Treatment program

All high risk patients were treated with nine alternating courses (days 1-6) of according to the ALL-BFM 90 regimen (Figure 17.11) at 3 weekly intervals. Criteria to commence chemotherapy included (1) neutrophil count (ANC) 0.2 X 109 l, (2) platelet count 50 X 109 l and (3) oral temperature < 38.5 C for at least 3 days. Children randomized to r-GCSF received 5 g kg day subcutaneously from day 7 of each cycle and continued till day 20. If ANC on day 20 was < 0.2 X 109 l, GCSF was continued...

Study design

This Associazione Italiana Ematologica Oncologia Pediatrica (AIEOP) (March 1991 and April 1995,1997) ALL-91 study was a prospective randomized multicenter trial and included all children with newly diagnosed intermediate risk acute lymphoblastic leukemia (IR ALL). Written informed consent was obtained for all patients registered on the study. Randomization was according to a minimization approach1. Previously untreated children and adolescents below the age of 15 with (IR ALL) according to the...

Study 8

Sullivan MP, Chen T, Dyment PG, Hvizdala E, Steuber CP. Equivalence of intrathecal chemotherapy and radiotherapy as central nervous system prophylaxis in children with acute lymphatic leukaemia a Pediatric Oncology Study Group. Blood 1982 60 948-58. South West Oncology Group Study 7420 (AlinC-11) was a prospective multicenter randomized study and ran from September 1974 to October 1976. Previously untreated children and adolescents below 18 years of age were enrolled on the study.

Study 4

Schrappe M, Reiter A, Zimmermann M, Harbott J, Ludwig W-D, Henze G, Gadner H, Odenwald E, Riehm H. Long-term results of four consecutive trials in childhood ALL performed by the ALL-BFM study group from 1981 to 1995. Leukaemia 2000 14 2205-22. ALL-BFM 83 was a multicenter prospective randomized study with treatment stratified according to the BFM (Berlin-Frankfurt-Munster) risk criteria. ALL-BFM 83 began in October 1983 and was closed in September 1986. The study was open to all patients less...

Study 17

Tubergen DG, Gilchrist GS, O'Brien RT, Coccia PF, Sather HN, Waskerwitz MJ, Denman Hammond G. Prevention of CNS disease in intermediate risk acute lymphoblastic leukemia comparison of cranial irradiation and intrathecal methotrexate and the importance of systemic therapy a Children's Cancer Group Report. J Clin Oncol 1993 11 520-6. This was a Children's Cancer Group Study (CCG-105) and was a prospective randomised trial that ran from May 1983 to April 1989. The trial was based on a 2 X 4...

Rf

*The range of the hemoglobin (Hb), white blood count (WBC), thrombocytes (Thr) and risk factors (RF) is given median is between brackets. The RF is calculated from the amount of blasts (BL) at diagnosis in the peripheral blood, liver enlargement (L) in cm, spleen enlargement (S) in cm (RF 0.2 log (BL + 1) + 6.06L + 0.04S). *The range of the hemoglobin (Hb), white blood count (WBC), thrombocytes (Thr) and risk factors (RF) is given median is between brackets. The RF is calculated from the amount...

Results economic assessment

Hospital stay was significantly shorter in the GCSF group compared to control group (53.9 days versus 63.5 days p 0.025), while the number of platelet units transfused were significantly higher in the GCSF group (4.7 versus 3.2 p 0.01). Red cell transfusions were similar in both groups (6 versus 5.7 p 0.898). Costing according to the resource category indicated that for the GCSF group, hospitalization cost was significantly reduced (US 21,883 versus US 25,780) while the costs of platelet...

Outcome

Eighty-five patients with histologically confirmed lymphoblastic lymphoma were entered. Eleven had localized (stage I and II) disease, 56 had stage III and 18 had stage IV. Fifty were randomized to A-COP and 35 to LSA2-L2. Nine patients were non-evaluable (failure to follow randomization in two, major protocol violation in six and inadequate data in one). Overall DFS for A-COP was 53 (SE 8 ) and 58 (SE 10 ) for LSA2-L2 at 3 years. This was not statistically significant. For stage IV disease,...

25th Anniversary

Figure 10.6 Comparisons of relapse-free survival by treatment and cooperative group for the randomized, eligible patients. Copyright 1990 American Cancer Society. Adapted and reprinted from Gehan et al. (full reference on p. 212) by permission of Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc. The 5-year relapse-free survival for IF plus MOPP was 97 versus 41 for IF alone (p 0.01) and for EF radiotherapy 67 versus IF plus MOPP 93 (p 0.01) (Figure 10.6). Despite the significant...

Hospitalization for FBN

Readmission rate with FBN was significantly reduced in the group that received prophylactic GCSF (34 of 46 patients (74 ) compared to 42 of 46 patients (91 ) in the control arm p 0.0386). Fever resolution was more rapid in the GCSF group compared with the control group, though this was not statistically significant 27 versus 9 p 0.0768 (two tailed) . There were no significant differences in the ANC on readmission to hospital between the two groups and, no evidence of any period effect....

Erythropoietin treatment

Children were randomly assigned to receive either rhEPO or a placebo for 16 weeks. The dose of rhEPO was 150IU kg three times week subcutaneously or intravenously. If the child required a transfusion or did not maintain a hemoglobin level > 11.5 g after 4 weeks of rhEPO treatment, the rhEPO dose was increased by increments of 50 IU kg (maximum dose 300 IU kg dose) every 4 weeks till the target hemoglobin value was achieved. Similarly, if the hemoglobin level was > 15 g , the dose was...

Details of the study

This was a multicenter, prospective randomized trial. Eligibility criteria were previously untreated patients aged under 21 years with biopsy proven non-Hodgkin's lymphoma (NHL), categorized as either Murphy stage I or II. Histology was reviewed by a panel of pathologists. Staging investigations included clinical evaluation, FBC, bone marrow aspirate, CSF examination, chest X-ray, bone scan and CT scan in children with head and neck tumors or intra-abdominal disease. Randomization was performed...

Commentary by Joann Ater

Medulloblastoma is one of the more common brain tumors in childhood, accounting for about 20 of CNS system tumors in children less than 21 years old. While it does occur in adults, the peak incidence is in early childhood. Despite the frequency, it is still a relatively rare tumor for performing clinical trials. Only approximately 300 cases of medulloblastoma are diagnosed in the United States each year. In its narrowest definition, it is a highly malignant neoplasm that originates in the...

Acute myeloid leukemia

Commentaries by Judith Chessells and Vaskar Saha The long-term survival for children with acute myeloid leukemia has improved steadily over the past 20 years.1-11 Acute myeloid leukemia is a rare disease in childhood and it is difficult to accrue sufficient numbers for randomized trials. Yet the need for such trials is pressing since as survival improves it becomes more important to refine therapy and avoid late effects of treatment. One approach to this problem, adopted by the UK Medical...

Randomized clinical trials

Randomized clinical trials in medulloblastoma have addressed the following important hypotheses 1 Adjuvant or neoadjuvant chemotherapy will improve survival. 2 A new chemotherapy regimen will be superior to the standard regimen in improving survival. 3 The dose of cranial-spinal radiotherapy can be reduced and thereby reduce long-term morbidity of therapy in some groups. 4 Utilizing chemotherapy with reduced dose cranial-spinal radiotherapy will improve survival rates while decreasing long-term...

Info

Cycles of consolidation chemotherapy to be given for a total of 4 times, up to week 41. MTX methotrexate (600mg m2 6 hour infusion) CF citrovorum factor (15mg 6 weekly X 12) VCR vincristine (1.5mg m2 IV max 2mg) ADR Adriamycin (doxorubicin) 70 mg m2 IV CYP cyclophosphamide (1200 mg m2 IV). This study was designed and executed by the EORTC between 1978 and 1983. Two hundred and forty patients below the age of 30 years were registered, of whom 205 were evaluable. Exclusions were due to low grade...

Evaluation of cardiotoxicity

MUGA scans using technetium 99 m pertechnetate labeled red blood cells was used to determine doxoru-bicin cardiotoxicity. These were performed at baseline and at 6-12 weeks after the 210,310,360 and 410 mg m2 cumulative doses of doxorubicin. All MUGA scans were reviewed by three nuclear medicine physicians who were blinded to the patient's randomization and clinical status. Dose-limiting cardiotoxicity was defined as a reduction in the LVEF to < 45 , or decrease in the LVEF by > 20...