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and 57 adults (37 AML and 20 ALL) were treated with L-asparaginase (Asnase) 200 or 1000 IU/kg daily for 30 days unless withdrawn on account of side effects.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.

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

Moderate dose methotrexate, vincristine, asparaginase, and dexamethasone for treatment of adult acute lymphocytic leukemia.

Treatment of acute lymphoblastic leukemia in adolescents and a-dults: A retrospective study of 41 patients (1970-1973)

Publisher Summary This chapter discusses the treatment of acute leukemia and describes the advances made in chemotherapy and bone marrow transplantation. The improvement in treatment is as much because of improved methods of drug administration as to the use of new drugs. Improvement in the results with chemotherapy would not have been possible without the development of improved methods of supportive treatment—for example, the treatment of infections with aminoglycosides, the intensification of blood product support, and improvement in intravenous feeding. For a minority of patients—that is, those with a human leukocyte antigen (HLA)-identical sibling—dramatic changes in the prospects for cure have been achieved by bone marrow transplantation. Immunotherapy, so far, has had little importance for the improved outcome for the patients. New ways to use monoclonal antibodies may change this poor role to the better. In addition, new drugs are being developed and one of them, acycloguanosine, has already proved to be effective for several herpes virus infections. Acute leukemia is no longer equated with early death. More than 50% of children will be cured and the proportion of cured adults is growing.

Treatment of Acute Leukemia–Advances in Chemotherapy, Immunotherapy, and Bone Marrow Transplantation

The management of adult acute lymphoblastic leukaemia.

Seventy-one adults with acute leukemia were randomized for treatment with a combination of cyclophosphamide, cytosine arabinoside, and prednisolone, with (CAPA) or without (CAP) the addition of L-asparaginase Remissions were induced with CAPA in 9 patients (33%) with AML, and 8 patients (67%) with ALL, and with CAP in 10 patients (40%) with AML, and 4 patients (57%) with ALL Thus, the addition of L-asparaginase did not improve the response significantly The over-all complete remission rate was significantly higher in females (45%) than in males (23%), and the rate below 50 years of age tended to be higher (45%) than above this age (27%) There was a slight tendency for a longer first remission time in AML with L-asparaginase (284 days) than without (74 days), but no such difference between the two ALL groups Hyper-sensitivity reactions, nausea, vomiting, psychiatric disturbances, and liver dys-function were more common side effects in patients treated with L-asparaginase

Induction of remission with l-Asparaginase, cyclophosphamide, cytosine arabinoside, and prednisolone in adult patients with acute leukemia.

[Bone marrow transplantation--an alternative treatment for aplastic anemia and leukemia].

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Induction of remission with l-Asparaginase, cyclophosphamide, cytosine arabinoside, and prednisolone in adult patients with acute leukemia.

[Bone marrow transplantation--an alternative treatment for aplastic anemia and leukemia].