Matthew A. Kutny

Leukemic mutations in the methylation-associated genes DNMT3A and IDH2 are rare events in pediatric AML: A report from the Children's Oncology Group†

Mutations in the DNMT3A, TET2, IDH1, and IDH2 genes carry prognostic significance and occur frequently in adult acute myeloid leukemia (AML). Leukemic mutations in all four genes have recently been implicated in aberrant DNA methylation, a hallmark of neoplasia. We previously reported that IDH1 mutations were absent, whereas TET2 mutations were present in 6%, of pediatric AML patients; in the present study, we determined the prevalence of DNMT3A and IDH2 mutations in pediatric AML.

Mutations in the DNMT3A exon 23 independently predict poor outcome in older patients with acute myeloid leukemia: a SWOG report.

Mutations in the DNMT3A exon 23 independently predict poor outcome in older patients with acute myeloid leukemia: a SWOG report

FLT3 mutation status is a predictor of early death in pediatric acute promyelocytic leukemia: A report from the Children's Oncology Group†‡

FLT3 mutations (FLT3/Mut) are prevalent in de novo AML and are associated with early relapse. The prevalence and prognostic significance of FLT3/Mut have not been well defined in childhood acute promyelocytic leukemia (APL).

Ethnic variation of TET2 SNP rs2454206 and association with clinical outcome in childhood AML: A report from the Children's Oncology Group

Ethnic variation of TET2 SNP rs2454206 and association with clinical outcome in childhood AML: a report from the Children’s Oncology Group

Arsenic Trioxide Consolidation Allows Anthracycline Dose Reduction for Pediatric Patients With Acute Promyelocytic Leukemia: Report From the Children's Oncology Group Phase III Historically Controlled Trial AAML0631

Purpose The Childrens Oncology Group AAML0631 trial for newly diagnosed pediatric acute promyelocytic leukemia (APL) was a phase III historically controlled trial to determine the survival of patients receiving arsenic trioxide (ATO) consolidation and reduced doses of anthracyclines. Patients and Methods Patients age 2 to 21 years with de novo APL confirmed by PML-RARα polymerase chain reaction were stratified as standard risk (SR) or high risk (HR) on the basis of diagnostic WBC count. All patients received all-trans retinoic acid (ATRA) during induction, each consolidation course, and maintenance. All patients received two cycles of ATO therapy during consolidation 1, an additional two (SR) or three (HR) consolidation courses that included high-dose cytarabine and anthracycline, and maintenance therapy comprising ATRA, oral methotrexate, and mercaptopurine. Results One hundred one patients (66 SR and 35 HR) were evaluable for outcome. The 3-year overall survival was 94%, and event-free survival (EFS) was 91%. For SR and HR patients with APL, the overall survival was 98% versus 86% ( P = .003), and EFS was 95% versus 83% ( P = .03), respectively. The EFS for SR patients in AAML0631 was noninferior to that of patients in the AIDA 0493 historical control, which used a significantly higher anthracycline dose and did not include ATO consolidation. Relapse risk for patients in AAML0631 from end consolidation 1 (after ATO treatment) was only 4% at 3 years and did not differ significantly between SR and HR patients. Conclusion ATO consolidation cycles were well tolerated in pediatric patients with APL and allowed significant reduction in cumulative anthracycline doses while maintaining excellent survival and a low relapse risk for both SR and HR patients with APL.

Inclusion of Adolescents and Young Adults in Cancer Clinical Trials

OBJECTIVES To discuss recent and current initiatives to increase enrollment of adolescents and young adult (AYA) cancer patients onto National Cancer Institute-funded clinical trials to improve outcomes. DATA SOURCES Peer-reviewed publications, websites of professional organizations. CONCLUSION Despite many challenges facing AYAs, recent studies illustrate that AYA-focused cancer clinical trials can be successfully developed and conducted. Development of the National Cancer Institute National Clinical Trials Network and related AYA-focused initiatives create new opportunities to expand clinical trials that serve AYAs. IMPLICATIONS FOR NURSING PRACTICE Nurses can influence AYA outcomes by leveraging their roles as educators and collaborators to increase participation in cancer clinical trials.

Treatment of paediatric APL: How does the therapeutic approach differ from adults?

Acute promyelocytic leukaemia (APL) in children and adolescents shares many features with APL in adults. There are important distinctions, however, between these age groups in the presentation, complications and treatment outcomes. Paediatric patients are more likely to present with high risk features including elevated WBC count or microgranular variant (M3v). Yet the early death rate is lower in paediatric patients compared to adult patients. Overall outcomes such as CR, OS and EFS appear similar in paediatric and adult patients treated on similar regimens except that very young children may have a higher risk of relapse. While contemporary studies have clearly demonstrated improved survival in adults receiving ATO therapy, currently there is more limited data on the role of ATO in paediatric patients. Here we highlight the similarities and important distinctions between paediatric and adult APL while reviewing available data on treatment of paediatric APL.

Management of relapsed and refractory childhood acute promyelocytic leukaemia: recommendations from an international expert panel.

Oussama Abla, Matthew A. Kutny, Anna Maria Testi, James H. Feusner, Ursula Creutzig, John Gregory Jr, Brenda Gibson, Guy Leverger, Raul C. Ribeiro, Owen Smith, Franco Locatelli and Gertjan Kaspers Division of Hematology/Oncology, Department of Pediatrics, the Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada, Department of Pediatrics, Division of Hematology/Oncology, University of Alabama at Birmingham, Birmingham, AL, USA, Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome, Rome, Italy, Division of Hematology/ Oncology, Children’s Hospital and Research Center Oakland, Oakland, CA, USA, Paediatric Haematology/Oncology, Hannover Medical School, Hannover, Germany, Atlantic Health System, Goryeb Children’s Hospital, Morristown, NJ, USA, Department of Haematology and Oncology, Royal Hospital for Children, Glasgow, UK, Haematology/Oncology, Hôpital Armand Trousseau, Paris, France, Department of Oncology, Division of Leukemia/Lymphoma, St. Jude Children’s Research Hospital, Memphis, TN, USA, Department of Haematology/Oncology, Our Lady’s Children’s Hospital, Dublin, Ireland, Department of Paediatric Haematology and Oncology, IRCCS Ospedale Pediatrico Bambino Ges u, Rome, University of Pavia, Pavia, Italy, Paediatric Oncology, VU University Medical Centre, Amsterdam and Academy of Princess Máxima Centre for Paediatric Oncology, Utrecht, The Netherlands

Acute myelogenous leukemia in adolescents and young adults

The incidence of acute myelogenous leukemia (AML) increases progressively with age. Favorable genetic mutations are most prevalent in children, and unfavorable profiles increase proportionately in adolescents and young adults (AYA) and into later adulthood. Survival rates of AYA have improved over recent decades to 50–60%, but their accrual to clinical trials remains poor. In contrast to AYA with acute lymphoblastic leukemia, the prognostic benefit for AYA with AML enrolled in pediatric compared with adult trials is minor and only seen when different protocols are used. The distinctive needs of AYA, including intensive psychological services, call for their treatment within specialized centers that offer complex supportive care.

Incidence and outcomes of paediatric myelodysplastic syndrome in the United States

Cagliari, Department of Reproduction and Growth, University Hospital Sant’Anna in Ferrara, Ferrara, Haemato-Oncology Unit, Azienda Ospedaliera “Pugliese-Ciaccio”, Catanzaro, Paediatric Unit, Ospedale di Sassari, Sassari, Department of Paediatrics, University of MilanoBicocca, Monza, Dipartimento di Oncoematologia Pediatrica, IRCCS Ospedale Bambino Ges u, Rome, and Dipartimento di Scienze Pediatriche Universit a di Pavia, Italy. E-mail: giona@bce.uniroma1.it