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Biomedical subjects

Z Arlin

Publications and source records attributed to Z Arlin.

At least 73 records · Page 4Linked to original sources
PubMed1984

Treatment of advanced Hodgkin's disease with chemotherapy and irradiation. Controlled trial of two versus three alternating, potentially non-cross-resistant drug combinations.

From January 1979 to June 1983, 71 evaluable, previously untreated patients with advanced Hodgkin's disease completed a randomized trial of two or three potentially non-cross-resistant drug combinations and low-dose radiotherapy to initially involved nodal regions (2,000 to 3,000 rads). All patients received nine cycles of alternating chemotherapy regimens and radiotherapy between cycles 6 and 7. Thirty-four patients received three combinations: lomustine, melphalan, vindesine (CAD), MOPP, and doxorubicin, bleomycin, vinblastine (ABV). The complete remission rate was 82 percent, partial remission rate 12 percent, and progression rate 6 percent. There were two relapses from complete remission and three deaths. Thirty-seven patients received MOPP and ABV plus dacarbazine (D). The complete remission rate was 78 percent, partial remission rate 16 percent, and progression rate 6 percent, with three relapses from complete remission and five deaths. Myelosuppression was more frequent with CAD/MOPP/ABV/radiotherapy, and nausea and vomiting with MOPP/ABVD/radiotherapy. The results for both are among the best reported, and CAD/MOPP/ABV/radiotherapy was more acceptable to patients.

Adolescent↗
PubMed1984

Acute nonlymphocytic leukemia following treatment of malignant glioma. Report of two cases.

Two patients with malignant brain tumors who developed acute nonlymphocytic leukemia after treatment with radiation and chemotherapy are described. Both patients survived more than 2 years after diagnosis of the brain tumor. Survival following the diagnosis of leukemia was short, and both patients died of hemorrhage secondary to thrombocytopenia. A review of the literature reveals that leukemia after combined-modality treatment of malignant brain tumors is rare. A prolonged survival period from diagnosis of the primary tumor, treatment with nitrosoureas and radiation, plus the development of a preleukemic myelodysplastic syndrome are all important features of therapy-related nonlymphocytic leukemia.

Acute Disease↗
PubMed1984

Primary therapy of acute promyelocytic leukemia: results of amsacrine- and daunorubicin-based therapy.

Remission rates for patients with acute promyelocytic leukemia (APL) have improved with the use of anthracyclines and proper management of disseminated intravascular coagulopathy. In a prospective randomized trial of chemotherapy in patients with acute nonlymphoblastic leukemia, there were 16 patients with APL. All 7 of the patients receiving the amsacrine-containing regimen and 5 of 9 receiving the daunorubicin-containing regimen achieved a remission. All patients, except 2 of the 3 who underwent bone marrow transplantation, remain alive and in remission from 1+ to 25+ mo. Amsacrine is an effective replacement for daunorubicin in the treatment of APL, and its use does not compromise the favorable remission duration characteristic of APL.

Adult↗
PubMed1983

Non-T, non-B acute lymphoblastic leukemia (L3) with t(8;22) and two 14q+ chromosomes.

A patient with L3 leukemia is reported whose leukemic cells were characterized cytogenetically by a duplication of the long arm segment 1q25 leads to q42, trisomy for chromosome 7, t(8;22)(q24;q11), and two 14q+ chromosomes. Immunologic marker analysis revealed the leukemic cells to be of the non-T, non-B ("null") type. This observation, when considered in conjunction with a previous report of heterogeneity in cell lineages of L3 leukemias, raises the possibility of some lymphoid neoplasms arising in stem cells.

Adult↗
PubMed1983

Phenomenon of formation of giant fat-containing cells in human bone marrow cultures induced by human serum factor: normal and leukemic patterns.

Normal human sera induce the formation of fat-containing cells (FCC) in human bone marrow cultures. A nearly complete monolayer of FCC is formed after 7-14 days of cultivation with 20% human sera in the medium. FCC-inducing activity (FCCIA) is nondialyzable through 14,900-dalton cutoff membrane and is stable at 56 degrees C for 30 min. Abundant FCCIA was found in 83% of normal human sera but in only 20% of sera from untreated patients with different hemopoietic disorders and in 32% of treated leukemic patients. It is suggested that FCCIA may be involved in regulation of the bone marrow microenvironment an that it varies in normal individuals and in patients with different diseases.

Adolescent↗
PubMed1983

[Comparison of the therapeutic efficacity of 2 induction protocols in acute myeloid leukemia using exact quantification of bone marrow cellularity].

Using a recently developed technique for the determination of the pure bone marrow cell count per mm3 bone marrow, two different induction regimens for AML were compared for their efficacy, i.e. the therapy induced cytoreduction. In both protocols cytosine arabinoside, daunorubicin and 6-thioguanine were applied at comparable doses but different schedules. In both regimens a blast cell reduction of more than 2.0 log10 within the first 5 to 6 days of therapy strongly correlated (p less than 0.001) with the achievement of an adequate blast clearance in the marrow and complete remission (n = 18), while an inadequate blast cell reduction was revealed in all patients with a cell kill of less than 2.0 log10 (n = 9). Total cytoreduction on day 5 or 6 of therapy was comparable for both protocols. However, on one protocol a continuous logarithmic blast cell reduction was found while the cell kill followed a biphasic function on the other regimen.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Philadelphia chromosome and terminal transferase-positive acute leukemia: similarity of terminal phase of chronic myelogenous leukemia and de novo acute presentation.

Twenty-eight patients with Philadelphia chromosome (Ph1)--positive and terminal transferase (TdT)--positive acute leukemia (AL) were treated with intensive chemotherapy used for adult acute lymphoblastic leukemia (L-10 and L-10M protocols). Fifteen patients had a documented chronic phase of Ph1-positive chronic myelogenous leukemia preceding the acute transformation (TdT + BLCML) while the remaining 13 patients did not (TdT + Ph1 + AL). An overall complete remission (CR) rate of 71% was obtained with a median survival of 13 months in the responders. Clinical presentation, laboratory data, cytogenetics, response to treatment, and survivals of the two groups of patients are compared. These results appear to be similar, suggesting a common or closely related origin. Since the overall survival of those receiving chemotherapy maintenance is poor, three patients underwent allogeneic bone marrow transplantation (BMT) from histocompatibility leukocyte antigen--matched siblings after they achieved CR. One of them is a long-term survivor (35 + months) with a Ph1-negative bone marrow. New techniques such as BMT should be considered in young patients with a histocompatibility leukocyte antigen--compatible sibling once a CR has been achieved.

Acute Disease↗
PubMed1983

Proliferative potential of subpopulations of granulocyte-macrophage progenitor cells in normal subjects and chronic myelogenous leukemia patients.

The studies described compare the subpopulations of granulocyte-macrophage progenitor cells present in normal marrow with those derived from the marrow of patients with Ph1-positive chronic myelogenous leukemia (CML). The subpopulations were separated on the basis of size by velocity sedimentation and measured for their proliferative capacity by the colony formation technique. A pattern of development of colonies in the individual fractions was obtained by assaying the absolute number of colonies present at time intervals from 3 to 21 days. The number of colonies present at 3 days was taken as 100%, and the percentage of increase or decrease from this value was determined on subsequent days. In the fractions containing the most rapidly sedimenting large cells, the pattern of development of colonies derived from normal and CML marrow was similar. The CML colony-forming units in culture (CFU-C) began to show a deviation from the normal CFU-C pattern of development in the fractions containing CFU-C intermediate in size, and this deviation became progressively more pronounced in the slowest sedimenting small cell fractions. In these latter fractions, the CFU-C derived from CML marrow decreased in number at a rate similar to those arising from the more rapidly sedimenting fractions. This is in contrast to CFU-C derived from normal marrow, which increased in number in the more slowly sedimenting fractions and in the intermediate fractions, remained constant in number, or decreased at a rate slower than those arising from the more rapidly sedimenting fractions. The most likely explanation for these findings is accelerated maturation of the early small granulocyte-macrophage progenitor cells in CML so that these cells show the same limited proliferative capacity as do the later larger progenitor cells.

Cell Division↗
PubMed1983

Phase I clinical trial of 13-cis-retinoic acid in myelodysplastic syndromes.

13-cis-Retinoic acid (13-cRA) induces maturation and differentiation of neoplastic myeloid cell lines in vitro. We conducted a phase I clinical trial of 13-cRA in patients with myelodysplastic syndromes (MDS), using a single daily oral dose schedule. Seventeen patients with MDS and one each with acute nonlymphoblastic leukemia and chronic myelogenous leukemia in blast crisis were treated with 13-cRA at doses ranging from 20 to 125 mg/m2/day. Hepatotoxicity was dose-limiting and was manifested by hyperbilirubinemia and increased SGOT levels. This effect was seen only at the highest dose level of 125 mg/m2/day and was completely reversible upon cessation of the drug. Other toxic effects were mild, and included cheilosis, hyperkeratosis, stomatitis, and elevation of serum triglyceride levels. Fifteen patients with MDS were evaluable for therapeutic response. Five patients showed improvement in hematologic parameters. These responses included normalization of bone marrow blast count and increases in leukocyte count, platelet count, and/or hemoglobin concentration. Responses were generally not seen until at least 3 weeks of therapy were completed. We conclude that further study of 13-cRA in myelodysplastic syndromes is warranted and recommend that future studies utilize a starting dose of 100 mg/m2.

Administration, Oral↗
PubMed1983

Phase I trial of 10-deaza-aminopterin in patients with advanced cancer.

The clinical effects of 10-deaza-aminopterin, an inhibitor of dihydrofolate reductase with a better therapeutic index against several murine tumors than that of methotrexate, were examined during the course of a phase I study in patients with advanced malignant neoplasms. Three escalating dose schedules were explored: single iv injections once daily, single iv injections twice weekly, and continuous infusion. The maximum tolerated doses were: single injections at a dose of 7 mg/m2/day for 5 days; single injections at a dose of 15 mg/m2 twice weekly for four to six doses; and continuous infusion at a dose of 3 mg/m2/day for 5-6 days in patients with solid tumors and until bone marrow hypoplasia in patients with leukemia. Mucositis was dose-limiting in all schedules. Occasionally, mild leukopenia, thrombocytopenia, and skin rash were noted. A minor antitumor response was seen in a patient with gallbladder carcinoma. Marked leukemic cell kill was observed in several patients with acute leukemia or blastic phase of chronic myelogenous leukemia. Disease-oriented phase II trials are planned at this Center for several tumor varieties.

Adult↗
PubMed1983

Specific translocations characterize Burkitt's-like lymphoma of homosexual men with the acquired immunodeficiency syndrome.

A Burkitt's-like B-cell lymphoma (BLL) has recently been shown to be associated with the acquired immunodeficiency syndrome (AIDS), which affects homosexual men. We report cytogenetic studies of two BLL tumors in homosexual men. Both tumors had chromosome translocations characteristic of Burkitt's lymphoma (BL), one the t(8;14) and the other the t(8;22). The pathway of lymphomagenesis in this disorder is discussed in the light of recent data on chromosome change and localization of immunoglobulin genes and oncogenes.

Acquired Immunodeficiency Syndrome↗
PubMed1982

Induction of in vitro proliferation and maturation of human aneuploid myelogenous leukemic cells.

Human leukemic cells were induced to proliferate and mature to macrophage-like cells in primary cultures supplemented with conditioned medium (CM) from phytohemagglutinin and alloantigen-stimulated normal T lymphocytes. Blast and promyelocyte-enriched preparations, isolated after depletion of adherent phagocytic cells and lymphoid cells from samples of myelogenous leukemia patients, were suspended in liquid cultures with 30% CM. Cell cycle analysis was performed throughout the course of induced cellular maturation. Within 24 h of exposure to CM, cells with macrophage-like morphology were identified among the developing adherent cells. Approximately 15-30% of the cells in culture suspensions also developed macrophage-like morphology and esterase reactivity with alpha-napthyl acetate after incubation for 2 d. The number of these nonproliferating cells increased and became predominant in the later culture period. Flow cytometric measurement of DNA content showed that these mature cells had the same aneuploid stemline as the undifferentiated leukemic cells, indicating that genetically abnormal leukemic cells can be induced to differentiate. Reduction in the total RNA content of the macrophage-like cells was also determined by flow cytometry. Reduction in RNA and development of adherent cells served as early markers of maturation, in addition to the later acquisition of complement receptors and phagocytic capacity. Cell cycle analysis showed that CM stimulated the proliferation of immature cells. This initial proliferation may precede intertwined events of proliferation and concurrent maturation of immature cells. Later in the culture period, cellular proliferation decreased, leading to termination of the cultures.

Adult↗
PubMed1982

Combination chemotherapy of advanced chronic lymphocytic leukemia: the M-2 protocol (vincristine, BCNU, cyclophosphamide, melphalan, and prednisone).

The M-2 protocol (vincristine, cyclophosphamide, BCNU, melphalan, and prednisone) was administered monthly to 63 evaluable patients with advanced chronic lymphocytic leukemia. Complete remission (absence of all clinical and bone marrow evidence of leukemia) and partial response (greater than 50% decrease in organ enlargement and reduction of WBC count to below 15,000 x 10(6)/liter) were achieved in 17% and 44%, respectively, for a total response rate of 61%. The median survivals from therapy of patients achieving a CR, RR, or no response were 73+, 40, and 14 mo respectively. The median survival time from onset of treatment for stages II, III, and IV disease were 47, 20 and 19 mo, respectively, which was not statistically different from historical controls. However, when untreated patients are compared to this latter group, a significant survival advantage from diagnosis was found (p = 0.01), stressing the importance of prior therapy as the only unfavorable prognostic factor. Although complete remissions in CLL, as reflected in apparently normal bone marrow B-lymphocyte markers, can be induced wih acceptable morbidity, the majority of patients relapse after cessation of therapy. An alternative approach to the M-2 protocol will be needed to eradicate the disease.

Antineoplastic Agents↗
PubMed1982

Multidisciplinary treatment of advanced Hodgkin's disease by an alternating chemotherapeutic regimen of MOPP/ABDV and low-dose radiation therapy restricted to originally bulky disease.

Ninety-one evaluable patients with advanced Hodgkin's disease (patients with stages IIB, IIIB, or IV disease and patients with IIIA disease who were greater than 35 years old or had mixed cellularity or lymphocyte depletion histology) received chemotherapy with MOPP and ABDV given in alternating months; radiation therapy (RT) (2000 rad in 2 weeks) was given during Month 5 of therapy to the previously untreated patients through ports that were limited to the originally bulky disease. The complete remission rates observed were: 88% in previously untreated patients, 69% in patients who had had prior RT but minimal chemotherapy, and 50% in patients who had had prior heavy chemotherapy. The actuarial relapse-free survival rates at 4 years, for patients who had complete remission, are: previously untreated, 84%; prior RT, 70%; and prior heavy chemotherapy, 30%. The total actuarial survival rates at 5 years for all 118 patients, evaluable and nonevaluable, who were entered in the study, are: previously untreated, 80%, prior RT, 57%; and prior heavy chemotherapy, 40%.

Adolescent↗
PubMed1982

Deoxycytidine and deoxythymidine kinase activities in plasma of mice and patients with neoplastic disease.

In C57BL x DBA/2 F1 (hereafter called BD2F1) mice inoculated with P815 neoplasms and in AKR mice with spontaneously developing leukemia, significant amounts of plasma deoxycytidine and thymidine kinase activities were detected in advanced disease. Undetectable or low levels of such kinase activities were observed in normal BD2F1 and in control AKR mice. Initial studies with leukemia patients revealed increased amounts of plasma deoxycytidine and thymidine kinase activities correlating favorably with the peripheral white blood cell counts. Initial studies with small numbers of patients with solid tumors revealed significant activities of both kinases in plasma of patients with four different cancers. Healthy volunteers revealed enzyme activities only insignificantly above background.

Adolescent↗