A practical classification of lymphomas.
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Biomedical subjects
Publications and source records attributed to D J Higby.
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Twenty-eight adult patients with nonirradiated malignant gliomas of the brain were administered a combination of methyl-CCNU (130 mg/m2, p.o., day 1), vincristine (2 mg/m2, i.v., day 1) and procarbazine (100 mg/m2, p.o., days 2 to 15) (MVP), scheduled to be given at successive 6 week intervals. Nineteen (67.9%) were not responsive to MVP and 9 (32.1%) were. Of 16 who had previous partial resection of their tumors, 8 (50%) responded to MVP and 8 (50%) did not. Of 12 who had previous biopsy, only 1 (8.3%) responded. Overall 1-year survival rate for the 28 patients was 28.6%. Major side effects of MVP were leukopenia, thrombocytopenia, pulmonary emboli, and thrombophlebitis, detected mainly during the first 20 to 24 weeks of treatment.
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Patients with acute nonlymphocytic leukemia were given remission induction therapy consisting of cytosine arabinoside and an anthracycline. Those patients who experienced complete remission received two courses of consolidation therapy and were randomized to receive maintenance therapy consisting of either daily chemotherapy with reinforcements every 3 mo or reinforcement therapy only every 6 wk. The overall complete remission rate was 66%, with 80% complete remission for previously untreated patients less than 60 yr of age who did not have a prior history of malignancy. Remission durations were the same for patients treated with both maintenance regimens. The major determinant for successful remission induction therapy was patient age, with older patients frequently succumbing to intercurrent infection. Documented leukemic cell resistance to the therapy employed was only rarely encountered. Once remission was achieved, age was no longer a determinant of patient survival, since duration of remission was independent of age. Remission durations were directly related to leukemic cell retention of cytosine arabinoside triphosphate. Hence therapy for acute nonlymphocytic leukemia can be divided into two separate areas: remission induction and remission maintenance.
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Patients with a wide variety of previously treated, advanced solid tumors were assigned to receive either adriamycin-cis-dichlorodiammineplatinum(II) (cis-platinum) or adriamycin-cyclophosphamide as combination chemotherapy. Hematologic toxicity was prominent but short-lived in most patients; renal toxicity occurred in 14 of 23 patients receiving cis-platinum and frequently precluded further administration of that agent. Of the patients receiving adriamycin-cis-platinum, 37.5% had useful responses, with four of six patients with bronchogenic carcinomas showing partial regression of disease and two patients with embryonal cell carcinoma of the testes showing complete response. In the patients receiving adriamycin-cyclophosphamide, one complete response occurred in a patient with a malignant lymphoma, and the overall response rate was 18%. The combination of adriamycin-cis-platinum merits further study, especially in bronchogenic carcinoma.
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This study describes the establishment of two permanent leukemic B-cell lines (BALM-1 and -2) originating from the blood cells of a patient with a B-cell type of acute lymphoblastic leukemia. The cells of BALM-1 and -2 exhibited cell surface markers compatible with B-cell origin. The identity between the leukemic cells in vivo and those of the BALM lines was established on the basis of the karyotypic picture, including marker chromosomes 14q+ and t(12;17;?) and cell surface immunoglobulins (K, delta, and mu chain determinants).
cis-Dichlorodiammineplatinum(II) (DDP) was studied in 16 children with far-advanced malignancies. Three dosage schedules were tried: regimen A, 20 mg/m2/day x 5 days for 3-4 weeks (11 patients); regimen B, 50 mg/m2 once a week (four patients); and regimen C, 60 mg/m2/day x 2 days every 3-4 weeks (one patient). Four of 16 patients (25%) showed partial response, including one with osteogenic sarcoma, one with neuroblastoma, one with seminoma, and one with medullary carcinoma of the thyroid. Two patients showed clinical improvement. The major toxic manifestations included nausea and vomiting (16 of 16), renal toxicity (three of 16), transient pancytopenia (six of 12), and hearing loss (two of 16). It is apparent that DDP has activity in pediatric tumors; however, a more precise response rate must be delineated in a larger series of patients.
Dexamethasone was administered to 51 donors prior to filtration leukapheresis. The results of this maneuver, including the consequences of transfusion, were contrasted with results in 52 donors who did not receive the steroid. Yields of polymorphonuclear leukocytes, the posttransfusion increments in recipients, themorphologic polymorphonuclear leukocytes obtained, and the incidence of donor and recipient reactions were all beneficially influenced by this manipulation. Possible mechanisms responsible for these observations are discussed. It is recommended that dexamethasone stimulation be used in filtration leukapheresis when circumstances do not otherwise contraindicate such a maneuver.
Twenty-three children with various stages and morphologic types of leukemia were treated with multiple granulocyte transfusions obtained by filtration leukapheresis when neutropenia-associated infection appeared unresponsive to antibiotics. All children meeting the above qualifications were given granulocyte transfusions during this time period. Twenty-one of 23 became afebrile during or shortly after the transfusions; one died with disseminated Herpes simplex; and one became well enough to be discharged, although he was never free of fever. Frequent mild to moderate fever and chills were noted. One child developed a severe pulmonary reaction followed by resolution of pneumonia. Filtration leukapheresis is a useful adjunct in controlling severe infections in neutropenic children.
To study the clinical efficacy of granulocytes obtained by filtration leukapheresis, patients with clinically evident infection and granulocyte counts of smaller than 500 per cubic millimeter were randomly assigned to receive conventional therapy alone or with a granulocyte transfusion obtained from a single donor each day for four days. Five of 19 control patients survived to day 20, and 15 of 17 in the transfused group survived. Comparison of the two populations for variables such as age, disease, and severity and type of infection revealed no other factor that could account for the difference in survival. Outcome was not demonstrated to be related to HL-A match, post-transfusion counts, or presence of leukocyte antibodies. Functional studies of granulocytes obtained by filtration leukapheresis showed only minor differences although appearance was altered. Granulocytes so obtained can be used safely and efficaciously as adjunctive therapy for infection associated with granulocytopenia.
A total of 33 leukaphereses were performed with the IBM continuous flow centrifuge on 28 normal healthy donors for the purpose of obtaining increased yields of granulocytes for infusion into leukopenic recipients. The pretreatment of donors within a 10- to 12-hour period prior to pheresis with a double dose of dexamethasone and the addition of hydroxyethyl starch to the input line of the continuous flow centrifuge, significantly increased the total quantity and efficiency of granulocyte collected as compared to a donor group receiving a single dose of dexamethasone in addition to hydroxyethyl starch. A mean of 25.5 times 10-9 total granulocytes were collected in addition to an efficiency of 2.11 times 10-9 granulocytes harvested per liter of blood processed in the double-dose-treated donors, in contrast to 19.6 times 10-9 total granulocytes collected and an efficiency of 1.82 times 10-9 granulocytes harvested per liter of blood processed in the single dose donor group. The results of the present study demonstrate that elevated quantities of granulocytes can be collected from normal donors by scheduling a double dose of dexamethasone prior to the pheresis procedure.
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