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Biomedical subjects

J M Bennett

Publications and source records attributed to J M Bennett.

At least 145 records · Page 8Linked to original sources

13-cis-retinoic acid in the treatment of elderly patients with acute myeloid leukemia. A phase II pilot study of the Eastern Cooperative Oncology Group.

The management of acute myeloid leukemia in the elderly (65 years and older) is unsatisfactory because of poor patient tolerance of standard myeloablative chemotherapy. The authors conducted a Phase II study to evaluate the effectiveness and toxicity of 13-cis-retinoic acid (CRA) in the therapy of elderly patients with acute myeloid leukemia (AML). Patients presenting with leukocyte counts less than 20,000/microliters were treated with CRA alone. Those with leukocyte counts of 20,000/microliters or greater were pretreated with hydroxyurea, followed by CRA. Twelve of 18 patients received at least 4 weeks of CRA and were thus considered evaluable for toxicity and response. No objective responses were observed. Cis-retinoic acid administration was well tolerated; only modest dermatologic, musculoskeletal, and gastrointestinal toxicity was observed. Alternative therapeutic strategies should be investigated in this subpopulation of AML patients.

Aged↗

High-dose dexamethasone for refractory or relapsing multiple myeloma.

In order to assess the efficacy and toxicity of dexamethasone as a single agent without the concomitant infusion of Adriamycin and vincristine (VAD), an ECOG pilot study was initiated using 40 mg by mouth daily for 4 days every week for 8 weeks. Patients who responded were then maintained on the same treatment, but at 2 week intervals. Of the 32 patients evaluable for response, three were completely refractory to all prior therapy. All patients had advanced disease and 26 had received multiple prior treatments. There were 13/32 (40%) objective responses by ECOG criteria. Of the 28 patients evaluable for subjective response, i.e., significant decrease in performance status and/or bone pain, eight (28.5%) responded. Of the 34 patients evaluable for toxicity, 19 patients (55%) had moderate to severe side effects, including nine who had central nervous system effects, three who had gastrointestinal bleeding, two who had pulmonary emboli, one with psychosis, and four who had serious infections with one death. Median survival for the entire group was 19 weeks, with 31 weeks in the responders and 9 weeks in the non-responders. Although high-dose dexamethasone is capable of producing a significant number of partial responses (40%), it is associated with excessive toxicity. Less frequent administration of the dexamethasone at 2 week intervals was well tolerated in the maintenance of partial response, but has not been studied for efficacy in induction of remission.

Adolescent↗

Treatment patterns in low-grade non-Hodgkin's lymphomas: a single institution study.

Ninety-two cases of low-grade non-Hodgkin's lymphoma were examined retrospectively to assess to what extent treatment deferral is practiced at a single university hospital with a local referral base. Clinical characteristics of this patient group were also analyzed; 70% of these cases were of nodular lymphocytic, poorly differentiated (NLPD) histology, and 74% were stage III or IV. Twenty-two cases were not treated initially. Nine eventually required treatment at a median of 16 months. Survival did not differ based on whether treatment was initially deferred. Nodal progression was the most common reason for beginning treatment after initial deferral, and most cases of advanced stage disease required treatment because of nodal involvement or B-type symptoms at diagnosis. Presence of intra-abdominal adenopathy often prompted initial treatment even in asymptomatic cases. In this series, as compared to previously reported series of treatment-deferred cases, more patients were judged to require treatment at disease outset, and the median time to treatment in those in whom treatment was initially deferred but then instituted was shorter. Despite this, for the entire population, 69% of total follow-up time was spent off therapy.

Actuarial Analysis↗

Unexpected immunoglobulin light chain gene rearrangements in myeloid antigen positive acute lymphoid leukemia.

Blast cells from 10 immunologically diagnosed adult acute lymphoid leukemias expressing myeloid antigens (M+ALL) were studied for immunoglobulin heavy (IgH) and light chain as well as T-cell receptor (TCR)-beta chain gene rearrangements. All but one leukemic isolate met the FAB-criteria for ALL. DNA from 2 patients with pre-pre-B-ALL (CD10-) and 1 patient with common ALL contained rearranged Ig light chain (kappa in two, lambda in one case) in addition to rearranged IgH genes. The TCR-beta chain gene was germline in all pre-pre-B leukemias and rearranged in common ALLs (bigenotypic features). One patient with mature B-ALL showed IgH and light chain gene rearrangements. DNA from 2 pre-T-ALLs contained rearranged TCR-beta chain genes plus rearranged IgH genes in one case. Ig light chain gene rearrangements in immature M+ALL were not associated with gross chromosomal abnormalities except for one Philadelphia chromosome positive case. The occurrence of Ig light chain gene rearrangements in M+ALL with immature lymphoid immunophenotype might represent an hitherto unrecognized aberrant differentiation potential of transformed multipotential stem cells with commitment towards the lymphoid lineage.

Adult↗

Long term survival in acute myeloid leukemia: the Eastern Cooperative Oncology Group (ECOG) experience.

A retrospective analysis of two ECOG adult AML trials conducted from 1976 to 1983 was carried out focusing on long term disease-free survival. This report summarizes the data on 545 patients with a minimum follow up of 7 1/2 years. The complete remission rate was 57% with an estimated cure rate of 12%. Of several prognostic variables examined only FAB type M3 (promyelocytic leukemia) was statistically significant (estimated cure rate of 33% vs 9% for other FAB subtypes).

Adult↗

Prognostic implication and characterization of the blast cell population in the myelodysplastic syndrome.

The bone marrow smears of 18 confirmed cases of MDS were analyzed carefully for the presence of "hypergranular type III blasts", defined as more than 20 fine azurophil primary granules per cells. The concordance was close to 80% among 5 observers. Thirty-nine percent (7 cases) were reclassified as RAEB-t rather than RAEB. The presence of these hypergranular blasts was not suggestive of increased differentiation but rather leukemic cells. The reassignment of cases altered the median survival for the various subcategories, providing a clearer separation with the introduction of type III blasts than without utilizing these cells which were separated from the promyelocyte family. The introduction of this new blast cell definition in a larger series of patients is recommended to confirm these preliminary observations.

Aged↗

Proposal for the recognition of minimally differentiated acute myeloid leukaemia (AML-MO)

We describe a form of acute myeloid leukaemia (AML), designated AML-MO, with minimal myeloid differentiation, not included previously in the FAB classification. AML-MO cannot be diagnosed on morphological grounds alone as the blast cells are large and agranular, sometimes resembling L2 or, rarely, L1 lymphoblasts, and should be identified by the following features: negative myeloperoxidase (MPO) and Sudan Black B reaction (or positive in less than 3% of blasts), negative B and T lineage markers and expression of myeloid antigens recognized by at least one monoclonal antibody, CD13 or CD33. Other myeloid markers are also often positive and these include CD11b and the enzyme MPO demonstrated by immunocytochemistry and/or electron microscopy analysis. The findings in a group of 10 cases satisfying the criteria for AML-MO are described. AML-MO represents 2-3% of all cases of AML and 1-1.5% of all acute leukaemias. Its clinical and biological significance is not yet apparent but its identification in a larger number of cases may achieve this aim.

Acute Disease↗

Pentostatin induces durable remissions in hairy cell leukemia.

Fifty patients with hairy cell leukemia were treated with pentostatin (2'-deoxycoformycin; dCF) for a median of 3 months; 32 (64%) patients achieved complete remission (CR), and 10 (20%) patients achieved partial remission (PR), for an overall response rate of 84%. After reaching maximal response, no maintenance therapy was administered. The median duration of follow-up is now 39 months, and only four of 32 patients in CR and two of 10 patients in PR have relapsed. dCF therapy produces durable long-term, disease-free survival in patients with hairy cell leukemia.

Humans↗

Medical surveillance for leukemia at a petrochemical manufacturing complex: four-year summary.

Four-year results are presented on 2086 participants of a medical surveillance program of current and retired employees at a manufacturing complex in Illinois. Annual complete blood cell count testing and intensive follow-up of all out-of-normal-range results began in 1985 on a voluntary basis. The program to date has not identified any evidence for an unusual distribution of out-of-range complete blood cell count results. Active employees with out-of-range complete blood cell count values had no increase in adverse health outcomes compared with those with in-range values. Retired employees with out-of-range values were more likely to have a serious underlying medical condition, but this appeared to be more a function of age than of occupational exposure. Four cases of myelodysplastic syndrome were brought to our attention as a result of the program, but there is no similarly followed population available for comparison to determine whether this represents an increase over expected cases. The lack of correlation of out-of-range complete blood cell count results in active employees with serious hematologic disease raises significant questions about the utility of such surveillance for chemically exposed groups (eg, benzene-exposed workers) when exposure levels are low and well controlled.

Adult↗

Appropriateness of composites in structural equation models.

The appropriateness of using composites instead of multiple indicators in a structural model of physical health was evaluated. Liang's (1986) specification of self-reported physical health is a relatively complex multiple indicators model which may not be practical in actual application. To simplify this formulation, a two-stage strategy was used. First, reliability was estimated for each composite to fix the measurement error variance and the regression of the composite on the latent variable. Second, the model was reestimated by constraining these parameters. Regression analyses were undertaken to assess the impact of using composites instead of multiple indicators. Parameter estimates for causal linkages and residual error variances based on multiple indicators approach were closely reproduced by using composites, thus providing justification for the proposed strategy.

Activities of Daily Living↗

Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia.

The National Cancer Institute (NCI) sponsored a workshop to develop a set of standardized diagnostic and response criteria for acute myeloid leukemia (AML) clinical trials. The French-American-British (FAB) classification was retained for diagnosing AML, with the addition of patients with bone marrow morphologic features of a myelodysplastic syndrome and less than 30% bone marrow blasts, but with greater than or equal to 30% blasts in the peripheral blood. In this report, there are four important subgroups of AML not defined in the FAB classification that are discussed: undifferentiated acute leukemia, MO (AML lacking definitive myeloid differentiation by morphology or conventional cytochemistry but with ultrastructural or immunophenotypic evidence for AML), mixed lineage leukemia, and hypocellular AML. Definitions of response for clinical trials are presented to facilitate comparisons among different studies. Complete remission is considered the only response worth reporting in phase III trials, since lesser responses do not improve survival. Partial remissions may be of interest to identify active new agents in phase I and II studies. Monoclonal antibodies and cytogenetic studies are not part of the routine assessment of remission or reassessment at relapse, and their role in the evaluation of patients with AML is currently being evaluated in clinical trials. Although we recognize that some of the definitions in this report are arbitrary, generalized use of these guidelines will make results of clinical trials more comparable and interpretable.

Antibodies, Monoclonal↗

Blastic phase of chronic myeloid leukemia (blCML): a proposal for standardization of diagnostic and response criteria.

The selection of optimal treatment among the alternatives that are available is especially difficult in blastic phase of chronic myeloid leukemia (blCML) because of the absence of universally agreed upon criteria for the diagnosis of this phase and the absence of definitions of response. Variable response rates, from less than 10 to greater than 90% have been reported, but the highest response rates, in general, have not been reproducible. The application of strict morphologic, cytogenetic, and molecular biologic studies should provide the means for selection of optimal treatment among the new therapies that will be introduced in the future.

Blast Crisis↗

Chronic myelomonocytic leukemia.

Thirty adult patients with CMML were evaluated to determine prognostic factors that might have an impact on conversion to acute leukemia and survival. Neither leukocyte count nor monocyte count correlated with survival. The median survival for all 30 cases was 41 months. Patients with less than 5% marrow blasts had a median survival of 60 months but those with 5-20% blasts had only a 9-month median survival.

Aged↗

Classifications of acute myeloid leukemia.

A detailed description of the various subtypes of the acute myeloid leukemias is provided. The importance of cytochemistry and monoclonal antibodies is discussed.

Antibodies, Monoclonal↗