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Biomedical subjects

B D Clarkson

Publications and source records attributed to B D Clarkson.

At least 109 records · Page 6Linked to original sources
PubMed1982

Multidisciplinary treatment of advanced Hodgkin's disease by an alternating chemotherapeutic regimen of MOPP/ABDV and low-dose radiation therapy restricted to originally bulky disease.

Ninety-one evaluable patients with advanced Hodgkin's disease (patients with stages IIB, IIIB, or IV disease and patients with IIIA disease who were greater than 35 years old or had mixed cellularity or lymphocyte depletion histology) received chemotherapy with MOPP and ABDV given in alternating months; radiation therapy (RT) (2000 rad in 2 weeks) was given during Month 5 of therapy to the previously untreated patients through ports that were limited to the originally bulky disease. The complete remission rates observed were: 88% in previously untreated patients, 69% in patients who had had prior RT but minimal chemotherapy, and 50% in patients who had had prior heavy chemotherapy. The actuarial relapse-free survival rates at 4 years, for patients who had complete remission, are: previously untreated, 84%; prior RT, 70%; and prior heavy chemotherapy, 30%. The total actuarial survival rates at 5 years for all 118 patients, evaluable and nonevaluable, who were entered in the study, are: previously untreated, 80%, prior RT, 57%; and prior heavy chemotherapy, 40%.

Adolescent↗
PubMed1982

Bone marrow cell count per cubic millimeter bone marrow: a new parameter for quantitating therapy-induced cytoreduction in acute leukemia.

A new technique is introduced for determining the number of bone marrow cells per cubic millimeter marrow, providing an accurate and objective means for quantitating therapy-induced cytoreduction. The method requires a correction for admixed peripheral blood in bone marrow aspirates to measure the fraction of remaining pure marrow. While cell kinetic differences between blood, aspirates, and biopsies identify the proportion of contaminating blood cells, the ratio of red cell hematocrits in blood and aspirate gives the volume of trapped blood. By combining both procedures, bone marrow cell counts per unit volume pure marrow result (BMC/cu mm BM), which were found highly reproducible. Blast cell counts (BMBC/cu mm BM) were obtained by additional morphological differentiation. BMC and BMBC/cu mm BM were monitored in 16 patients with acute nonlymphoblastic leukemia treated with daunorubicin, cytosine arabinoside, and 6-thioguanine in combination and in 4 patients with end-stage acute leukemias and non-Hodgkin's lymphomas during high-dose thymidine therapy. Total and daily therapy-induced cytoreduction rates were significantly greater (P less than 0.01) in responders than nonresponders to either regimen. Changes in BMC/cu mm BM were also found representative for changes in BMBC/cu mm BM, since the majority of bone marrow cells were blasts. In acute leukemia. BMC/cu mm BM thus provides accurate and objective measurements of treatment efficacy in vivo and after short periods of drug exposure. Differences in cytoreduction rates within the group of responders also suggest possible prognostic implications.

Acute Disease↗
PubMed1981

Angioimmunoblastic lymphadenopathy: clinical spectrum of disease.

The clinical features of 13 patients with angioimmunoblastic lymphadenopathy were analyzed to determine prognostic factors and response to therapy. Eleven patients presented with sudden onset of fever, weight loss, generalized lymphadenopathy, and hepatosplenomegaly. Laboratory features included autoimmune hemolytic anemia and polyclonal hypergammaglobulinemia. Pulmonary involvement was seen in six cases and skin rash in four. Two patients had localized lymphadenopathy without systemic symptoms. Both are alive at 5.5 and 2.5 years, respectively, after diagnosis, although the latter patient has required intermittent prednisone for recurrent lymphadenopathy. An additional patient is alive on treatment for months following diagnosis. The remaining ten have died, nine of sepsis and one of cerebral hemorrhage. The immunosuppression and myelosuppression of combination chemotherapy may have hastened their deaths. An individualized, conservative treatment approach is recommended.

Aged↗
PubMed1981

The treatment of advanced hodgkin's disease.

Between January, 1975, and December, 1978, 118 patients with advanced Hodgkin's disease were treated with 8 months of alternating MOPP and adriamycin, bleomycin, dacarbazine and vinblastine (ABDV) combined with 1 month of low-dose radiation therapy (2,000 rad) to areas initially involved with bulky disease. Among 57 evaluable previously-untreated patients, 50/57 (88%) achieved complete and 7/57 (12%) partial remissions. The estimated relapse rate among the complete responders was 16% at 36 months from date of remission. Toxicity was comparable to that of other combination chemotherapy regimens. These results are among the best reported for the treatment of patients with advanced Hodgkin's disease.

Adolescent↗
PubMed1981

Chronic myelogenous leukemia: in vitro studies of hematopoietic regulation in a patient undergoing intensive chemotherapy.

A patient heterozygous for the X-linked enzyme glucose-6-phosphate dehydrogenase and with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) was treated with combination chemotherapy and had a partial loss of Philadelphia chromosome accompanied by partial restoration of nonclonal hematopoiesis as determined by glucose-6-phosphate dehydrogenase. Studies of in vitro hematopoiesis were performed after chemotherapy to evaluate the influences of neoplastic stem cells on normal cells and to determine whether there were physical and cell kinetic differences between leukemic stem cells and their normal counterparts. The data revealed the following: (a) The frequencies of normal committed granulocytic stem cells (CFU-C) and erythroid stem cells (BFU-E) in blood did not differ from the frequencies in marrow. (b) Normal late erythroid progenitors (CFU-E) were found at a significantly lower frequency that the more primitive BFU-E. Calculations indicated that not only was there a decrease in CFU-E production by normal BFU-E, but there was also abnormal clonal expansion of CML BFU-E (CFU-E:BFU-E ratio for normal progenitors was 1.1, whereas for the CML clone it was 11.5). (c) No increase in frequency of normal CFU-C was found after marrow cells were exposed to high specific activity tritiated thymidine. (d) Normal CFU-C and those from the CML clone were not separable on the basis of density. (e) The frequency of normal BFU-E was consistently greater than that of CFU-C, suggesting that regulatory differences influence the commitment of normal progenitors to the two pathways.

Adult↗
PubMed1981

Treatment of acute leukemia in relapse with 4'(9-acridinylamino) methanesulfon-m-anisidide (AMSA) in combination with cytosine arabinoside and thioguanine.

Thirty-seven patients with acute leukemia in relapse were treated with a three-drug combination that included a 3- or 4-day course of AMSA with total doses ranging from 600 mg/m2 to 740 mg/m2 I.V., cytosine arabinoside 25 mg/m2 I.V. followed by 200 mg/m2 by continuous infusion daily for 5 days, and thioguanine 100 mg/m2 p.o. q 12h for 5 days. Eight of the 25 patients with acute nonlymphoblastic leukemia achieved a complete remission and 3 a partial remission. None of the five patients with acute lymphoblastic leukemia achieved a response and there was one partial remission in the seven patients with myelodysplastic syndrome or blastic CML. Reversible toxicity included nausea and vomiting (78%), alopecia (100%), pancytopenia (100%), mild stomatitis (63%), and hepatic dysfunction (24%). One patient developed seizures and cardiac arrhythmias. The activity of this combination in heavily treated patients with ANLL is comparable to that of the anthracycline-containing regimens, and its use in previously untreated patients with ANLL should now be explored.

Acute Disease↗
PubMed1981

The elusive goal: presidential address.

The advances in treatment of cancer which have taken place during the last 25 years are quite remarkable considering that therapists have had at their disposal only what has been called half-way technology. About 45% of serious cancers are now curable with surgery, radiotherapy, and chemotherapy or combined forms of these treatments, but prospects for developing curative therapy for the other half of cancer patients are not bright unless more selective forms of treatment can be developed. Recent advances in basic biology have opened doors to marvelous new research opportunities hardly imaginable a few years ago, and the time is opportune to make a concerted effort to develop more selective treatment.

Animals↗
PubMed1981

Cytotoxic and cytokinetic effects of thymidine, 5-fluorouracil, and deoxycytidine on HeLa cells in culture.

Exponentially growing HeLa cells were exposed to thymidine (dThd), 5-fluorouracil (FUra), and deoxycytidine (dCyd) singly and in combination for up to 3 days. Survivals were measured using a colony forming assay, and cytokinetic effects of the drugs were evaluated by flow cytometry and by determination of population growth rates. Increasing concentrations of dThd alone (up to 4 mM) progressively slowed the movement of cells through the cycle; dThd was toxic above 1 mM. Nontoxic levels of FUra (10(-5) M) inhibited cell progression, but this was abolished by very low concentrations (3 microM) of dThd. The cytotoxic effects of FUra were not reversed by dThd; in fact, the lethality of FUra was enhanced in some cases. dCyd alone had neither cytotoxic nor cytokinetic effects on HeLa cells up to 4 mM, but low concentrations reversed the cytotoxic effects of 4 mM dThd and high concentrations reversed its cytokinetic effects. When dCyd was added to the combination of dThd and FUra, synergistic lethality resulted even at 10(-5) M FUra. The mechanism by which this synergism was achieved was not simply increased incorporation of FUra into RNA since, while dThd did enhance this incorporation, dCyd did not further increase it. Our results suggest instead that dCyd either directly or indirectly inhibited the repair of FUra-associated damage or else enabled the cells to progress into a more sensitive phase of the cell cycle during exposure.

Cell Division↗
PubMed1981

Induction of giant fat cells in human bone marrow culture by human serum factor.

Evidence is presented below that normal human sera contain a potent non-dialyzable factor inducing abundant giant fat cells in human bone marrow culture, normal as well as CML. Media with 20% heated (56 degrees C) human serum induce during 7-14 days almost complete monolayer of fat cells on the bottom of the plastic flasks or dishes. Fetal bovine sera do not exhibit this effect and shift cultures to the proliferation of fibroblasts. We are studying the functions of fat cells in hemopoiesis as well as the biochemical nature of fat cell-inducing factor in human sera.

Adipose Tissue↗
PubMed1981

Cytotoxic and cytokinetic effects of 1-beta-D-arabinofuranosylcytosine, daunorubicin, and 6-thioguanine on HeLa cells in culture.

Exponentially growing HeLa cells were exposed to 1-beta-D-arabinofuranosylcytosine, daunorubicin, and 6-thioguanine singly and in combination for 21 hr. Survivals were determined by a colony-counting assay, and cytokinetic effects of the drugs were evaluated by flow cytometry. When used in two-drug combinations (concurrent exposures). 1-beta-D-arabinofuranosylcytosine was found to protect cells against both 6-thioguanine- and daunorubicin-induced lethality, the former to a greater extent than the latter. Protection against 6-thioguanine appeared to be related to the degree of inhibition of DNA synthesis by 1-beta-D-arabinofuranosylcytosine, but this was not the case with daunorubicin. When cells were exposed to the three drugs simultaneously, survivals were in agreement with those predicted from the various two-drug combinations. This implies that no additional drug interactions occurred when a third drug was added to the two-drug combinations.

Cell Cycle↗
PubMed1980

The eight-drug/radiation therapy program (MOPP/ABDV/RT) for advanced Hodgkin's disease: a follow-up report.

Eighty-four evaluable patients with advanced Hodgkin's disease (Stages IIB, IIIA age greater than 35 or mixed cellularity or lymphocyte depletion histology, IIIB, IVA, and IVB) were treated with alternating monthly MOPP and Adriamycin, bleomycin, dacarbazine, and vinblastine (ABDV). Radiation therapy (RT), 2000 rads in two weeks, was given to areas of initial bulky disease in untreated patients. Complete remission (CR) rates were 80% for previously untreated, 65% for prior RT or minimal chemotherapy treated, and 50% for heavily pretreated patients. Among 49 previously untreated patients there were no primary treatment failures. The estimated two-year relapse rate for the CR group was 9%. The therapeutic effectiveness of this program may have been due to either or both of the following elements: (1) two non-cross-resistant drug combinations, (2) low dose adjuvant RT to initial sites of bulky disease. These early results are among the best reported for the treatment of advanced Hodgkin's disease.

Adolescent↗
PubMed1980

A long-term clinical follow-up of children with acute lymphoblastic leukemia treated with intensive chemotherapy regimens.

One hundred and thirty-three children 15 years old and younger with acute lymphoblastic leukemia were treated with two different protocols. Both regimens consist of a multi-drug program, without CNS irradiation, administered for three years. Seventy-five children were enrolled on the first protocol, L-2; and 58 were treated on the subsequent regimen, L-10. Of the 70 evaluable patients on the L-2 program, 40 continue in complete remission from 72-111 months. Seventy-four percent of the children qualified for treatment cessation, and 59% have remained in continuous remission for six years. The estimated seven year disease-free survival for the 70 evaluable children on the L-2 protocol is 57% and for all entries is 53%. Of the 57 evaluable patients on the L-10 program, 35 are in complete remission from 15-67 months. The combined frequency of primary CNS leukemia for the two regimens is 7%. The off-therapy results of the L-2 protocol cannot be compared to the L-10 at present, but the on-therapy outcomes, despite the modifications that were designed to improve the L-10 regimen, are comparable.

Adolescent↗
PubMed1980

Bone marrow transplantation for the therapy of refractory adult T cell acute lymphoblastic leukemia.

Two adult patients with T cell acute lymphoblastic leukemia (ALL) received an intensive multiagent therapeutic regimen and failed to enter remission. Following cytoreduction with cyclophosphamide (60 mg/kg x 2) and total body irradiation (1000 rads) they underwent bone marrow transplantation. One patient received marrow from his identical twin brother and the other from his HLA-matched sister. Both patients promptly went into remission. The identical twin recipient is alive and free of disease at 20+ months, but the allogeneic patient died of P. carinii pneumonia at eight months with no evidence of leukemia. These results suggest that even some refractory patients whose disease has multiple negative prognostic features may respond to pretransplant chemoradiotherapy and attain a clinically useful complete remission. Additional patients with longer follow-up will be necessary before the curative potential of bone marrow transplantation in T cell ALL can be assessed.

Adult↗
PubMed1980

Plasma beta-thromboglobulin values in thrombocytopenic patients with acute leukemia.

Plasma beta-thromboglobulin (beta-TG) levels were measured in 14 healthy subjects and in 20 acute leukemia (AL) patients, newly diagnosed, with highly variable values for venous platelet counts. For healthy subjects the plasma beta-TG levels ranged 12-38 (mean 17) ng/ml. In this group of patients with AL, a highly significant positive correlation (P < 0.001) between the values for plasma beta-TG and venous platelet count was present. During a thrombocytopenic period, the plasma beta-TG concentraton was measured in nine of the AL patients immediately before and 10 to 12 hours after platelet transfusion therapy. Fourteen platelet transfusions were administered when the patient's highest temperature of the day was < 38.5 degrees C, and 18 when the highest temperature of the day was greater than or equal to 38.5 degrees C. The mean pre-transfusion and post-transfusion beta-TG values for the 14 platelet transfusions were 7 +/- 2 and 20 +/- 5 ng/ml, respectively. The corresponding means for the 18 transfusions given to febrile patients were 5 +/- 2 ng/ml and 11 +/- 2 ng/ml, respectively. Of the pretransfusion values, 11/14 and 14/18 were below the control range. We conclude that the plasma beta-TG values are considerably lower in thrombocytopenic patients than in subjects with normal platelet counts. Further work should provide reference values for plasma beta-TG over a wide range of venous platelet counts.

Adolescent↗
PubMed1980

A micromethod for determination of terminal deoxynucleotidyl transferase (TdT) in the diagnostic evaluation of acute leukemias.

A micromethod for the determination of TdT in peripheral leukocytes and bone marrow cells has been developed that allows unequivocal identification and quantitation of TdT in less than 1 X 10(6) leukocytes from ALL patients, i.e., in 1 ml of peripheral blood and/or 0.5 ml of bone marrow obtained during routine clinical sampling. The method involves disruption of cell pellet with high salt and detergent followed by centrifugation of extracts at 12,000 X g and partial purification on phosphocellulose matrix by a batch elution technique using a standard laboratory microcentrifuge. Using this microassay, TdT activities have been determined in 500 samples of peripheral blood and bone marrow of 240 adult patients with acute leukemias (86 ALL, 108 ANLL, 44 blastic CML, two acute leukemias following P. vera). From an analysis of our data based on TdT activity, cell surface markers and growth patterns in soft agar and observations published in the literature, it can be concluded that the frequencies of TdT + phenotypes in the various clinical-morphological diagnostic groups are approximately 95% in ALL, 10% in ANLL, 50% in AUL, and 35% in blastic CML. Since the presence of high TdT activity is clearly associated with clinical response to specific forms of chemotherapy in blastic CML and most probably, also in ANLL, the determination of TdT should be considered in all cases of acute leukemias to objectively define prognostically important subgroups which can not be diagnosed by conventional means.

Acute Disease↗