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J M Bennett

Publications and source records attributed to J M Bennett.

At least 109 records · Page 6Linked to original sources
PubMed1994

Use of cell surface antigen phenotype in guiding therapeutic decisions in chronic myelomonocytic leukemia.

The myelodysplastic syndromes are a heterogeneous group of hematopoietic stem cell diseases in which both diagnosis and prognosis are determined by cellular morphologic criteria. In some patients, prognosis is poor due to proliferation of immature cells, i.e. development of acute leukemia. An important clinical decision for patients with myelodysplastic syndromes is whether to treat with supportive care or to use cytoreductive drugs to control the proliferative component of these illnesses. Two cases of chronic myelomonocytic leukemia are presented where cell surface antigen phenotype analysis showed characteristics suggestive of proliferative disease and the patients were treated and obtained remission with cytoablative therapy. Cell surface marker analysis may be useful in guiding therapeutic decisions in myelodysplasia.

Aged↗
PubMed1994

B-cell acute lymphoblastic leukemia with L1 morphology and coexistence of t(1;19) and t(14;18) chromosome translocations.

We report a case of adult de novo acute lymphoblastic leukemia (ALL) with unique cytogenetic abnormalities and discrepant morphologic and immunologic features. Morphology was L1 by the French-American-British classification, but flow cytometry was consistent with a mature B-cell phenotype. Cytogenetic analysis showed numerous chromosome abnormalities nonspecific for lymphoid neoplasm except for t(1;19) and t(14;18). The former is characteristic of pre-B-ALL and the latter is characteristic of follicular lymphoma. This is the first report of these two translocations occurring concurrently in ALL.

Bone Marrow↗
PubMed1994

The chronic myeloid leukaemias: guidelines for distinguishing chronic granulocytic, atypical chronic myeloid, and chronic myelomonocytic leukaemia. Proposals by the French-American-British Cooperative Leukaemia Group.

We have reviewed our experience with four of the entities that are included under the generic term chronic myeloid leukaemia (CML), namely the classic Ph+ CGL, both BCR+ and BCR-, aCML and CMML. We have developed a statistical model that confirms that CGL, aCML and CMML can be distinguished from each other with reasonable success employing five quantitative parameters (WBC, percentage immature granulocytes, percentage monocytes, percentage basophils, percentage erythroid precursors in bone marrow) and one qualitative parameter (granulocytic dysplasia). It is hoped that these detailed recommendations will enable investigators to improve their diagnostic accuracy. This should permit more uniform comparisons of molecular biologic and clinical studies.

Bone Marrow↗
PubMed1993

Three cases of familial hairy cell leukemia.

In a 10-year interval, a total of 12 cases of familial hairy cell leukemia have been published. They were noted in first degree relatives, mostly in men. In some instances, when the HLA type was performed, a specific HLA type was found in the studied family, but a different haplotype was seen in other families. It appeared that familial cases of hairy cell leukemia were not associated with a "specific HLA antigen" and other factor(s) such as environmental, or some kind of occupational exposure, were suggested to play a role in the familial occurrence of hairy cell leukemia. We add three more familial hairy cell leukemia cases which are different from other published cases, showing a female predominance. The HLA typing revealed interesting findings. The HLA type shared by case 1 and 3 was A2, A30/31(19), B27, Bw4, Bw6. From these, HLA A2, Bw4, and Bw6 were previously reported (Ward FT, Baker J, Krishnan J, Dow N, Kjobech CH: Cancer 65:319-321, 1990). Case 2, shared with the other two the antigen Bw6. Its specific HLA type was A3 and B7, the type previously reported in a family (Begley CG, Tait B, Crapper RM, Briggs RG, Brodie GN, Mackay IR: Leuk Res 11:1027-1028, 1987). Based on these observations, we may conclude that a "specific HLA type," A2, Bw4, Bw6 and A3, B7 might have a role in the genetic predisposition for hairy cell leukemia.

Adult↗
PubMed1993

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.

Adult↗
PubMed1993

Differential expression of terminal transferase (TdT) in acute lymphocytic leukaemia expressing myeloid antigens and TdT positive acute myeloid leukaemia as compared to myeloid antigen negative acute lymphocytic leukaemia.

We examined whether the allegedly aberrant expression of the lymphoid lineage associated DNA polymerase, terminal deoxynucleotidyl transferase (TdT), in acute myeloid leukaemia (AML) is associated with alterations of the enzyme at the cellular, biochemical or transcriptional level when compared to lymphoid leukaemia (ALL), either lacking or expressing myeloid antigens. By flowcytometric analysis, the intensity of TdT staining with monoclonal anti-TdT antibody was considerably weaker in TdT+ AML and myeloid+ ALL (M+ ALL) than in myeloid- ALL (M- ALL). TdT enzyme activity in TdT+ AML was on an average 10%, and in M+ ALL 25% of that measured in M- ALL. Anti-TdT antibodies precipitated a major specific protein of identical relative molecular mass (58 kD) from metabolically labelled TdT+ myeloblasts and lymphoblasts. By Northern blot analysis and ribonuclease protection assay, TdT transcript levels were significantly lower in TdT+ myeloblasts and M+ lymphoblasts than in M- ALL (P < 0.0001). The level of TdT transcription in AML was independent of the simultaneous expression of lymphoid-specific antigens, such as CD2 and CD19. Our data demonstrate that TdT expression is downregulated in association with myeloid features, not only in AML but also in ALL. This observation may provide the molecular basis for the differential therapeutic responsiveness, particularly to glucocorticoids, in these various leukaemia subtypes.

Acute Disease↗
PubMed1993

Adjuvant tamoxifen versus placebo in elderly women with node-positive breast cancer: long-term follow-up and causes of death.

PURPOSE: This study analyzes the long-term results and causes of death in elderly women with node-positive breast cancer who participated in a double-blind adjuvant trial that compared tamoxifen with placebo to determine the benefit of 2 years of treatment. PATIENTS AND METHODS: One hundred eighty-one women 65 to 84 years old were given 20 mg of tamoxifen or placebo daily for 2 years after stratification by estrogen receptor status, tumor size, and degree of lymph node involvement. Approximately 30% of patients were older than 70 years and 20% were older than 75 years. Eighty-five percent were estrogen receptor-positive. Median follow-up was 10 years. RESULTS: Among the 168 eligible patients, there have been 98 recurrences (59 placebo v 39 tamoxifen), with reduced distant and bone-only first sites in patients treated with tamoxifen. Median time to failure was 4.4 years for placebo versus 7.4 years for tamoxifen (log-rank P = .001). A similar number of new nonbreast cancers occurred in each arm (seven placebo v six tamoxifen), but a reduced number of opposite-breast cancers (five placebo v one tamoxifen) was noted. Overall, there were 102 deaths (57 placebo v 45 tamoxifen). Median survivals were 8.0 years with placebo and 8.5 years with tamoxifen (log-rank P = .063); 50% of the tamoxifen patients and 33% of the placebo patients are still alive. Sixty-one percent of the deaths were reported to have been caused by breast cancer recurrence, 4% by other cancers, and 22% by the sequelae of non-cancer-related illness, with equal distributions for cardiovascular and cerebrovascular disease. There was no increase in the number of endometrial or other types of cancer, or thrombotic or orthopedic complications in this older group. CONCLUSION: Tamoxifen currently is the treatment of choice for elderly women with breast cancer. It extends the time to treatment failure by 3 years and reduces the number of recurrences, deaths, distant and bone-only first recurrences, and second breast cancers.

Aged↗
PubMed1993

Autologous bone marrow transplant in acute myeloid leukemia in first remission.

PURPOSE: The Eastern Cooperative Oncology Group conducted a prospective study of postremission high-dose chemotherapy and autologous bone marrow transplantation (autoBMT) in a group of uniformly treated adults with de novo acute myeloid leukemia (AML) to evaluate whether intensive, myeloablative therapy in first complete remission (CR) could improve the disease-free survival. PATIENTS AND METHODS: After initial CR was induced by the combination of daunorubicin, cytarabine, and thioguanine, patients not eligible for allogeneic bone marrow transplantation (alloBMT) were offered autoBMT. Within a median of 2 months after CR, and without intervening postremission therapy, bone marrow was obtained, purged by exposure to 4-hydroperoxycyclophosphamide (4-HC), and cryopreserved. High-dose therapy consisted of oral busulfan over 4 days (16 mg/kg total) followed by intravenous (IV) cyclophosphamide 50 mg/kg daily for 4 days. The cryopreserved marrow was then reinfused. RESULTS: Of the 39 patients scheduled for autoBMT, four relapsed before transplantation. Two of the 35 (6%) transplant patients died of transplant-related complications, and 11 (33%) relapsed a median of 8 months after marrow reinfusion. No relapse has occurred after 24 months posttransplant. With a median follow-up of 31 months, the median disease-free survival period for all 39 patients has not been reached; however, 54% +/- 16% of patients are projected to be alive and disease-free at 3 years. CONCLUSION: Long-term, disease-free survival after autoBMT in AML seems to be better than the outcome after conventional-dose postremission therapy and rivals the results of alloBMT.

Adolescent↗
PubMed1993

Recommended procedures for the classification of acute leukaemias. International Council for Standardization in Haematology (ICSH).

The classification of acute leukaemias is now widely based on a combined morphological, cytochemical and immunophenotyping approach. Difficulties are frequently encountered however in reaching an acceptable degree of diagnostic concordance between different laboratories because of variations in the techniques used (in terms of methodologies, reagents and equipment) and diagnostic interpretation. The International Council for Standardization in Haematology (ICSH) convened an expert panel to consider currently available diagnostic techniques with the aim of defining a minimum cytochemical and immunological diagnostic panel that could be used as core components for the classification of acute leukemia. The proposed ICSH scheme, which attempts to balance the basic requirement for providing precise and informative diagnostic information without limiting its use to only those laboratories with sophisticated facilities, is based on three sequential levels of investigation; primary cytochemistry, intracellular phenotyping and membrane immunophenotyping. The minimum ICSH recommended cytochemistries comprise myeloperoxidase (MPO), chloroacetate esterase (ChlorE) and alpha-naphthyl acetate esterase (ANAE), and standardised methods for these cytochemistries are detailed in this communication. For cases of acute leukaemia that remain unclassified by primary cytochemistry, subsequent immunological analyses for cytoplasmic CD3, CD22, MPO and nuclear TdT are recommended. The ICSH panel considers that the use of these minimum primary cytochemical and intracellular phenotyping procedures will lead to the consistent classification of most acute leukaemias, and that the third level of investigation (membrane immunophenotyping) should be used for the purposes of confirmation, diagnostic clarification of atypical leukaemias, and the subtyping of acute lymphoblastic leukaemias (ALL). The ICSH panel also recognised that there are a number of additional technologies which can provide definitive diagnostic information, such as cytogenetics and DNA genotyping, but these were excluded from the minimum panel because of their restricted availability. While many specialised laboratories, particularly in the areas of diagnostic research, will continue to use individual investigatory protocols, it is considered that the inclusion of the ICSH scheme as core components would lead to greater consistency when comparing independent studies of acute leukemia.

Acute Disease↗
PubMed1993

Neovascularization of canine sutured and stapled small intestinal anastomoses.

New blood vessels develop as a gastrointestinal anastomosis heals. The morphologic aspects of this neovascularization were studied in 22 dogs, each of which underwent one sutured and one stapled small bowel anastomosis. At intervals ranging from three to 24 days after surgery, the dogs were killed, and the bowel was injected with Batson's compound or india ink. The pattern of vascular growth across the anastomotic site was studied. Both stapled and sutured anastomoses caused an increase in submucosal capillary density at day three compared with control specimens taken from bowel remote from the anastomotic site. This increase was maintained consistently through day 24 in sutured anastomoses but had decreased by day five in stapled anastomoses. Growth of submucosal vessel across the anastomotic site could be demonstrated by day three in sutured and day four in stapled anastomoses. The more vigorous inflammatory response associated with sutured anastomoses may be responsible for more rapid and prominent neovascularization.

Anastomosis, Surgical↗
PubMed1992

Varying intensity of postremission therapy in acute myeloid leukemia.

The Eastern Cooperative Oncology Group (ECOG) conducted a randomized trial in patients less than or equal to 65 years old (median, 44 years) to determine whether increasing the intensity of postremission therapy in acute myeloid leukemia (AML) would improve the outcome. After uniform induction therapy, patients in complete remission (CR) who were less than 41 years old and who had a histocompatible sibling underwent allogeneic bone marrow transplantation (alloBMT) (54 patients). The remainder of patients in CR were randomized to receive either 2 years of continuous outpatient maintenance therapy with cytarabine and 6-thioguanine (83 patients) or a single course of inpatient consolidation therapy consisting of 6 days of high-dose cytarabine plus 3 days of amsacrine (87 patients). The median duration of follow-up is now 4 years, and patients are included in the analyses of outcome regardless of whether they relapsed before starting the intended treatment. Four-year event-free survival (EFS) was 27% +/- 10% for consolidation therapy versus 16% +/- 8% for maintenance therapy (P = .068) and 28% +/- 11% versus 15% +/- 9% (P = .047) in patients less than 60 years old. The outcome for patients receiving alloBMT was compared with the subset of patients less than 41 years old who received consolidation therapy (N = 29) or maintenance therapy (N = 21). Four-year EFS was 42% +/- 13% for alloBMT, 30% +/- 17% for consolidation therapy, and 14% +/- 15% for maintenance therapy. AlloBMT had a significantly better EFS (P = .013) than maintenance therapy, but was not different from consolidation therapy. In patients less than 41 years old, 4-year survival after alloBMT (42% +/- 14%) did not differ from consolidation therapy (43% +/- 18%), but both were significantly better than maintenance therapy (19% +/- 17%), P = .047 and .043, respectively. The mortality rate for maintenance therapy was 0%, consolidation therapy, 21%; and alloBMT, 36%. Consolidation therapy caused an especially high mortality rate in the patients greater than or equal to 60 years old (8 of 14 or 57%). The toxicity of combined high-dose cytarabine and amsacrine is unacceptable, especially in older patients, and alternative approaches to consolidation therapy such as high-dose cytarabine alone need to be tested. In AML, a single course of consolidation therapy or alloBMT after initial CR produces better results than lengthy maintenance therapy. Although EFS and survival of alloBMT and consolidation therapy do not differ significantly, a larger number of patients need to be studied before concluding that they are equivalent.

Acute Disease↗
PubMed1992

Malignant melanoma: primary presentation in bone marrow and lymph node.

We describe an unusual presentation of malignant melanoma with simultaneous lymph node and bone marrow metastasis. In addition the disease was associated with immune-mediated thrombocytopenia. A brief remission was obtained with combination chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

The evaluation of low-dose cytarabine in the treatment of myelodysplastic syndromes: a phase-III intergroup study.

One hundred and forty one patients were treated in a combined Eastern Cooperative Oncology Group and Southwest Oncology Group phase-III study evaluating low-dose cytarabine (LDAC) versus supportive therapy for the treatment of myelodysplastic syndrome (MDS). Patients were randomized to either cytarabine 10 mg/m2 subcutaneously BID or supportive therapy. Central pathology review was required. All patients were classified according to the FAB criteria for MDS. The overall concordance rate for the MDS subtype was 52%, and 25 patients were pathology exclusions, including 20 with AML. The overall response rate to a single cycle of LDAC was 32%, with 11% complete and 21% partial responses. The median duration of response was 5.9 months, with a range of 1.4-33.5 months. Responses were seen in all subtypes. Infections were more common in the LDAC arm. There was no difference in the time to progression or the overall survival for patients treated with LDAC or supportive therapy. The incidence of leukemic transformation was similar in both arms at 15%, but it differed according to the MDS subtype. Patients receiving LDAC had a decreased transfusion requirement after 3 months. There was a significant correlation between the degree of cytoreduction after receiving a single cycle of LDAC and survival. This survival difference was most marked in patients with the RAEB and RAEB-T subtypes. Although LDAC produced responses in all subtypes of the MDS, there was no effect on overall survival or transformation to AML. However, selected patients benefited from a single cycle of LDAC with durable responses. A cytoreductive effect appears to be required for a durable response. Future studies should include pathology review and must address the clinical and biological heterogeneity of MDS.

Adult↗