Rob Pieters1,2, Paola De Lorenzo3, Philip Ancliffe4, Luis Alberto Aversa5, Benoit Brethon6, Andrea Biondi3,7,8, Myriam Campbell9, Gabriele Escherich10, Alina Ferster11, Rebecca A Gardner12, Rishi Sury Kotecha13,14, Birgitte Lausen15, Chi Kong Li16, Franco Locatelli3,7,8, Andishe Attarbaschi17, Christina Peters18, Jeffrey E Rubnitz19, Lewis B Silverman20, Jan Stary21, Tomasz Szczepanski22, Ajay Vora4, Martin Schrappe23, Maria Grazia Valsecchi3. 1. Dutch Childhood Oncology Group, Utrecht, the Netherlands. 2. Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands. 3. University of Milano-Bicocca, Monza, Italy. 4. United Kingdom Children Cancer Study Group, London, United Kingdom. 5. GATLA, Buenos Aires, Argentina. 6. French Acute Lymphoblastic Leukemia Study Group, Paris, France. 7. Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital, Rome, Italy. 8. University of Pavia, Pavia, Italy. 9. Chilean National Pediatric Oncology Group, Santiago, Chile. 10. German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia, Hamburg, Germany. 11. European Organisation for Research and Treatment of Cancer Children Leukemia Group, Brussels, Belgium. 12. Seattle Children's Hospital and Research Institute, Seattle, WA. 13. Australian and New Zealand Children's Haematology/Oncology Group, Perth, Australia. 14. University of Western Australia, Perth, Western Australia, Australia. 15. Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 16. The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region, People's Republic of China. 17. St Anna Children's Hospital, Medical University of Vienna, Vienna, Austria. 18. Children Cancer Research Institute, Vienna, Austria. 19. St Jude Children's Research Hospital, Memphis, TN. 20. Dana-Farber Cancer Institute, Boston, MA. 21. Czech Working Group for Pediatric Hematology, Prague, Czech Republic. 22. Polish Pediatric Leukemia/Lymphoma Study Group, Zabrze, Medical University of Silesia, Katowice, Poland. 23. Berlin-Frankfurt-Münster Group Germany, Kiel, Germany.
Abstract
PURPOSE:Infant acute lymphoblastic leukemia (ALL) is characterized by KMT2A (MLL) gene rearrangements and coexpression of myeloid markers. The Interfant-06 study, comprising 18 national and international study groups, tested whether myeloid-style consolidation chemotherapy is superior to lymphoid style, the role of stem-cell transplantation (SCT), and which factors had independent prognostic value. MATERIALS AND METHODS:Three risk groups were defined: low risk (LR): KMT2A germline; high risk (HR): KMT2A-rearranged and older than 6 months with WBC count 300 × 109/L or more or a poor prednisone response; and medium risk (MR): all other KMT2A-rearranged cases. Patients in the MR and HR groups were randomly assigned to receive the lymphoid course low-dose cytosine arabinoside [araC], 6-mercaptopurine, cyclophosphamide (IB) or experimental myeloid courses, namely araC, daunorubicin, etoposide (ADE) and mitoxantrone, araC, etoposide (MAE). RESULTS: A total of 651 infants were included, with 6-year event-free survival (EFS) and overall survival of 46.1% (SE, 2.1) and 58.2% (SE, 2.0). In West European/North American groups, 6-year EFS and overall survival were 49.4% (SE, 2.5) and 62.1% (SE, 2.4), which were 10% to 12% higher than in other countries. The 6-year probability of disease-free survival was comparable for the randomized arms (ADE+MAE 39.3% [SE 4.0; n = 169] v IB 36.8% [SE, 3.9; n = 161]; log-rank P = .47). The 6-year EFS rate of patients in the HR group was 20.9% (SE, 3.4) with the intention to undergo SCT; only 46% of them received SCT, because many had early events. KMT2A rearrangement was the strongest prognostic factor for EFS, followed by age, WBC count, and prednisone response. CONCLUSION: Early intensification with postinduction myeloid-type chemotherapy courses did not significantly improve outcome for infant ALL compared with the lymphoid-type course IB. Outcome for infant ALL in Interfant-06 did not improve compared with that in Interfant-99.
RCT Entities:
PURPOSE:Infantacute lymphoblastic leukemia (ALL) is characterized by KMT2A (MLL) gene rearrangements and coexpression of myeloid markers. The Interfant-06 study, comprising 18 national and international study groups, tested whether myeloid-style consolidation chemotherapy is superior to lymphoid style, the role of stem-cell transplantation (SCT), and which factors had independent prognostic value. MATERIALS AND METHODS: Three risk groups were defined: low risk (LR): KMT2A germline; high risk (HR): KMT2A-rearranged and older than 6 months with WBC count 300 × 109/L or more or a poor prednisone response; and medium risk (MR): all other KMT2A-rearranged cases. Patients in the MR and HR groups were randomly assigned to receive the lymphoid course low-dose cytosine arabinoside [araC], 6-mercaptopurine, cyclophosphamide (IB) or experimental myeloid courses, namely araC, daunorubicin, etoposide (ADE) and mitoxantrone, araC, etoposide (MAE). RESULTS: A total of 651 infants were included, with 6-year event-free survival (EFS) and overall survival of 46.1% (SE, 2.1) and 58.2% (SE, 2.0). In West European/North American groups, 6-year EFS and overall survival were 49.4% (SE, 2.5) and 62.1% (SE, 2.4), which were 10% to 12% higher than in other countries. The 6-year probability of disease-free survival was comparable for the randomized arms (ADE+MAE 39.3% [SE 4.0; n = 169] v IB 36.8% [SE, 3.9; n = 161]; log-rank P = .47). The 6-year EFS rate of patients in the HR group was 20.9% (SE, 3.4) with the intention to undergo SCT; only 46% of them received SCT, because many had early events. KMT2A rearrangement was the strongest prognostic factor for EFS, followed by age, WBC count, and prednisone response. CONCLUSION: Early intensification with postinduction myeloid-type chemotherapy courses did not significantly improve outcome for infant ALL compared with the lymphoid-type course IB. Outcome for infant ALL in Interfant-06 did not improve compared with that in Interfant-99.
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