and became subnormal in nine patients. The data suggest that the reduction of serum thyroxine levels after transplantation is attributable, at least in part, to inhibition of thyrotropin secretion.

Adult↗