Leukemiawww.nature.com/leuREVIEW ARTICLEOPEN周Check for updatesCHRONIC MYELOGENOUS LEUKEMIAManagement of children and adolescents with chronic myeloidleukemia in blast phase:International pediatric CML expertpanel recommendationsStephanie Sembill12,Maria Ampatzidou3,Sonali Chaudhury,Michael Dworzak5,Krzysztof Kalwaks,Axel Karow 2,Alexander Kiani?,Manuela Krumbholz2,Maaike Luesink3,Nora Naumann-Bartsch'2,Barbara De Moerloose,Michael Osborn 0Kirk R.Schultz,Petr Sedlacek,Fiorina Giona,Christian Michel Zwaan15,Hiroyuki Shimada,Birgitta Versluijs,Frederic Millot Nobuko Hijiya Meinolf Suttorpand Markus Metzlere The Author(s)2023Treatment of chronic myeloid leukemia has improved significantly with the introduction of tyrosine kinase inhibitors(TKIs),andtreatment guidelines based on numerous clinical trials are available for chronic phase disease.However for CML in the blast phase(CML-BP),prognosis remains poor and treatment options are much more limited.The spectrum of treatment strategies for childrenand adolescents with CML-BP has largely evolved empirically and indudes treatment principles derived from adult CML-BP andpediatric acute leukemia.Given this heterogeneity of treatment approaches,we formed an international panel of pediatric CMLexperts to develop recommendations for consistent therapy in children and adolescents with this high-risk disease based on thecurrent literature and national standards.Recommendations include detailed information on initial diagnosis and treatmentmonitoring,differentiation from Philadelphia-positive acute leukemia,subtype-specific selection of induction therapy,andcombination with tyrosine kinase inhibitors.Given that allogeneic hematopoietic stem cell transplantation currently remains theprimary curative intervention for CML-BP,we also provide recommendations for the timing of transplantation,donor and graftselection,selection of a conditioning regimen and prophylaxis for graft-versus-host disease,post-transplant TKI therapy,andmanagement of molecular relapse.Management according to the treatment recommendations presented here is intended toprovide the basis for the design of future prospective clinical trials to improve outcomes for this challenging disease.Leukemia;https://doi.org/10.1038/s41375-023-01822-2INTRODUCTIONdecreased to 1-1.5%from more than 20%[1,2].However,theChronic myeloid leukemia (CML)blast phase (CML-BP)isprognosis for adult patients with de novo or secondary CML-BPcharacterized by dlinical,phenotypic,and genetic features ofremains poor;median survival is less than 1 year [3].The lowacute leukemia.CML-BP can occur as an initial presentation ofincidence of CML in pediatric patients (1-2.2 cases per million perCML(de novo CML-BP)or as a progression from the chronic (CP)oryear,with 7-10%being diagnosed with BP)and the lack ofaccelerated(AP)phases of CML (secondary CML-BP).specific clinical trials mean that there is minimal evidence toAfter the introduction of tyrosine kinase inhibitors (TKIs),theinfo
