Improved therapy for children with acute lymphoblastic leukemia and unfavorable presenting features: a follow-up report of the Childrens Cancer Group Study CCG-106.

PURPOSE: On past Childrens Cancer Group (CCG) trials, children with acute lymphoblastic leukemia and unfavorable presenting features had obtained an event-free survival (EFS) rate of no better than 50%. Following promising pilot experience, this study was conducted to determine the benefit and morbidity of two intensive experimental regimens, Reg A, based on the Berlin-Frankfurt-Münster (BFM) 1976 regimen, and Reg B, the New York regimen. PATIENTS AND METHODS: Between February 1983 and November 1984, 217 eligible children with acute lymphoblastic leukemia and unfavorable presenting features were entered and randomly assigned to receive Reg A, Reg B, or Reg C, the control regimen. Assignment to Reg C was halted in November 1984 after interim analyses showed an inferior outcome. Subsequently, between November 1984 and March 1987, an additional 328 patients were randomly allocated to receive Reg A or Reg B. RESULTS: The 7-year EFS rate was 63% (+/- 6%, 1 SD) for Reg A, 61% (+/- 6%) for Reg B, and 40% (+/- 6%) for Reg C (P < .006). The difference between Reg A or Reg B and Reg C remained greater than 20 percentage points for EFS at 7 years and 15 percentage points for survival. Relative to Reg C, patients on Reg A accrued 16.3 additional days of hospitalization on average and, on Reg B, 20.2 days. EFS and survival were similar on Reg A and Reg B, but Reg B required more days of parenteral therapy and greater exposure to anthracyclines and alkylating agents. CONCLUSION: Both Reg A and Reg B provided a better outcome than Reg C for children with acute lymphoblastic leukemia and unfavorable presenting features. Outcomes on Reg A and Reg B were similar. Use of the more effective but more toxic regimens resulted in 78 additional hospital days per relapse prevented on Reg A and 101 days on Reg B. The current CCG trial for this population builds on Reg A.

Neuropsychological effects of cranial irradiation in young children with acute lymphoblastic leukemia 9 months after diagnosis. The Children's Cancer Group.

STUDY OBJECTIVE: To determine the effects of cranial irradiation on neuropsychological test performance evident 9 months after diagnosis. DESIGN: A companion study to a randomized clinical trial (CCG-105). SETTING: Institutions participating in Childrens Cancer Group cooperative treatment trials. PATIENTS: Seventy-four children aged 3.0 to 6.5 years with average-risk acute lymphoblastic leukemia. Children with central nervous system leukemia at the time of diagnosis, preexisting mental retardation, or Down's syndrome or for whom English was not the primary language were not eligible for study. INTERVENTIONS: Children were randomized to receive treatment with one of four systemic chemotherapy regimens and either intrathecal methotrexate sodium during induction and consolidation plus 18 Gy of cranial irradiation or intrathecal methotrexate during induction, consolidation, and maintenance as central nervous system prophylaxis. MEASUREMENT AND RESULTS: The groups were comparable with regard to chronologic age, sex, and family socioeconomic status. Children who received cranial irradiation plus intrathecal methotrexate scored significantly lower on the McCarthy Motor Scale (P < .05) and the Token Test (P < .05) than children who received intrathecal methotrexate alone. The groups did not differ significantly on the McCarthy General Cognitive Index, Developmental Test of Visual Motor Integration, or Peabody Picture Vocabulary Test-Revised. CONCLUSIONS: Findings suggest that the combined effects of cranial irradiation and intrathecal methotrexate therapy on neuropsychological performance may be evident in young children as early as 9 months after diagnosis. Follow-up assessment of these children will reveal whether these effects remain constant, intensify, or resolve.

Combination radiotherapy and chemotherapy in murine bladder cancer.

A murine transitional cell carcinoma tumor model has been used to evaluate the combined use of radiotherapy and three chemotherapeutic agents, doxorubicin hydrochloride (Adriamycin), cyclophosphamide, and cis-diamminedichloroplatinum. The preliminary radiation therapy evaluation demonstrated that the tumor is radiosensitive. The combined use of cyclophosphamide and radiation therapy was the most effective regimen, especially when the drug was started prior to radiotherapy. Cis-diamminedichloroplatinum and radiation were a lethal combination, but a synergistic effect was produced when the drug was given after completion of radiotherapy. Doxorubicin hydrochloride and radiotherapy may be synergistic, but more evaluation is necessary.

Radiotherapy of the central nervous system in acute leukemia.

The central nervous system (CNS) is a site of occult and overt involvement with acute lymphoblastic leukemia (ALL) in children. Prophylactic treatment of the cranial and spinal meninges can significantly reduce the incidence of CNS relapse. This review addresses the issues associated with the role of radiation therapy in the treatment of the CNS in ALL.

High-dose cytosine arabinoside and fractionated total-body irradiation: an improved preparative regimen for bone marrow transplantation of children with acute lymphoblastic leukemia in remission.

Twenty children with acute lymphoblastic leukemia in second (18 patients) or third (two patients) complete remission after bone marrow relapse received allogeneic bone marrow transplants from histocompatible sibling donors. The preparative regimen for marrow transplantation consisted of 12 doses of 3,000 mg/m2 cytosine arabinoside twice daily for six days followed by 1,200 cGy total-body irradiation (six doses of 200 cGy twice daily for three days). The preparative regimen was well tolerated, and all patients showed marrow engraftment promptly. Twelve patients are alive in complete remission 12+ to 79+ months posttransplant; eight patients are over 48 months posttransplant. Six patients died 1 to 9 months posttransplant of nonleukemic causes: (two each of graft-v-host disease, interstitial pneumonitis, and infection). Two patients developed recurrent leukemia at 15 and 30 months posttransplant. Both have died at 19 and 36 months posttransplant. Life table analysis reveals an actuarial survival and event-free survival rate of 58% and a marrow relapse rate of 17%. These results suggest that high-dose cytosine arabinoside and fractionated total-body irradiation is a relatively nontoxic and highly effective preparative regimen for allogeneic bone marrow transplantation for acute lymphoblastic leukemia that deserves further evaluation.