Janet Cuttner

Clinical Importance of Myeloid Antigen Expression in Adult Acute Lymphoblastic Leukemia

To determine the clinical importance of immunophenotypes in adult acute lymphoblastic leukemia (ALL), we prospectively studied 76 patients with this condition. Before treatment, lymphoblasts were tested for reactivity with monoclonal antibodies to B-cell, T-cell, and myeloid (My) antigens. Unexpectedly, myeloid antigens (MCS-2 or MY9) were identified in 25 patients (33 percent), usually in conjunction with B-cell or T-cell antigens. Among My+ patients, 15 (60 percent) expressed B-cell antigens (B+T-My+); all 6 tested had rearranged immunoglobulin genes. Five patients (20 percent) expressed T-cell antigens (B-T+My+), and one My+ patient expressed both B-cell and T-cell antigens. Only myeloid antigens (B-T-My+) were expressed in four patients (16 percent); three who were tested had germ-line immunoglobulin and T-cell-receptor gene configurations. Although no significant differences in presenting clinical features were found, My+ patients had fewer complete remissions than My- patients (35 vs. 76 percent, P less than 0.01). No differences in response or survival were observed between My+ and My- patients expressing T-cell antigens. However, among those expressing B-cell antigens, My+ patients had fewer complete remissions (29 vs. 71 percent, P = 0.02) and shorter survival (P = 0.03; median, 8.1 vs. greater than 26 months). These findings indicate that expression of myeloid antigen identifies a high-risk group of patients with adult ALL for whom alternative forms of treatment should be investigated.

Pulmonary leukostasis as the single worst prognostic factor in patients with acute myelocytic leukemia and hyperleukocytosis

Patients with acute myelocytic leukemia and hyperleukocytosis have a poor prognosis due to vascular leukostasis and infiltration in the central nervous system and lungs. The clinical records of all patients with a new diagnosis of acute myelocytic leukemia and initial white blood cell count greater than 100,000 X 10(9)/liter admitted to the Mount Sinai Medical Center between the years 1974 and 1983 were examined. Forty-three patients were identified, 22 of whom had clinical and/or pathologic evidence of leukostasis of the central nervous system and/or lung. All patients received induction chemotherapy with daunorubicin and a continuous infusion of cytosine arabinoside. Thirty-five patients also underwent therapeutic leukapheresis prior to induction chemotherapy. The overall remission induction rate in these 43 patients was 51 percent. Fifteen patients had lung leukostasis; the remission rate for these patients was 27 percent (three complete remissions, one partial remission), as compared with a remission rate of 64 percent (18 of 28) for those without pulmonary leukostasis (chi 21 = 5.53; p = 0.02). Thirteen patients had central nervous system infiltration; the remission rate for these patients was 46 percent (five complete remissions, one partial remission), as compared with 53 percent (16 of 30) for patients without central nervous system involvement (chi 21 = 0.19; p = 0.67). The median survival of 21 patients without leukostasis was 10.8 months, as compared with 15.4 months for seven patients with central nervous system involvement and no lung leukostasis and 0.2 months for 15 patients with pulmonary leukostasis (chi 22 = 19.9; p less than 0.001). Thus, pulmonary leukostasis was found to be the single worst prognostic factor in this group of patients.

Comparative study of cytosine arabinoside therapy alone and combined with thioguanine, mercaptopurine, or daunorubicin in acute myelocytic leukemia.

Three hundred twenty‐six patients with acute myelocytic leukemia were randomly and prospectively assigned to four therapeutic regimens: cytosine arabinoside either alone or in combination with daunorubicin, 6‐mercaptopurine, or 6‐thioguanine. The results in 231 qualified previously untreated patients were analyzed. The combination treatments produced a significantly greater frequency of complete or partial remission than single drug therapy. Treatment with cytosine arabinoside and thioguanine led to 48% ageadjusted complete and partial responses. The median survival from diagnosis of all 66 evaluable patients treated with these two drugs was 18 weeks, while the median survival for those who responded to this combination was 15 months.

Intracerebral involvement in Hodgkin's disease: a report of 6 cases and review of the literature.

Intracerebral involvement in Hodgkins disease is an unusual complication. Only 28 cases have been reported. During the past twenty‐four months, we have seen six patients with intracranial involvement. Five of the six patients were male and all had mixed cellular histology. We have found the cytocentrifuge examination of the cerebrospinal fluid, brain scan, angiography, and computerized axial tomography to be the most important diagnostic examinations. We feel that intracranial disease will be seen with increasing frequency as patients are living longer.

The frequency of long‐term remission in patients with acute myelogenous leukaemia treated with conventional maintenance chemotherapy: a study of 760 patients with a minimal follow‐up time of 6 years

Summary Remission duration associated with the administration of conventional maintenance chemotherapy to patients with acute myelogenous leukaemia was evaluated. The records of 760 patients who entered remission between 1974 and 1979 were reviewed. The median duration of remission was 1.1 years with 16% of patients remaining in remission at 8 years. The relapse curve was biphasic with a high rate of relapse during the first 2½ years of remission followed by a much lower relapse rate thereafter. Leukaemic relapses were noted through 8 years of remission. A plateau phase indicating freedom from the risk of leukaemic recurrence is not clearly apparent yet but may exist after the eighth year of remission.

Central nervous system involvement at presentation in acute granulocytic leukemia: A prospective cytocentrifuge study

We have undertaken a perspective study of the prevelance of the central nervous disease in acute granulocytic leukemia (AGL). Thirty-nine newly diagnosed patients with AGL underwent cytocentrifuge examination of cerebral spinal fluid. Seven of the 39 patients had blast cells in their cerebral spinal fluid. All seven of these patients had acute myelomonocytic leukemia (AMML). No patients with other variants of AGL demonstrated blast cells in their cerebral spinal fluid. Other high risk factors associated with meningeal infiltration were elevated serum lysozyme levels, high peripheral white blood cell count, low age, splemomegaly and the presence of infiltration in other organs. The admission rates for patients with meningeal leukemia were lower and the survival time was shorter than in both the 32 noninvolved patients and the noninvolved patients with AMML. We believe that a lumbar puncture is indicated in all patients with newly diagnosed AMML.

Combination chemotherapy and radiotherapy for acute lymphocytic leukemia in adults: results of CALGB protocol 7113.

Abstract One hundred and forty-nine adult patients with acute lymphocytic leukemia (ALL) were treated with protocol defined combination chemotherapy-radiotherapy by 25 member institutions of the Cancer and Leukemia Group B. Induction of remission was attempted with vincristine (V), prednisone (P), L-asparaginase (A), with or without intrathecal methotrexate (IT-MTX) and followed by daunorubicin (D) in those patients not in complete remission after 4 weeks. The overall complete remission (CR) rate was 72%; daunorubicin was needed to achieve CR in 20 of the 107 remitting patients. The administration of IT-MTX during remission induction, especially when given simultaneously with A, was found to increase toxicity without therapeutic benefit. Remissions were maintained with either parenteral courses of 6-mercaptopurine (6-MP), and methotrexate (MTX), plus intermittent doses of V, P, and bis-β-chloroethylnitrosourea(BCNU) or with daily oral 6-MP, weekly oral MTX, and periodic VP reinforcements. All patients remaining in remission for 3 months or longer received CNS chemoradiotherapy. Median remission duration was 15 months. Continuous oral maintenance proved at least equivalent to intermittent parenteral remission therapy. Median survival was 17 months for all patients and 29 months for qualified patients achieving CR. Frequency and duration of response, and duration of survival were independent of age between ages 30 and 60. Above age 60 the prognosis is significantly less good. Thirty-two percent of the responders (life table estimate) remain in continuous first remission at 5 y. Toxicity was acceptable, except for an excessive frequency and severity of infections: (1) when V, P. A, and IT-MTX were given simultaneously; and (2) early in remission when full doses of maintenance chemotherapy were employed prior to complete recovery of normal bone marrow function. Results of treatment of ALL in adults have improved markedly during the last decade but lag behind those observed in children for reasons as yet unexplained.

Association of monocytic leukemia in patients with extreme leukocytosis

Fifteen of 73 newly diagnosed patients with acute myeloid leukemia (AML), admitted to Mount Sinai Hospital between July 1977 and October 1979, presented with leukocyte counts greater than 100,000/microliter. Eleven of these 15 patients with hyperleukocytosis had myelomonocytic (AMML-M4) or monocytic (AMOL-M5) leukemia compared to 15 of 58 patients with lower white cell counts (p < 0.001). Identification of type of leukemia, using the FAB classification, was based on morphology and special stains, including myeloperoxidase, Sudan black B, periodic acid-Schiff and nonspecific esterase with and without inhibition by fluoride. The proportion of patients with splenomegaly is higher in those with hyperleukocytosis (73 percent) than in those with lower white blood cell counts (p < 0.001) regardless of cell type. Leukemic infiltration of the skin, gums and central nervous system was seen exclusively in patients with AMML and AMOL. The serum lysozyme levels were significantly higher for all patients with AMML and AMOL regardless of the white blood cell count. The mean serum lysozyme for M-4, M-5 patients was 59.7 microgram/ml compared to 18.9 microgram/ml in patients with other cell types (p < 0.0001). Patients with a white blood cell count less than or equal to 100,000/microliter had a complete remission rate of 69 percent compared to 47 percent for patients with higher white blood cell counts.

Clinical trial of VP 16–213 (NSC 141540) I.V. Twice weekly in advanced neoplastic disease a study by the cancer and leukemia group B

The epipodophyllotoxin derivative VP 16–213 (NSC 141540) was studied by the Cancer and Leukemia Group B in a broad phase II trial at three dose levels: 60 mg/m2, 90 mg/m2, and 135 mg/m2 I.V. twice weekly. No correlation between dose of VP 16–213 and response frequency in a particular disease category could be demonstrated. Of the 382 patients, 8% obtained a complete (CR) or partial remission (PR), 8% showed improvement, and 14% had stable disease. By tumor type the best responses were obtained in lymphomas (8/31 CR + PR), uterus (2/9), prostate (1/5), rhabdomyosarcoma (2/6), neuroblastoma (2/4), colon/rectum (5/81), other gastrointestinal (4/32). In lung tumors, 4/80 patients obtained CR or PR. VP 16–213 has definite antineoplastic activity but the response frequency with the twice weekly schedule may be lower than that reported with other schedules.

A new effective four-drug combination of CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea) (NSC-79038), vinblastine, prednisone, and procarbazine for the treatment of advanced Hodgkin's disease

Five hundred and sixty‐six patients with either Stage III or IV Hodgkins disease were prospectively randomized to test whether CCNU and/or vinblastine are more effective than mechlorethamine and/or vincristine with procarbarine and prednisone. The combination of CCNU, vinblastine, procarbazine, and prednisone (CVPP) was shown to be a highly effective program with a complete response frequency of 69%. The use of CCNU as part of the induction program was also shown to be the most significant determinant of prolonged remissions (P = .025). Reduced vomiting and neurotoxicity, as well as the oral administration, were the chief advantages of the CVPP as compared with MOPP. These factors resulted in improved patient and physician compliance. The MVPP regimen was also shown to be a highly effective regimen with a complete response frequency of 73% in patients without prior exposure to chemotherapy. However, the induction regimens containing vinblastine were associated with a significantly higher frequency of fatal hematopoietic toxicities than the induction regimens containing vincristine (P = .05). This higher frequency was almost exclusively seen in the elderly or in patients previously treated with both chemotherapy and radiotherapy. At this time, the remission durations maintained by vinblastine with periodic reinforcement are longer when compared with vinblastine maintenance alone (P = .06), but there is no corresponding increase in survival.