Karyotype is prognostically more important than the FAB system's distinction between myelodysplastic syndrome and acute myelogenous leukemia.

Patients with myelodysplastic syndrome (MDS) and patients with acute myelogenous leukemia (AML) share certain specific karyotypes. Therefore, we compared the relative importance of karyotype and morphology (MDS vs. AML) in determining survival in these patients.

Acute myelomonocytic leukemia associated with abnormalities of chromosome 16: a light and electron microscopic study.

We investigated the light and ultrastructural morphology of 37 patients with acute nonlymphocytic leukemia (ANLL) and inv(16)(p13q22) or del (16)(q22) with specific emphasis on the changes in the eosinophils (EOS). All but one of the 37 patients were classified as French-American-British M4 with eosinophilia (FAB M4-E) on the basis of the monocytoid nature of the leukemic cells and the presence of large EOS with interspersed basophilic-staining granules. A median of 92% of the blasts were peroxidase positive, and Auer rods were found in 71% of cases.

Augmentation of antileukemia lytic activity by OKT3 monoclonal antibody: synergism of OKT3 and interleukin-2.

We have shown that short-term incubation (45 min) of peripheral blood lymphocytes of normal donors with OKT3 monoclonal antibody (MoAb), directed against T-cell-associated antigen CD3, resulted in an acquisition of lytic activity against fresh leukemic cells. Induction of such antileukemia activity was specific for OKT3, since Leu-1 MoAb (directed against another T cell surface molecule, CD5) did not induce a lytic effect. The OKT3-generated antileukemia effect was displayed against various types of leukemia including chronic myelogenous leukemia and acute myelogenous leukemia of various histological subtypes (M1, M2, M5).

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.

Comparison of results of salvage therapy in adult acute myelogenous leukemia.

The results of initial salvage therapy for refractory and relapsed acute myelogenous leukemia for patients treated between 1973 and 1986 have been evaluated. There was no significant improvement in complete remission (CR) rate and survival in patients treated between 1973 and 1980, and the second group between 1981 and 1986. The remission duration was slightly longer in the second time period than in the initial time period.

New strategies in the management of acute leukemias.

The rapidly emerging knowledge of cytogenetics, cell surface markers, cytochemistry, electron microscopy and flow microspectrophotometry makes the objective identification of subsets of acute leukemia patients possible. These new classification schemes have revealed a unique biology and response to therapy for the different subsets. New regimens result in a significant cured fraction of patients.

T-cell receptor gamma chain gene rearrangement in acute myelogenous leukemia--evidence for lymphoid lineage prematurity.

The T-cell receptor gamma chain (TcR gamma) gene is rearranged in early T-cell differentiation. However, rearrangement of the TcR gamma gene is not specific for T lineage since it has also been noted in B-cell neoplasia. TcR beta gene rearrangement and heavy chain immunoglobulin gene rearrangement have also been reported in acute myelogenous leukemia (AML).

Intensive combination chemotherapy and interferons in the management of chronic myelogenous leukemia.

Compared to single-agent therapy with hydroxyurea or myleran (155 patients), intensive chemotherapy with vincristine, cytosine arabinoside, prednisone and cyclophosphamide (60 patients) or anthracyclines (37 patients) showed significant survival improvement overall (p less than 0.01) and among intermediate- and high-risk patients. Of 51 patients treated with human leukocyte alpha interferon (IFN-alpha), 36 (71%) had complete hematologic remission (CHR); 20 patients (39%) showed Ph suppression which was persistent in 13 for greater than 21 months.

Hematologic response of four patients with smoldering acute myelogenous leukemia to partially pure gamma interferon.

In vitro and in vivo studies were conducted to obtain basic information on the activity of gamma interferon (IFN-gamma) in acute myelogenous leukemia (AML). In a selected case of AML, recombinant IFN-gamma, but not IFN-alpha, induced differentiation of primary leukemic blasts in vitro. Similarly, IFN-gamma inhibited leukemic colony formation in vitro.

Therapy-related leukemia and myelodysplastic syndrome: clinical, cytogenetic, and prognostic features.

One hundred twelve patients who developed acute leukemia or a myelodysplastic syndrome (MDS) after chemotherapy or irradiation for another malignancy were reviewed. The median time from initial therapy to development of secondary leukemia or MDS was 71 months (range, 7 to 331 months). The initial malignancy was hematologic in 43%.

Clinical and prognostic features of Philadelphia chromosome-negative chronic myelogenous leukemia.

Between 1965 and 1982, 105 patients with a diagnosis of Philadelphia chromosome-negative chronic myelogenous leukemia were referred to our institution with minimal or no prior therapy. The median age was 63 years and 64% were males. The overall median survival from time of referral was 14 months; 53% of patients survived 1 year and only 10% survived beyond 5 years.

Early intensification and short-term maintenance chemotherapy does not prolong survival in acute myelogenous leukemia.

Forty-one previously untreated patients with a diagnosis of acute myelogenous leukemia (AML) were entered on a study using early intensification followed by a short-term maintenance chemotherapy. Induction and early intensification consisted of three to four cycles of doxorubicin, vincristine, cytosine arabinoside (Ara-C) and prednisone (ADOAP) in escalating dosages. Maintenance therapy used three cycles of Ara-C thioguanine (AT), followed by three cycles of cyclophosphamide and rubidazone with vincristine and prednisone (CROP).

A 10-year update of CHOP-Bleo in the treatment of diffuse large-cell lymphoma.

Long-term follow-up results of two studies using cyclophosphamide, doxorubicin, vincristine, and prednisone plus bleomycin (CHOP-Bleo) for the treatment of diffuse large-cell lymphoma are presented. Twenty-eight patients were treated with conventional-dose CHOP-Bleo and 36 patients with maximally tolerated doses of CHOP-Bleo. The maximal duration of follow-up was 10.

Phase I-II clinical and pharmacologic studies of high-dose cytosine arabinoside in refractory leukemia.

Sixty-four patients with refractory acute leukemia were treated with high-dose cytosine arabinoside given at a dosage of 3 g/m2 intravenously over two hours every 12 hours for four to 12 doses, repeated at two- to three-week intervals. Complete remissions were observed in 16 patients (25 percent), and the median duration of remission was three months (range, one to 10 months). Remission rates were similar for patients with acute myelogenous and acute lymphocytic leukemia (24 and 27 percent, respectively).

The association of specific "favorable" cytogenetic abnormalities with secondary leukemia.

Eight patients with secondary leukemia and specific cytogenetic abnormalities involving inversion of chromosome 16, or translocations between chromosomes 15 and 17, or 8 and 21, are presented. Seven of them (87%) achieved complete remission with chemotherapy. The occurrence of these karyotypes, which is unusual in secondary leukemia, and the favorable response to chemotherapy are discussed in relation to the pathogenesis of the disease.

High-dose cytosine arabinoside: treatment and cellular pharmacology of chronic myelogenous leukemia blast crisis.

Twenty-one patients with chronic myelogenous leukemia (CML) in blastic transformation underwent 22 remission induction attempts with high-dose cytosine arabinoside (ara-C), administered as a two-hour infusion of 3 g/m2 for six to 12 doses. Ara-C doses were administered every 12 hours in 15 patients and every six to ten hours in six patients. Median patient age was 35 years (range, 20 to 62).

Acute promyelocytic leukemia. M.D. Anderson Hospital experience.

Sixty patients with acute promyelocytic leukemia were treated between 1973 and 1984. The overall median survival was 16 months with a five-year survival rate of 31 percent. The complete remission rate was 53 percent and was similar whether they received amsacrine- or anthracycline-based regimens (60 percent versus 51 percent).

Role of murine tumor models in cancer treatment research.

Two major factors have contributed to a widely held disenchantment with murine tumor models for drug screening in cancer research: (a) the higher costs of these models in comparison to studies performed with tumor cells in vitro; and (b) the perception that these models have failed to demonstrate satisfactory correlation of chemosensitivity with analogous human tumor types; i.e., murine tumors generally have proved to be sensitive to many more agents than are found to be active in the clinic.

Prognostic factors for survival of 194 patients with low infiltrate leukemia.

Prognostic factors were identified from the histories of 194 patients diagnosed as having low infiltrate leukemia (LIL) between 1973 and 1981, when the policy was to delay treatment until there was evidence of progressive disease or life-threatening morbidity. Their median age was 59 yr; 63% were male; 30 had had a malignant disease previously. Presenting symptoms included anemia, 82%; infections, 15%; and hemorrhage, 16%.

Chronic myelogenous leukemia: a multivariate analysis of the associations of patient characteristics and therapy with survival.

The prognostic importance of patient pretreatment clinical and laboratory features was investigated in a group of 303 patients with Philadelphia chromosome-positive benign-phase chronic myelogenous leukemia. Intensive chemotherapy was given to 97 patients, and 78 underwent an early elective splenectomy. The overall median survival time, dated from hospital admission, was 39 months.

Subacute pulmonary failure complicating therapy with high-dose Ara-C in acute leukemia.

Seventy-four adult patients with acute leukemia in relapse were studied. They received high-dose intravenous boluses of cytosine arabinoside (Ara-C) according to the following schedules: 3 g/m2 over 2 hours, every 12 hours for 4 to 12 consecutive doses, or a continuous infusion over 5 days at 200, 400, or 800 mg/m2/day. The patients' ages ranged from 16 to 68 years (median, 35).

Sequential administration of thymidine, 5-fluorouracil, and PALA. A phase I-II study.

Twenty-seven patients with colorectal adenocarcinoma, (12) non-small cell bronchogenic carcinoma, (11) gastric adenocarcinoma (3), and adenocarcinoma of unknown primary lesion (1) were treated with the combination of thymidine (TdR), 5-fluorouracil (FU), and N-phosphonacetyl-L-aspartic acid (PALA). PALA 1 g/m2 was given over 1 hour on day 1, followed on day 2 by 30 g of TdR given over 3 hours. FU, 150-300 mg/m2, was administered sequentially over 1 hour immediately following TdR infusion.

Remission from central nervous system involvement in adults with acute leukemia. Effect of intensive therapy and prognostic factors.

Eighty-seven adult patients who had achieved bone marrow remission of leukemia developed one or more episodes of meningeal leukemia. Multiple patient characteristics were examined for their effect on probability of achieving complete remission from meningeal disease and for their effect on duration of meningeal remission. Presence of obtundation (P less than 0.