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This phase 2 study (N = 116) evaluated single-agent vosaroxin, a first-in-class anticancer quinolone derivative, in patients ≥60 years of age with previously untreated unfavourable prognosis acute myeloid leukaemia. Dose regimen optimization was explored in sequential cohorts (A: 72 mg/m2 d 1, 8, 15; B: 72 mg/m2 d 1, 8; C: 72 mg/m2 or 90 mg/m2 d 1, 4). The primary endpoint was combined complete remission rate (complete remission [CR] plus CR with incomplete platelet recovery [CRp]). Common (>20%) grade ≥3 adverse events were thrombocytopenia, febrile neutropenia, anaemia, neutropenia, sepsis, pneumonia, stomatitis and hypokalaemia. Overall CR and CR/CRp rates were 29% and 32%; median overall survival (OS) was 7·0 months; 1-year OS was 34%. Schedule C (72 mg/m2) had the most favourable safety and efficacy profile, with faster haematological recovery (median 27 d) and lowest incidence of aggregate sepsis (24%) and 30-d (7%) and 60-d (17%) all-cause mortality; at this dose and schedule, CR and CR/CRp rates were 31% and 35%, median OS was 7·7 months and 1-year OS was 38%. Overall, vosaroxin resulted in low early mortality and an encouraging response rate; vosaroxin 72 mg/m2 d 1, 4 is recommended for further study in this population. Registered at www.clinicaltrials.gov: #{"type":"clinical-trial","attrs":{"text":"NCT00607997","term_id":"NCT00607997"}}NCT00607997.

Objective: To determine the safety and efficacy of targeted antitumor therapy with cisplatin/epinephrine injectable gel in patients with advanced squamous cell carcinoma of the head and neck. Design: Two prospective, double-blind, placebo-controlled phase III trials of identical design. Crossover from blinded to open-label phase was permitted for patients with disease progression. Setting: Tertiary referral centers in North America and Europe. Patients: One hundred seventy-nine intensively pretreated patients with recurrent or refractory squamous cell carcinoma of the head and neck. Intervention: Cisplatin/epinephrine injectable or placebo gel was administered by direct intratumoral injection; up to 6 weekly treatments. Dose was 0.25 mL of active or placebo gel per cubic centimeter of tumor up to 10 mL total. Patient benefit after local tumor control of the most symptomatic tumor was assessed by patients and physicians using the Treatment Goals Questionnaire. Main Outcome Measures: Local tumor response and patient benefit attributable to improvements in tumor-related symptoms. Results: Combined results for the 178 patients with evaluable data in the 2 trials confirmed objective tumor responses in 35 (29%) of 119 patients, including 23 (19%) complete responses achieved with cisplatin/epinephrine gel, vs 1 (2%) of 59 for placebo (P

Half-gram quantities of phytohemagglutinin lectins are purified from saline extracts of red kidney beans (Phaseolus vulgaris) by affinity absorption on porcine thyroglobulin-Sepharose. All of the mitogenic and erythroagglutinin activity of the saline extract is removed by this absorbent, and 74% of the original erythroagglutinating activity elutes from the affinity absorbent representing a 25-fold purification. Five distinct proteins appear in the polyacrylamide gel electrophoresis of the affinity absorbent eluate. Although all five proteins specifically bind to porcine thyroglobulin, the cathodal migrating proteins bind more strongly than the anodal migrating proteins. The most cathodal proteins are potent erythroagglutinins. This simple, efficient method is used to prepare all the active components of the phytohemagglutinin family in large yield and high purity.

A patient with Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia (CML) entered a blast crisis localized to lymph nodes. On light microscopy, by morphology and histochemical staining, the blasts were undifferentiated. In spite of terminal deoxynucleotidyl transferase positivity, some of the lymph node cells expressed a myeloid differentiation antigen, OKM1, and were peroxidase positive by transmission electron microscopy (TEM). However, the majority of cells were peroxidase negative on TEM and expressed OKT-10, a marker found on both primitive myeloid and lymphoid cells. Cultures of lymph node cells stimulated with Epstein-Barr virus or lipopolysaccharide (LPS) revealed the Ph1, indicating B cell involvement in the CML. T cells from cultures stimulated with L4-phytohemagglutinin and T cell growth factor were negative for the Ph1. In unstimulated lymph node cells, the uncomplicated Ph1 could not be demonstrated; instead, a unique complex karyotype involving a masked Ph1 was identified in these and the LPS cultures. This karyotype was not found in bone marrow (BM) metaphase cells. Instead, BM cells showed either the simple Ph1 or the Ph1 with a rearrangement involving chromosomes 13 and 20. The patient had transient responses to three chemotherapy regimens, two of which were designed to treat acute lymphocytic leukemia, but he died 8 months after disease acceleration without BM blast crisis. These findings are compatible with an extramedullary blast crisis originating in a primitive cell with both myeloid and lymphoid characteristics.

Unusual cytogenetic findings are described in two patients with acute leukemia and rearrangements involving chromosomes 4 and 11. Both patients had clinical and phenotypic features often found in leukemia with t(4;11)(q21;q23). At initial diagnosis, one patient showed a standard t(4;11) with duplication of the 4q-translocation derivative. The latter finding has been described previously in a few patients with t(4;11) in association with disease progression. By analogy with the Ph1 chromosome in chronic myelogenous leukemia, duplication of the 4q-suggests that this derivative is the critical recombinant in the t(4;11). The second patient has a novel complex translocation, t(4;11;15)(q21;q23;q21). Analysis of this variant trans-location implies that the 11 q + is the consistent chromosome rearrangement in this type of leukemia. The apparent contradiction of the findings in these and other relevant reported cases reviewed here suggests that genes on both the 11q+ and 4q-recombinant chromosomes are important, in either the etiology or the progression of this disease.

Ten of 136 consecutive adult patients with previously untreated acute leukemia had morphologically undifferentiated leukemia by light microscopy. Leukemic cells from these patients were characterized by agranular cytoplasm, negative histochemical staining with sudan black (SB) and nonspecific esterase, and absent lymphoid cell surface markers and therefore were not classifiable according to the French-American- British (FAB) system. Electron microscopy with myeloperoxidase (MPO) staining revealed the presence of peroxidase positive cytoplasmic granules and endoplasmic reticulum in eight of the nine patients studied. Cells from the patient who was negative for MPO were also negative for platelet peroxidase. A series of monoclonal antibodies to myeloid antigens also revealed myeloid features with all patients having at least one myeloid differentiation antigen present on the surface of their cells. Common acute lymphoblastic leukemia (ALL) antigen was absent in the nine patients tested. Cytogenetic analysis of blast cells was abnormal in seven patients on whom adequately banded chromosomes were obtained although there were no consistent abnormalities. No patient had a Ph1 chromosome. Only two of the ten patients achieved a complete remission. Morphologically undifferentiated leukemia may have myeloid features when studied by transmission electron microscopy or with monoclonal antibodies for cell surface markers. Such studies should be performed when the leukemia cannot be classified using either light microscopy or lymphoid cell surface markers. Such patients infrequently achieve remission with standard therapy and constitute a distinct entity.

134 patients with a variety of malignancies were treated in two Phase 1 clinical trials of recombinant leukocyte A interferon (IFN) produced by recombinant DNA methodology by Hoffmann-La Roche Inc. in collaboration with Genentech Inc. IFN was given either twice daily or three times weekly for 28 days. Extensive monitoring of immune function was done on these patients, in an attempt to define the range of doses of interferon and timing of administration that would optimally alter immune functions which might have beneficial anti-tumor effects. These two protocols failed to result in an appreciable increase in NK activity but rather in the majority of patients there was no significant change in NK activity from the pretreatment baseline levels. A particularly unexpected finding was the depresssion in NK activity seen in 30% of the patients. In contrast, the IFN preparation did induce significant augmentation of monocyte function, as measured in a monocyte-mediated cytostatic assay, with increases observed in 80% of the patients. There is some evidence for the presence of a suppressor factor in the sera of these patients which interfered with in vitro boosting of NK activity by IFN and therefore might have been responsible for the paradoxical NK results. These data have also been analyzed in terms of their possible relationship to doses, and protocol of IFN administration, and to tumor response.

L4-PHA (L4) and E4-PHA (E4) lectins isolated from Phaseolus vulgaris have different mitogenic properties. The mechanisms of the differences in mitogenic behavior were sought in the interaction of lectin, lymphocyte subsets, and T-cell growt factor (TCGF) also known as interleukin 2 (IL-2). TCGF activity in culture supernatants ( L4S ; E4S ) from L4- and E4-stimulated, freshly isolated lymphocytes was assayed as stimulation of DNA synthesis in TCGF-dependent continuous T-cell cultures (CTC). E4S contained less TCGF than did L4S . Addition of partially purified TCGF does not increase the stimulation of fresh lymphocytes by L4 or E4. L4 and E4 equally stimulate both helper (OKT4+) and suppressor (OKT8+) cells. The ability of L4 to further stimulate CTC is slowly lost (15 greater than 30 greater than 45 days). It is concluded that production of TCGF is not rate limiting in E4 and L4 stimulation of lymphocytes. The growth of CTC, which requires the presence of TCGF, remains sensitive to, but not dependent on, L4 for at least 30 days.

Studies with human myeloid leukemia cell lines indicate that combined interferon (INF) and retinoic acid (RA) have greater effects in inhibiting cell growth and in inducing terminal differentiation than either agent alone. Consequently, we studied the effects of these agents, singly and in combination, on fresh leukemic blast cells obtained from 13 acute myelogenous leukemia (AML) patients, most of whom were subsequently treated with recombinant leukocyte-alpha A interferon (rINF-alpha A). The in-vitro response to rINF-alpha A and RA was assessed in an established myeloid leukemic blast cell clonogenic assay containing conditioned medium from phytohemagglutinin-stimulated lymphocytes. Strong inhibition of colony cell growth (greater than or equal to 50%) was observed in 4/10 cases treated with rINF-alpha A alone, but only at high concentration (greater than or equal to 2500 U/ml) and in 4/10 cases treated with RA alone (5 X 10(-8) M or 5 X 10(-7) M). Combined rINF-alpha A and RA augmented the inhibition of primary or secondary colony cell growth in 5/8 evaluable cases. Stimulation of leukemic cell differentiation was observed in 1/8 cases by rINF-alpha A alone and in 4/7 cases by RA alone. Combined rINF-alpha A and RA enhanced cell differentiation in 4/7 cases. In addition, increased inhibition of clonal cell growth and/or differentiation by RA alone was observed in 2/5 cases following in-vivo rINF-alpha A treatment. These results suggest that treatment with combined rINF-alpha A and RA may be rewarding in some cases of AML.

1. 1. Isolectins from Phaseolus vulgaris phytohemagglutinin show increasing sera precipitation activities in the order LPHA, E1-PHA, E2-PHA, E3-PHA, and E4-PHA for 14 different animal sera. 2. 2. Sera precipitation with LPHA is usually weak or nonexistent while E4-PHA precipitates all sera strongly. 3. 3. Rabbit, monkey, and human sera contain an electrophoretically heterogeneous population of precipitating components. 4. 4. The major precipitating components of fetal calf and human sera are fetuin and α2-macroglobulins, respectively.

The subunit compositions of individual phytohemagglutinin isolectins from red kidney bean Phaseolus vulgaris were examined by isoelectric focusing and sodium dodecyl sulfate electrophoresis on polyacrylamide gels. Isoelectric focusing reveals heterogeneous but unique and non-overlapping protein band patterns for each of the homotetrameric isolectins, E4 and L4. Isoelectric focusing of the intermediate isolectins which contain both subunits (E3L1, E2L2, and E1L3) show all the protein bands common to isolectins E4 or L4 in proportions relative to their suggested subunit compositions. Polyacrylamide gel electrophoresis in a continuous sodium dodecyl sulfate buffer system gives a single protein band for all of the isolectins. In contrast, a discontinuous sodium dodecyl sulfate buffer procedure resolves isolectins E4 and L4 into single major protein bands of apparent molecular weights 31 700 (±600) and 29 900 (±200), respectively. Each of the intermediate isolectins contained both protein bands and their relative proportion, as determined by absorbance scanning, confirms the phytohemagglutinin isolectin subunit compositions as E4, E3L1, E2L2, E1L3, and L4.

A 25-year-old black male homosexual with AIDS presented with Kaposi's sarcoma of the tongue, palate and skin. The definition, epidemiology, diagnosis, treatment and prognosis of AIDS are discussed. The role of the otolaryngologist-head and neck surgeon in diagnosing this disease is outlined.