Treatment of chronic myeloid leukemia has improved significantly with the introduction of tyrosine kinase inhibitors (TKIs), and treatment 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 children and adolescents with CML-BP has largely evolved empirically and includes treatment principles derived from adult CML-BP and pediatric acute leukemia. Given this heterogeneity of treatment approaches, we formed an international panel of pediatric CML experts to develop recommendations for consistent therapy in children and adolescents with this high-risk disease based on the current literature and national standards. Recommendations include detailed information on initial diagnosis and treatment monitoring, differentiation from Philadelphia-positive acute leukemia, subtype-specific selection of induction therapy, and combination with tyrosine kinase inhibitors. Given that allogeneic hematopoietic stem cell transplantation currently remains the primary curative intervention for CML-BP, we also provide recommendations for the timing of transplantation, donor and graft selection, selection of a conditioning regimen and prophylaxis for graft-versus-host disease, post-transplant TKI therapy, and management of molecular relapse. Management according to the treatment recommendations presented here is intended to provide the basis for the design of future prospective clinical trials to improve outcomes for this challenging disease.

Comprehensive Cancer Center Erlangen EMN Erlangen Germany

Department of Pediatric Hematology and Oncology University Hospital Motol Prague Czech Republic

Department of Pediatric Hematology Oncology Aghia Sophia Children's Hospital Athens Greece

Department of Pediatric Hematology Oncology and BMT Wroclaw Medical University Wroclaw Poland

Department of Pediatric Hematology Oncology and Stem Cell Transplantation Ghent University Hospital Ghent Belgium

Department of Pediatrics Keio University School of Medicine Tokyo Japan

Department of Translational and Precision Medicine Sapienza University of Rome Rome Italy

Departments of Paediatric Oncology Haematology Poitiers University Hospital Poitiers France

Division of Hematology Oncology BMT British Columbia Children's Hospital Research Institute Vancouver BC Canada

Division of Pediatric Hematology Oncology Stem Cell Transplantation Ann and Robert H Lurie Children's Hospital of Chicago Northwestern University Feinberg School of Medicine Chicago IL USA

Division of Pediatric Hematology Oncology Transplant Columbia University Irving Medical Center New York NY USA

Erasmus MC Sophia Children's Hospital Rotterdam the Netherlands

ITCC Hematological Malignancies Committee Rotterdam the Netherlands

Medizinische Klinik 4 Klinikum Bayreuth GmbH Bayreuth Germany

Pediatric Hemato Oncology Medical Faculty Technical University Dresden Dresden Germany

Pediatric Oncology and Hematology Department of Pediatrics and Adolescent Medicine University Hospital Erlangen Erlangen Germany

Princess Máxima Center for Pediatric Oncology Utrecht the Netherlands

St Anna Kinderspital Department of Pediatrics Medical University Vienna Austria

Women's and Children's Hospital and Royal Adelaide Hospital Adelaide SA Australia

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Management of children and adolescents with chronic myeloid leukemia in chronic phase: International pediatric chronic myeloid leukemia expert panel recommendations

Management and outcome of patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era - analysis of the European LeukemiaNet Blast Phase Registry