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.

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. METHODS: All patients had a wide local excision and lower lymph axillary node dissection followed by radiation therapy. The entire breast received an external beam dose of 4500 cGy at 180 cGy/5 days/week. An additional boost dose of 2000 cGy to the tumor bed was given at the time of lumpectomy (perioperative) with an Ir-192 implant or with electron beam therapy after the external beam therapy. RESULTS: The 5- and 10-year disease specific survival results were 97 and 90%, respectively for Stage I and 87 and 69% for patients with Stage II disease. The 5- and 10-year local control rates were 93 and 85% for Stage I and 92 and 87% for Stage II, respectively. The risk factors for local failure were premenopausal status and estrogen receptor-negative status at the univariate level but at the multivariate level the premenopausal and margins status were significant. CONCLUSION: These 10-year results were at least equivalent to reported series of similarly staged patients treated by mastectomy. This should encourage more surgeons to offer conservative treatment as an alternative to mastectomy to patients with Stage I and II breast cancer.

Dual isotope SPECT in the evaluation of recurrent brain tumor.

Dual isotope brain SPECT was performed in a patient with recurrent brain tumor (grade II astrocytoma). In this case, a good coregistration of brain perfusion and tumor images was obtained because Tc-99m HMPAO and the Tl-201 chloride imaging were done simultaneously using a Triad SPECT unit. This method might play an important clinical role in the evaluation of patients with recurrent brain tumors.

Combined modality preoperative therapy in poor prognostic rectal adenocarcinoma.

Between 1976 and 1986, 64 patients with rectal adenocarcinoma who were considered unresectable or had prognostic signs suggestive of high risk for local failure received preoperative adjuvant therapy. They were treated with pelvic irradiation (40 Gy) combined with 5-fluorouracil (5-FU) and mitomycin-C, followed by surgery. All had definitive resections resulting in 12.5% of operative specimens free of tumor and only 26.5% containing nodal metastases. The projected 5-year disease-free survival rate is 64% with an actuarial survival of 68%. No mortality or severe morbidity has been observed. Combined modality therapy is a safe and effective regimen for those rectal tumors in the high risk category.

Carcinoma of the nasopharynx. A 25-year study.

Between 1958-1983, 79 patients with a diagnosis of epithelial tumor of the nasopharynx received definitive irradiation at Thomas Jefferson University Hospital. Seventy-two percent of the patients had a Stage IV lesion. The dose to the nasopharynx was over 6,000 cGy in all but four patients. The 5- and 10-year actuarial survivals were 33% and 19% respectively. The 5-year disease-free survival was 33%. Histology had no bearing on survival. Survival was influenced by the stage of primary tumor and nodes. Advanced nodal disease correlated with distant metastasis, being present in 13/15 cases with hematogenous spread.

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 less than 5 years of age at the time of diagnosis showed a lesser degree of immunosuppression after long-term chemotherapy compared with those who were greater than or equal to 5 years of age. The analysis of the data indicated a relationship between the low serum immunoglobulins (IgG, IgA) and disease status.

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 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.

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.

Childhood CML in blastic stage: an analysis of cell markers and cell kinetics.

The clinical course of Ph+CML and their terminal blastic stage is described in the following case histories. During blastic phase, cell surface markers, terminal deoxynucleotidyl transferase (TdT) activity, and flow cytometric measurements were used or determination of the blast cell phenotype which was undifferentiated by morphological and cytochemical criteria. A high proportion of blast cells expressed Fc receptors for IgG, TdT activity was normal in both children and RNA measurements of single cells flow cytometry showed a high RNA content in the majority of blasts. These findings are compatible with the phenotype seen in the myelomonocytic leukemias. Flow cytometry appears to be a useful adjunct to immunological methods and TdT activity for the rapid characterization of CML in blastic phase.

Erythroid progenitors (BFU-e and CFU-e) in acute leukaemia.

Bone marrow erythroid progenitor cells were examined from 50 cases of acute leukaemia and from 20 normal subjects using an in vitro semisolid culture method. Numbers of both primitive erythroid progenitor cells (BFU-e) and later-stage erythroid progenitor cells (CFU-e) were remarkably depressed in patient with acute leukaemia in active phase. However, both BFU-e and CFU-e recovered to within normal range when the patients achieved remission. Peripheral blood BFU-e of children with acute lymphocytic leukaemia in remission were also examined and found to have values not significantly different from those of control subjects. There was no distinct correlation between the numbers of erythroid bursts or colonies and the duration of remission in patients with acute leukaemia in remission. The reduction of BFU-e and CFU-e in active acute leukaemia suggests the involvement of erythropoietic progenitors in the pathophysiology of this type of leukaemia.

Use of the Ommaya reservoir in the prevention and treatment of CNS leukemia.

Insertion of an indwelling ventricular cannula via the transfrontal approach by the method described, and the use of an attached reservoir is a safe technique in the hands of experienced personnel. Intraventricular chemotherapy prolongs the duration of remission in those individuals who have evidence of meningeal leukemia. The superiority of this method over intralumbar therapy as a preventive measure has not been demonstrated.

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, addition 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.

Antimetaboliths in the prophylaxis and treatment of central nervous system leukemia.

The results of the administration of two antimetabolites, methotrexate (MTX) and cytosine arabinoside (Ara-C), for the prevention and treatment of established central nervous system (CNS) disease in children with acute lymphoblastic leukemia are discussed. Two protocols (L-2 and L-10) for the management of patients with acute lymphoblastic leukemia have been developed. In the L-2 protocol, prophylaxis consists of repeated intralumbar injections of MTX alone, and in the L-10 regimen, both MTX and Ara-C are administered; for the patients with an initial leukocyte count of greater than or equal to 25,000/mm3, the two drugs are given intraventricularly instead of by the usual intralumbar route. In the treatment of established CNS leukemia, intralumbar MTX and Ara-C in addition to CNS irradiation are employed; for maintenance, periodic intraventricular MTX injections are given. Of the 70 children receiving the L-2 protocol, four developed CNS leukemia and in a fifth patient, CNS and bone marrow relapse were concurrent. Among the 31 children receiving the L-10 regimen, CNS disease has been observed in only one child. Of the five children treated for the established CNS leukemia, recurrence was observed in two at 19 and 29 months after remission; the other three remain in remission for 2, 15, and 39 months, respectively.

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 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.

Chemotherapy of acute lymphoblastic leukemia in children.

Between 1969-1973, 75 consecutive children under the age of 15 years with acute lymphoblastic leukemia were treated with a multiple-drug regimen (L-2). Prophylaxis for meningeal leukemia was limited to the repeated intrathecal injections of methotrexate. Seventy-four patients achieved remission; the duration of remissions could be evaluated only for 70. Relapse terminated complete remission within 1-54 months in 21 children. Four of these relapses were confined to the central nervous system. Forty-nine patients continue in complete remission from 23 to 63 months. Chemotherapy has been discontinued in 29 children, and 25 of these remain without evidence of recurrence for 2-27 months posttreatment.

Treatment of acute lymphoblastic leukemia in childreq with "prophylactic" intrathecal methotrexate and intensive systemic chemotherapy.

Sventy-five children under the age of 15 years, with acute lymphoblastic leukemia, were treated with a multiple drug chemotherapy regimen (L-2) and intrathecal methodtrexate. Remission was achieved in all except 1. Three died from infection early in remission and 1 was lost to follow-up. Of the remaining 70, relapse occurred in 19; in 3 children this was confined to the central nervous system (CNS) and in 1 was in both the CNS and bone marrow. Fifty-one children continue in complete remission from 14 to 54 months. Fourteen of these children have completed 3 years of chemotherapy and are disease free 2 to 18 months posttreatment. The results indicate that periodic administration on intrathecal methotrexate with no CNA irradiation, plus intensive systemic chemotherapy, can effectively control CNA leukemia and prolong the duration of complete remissions.

Anti-Pseudomonas heat-stable opsonins in acute lymphoblastic leukemia of childhood.

Heat-stable opsonic activity against Pseudomonas aeruginosa and Staphylococcus epidermidis was measured in sera of 33 children with acute lymphoblastic leukemia at selected times during treatment of their disease. Compared to adults, opsonization of P. aeruginosa was normal in children tested at the time of diagnosis and before chemotherapy. Immediately after achievement of remission, opsonic activity against Pseudomonas was significantly decreased (P smaller than 0.05) compared with pretreatment activity. Activity usually returned to normal and remained so during long-term remission maintenance therapy. In children studied just prior to death from unremitting leukemia, however, anti-Pseudomonas opsonic activity was significantly decreased when compared with that of a group of children before any leukemic treatment (p smaller than 0.005). Anti-S. EPIDERMIDIS OPSONIC ACTIVITY SHOWED NO CHANGES DURING THE PATIENT'S COURSE. Decreased serum opsonic activity may significantly contribute to the increased incidence of severe Pseudomonas infections in patients with acute lymphoblastic leukemia.