Inv(16) and eosinophilia in CMMoL.
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Chromosome Inversion↗
Biomedical subjects
J M Bennett
Publications and source records attributed to J M Bennett.
Phase II study of carboplatin in blast crisis of chronic myeloid leukemia: Eastern Cooperative Oncology Group Study E1992.
This study was a phase II evaluation of the activity of carboplatin in patients with Philadelphia chromosome positive accelerated or blastic phase of CML. Carboplatin, 250 mg/m2/day as an intravenous continuous infusion was given for 5 days, for a total dose of 1250 mg/m2 per course. If necessary, a second induction course could be given, and patients achieving complete remission were to receive an additional consolidation cycle at the same dose. Thirty-six patients were eligible and evaluable. There were five complete and three partial remissions for an overall response rate of 22% (95% CI 10.1-39.1%). The complete remission rate was 13.9% (95% CI 4.7-29.9%). The median remission duration was 3 months (range 1.4-8.94 months) and the median survival on study for all patients was 3.5 months (95% CI, 2.4-11.4 months). The median survival of responders was 12.8 months (95% CI, 3.6-17.2 months). Three eligible patients survived 2.0, 2.5 and 3.5 years following carboplatin therapy. Carboplatin has activity in blast crisis of CML, but responses are brief. Response did allow one patient to proceed to bone marrow transplantation and two other patients to continue therapy for chronic phase disease before returning to blast crisis. Activity in combination regimens should be explored.
Adult↗
Biologic heterogeneity in Philadelphia chromosome-positive acute leukemia with myeloid morphology: the Eastern Cooperative Oncology Group experience.
Evaluable karyotypes were available in 776 of 1148 adult patients who were entered on acute myeloid leukemia (AML) treatment protocols of the Eastern Cooperative Oncology Group. Among these, we found seven patients (0.9%) with t(9;22)(q34;q11), the Philadelphia (Ph) chromosome, in bone marrow metaphases. All fulfilled the FAB criteria for AML (three M0, two M1, two M2), although one patient presented with an additional, distinct lymphoid blast cell population. Chromosomal aberrations in addition to the Ph chromosome were seen in four patients (including two cases of monosomy 7). Molecular analysis by polymerase chain reaction in four patients tested revealed variable BCR/ABL transcript forms (ela2, b2a2, b3a2, b2a3+ela2). By immunophenotyping, all seven patients were myeloid based on the overall antigen expression pattern. However, all but one demonstrated lymphoid-associated antigens on the myeloid blast cells. The six evaluable patients failed to respond to treatment with a standard anthracycline/cytosine arabinoside-containing regimen. We conclude that the incidence of the Ph chromosome in AML is very low. Although both genotypically and phenotypically heterogenous, Ph chromosome-positive AML, represents a clinically distinct entity with poor outcome.
Adult↗
Acute myeloid leukaemia expressing the leucocyte integrin CD11b-a new leukaemic syndrome with poor prognosis: result of an ECOG database analysis. Eastern Cooperative Oncology Group.
While assessing the prognostic implications of immunophenotyping in 382 patients enrolled in treatment protocols of the Eastern Cooperative Oncology Group (ECOG) for de novo adult acute myeloid leukaemia, we identified 95 patients with a unique antigen profile characterized by high expression of the leucocyte integrin CD11b (CD11b+ AML). High expression of CD11b was defined as > or = 32% positive blasts based on the retrospectively established prognostic cut-off point for this antigen. Although CD11b is normally expressed by mature monocytes, natural killer cells and granulocytes, leukaemic blasts in CD11b+ AML lacked other immunologic monocytic features (e.g. CD14 and CD122, the interleukin-2 receptor beta chain) and demonstrated a high degree of immaturity, as reflected by a high incidence of blasts expressing the stem cell factor receptor, CD117, and few blasts positive for the myeloid differentiation antigen CD15. Furthermore, by FAB criteria, only 41% of CD11b+ AML cases were classified as M4/M5. Patients with CD11b+ AML had a low response rate (54%) when compared with acute monocytic leukaemia (AMOL; 82%, P = 0.006) or AML overall (68%, P = 0.031), independent of age, cytogenetic abnormalities and P-glycoprotein expression. Because of its poor prognosis, recognition of CD11b+ AML is clinically warranted and, given its morphologic and cytogenetic ambiguity, must be based on the unique antigen profile.
Acute Disease↗
Medical surveillance for hematological disorders among active and retired oil refinery workers.
Ten-year (1985-1995) results of an expanded medical surveillance program of 2475 active employees and retirees of an oil refinery and petrochemical complex in Illinois are presented. At the end of the program, 116 participants with persistent abnormalities of complete blood cell count had been referred for hematologic evaluation, and most were found to have benign conditions. Fifteen of the 116 were referred for bone marrow and cytogenetic studies. All of the referred active employees (seven) were found to have completely normal bone marrows with no evidence of any myelopathic process. Among the eight retirees, two had normal bone marrows, one was diagnosed with Philadelphia chromosome-positive chronic myelogenous leukemia, one declined to participate, and four were diagnosed to have myelodysplastic syndrome (MDS) of various subtypes. A total of eight cases of MDS were identified, including six cases among program participants and two cases among nonparticipants. The MDS standardized incidence ratio of 1.26 (95% confidence interval = 0.54-2.47) was not statistically significant, and there was virtually no increase of MDS in persons less than 80 years of age (4 observed and 3.8 expected). This MDS increase was entirely from program participants, probably because of intensive follow-up and diagnostic screening. Routine surveillance of complete blood cell count information did not identify any new cases of leukemia or MDS in active employees. These findings suggest that the utility of expanded medical surveillance program in this population is very limited.
Adult↗
Phase II study of mitoguazone, cyclophosphamide, doxorubicin, vincristine and prednisone for patients with diffuse histologic subtypes of non-Hodgkin's lymphoma: an Eastern Cooperative Oncology Group Study (PE481).
Mitoguazone, an investigational agent with significant activity in advanced lymphoma, was added to a modified CHOP regimen (COPA) in an effort to improve the activity of standard therapy in 66 previously untreated patients with stages II-IV lymphoma and diffuse histology of intermediate or high grade other than lymphoblastic in this phase II pilot study. The regimen was well tolerated and the complete response rate in diffuse large cell lymphoma was 55%. Sixty-five percent of all complete responders were in complete response for at least one year. Despite these excellent results. it is unlikely that the addition of mitoguazone improved results compared with those obtained with standard therapy alone, since similar results have been frequently reported with the latter.
Adult↗
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.
Acute Disease↗
Medical oncology and geriatric medicine: is it time for fellowship integration?
Although training programs exist in both medical oncology and geriatrics (approved by the American Board of Internal Medicine), neither is adequate to ensure an appropriate supply of physicians to assume a leadership role in the treatment of the increasing number of geriatric patients who have or will develop a malignancy. A proposal for offering a 3-4 year program leading to dual certification is under consideration. A careful review of both the medical oncology training program and added qualifications in geriatrics has identified key components of each that can serve as a basis for a combined program. Such a program can encourage research into behavior modification of existing biases in referring geriatric oncology patients for treatment as well as a better understanding of the biology of aging, addressing in particular the pharmacology of anticancer agents in this unique population. It is anticipated that pilot projects will be undertaken to develop common pathways for developing combined programs in medical oncology and geriatrics. The second phase will include recruitment of selected candidates who are interested in an academic career in geriatric oncology. A need for additional academic-based geriatric oncologists has been identified that can address the anticipated increase in the incidence and presence of cancer in an aging population. Such a cadre of specialists will be in an excellent position to recommend changes in the current (mostly negative) approach to the management of cancer in patients age > 65 years.
Aged↗
An atypical case of plasma cell leukemia.
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Aged↗
Automated VO2max calibrator for open-circuit indirect calorimetry systems.
The complete calibration of indirect calorimetry systems involves simultaneous checks of gas analyzers, volume device, and software, and this requires a machine that can mimic accurately and precisely the ventilation and expired gases of an athlete. While previous calibrators have been built successfully, none have matched the ventilatory flows produced by athletes during high intensity exercise. A calibrator able to simulate high aerobic power (VO2max calibrator) was fabricated and tested against conventional indirect calorimetry systems that use chain-compensated gasometers to measure expired volume (VE systems) and calibrated electronic gas analyzers. The calibrator was also checked against a system that measures inspired volume (VI system) with a turbine ventilometer. The pooled data from both VE and VI systems for predicted VO2 ranging from 2.9 to 7.9 L.min-1 and ventilation ranging from 89 to 246 L.min-1 how that the absolute accuracy (bias) of values measured by conventional indirect calorimetry systems compared with those predicted by the calibrator was excellent. The bias was < 35 mL.min-1 for VO2 and carbon dioxide production, < 0.50 L.min-1 for ventilator (VE BTPS), -0.02% absolute for the percentage of expired O2 and +0.02% absolute for the percentage of expired CO2. Overall, the precision of the measured VO2, VCO2, and VE BTPS was approximately 1%. This VO2max calibrator is a versatile device that can be used for routine calibration of most indirect calorimetry systems that assess the ventilation and aerobic power of athletes.
Blood Gas Analysis↗
Trilineage extramedullary myeloid cell tumor in myelodysplastic syndrome.
A patient with a 17-month history of myelodysplastic syndrome (refractory anemia with excess blasts that evolved into chronic myelomonocytic leukemia), which was treated with transfusions and erythropoietin, developed abdominal and inguinal lymphadenopathy. Biopsies of the abdominal nodes revealed virtual obliteration of the architecture by myeloid blasts admixed with maturing granulocytic, erythroid, and megakaryocytic precursors. The lymph node findings appeared to represent extramedullary dyshematopoiesis undergoing a tissue phase blast transformation. Four months later, the patient developed rising peripheral blast counts consistent with acute leukemia. Although the development of granulocytic sarcoma (also called extramedullary myeloid cell tumor) is well known to occur in patients with myelodysplastic syndromes, to our knowledge this is the first description of an extramedullary myeloid cell tumor associated with trilineage differentiation.
Anemia, Refractory, with Excess of Blasts↗
National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment.
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Antineoplastic Combined Chemotherapy Protocols↗
Characterisation of the Aspergillus nidulans frA1 mutant: hexose phosphorylation and apparent lack of involvement of hexokinase in glucose repression.
Hexose phosphorylation was studied in Aspergillus nidulans wild-type and in a fructose non-utilising mutant (frA). The data indicate the presence of at least one hexokinase and one glucokinase in wild-type A. nidulans, while the frA1 mutant lacks hexokinase activity. The A. nidulans gene encoding hexokinase was isolated by complementation of the frA1 mutation. The absence of hexokinase activity in the frA1 mutant did not interfere with glucose repression of the enzymes involved in alcohol and L-arabinose catabolism. This suggest that, unlike the situation in yeast where mutation of hexokinase PII abolishes glucose repression, the A. nidulans hexokinase might not be involved in glucose repression.
Amino Acid Sequence↗
Diagnostic criteria for hypocellular acute leukemia: a clinical entity distinct from overt acute leukemia and myelodysplastic syndrome.
In order to establish diagnostic criteria for hypocellular acute leukemia (HL), we have reviewed 32 cases selected on the basis of hypothetical 40% or less cellularity, by focusing on morphology, immunophenotype, karyotype and response to low dose Ara-C (LDAC) regimen and compared them with 40 cases of myelodysplastic syndrome (MDS) and 66 cases of overt acute myeloid leukemia (AML). The onset age ranged from 44 to 75 years (median 67 years). Bone marrow (BM) cellularity ranged from 12.4 to 39.8% (mean 29.8%) in HL, being significantly lower than in MDS (mean 80.7%) or AML (mean 86.4%) (P < 0.001). All reviewed cases characteristically showed smoldering clinical course, bi- or pancytopenia with rare leukemic blasts in the peripheral blood (PB), proliferation of type I leukemic blasts in the BM and markedly reduced background hematopoietic cells with some dysplastic changes in 12/32 cases (37.50/6). Blast percentage (blast %) in the BM ranged from 38.2 to 93.7% (mean 57.3%) in all nucleated cells (ANC). Although a considerable number of cases had blasts with negative or very low myeloperoxidase activity, immunophenotyping revealed that the leukemic blasts in HL had only myeloid markers. Karyotyping revealed non-random chromosome abnormalities in 30% of cases analyzed, which were considerably different from those seen in MDS. With LDAC regimen, a significantly higher CR rate (13/20 cases: 65.0%) was gained in HL than in RAEB/RAEB-t (0%) and overt AML in the elderly cases (27.3%) (P < 0.05). In CR, most cases showed recovery to normocellular BM with an apparent normalization of PB parameters. However, 12 CR cases relapsed 4-12 months later; most of which again showed hypocellular BM. These results indicate that HL is a distinct subtype of AML characterized by slow but distinct proliferation of immature myeloid blasts and by unique hematological features distinct from MDS or overt AML in the elderly. We propose the following diagnostic criteria: (1) pancytopenia with rare appearance of blasts in PB; (2) less than 40% BM hypocellularity; (3) more than 30% blasts in BM-ANC; and (4) myeloid phenotypes of leukemic blasts by MPO staining and/or immunophenotyping.
Acute Disease↗
Acute leukemia with t(10;11)(p11-p15;q13-q23).
We report six patients with acute leukemia characterized by the presence of a t(10;11)(p11-15;q13-q23), either as sole cytogenetic abnormality (three patients) or as part of a complex abnormal karyotype. The morphologic and cytochemical features of four patients were consistent with FAB-M5A, while two patients presented with FAB-L1 characteristics. By immunophenotyping, myeloid leukemia was diagnosed in five patients, including one patient with FAB-L1 leukemia who typed as terminal transferase (TdT)+, CD7 T-cell antigen+ acute myelomonocytic leukemia. Differentiated acute myeloid leukemia (AML) with expression of terminal transferase was found in two of the other cases and monocytic leukemia in two, with co-expression of T-cell antigens in one of them. The second FAB-L1 patient typed as undifferentiated acute lymphocytic leukemia (ALL) expressing myeloid antigens. Serial phenotypic studies in patient 3 during the course of the disease demonstrated a switch from monocytic to lymphoid morphology at the time of first and second relapse, which was paralleled by the appearance of a pre-T ALL immunophenotype with co-expression of the myeloid antigen CD33. These phenotypic changes occurred without apparent alteration in the genotype since t(10;11)(p11.2;q23) remained the only cytogenetic aberration at all stages of the disease. Our observations suggest that the (10;11) variant of 11q aberrations occurs in a bipotential myelomonocytic/T-lymphoid stem cell.
Adult↗
Prophylactic antibiotics for the prevention of early infection in multiple myeloma.
PURPOSE: Patients with multiple myeloma are at increased risk for bacterial infection. During the first 2 months of initial chemotherapy the rate of infection is twice that experienced during the remainder of the disease course. As many as one-third of these early infections are fatal, and many more prevent adequate administration of chemotherapy. This study was designed to determine whether the morbidity and mortality of early infection can be prevented by prophylactic administration of trimethoprim-sulfamethoxazole (TMP-SMX). PATIENTS AND METHODS: Eligible patients about to begin chemotherapy for multiple myeloma were randomly assigned to prophylaxis for 2 months or to no prophylaxis (control). Antibiotic prophylaxis consisted of TMP-SMX 160/800 mg orally every 12 hours administered for the first 2 months of initial chemotherapy. All patients were observed for infection for 3 months after the start of chemotherapy. RESULTS: Of 57 patients entered into the study, 54 were evaluable, representing 13.1 patient-years of observation. The 28 TMP-SMX patients and 26 control patients were comparable in terms of chemotherapy regimen, age, gender, stage, and bone marrow function. Bacterial infection during the 3-month study period occurred in 11 control patients but in only 2 patients assigned TMP-SMX (P = 0.004). Eight severe infections occurred in controls compared with 1 in a TMP-SMX patient (P = 0.010) leading to 4 and 1 infection deaths, respectively (P = not significant). Severe infections included 5 pneumonias (3 with sepsis), 2 urinary tract infections with complicating pneumonia or sepsis, 1 diverticulitis with perforation, and 1 staphylococcal scalded skin syndrome. None of the 4 nonbacterial infections was severe. The rate of bacterial infection was 2.43 per patient-year for controls and 0.29 per patient-year for the TMP-SMX group (P = 0.001). Toxicity (skin rash 6 patients, nausea 1 patient) was not life-threatening but required discontinuation of TMP-SMX in 25% of patients. CONCLUSION: Administering TMP-SMX for the first 2 months of initial chemotherapy is effective, inexpensive prophylaxis for early bacterial infection in multiple myeloma.
Aged↗
Clinical use of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in neutropenia associated with malignancy.
G-CSF and GM-CSF have been shown in each clinical setting to reduce the duration of neutropenia, with the exception of the scant data available in the unrelated bone marrow transplant setting. These growth factors also have been shown to have no leukemogenic effect during the observation periods of the trials discussed. In MDS, one major randomized trial has demonstrated a reduction in incidence of infection. This has not yet been demonstrated in AML and allogeneic BMT. Data from ongoing and future trials will be helpful in elucidating their effect on treatment-related morbidity and overall survival.
Granulocyte Colony-Stimulating Factor↗
Application of psychometric standards to scoring system evaluation: is "new" necessarily "improved"?
Psychometric guidelines are suggested that expand the evaluation of scoring systems beyond the most frequently (and often singly) considered criterion, that of interrater reliability. Principles of reliability and validity are elaborated and discussed with regard to scoring systems. Also addressed are assays for efficiency in applying a new system, the effects of rater proficiency on outcome scores, the comparison of costs and benefits of new scoring systems, and the comparison of a new scoring system to an existing system to demonstrate its advantage. As a timely example to illustrate these principles, a new scoring system is introduced for the Rey-Osterrieth Complex Figure Test and is compared to the most popular scoring system for this test (Lezak, 1983, p. 400). The proposed principles would be relevant to any scoring system that codes subjective behavioral data into objective values.
Adult↗