Biomedical subjects

M J Keating

Publications and source records attributed to M J Keating.

At least 253 records · Page 14Linked to original sources

PubMed1988

Alterations in human circulating and bone marrow mononuclear cell polyamine levels in hematologic malignancies as a consequence of difluoromethylornithine administration.

The effect of administering increasing intravenous doses of difluoromethylornithine on human tumor cell polyamine levels was determined in patients with hematologic malignancies. Difluoromethylornithine from 5.5. to 64 gm/m2 per day was administered to nine patients with refractory acute leukemia or multiple myeloma. Putrescine, spermidine, and spermine levels were determined on a daily basis in the circulating mononuclear cells and on a weekly basis in the mononuclear cells of the bone marrow. Tumor cell putrescine levels declined in 5 patients, spermidine levels declined in 4 patients, and spermine levels declined in 3 patients. Alterations in the polyamine levels of the bone marrow mononuclear cells paralleled those occurring in the peripheral blood mononuclear cells in the patients with leukemia. Seven to ten days of DFMO treatment were required for mononuclear cell polyamine levels to decrease. The higher drug doses were not significantly more effective than the lower doses in bringing about a decline in tumor cell polyamine levels, either with respect to treatment time required for onset of response or with respect to the ultimate extent of response.

Adolescent↗

PubMed1988

Mucocutaneous herpetic infections during cancer chemotherapy.

Adults who are given immunosuppressive and myelosuppressive cancer chemotherapy have a heightened risk for development of herpetic infections during treatment. The impact is much greater in patients who are given antineoplastic drugs for leukemia and lymphoma than in those who are given such drugs for carcinoma and sarcoma. In the series reported here, the incidence of herpes simplex infections exceeded that of herpes zoster infections in patients treated for leukemia by a ratio of more than 12:1, compared to slightly more than 2:1 in patients treated for solid tumor. The frequency of herpes simplex and herpes zoster infections during treatment for leukemia was 25%. Corresponding frequencies for patients with lymphoma, carcinoma, and sarcoma were 28%, 8%, and 3%, respectively.

Adult↗

PubMed1988

Polyamines increase in human peripheral blood and bone marrow mononuclear cells following administration of methylglyoxal bis(guanylhydrazone).

Eight patients who had refractory leukemia and 1 patient with refractory multiple myeloma were treated with the polyamine biosynthesis inhibitors methylgloxal bis(guanylhydrazone) (MGBG) and difluoromethylornithine (DFMO). After the first dose of MGBG there was an increase in polyamine content in the mononuclear cells of both the peripheral blood and the bone marrow despite the administration of DFMO in all patients with leukemia. Putrescine levels increased in the mononuclear cells of all patients, cellular spermidine levels increased in 4 and cellular spermine levels increased in 5 patients. The cellular polyamine levels remained elevated above the pretreatment levels for up to 1 week in some patients. Subsequent treatment with MGBG, administered after 1-2 weeks of DFMO treatment, also promoted increases in mononuclear cell polyamine concentrations. Since enhanced tumor cell uptake of MGBG after DFMO priming is hypothesized to be dependent on a decrease in cellular polyamine levels, the increase in cellular polyamines after MGBG has important implications for the scheduling of this drug combination. From these observations, withholding MGBG until DFMO treatment has produced a decrease in tumor cell polyamine concentrations would be the schedule most likely to enhance the uptake of MGBG.

Adult↗

PubMed1988

The characteristics and outcome of patients with late relapse acute myelogenous leukemia.

The characteristics and outcome of 58 patients with acute myelogenous leukemia (AML) who experienced relapse after a first remission duration longer than 18 months (late-relapse AML) were analyzed and compared with those of 278 patients with earlier relapses. Late-relapse AML was associated with a lower incidence of antecedent hematologic disorder, leukocytosis, and elevated creatinine and lactic acid dehydrogenase (LDH) levels. A favorable karyotype (inversion of chromosome 16; translocations between chromosomes 8 and 21, or 15 and 17) was more frequent in patients whose first remission was 12 months or longer compared with less than 12 months (30% v 10%; P less than .0001). An unfavorable karyotype (chromosome 5 and 7 abnormalities, trisomy 8, other changes) was more frequent in the latter category (16% v 42%; P less than .0001). Thirty-seven of the 58 patients (64%) with late-relapse AML achieved complete remission (CR). The incidence of CR increased significantly with an increased first remission duration from less than 12, 12 to 18, and greater than 18 months (17% v 41% v 64%; P less than .0001), while the incidence of resistant disease was significantly lower (59% v 36% v 19%; P less than .0001). When effective antileukemic regimens were considered, remission rates were also significantly increased by the duration of first remission (24% v 48% v 72%; P less than .001). Compared with patients with earlier relapse, those with late-relapse AML had a longer median survival from salvage therapy (3.5 v 12 months; P less than .01), and longer median second remission durations (3.5 v 11 months; P less than .01). We conclude that late-relapse AML has unique clinical, cytogenetic, and prognostic characteristics, and remains extremely sensitive to chemotherapy with a potential cure fraction. The duration of first remission is an important prognostic parameter in AML relapse and may be useful in the design and analysis of future salvage programs.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1988

Fludarabine therapy in chronic lymphocytic leukemia (CLL).

Fludarabine (9-beta-D-arabinofuranosyl 2-fluoro-adenine monophosphate) is a fluorinated analogue of adenine which is relatively resistant to deamination by adenosine deaminase. Phase I clinical trials disclosed significant antitumor activity in lymphoid malignancies. Fludarabine has been used in the treatment of CLL since March, 1985, at a dose of 25-30 mg/m2/day x 5 days each 3-4 weeks by short intravenous infusion. Sixty-eight previously treated patients with CLL are evaluable for response. The median age was 60 years, 50 were male the median number of prior chemotherapy regimens was 2, and the median time from initial chemotherapy to fludarabine was 45 months. Forty-three (63%) were Rai stages 3 and 4, 31 (46%) were Binet Stage C. Twenty patients (29%) obtained a complete remission (CR), defined as peripheral lymphocytes less than 4,000/microliters, no clinical evidence of disease, less than 30% of lymphocytes in the bone marrow (with no residual nodules), or a nodular partial remission, NPR (CR except for residual lymphoid nodules), and 19 (28%) a partial remission (less than 50% reduction in tumor in nodes, liver, spleen and bone marrow and greater than 1 log reduction in the lymphocyte count). The complete remission rate for the various involved sites were blood (69%), liver (52%), spleen (55%), and nodes (48%). The bone marrow was the least responsive site with 16% CR and 44% PR. The number of prior regimens did not have a significant response rate or survival. The serum albumin , alkaline phosphatase, platelet and hemoglobin level all were associated with survival from the start of fludarabine.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimetabolites, Antineoplastic↗

PubMed1988

Identification of risk groups for development of central nervous system leukemia in adults with acute lymphocytic leukemia.

The risk of development of CNS leukemia was investigated in 153 adults with acute lymphocytic leukemia (ALL) who received systemic combination chemotherapy without CNS prophylaxis. Overall, 31 patients (20%) developed CNS leukemia after a median of 6 months of therapy; the estimated 1-year incidence of CNS leukemia was 21% (SE, 3.9%). Characteristics significantly associated with CNS involvement included the presence of elevated hemoglobin creatinine, alkaline phosphatase, fibrinogen, and lactic dehydrogenase levels; B-cell leukemia; and high leukemic cell proliferative activity. Multivariate analysis identified lactic dehydrogenase levels of greater than or equal to 600 U/L and greater than or equal to 14% of cells in the S + G2M compartment to have independent additive poor prognostic significance. Patients were categorized into different risk groups for CNS leukemia with 1-year incidences ranging from 4% to 55%. While related to a high occurrence of CNS leukemia at diagnosis (33%) and subsequently (100%), the low incidence of B-cell disease excluded it from the multivariate analysis. The use of systemic chemotherapy containing multiple agents with good CNS penetration and in high doses (VAD regimen) in 90 patients was associated with a trend for lower CNS leukemia at 1 year (15% v 31%), especially in the low-risk category. We propose to develop future therapies for adults with ALL that include risk-oriented CNS prophylactic approaches.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1988

Antileukemic effect of recombinant tumor necrosis factor alpha in vitro and its modulation by alpha and gamma interferons.

The effect of recombinant human tumor necrosis factor alpha (rTNF-alpha) on human myelogenous leukemia clonogenic cells growing either in semisolid media or in suspension cultures was studied and compared with the effect on normal granulocyte-macrophage progenitors (GM-CFC). Exposure of cells to a range of rTNF-alpha doses including pharmacologically achievable plasma concentrations revealed a large heterogeneity in the response of leukemic clonogenic growth to rTNF-alpha. Only one of 13 specimens was highly resistant to rTNF-alpha. Eight of ten leukemic samples were significantly more sensitive than were normal GM-CFC, particularly within the in vivo achievable dose range (1 x 10(0) to 1 x 10(2) ng/mL). No significantly increased inhibition of either normal or leukemic clonogenic growth could be achieved by increasing the rTNF-alpha concentration above 250 ng/mL. Proliferation of leukemic clonogenic cells (L-CFC) was studied in suspension cultures. In five cases the clonogenic cells were significantly inhibited by rTNF-alpha while in one case no inhibition was observed. The inhibition of L-CFC growth by rTNF-alpha was dose dependent between 1 x 10(0) and 1 x 10(2) ng/mL. In suspension cultures, the TNF effect on L-CFC was a function of time of exposure, particularly with low concentrations of TNF. A remarkably higher inhibition of L-CFC as compared with the total leukemic population was observed in suspension cultures. Stimulation of L-CFC growth by rTNF-alpha was not observed. Normal GM-CFC were inhibited by alpha and gamma interferons (INF-alpha, -gamma) in a dose-related manner, with higher sensitivity of colonies than clusters. The response of GM-CFC to combination of recombinant IFNs and TNF was influenced by the size of clones scored and the source of colony-stimulating activity. The response of L-CFC to recombinant IFN-alpha and/or -gamma was highly variable, and sensitivity to one of the lymphokines did not predict for sensitivity to another. The response of L-CFC to combinations of rTNF-alpha and either IFN-alpha or IFN-gamma was complex, varying from synergistic to additive and indifferent. In three of six specimens, IFN-gamma acted antagonistically with rTNF-alpha, a phenomenon not observed with IFN-alpha. These observations suggest that the action of rTNF-alpha in acute myelogenous leukemia could be exploited therapeutically and the dose-time-response relationship should be considered in designing treatment schedules.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Division↗

PubMed1988

Cytogenetic pattern in acute myelogenous leukemia: a major reproducible determinant of outcome.

An analysis was conducted of clinical and laboratory variables associated with response to remission induction therapy and remission duration in 440 patients with acute myelogenous leukemia treated between 1975 and 1983. The complete remission rate was 259/440 (59%). Specific cytogenetic abnormalities such as t(8;21), t(15;17), and inv16 were found to be favorable for response to therapy and/or remission duration, whereas those with a normal (diploid) karyotype had an intermediate prognosis. All other karyotypic abnormalities were associated with lower response rates and short complete remission durations. The karyotypes were classified as favorable, intermediate, and unfavorable groups for response and remission duration after allowing for all the other observed clinical and laboratory values related to prognosis. The cytogenetic classification was prospectively validated in an independent test group of 130 patients treated between 1983 and 1986 and showed a consistent relationship to response and remission duration. Logistic regression and proportional hazard models developed from the initial 440 patients were prospectively evaluated in the test group of 130 patients. Clear stratifications of patients into good, intermediate, and poor risk groups were obtained in the prospective tests. The karyotype of the leukemia cells is an independent prognostic variable for response and remission duration in acute myelogenous leukemia.

Analysis of Variance↗

PubMed1988

Multiple agent chemotherapy (POACH) in previously treated and untreated patients with chronic lymphocytic leukemia.

A multiple agent chemotherapy protocol utilizing cyclophosphamide, adriamycin, cytosine-arabinoside, vincristine, and prednisone (POACH) was administered to 65 patients with chronic lymphocytic leukemia. Nineteen (56%) of the 34 previously untreated patients responded, with (21%) of the patients obtaining a complete remission. The response rate for the 31 previously treated patients was significantly lower, with 2 complete remissions and 6 partial remissions. The median survival of the untreated patients was 58 months, compared with 15 months for the previously treated group (p less than 0.01). In both groups, patients who achieved a complete or partial remission had a significantly longer survival than did patients who did not respond. The response rates for all sites of involvement were similar. Sixteen (47%) of 34 previously untreated patients and 9 of 31 (29%) previously treated patients returned to Rai stage 0. The survival of patients who returned to stage 0 was significantly superior to that of others in both groups. The overall mortality during the study was significantly higher for previously treated patients. Pretreatment Rai stage was strongly predictive of death on study. Rai and Binet stages were not strongly predictive of response or length of survival in untreated patients but stages were predictive for survival and in treated patients. The regimen was well tolerated, with infectious complications being the major morbidity. Patients who responded to POACH had a significantly longer survival than did those who did not, and further attempts to improve the complete and partial remission rates in chronic lymphocytic leukemia will be undertaken.

Adult↗

PubMed1987

Therapy of lymphoid and undifferentiated chronic myelogenous leukemia in blast crisis with continuous vincristine and adriamycin infusions plus high-dose decadron.

Thirty patients with Philadelphia chromosome-positive lymphoid (20 patients) or undifferentiated (ten patients) chronic myelogenous leukemia in blast crisis were treated with 0.4 mg of vincristine by continuous intravenous infusion (CIV) daily for 4 days; (doxorubicin) 12 mg/m2 of Adriamycin (Adria Laboratories, Columbus, OH) by continuous intravenous infusion daily for 4 days; and 40 mg of decadron daily on days 1 through 4, 9 through 12, and 17 through 20 (VAD). Course 2 was given starting on day 24 with the addition of cyclophosphamide 1 g/22. Overall nine patients achieved complete remission (30%) and three attained a partial remission (10%), for an overall response rate of 40%. Four patients expired during induction whereas 14 had resistant disease. Response rate was significantly higher for patients with lymphoid compared to undifferentiated morphology (55% versus 10%; P = 0.05). In lymphoid blast crisis, Calla-positive disease was associated with a higher response rate compared to Calla-negative disease (75% versus 25%; P = 0.08). Eleven patients developed infections, and seven had fever without documented infections. The median overall survival was 29 weeks. Median survival was 43 weeks for patients achieving complete remission and 20 weeks for those with resistant disease. Remission duration was 39 weeks. After primary and salvage therapy, nine patients are alive, six of them in continuous remission for 19+ to 112+ weeks. The authors conclude that VAD chemotherapy is an effective regimen with acceptable toxicity in patients with lymphoid blast crisis especially those with Calla-positive disease. Alternate induction regimens for undifferentiated disease and for maintenance therapy are currently being investigated.

Adult↗

PubMed1987

Intensive treatment of acute leukemia in adults 70 years of age and older.

The results of treatment for acute leukemia since 1973 in 87 patients aged 70 years or more are summarized. The overall complete remission rate was 27/78 (35%) in acute myelogenous leukemia and 5/9 (56%) in acute lymphocytic leukemia or acute undifferentiated leukemia for cytosine arabinoside combined with either anthracyclines (rubidazone or Adriamycin [doxorubicin]) or m-AMSA (amsacrine). The remission duration was short with a median of 33 weeks, and the median overall survival was only 6 weeks. Those patients without identifiable infection, liver enlargement, and a serum glutamic oxaloacetic transaminase less than or equal to 40 U/ml constituted a more favorable subgroup. Although the complete remission rate improved further research is needed to develop effective maintenance strategies.

Aged↗

PubMed1987

Saturation of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate accumulation in leukemia cells during high-dose 1-beta-D-arabinofuranosylcytosine therapy.

Twenty-seven patients with refractory leukemia were treated with 1-beta-D-arabinofuranosylcytosine (ara-C), 0.3 to 3.0 g/m2 as i.v. infusions over 1, 2, 4, or 24 h. The pharmacokinetics of ara-C in plasma and its 5'-triphosphate (ara-CTP) in leukemic cells from peripheral blood were studied after a single infusion of 3 g/m2 over 2 h in 13 patients. Accumulation of ara-CTP in leukemic cells remained linear until 1 to 2 h after the infusion. At the time when the rate of ara-CTP accumulation deviated from linearity, the plasma concentration of ara-C was 5- to 20-fold lower [8.1 +/- 4.4 (SD) microM] than the steady-state level during the infusion. Plasma ara-C and cellular ara-CTP pharmacokinetics were studied after two serial infusions in 14 additional patients. Varying the duration of infusion of an ara-C dose between 1, 2, and 4 h (corresponding to infusion rates of 3000, 1500, and 750 mg/m2/h) did not substantially change the rate of ara-CTP accumulation by leukemic cells. The peak ara-CTP concentration and the area under the concentration times time curve (AUC) of ara-CTP in leukemic cells increased with prolongation of the infusion. Although steady-state concentration of ara-C and AUC of ara-C in plasma were proportionally reduced by 1.0 or 0.5 g/m2 infusion over 2 h, ara-CTP accumulation rate and AUC in leukemic cells did not change compared with administration of 3 g/m2 over 2 h. However, when the infusion rate was further reduced to 0.4 or 0.3 g/m2 over 2 h, resulting in steady-state plasma ara-C concentrations of less than 7 microM, the accumulation rate of ara-CTP was substantially reduced as was the ara-CTP intracellular AUC. The cellular elimination rate of ara-CTP remained constant under all infusion conditions. These findings support the conclusion that high-dose ara-C therapy, as currently administered, results in plasma ara-C concentrations that saturate the accumulation of ara-CTP by circulating leukemic cells. We recommend that intermediate dose rates, 200 to 250 mg/m2/h, be evaluated in future studies as an alternative to the substantially higher ara-C dose rates currently in use.

Arabinofuranosylcytosine Triphosphate↗

PubMed1987

The relevance of reticulin stain-measured fibrosis at diagnosis in chronic myelogenous leukemia.

Although collagen myelofibrosis indicates poor prognosis in late stages of chronic myelogenous leukemia, the significance of reticulin stain-measured fibrosis in newly diagnosed patients is unknown. One hundred and thirty-eight patients with untreated or minimally treated chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia had reticulin stain studies made on their bone marrows at diagnosis. Reticulin fibrosis was graded on a scale of 1 to 4. Significant (Grade 3 or 4) fibrosis was noted in 65 patients (47%). Compared with patients with mild (Grade 1 to 2) reticulin fibrosis, those with significant fibrosis had a higher incidence of splenomegaly greater than or equal to 10 cm (29% versus 49%; P = 0.02), hemoglobin less than 10 g/dl (19% versus 49%; P less than 0.01), weight loss greater than or equal to 6.75 kg (10% versus 30%; P = 0.11), marrow blasts greater than or equal to 5% (7% versus 28%; P less than 0.01), peripheral blasts greater than or equal to 3% (30% versus 46%; P = 0.09), and additional karyotypic abnormalities (1% versus 17%; P less than 0.01). The incidence of thrombocytosis was similar in the two groups. Prognostically, median survival was significantly shorter for the 26 patients with Grade 4, compared with the 39 patients with Grade 3, and the 73 patients with Grade 1 or 2 reticulin fibrosis (32 versus 49 versus 57 months; P = 0.03). Reticulin fibrosis is a useful biologic and prognostic index in newly diagnosed patients with chronic phase chronic myelogenous leukemia.

Actuarial Analysis↗

PubMed1987

Role of maintenance chemotherapy in acute promyelocytic leukemia.

The effect of maintenance chemotherapy on remission duration was analyzed in 39 of 70 patients (56%) with acute promyelocytic leukemia (APL) who achieved complete remission on induction chemotherapy. Overall, the median remission duration was 26 months, with a 3-year remission rate of 42%. The 3-year remission rate was significantly higher in patients who received 6-mercaptopurine and methotrexate (POMP) during maintenance, compared with those who did not (56% versus 30%; P less than 0.01), and in patients who received long-term maintenance therapy (P less than 0.01). A multivariate regression analysis selected maintenance therapy with POMP to be the only statistically significant factor associated with long-term remission duration. The type of maintenance chemotherapy is important in overall prognosis of patients with APL, and should be investigated further.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1987

Analysis of P210bcr-abl tyrosine protein kinase activity in various subtypes of Philadelphia chromosome-positive cells from chronic myelogenous leukemia patients.

An altered c-abl gene product (P210bcr-abl) possessing associated tyrosine protein kinase activity was recently been reported in several blast chronic myelogenous leukemia (CML) cell lines. We have examined different morphological types of leukocytes directly obtained from patients at the blast crisis stage of CML for expression of P210bcr-abl tyrosine protein kinase activity. Phosphorylation of P210bcr-abl in an immune complex kinase assay using an anti-v-abl peptide serum was observed in blast cells from four Philadelphia chromosome (Ph1)-positive CML patients in blast crisis. P210bcr-abl protein kinase activity was detected regardless of whether the blast cells were of myeloid, lymphoid, or undifferentiated morphology. P210bcr-abl protein kinase activity was not detected in immune complexes either from leukocytes of four Ph1-negative CML patients in blast crisis, of five acute myelogenous leukemia patients, or in the promyelocytic cell line HL-60. Mature myeloid cells are associated with an inhibitory factor for not only P210bcr-abl protein kinase activity, but also protein kinases in general. Therefore, analyses of Ph1-positive benign phase CML myeloid cells, the majority of which are well differentiated, could not be successfully performed. The inhibition of P210bcr-abl protein kinase activity is not a specific property of mature cells from CML patients since granulocytes from a normal volunteer also demonstrated a similar effect. However, extracts of Ph1-positive cultured B-lymphocytes from a patient in benign phase demonstrated active P210bcr-abl protein indicating that the P210bcr-abl protein is expressed in an enzymatically active form in the earlier phases of CML. In addition to the previously reported P210 and P190 abl-related proteins, a novel Mr 53,000 protein was found to undergo phosphorylation at serine and tyrosine in immune complex kinase assays of two blast crisis CML cell lines (K562 and EM2) and in samples from blast crisis patients in which P210bcr-abl was detected. Peptide mapping by the Cleveland technique suggested that Mr 53,000 protein is unrelated to P210bcr-abl. Immune complex kinase assays of K562 cells with an anti-src serum (GD-11) yielded active c-src kinase and a Mr 50,000 phosphorylated protein, both of which were resistant to alkaline hydrolysis. Peptide mapping suggested that Mr 53,000 protein is related to Mr 50,000 protein which is precipitated with P210bcr-abl as an Mr 300,000 protein complex.

Amino Acids↗

PubMed1987

Chronic myelogenous leukemia in blast crisis. Analysis of 242 patients.

Two hundred forty-two patients with Philadelphia chromosome-positive chronic myelogenous leukemia in blast crisis were reviewed to identify significant biologic and prognostic associations. Twenty percent of patients had lymphoid blast crisis. Clonal evolution was present in 60 percent of patients at blast crisis and involved most frequently the development of a double Philadelphia chromosome, trisomy 8, or isochromosome 17. The overall median survival from blast crisis was 18 weeks. Patient characteristics demonstrated to have significant association with short survival were: anemia; thrombocytopenia; myeloid or undifferentiated blast cell morphology; clonal evolution involving the presence of a double Philadelphia chromosome, trisomy 8, or isochromosome 17; and low marrow blast percentage. Of 195 patients who received therapy for blast crisis, complete remission was achieved in 44 (23 percent) patients, and 24 (13 percent) patients had a partial remission or hematologic improvement. Lower complete remission rates were associated with old age, thrombocytopenia, myeloid or undifferentiated blast cell morphology, clonal evolution--especially isochromosome 17 and trisomy 8--and long interval from diagnosis to onset of blast crisis. A multivariate analysis identified two characteristics to have independent prognostic importance for both survival and remission: platelet counts and blast cell morphology. In addition, clonal evolution had additive prognostic value for survival (double Philadelphia chromosome) and for response (isochromosome 17). The beneficial association of therapy with survival was demonstrated by the significantly longer median survival of patients treated since 1981 compared with those treated earlier, even after accounting for the pretreatment prognostic factors, and by the significant improvement in survival of patients achieving remission using the "landmark" analysis technique.

Blast Crisis↗

PubMed1987

Toward a clinically relevant cytogenetic classification of acute myelogenous leukemia.

Cytogenetic studies with Giemsa banding were performed on the bone marrow cells of 384 patients with acute myelogenous leukemia treated between 1975 and 1983. An abnormal karyotype was detected in 54% of patients, being present in 100% of metaphases (AA) in 31% and only a proportion of cells (AN) in 22%. Specific translocations or other abnormalities were noted in 22% of patients, the most common of which were t(8;21) (q22;q22) in 7%, t(15;17) (q22;q21) and inv (16) (p13q22) in 5.5%, t(9;22) (q34;q11) in 3% and abnormalities of 11q23 in 1.3%. Loss of the Y chromosome was noted in 21 patients, associated with t(8;21) in 11 patients and the sole abnormality in eight patients (45, X, -Y). Most (66%) of the other abnormalities involved addition of chromosome 8 or loss or deletion of 5 or 7 (+8, -5 or -7, 5q- or 7q- group). The remaining patients had miscellaneous abnormalities (MA). A marked assymetry was noted in the distribution of important clinical prognostic variables such as age, sex, history of an antecedent hematologic disorder and presence of Auer rods within the various cytogenetic categories. The specific translocation/abnormalities were more common in younger patients (p less than 0.01). Analysis of response, remission duration and survival demonstrated that inv 16 and t(8;21) were favorable prognostic categories; diploid, t(15;17) and 45,X,-Y had intermediate prognosis, and all other categories were unfavorable prognostic groups. The response rate and survival for diploid patients (NN) was superior to patients with abnormalities. No difference in response rate, CR duration or survival was noted between the AA and AN groups. A prognostic classification according to cytogenetic category based on clinical associations is proposed which will be tested prospectively in subsequent studies.

Adult↗

PubMed1987

Signal processing technique to extract neuronal activity from noise.

A method of extracting extracellularly recorded action potentials from background electronic noise is described. Segments of traces containing stimulus-induced activity are Fourier transformed and the increase in the total power density over that of control noise segments is used as a measure of stimulus-induced neuronal activity. We show first, with observations from the amphibian visual system and mammalian auditory system, that our technique yields similar quantitative information to that obtained from the conventional spike counting method when the recording arrangement is optimal. Moreover, the size and centre of a visual receptive field can be determined even when the evoked action potentials are buried in the background noise. To investigate the potential of this technique further, we have used it to study the auditory responses in the amphibian midbrain. The power spectral density, we demonstrate here, is proportional to the stimulus intensity over a wide range, and varies systematically with stimulus frequency and the direction of sound source. Other possible applications of this technique, together with the theoretical basis for it, are discussed.

Action Potentials↗