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.

Australian and New Zealand Children's Haematology Oncology Group Perth Australia

Berlin Frankfurt Münster Group Germany Kiel Germany

Children Cancer Research Institute Vienna Austria

Chilean National Pediatric Oncology Group Santiago Chile

Czech Working Group for Pediatric Hematology Prague Czech Republic

Dana Farber Cancer Institute Boston MA

Dutch Childhood Oncology Group Utrecht the Netherlands

European Organisation for Research and Treatment of Cancer Children Leukemia Group Brussels Belgium

French Acute Lymphoblastic Leukemia Study Group Paris France

GATLA Buenos Aires Argentina

German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia Hamburg Germany

Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children's Hospital Rome Italy

Polish Pediatric Leukemia Lymphoma Study Group Zabrze Medical University of Silesia Katowice Poland

Princess Maxima Center for Pediatric Oncology Utrecht the Netherlands

Rigshospitalet University of Copenhagen Copenhagen Denmark

Seattle Children's Hospital and Research Institute Seattle WA

St Anna Children's Hospital Medical University of Vienna Vienna Austria

St Jude Children's Research Hospital Memphis TN

The Chinese University of Hong Kong Shatin Hong Kong Special Administrative Region People's Republic of China

United Kingdom Children Cancer Study Group London United Kingdom

University of Milano Bicocca Monza Italy

University of Pavia Pavia Italy

University of Western Australia Perth Western Australia Australia

References provided by Crossref.org

ETV6::RUNX1 Acute Lymphoblastic Leukemia: how much therapy is needed for cure?

Low rate of nonrelapse mortality in under-4-year-olds with ALL given chemotherapeutic conditioning for HSCT: a phase 3 FORUM study

Outcomes of Childhood Noninfant Acute Lymphoblastic Leukemia With 11q23/KMT2A Rearrangements in a Modern Therapy Era: A Retrospective International Study

Pediatric Precursor B-Cell Lymphoblastic Malignancies: From Extramedullary to Medullary Involvement

Favorable outcome of NUTM1-rearranged infant and pediatric B cell precursor acute lymphoblastic leukemia in a collaborative international study

Clinical Implications of Minimal Residual Disease Detection in Infants With KMT2A-Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 Protocol

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EudraCT
2005-004599-19

ClinicalTrials.gov
NCT00550992