Dexamethasone-based therapy for childhood acute lymphoblastic leukaemia: results of the prospective Dutch Childhood Oncology Group (DCOG) protocol ALL-9 (1997-2004). Export

@article{citeulike:5785850, abstract = {BACKGROUND: A population-based cohort of children aged 1-18 years with acute lymphoblastic leukaemia (ALL) was treated with a dexamethasone-based protocol (Dutch Childhood Oncology Group [DCOG] ALL-9). We aimed to confirm the results of the most effective DCOG ALL protocol for non-high-risk (NHR) patients to date (ALL-6), compare results with ALL-7 and ALL-8, and study prognostic factors in a non-randomised setting. METHODS: From Jan 1, 1997, until Nov 1, 2004, patients with ALL were treated according to the ALL-9 protocol in eight Dutch academic centres with their affiliated peripheral hospitals. Patients were stratified into NHR and high risk (HR) groups. HR criteria were white-blood-cell count of 50 000 cells per muL or more, T-cell phenotype, mediastinal mass, CNS or testicular involvement, and Philadelphia chromosome or MLL rearrangement; patients who did not fulfil these criteria were deemed to be NHR. The NHR group was treated with a three-drug induction (dexamethasone, vincristine, and asparaginase) for 6 weeks, medium-dose methotrexate for 3 weeks, then maintenance therapy. HR patients received a four-drug induction (as for the NHR patients plus daunorubicin) for 6 weeks, high-dose methotrexate for 8 weeks, and two intensification courses before receiving maintenance therapy. Triple intrathecal medication was given 13 times in NHR patients, 15 times in HR patients (17 times for patients with initial CNS involvement). No patient received cranial irradiation. Maintenance therapy was given until 109 weeks for all patients and consisted of mercaptopurine and methotrexate for 5 weeks, alternated with dexamethasone and vincristine for 2 weeks. Kaplan-Meier analysis was done on an intention-to-treat basis with event-free survival as the primary endpoint. This trial is registered at trialregister.nl, number NTR460/SNWLK-ALL-9. FINDINGS: 859 patients were recruited to the study. Complete remission was achieved in 592 (98.5\%) of the 601 patients in the NHR group and 250 (96.9\%) of the 258 in the HR group. Five patients in the NHR group and four in the HR group died during induction. Median follow-up for patients alive was 72.2 (range 4.8-132.7) months as of August, 2008. 5-year event-free survival was 81\% (SE 1\%) in all patients: 84\% (2\%) in NHR patients, and 72\% (3\%) in HR patients. Isolated CNS relapses occurred in 22 (2.6\%) of 842 patients. In a multivariate analysis, DNA index was the strongest predictor of outcome (<1.16 vs >/=1.16; relative risk 0.42, 95\% CI 0.22-0.78), followed by age (1-9 vs >/=10 years; 2.23, 1.60-3.11) and white-blood-cell count (<50 000 vs >/=50 000 cells per muL; 1.60, 1.13-2.26). INTERPRETATION: The overall results of the dexamethasone-based DCOG ALL-9 protocol are better than those of our previous Berlin-Frankfurt-M\"{u}nster-based protocols ALL-7 and ALL-8. The results for NHR patients were achieved with high cumulative doses of dexamethasone and vincristine, but without the use of anthracyclines, etoposide, cyclophosphamide, or cranial irradiation, therefore minimising the risk of side-effects. FUNDING: Dutch Health Insurers.}, author = {Veerman, Anjo J. and Kamps, Willem A. and van den Berg, Henk and van den Berg, Eva and B\"{o}kkerink, Jos Pm P. and Bruin, Marrie Ca C. and van den Heuvel-Eibrink, Marry M. and Korbijn, Carin M. and Korthof, Elisabeth T. and van der Pal, Karin and Stijnen, Theo and van Weel Sipman, Margreet H. and van Weerden, J. Fransje and van Wering, Elisabeth R. and van der Does-van den Berg, Anna and {for the Dutch Childhood Oncology Group}}, citeulike-article-id = {5785850}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/S1470-2045(09)70228-1}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S1470204509702281}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19747876}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19747876}, day = {9}, doi = {10.1016/S1470-2045(09)70228-1}, issn = {1474-5488}, journal = {The lancet oncology}, keywords = {all, dcog, dexamethasone}, month = {September}, posted-at = {2009-09-25 00:31:27}, priority = {2}, title = {Dexamethasone-based therapy for childhood acute lymphoblastic leukaemia: results of the prospective Dutch Childhood Oncology Group (DCOG) protocol ALL-9 (1997-2004).}, url = {http://dx.doi.org/10.1016/S1470-2045(09)70228-1}, year = {2009} }

TY - JOUR ID - citeulike:5785850 L3 - citeulike-article-id:5785850 N2 - BACKGROUND: A population-based cohort of children aged 1-18 years with acute lymphoblastic leukaemia (ALL) was treated with a dexamethasone-based protocol (Dutch Childhood Oncology Group [DCOG] ALL-9). We aimed to confirm the results of the most effective DCOG ALL protocol for non-high-risk (NHR) patients to date (ALL-6), compare results with ALL-7 and ALL-8, and study prognostic factors in a non-randomised setting. METHODS: From Jan 1, 1997, until Nov 1, 2004, patients with ALL were treated according to the ALL-9 protocol in eight Dutch academic centres with their affiliated peripheral hospitals. Patients were stratified into NHR and high risk (HR) groups. HR criteria were white-blood-cell count of 50 000 cells per muL or more, T-cell phenotype, mediastinal mass, CNS or testicular involvement, and Philadelphia chromosome or MLL rearrangement; patients who did not fulfil these criteria were deemed to be NHR. The NHR group was treated with a three-drug induction (dexamethasone, vincristine, and asparaginase) for 6 weeks, medium-dose methotrexate for 3 weeks, then maintenance therapy. HR patients received a four-drug induction (as for the NHR patients plus daunorubicin) for 6 weeks, high-dose methotrexate for 8 weeks, and two intensification courses before receiving maintenance therapy. Triple intrathecal medication was given 13 times in NHR patients, 15 times in HR patients (17 times for patients with initial CNS involvement). No patient received cranial irradiation. Maintenance therapy was given until 109 weeks for all patients and consisted of mercaptopurine and methotrexate for 5 weeks, alternated with dexamethasone and vincristine for 2 weeks. Kaplan-Meier analysis was done on an intention-to-treat basis with event-free survival as the primary endpoint. This trial is registered at trialregister.nl, number NTR460/SNWLK-ALL-9. FINDINGS: 859 patients were recruited to the study. Complete remission was achieved in 592 (98.5%) of the 601 patients in the NHR group and 250 (96.9%) of the 258 in the HR group. Five patients in the NHR group and four in the HR group died during induction. Median follow-up for patients alive was 72.2 (range 4.8-132.7) months as of August, 2008. 5-year event-free survival was 81% (SE 1%) in all patients: 84% (2%) in NHR patients, and 72% (3%) in HR patients. Isolated CNS relapses occurred in 22 (2.6%) of 842 patients. In a multivariate analysis, DNA index was the strongest predictor of outcome (<1.16 vs >/=1.16; relative risk 0.42, 95% CI 0.22-0.78), followed by age (1-9 vs >/=10 years; 2.23, 1.60-3.11) and white-blood-cell count (<50 000 vs >/=50 000 cells per muL; 1.60, 1.13-2.26). INTERPRETATION: The overall results of the dexamethasone-based DCOG ALL-9 protocol are better than those of our previous Berlin-Frankfurt-Münster-based protocols ALL-7 and ALL-8. The results for NHR patients were achieved with high cumulative doses of dexamethasone and vincristine, but without the use of anthracyclines, etoposide, cyclophosphamide, or cranial irradiation, therefore minimising the risk of side-effects. FUNDING: Dutch Health Insurers. JF - The lancet oncology SN - 1474-5488 TI - Dexamethasone-based therapy for childhood acute lymphoblastic leukaemia: results of the prospective Dutch Childhood Oncology Group (DCOG) protocol ALL-9 (1997-2004). KW - all KW - dcog KW - dexamethasone AU - Veerman, Anjo AU - Kamps, Willem AU - van den Berg, Henk AU - van den Berg, Eva AU - Bökkerink, Jos Pm AU - Bruin, Marrie Ca AU - van den Heuvel-Eibrink, Marry AU - Korbijn, Carin AU - Korthof, Elisabeth AU - van der Pal, Karin AU - Stijnen, Theo AU - van Weel Sipman, Margreet AU - van Weerden, Fransje AU - van Wering, Elisabeth AU - van der Does-van den Berg, Anna PY - 2009/09/09/ UR - http://dx.doi.org/10.1016/S1470-2045(09)70228-1 ER -