Cytosine arabinoside/cyclophosphamide pulses during continuation therapy for childhood acute lymphoblastic leukemia. Potential selective effect in T-cell leukemia.

One hundred seventy-seven children with acute lymphoblastic leukemia (ALL) were admitted to a study designed to determine whether pulses of cytosine arabinoside (ara-C) and cyclophosphamide (cyclo) would improve disease-free survival (DFS). All patients received vincristine, prednisone, and asparaginase for remission induction, CNS prophylaxis with cranial irradiation and intrathecal methotrexate, and continuation therapy with 6-mercaptopurine plus methotrexate. Forty-seven of 101 patients with non-T ALL and 18 of 26 patients with T-cell ALL received ara-C/cyclo pulses every eight weeks during continuation therapy. The age, sex, and initial white cell count distributions were similar in both treatment groups. Patients with non-T-cell ALL had similar DFS with or without ara-C/cyclo pulses (36% versus 48%; P = 0.32). Ara-C/cyclo pulses significantly improved DFS in children with T-cell ALL (36% versus 0%; P = 0.015). Toxicities of the ara-C/cyclo pulses included reversible pancytopenia, drug induced fever, fever associated with neutropenia, and death in one patient from systemic candidiasis while neutropenic. This is the first clinical evidence to indicate that the combination of ara-C/cyclo used during continuation therapy is selectively beneficial in T-cell ALL.

In vitro enhancement of peripheral blood mononuclear cell natural killer activity following short term incubation with fetal calf serum.

This study demonstrates that short term incubation of blood mononuclear cells (MC) in heterologous sera enhances their natural killer (NK) but not their antibody dependent killer (K) activity, and confirms that NK stimulation is not related to blastogenesis. MC were obtained from healthy donors and incubated with RPMI 1640 supplemented with various serum sources. NK and K activity of incubated vs. fresh MC against SK-N-SH, Chang or Raji cell line targets were compared in a 4-hr 51Cr release assay. A significant (p less 0.01) increase in NK cytotoxicity was detected when MC were incubated with fetal calf serum (FCS) or human AB serum (ABS) at 37 degrees C. When a more sensitive NK target cell (K-562) was used only the cells incubated in FCS demonstrated increased NK cytotoxicity. Augmentation of NK cell activity by FCS was not related to blastogenesis, mitosis, natural antibodies against lymphocytes or target cells, immunoglobulin complexes or alterations in MC OKT4 and OKT8 subpopulations. In contrast to NK activity, K cytotoxicity was not increased after incubation at 37 degrees C in FCS or ABS, and it was depressed in IPT (p less than 0.05). Thus FCS is capable of stimulating NK cell activity against human tumor cell lines in less in less than 24 hr.

Radiotherapy in leukemia and lymphoma of children.

Radiotherapy is important in the treatment of leukemia and lymphoma of children. In acute lymphocytic leukemia administration of cranial irradiation early during chemotherapy-induced remission prevents initial meningeal relapse. When cranial irradiation is combined with a 3-year course of multiple drug systemic chemotherapy approximately one-half of the children remain in complete remission for 5 years or more and are at little risk of relapse. Preventive cranial irradiation is effective in children with acute myelocytic leukemia, also, but this does not affect survival because of the inadequacy of chemotherapy in controlling bone marrow disease. Low dose palliative irradiation can be helpful in caring for some children with obstructive, painful or disabling leukemic lesions. In Hodgkin's disease of children radiotherapy is effective in curing stages IA, IIA, and IIIA disease and contributes to chemotherapy control of stages IIIB and IV disease. The role of radiotherapy in non-Hodgkin's lymphoma is less clear. Children with T-lymphoblastic lymphoma tend to have rapid dissemination to bone marrow and meninges and appear to benefit more from multiple agent chemotherapy and preventive meningeal irradiation. Children with B-lymphoblastic lymphoma usually benefit from cyclophosphamide therapy; the value of irradiation is yet to be established. However, radiotherapy is frequently curative in stage I B-lymphocytic nodular and histiocytic lymphomas. The indications for radiotherapy in children with leukemia and lymphoma are constantly changing. Before each child is treated the multi disciplinary evaluation and treatment team must consider the rationale in relation to the specific child and current knowledge.