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Biomedical subjects

J M Bennett

Publications and source records attributed to J M Bennett.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Perceived intergenerational solidarity and psychological distress among older Mexican Americans.

A model separating and relating dimensions of intergenerational solidarity with measures of psychological distress was investigated for older Mexican Americans. Solidarity consisted of measures of similarity, affection, and association. Measures of psychological distress were somatic/retarded symptoms, depressed affect, and positive affect. To evaluate whether emotional closeness with a particular child modified the linkages, the model was analyzed separately based on whether or not the elderly participant reported that the child included in the intergenerational study was her or his closest child. The findings indicated that the impact of affection and association was a function of the particular dimension of distress and the emotional closeness of the child. Although the proposed model needs expanding, it provides some support for the expectation that family solidarity has important consequences for elderly Mexican Americans.

Aged↗
PubMed1992

Sequential administration of recombinant interferon alpha and deoxycoformycin in the treatment of hairy cell leukaemia.

Both recombinant interferon alpha and deoxycoformycin (dCF) are effective in the treatment of hairy cell leukaemia. In an attempt to reduce the complications from dCF therapy, a pilot study of the Eastern Cooperative Oncology Group (ECOG) first treated patients with interferon to improve peripheral blood cell counts before dCF treatment began. Thirty-four patients were treated for 3 months with recombinant interferon alpha-2a (rIFN alpha-2a), 3 x 10(6) IU subcutaneously three times a week for 3 months, and then by dCF, 4 mg/m2 intravenously every 2 weeks for a maximum of 12 months. The overall response rate was 94% (32/34); 76% of patients (26/34) had complete response (CR) (90% confidence interval, 62-88%) and 18% (6/34) partial response. One patient was found to have a Mycobacterium avium infection while receiving rIFN alpha-2a. Without specific antimycobacterial therapy and with continued administration of rIFN alpha-2a and dCF, the infection resolved and he achieved CR. Three patients had culture-negative febrile episodes during the dCF phase of treatment. Non-disseminated herpes zoster developed in four patients, but three of the episodes occurred only after treatment was discontinued. Sequential administration of rIFN alpha-2a and dCF resulted in fewer infections (P = 0.027) than in ECOG's previous study of dCF used alone. Two patients died, one of combined hairy cell leukaemia and non-Hodgkin's lymphoma of intermediate histologic type 17 months after entry into the study and the other of cardiac arrest 20 months after entry. Thirty-two patients were alive with a median follow-up of 21 months (range 13-31 months). This combination produces durable CRs with a low incidence of infection.

Adult↗
PubMed1992

The selective use of AMSA following high-dose cytarabine in patients with acute myeloid leukaemia in relapse: a Leukemia Intergroup study.

This clinical trial was designed to evaluate the role of high-dose cytarabine (ara-C) in the treatment of adults with acute myeloid leukaemia (AML) in first relapse. We also tested the hypothesis that the selective use of AMSA (100 mg/m2/d on days 7, 8 and 9) would increase the complete remission (CR) rate when leukaemia cells remained in the bone marrow immediately following 6 d of Ara-C (2-3 g/m2/12 h) alone. Of 155 patients evaluable for response, 115 (74%) experienced marked cytoreduction by day 6 and received no further induction chemotherapy; 53 (45%) of these patients achieved CR after one course and 45 (38%) had resistant disease. The 36 patients (23%) with inadequate cytoreduction after the 6 d of ara-C alone were randomly assigned either to no further chemotherapy (21 patients) or to 3 d of AMSA (15 patients). The CR rates after one course were 14% and 53%, respectively (P = 0.01), and the fractions with resistant disease were 76% and 40%, respectively. The fractional reduction of leukaemia cells in the day 6 bone marrow aspirate specimen (P < 0.0001) and the reduction in the leukaemia cell mass measured in the day 6 marrow biopsy (P = 0.001) were the strongest predictors for achieving CR versus having residual disease in univariate analyses. The median duration of remission was 5 months, but seven patients (10%) remain in CR after 30-92 + months. Among the 140 patients who received only the 6 d of ara-C, the pretreatment albumin (P = 0.002) and lactate dehydrogenase (P = 0.01) levels were the strongest predictors of response in univariate analyses, but only the albumin remained significant (P = 0.01) in a stepwise logistic regression analysis. Those patients with albumin > 4.0 mg/dl and LDH < 125% of normal had a 71% CR rate, and only 16% had resistant disease. Thus, pretreatment characteristics and rapid cytoreductin in the day 6 bone marrow sample identified a favourable subset of patients with AML in first relapse, some of whom responded quite well to 6 d of ara-C alone and have had long disease-free remissions.

Acute Disease↗
PubMed1992

Acute myeloid leukaemia with an unusual phenotype: myeloperoxidase (+), CD13 (-), CD14 (-) and CD33 (-).

We herein describe an unusual case of acute myeloid leukaemia (AML) showing strong cytochemical reactivity for myeloperoxidase (MPO) but surprisingly no reactivity using flow cytometry for any of the lineage-specific cell surface markers, i.e. myelomonocytic antigens CD13, CD14 and CD33; or B-lymphoid antigens CD19, CD20 and immunoglobulins; or T-lymphoid antigens CD2, CD3 and CD5. The strong reactivity for MPO and the complete absence of reactivity for CD13 and CD14 was verified by an independent assay involving alkaline phosphatase-anti-alkaline phosphatase (APAAP). Our case is of interest for at least two reasons: First, a poorly differentiated variant of AML (negative for MPO but positive for one or more of the myeloid-lineage CD antigens) has been designated FAB M0. In terms of the expression of phenotypic markers, our case may be considered as an 'MPO (+), CD antigen (-) AML'. The CD antigens are known to be expressed very early during myeloid differentiation whereas MPO (in its functional form) is viewed as being expressed relatively late in the process. It is therefore intriguing from a biological standpoint why the supposedly early antigens (CD33 and CD13) remain unexpressed; this may represent an example of 'asynchronous differentiation' in leukaemia. Second, from a practical standpoint, the use of immunophenotyping as a first-line diagnosis would fail to detect such cases. This case strengthens the notion that immunophenotyping by flow cytometry does not eliminate the necessity of performing peroxidase cytochemical staining.

Acid Phosphatase↗
PubMed1992

Evaluation of the dysmyelopoiesis in 336 patients with de novo acute myeloid leukemia: major importance of dysgranulopoiesis for remission and survival.

Myelodysplastic features and myeloperoxidase (MPO) deficiency have been investigated in a series of 336 cases of de novo acute myeloid leukemia (AML) to clarify their impact on the outcome of such patients and to compare with the previous results from the literature. Dysplastic features were defined according to the FAB criteria. Trilineage disease (TLD) was observed in 11.6% of patients (39 cases), and the complete remission rate (CR) was 56.4% for TLD patients compared to 74.4% for patients without any dysplastic features (p = 0.03). The effects of dysgranulopoiesis (DysM) alone or in combination were assessed using a logistic regression analysis. This analysis revealed that only DysG had any effect on CR rate (p = 0.013). The CR rate for patients with DysG was 56.6% and 71.5% for patients without DysG. We were unable to find any correlation between MPO deficiency, dysplastic features and CR rate. Cytogenetic analysis could be assessed for 119 patients. For patients with DysG, 10 karyotypes were normal and 20 were abnormal compared to 48 normal and 41 abnormal for patients without DysG (p = 0.05). We conclude that the presence of DysG in de novo AML exerts a negative effect on the ability to achieve a CR and is related to a higher frequency of cytogenetic abnormalities.

Adolescent↗
PubMed1992

Phase II study of mitoxantrone and 5-azacytidine for accelerated and blast crisis of chronic myelogenous leukemia: a study of the Eastern Cooperative Oncology Group.

A total of 40 evaluable patients were treated for blastic crisis of chronic myelogenous leukemia with mitoxantrone, 12 mg/m2 per day for three days and 5-azacytidine 150 mg/m2 per day for 5 days. Toxicity was primarily hematologic and was manageable. The overall response rate was 23%, including five complete responders, two partial responders, and two with hematologic improvement. Cytogenetic and immunophenotypic characterization of the leukemia was performed on all patients with aspirable bone marrow, and these results were correlated with response and survival, but did not have predictive value once the patient was in blastic crisis. Only initial platelet count (p = 0.02), hemoglobin (p = 0.03), and lower white blood cell count (p = 0.09) were somewhat predictive of response. Lack of hepatic involvement (p = 0.05), lower white blood cell count (0.05), and higher platelet count (p = 0.02) were predictive of prolonged survival. Although response did not strongly correlate with survival, one third of responders were alive at one year. This regimen produces results similar to those of other recently published regimens in this disease. Earlier intervention and more effective therapy is necessary in these patients.

Adult↗
PubMed1992

Phase II clinical trial of carboplatin in relapsed and refractory leukemia.

Carboplatin is a second-generation platinum complex drug which has demonstrated activity against a variety of neoplasms including acute leukemia, particularly when given by continuous intravenous (i.v.) infusion. Adults with acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL), either refractory or in first or second relapse, were given a continuous i.v. infusion of carboplatin at a dose of 315 mg/m2 daily for 5 days. A second course was given if the bone marrow at day 14 showed persistent leukemia. If the marrow was hypoplastic, treatment was delayed until marrow recovery was documented. Those with residual leukemia were given a second course. Those achieving complete remission (CR) were given an additional course as consolidation. Of the 46 eligible patients entered (36 AML and 10 ALL) eight achieved CR (17%) of which 6 were AML and 2 ALL. Of nine primary refractory patients, two achieved CR, one AML and one ALL. Excluding the inevaluable patients (protocol violations, patient refused further therapy, early deaths prior to day 14, the CR rate was eight of 28 (29%). All except two CRs required two courses of induction. The non-hematologic toxicity was minimal except for renal and auditory toxicity. Renal toxicity greater than grade 2 was seen in 17 patients and was associated with concomitant use of nephrotoxic antibiotics. In two patients, renal failure was a major factor in the cause of death. Ototoxicity was observed in 11 patients, but was grade 3 in only three. There were 18 deaths during the study. Fourteen died of infection, two died of infection and hemorrhage, one died of hemorrhage while aplastic, and one died of other causes. This trial indicates that carboplatin is an active agent in acute leukemia and warrants further investigation.

Bone Marrow↗
PubMed1992

Escalating the intensity of post-remission therapy improves the outcome in acute myeloid leukemia: the ECOG experience. The Eastern Cooperative Oncology Group.

These ECOG trials have demonstrated that progressive increments in the intensity of post-remission therapy result in improving long-term, disease-free survival in adults with AML. The median duration of disease-free survival and long-term outcome from different post-remission therapies are summarized in Table 4. [table: see text] Despite the suggestive evidence of the ordered increment in value of intensive consolidation therapy, allogeneic and autologous bone marrow transplantation, it remains to be proved that the differences observed in our preceding studies are statistically significant and clinically meaningful. These remaining questions led to the current ECOG study, EST 3489, a randomized intergroup study conducted with members of the Southwest Oncology Group. The study includes all patients with de novo AML up to age 55; the schema is shown in Figure 3. Induction therapy consists of idarubicin plus cytarabine instead of DAT. A modified short course of this induction therapy is repeated after CR. Patients who have a histocompatible sibling are offered allogeneic bone marrow transplantation. The remaining patients are randomized to receive either autologous bone marrow transplantation or a single course of high-dose cytarabine. Autologous bone marrow transplantation utilizes the previously described high-dose busulfan and cyclophosphamide regimen plus 4-HC purging of the bone marrow. The dosage of cytarabine in the intensive consolidation arm is 3 gm/M2/day IV on days 1-6. The results of this study should determine the relative merits of these different approaches to post-remission therapy. [table: see text] As mentioned earlier, demonstration of improved CR rates is limited by the morbidity and mortality from the myelosuppression that results from induction therapy. This is especially marked for older patients with AML. In patients, ages 55-70 years old, the ECOG is conducting a randomized trial (EST 1490) of conventional induction therapy +/- GM-CSF to determine if accelerated neutrophil recovery can reduce the mortality of induction therapy and thereby increase the remission rate. It may be that the application of GM-CSF and other colony-stimulating factors can increase the CR rate for all patients, increasing the number of patients potentially eligible for cure by post-remission therapy.

Acute Disease↗
PubMed1992

Burkitt cell leukemia with myelodysplasia as a presentation of HIV infection.

Hematologic manifestations of human immunodeficiency virus (HIV) infection include cytopenias, non-Hodgkin's lymphoma, and myelodysplasia. Acute lymphocytic leukemia has rarely been reported in association with HIV infection. We describe a patient who presented with Burkitt cell leukemia and myelodysplasia as her initial manifestation of HIV infection. The dysplastic features included circulating asymmetric binucleated red blood cells as well as pseudo Pelger-Huet cells. To the best of our knowledge, this has not been previously reported.

Adult↗
PubMed1992

Morphology and classification of myelodysplastic syndromes.

The FAB classification has provided a common language for clinicians and pathologists in the investigation of myelodysplasia. It has also provided prognostic information, given the excellent correlation between FAB subgroup and survival (see Table 2). Refinements in immunologic and cytogenetic typing should provide further prognostic power and correlation with the underlying biologic processes.

Hematopoiesis↗