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F Davey

Publications and source records attributed to F Davey.

11 recordsLinked to original sources

Extramedullary leukemia adversely affects hematologic complete remission rate and overall survival in patients with t(8;21)(q22;q22): results from Cancer and Leukemia Group B 8461.

PURPOSE: To examine the prognostic significance of extramedullary leukemia (EML) at presentation in patients with t(8;21)(q22;q22) karyotype. PATIENTS AND METHODS: Consecutive patients with t(8;21) treated on Cancer and Leukemia Group B de novo acute myeloid leukemia (AML) treatment studies were examined for the presence of EML (granulocytic sarcoma, subcutaneous nodules, leukemia cutis, or meningeal leukemia) at initial presentation. Clinical features and outcome of t(8;21) patients with and without EML were compared. RESULTS: Of 84 patients with t(8;21), eight (9.5%) had EML manifesting as granulocytic sarcoma (five paraspinal, one breast, and one subcutaneous) or symptomatic meningeal leukemia (n = 1). The pretreatment prognostic variables of t(8;21) patients with and without EML were similar. The hematologic complete remission (CR) rate for t(8;21) patients with EML was 50% versus 92% for those without EML (P=.006). The median CR duration for EML patients was 14.7 months. Patients with EML had a shorter survival (P = 0.002, median 5.4 months versus 59.5 months). This poor outcome may relate to inadequate local (radiation or intrathecal) therapy for patients with spinal or meningeal EML, resulting in residual/recurrent EML following induction chemotherapy (n = 2) or at relapse (n = 1) and permanent neurologic deficits (n = 4). Only one of the EML patients received high-dose cytarabine (HDAC) intensification; this is the only EML patient remaining alive in CR. CONCLUSION: Patients with t(8;21) and EML have a low CR rate and overall survival. An aggressive local and systemic induction therapy should be considered for this patient subset. The effectiveness of HDAC intensification in t(8;21) patients with EML is uncertain and warrants further study.

Adult

Recombinant alpha-2b-interferon in therapy of previously untreated hairy cell leukemia: long-term follow-up results of study by Cancer and Leukemia Group B.

In 1985, Cancer and Leukemia Group B initiated a multi-institutional study to define the role of interferon alpha in therapy of previously untreated active hairy cell leukemia (HCL). This is a long-term follow-up report of the study. Fifty-five evaluable patients were treated with recombinant interferon-2b 2 million units/m2 subcutaneously three times a week for 1 year. Treatment was well tolerated; toxicity mainly consisted of flu-like syndrome and pancytopenia, both of a transient nature. Seventy-three percent of patients had objective beneficial responses with 8.3 months median time to achieve at least a partial response (PR). After 1 year of therapy, the patients have been observed for a median of 5 years. There was a continual trend towards relapse throughout this period but 28% have remained in remission beyond 6 years. Forty-six patients (83%) are alive at 6 years. Among the 40 patients who achieved at least a PR, there were 28 with splenomegaly at the beginning of study: the spleen size was reduced in all with interferon alpha therapy and none required splenectomy. This study confirms the results of other investigators, and demonstrates that recombinant alpha interferon-2b is an effective agent for treatment of hairy cell leukemia.

Adult

Myths surrounding the use of urinary catheters: a summary of key beliefs that inhibit acute care nurses from altering their use of urinary catheters.

Nurses frequently base their use and care of indwelling urinary catheters on long held beliefs that contemporary research is disproving. As an excellent place of attachment, the catheter permits rapid migration of organisms into the bladder, independent of the position of the catheter bag. For treatment of bladder distension, intermittent catheterization is preferable to leaving an indwelling catheter in place. Regardless of the amount of urine obtained, intermittent catheters are usually not intended to remain in the bladder. Irrigation of a bypassing urinary catheter forces organisms into the upper urinary tract. The process of irrigating blocked catheters (except for urology patients) is no longer the preferred intervention. Instead, catheters obstructed from prolonged use must be replaced with new ones or, whenever possible, left out. As a foreign device, urinary catheters in acute care must be recognized as a potential health threat. Indwelling urinary catheter must not be used for nursing convenience to ease heavy workloads, nor left in place as a result of patient coercion.

Acute Disease

Clinical significance of the BCR-ABL fusion gene in adult acute lymphoblastic leukemia: a Cancer and Leukemia Group B Study (8762).

The Philadelphia (Ph1) chromosome, or its molecular counterpart, the BCR-ABL fusion gene, is a rare but important prognostic indicator in childhood acute lymphoblastic leukemia (ALL), but its impact on adult ALL has not been well ascertained. A prospective study of the BCR-ABL fusion gene was begun on patients entered on clinical trials conducted by the Cancer and Leukemia Group B (CALGB). All patients received intensive, multiagent chemotherapy that included daunorubicin. Over 2 years, 56 patients were studied for molecular evidence of a BCR-ABL gene using Southern blot and pulsed-field gel hybridization analysis. Results were compared with cytogenetic detection of a Ph1 chromosome, and clinical features were compared for the BCR-ABL-positive and -negative groups. Molecular methods detected the BCR-ABL gene in 30% of cases compared with cytogenetic detection of the Ph1 chromosome in only 23%. The majority of cases (76%) showed the p190 gene subtype similar to pediatric ALL; the BCR-ABL-positive cases displayed a more homogeneous immunophenotype than the BCR-ABL-negative cases and were predominantly CALLA positive (86%) and B-cell surface antigen positive (82%). The rate of achieving complete remission was similar in the BCR-ABL-positive and -negative groups (71% and 77%, respectively, P = .72). There were more early relapses in the BCR-ABL-positive group, resulting in a shorter remission duration that was especially marked in the CALLA-positive and B-cell antigen-positive populations. These preliminary data suggest that the impact of the BCR-ABL gene on clinical outcome in ALL may be on maintenance of complete remission (CR) rather than achievement of CR when aggressive, multiagent chemotherapy is used. This study identifies the BCR-ABL gene as an important factor in adult ALL and demonstrates the utility of molecular methods for its accurate diagnosis.

Adolescent

Glove talk.

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Cross Infection

Phase III trial of brief intensive treatment of adult acute lymphocytic leukemia comparing daunorubicin and mitoxantrone: a CALGB Study.

This paper reports a study of the Cancer and Leukemia Group B (CALGB) comparing daunorubicin (DNR) or mitoxantrone (DHAD) in induction followed by multidrug intensification over 8 months in adult patients with acute lymphocytic leukemia (ALL). A total of 164 newly diagnosed patients were randomly assigned to either DNR or DHAD plus vincristine, prednisone and methotrexate given intravenously (i.v.) and interthecally (i.t.). Patients received four more intensification courses of chemotherapy and then all therapy was stopped. Central nervous system (CNS) prophylaxis consisted of nine infusions of intermediate dose methotrexate (MTX) and intrathecal MTX. DHAD and DNR were equally effective in producing complete remissions (63 and 65%, respectively). The estimated median remission duration is 10.2 and 12.3 months for the DHAD and DNR arms, respectively (p = 0.56). This study was stopped earlier than planned when it became apparent that remission duration for both arms was shorter than seen in our prior study in which all patients received more than 1 year of maintenance therapy. The estimated median survival is 18.3 and 20.6 months for the DHAD and DNR arms, respectively (p = 0.90). Younger patients and patients with a pre-treatment white blood count of less than 30,000/microliters had a significantly longer remission duration and survival. Eleven per cent of patients who achieved a complete remission have had a CNS relapse to date, which is not different from the rate in our prior study using cranial irradiation and i.t. MTX, implying that intermediate dose MTX with i.t. MTX may be as effective as cranial irradiation and i.t. MTX. This study suggests that some form of maintenance chemotherapy is required for the eradication of residual leukemia cells.

Adolescent

Efficient transformation of previously activated and dividing T lymphocytes by human T cell leukemia-lymphoma virus.

Modifying previously reported techniques, we attempted to increase the efficiency of human T cell leukemia-lymphoma virus (HTLV) transformation of human T lymphocytes. Lethally irradiated donor cells (DCs) were cultured with target mononuclear cells (TMCs). DCs included ten HTLV+ T cell lines with varying degrees of virus expression or seven cell lines that do not express HTLV. TMCs were prepared from 20 cord and 16 adult peripheral blood samples, including eight patients with acquired immunodeficiency syndrome (AIDS). TMCs were either added directly to the DCs or were first stimulated with phytohemagglutinin (PHA) (5 micrograms/mL) and grown in T cell growth factor (TCGF) prior to exposure to DCs. The presence of integrated HTLV proviral DNA in the transformed cells was determined by dot blot hybridization, utilizing a cloned probe to the HTLV-I genome. HTLV production by transformed TMCs was assessed for HTLV p19, reverse transcriptase, and virus particles. No transformation occurred with T cell donor lines that do not express HTLV. Low virus expressor DCs could only, with rare exception, transform preactivated TMCs. High-titer virus-producing DCs could transform activated and nonactivated cord blood cells and activated adult TMCs. Only MT-2 could routinely transform nonactivated normal adult and activated AIDS TMCs. HUT 102 B2 could transform only one activated AIDS sample, the cells of which initially expressed HTLV-like proteins and virions. Transformed cell lines contained subsets of mature T lymphocytes with variable HTLV expression. Prior activation and culture of the T lymphocytes increases the probability and rate of transformation by HTLV, allowing for biologic detection of low HTLV-producing cells and for in vitro expansion of T lymphocyte subsets from selected patients.

Acquired Immunodeficiency Syndrome

Pharmacokinetics of vinblastine-loaded platelets utilized in the treatment of platelet-phagocytizing tumors.

Vinblastine-loaded platelets (VLP) have been successfully used in the treatment of idiopathic thrombocytopenic purpura. Three patients with platelet-phagocytizing tumors and thrombocytopenia were treated with VLP. Patient 1 has sustained a response for 11 months. Patient 2 was not evaluable for response because of early death. Patient 3 had a brief partial response. Vinblastine levels were measured by radioimmunoassay in the platelet-rich plasma, platelet-poor plasma, and serum. The pharmacokinetic data obtained on the patients suggest that: (a) the amount of vinblastine bound to platelets in vivo is a function of the platelet-poor plasma vinblastine level and the platelet count; (b) VLP will probably not have any therapeutic advantage, compared with iv vinblastine alone in patients with normal platelet counts; and (c) it appears that delivery of vinblastine was tumor-specific, since the bone marrow serum vinblastine level in patient 2, obtained when the marrow was replaced by tumor cells, was 2.5-fold higher than a simultaneous peripheral blood serum vinblastine level after VLP. Additional studies with VLP appear warranted in patients with platelet-phagocytizing tumors resulting in thrombocytopenia.

Adult

TrkB signalling inhibits p75-mediated apoptosis induced by nerve growth factor in embryonic proprioceptive neurons.

Neurotrophins mediate their effects by binding to members of the Trk family of receptor tyrosine kinases and the neurotrophin receptor p75 [1]. Whereas Trks are essential for the trophic effects of neurotrophins [1], p75 has distinct functions in different cells. For example, it enhances the survival response of certain neurons to nerve growth factor (NGF) [2], but mediates a cytotoxic response to NGF in certain other cell types and neurons [3] [4] [5] [6]. We investigated whether the p75-mediated responses to NGF can be modulated through the activation of different signalling pathways in the same neurons. Neurons of the embryonic trigeminal mesencephalic nucleus (TMN) are supported in culture by brain-derived neurotrophic factor (BDNF) and an unrelated neurotrophic factor, ciliary neurotrophic factor (CNTF), but not by NGF [7] [8] [9]. We found that NGF killed TMN neurons that were grown in the presence of CNTF; this effect of NGF was inhibited by anti-p75 antibodies and therefore occurred via a p75-dependent mechanism. NGF did not affect the survival of neurons grown in the presence of BDNF, and very low concentrations of BDNF inhibited NGF cytotoxicity. These results indicate that the activation of different signalling pathways in TMN neurons influences their susceptibility to p75-mediated NGF cytotoxicity.

Animals

Characterization of the B lymphocyte response to pokeweed mitogen.

Human B lymphocytes activated by pokeweed mitogen (PWM) undergo a proliferative response, differentiate into immunoglobulin producing cells (IPC), and release immunoglobulin into the supernatant fluid of the lymphocyte cultures. Since the number of IPC and amount of immunoglobulin produced may be determined in part by the proportions of T and non-T lymphocytes in the culture, studies were undertaken on the kinetics of the PWM induced response in cultures containing 1 : 1 proportions of T and non-T cells from nine healthy adults. Blood samples were obtained from each individual on two occasions and the results compared. The proliferative response, number of cells containing intracytoplasmic immunoglobulin (ICIg) and the concentration of supernatant immunoglobulin (SIg) were serially determined. The mean peak proliferative response and the mean peak number of ICIg positive cells were observed on the fifth day of culture. The mean peak concentration of SIg was noted on the ninth to eleventh day of culture. The results of the initial specimens were not significantly different from those of the repeat samples. It is concluded that a 1 : 1 mixture of T and non-T cells respond reproducibly to PWM and that the level of response varies with the length of incubation of the cultures. It is believed these assays might be helpful in the investigation of various lymphoproliferative and immunodeficiency disorders.

Adult