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Biomedical subjects

B Clarkson

Publications and source records attributed to B Clarkson.

At least 73 records · Page 4Linked to original sources
PubMed1986

Prognostic significance of terminal deoxynucleotidyl transferase activity in acute nonlymphoblastic leukemia.

Bone marrow and/or peripheral blood samples from 133 (75%) of a total of 177 consecutive previously untreated protocol patients with acute nonlymphoblastic leukemia (ANLL) were analyzed for terminal deoxynucleotidyl transferase (TdT) activity at the time of presentation. Twenty-nine (22%) were found to exhibit TdT activity (greater than or equal to 0.10 U/10(8) cells, TdT+) as measured in a biochemical microassay. There were no differences between TdT+ as compared with TdT-negative (TdT-) patients with respect to age, sex, French-American-British (FAB) classification, or the presence of Auer's rods. Remission induction rates were higher for the TdT- patients, with 68% v 48% for the TdT+ patients (P = .05). TdT- patients also experienced longer remissions (P = .003) than TdT+ patients, especially in the Auer's rod-positive subgroup (P = .002). None of five patients with TdT+ ANLL treated with vincristine and prednisone as initial therapy achieved complete remission; all required induction regimens containing daunorubicin or amsacrine in combination with cytosine arabinoside and 6-thioguanine. It is concluded that TdT activity in ANLL indicates biphenotypia or lineage infidelity and is associated with a poor prognosis on chemotherapy protocols currently used for the treatment of ANLL.

Bone Marrow↗
PubMed1986

Growth and development of children born to patients after cancer therapy.

Eighteen children born to parents who had previously received chemotherapy or radiotherapy were examined for physical health, growth, and development. The immunologic and the hematologic status of these children was also evaluated. Their ages ranged from birth to 15 years. The children had a careful history and physical examination to detect any abnormal symptoms or signs, and the parent's previous treatment was carefully documented. Four sets of parents had children while one of the parents was on active treatment (2 male and 2 female). Of the male patients, one patient's wife had a baby that was "small for gestational age" at birth and had transient failure to thrive; the other child was normal. Of the female patients, one offspring was small for gestational age at birth and the other was normal, but both continued to have failure to thrive for up to 17 months and 26 months, respectively. Ten parents procreated after being treated with chemotherapy and/or radiotherapy, to whom 14 children were born. One child was a stillbirth with multiple congenital abnormalities, and another child had trisomy 13-15 and died 6 months later. The other 12 children were normal at birth, but one child is under the 5th percentile for growth at twelve months of age. In all children studied, immune function test, complete blood count, and viral titers were considered normal for age. In our study, we found that three out of four children born to parents who were on chemotherapy had failure to thrive. Of the 14 children born to parents who conceived after being off chemotherapy, 11 were found to be normal in growth and development. These results imply that there is a high risk of complications in children born to parents who procreated while receiving chemotherapy. Further studies are needed to develop better guidelines for counseling cancer patients who want to have children.

Abnormalities, Multiple↗
PubMed1986

Predictive model for prognosis in advanced diffuse histiocytic lymphoma.

The purpose of this study was to examine the validity of a predictive model for response to treatment and survival in advanced diffuse histiocytic lymphoma. One hundred twenty-seven consecutive patients with Ann Arbor stage II-IV diffuse histiocytic lymphoma, who completed treatment between 1974 and 1984 in one of four different Memorial Hospital combination chemotherapy protocols, were reviewed. The median follow-up time was 66.9 months for survivors (range, 21-153.1 months). Factors studied included: age; sex; Ann Arbor stage; prior therapy; B symptoms; serum lactic dehydrogenase (LDH); sites of initial disease; and tumor bulk. LDH was grouped accordingly (units/liter): low, less than 225; medium, 225-500; high, greater than 500. Each patient was assigned an overall level of site involvement (LSI) from the following mutually exclusive groups: group I, peripheral lymph node (PLN) (including +/- Waldeyer ring involvement, +/- spleen); group II, extranodal disease (EN) +/- PLN; group III, retroperitoneal lymph node (RLN) +/- PLN; group IV, bulky mediastinal disease (MED) +/- any other disease; group V, EN with RLN +/- PLN. The Ann Arbor staging system failed to dissect patient groups differing significantly in their prognosis. Serum LDH, LSI, and age were the only factors important for predicting response and survival after multivariate logistic regression and a parametric Weibull survival analysis. Using three levels of serum LDH and correlating them with the different LSI, four tentative "stages" differing significantly in their survival at 48 months were defined: stage I, low LDH, any LSI (80% alive); stage II, medium LDH, PLN, and/or EN (50% alive); stage III, high LDH, PLN, and/or EN or medium LDH, RLN +/- PLN +/- EN, and/or MED (35% alive); stage IV, high LDH, RLN +/- PLN +/- EN, and/or MED (15% alive). Identification of prognostic stages on the basis of LDH level and LSI will allow more accurate comparison of clinical trials for patients with advanced diffuse histiocytic lymphoma.

Adult↗
PubMed1985

Relationship of Auer rods and chromosome findings to outcome in eighty-nine adults with acute nonlymphoblastic leukemia.

We performed cytogenetic analyses using banding techniques on 89 adults with acute nonlymphoblastic leukemia prior to receiving protocol chemotherapy. The relationships of cytogenetic findings both to outcome and to other pretreatment variables (particularly the presence or absence of Auer rods) were analyzed. Patients were followed up to 90+ months. When patients were grouped according to cytogenetic findings (NN: all normal metaphases; AA: all abnormal metaphases; AN: both normal and abnormal metaphases; F: no evaluable metaphases; I: insufficient (less than three) metaphases) no significant differences were noted with regard to age, sex, terminal transferase positivity, complete remission rate, remission duration or survival. The marrow aspirates of patients with only normal (69%) metaphases or no evaluable metaphases (64%) were more likely to display Auer rods than specimens from individuals with only abnormal (26%) or a mixture of normal and abnormal (42%) metaphases (p = 0.03). The presence of Auer rods in the pretreatment marrow aspirate was associated with an increased complete remission rate (71% vs 41%, p = 0.004), median remission duration (12 months vs 9 months, p = 0.02), and median survival (13 months vs 4 months, p = 0.01). Using multivariable analyses, the presence or absence of Auer rods was the pretreatment factor that most significantly predicted response and survival in this group of patients. The presence of a normal karyotype in the initial cytogenetic preparation is associated with the presence of Auer rods. The finding of Auer rods in the initial bone marrow predicts greater response and longer survival in acute nonlymphoblastic leukemia.

Acute Disease↗
PubMed1985

Growth of human bone marrow in vitro.

Attempts were made to establish human bone marrow (HBM) culture. Cell proliferation was triggered by medium conditioned by acute myelocytic leukemic (AML) cells exposed to 12-0-tetradecanoyl-phorbol-13-acetate (TPA). A 6-15 fold multiplication of myelomonocytic cells was obtained in tissue culture from HBM cells. Proliferation of granulocyte-macrophage colony forming cells (CFC-GM) occurred up to 30-fold. The morphology of the cells and cytochemical markers were investigated at all stages of the culture.

Bone Marrow Cells↗
PubMed1985

Incidence of involvement of the B and T lymphocyte lineages in chronic myelogenous leukemia.

Peripheral blood specimens were obtained from 22 patients with Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia (CML) (16 in chronic phase, 2 in an accelerated phase, and 4 in blast crisis). Studies were performed to determine the frequency of the presence of the Ph1 chromosome in cells of lymphoid lineages. Rosetted (E+) lymphocytes (T lymphocytes) from nine patients in chronic phase and one patient in blast crisis were stimulated with T cell growth factor interleukin 2 (IL-2) and/or phytohemagglutinin (PHA). All ten patients had sufficient T lymphocyte metaphases for analysis and of a total of 461 metaphases examined, only one contained the Ph1 chromosome. Nucleated cells of density less than 1.077 g/mL were infected with Epstein-Barr virus (EBV). Following infection, cell lines were established from individual colonies attached to egg albumin-coated Lab-Tek slide chambers (clonal cell lines) or from suspension culture in 96-well tissue culture cluster dishes (nonclonal cell lines). Cell surface and intracellular marker analysis confirmed the B lymphocyte phenotype of all the cell lines examined. B lymphoblastoid cell lines were established from 16 of the 22 patients. All lines from 12 patients were Ph1-negative. From two chronic phase patients, both Ph1-positive and Ph1-negative lines were established. From one patient in an accelerated phase, only Ph1-positive lines were established. From another patient in blast crisis (of myeloblastic phenotype), only Ph1-positive lines were established initially; however, five months later, after the patient had been treated with mitoxantrone, only Ph1-negative lines were derived from this patient. Based on these results, it appears that most B cells and mature T cells in most CML patients are Ph1-negative, but that about 25% of patients have predominantly Ph1-positive B cells or a mixture of Ph1-positive and Ph1-negative B cells that are capable of growing as established cell lines after transformation with EBV.

Adolescent↗
PubMed1985

Regulation of human peripheral blood erythroid burst-forming unit growth by T lymphocytes and T lymphocyte subpopulations defined by OKT4 and OKT8 monoclonal antibodies.

To reexamine the influence that T lymphocytes have on the regulation of human peripheral blood burst-forming unit (BFU-E) proliferation in the absence of a statistically significant number of monocytes, very low numbers (3 to 10 X 10(3)/mL) of a null cell fraction highly enriched for BFU-E were cultured alone and in the presence of 5 X 10(5) sheep erythrocyte-purified, autologous T lymphocytes in a methylcellulose culture system containing erythropoietin. T lymphocytes consistently enhanced the growth of BFU-E from the null cell fraction, as reflected in both their number and size. Irradiation of T lymphocytes prior to coculture with null cells markedly reduced this enhancement, strongly suggesting that T lymphocytes synthesize erythroid burst-promoting factors (BPA). To determine whether there were functional differences between the two major T lymphocyte populations as defined by OKT4 (T helper/inducer) and OKT8 (T suppressor/cytotoxic) murine monoclonal antibodies to stimulate the growth of BFU-E, both T cell subpopulations were isolated by negative (panning) or positive (fluorescence-activated cell sorting) selection and cocultured with null cells. No statistically significant differences emerged between unseparated, OKT4+ and OKT8+ T lymphocytes in their ability to stimulate the growth of BFU-E. Thus, these studies provide further evidence that T lymphocytes are a major population of BPA-producing cells and further that OKT4+ and OKT8+ T lymphocytes equally elaborate these factors.

Animals↗
PubMed1984

Treatment of diffuse poorly differentiated lymphocytic lymphoma. An analysis of prognostic variables.

Forty patients with diffuse poorly differentiated lymphocytic lymphoma (DPDL) Stages II-IV were treated with three different and successive combination chemotherapy protocols. Seventeen patients were treated with the cyclophosphamide (CTX) L2 protocol which included maintenance chemotherapy for 3 years. Only three patients were treated with the NHL-3 (non-Hodgkin's lymphoma) protocol, and 20 patients received the NHL-5 program. All protocols included radiotherapy (1500-4800 rad) to areas of initial bulky disease or persistent tumor, as well as central nervous system (CNS) prophylaxis with intrathecal methotrexate in patients with bone marrow involvement. Seventy-eight percent of local recurrences occurred in previously irradiated areas. Two-year survival rates were 55% and 70% for the CTX-L2 and NHL-5 protocols, respectively. Median disease-free survival for 24 complete response (CR) patients was 16.5 months. Of the 40 patients, 37 were evaluable for response to therapy. The CTX-L2 produced an 80% total response (TR) rate, a 60% CR, and a 20% partial response (PR). The patients on the NHL-5 achieved a TR rate of 95%, 74% CR, and 21% PR. Differences in TR and CR between the two protocols were not significant. Only 1 of 3 patients on the NHL-3 protocol achieved a CR. There was a trend for age greater than 50 years to lessen the chances of CR (P = 0.091); however, sex, symptoms, stage of disease, and LDH level were not significantly related to CR rate. Response to treatment (CR versus PR versus failure) was the most important factor influencing survival (P less than 0.001); age (greater than 50 years) was also significant (P = 0.008). Lactate dehydrogenase (LDH) was of borderline significance (P = 0.06). Cox regression model showed age (greater than 50 versus less than 50 years, P = 0.001), LDH (greater than 500 versus less than or equal to 500 U/L, P = 0.019) and symptoms (A or B) to be the best predictors of survival.

Adult↗
PubMed1984

Oral trimethoprim/sulfamethoxazole in attempt to prevent infection after induction chemotherapy for acute leukemia.

The efficacy of orally administered trimethoprim/sulfamethoxazole for infection prevention following induction chemotherapy was evaluated in 43 patients with acute leukemia. Twenty patients were randomly assigned to treatment with trimethoprim/sulfamethoxazole during 20 episodes of profound granulocytopenia; 23 patients in the control group were followed through 25 granulocytopenic episodes. The incidences of superficial skin and overall infections were significantly lower in those patients with multiple relapses who received trimethoprim/sulfamethoxazole (p = 0.008); however, there was no difference between the groups in regard to days of fever, days of antibiotic administration, days of hospitalization, or gram-negative rod bacteremia. As a result of this study, this regimen cannot be unequivocally recommended for infection prevention in neutropenic patients with acute leukemia undergoing induction or reinduction chemotherapy.

Acute Disease↗
PubMed1984

Establishment of a near-tetraploid B-cell lymphoma line with duplication of the 8;14 translocation.

The neoplastic cells of a patient with diffuse histiocytic lymphoma were grown in three systems: Soft agar, liquid culture, and by heterotransplantation into the nude mouse. In each case, the growing cells were shown to bear the same immunoglobulin heavy and light chain type as the original neoplastic cells (IgM-lambda). In both the liquid culture and nude mouse heterotransplant tumors, karyotypic analysis revealed the presence of pseudodiploid and near-tetraploid metaphases bearing one and two copies of an 8;14 translocation, respectively. From the liquid culture separate clones of pseudodiploid and near-tetraploid cells were isolated in soft agar, and separate cell lines SK-DHL2A and SK-DHL2B were established. Studies comparing the proliferative characteristics of the two lines showed no difference in cell population doubling time or clonigenicity in soft agar. Hence, the presence of two copies of the translocated material did not confer a proliferative advantage on cells containing it. Theses lines may be valuable in future studies of cell proliferation and oncogenesis in the human immune system.

Adult↗