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Biomedical subjects

M M Oken

Publications and source records attributed to M M Oken.

At least 127 records · Page 7Linked to original sources
PubMed1984

A phase II trial of VP 16-213 in adults with refractory acute myeloid leukemia. An Eastern Cooperative Oncology Group study.

VP-16-213 was studied in 38 adult patients with relapsed or refractory acute myeloid leukemia as part of a randomized trial in an ECOG master protocol. In this group of heavily pretreated patients, an overall response rate of 18% was achieved (5% CR, 13% PR). Toxicity was mild, and aplasia was rarely observed. Responses were seen in all of the FAB myeloid subtypes. Patients who had never achieved remission status responded as well as patients who had relapsed.

Adult↗
PubMed1984

A critical comparison of allogeneic bone marrow transplantation and conventional chemotherapy as treatment for acute nonlymphocytic leukemia.

Published data from two centers conducting bone marrow transplantation on patients with acute nonlymphocytic leukemia in first remission were pooled and compared with results from an Eastern Cooperative Oncology Group (ECOG) study in which patients were treated with conventional chemotherapy. A series of adjustments were made to the ECOG sample to account for selection factors that restrict access of patients to transplantation. The transplant sample exhibits considerably higher disease-free survival when compared to the adjusted ECOG series (53% versus 21% at three years). The transplant series is somewhat younger than the ECOG series (median, 24 years versus 28 years). The impact of age on the disease-free survival results is difficult to assess because of the relatively small samples in the different age groups. However, by defining a suitable control group, methodology for making a critical comparison between the two modalities is presented which, if applied to larger samples of patients, should help to resolve the issue. In the absence of data from a large, prospective randomized study, a critical retrospective comparison of available data is essential in the assessment of treatment options.

Acute Disease↗
PubMed1984

High-dose cytosine arabinoside and m-AMSA is effective therapy in relapsed acute nonlymphocytic leukemia.

High-dose cytosine arabinoside ( HDARAC ) and 4'-(9 acridinylamino) methane sulfon -m-anisidine (m-AMSA) was administered as induction therapy to 40 patients with relapsed or refractory acute nonlymphocytic leukemia (ANLL) with the following results: 28 patients (70%) achieved complete remission, one patient achieved a partial remission; five patients died with hypoplastic bone marrows containing less than 5% blasts; four patients died with hypoplastic marrowing containing greater than 5% blasts; and three patients failed to achieve marrow aplasia and died without significant cytoreduction in percentage of blasts. Consolidation therapy was not used and maintenance therapy was given to less than 10% (three patients) of remission patients. The median duration of remission for all patients was 6.0 months and the median time for the complete remission patients exceeded eight months. This regimen has acceptable toxicity and the results are equivalent to those obtained from conventional induction therapy of de novo ANLL patients.

Acute Disease↗
PubMed1983

Thermoregulatory effects of purines and caffeine.

Purines are putative neurotransmitters which appear to be involved in regulating several vegetative functions. We examined the effect of purines and their antagonist, caffeine, on colonic temperature of rats. Adenosine injected ip lowered colonic temperature in a dose responsive manner at ambient room temperatures. Adenine and AMP also lowered body temperature whereas 7-methylinosine and inosine only slightly influenced colonic temperature. Caffeine (50 mg/kg) injected sc, increased colonic temperature and when injected within 60 seconds of adenosine, counteracted the hypothermic effect of adenosine (50 mg/kg). Low ambient temperature (4 degrees C) accentuated the thermoregulatory effects of adenosine. Thus adenosine appears to have a hypothermic effect on body temperature regulation when administered peripherally which can be reversed by caffeine.

Adenosine↗
PubMed1983

Sequential cyclophosphamide-prednisone and vincristine-bleomycin (CPOB). An effective, schedule-dependent treatment for advanced diffuse histiocytic lymphoma.

In an Eastern Cooperative Oncology Group non-Hodgkin's lymphoma clinical trial, 90 patients with Stage III or IV diffuse histiocytic lymphoma (DHL) were treated with one of four chemotherapy regimens. All patients were previously untreated with chemotherapy, and careful restaging was required to document responses. Each treatment included cyclophosphamide, vincristine and prednisone (COP) plus Adriamycin (COPA), BCNU (BCVP) or bleomycin (COPB and CPOB). The two bleomycin-containing regimens differed only in the schedule of drug administration. CPOB-treated patients received cyclophosphamide on day 1, prednisone on days 1 to 5 and vincristine and bleomycin on day 15 of each 21-day cycle. COPB-treated patients received the same four drugs in the same dosage; however, the schedule was changed so that vincristine and bleomycin were given on day 1. Treatment of responders was continued for 8 cycles. Those with a complete response (CR) were randomized to maintenance therapy with BCVP or no treatment. Treatment with CPOB yielded a CR rate of 55% compared to 25% for COPB (P = 0.07). In contrast to COPB, treatment with CPOB was associated with a significantly longer median duration of CR (26.5 versus 5.7 months; P less than 0.05) and median survival (27.7 versus 11.2 months; P less than 0.02). The CR rate was 31% for BCVP and 45% for COPA, and the median survivals were 10.7 months and 14.4 months, respectively. One half of the CPOB-treated patients who achieved CR remained alive in continuous CR after 30 to 72 months. No advantage for maintenance therapy was observed. Myelotoxicity was greater with CPOB than COPB, but comparable to COPA. This trial demonstrated that the results of treatment of DHL with COP plus bleomycin were strikingly dependent upon the schedule of administration of bleomycin and vincristine. Bleomycin effectively combined with COP, as in CPOB, yielded results comparable to those obtained when Adriamycin was added to COP. CPOB appears to be an effective treatment for DHL that should be considered as an alternative to other regimens, particularly for patients who cannot receive Adriamycin.

Antineoplastic Agents↗
PubMed1983

Chronic myelodysplastic syndrome: short survival with or without evolution to acute leukaemia.

The myelodysplastic syndromes represent a prognostically diverse group of disorders. Their study has recently been facilitated by the classification proposed by the French-American-British (FAB) Cooperative Group. Using this scheme it is now possible to define more precisely their natural history and clinical relationship to acute leukaemia. Using the longitudinal case control technique, we reviewed the clinical data and morphology of 69 patients (all elderly males) with chronic irreversible haematological cytopenia and dysplasia. Applying FAB criteria we found: refractory anaemia (RA) in 43%; sideroblastic anaemia (RA-S) in 33%; refractory anaemia with excess blasts (RAEB) in 13%; RAEB in transformation (RAEB-T) in 9% and chronic myelomonocytic leukaemia (CMML) in 1%. The median survival for the entire group was 27 months (RA, 52; RA-S, 29; RAEB, 12; RAEB-T 11; and CMML, 2 months). Short survival was predicted by transfusion requirement and other manifestations of severe cytopenia, as well as by myeloid immaturity. The presence or absence of sideroblastosis did not correlate with survival. Acute leukaemia developed in only eight patients (12%), six of whom initially had RA. Leukaemic transformation was not predicted by progressive cytological immaturity. This study demonstrates that even in the absence of leukaemic transformation, chronic myelodysplasia is a lethal haematological disorder.

Adult↗
PubMed1983

The influential T cell in B-cell neoplasms.

Investigations of human B-cell malignancies have generally focused on the monoclonal B-cell populations. Until recently there has been little emphasis on the thymus (T) lymphocyte in these disorders. Current studies, however, suggest that quantitative and qualitative disorders of T cells are generally seen both in chronic lymphocytic leukemia and in multiple myeloma. This review will focus on two major concepts. First, it will define the quantitative and functional T-cell abnormalities in B-cell malignancies including evidence suggesting a causal link between the T-cell abnormalities and certain observed disease manifestations in chronic lymphocytic leukemia and multiple myeloma. Secondly, it will review data demonstrating that these T cells may be influenced by in vivo and in vitro manipulations and will outline some of the possible resultant clinical effects.

B-Lymphocytes↗
PubMed1982

Distinctive chromosomal abnormalities in histologic subtypes of non-Hodgkin's lymphoma.

Using a new high-resolution technique for chromosomal analysis, we have successfully studied biopsy specimens of lymph nodes from 42 of 44 patients with non-Hodgkin's lymphoma and have categorized them using the new international histologic formulation and immunologic markers. Abnormalities of the clonal chromosomes were detected in all 42 patients. Three recurrent chromosomal aberrations were found to correlate with certain histologic types: a translocation between chromosomes 18 and 14 in 16 of 19 patients with follicular lymphomas (small cleaved cell, mixed cell, and large cell); a translocation between chromosomes 8 and 14 in 5 of 6 patients with small noncleaved-cell (non-Burkitt's) or large-cell immunoblastic lymphoma; and a trisomy 12 in 4 of 11 patients with small-cell lymphocytic lymphoma. Our findings suggest that characteristic chromosomal defects occur in certain lymphoma subtypes and that high-resolution chromosomal analysis promises to become an important tool in improving our basic understanding of lymphoid cancers.

Adolescent↗
PubMed1982

Non-Hodgkin's lymphoma after treatment for Hodgkin's disease.

A patient is described who developed a diffuse histiocytic lymphoma (DHL) 9 years after radiation therapy for Hodgkin's disease. This occurrence is of particular interest because the treatment for Hodgkin's disease included no chemotherapy and the second tumor appeared to originate remote from the irradiated site. Thus, the role of Hodgkin's disease treatment in the etiology of this patient's second lymphoma appears doubtful. The development of DHL in this patient could represent an unrelated event or conceivably an event facilitated by Hodgkin's disease itself.

Aged↗
PubMed1982

Enhanced T cell suppression is directed toward sensitive circulating B cells in multiple myeloma.

Multiple myeloma, a disorder typically accompanied by monoclonal immunoglobulin excess and hypogammaglobulinemia was evaluated to delineate the status of T cell regulation on malignant B cell proliferation. Intact T cells and T cell subsets previously noted by us to be suppressor (T gamma) and helper (T non-gamma) were isolated from 10 controls and 10 myeloma patients. Various concentrations of control and patient T cell subsets were mixed with control and patient B cells and stimulated with PWM. T cell effect on B cell proliferation as measured by [3H]thymidine incorporation was then determined. Myeloma T gamma cells were more effective than control T gamma cells in suppressing control or myeloma B cell [3H]thymidine incorporation. Interestingly, myeloma B cells, when added to myeloma T gamma cells, were suppressed to a greater extent than were control B cells when mixed with a similar concentration of myeloma T gamma cells. These in vitro studies suggest a complexity of B and T cell abnormalities in multiple myeloma; first, the myeloma B cells are extremely sensitive to T gamma cell suppression, and second, myeloma T gamma cells have excessive suppressor capacity. It is yet unclear whether these results are associated with an immunoregulatory response to this malignancy or represent part of the basic disease process.

B-Lymphocytes↗
PubMed1982

Effect of endotoxin fever on plasma clearance of thyroxine and tri-iodothyronine: concise communication.

Endotoxin-induced fever in rabbits causes a rapid decrease in serum T3, a reciprocal rise of 3,3',5'-tri-iodothyronine (rT3), and a less marked reduction in T4 with a rebound at 24 hr. To answer the question whether the alteration in hormone levels was the result of a decrease in T3 or T4 production and release or of an increase in T3 and T4 metabolism, we measured the disappearance of [125I]T4 and [125I]T3 during endotoxin-induced fever and externally applied heat. Results showed no significant difference in disappearance of [125I]T4 or [125I]T3. This suggests that the rapid change in T3 levels associated with endotoxin fever is due to an inhibition of thyroid production and peripheral conversion, and not to increased metabolism of hormones.

Animals↗
PubMed1981

Capping of peripheral blood lymphocyte C3 receptors in chronic lymphocytic leukemia: relationship to chemotherapy.

The data show that in chronic lymphocytic leukemia (CLL) there are elevated numbers of peripheral blood lymphocytes (PBL) capable of rosette formation (complement-rosetting lymphocytes, CRL) with bacteria (B)-antibody-(A)-complement (C) (BAC) complexes. In most of the CLL patients studied, large percentages of CRL were impaired in their ability to undergo BAC-C3R cap formation compared to normal donors. The degree of impairment varied from one patient to the next. A consideration of clinical information suggested that the variation was related to the clinical response of patients to chemotherapy. Four categories of CLL patients could be identified on the basis of clinical data: (1) patients never received therapy for CLL; (2) those whose clinical history indicated a failure to respond to ongoing chemotherapy; (3) patients who had received successful prior chemotherapy and who were asymptomatic or stable and were receiving no therapy at the time of study; and (4) those who were undergoing therapy at the time of study and who subsequently became stable or asymptomatic and were removed from therapy. The first two categories of patients failed to show significant BAC-C3R capping, whereas the last two were able to form C3R caps on significant percentages of CRL. No direct relationship could be discerned between C3R capping and currently accepted classifications on stages (Rai) of CLL. These results suggest that monitoring the percentages of BAC-C3R cap-forming CRL may be useful in determining the success of chemotherapy of CLL patients. The microtubule-disrupting agent colchicine enhanced BAC-C3R capping in all CLL patients to normal levels, whereas the microfilament-disrupting agents cytochalasin B(CB) had no effect on CLL RBL C3R capping. CB totally abolished C3R capping of CRL from normal donors. These results suggest that abnormalities exist in both cytoskeletal and contractile systems of CR from CLL peripheral blood.

Antineoplastic Agents↗
PubMed1981

Auer rod positive dysmyelopoietic syndrome.

Twenty-five patients with refractory anemia with excess blasts (RAEB) were studied. Five of these patients showed Auer rods in their myeloblasts, but met other criteria for RAEB. Median survival of the Auer rod-positive group was 14 months (range 2-27) from diagnosis with survival of 7 months after Auer rods were first observed. Median survival for the Auer rod-negative group was 12 months. Two patients developed overt acute leukemia, both from the Auer rod-negative group. The clinical course of Auer rod-positive RAEB, like that of Auer rod-negative RAEB, was one of progressive bone marrow failure complicated by infection, serious bleeding and the development of absolute transfusion requirement. These findings suggest that Auer rod-positive RAEB is a morphologic variant dysmyelopoietic syndrome that may pursue a similar clinical course to Auer rod-negative disease. Formulation of a separate treatment approach for those RAEB patients who possess Auer rods would appear ill advised.

Aged↗
PubMed1981

Influence of treatment and response status on infection risk in multiple myeloma.

The clinical course of 60 patients with multiple myeloma was examined for risk factors associated with infection. The overall incidence of infusion was 1.46 per patient-year. The greatest risk period for the occurrence of infection was the first two months after the start of initial chemotherapy. The incidence of infection during this period was 4.68 infections per patient-year compared with 1.04 infections per patient-year for subsequent months. Serum creatinine levels of 2 mg/dl or more (p less than 0.03) and decreased polyclonal serum immunoglobulins (p less than 0.01) predicted increased risk of early infections. Patients infected during the first two months of initial chemotherapy had the same rate of infection during the subsequent clinical course as did patients free of infection during the early treatment period. Thus, the early risk period does not represent only the attrition of susceptible patients. Patients who achieved an objective response had a decrease in infection risk during the time of the response (0.44 infections per patient-year). While response to chemotherapy prolongs life in multiple myeloma, the initiation of chemotherapy is associated with a definable risk period for infections.

Adult↗
PubMed1981

T-cell subpopulations in multiple myeloma: correlation with clinical disease status.

T-lymphocyte subpopulations bearing Fc receptors for IgM (T mu) or for IgG (T gamma) were studied in blood specimens obtained from 40 normal volunteers and from 16 patients with multiple myeloma. The myeloma patients showed a significant imbalance in T-cell subpopulations characterized by an increase in the percentages of T gamma cells to 30.0 +/- 3.9% (mean +/- SEM) compared with 12.0 +/- 3.0% for the controls (P less than 0.001). The patients exhibited a decreased proportion of T mu cells (13.4 +/- 4.1%) compared with the control value of 55 +/- 7% (P less than 0.001). When the results were analysed according to clinical status it was the patients with indolent or well-controlled disease and not those with progressive disease who exhibited an elevated proportion of T gamma cells. The elevation of T gamma cells or of a subpopulation of suppressor cells should be further studied as a possible mechanism of disease control in multiple myeloma.

Aged↗