Mahroo Haghbin

Ten-year results in 1070 patients with stages I and II breast cancer treated by conservative surgery and radiation therapy

Background. One thousand seventy patients treated conservatively for Stages I and II breast cancer between the years 1982 and 1994 were reviewed. The median follow‐up was 40 months with a maximum follow‐up of 152 months.

Acute lymphoblastic leukemia in adults and children. Differences in response with similar therapeutic regimens.

Twenty‐three adult patients (ages greater than 15 years) and 75 children with acute lymphoblastic leukemia were treated with similar intensive, sequential cytotoxic protocols (L‐2). The adult patients have a lower remission rate (78%) than the children (98%). The duration of remission and the length of survival are also shorter in adults. The incidence of central nervous system (CNS) relapse in adults (27.7%) is higher than in children (7.1%) suggesting that prolonged prophylactic intrathecal methotrexate as given to the children is more effective than the schedule used for adults where intrathecal methotrexate was given only in the first 2 months of therapy. The low incidence of CNS involvement in children on the L‐2 protocol compares favorably with other series reported using a combination of cranial irradiation and intrathecal methotrexate. In both adults and children there seemed to be a higher incidence of CNS involvement in patients with initial white blood cell counts greater than 25,000 cells/mm3.

A long-term clinical follow-up of children with acute lymphoblastic leukemia treated with intensive chemotherapy regimens

One hundred and thirty‐three children 15 years old and younger with acute lymphoblastic leukemia were treated with two different protocols. Both regimens consist of a multi‐drug program, without CNS irradiation, administered for three years. Seventy‐five children were enrolled on the first protocol, L‐2; and 58 were treated on the subsequent regimen, L‐10. Of the 70 evaluable patients on the L‐2 program, 40 continue in complete remission from 72–111 months. Seventy‐four percent of the children qualified for treatment cessation, and 59% have remained in continuous remission for six years. The estimated seven year disease‐free survival for the 70 evaluable children on the L‐2 protocol is 57% and for all entries is 53%. Of the 57 evaluable patients on the L‐10 program, 35 are in complete remission from 15–67 months. The combined frequency of primary CNS leukemia for the two regimens is 7%. The off‐therapy results of the L‐2 protocol cannot be compared to the L‐10 at present, but the on‐therapy outcomes, despite the modifications that were designed to improve the L‐10 regimen, are comparable.

Controlled prospective trial of Pseudomonas aeruginosa vaccine in children with acute leukemia

Seventy‐four children under the age of 15 years, with acute leukemia were enrolled in a study to ascertain the protective effect of Pseudomonas aeruginosa vaccine, derived from the lipopolysaccharide antigens of the 7 Fisher, Devlin, and Gnabasik immunotypes. Thirteen patients received immunization initially as a pilot trial. The remaining 61 were randomized between vaccine (31) and control (30). The primary immunization consisted of 4 weekly injections. Booster doses were administered at 3 month intervals. In 85% of the patients antibodies were produced in response to the vaccination, but their levels tended to decline rapidly. The incidence of P. aeruginosa infection in each group was: pilot trial, 3, vaccine 5, and control 3. These results indicate that immunological control of P. aeruginosa infection could not be achieved by vaccination with the present vaccine alone in children with acute leukemia.

Treatment of acute nonlymphoblastic leukemia in children with a multiple-drug protocol.

Twenty‐one children with acute nonlymphoblastic leukemia (ANLL) were treated with a combination regimen consisting of arabinosyl cytosine (Ara‐C), 6‐thioguanine (TG), and Adriamycin. The incidence of complete remission was 74%. For consolidation, additional courses of Ara‐C and TG were given, followed by L‐asparaginase. The maintenance program was the same as that for the lymphoblastic type (L‐2) including intrathecal methotrexate for prophylaxis of meningeal leukemia. Of the 16 who were evaluable for the duration of complete remission, six developed bone marrow relapse, one meningeal leukemia within 3‐14 months after entering complete remission and one was lost to follow‐up. Eight remain in complete remission for 9‐72 months. In five of eight, chemotherapy has been terminated after 3 years, and all continue in remission for 11‐32 months post‐treatment. Although the results do not compare well to those of the lymphoblastic morphology, long‐term disease‐free survival can be achieved with multiple‐drug intensive treatment in childhood ANLL.

Subpopulations of human T lymphocytes. VI. Analysis of cell markers in acute lymphoblastic leukemia with special reference to Fc receptor expression on E-rosette-forming blasts.

A variety of surface markers, terminal deoxynucleotidyl transferase (TdT) activity, morphologic appearance, and cytochemical composition were studied in a group of 16 patients (13 children, 3 adults) with acute lymphoblastic leukemia (ALL). In 9 children, no surface markers were detected on lymphoblasts (null‐type ALL). Leukemic blasts of 4 children formed E‐rosettes. These E‐rosette‐forming blasts from childhood ALL, and E‐rosette‐forming lymphoblasts from 3 adult patients with ALL, were studied for the presence of Fc receptors. Of the leukemic blasts from these 7 patients, 2–76% expressed receptors for IgG Fc. Only 3 of 7 patients showed 9–42% receptors for IgM Fc. In addition, complement receptors were investigated in 6 of those 7 patients with T‐cell ALL. Complement receptors were detected on 9–70% of the E rosette forming blasts from all 6 patients. TdT activity was elevated in T‐cell ALL and in children with null‐type ALL. The heterogeneity of Fc receptor expression on leukemic blasts in these patients demonstrates a malignant proliferation of T cells in different stages of differentiation or maturation. This observation might be helpful in subclassifying T‐cell leukemias with regard to prognosis and the response to therapy. Cancer 46:45–49, 1980.

Correlation of flow cytometry to clinical factors, hormone receptors, and histopathological grade in stage I and II invasive breast carcinoma

DNA index (ploidy) and S-phase fraction (SPF) were measured by flow cytometry in 131 invasive stage I and II breast carcinomas. Ploidy showed a strong correlation with SPF (p = 0.0001), with aneuploid tumors having a high SPF. Both cytometric parameters correlated with tumor size and hormonal receptor status. Smaller tumors tended to be diploid and have low SPF. Nodal status did not demonstrate an association with cytometric findings. There was a highly significant connection between tumor grade, especially nuclear grade, and SPF (p = 0.0001). The study demonstrates the relationship between conventional prognostic factors, DNA content, and proliferative activity of breast tumors.

Immunotherapy with oral BCG and serial immune evaluation in childhood lymphoblastic leukemia following three years of chemotherapy.

Thirty‐nine children with ALL who had completed three years of chemotherapy were randomized to receive oral BCG for immunotherapy or no treatment as controls. There was not a significant difference between the two groups in the relapse rate. Among the immune parameters, only in vitro blastogenic responses to PHA and PPD rose significantly in the BCG group compared with the controls. Skin testing also revealed evidence of tuberculin sensitization. The group as a whole was studied for the kinetic recovery of immune functions after the cessation of chemotherapy, which revealed a dissociation in both cellular and humoral systems. At three weeks after therapy, only peripheral blood lymphocyte count, non‐T‐cells, and serum IgM showed a significant abnormality. There was a rise in these parameters in the subsequent weeks, and the non‐T‐cell count reached normal levels sooner than the other two parameters. Children who were <5 years of age at the time of diagnosis showed a lesser degree of immunosuppression after long‐term chemotherapy compared with those who were ⩾5 years of age. The analysis of the data indicated a relationship between the low serum immunoglobulins (IgG, IgA) and disease status.

Antibody Response to a Polyvalent Pseudomonas Vaccine in Children with Leukemia

Pseudomonas aeruginosa infection accounts for 30% of gram-negative bacteremias in children with acute leukemia at Memorial Hospital. There is a mortality rate of 87% despite antimicrobial therapy. Previous studies in animals and man following severe burns suggest that P. aeruginosa infection may be subjected to immunological control. Active immunization of 20 leukemic children in bone marrow remission was attempted with a lipopolysaccharide antigen derived from 7 strains of P. aeruginosa (Fisher-Devlin immunotypes). Vaccination consisted of 4 intramuscular injections at weekly intervals. Febrile and local reactions occurred in all, but were not severe enough to discontinue the procedure. The appearance of antibody was demonstrated by 1 to 5 preipitin bands using the Oucterlony immunodiffusion technique. This was correlated with a rise in hemagglutinating antibody titers. Sixteen children demonstrated antibody response within one month, despite the immunosupressive antileukemic therapy that they were receiving. If this antibody proves to be protective against P. aeruginosa infection by further control studies in progress, vaccination of patients early in the course of leukemia would be indicated.

578 SURFACE MARKERS AND RNA CONTENT OF LEUKEMIC BLASTS IN ACUTE MYELOID LEUKEMIA OF CHILDHOOD AS A MEASURE OF STAGE OF MATURATION

Peripheral blood and bone marrow myeloid cells from 5 children with acute myeloid leukemia were examined using a panel of surface markers and by flow cytofluometry. DNA and RNA content of individual blast cells were measured using acridine orange as a dye. RNA content of leukemic blasts from all 5 patients was higher compared to normal peripheral blood lymphocytes. Eighty-one to 85% of blast cells from 2 of 5 children had IgG Fc receptors and 14-28% of blast cells phagocytized latex particles in vitro. By contrast, the 3 remaining patients had only 11-40% blast cells which had IgG Fc receptors and only 1-3% cells ingested latex particles in vitro. Receptors for complement (C3) were present on 1-6% of the blast cells from each of the 5 patients. The high RNA content of leukemic blasts probably indicates that these cells represent a malignant deviation representing a maturation arrest of myeloid cells at an early stage of differentiation. The expression of IgC Fc receptors and the phagocytic property of blast cells in the present study demonstrate that there exists heterogeneity of the cells involved in acute leukemia of childhood and that this heterogeneity is reflected in the presence of blast cells representing different stages of maturation along the myeloid cell line. (Supported in part by fellowships from the Deutsche Forschungsgemeinschaft, J.M. Foundation and NIH grants CA-17404, CA-19267 and AI-11843)