Search

Between 1972 and 1981, 247 patients with acute lymphoblastic leukemia were treated with prophylactic CNS irradiation. Cranial irradiation (2400 rad) plus intrathecal methotrexate was the prophylactic CNS therapy of choice. At 5 years, the overall, relapse-free and CNS relapse-free survival rates were 51%, 47% and 79%, respectively. Our findings suggest that more attention should be paid to the inferior border of the radiation field, since the anterior and middle cranial fossae were sometimes not included and the second spine was almost always excluded.

Between July, 1976 and June, 1984, 43 adults with acute lymphocytic leukemia were treated with a V(V') P [vincristine (vindesine), prednisolone] followed by DV(V')MP [daunomycin, vincristine (vindesine), 6-mercaptopurine, prednisolone] and V(V')AP [vincristine (vindesine), 1-asparaginase, prednisolone] regimen. They were all previously untreated and aged 15 and over. Complete remission (CR) was attained in 41.9% of cases by V(V')P alone, the CR rate being increased up to 62.8% by the sequential administration of DV(V')MP, and to 74.4% by the further administration of V(V')AP. The median duration of CR was 5.6 months; it was 10.9 months for patients with the maintenance therapy and 1.3 months for patients without it. For patients who achieved CR, the median survival time (MST) was 21.3 months compared to 2.7 months for those who failed to achieve CR. As for the maintenance therapy, MST was 22.3 months for patients who received it, and 9.5 months for patients who did not. Factors associated with significantly lower rate of CR were: lymphadenopathy and hepatomegaly and/or splenomegaly. The CR rate was somewhat lower for patients aged over 20 and with hyperleukocytosis (above 40,000/cmm). Shorter remissions tended to be associated with ages over 20 and with hepatomegaly and/or splenomegaly. Patients who obtained CR by the sequential administration of the V(V')AP regimen showed somewhat shorter CR duration compared with to those who obtained CR by V(V')P alone and by the sequential administration of DV(V')MP. Survival was significantly shorter for patients who failed to achieve CR, with B-ALL and with hyperleukocytosis. Shorter survival was also observed among patients with ages above 60 compared to those with ages below 20.

Progress in the study, treatment and cure of hematologic malignancies in children is one of the most gratifying accounts in the entire history of cancer therapy. It is important to note that progress in treatment and cure have been the direct result of formal study of childhood cancers and the development and clinical trial of new treatments designed to improve the response and cure rate. In the experience of the Children's Cancer Study Group (CCSG), approximately half of the children with cancer which are registered have hematologic malignancies. By far the most significant of these is acute lymphoblastic leukemia (ALL), which accounts for 33% of all the cancers registered with the Group. Acute non-lymphoblastic types of leukemia have amounted to 6% of all cancers in our experience, non-Hodgkin's lymphoma for another 6% and Hodgkin's disease for approximately 5%. The cancer death rate in children under the age of fifteen years has declined very significantly in the United States since 1950. In 1955 the National Cancer Institute organized the first national cooperative groups in order to develop and test new treatments for acute lymphoblastic leukemia. The CCSG was the first of these. The success which has been achieved in treating acute leukemia is remarkable, particularly when one recalls that in 1950 the disease was 100% fatal. The death rate due to Hodgkin's disease has also shown a sharp decline, and more recently, deaths due to non-Hodgkin's lymphomas have also declined.

Documentation on 324 children with leukemia who underwent cranial irradiation between 1972 and 1981 was collected from 15 participating hospitals in the Kansai Cancer therapy Group. Among 182 children with acute lymphoblastic leukemia, records on 90 children treated with prophylactic cranial irradiation (2,400 rads) plus intrathecal methotrexate in 12 hospitals were available for analysis. There was no significant difference in survival between the two prognostic groups based on age and initial WBC count at diagnosis, i.e., overall, relapse-free and CNS relapse-free 5-year survivals in the good and intermediate prognostic groups were 57% vs. 51%, 55%, vs. 49%, and 83% vs. 95%, respectively.

Controlled clinical trials of therapy for childhood acute leukemia are reviewed in the Children's Cancer & Leukemia Group Studies 1972-1981. The mortality of acute lymphocytic leukemia in children has been reduced about one-half in the past 10 years. Continued progress depends on maintaining our objective of curing all children and in conceiving and testing new ideas that might contribute to cure. Nowadays, the end result of most importance is long-term leukemia-free survival, i.e., the freedom from relapse after off therapy. Advances in the childhood leukemia have paved the way for encouraging progress in the management of the much more common malignancies that affects adults.