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

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...

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...

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).

Evaluation of cardiac function

Baseline resting LVEF was 59.6 2.2 and 59.8 2.5 for the control and DXN group respectively (p 0.78). Only 33 of the 38 assessable patients were assessable for cardiotoxicity analysis 5 patients developed either progressive cardiac failure (3 control patients) or electively discontinued DXN before the first on therapy MUGA scan at week 24. The mean decrease in LVEF per 100mg m2 of dox-orubicin was 2.7 percentage points in the control group compared to 1 percentage point in the DXN group (p...

Details of the study

Previously untreated children and adolescents less than 20 years of age with ALL were enrolled on the study. All patients with hepatic or renal dysfunction, CNS disease at diagnosis or hyperuricaemia were excluded from entry until these abnormalities normalized. Patients were stratified as standard or high risk according to age and diagnostic white cell count. Standard risk (SR) children were between 2 and 8 years of age and had a diagnostic white cell count of < 30 X 109 l. All others were...

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...