References

1 Mitchell CD, Richards SM, Kinsey SE, Lilleyman J, Vora A, Eden TO. Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia results of the UK Medical Research Council ALL97 randomized trial. Br J Haematol 2005 129(6) 734-45. 2 Einsiedel HG, von Stackelberg A, Hartmann R, Fengler R, Schrappe M, Janka-Schaub G, Mann G, Hahlen K, Gobel U, Klingebiel T, Ludwig WD, Henze G. Long-term outcome in children with relapsed ALL by risk-stratified salvage therapy...

Commentary by Tim Eden and Ross Pinkerton

It is difficult for the current practitioner to realize that before the mid-1970s the outcome for children with non-Hodgkin's lymphoma (unless they had truly localized disease treated with surgery and local radiation) was very poor. The use of pulsed chemotherapy with regimens such as CHOP yielded 5-year event-free survival rates of 20 or less. The advent of truly intensive regimens for acute lymphoblastic leukemia (ALL) protocols and their application to the non-Hodgkin's lymphomas (NHL)...

Continuing maintenance therapy

Long-term, relatively low dose, continuing (maintenance) therapy with daily oral mercaptopurine and weekly methotrexate has been part of treatment of ALL for over 30 years. Usually 6-MP is given daily and methotrexate once weekly.54 While some groups use monthly pulses of vincristine and steroids, others do not. Continuing treatment is unique to ALL and some types of non-Hodgkin's lymphomas (NHL) (see Chapter 9) but its precise mode of action is unknown. Continuing treatment is...

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

Patients received standard induction chemotherapy with ifosfamide and etoposide, cyclophosphamide and doxorubicin (see Figure 3.8). Local control from week 9 consisted of surgical resection and radiation therapy depending on tumor size and response (see Table 3.1). Following this, patients were randomized to receive cyclophosphamide at 1 g m2 versus 1.5 g m2 combined with doxorubicin and alternated with ifosfamide and etoposide (see Figure 3.8). Treatment lasted 41 weeks.

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...

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

Two hundred and eleven patients were registered onto the study. Nine were non-eligible due to prior chemotherapy or performance status, and 10 were excluded due to inadequate data collection. One hundred and eighty-three patients completed induction chemotherapy. Ninety-one patients were randomized on the schedule study 43 received continuous infusion platinum and 48 bolus. They were well matched for age, sex, primary location, catecholamine increase, MIBG, marrow positivity and other secondary...

25th Anniversary

BPatient average number of days per cycle. bPatient average number of days per cycle. difference between the two groups of patients with regard to delay in chemotherapy (p 0.16) or duration of hospitalization (p 0.22), there was statistically significant difference in the number days of ANC < 500 il favoring the r-metHuGCSF group (p 0.017). There was no difference in the 2-year event-free survival (EFS) rates (71 ) between the r-metHuGCSF and non-r-metHuGCSF groups (log rank p-value, 0.52).

Details of the study

According to risk status, children with low risk acute lymphoblastic leukemia (ALL) were assigned to CCG study 161, those with intermediate risk to CCG study 162, and high risk children to CCG study 163. Treatment details are not available in the report. Children, who were in continuous clinical remission 2 years after diagnosis, were randomized either to stop treatment or to continue maintenance therapy for an additional year. Boys underwent bilateral testicular biopsies prior to randomization...

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...