Use of point-of-care HbA1c measurement to estimate the level of undiagnosed diabetes mellitus among 67-year-old participants in a cardiovascular screening programme in the municipality of Viborg, Denmark.

AIMS: To determine the prevalence of unidentified diabetes mellitus among 67-year-olds in Denmark participating in a screening programme focusing on cardiovascular disease and diabetes, and to describe glycaemic levels in individuals according to point-of-care HbA1c combined with self-reported diabetes status. METHODS: In this cross-sectional, retrospective, population-based study, all people aged 67 years living in the Viborg municipality were invited to take part in the Viborg Inter-sectorial Screening Programme (VISP), which focuses on cardiovascular disease and diabetes. The VISP study was initiated in August 2014 and is ongoing. During the first 2 years of the programme, we stratified participants into groups based on their self-reported diabetes status and a single HbA1c measurement. RESULTS: A total of 1802 individuals were invited to participate, and 1501 consented, seven of whom were excluded because of missing data (HbA1c or diabetes status), resulting in an 82.9% participation rate (n=1494). Among those reporting not to have diabetes, 3.3% (n=45) had an HbA1c level ≥48 mmol/mol (6.5%). In the same group, 16.7% (n=226) had an HbA1c level of 41-48 mmol/mol (5.9-6.5%). Among those self-reporting the presence of diabetes, 30.1% (n=43) had an HbA1c level ≥58 mmol/mol (7.5%). CONCLUSIONS: The prevalence of unidentified diabetes was 3.3% based on a single HbA1c measurement. Furthermore, 16.7% of those reporting not to have diabetes had an HbA1c level of 41-48 mmol/mol (5.9-6.5%), representing a subgroup with an increased risk of developing diabetes. Among those with self-reported diabetes, 30.1% had an HbA1c level ≥58 mmol/mol (7.5%) and 6.3% had a level >74 mmol/mol (8.9%).

Health-related quality of life in subjects with HCV/HIV coinfection: results from ACTG 5178 study.

Although health-related quality of life (HRQOL) is diminished in HCV/HIV, the relationship between virologic response and maintenance therapy with HRQOL in this population is unknown. ACTG 5178 was a phase 2, randomized trial, with three steps - Step 1: all subjects received pegylated interferon (PEG-IFN)/ribavirin (P/R) for 12 weeks. Step 2: subjects who failed to achieve early viral response (EVR) were randomized to PEG-IFN or observational control for an additional 72 weeks. Step 3: subjects with EVR from step 1 continued on P/R for a total of 72 weeks with 24 weeks follow-up off-therapy. HRQOL, symptom distress and depression levels were measured at multiple time points. In step 1 (n = 329), there was a significant decline in HRQOL in all dimensions. In step 3 (n = 169), the overall HRQOL and three of its eight dimensions (general health, role function and pain score) were increased, and achievement of sustained virologic response was associated with increased general health and cognitive function. In step 2 (n = 85), there was no significant change in HRQOL and no significant difference between groups (PEG-IFN vs observational control). There was a significant decline in HRQOL during the initial 12 weeks of therapy. Thereafter, the HRQOL profile differed for subjects with EVR vs without EVR. Maintenance therapy with PEG-IFN had no impact on the HRQOL.

The incidence, predictors and management of anaemia and its association with virological response in HCV / HIV coinfected persons treated with long-term pegylated interferon alfa 2a and ribavirin.

BACKGROUND: The association of anaemia with outcomes in the HCV/HIV coinfected persons undergoing HCV treatment remains unclear. AIMS: To study the incidence, predictors and management of anaemia, and its association with outcomes among persons treated with pegylated interferon and weight-based ribavirin. METHODS: Retrospective analysis of a prospective controlled treatment trial of HCV/HIV coinfection. RESULTS: Among 329 subjects enrolled, 40% developed anaemia during the first 12-18 weeks of treatment (median haemoglobin decrease at week 4: 2.2 g/dL). Among 169 subjects who achieved early virological response and received therapy for 72 weeks, 55% eventually developed anaemia. However, median haemoglobin levels stayed stable after 12-18 weeks of initial therapy. Among these 169 subjects, 45% were prescribed an erythropoiesis stimulating agent (ESA), with 17% receiving it prior to a drop in haemoglobin meeting protocol definition of anaemia. Only 27% completed the study without any ribavirin dose modification. Age >40 years, lower BMI, zidovudine use and lower entry haemoglobin were significant predictors of anaemia in the multi-covariate model. Among all 329, sustained virological response (SVR) rate was similar in those with or without anaemia (23% vs. 30%; P=0.17) with no evidence of association between anaemia or ESA use and treatment response. CONCLUSIONS: Anaemia is common in HCV/HIV coinfected persons undergoing HCV treatment, and only a minority of them are able to maintain ribavirin dose. Persons with age >40 years, lower baseline haemoglobin and lower baseline BMI should be monitored carefully. Prescription of erythropoiesis stimulating agent is common, but anaemia or erythropoiesis stimulating agent use is not associated with SVR.

Molecular analysis and clinical outcome of adult APL patients with the type V PML-RARalpha isoform: results from intergroup protocol 0129.

The type V (for variable) promyelocytic leukemia retinoic acid receptor (PML-RAR)alpha transcript, found in approximately 8% of adult patients with acute promyelocytic leukemia (APL), is defined molecularly by truncation of PML exon 6 and frequent insertion of genetic material from RARalpha intron 2. To more fully characterize the molecular features of PML-RARalpha V-type transcripts and to determine whether V-form APL patients have a distinct clinical presentation or prognosis, we analyzed 18 adult V-form APL patients enrolled on Intergroup protocol 0129 (INT-0129). Truncations in PML exon 6 ranged from 8 to 146 nucleotides, and 3 to 127 extra nucleotides (1 to 42 extra amino acids) were inserted at the PML exon 6/RARalpha exon 3 junction in 13 cases. No distinguishing morphologic, cytogenetic, or immunophenotypic features of V-form blasts were identified. A total of 5 of 7 patients induced with ATRA and 8 of 11 patients who received chemotherapy for induction achieved complete remission (CR). Six patients have relapsed, 4 after chemotherapy induction and 2 after ATRA. Nine patients (50%) are alive, 6 in continuous CR, 2 after salvage therapy for relapsed or refractory disease, and 1 after alternative treatment following early removal from protocol. Although the failure rate for V-form APL patients was high (61%), the low power of the current study to detect clinically significant differences precludes a meaningful comparison of clinical outcomes between the 18 V-form cases and non-V-form adult APL patients enrolled on INT-0129. (Blood. 2000;95:398-403)

Clinical description of 44 patients with acute promyelocytic leukemia who developed the retinoic acid syndrome.

We examined the incidence, clinical course, and outcome of patients with newly diagnosed acute promyelocytic leukemia (APL) who developed the retinoic acid syndrome (RAS) treated on the Intergroup Protocol 0129, which prospectively evaluated the role of alltrans retinoic acid (ATRA) alone during induction and as maintenance therapy. Forty-four of 167 (26%) patients receiving ATRA for induction developed the syndrome at a median of 11 days of ATRA (range, 2-47). The median white blood cell (WBC) count was 1,450/microL at diagnosis and was 31,000/microL (range, 6,800-72,000/microL) at the time the syndrome developed. ATRA was discontinued in 36 of the 44 patients (82%) and continued in 8 patients (18%), with subsequent resolution of the syndrome in 7 of the 8. ATRA was resumed in 19 of the 36 patients (53%) in whom ATRA was stopped and not in 17 (47%). The syndrome recurred in 3 of those 19 patients, with 1 death attributable to resumption of the drug. Ten of these 36 patients received chemotherapy without further ATRA, and 8 achieved complete remission (CR). Among 7 patients in whom ATRA was not restarted and were not treated with chemotherapy, 5 achieved CR and 2 died. Two deaths were definitely attributable to the syndrome. No patient receiving ATRA as maintenance developed the syndrome. (Blood. 2000;95:90-95)

Long-term survival in acute myeloid leukemia: the Eastern Cooperative Oncology Group experience.

BACKGROUND: The data base of the Eastern Cooperative Oncology Group (ECOG) provides access to data on a large adult patient population drawn from more than 25 major university institutions and hundreds of participating hospitals. Extensive medical files are maintained at the ECOG Coordinating Center and are updated regularly. METHODS: Data on 1414 eligible patients with acute myeloid leukemia (AML), treated on 6 ECOG protocols during the period 1976-1994, were reviewed to determine the number of long-term survivors (LTS) and to identify factors that predicted LTS. Disease free survival and factors impacting quality of life were examined as well. RESULTS: Of the 1414 patients, 274 survived for > or = 3 years and were considered LTS. A logistic regression analysis revealed that factors predicting LTS included age < 55 years, female gender, treatment between 1985 and 1990, white blood cell count < 10,000 cells/mm3, and hemoglobin > 10 g/dL. Disease free survival improved with escalating intensity of therapy. Quality-of-life data showed that infections were fairly common. Significant graft-versus-host disease occurred in 6 of 40 patients who received allogeneic bone marrow transplantation and contributed to the deaths of 4 individuals. Information on employment, insurance, social or marital difficulties, and psychosocial issues was more difficult to obtain. CONCLUSIONS: Prognosis in AML is a complex interaction involving the cellular origin of the malignant clone, morphology, and evolving therapeutic strategies. The most recent ECOG studies incorporate these variables and should provide additional insights into factors affecting LTS in patients with AML.

All-trans-retinoic acid in acute promyelocytic leukemia.

BACKGROUND: All-trans-retinoic acid induces complete remission in acute promyelocytic leukemia. However, it is not clear whether induction therapy with all-trans-retinoic acid is superior to chemotherapy alone or whether maintenance treatment with all-trans-retinoic acid improves outcome. METHODS: Three hundred forty-six patients with previously untreated acute promyelocytic leukemia were randomly assigned to receive all-trans-retinoic acid or daunorubicin plus cytarabine as induction treatment. Patients who had a complete remission received consolidation therapy consisting of one cycle of treatment identical to the induction chemotherapy, then high-dose cytarabine plus daunorubicin. Patients still in complete remission after two cycles of consolidation therapy were then randomly assigned to maintenance treatment with all-trans-retinoic acid or to observation. RESULTS: Of the 174 patients treated with chemotherapy, 120 (69 percent) had a complete remission, as did 124 of the 172 (72 percent) given all-trans-retinoic acid (P=0.56). When both induction and maintenance treatments were taken into account, the estimated rates of disease-free survival at one, two, and three years were 77, 61, and 55 percent, respectively, for patients assigned to chemotherapy then all-trans-retinoic acid; 86, 75, and 75 percent for all-trans-retinoic acid then all-trans-retinoic acid; 75, 60, and 60 percent for all-trans-retinoic acid then observation; and 29, 18, and 18 percent for chemotherapy then observation. By intention-to-treat analysis, the rates of overall survival at one, two, and three years after entry into the study were 75, 57, and 50 percent, respectively, among patients assigned to chemotherapy, and 82, 72, and 67 percent among those assigned to all-trans-retinoic acid (P= 0.003). CONCLUSIONS: All-trans-retinoic acid as induction or maintenance treatment improves disease-free and overall survival as compared with chemotherapy alone and should be included in the treatment of acute promyelocytic leukemia.

Induction chemotherapy with cisplatin, fluorouracil, and high-dose leucovorin for squamous cell carcinoma of the head and neck: long-term results.

PURPOSE: A phase II trial of cisplatin, fluorouracil, and leucovorin (PFL) induction chemotherapy in patients with locally advanced squamous cell carcinomas of the head and neck region (HNCA). PATIENTS AND METHODS: One hundred two patients (stage III/IV, previously untreated) were treated with induction PFL. Patients with resectable primary tumor site lesions and clinical complete response (CR) were offered radiotherapy (RT) without surgery to the primary tumor site. Response, toxicity, local-regional therapy, survival, and preservation of the primary tumor site were assessed. RESULTS: Among 279 courses, the overall response rate was 81%. Nineteen (19%) failed to respond, including three who died during therapy. Sixty-seven (69%) of 97 with assessable primary lesions had a clinical CR at the primary tumor site. Pathologic CR was recorded in 46 of 55 (84%) clinical CR patients who had biopsies performed on the primary tumor site. Toxicities resulted in unexpected hospitalizations in 19% of cases. After definitive local-regional therapy, 84 (82%) were disease-free including 71 (69%) with preserved primary tumor site anatomy. With a median follow-up time of 63 months, the cause-specific, overall (OS), and failure-free survival (FFS) rates at 5 years are 58%, 52%, and 51%. Local failure occurred in 29 of 102 (29%) and the local control rate at 5 years was 68%. CONCLUSION: PFL has significant activity with acceptable toxicity in patients with advanced disease who have a good performance status. Preservation of the primary tumor site could be achieved without apparent loss of local control or survival. Management of neck disease by surgery or RT must be individualized and separate from management of primary tumor. Survival compares favorably with similar trials of induction chemotherapy or chemoradiotherapy.

Association of PML-RAR alpha fusion mRNA type with pretreatment hematologic characteristics but not treatment outcome in acute promyelocytic leukemia: an intergroup molecular study.

In each case of acute promyelocytic leukemia (APL) one of three PML-RAR alpha mRNA types is produced, depending on the break/fusion site in the PML gene that is linked to a common RAR alpha gene segment: a short (S)-form type, PML exon 3 RAR alpha exon 3; a long (L)-form type, PML exon 6 RAR alpha exon 3; or a variable (V)-form type, variably deleted PML exon 6 RAR alpha exon 3. We evaluated whether PML-RAR alpha mRNA type is associated with distinct pretreatment clinical characteristics and therapeutic outcome in previously untreated adult APL patients registered to protocol INT 0129 by the Eastern Cooperative Oncology Group, the Southwest Oncology Group, and the Cancer and Leukemia Group B. Of 279 clinically eligible cases, 230 were molecularly evaluable, and of these, 111 were randomized to receive remission induction therapy with all-trans retinoic acid (ATRA) and 119 with conventional chemotherapy. Nine cases not excluded by central pathology review were PML-RAR alpha negative, and notably, none of five of these cases treated with ATRA achieved complete remission (CR). Among 221 PML-RAR alpha-positive cases, there were 82 S-form cases (37%), 121 L-form cases (55%), and 18 V-form cases (8%). Before any antileukemic therapy, the S-form type, compared with the L-form type, was associated with higher values for the white blood cell (WBC) count (median 2,500/microL v 1,600/microL; P = .009), the percentage of blood blasts plus promyelocytes (median 29% v 8.5%; P = .03), and the absolute blood blasts plus promyelocytes (884/microL v 126/microL; P = .019). Also, an increased percentage of S-form versus L-form cases had the M3 variant phenotype, 24% v 12% (P = .036). There were no differences between S-form and L-form cases in either CR rate (79% v 69%; P = .14) or disease free survival distribution (multivariate analysis adjusting for the association of S-form type and higher WBC count; P = .40). We conclude that the S-form type is associated with previously-identified adverse risk WBC parameters but that the identification of the S-form or L-form type of PML-RAR alpha mRNA, per se, does not predict clinical outcome or add to the value of an increased WBC count as a negative prognostic indicator in APL patients.

In vivo adsorption of isohemagglutinins with fresh frozen plasma in major ABO-incompatible bone marrow transplantation.

Despite techniques to deplete red cells from major ABO-incompatible allogeneic bone marrow (BM) or to remove recipient isohemagglutinins (IHGs) before transplantation, delayed erythropoiesis and hemolysis, red cell aplasia, and increased red cell transfusion requirements may occur. Twenty-nine recipients of major ABO-incompatible allografts received donor-type frozen fresh plasma (FFP) infusions twice daily to adsorb IHGs in vivo. Engraftment and transfusion requirements were compared between the 29 FFP-treated major ABO-incompatible allograft recipients, 5 recipients of major ABO-incompatible BM who did not receive FFP infusions, 35 recipients of minor ABO-incompatible BM, and 172 recipients of ABO-compatible BM. No significant differences in either transfusion requirements or engraftment were seen in the FFP-treated major ABO-incompatible vs. minor ABO-incompatible or ABO-compatible groups (p values > or = 0.10). The infusion of donor-type FFP represents a simple, effective treatment strategy to neutralize IHGs and to prevent adverse consequences of major ABO incompatibility in the setting of allogeneic BM transplantation. The role of this strategy in the care of patients receiving ABO-incompatible solid organs remains to be defined.

Acute myeloid leukemia with translocation (8;21). Cytomorphology, dysplasia and prognostic factors in 41 cases. AML Cooperative Group and ECOG.

The translocation t(8;21) is one of the most common structural aberrations in acute myeloid leukemia (AML). Excellent response rates and a better relapse-free survival have been described. We analyzed specific morphologic and cytochemical features including dysplasia and other prognostic factors in 41 patients with AML and t(8;21) who underwent aggressive chemotherapy in two national cooperative group studies. Five patients were classified as AML M1 and 36 as AML M2 according to the FAB criteria. Auer rods were detected in 28 patients (68%), however in only 16 patients were they "thin and elongated" as has been described as typical for t(8;21). The presence or absence of Auer rods did not appear to be associated with disease-free survival in this sample. Dysgranulopoiesis was detected in 31/41 patients (90%); five of these patients additionally had dyserythropoiesis (12%). In six cases (15%), dysmegakaryopoiesis was seen in combination with dysgranulopoiesis. Only one patient had trilineage dysplasia. Dysplastic features had no influence on prognosis. Additional cytogenetic abnormalities were detected in 24/41 patients. Twelve male (48%) and four female (25%) had a loss of a sex chromosome. This was correlated with a better disease-free survival (p = 0.039). The complete remission rate (CR) to chemotherapy was 90%. The early death rate was 10%. Disease-free survival of the complete responders was 60% at two years with no relapses observed in ten patients with 2-6 years of follow up. This favorable disease-free survival was observed with a variety of post-induction regimens and t(8;21) had been detected as an independent factor for good prognosis. The need for very intensive therapy, such as bone marrow transplantation, is unanswered at this time.

Sources and sequelae of bacterial contamination of hematopoietic stem cell components: implications for the safety of hematotherapy and graft engineering.

BACKGROUND: It is important to compare the incidence of bacterial contamination of components collected from the peripheral blood or bone marrow (BM), as well as of components processed with or without cell selection or depletion, and to evaluate the sequelae of such contamination. STUDY DESIGN AND METHODS: Bacterial contamination rates were compared in 1380 untreated autologous peripheral blood progenitor cells (PBPCs), 291 untreated autologous BM samples, 916 monoclonal antibody (MoAb)-treated autologous and allogeneic BM samples, and in 45 autologous PBPC components from which the CD34+ cells were selected. Bacterial cultures were performed at sequential time points during the processing of MoAb-treated BM. RESULTS: Bacterial contamination was documented in 44 of 2632 components from 1593 patients (1.67% of components, 2.76% of patients) before cryopreservation. Although only 0.65% of untreated PBPCs were contaminated before cryopreservation, each patient was more likely to have given a contaminated PBPC component than a contaminated BM component (2.41% vs. 0%, p < 0.01). Bacterial contamination of MoAb-treated BM was greater during or after manipulation than it was before (2.33% vs. 0.77%, p < 0.05). At thawing, contamination was documented in 42 (1.97%) of 2136 components cultured. Ten (13.7%) of 73 patients who received hematopoietic progenitor cells that were contaminated before cryopreservation or at thawing developed fever or positive blood cultures within 48 hours of transfusion. Fever was associated with bacteremia in two cases, but no irreversible clinical sequelae were noted. CONCLUSION: These studies suggest that, despite careful attention to sterile procedures, low-level contamination of hematopoietic stem cell components can be introduced before or during manipulation as well as at thawing, and that standards for monitoring of the procedures for collection, processing, cryopreservation, thawing, and transfusion of hematopoietic progenitor cells are necessary.

Characterization of reactions after transfusion of cellular blood components that are white cell reduced before storage.

BACKGROUND: During the storage of cellular components before transfusion, cytokines that may mediate transfusion reactions are released from white cells (WBCs). Adverse effects of transfused cellular blood components therefore depend not only on the number of residual WBCs in blood components, but also on the timing of WBC reduction. STUDY DESIGN AND METHODS: Febrile nonhemolytic transfusion reactions (FNHTRs), allergic reactions, and other reactions were characterized in recipients of 4728 units of red cells (RBCs) and 3405 bags of single-donor apheresis platelets (SDAPs), all of which underwent prestorage WBC reduction. To delineate the impact of prestorage versus poststorage WBC reduction of RBCs on transfusion reactions, these results were compared with reactions occurring after the transfusion to similar recipients of 6447 bags of RBCs that underwent poststorage WBC reduction by bedside filtration and 5197 units of SDAPs that underwent prestorage WBC reduction. The levels of interleukin (IL) 1 beta, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) were measured in a subset of 20 implicated cellular blood components at the time of transfusion reactions and correlated with the duration of storage before transfusion. RESULTS: The incidence of reactions was greater after transfusions of SDAPs (5.49%) than of RBCs (1.63%). The incidence of FNHTRs after transfusion of RBCs that were WBC reduced before storage (1.1%) was significantly lower (p = 0.0045) than that after transfusion of RBCs that were WBC reduced after storage (2.15%). Although allergic reactions to RBCs that were WBC reduced before storage were also less common (0.41%) than those to RBCs that were WBC reduced after storage (0.51%), the difference was not significant (p = 0.067). At the time of reactions to RBCs and SDAPs that were reduced before storage, the level of IL-6 was negatively correlated (r = -0.54, p = 0.014) with the duration of storage before transfusion, and there was no correlation between the level of either IL-1 beta or IL-8 and the interval before transfusion. TNF-alpha was not detectable in any implicated component. CONCLUSION: FNHTRs, but not allergic reactions, were less common after transfusion of RBCs that were WBC reduced before storage than after the transfusion of those WBC reduced after storage at the bedside by filtration. The level of IL-6 in implicated cellular blood components that were WBC reduced before storage was inversely correlated with the length of storage before transfusion. Further studies are needed to determine whether the transfusion of cellular blood components that were WBC reduced before storage can both diminish the incidence of adverse reactions and improve outcome.

c-fos is not essential for v-abl-induced lymphomagenesis.

Recent studies have suggested that cellular transformation by abl oncoproteins may be mediated by the ras signaling pathway. One of the main nuclear targets of this signal transduction cascade is the Fos and Jun family of transcription factors. To test the relevance of the c-fos proto-oncogene for v-abl-induced cancer development, we inoculated c-fos-deficient mice with the Abelson murine leukemia virus. Neonatal c-fos-deficient mice infected with the Abelson complex are able to develop the pre-B-cell lymphoma that characterizes Abelson disease. c-fos-deficient animals succumb to the disease with similar kinetics as their wild-type and heterozygous littermates. Moreover, the transformed cell that brings about the malignancy in mutant mice is the same pre-B-cell lymphoblast that is seen in control animals. These results demonstrate that c-fos is not required for in vivo transformation by v-abl.

Aggressive chemotherapy in the treatment of Burkitt's and non-Burkitt's undifferentiated lymphoma.

Because of the aggressive nature and frequent recurrence of malignant lymphomas of the undifferentiated type, we used a multi-drug induction chemotherapy regimen that has met with some success in children with similar type of histopathology followed by intensification and 8 cycles of consolidation chemotherapy in an attempt to prolong the duration of remission and survival in adult patients with this diagnosis. Fifty-one patients (median age 35 years) with undifferentiated malignant lymphoma were collected over a 4 year period (1984-1988) and entered into a phase III protocol done under the auspices of the Eastern Cooperative Oncology Group (ECOG). Six patients who had their diagnosis made at surgery and had resection of their tumor were excluded from analysis of response to therapy. Sixty percent of the patients had Stage IV disease. Sixteen patients had marrow involvement and five had central nervous system (CNS) disease. None of the patients received CNS radiation therapy. The 45 patients evaluated for response showed a response rate of 67% (30/45) and a complete response rate of 40% (18/45). Thirteen responders continue disease-free with a median follow-up of > 40 months and have an estimated 5 year survival of 80%. Only two treatment related deaths were reported for the entire group. Patients with undifferentiated non-Burkitt's lymphoma had a longer survival than those with undifferentiated Burkitt's. We concluded that adult patients with undifferentiated lymphomas could be treated successfully with an aggressive multi-drug chemotherapy regimen, consisting of multiple alternating cycles of non-crossed-resistant chemotherapy. Toxicity with this aggressive prolonged regimen was acceptable.

A randomized placebo-controlled phase III study of granulocyte-macrophage colony-stimulating factor in adult patients (> 55 to 70 years of age) with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490).

The treatment of adult patients greater than 55 to 70 years of age with acute myelogenous leukemia (AML) is associated with a treatment-related mortality of approximately 25%. This prospective, double-blind randomized study was designed to see if the use of granulocyte-macrophage colony stimulating factor (GM-CSF; yeast-derived) could shorten the period of neutropenia and to determine any effect this would have on therapy-related morbidity and mortality. A total of 124 patients entered this study. Induction consisted of standard daunorubicin and cytarabine. A day-10 bone marrow was examined; if this was aplastic without leukemia, patients received blinded placebo or GM-CSF from day 11 until neutrophil recovery. Patients who entered complete remission received the identical study medication (blinded GM-CSF or placebo) in consolidation that they had received during induction. The overall complete remission rate was 52%; 60% for the GM-CSF arm and 44% for the placebo arm (P = .08). Median times to neutrophil recovery were significantly shortened on the GM-CSF arm. The overall treatment-related toxicity from start of GM-CSF/placebo was reduced on the GM-CSF arm (P = .049). Similarly, the infectious toxicity was significantly reduced on the GM-CSF arm (P = .015). The median survival for all patients was 10.6 months in the GM-CSF group and 4.8 months in the placebo arm (P = .048). It appears that GM-CSF is safe and efficacious for adult patients greater than 55 to 70 years of age with AML; its major impact is in reducing the duration of neutropenia and therapy-related mortality and morbidity. This may result in a better response rate.

Characterization of reactions after exclusive transfusion of white cell-reduced cellular blood components.

BACKGROUND: Potential adverse effects of white cells (WBCs) within transfused cellular blood components include febrile nonhemolytic transfusion reactions (FNHTRs), alloimmunization, transmission of infectious diseases, transfusion-related acute lung injury, and immunomodulation. Although exclusive use of WBC-reduced components to prevent alloimmunization and cytomegalovirus transmission has been studied, the use of these components to avert FNHTR has not been examined. STUDY DESIGN AND METHODS: Transfusion reactions (FNHTRs, allergic reactions, and others) were characterized in recipients of 12,277 WBC-reduced single-donor apheresis platelets (SDAPs) and/or red cells (RBCs). Medical and laboratory evaluations for possible infectious and immunologic (alloimmunization) causes of each reaction were undertaken, and the benefit of further modification of components for the prevention of subsequent reactions was also evaluated. RESULTS: Transfusion reactions occurred after 481 (3.92%) of 12,277 transfusions. Allergic reactions occurred more commonly after transfusion of SDAPs (3.69%) than of RBCs (0.51%). Conversely, FNHTRs occurred more commonly after transfusion of RBCs (2.15%) than of SDAPs (1.58%). HLA antibodies were present in a posttransfusion sample from 27 (10.6%) of 255 patients; bacterial contamination was a possible cause of only 2 (0.42%) of 481 reactions. In patients with recurrent FNHTRs, further WBC reduction in components did not wholly prevent further FNHTRs. CONCLUSION: The incidence of FNHTRs and alloimmunization after exclusive transfusion of WBC-reduced RBCs and SDAPs was low. Further WBC reduction in components transfused to patients with a history of recurrent FNHTRs does not completely prevent subsequent reactions.

Hormonal treatment for metastatic breast cancer. An Eastern Cooperative Oncology Group Phase III trial comparing aminoglutethimide to tamoxifen.

BACKGROUND: Tamoxifen and aminoglutethimide are two hormone therapies reported to be effective palliative approaches for patients with metastatic breast cancer. The current trial was designed to evaluate their relative therapeutic effectiveness. METHODS: Two hundred forty-nine postmenopausal women with advanced breast cancer were randomized in an Eastern Cooperative Oncology Group (ECOG) Phase III study to treatment with adrenalectomy, aminoglutethimide, or tamoxifen with crossover to alternate therapy if disease progressed. Adrenalectomy was dropped as a treatment after 2 years because of low patient accrual. RESULTS: There were 216 evaluable patients entered in the study with 108 initially randomized to aminoglutethimide and 108 to receive tamoxifen therapy. The overall response rate for aminoglutethimide was 45%, and for tamoxifen it was 27%. One institution had a response rate of 60% with aminoglutethimide and only 4% with tamoxifen, whereas all of the other institutions combined had a response rate of 41% with aminoglutethimide and 34% with tamoxifen. Eighty-seven evaluable patients crossed over to the other drug (44 to aminoglutethimide and 43 to tamoxifen). There was a 36% response rate to aminoglutethimide and 19% to tamoxifen, with stable disease in 36% of both groups. The overall survival rates were identical. Toxicity was greater with aminoglutethimide (dermatitis) but was not life-threatening. Glucocorticoid support with either dexamethasone or hydrocortisone was acceptable. CONCLUSIONS: Both aminoglutethimide and tamoxifen produced responses in postmenopausal patients with breast cancer, and a significant number of crossover responses were observed. Of interest in this randomized study was the observation that one institution had a markedly different response rate on induction, reinforcing the need for multi-institution trials in Phase III studies.

Age and Hodgkin's disease: the impact of competing risks and possibly salvage therapy on long term survival: an E.C.O.G. study.

A detailed review of factors associated with survival was carried out in a cohort of 560 patients treated in two successive E.C.O.G. studies on advanced Hodgkin's disease. The study was undertaken to explore the impact of age on survival and to attempt to identify reasons for any observed differences. Data from two E.C.O.G. studies of patients with advanced Hodgkin's disease were examined separately and then pooled together. A special data request form was developed to capture additional information on treatments utilized for patients who were treated at relapse. The complete remission percentages were identical in both studies (72%) with no significant difference between the three age groupings (< 40, 40-59, and > 60 yr). This was true as well for disease-free survival. Nevertheless, overall survival was significantly better for the under aged 40 group and this difference was narrowed but not eliminated by competing risks. Our analysis of salvage therapy revealed a marginally significant difference in the CR% between the three groups, favoring the youngest cohort (< age 40 yr). The identical remission rate is probably a reflection of the entry criteria eliminating poor risk patients. Among the small number of patients who received radiation therapy, the response rate was 75% (9/12) in the young cohort. Elderly patients appeared to receive less salvage therapy and certainly fewer responses. Survival after relapse showed a similar pattern with the best survival in the youngest group of patients followed closely by the 40-59 yr group, with a poor outcome for those over age 60 yr. We conclude that a variety of conditions, both age and non-age dependent, impact on the survival of patients with advanced Hodgkin's disease who fulfill the rigid criteria for entry into cooperative group trials.