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Biomedical subjects

Charles A Schiffer

Publications and source records attributed to Charles A Schiffer.

At least 19 recordsLinked to original sources
PubMed2006

Fifty years of clinical research by the leukemia committee of the cancer and leukemia group B.

Progress in the care of patients with leukemia has been one of the great success stories in the field of oncology, and clinical research in leukemia has been the "flagship" of the Cancer and Leukemia Group B since the inception of this organization. Lessons learned from the founders' emphasis on childhood and adult leukemia have been extended broadly over the past 50 years to virtually all types of malignant diseases, and the Leukemia Committee has continued to provide leadership and key contributions. The Leukemia Committee is focused on the individualization of treatment based on distinctive biological and clinical characteristics with the aim of increasing efficacy and decreasing nonspecific toxicity. Our clinical trials in leukemia and myeloma have shifted from primarily empirically derived comparisons of different chemotherapeutic regimens to testing novel concepts such as the role of dose intensity, inhibition of specific mechanisms of drug resistance, the use of hematopoietic growth factors and monoclonal antibodies, and the utility of targeted agents. The Cancer and Leukemia Group B was the pioneer among the cooperative groups in the creation of centralized tissue repositories and the incorporation of correlative laboratory studies as an integral feature of clinical trials, a practice now termed "translational research." Considerable effort has focused on the identification of important pretreatment characteristics, such as morphologic features, immunophenotype, chromosomal abnormalities, and molecular defects, which are significantly associated with outcome in multivariable analyses and which enhance our understanding for the complex biology of these diseases.

Biomedical Research↗
PubMed2006

2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline.

PURPOSE: To update the 2000 American Society of Clinical Oncology guideline on the use of hematopoietic colony-stimulating factors (CSF). UPDATE METHODOLOGY: The Update Committee completed a review and analysis of pertinent data published from 1999 through September 2005. Guided by the 1996 ASCO clinical outcomes criteria, the Update Committee formulated recommendations based on improvements in survival, quality of life, toxicity reduction and cost-effectiveness. RECOMMENDATIONS: The 2005 Update Committee agreed unanimously that reduction in febrile neutropenia (FN) is an important clinical outcome that justifies the use of CSFs, regardless of impact on other factors, when the risk of FN is approximately 20% and no other equally effective regimen that does not require CSFs is available. Primary prophylaxis is recommended for the prevention of FN in patients who are at high risk based on age, medical history, disease characteristics, and myelotoxicity of the chemotherapy regimen. CSF use allows a modest to moderate increase in dose-density and/or dose-intensity of chemotherapy regimens. Dose-dense regimens should only be used within an appropriately designed clinical trial or if supported by convincing efficacy data. Prophylactic CSF for patients with diffuse aggressive lymphoma aged 65 years and older treated with curative chemotherapy (CHOP or more aggressive regimens) should be given to reduce the incidence of FN and infections. Current recommendations for the management of patients exposed to lethal doses of total body radiotherapy, but not doses high enough to lead to certain death due to injury to other organs, includes the prompt administration of CSF or pegylated G-CSF.

Age Factors↗
PubMed2006

Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia.

The myelodysplastic syndromes (MDSs) are heterogeneous with respect to clinical characteristics, pathologic features, and cytogenetic abnormalities. This heterogeneity is a challenge for evaluating response to treatment. Therapeutic trials in MDS have used various criteria to assess results, making cross-study comparisons problematic. In 2000, an International Working Group (IWG) proposed standardized response criteria for evaluating clinically significant responses in MDS. These criteria included measures of alteration in the natural history of disease, hematologic improvement, cytogenetic response, and improvement in health-related quality of life. The relevance of the response criteria has now been validated prospectively in MDS clinical trials, and they have gained acceptance in research studies and in clinical practice. Because limitations of the IWG criteria have surfaced, based on practical and reported experience, some modifications were warranted. In this report, we present recommendations for revisions of some of the initial criteria.

Humans↗
PubMed2006

Granulocyte transfusion.

PURPOSE OF REVIEW: Granulocyte transfusions have been used for more than four decades. Several issues have complicated the analysis of previous studies, including the utilization of improved antimicrobials, the effects of recipient alloimmunization and variable cell dose. The use of granulocyte colony-stimulating factor for donor stimulation has revived interest in granulocyte transfusion. The aim of this review is to evaluate the most recent studies in granulocyte transfusion therapy and their clinical applicability. RECENT FINDINGS: Granulocyte colony-stimulating factor use has increased the granulocyte yield by approximately fourfold. Multiple recent studies have shown that granulocyte transfusions can be helpful in controlling severe infections progressing despite the use of appropriate antibiotics, with a response rate of 40-80% with variability in results depending on patient characteristics. This benefit is limited to a small patient population as the incidence of prolonged reversible neutropenia is relatively small. Severe side effects have been rare in those studies. SUMMARY: Granulocyte transfusions are beneficial in neutropenic patients with severe uncontrolled infection. The underlying disease process is the major determinant of outcome in these patients. Because granulocyte transfusions are not commonly used, centers are not currently able to provide transfusions in a timely fashion. Nonalloimmunized patients can receive cells from nonmatched ABO compatible donors, while alloimmunized patients should receive granulocytes from either HLA-matched donors or donors selected by leukoagglutination or lymphocytotoxicity crossmatching. Further studies are needed to clarify the optimal starting time and frequency of transfusions, and the best method for identifying donor-recipient compatibility.

ABO Blood-Group System↗
PubMed2006

Clinical issues in the management of patients with myelodysplasia.

The management of patients with myelodysplasia (MDS) can be quite complex and varies according to both the clinical manifestations in individual patients as well as complicating medical conditions. Allogeneic stem cell transplantation is the only curative treatment, but because of the older age of the patient population must be applied selectively, particularly in those with lower risk MDS as well as in patients whose clinical course is more frankly "preleukemic." Issues pertinent to the use of 5-azacytidine, decitabine and lenalidomide in patients with both higher and lower International Prognostic Staging System (IPSS) stage disease are discussed.

Age Factors↗
PubMed2005

Prognostic factors and outcome of core binding factor acute myeloid leukemia patients with t(8;21) differ from those of patients with inv(16): a Cancer and Leukemia Group B study.

PURPOSE: Because both t(8;21) and inv(16) disrupt core binding factor (CBF) in acute myeloid leukemia (AML) and confer relatively favorable prognoses, these cytogenetic groups are often treated similarly. Recent studies, however, have shown different gene profiling for the two groups, underscoring potential biologic differences. Therefore, we sought to determine whether these two cytogenetic groups should also be considered separate entities from a clinical standpoint. PATIENTS AND METHODS: We analyzed 144 consecutive adults with t(8;21) and 168 with inv(16) treated on Cancer and Leukemia Group B front-line studies. We compared pretreatment features, probability of achieving complete remission (CR), overall survival (OS) and cumulative incidence of relapse (CIR) between the two groups. RESULTS: With a median follow-up of 6.4 years, for CBF AML as a whole, the CR rate was 88%, 5-year OS was 50% and CIR was 53%. After adjusting for covariates, patients with t(8;21) had shorter OS (hazard ratio [HR] = 1.5; P = .045) and survival after first relapse (HR = 1.7; P = .009) than patients with inv(16). Unexpectedly, race was an important predictor for t(8;21) AML, in that nonwhites failed induction more often (odds ratio = 5.7; P = .006) and had shorter OS than whites when certain secondary cytogenetic abnormalities were present. In patients with t(8;21) younger than 60 years, type of induction also correlated with relapse risk. For inv(16) AML, secondary cytogenetic abnormalities (especially +22) and male sex predicted better outcome. CONCLUSION: When the prognostic impact of race, secondary cytogenetic abnormalities, sex, and response to salvage treatment is considered, t(8;21) and inv(16) AMLs seem to be distinct clinical entities and should be stratified and reported separately.

Acute Disease↗
PubMed2005

"Acute myelogenous leukemia like" translocations in CML blast crisis: two new cases of inv(16)/t(16;16) and a review of the literature.

We describe two patients with CML blast crisis with clonal evolution affecting 16q22 (t(16;16)(p13;q22) and inv(16)(p13;q22), abnormalities of core binding factor, usually found in de novo acute myeloid leukemia (AML)). The bone marrow of both cases showed myelomonocytic (M4) differentiation and eosinophilia. Both patients had prominent extramedullary disease and had poor response to treatment. A literature search focused on patients with CML and additional chromosome changes more typical of AML, revealed that the morphology of the blasts correlated with the finding typical of the underlying "AML" cytogenetic abnormality and an overall very poor clinical outcome, even in the groups with "favorable" AML type translocations.

Blast Crisis↗
PubMed2005

Factors affecting posttransfusion platelet increments, platelet refractoriness, and platelet transfusion intervals in thrombocytopenic patients.

A variety of patient and product-related factors influenced the outcome of 6379 transfusions given to 533 patients in the Trial to Reduce Alloimmunization to Platelets (TRAP). Responses measured were platelet increments, interval between platelet transfusions, and platelet refractoriness. Patient factors that improved platelet responses were splenectomy and increasing patient age. In contrast, at least 2 prior pregnancies, male gender, splenomegaly, bleeding, fever, infection, disseminated intravascular coagulation, increasing height and weight, lymphocytotoxic antibody positivity, an increasing number of platelet transfusions, or receiving heparin or amphotericin were associated with decreased posttransfusion platelet responses. Platelet factors that were associated with improved platelet responses were giving ABO-compatible platelets, platelets stored for 48 hours or less, and giving large doses of platelets while ultraviolet B (UV-B) or gamma irradiation decreased platelet responses. However, in alloimmunized lymphocytoxic antibody-positive patients, the immediate increment to UV-B-irradiated platelets was well maintained, whereas all other products showed substantial reductions. Refractoriness to platelet transfusions developed in 27% of the patients. Platelet refractoriness was associated with lymphocytotoxic antibody positivity, heparin administration, fever, bleeding, increasing number of platelet transfusions, increasing weight, at least 2 pregnancies, and male gender. The only factors that reduced platelet refractoriness rates were increasing the dose of platelets transfused or transfusing filtered apheresis platelets.

Blood Platelets↗
PubMed2004

A single dose of rasburicase is sufficient for the treatment of hyperuricemia in patients receiving chemotherapy.

Hydration, urinary alkalization, and allopurinol are the standard of care in the treatment and prevention of hyperuricemia. Rasburicase is a new alternative for the management of hyperuricemia in cancer patients. Criteria for the use of rasburicase were developed by the Hematology/Oncology Pharmacy and Therapeutics Subcommittee of the Detroit Medical Center and implemented in 2003. The guidelines limit rasburicase use to one dose, with additional doses as needed, compared to the five doses recommended by the manufacturer, in cancer patients with hyperuricemia and bulky tumor who require immediate chemotherapy. During the period of March to September 2003, eight patients received rasburicase, according to the guidelines, for the management of hyperuricemia. One dose of rasburicase produced a rapid and sustained therapeutic effect of lowering the plasma uric acid levels in all patients. The levels remained below 4 mg/dL throughout the administration of chemotherapy for up to 96 h. Utilizing the guidelines resulted in a significant cost savings of 100,000 US dollars.

Adult↗
PubMed2004

Sequential multiagent chemotherapy is not superior to high-dose cytarabine alone as postremission intensification therapy for acute myeloid leukemia in adults under 60 years of age: Cancer and Leukemia Group B Study 9222.

The Cancer and Leukemia Group B (CALGB) study 9222 tested the hypothesis that treatment intensification of acute myeloid leukemia (AML) in first remission with multiple chemotherapy agents is superior to high-dose cytarabine (HiDAC) alone. We enrolled 474 patients younger than 60 years old with untreated de novo AML. Daunorubicin and cytarabine resulted in complete remission (CR) in 342 patients (72%), and 309 of these patients were randomized to receive one of 2 different intensification regimens. The first regimen consisted of 3 courses of HiDAC. The second regimen consisted of one course of HiDAC, a second course with etoposide and cyclophosphamide, and a third course with diaziquone and mitoxantrone. After a median follow-up time of 8.3 years, the median survival for all randomized patients was 2.8 years (95% CI, 1.9-6.8 years). There was no difference in disease-free survival (DFS) between the 2 regimens (P = .66). The median DFS was 1.1 years (95% CI, 0.9-1.7 years) for patients receiving HiDAC and 1.0 year (95% CI, 0.9-1.3 years) for those receiving multiagent chemotherapy. Cytogenetics was the only pretreatment characteristic prognostic for DFS, but there was no evidence of a differential treatment effect within cytogenetic risk groups. Toxicity was greater with multiagent chemotherapy. These 2 postremission regimens produced similar outcomes.

Acute Disease↗
PubMed2004

Outcome of induction and postremission therapy in younger adults with acute myeloid leukemia with normal karyotype: a cancer and leukemia group B study.

PURPOSE: Evaluate the outcome of induction and postremission therapy in adults younger than 60 years with normal cytogenetics acute myeloid leukemia (AML). PATIENTS AND METHODS: In 490 patients, induction included cytarabine and daunorubicin (AD) or cytarabine and escalated doses of daunorubicin and etoposide +/- PSC-833 (ADE/ADEP). Intensification included one cycle of high-dose cytarabine (HDAC) followed by etoposide/cyclophosphamide and mitoxantrone/diaziquone (group I), three HDAC cycles (group II), four intermediate-dose cytarabine (IDAC) or HDAC cycles (group III), or one HDAC/etoposide cycle and autologous stem-cell transplantation (ASCT; group IV). RESULTS: Of 350 patients receiving AD, 73% achieved complete remission (CR), compared with 82% of 140 receiving ADE/ADEP (P = .04). Splenomegaly was associated with a lower CR rate (P < .001), and ADE/ADEP, with a higher CR rate in younger patients (P = .005). The 5-year disease-free survival (DFS) rate was 28% each for intensification groups I and II, compared with 41% and 45% for groups III and IV, respectively (P = .02). The 5-year cumulative incidence of relapse (CIR) was 62% and 67% for groups I and II, respectively, compared with 54% and 44% for groups III and IV, respectively (P = .049). The type of postremission intensification remained significant for DFS and CIR in multivariable analysis. CONCLUSION: In younger adults with normal cytogenetics AML, splenomegaly predicts a lower CR rate, and the postremission strategies of either four cycles of I/HDAC or one cycle of HDAC/etoposide followed by ASCT are associated with improved DFS and reduced relapse compared with therapies that include fewer cycles of cytarabine or no transplantation.

Acute Disease↗
PubMed2004

Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia: an updated retrospective comparative analysis of CALGB 9712 and CALGB 9011.

Fludarabine and rituximab combination therapies in chronic lymphocytic leukemia (CLL) have yielded promising early results, but no comparative efficacy data relative to standard fludarabine treatment regimens have been reported. To assess the effect of the addition of rituximab to fludarabine therapy, we retrospectively compared the treatment outcome of patients with similar clinical characteristics enrolled on 2 multicenter clinical trials performed by the Cancer and Leukemia Group B and the US Intergroup that used fludarabine and rituximab (CALGB 9712, n = 104) or fludarabine (CALGB 9011, n = 178). In multivariate analyses controlling for pretreatment characteristics, the patients receiving fludarabine and rituximab had a significantly better progression-free survival (PFS; P < .0001) and overall survival (OS; P = .0006) than patients receiving fludarabine therapy. Two-year PFS probabilities were 0.67 versus 0.45, and 2-year OS probabilities were 0.93 versus 0.81. Infectious toxicity was similar between the 2 treatment approaches. These comparative data are retrospective and could be confounded by differences in supportive care or dissimilar enrollment of genetic subsets on each trial. Confirmation of these findings will require a prospective randomized trial comparing fludarabine and rituximab to fludarabine.

Adult↗
PubMed2004

Intensive chemotherapy with and without cranial radiation for Burkitt leukemia and lymphoma: final results of Cancer and Leukemia Group B Study 9251.

BACKGROUND: The objective of the current study was to evaluate the efficacy of intensive chemotherapy with and without cranial radiation for central nervous system (CNS) prophylaxis in adults with Burkitt leukemia or lymphoma. METHODS: Patients received 18 weeks of therapy. Prophylactic cranial radiation (2400 centigrays) and 12 doses of triple intrathecal chemotherapy were administered to the first cohort of patients. A subsequent cohort received the same therapy, with the exceptions that intrathecal therapy was reduced to six doses and radiotherapy was administered only to high-risk individuals. RESULTS: The median follow-up durations were 6.8 years in Cohort 1 and 4.1 years in Cohort 2. Three occurrences of transverse myelitis, 2 severe neuropathies, 3 cases of aphasia, and 1 case of blindness were documented in the first cohort of 52 patients (Cohort 1). In the subsequent cohort of 40 patients (Cohort 2), none of these occurrences were observed, and patients experienced less neurologic toxicity overall (61% vs. 26%; P=0.001). Responses were similar, and the 3-year event-free survival rate was 0.52 (95% confidence interval, 0.38-0.65) for Cohort 1 and 0.45 (0.29-0.60) for Cohort 2. CONCLUSIONS: Intensive, short-duration chemotherapy with less intensive CNS prophylaxis led to control at this sanctuary site with little neurotoxicity and may be curative for adults with Burkitt leukemia or lymphoma.

Adolescent↗
PubMed2004

Differences in prognostic factors and outcomes in African Americans and whites with acute myeloid leukemia.

Whites have a more favorable prognosis than African Americans for a number of cancers. The relationship between race and outcome is less clear in acute myeloid leukemia (AML). Using data from 7 Cancer and Leukemia Group B studies initiated from 1985 to 1997, we conducted a retrospective cross-sectional analysis of 2570 patients (270 African American and 2300 white) with de novo AML who received induction chemotherapy. African Americans were younger than whites (48 versus 54 years, P <.001). African Americans also had different cytogenetic risk group distributions than whites (P <.001): they were more commonly classified in the favorable (23% versus 14%) and unfavorable (31% versus 23%) groups, and less commonly classified in the intermediate group (47% versus 63%). African American men had a lower complete remission (CR) rate (54%, compared with 64% for white men, 65% for white women, and 70% for African American women, P =.001) and a worse overall survival compared with all other patients (P =.004), when known risk factors are taken into account. African Americans and whites with AML differ with respect to important prognostic factors. African American men have worse CR rates and overall survival than whites and African American women, and should be considered a poor-risk group.

Acute Disease↗