Hypersensitive reactions and antibody formation during L-asparaginase treatment of children and adults with acute leukemia.

One hundred and fourteen patients with acute leukemia, 57 children (10 AML and 47 ALL) and 57 adults (37 AML and 20 ALL) were treated with L-asparaginase (Asnase) 200 or 1000 IU/kg daily for 30 days unless withdrawn on account of side effects. Combinations with other cytotoxic drugs were used in all but eight patients. Hypersensitive reactions, decrease in Asnase activity in plasma, and bivalent antibodies to Asnase appeared more frequently in adults (28%, 46%, and 79%, respectively) than in children (16%, 17%, and 25% respectively). There was a clear association between these three parameters. Thus hypersensitive reactions generally developed at the time of or after the decrease in plasma Asnase activity. Antibodies were detected only where Asnase activity had disappeared from the plasma. This time sequence, and in vitro experiments, suggest the formation of antigen-antibody complexes which might be responsible for inactivation of Asnase and for the development of hypersensitive reactions. However in many cases antibodies were found without concomitant enzyme inactivation or hypersensitive reactions. Antibodies to Asnase of IgE type (reagins) were found in only 10 children and 6 adults. There was no correlation between hypersensitive reactions, decrease in Asnase activity, and IgE antibodies. The frequency of remission among patients developing bivalent antibodies to Asnase was 68% (13/19) in contrast to 27% (3/11) among patients whose sera contained no detectable antibodies to Asnase, but the difference was not statistically significant.     

The effect of a calf thymus acid lysate on bone marrow cell growth in vitro

Granulocyte-macrophage colony forming units (CFU-GM) were studied in cultures of bone marrow from 16 apparently healthy normal controls, 9 patients with the myelodysplastic syndrome, 5 patients with myeloproliferative disease and 2 with myeloma. Supernatants from non-stimulated 72 hr cultures of nonadherent mononuclear blood cells ("lymphocytes") stimulated the forming of an average of 38.4 colonies per 100,000 cells from normal marrow. The addition of GIBCO's commercial conditioned medium or of a medium produced by lymphocytes stimulated with different concentrations (5, 10 and 20 mcg/ml) of an acid lysate of thymus (thymomoduline), increased growth to 65.2 - 55.4 colonies (p less than 0.001 to 0.05). Similarly, a significant increase (p less than 0.05) was found in the number of clusters and colonies formed in cultures of marrow from patients with the myelodysplastic syndrome. In contrast, no growth was found when the thymus acid lysate was added directly to the bone marrow cultures, suggesting that the lysate induces the production of colony stimulating activity by lymphocytes, but does not contain it. Similarly no significant increase was found as regards the initially high number of colonies from the five patients with myeloproliferative disease, or as regards the initially low number in the two myeloma patients.     

Doxorubicin, vincristine, bleomycin, cytembena and cisplatin as combination chemotherapy for squamous cell lung cancer

Thirty-nine evaluable patients with squamous cell lung carcinoma were treated with combination chemotherapy consisting of doxorubicin, oncovin, bleomycin, cytembena and cis-platin. Objective responses were seen in 46 per cent of the patients. Patients with limited disease had a response rate of 56 per cent. Two of the four complete responses were endoscopically and histologically verified. The median survival time was 37.6 and 26.3 weeks for patients with limited and extensive disease, respectively (p less than 0.05), and 29.9 weeks for the whole group. Hematologic and gastrointestinal toxicities were moderate. There was one drug-related death due to septicemia and 2 reversible acute renal failures. The chemotherapeutic combination appears to be relatively effective. It causes some tumor regression and may extend the survival of responding patients with acceptable quality of life. Maintenance chemotherapy with CCNU, cyclophosphamide, methotrexate, procarbazine alternating with vinblastine, nitrogen-mustard, methotrexate, procarbazine, frequently had to be discontinued because of severe toxicity.     

Difference between monoclonal antibodies against the common acute leukemia antigen from two different hybridomas

Antibodies directed against the common acute lymphoid leukemia antigen (CALLA) were obtained from 2 hybridomas: J5 (Schlossman, mice sensitized with patient ALL cells), and Vil-A1 (Knapp, sensitization with the Reh cell line). The percentage of lymphoid cells reacting with these 2 monoclonal antibodies were compared. Antibody dilution curves indicated that the dilutions used yielded maximum percentages of positive cells. The percentage of CALLA-positive cells with the J5 antibody was significantly (p less than 0.001) higher than that found with the Vil-A1 antibody in 16 non-neoplastic inflammatory tonsils and in 13 non-Hodgkin lymphoma and chronic lymphatic leukemia lymph-nodes (p less than 0.05). In contrast, the difference between CALLA positive cells with J5 and Vil-A1 was not significant (p greater than 0.5) in 19 acute lymphoid leukemias. The difference between the ALL-cells, presumably pre-B, and the B-cells from the non-ALL subjects was also statistically significant (p less than 0.01). The results suggest that the two hybridomas form antibodies against different CALLA epitopes. Vil-A1 seems somewhat more specific for ALL than J5.     

Electrochemotherapy – possible benefits and limitations to its use in the head and neck region

Conclusion: Electrochemotherapy (ECT) is an efficacious treatment. It should, however, be used with some caution in the treatment of head and neck cancer. Objectives: To assess local tumor control, safety, survival, and functional outcome after treatment of cancer in the head and neck region with ECT. Methods: Four patients with primary T2 cancer of the oral cavity or oropharynx and one patient with a metastasis of renal cancer in the masseter muscle were treated with ECT with intratumorally administered bleomycin. Control biopsies were carried out 2 months after treatment. Postoperative radiotherapy was performed based on tumor T-stage and the depth of tumor infiltration. Serious adverse events and treatment malfunctions were recorded. The follow-up time was 24 months for the surviving patients and 20 months overall. The PSS-HN scale was used to assess the functional outcome. Results: No local recurrence was recorded in any patient during the follow-up. However, only one patient was treated with ECT alone. There were four serious adverse events: one nearly lethal bleeding, two cases of osteoradionecrosis, and a fistula. One patient died from distant metastasis. The other patients were tumor-free both locally and overall at 24 months. The median functional outcome in all parameters was worse 1 year after treatment.     

Long-term follow-up in patients treated with curative electrochemotherapy for cancer in the oral cavity and oropharynx

Conclusion: ECT can be a safe curative mono modality treatment, especially in tongue cancer. The future role for ECT in head and neck cancer needs to be further investigated. Introduction: Electrochemotherapy (ECT) is a cancer treatment modality that uses electroporation to increase the intracellular accumulation of hydrophilic chemotherapeutic drugs, especially bleomycin. Objectives: To report the 5-year local tumor control, safety of treatment and survival after ECT, and the 1-year quality-of-life (QoL) data. Materials and methods: Nineteen patients with primary head and neck cancer were included and treated with ECT with curative intent. All except one patient had squamous cell carcinoma (SCC). Radiotherapy (RT) was performed in all patients with SCC and tumor infiltration ≥5 mm. The EORTC H&N 35 questionnaire was used at baseline and 12 months after treatment. The Wilcoxon signed rank test and McNemar’s test were used for paired data and Mann Whitney U-test and Fishers exact test were used for independent data (sub-group comparison). Results: There were no local recurrences in the follow-up period. Thirteen patients were treated with adjuvant RT. The six patients that were treated with ECT alone were tumor-free and alive 5 years after treatment. There was one serious adverse event reported; aspiration after treatment of a tongue base tumor. The tumor-specific 5-year survival was 75%. The QoL outcome 1 year after ECT showed a significant increase in problems with senses (taste, smell), speech, mouth opening and xerostomia. The QoL outcome also showed worse outcome in the smoking patients regarding speech, in the patients receiving adjuvant RT regarding mouth dryness and swallowing and in the patients with non-tongue oral cavity cancer regarding need for painkillers.