Sequential mitoxantrone, daunorubicin, and cytosine arabinoside for patients with newly diagnosed acute myelocytic leukemia.

Mitoxantrone (M) is a synthetic aminoanthraquinone with anti-leukemic activity in patients with daunorubicin (D) resistant acute leukemia. The Cancer and Leukemia Group B (CALGB) has undertaken a limited access pilot study in which M, 12 mg/m2, over 30 min, daily for 3 days, and cytosine arabinoside (Ara-C), 100 mg/m2/day by constant infusion for 7 days were used for the induction of newly diagnosed patients with AML. Responding patients were consolidated with daunorubicin, 45 mg/m2/day for 3 days, and 7 days of Ara-C.

A phase III trial of high-dose cytosine arabinoside with or without etoposide in relapsed and refractory acute myelogenous leukemia. A Southeastern Cancer Study Group trial.

A phase III clinical trial was developed to test whether the addition of etoposide to a high-dose cytosine arabinoside regimen would improve the remission rate, duration of remission, and survival in relapsed and refractory patients with acute myelogenous leukemia. One hundred and thirty-one patients stratified by age, performance status, percentage of marrow blasts, platelet count, bilirubin and presence or absence of clinical infection, refractory or relapsed (+/- 9 months) were randomized to receive high-dose cytosine arabinoside, 3 g/m2 every 12 h for 6 days with or without three doses of etoposide, 100 mg/m2 days 7-9. Of 67 patients randomized to cytosine arabinoside alone, 31% obtained a complete remission with a median remission duration of 11.

Late intensification therapy in adult acute lymphoid leukemia: long-term follow-up of the Southeastern Cancer Study Group experience.

One hundred and ninety-two evaluable patients were treated on a multicenter protocol for adult acute lymphoid leukemia to determine in a prospective randomized fashion if late intensification chemotherapy beginning after about six months of treatment would improve remission duration and survival. The complete remission rate was 60%. The median remission duration from beginning of maintenance was 18.

Enzymatic and immunohistochemical evaluation of tyrosine phosphorylation in breast cancer specimens.

Using a synthetic peptide substrate, tyrosine protein kinase (TPK) activity was measured in 21 tumors from patients with histologically confirmed breast cancer and in five normal breast tissues from patients undergoing reduction mammoplasty. In 20 of 21 cancer specimens, tumor was available to assess phosphotyrosine (PT) immunohistochemically. Breast cancer specimens possessed significantly more TPK activity than normal breast tissues (Cancer = 43.

Increased tyrosine protein kinase activity in hairy cell and monocytic leukemias.

Tyrosine protein kinases (TPK) help regulate cellular growth and differentiation. Several proto-oncogenes encode for protein products with associated tyrosine kinase activity. An assay for TPK activity was performed in cell extracts using a synthetic peptide substrate and [32P] adenosine triphosphate (ATP).

Late intensification therapy in adult acute lymphoid leukemia. The Southeastern Cancer Study Group Experience.

One hundred ninety-two evaluable patients were treated on a multicenter protocol for adult acute lymphoid leukemia to determine in a prospective randomized fashion if late intensification chemotherapy beginning after about six months of treatment would improve remission duration and survival. The complete remission rate was 60%. The median remission duration was 13.

Mitoxantrone and constant infusion etoposide for relapsed and refractory acute myelocytic leukemia.

In an effort to search for new, synergistic and non-cross-resistant antileukemic regimens, the Cancer and Leukemia Group B (CALGB) investigated the activity and toxicity of mitoxantrone in combination with etoposide for the reinduction of patients with relapsed or refractory acute myelocytic leukemia (AML). Mitoxantrone, 12 mg/m2 daily for 3 days, was combined with three dose levels of etoposide, 100, 150 and 200 mg/m2 daily by constant infusion for 5 days. There were 19 male and 13 female patients, with a median age of 46 (range, 21-74).

Ifosfamide plus doxorubicin in metastatic adult sarcomas: a multi-institutional phase II trial.

Between April 1986 and March 1987, 42 patients with advanced sarcoma were entered in this multi-institutional trial evaluating ifosfamide plus doxorubicin. The majority of patients had leiomyosarcoma and malignant fibrous histiocytoma although two patients with sarcomas of osseous origin were included. Doxorubicin was administered at a dosage of 60 mg/m2 by continuous push and ifosfamide 5.

The anemia of sarcoidosis.

Anemia and leukopenia have been reported in sarcoidosis. In order to characterize the prevalence and association with disease activity, 75 patients with active pulmonary sarcoidosis were studied. One or more hematologic abnormalities were identified in 87% of patients studied.

The 24-hour posttransfusion survival and lifespan of autologous baboon red cells treated with inositol hexaphosphate-polyethylene glycol or inositol hexaphosphate-adenosine triphosphate-polyethylene glycol to decrease oxygen affinity.

Baboon red cells were treated to reduce oxygen affinity by an osmotic-pulse procedure using dimethyl-sulfoxide. Inositol hexaphosphate (IHP) alone or IHP and adenosine triphosphate (ATP) were incorporated into the red cells in the presence of polyethylene glycol (PEG). The procedure produced variable increases in the red cell P50 value, i.

Amino acid requirements of a rat sarcoma as determined by a stem cell assay.

Knowledge of the amino acid requirements of a neoplasm is valuable in determining optimal nutritional support and antineoplastic therapy for the tumor-bearing host. The standard human tumor stem cell assay (HTSCA) was modified by reducing an individual amino acid below the normal plasma concentration of the Fischer 344 rat. All other amino acids were maintained at levels sufficient for normal HTSCA tumor colony growth.

Electron spin resonance (ESR) studies of skeletal protein interactions in human erythrocyte membranes exposed to polyanions and in membranes prepared from inositol hexaphosphate (IHP)-incorporated low-affinity erythrocytes.

Previous biophysical investigations, including those from our laboratories, have reported that polyphosphates weaken RBC membrane skeletal protein-protein interactions and decrease hemoglobin affinity for oxygen. We have additionally demonstrated that low-affinity intact RBC's may be produced by inositol hexaphosphate (IHP) incorporation via an osmotic pulse method. In the present electron spin resonance (ESR) study, IHP was shown to cause a concentration-dependent increase in the segmental motion of ghost membrane skeletal proteins, but no alterations in spin-labeled terminal sialic acid.

Immunohistochemical classification of acute leukemias using peripheral blood smears.

Immunophenotypic classification of the acute leukemias (AcL) is of well documented value in those of lymphoid or uncertain origin and of increasing importance in those of nonlymphoid origin. Most of these studies have been performed on viable cell suspensions. To study the efficacy of a simpler immunohistochemical approach to the classification of the acute leukemias requiring only peripheral blood smears, 15 AcL (including three CGL-BC) were studied using an immunoalkaline phosphatase method and a panel of anti-lymphoid and anti-myeloid monoclonal antibodies.

Improved survival in squamous esophageal cancer. Preoperative chemotherapy and irradiation.

Initial trials of irradiation and chemotherapy followed by operation for squamous carcinoma of the esophagus have produced encouraging results. Over the past three years, with palliative and curative intent, we have treated 27 unselected patients initially with two courses of chemotherapy (fluorouracil and either cisplatin, mitomycin, or cisplatin and vincristine sulfate) given 29 days apart and 3000 rad (30 Gy) of radiation. Ten patients have then undergone esophageal resection and two patients have undergone esophageal bypass.

Effect of inositol hexaphosphate on the transient behavior of red cells following a DMSO-induced osmotic pulse.

An osmotic pulse can be used to incorporate inositol hexaphosphate (IHP) into red cells. The pulse is induced by equilibrating a red cell suspension with DMSO and then rapidly diluting with an isotonic IHP solution. Since IHP binds to hemoglobin and lowers the affinity for oxygen, this method may find application in the preparation of low-affinity cells for experimental and clinical use.

Phase II evaluation of cisplatin, bleomycin, and vindesine in advanced squamous cell carcinoma of the esophagus: a Southeastern Cancer Study Group Trial.

Adults with advanced, measurable, squamous cell carcinoma of the esophagus were treated with a combination of cisplatin, bleomycin, and vindesine. Of 27 evaluable patients, seven (29%) had partial response, all occurring within the first two cycles of therapy. Of 13 patients receiving more than two cycles, only five completed the five planned cycles of therapy and did not progress while receiving the additional three cycles.

Follicular center-cell lymphoma with plasmacytic differentiation, monoclonal paraprotein, and peripheral blood involvement. Recapitulation of normal B-cell development.

A patient with a nodular and diffuse small-cleaved follicular center-cell lymphoma that exhibited definite plasmacytic differentiation, a related monoclonal gammopathy, and circulating population of small lymphocytes is presented. Aside from showing that the presence of numerous plasma cells is not a reliable criterion for the diagnosis of a reactive follicular proliferation, the case is an example of a lymphoma without a block in maturation. The "neoplastic" B-cells show development to follicular center cells and beyond, to functioning plasma cells, and probably also to recirculating "memory" cells.

Sequentially administered 5-azacitidine and amsacrine in refractory adult acute leukemia: a phase I-II trial of the Southeastern Cancer Study Group.

The Southeastern Cancer Study Group conducted a phase I-II trial of sequentially administered 5-azacitidine and amsacrine in patients with refractory adult acute leukemia from September 1980 to March 1983. The 5-azacitidine was administered by continuous iv infusion on Days 1-4 at doses ranging from 112 to 200 mg/m2/day, while amsacrine was given at doses ranging from 75 to 150 mg/m2/day on Days 5-8. The doses of 5-azacitidine and amsacrine were alternately escalated through six dose levels during the phase I portion of the trial.

Storage of chemotherapy drugs for use in the human tumor stem cell assay.

Tumor chemosensitivity assays require the frequent in vitro use of antineoplastic drugs. Economy and convenience are greatly enhanced if these drugs are stored in aliquots for use as needed. This study investigated the stability of eight common antineoplastic agents at -60 degrees C.

Preparation of low-affinity red cells with dimethylsulfoxide-mediated inositol hexaphosphate incorporation: hemoglobin and ATP recovery using a continuous-flow method.

Incorporation of IHP into red cells decreases oxygen affinity as a result of the binding of this compound to the 2,3-DPG site of hemoglobin. This investigation describes a continuous-flow method which utilizes the osmotic pulse technique to transport IHP into RBC. Using this procedure, it is possible to obtain a significant increase in P50 while maintaining in vitro cellular integrity.

Incorporation of inositol hexaphosphate into red blood cells mediated by dimethyl sulfoxide.

Inositol hexaphosphate (IHP) binds to deoxyhemoglobin and markedly decreases the affinity of hemoglobin for oxygen. We introduce here a method for incorporating this polyphosphate into erythrocytes, thus preparing very low affinity cells for use in respiration research. The method uses dimethyl sulfoxide (DMSO) to facilitate entry of IHP.