Mixed‐phenotype acute leukemia: A cohort and consensus research strategy from the Children’s Oncology Group Acute Leukemia of Ambiguous Lineage Task Force
Background Optimal chemotherapy for treating mixed‐phenotype acute leukemia (MPAL) and the role of hematopoietic stem cell transplantation (HSCT) remain uncertain. Major limitations in interpreting available data are MPAL's rarity and the use of definitions other than the currently widely accep...
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| Published in | Cancer Vol. 126; no. 3; pp. 593 - 601 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Wiley Subscription Services, Inc
01.02.2020
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Background
Optimal chemotherapy for treating mixed‐phenotype acute leukemia (MPAL) and the role of hematopoietic stem cell transplantation (HSCT) remain uncertain. Major limitations in interpreting available data are MPAL's rarity and the use of definitions other than the currently widely accepted criteria: the World Health Organization 2016 (WHO2016) classification.
Methods
To assess the relative efficacy of chemotherapy types for treating pediatric MPAL, the Children's Oncology Group (COG) Acute Leukemia of Ambiguous Lineage Task Force assembled a retrospective cohort of centrally reviewed WHO2016 MPAL cases selected from banking studies for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Patients were not treated in COG trials; treatment and outcome data were captured separately. The findings were then integrated with the available, mixed literature to develop a prospective trial in pediatric MPAL.
Results
The central review confirmed that 54 of 70 cases fulfilled WHO2016 criteria for MPAL. ALL induction regimens achieved remission in 72% of the cases (28 of 39), whereas AML regimens achieved remission in 69% (9 of 13). The 5‐year event‐free survival (EFS) and overall survival (OS) rates for the entire cohort were 72% ± 8% and 77% ± 7%, respectively. EFS and OS were 75% ± 13% and 84% ± 11%, respectively, for those receiving ALL chemotherapy alone without HSCT (n = 21).
Conclusions
The results of the COG MPAL cohort and a literature review suggest that ALL chemotherapy without HSCT may be the preferred initial therapy. A prospective trial within the COG is proposed to investigate this approach; AML chemotherapy and/or HSCT will be reserved for those with treatment failure as assessed by minimal residual disease. Embedded biology studies will provide further insight into MPAL genomics.
Acute lymphoblastic leukemia–directed chemotherapy without hematopoietic stem cell transplantation may be sufficient therapy for most children with World Health Organization 2016 classification–defined mixed‐phenotype acute leukemia. A proposed prospective trial will investigate this approach and explore mixed‐phenotype acute leukemia genomics and correlative biology. |
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| AbstractList | ALL-directed chemotherapy without hematopoietic stem cell transplantation may be sufficient therapy for most children with WHO2016-defined MPAL. The proposed prospective trial will investigate this approach and explore MPAL genomics and correlative biology. Background Optimal chemotherapy for treating mixed‐phenotype acute leukemia (MPAL) and the role of hematopoietic stem cell transplantation (HSCT) remain uncertain. Major limitations in interpreting available data are MPAL's rarity and the use of definitions other than the currently widely accepted criteria: the World Health Organization 2016 (WHO2016) classification. Methods To assess the relative efficacy of chemotherapy types for treating pediatric MPAL, the Children's Oncology Group (COG) Acute Leukemia of Ambiguous Lineage Task Force assembled a retrospective cohort of centrally reviewed WHO2016 MPAL cases selected from banking studies for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Patients were not treated in COG trials; treatment and outcome data were captured separately. The findings were then integrated with the available, mixed literature to develop a prospective trial in pediatric MPAL. Results The central review confirmed that 54 of 70 cases fulfilled WHO2016 criteria for MPAL. ALL induction regimens achieved remission in 72% of the cases (28 of 39), whereas AML regimens achieved remission in 69% (9 of 13). The 5‐year event‐free survival (EFS) and overall survival (OS) rates for the entire cohort were 72% ± 8% and 77% ± 7%, respectively. EFS and OS were 75% ± 13% and 84% ± 11%, respectively, for those receiving ALL chemotherapy alone without HSCT (n = 21). Conclusions The results of the COG MPAL cohort and a literature review suggest that ALL chemotherapy without HSCT may be the preferred initial therapy. A prospective trial within the COG is proposed to investigate this approach; AML chemotherapy and/or HSCT will be reserved for those with treatment failure as assessed by minimal residual disease. Embedded biology studies will provide further insight into MPAL genomics. Acute lymphoblastic leukemia–directed chemotherapy without hematopoietic stem cell transplantation may be sufficient therapy for most children with World Health Organization 2016 classification–defined mixed‐phenotype acute leukemia. A proposed prospective trial will investigate this approach and explore mixed‐phenotype acute leukemia genomics and correlative biology. BackgroundOptimal chemotherapy for treating mixed‐phenotype acute leukemia (MPAL) and the role of hematopoietic stem cell transplantation (HSCT) remain uncertain. Major limitations in interpreting available data are MPAL's rarity and the use of definitions other than the currently widely accepted criteria: the World Health Organization 2016 (WHO2016) classification.MethodsTo assess the relative efficacy of chemotherapy types for treating pediatric MPAL, the Children's Oncology Group (COG) Acute Leukemia of Ambiguous Lineage Task Force assembled a retrospective cohort of centrally reviewed WHO2016 MPAL cases selected from banking studies for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Patients were not treated in COG trials; treatment and outcome data were captured separately. The findings were then integrated with the available, mixed literature to develop a prospective trial in pediatric MPAL.ResultsThe central review confirmed that 54 of 70 cases fulfilled WHO2016 criteria for MPAL. ALL induction regimens achieved remission in 72% of the cases (28 of 39), whereas AML regimens achieved remission in 69% (9 of 13). The 5‐year event‐free survival (EFS) and overall survival (OS) rates for the entire cohort were 72% ± 8% and 77% ± 7%, respectively. EFS and OS were 75% ± 13% and 84% ± 11%, respectively, for those receiving ALL chemotherapy alone without HSCT (n = 21).ConclusionsThe results of the COG MPAL cohort and a literature review suggest that ALL chemotherapy without HSCT may be the preferred initial therapy. A prospective trial within the COG is proposed to investigate this approach; AML chemotherapy and/or HSCT will be reserved for those with treatment failure as assessed by minimal residual disease. Embedded biology studies will provide further insight into MPAL genomics. Optimal chemotherapy for treating mixed-phenotype acute leukemia (MPAL) and the role of hematopoietic stem cell transplantation (HSCT) remain uncertain. Major limitations in interpreting available data are MPAL's rarity and the use of definitions other than the currently widely accepted criteria: the World Health Organization 2016 (WHO2016) classification. To assess the relative efficacy of chemotherapy types for treating pediatric MPAL, the Children's Oncology Group (COG) Acute Leukemia of Ambiguous Lineage Task Force assembled a retrospective cohort of centrally reviewed WHO2016 MPAL cases selected from banking studies for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Patients were not treated in COG trials; treatment and outcome data were captured separately. The findings were then integrated with the available, mixed literature to develop a prospective trial in pediatric MPAL. The central review confirmed that 54 of 70 cases fulfilled WHO2016 criteria for MPAL. ALL induction regimens achieved remission in 72% of the cases (28 of 39), whereas AML regimens achieved remission in 69% (9 of 13). The 5-year event-free survival (EFS) and overall survival (OS) rates for the entire cohort were 72% ± 8% and 77% ± 7%, respectively. EFS and OS were 75% ± 13% and 84% ± 11%, respectively, for those receiving ALL chemotherapy alone without HSCT (n = 21). The results of the COG MPAL cohort and a literature review suggest that ALL chemotherapy without HSCT may be the preferred initial therapy. A prospective trial within the COG is proposed to investigate this approach; AML chemotherapy and/or HSCT will be reserved for those with treatment failure as assessed by minimal residual disease. Embedded biology studies will provide further insight into MPAL genomics. Acute lymphoblastic leukemia–directed chemotherapy without hematopoietic stem cell transplantation may be sufficient therapy for most children with World Health Organization 2016 classification–defined mixed‐phenotype acute leukemia. A proposed prospective trial will investigate this approach and explore mixed‐phenotype acute leukemia genomics and correlative biology. |
| Author | Alexander, Thomas B. Wood, Brent L. Mullighan, Charles G. Loh, Mignon L. Devidas, Meenakshi Rabin, Karen R. Dai, Yunfeng Carroll, Andrew J. Heerema, Nyla A. Woods, William G. Horan, John T. Kahwash, Samir B. Alonzo, Todd A. Inaba, Hiroto Hunger, Stephen P. Orgel, Etan Gamis, Alan S. Raetz, Elizabeth A. Zweidler‐McKay, Patrick A. Berman, Jason N. |
| AuthorAffiliation | 11. Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 20. ImmunoGen, Inc., Waltham, MA 12. Department of Pediatrics, NYU Langone Health, New York, NY 5. Department of Pathology and Laboratory Medicine, Nationwide Children’s Hospital, Columbus, OH 14. Department of Pediatrics, Baylor College of Medicine, Houston, TX 7. Department of Biostatistics, University of Florida, Gainesville, FL 4. Departments of Laboratory Medicine and Pathology, Division of Hematopathology, University of Washington, Seattle, WA 15. University of Alabama at Birmingham, Birmingham, AL 9. Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN 19. Department of Pediatrics, Benioff Children’s Hospital and the Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA 13. Children’s Mercy Cancer Center, Kansas City, MO 16. Department of P |
| AuthorAffiliation_xml | – name: 12. Department of Pediatrics, NYU Langone Health, New York, NY – name: 5. Department of Pathology and Laboratory Medicine, Nationwide Children’s Hospital, Columbus, OH – name: 6. Department of Global Pediatric Medicine, St Jude Children’s Research Hospital, Memphis, TN – name: 13. Children’s Mercy Cancer Center, Kansas City, MO – name: 3. University of North Carolina, Chapel Hill, NC – name: 14. Department of Pediatrics, Baylor College of Medicine, Houston, TX – name: 18. Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta/Emory University, Atlanta, GA – name: 15. University of Alabama at Birmingham, Birmingham, AL – name: 1. Division of Pediatric Hematology Oncology and BMT, Children’s Hospital Los Angeles, Los Angeles, CA – name: 9. Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN – name: 10. Department of Oncology St. Jude Children’s Research Hospital, Memphis, TN – name: 8. Department of Preventive Medicine, University of Southern California, Los Angeles, CA – name: 2. Department of Pediatrics, University of Southern California, Los Angeles, CA – name: 16. Department of Pathology, College of Medicine, The Ohio State University, Wexner Medical Center, Columbus, OH – name: 20. ImmunoGen, Inc., Waltham, MA – name: 19. Department of Pediatrics, Benioff Children’s Hospital and the Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA – name: 17. IWK Health Centre, Halifax, NS, CAN – name: 7. Department of Biostatistics, University of Florida, Gainesville, FL – name: 4. Departments of Laboratory Medicine and Pathology, Division of Hematopathology, University of Washington, Seattle, WA – name: 11. Department of Pediatrics and the Center for Childhood Cancer Research, Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31661160$$D View this record in MEDLINE/PubMed |
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| Copyright | 2019 American Cancer Society 2019 American Cancer Society. 2020 American Cancer Society |
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| Keywords | hematopoietic stem cell transplantation mixed-phenotype acute leukemia acute leukemia of ambiguous lineage biphenotypic acute leukemia pediatric leukemia |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 PAZM and JTH should be considered joint senior authors. Author Contributions: Etan Orgel & John T. Horan: Conceptualization, investigation, methodology, data curation, writing- original draft, writing- review/editing. Patrick A. Zweidler- McKay: Conceptualization, investigation, methodology, writing review/editing. Meenakshi Devidas & Yunfeng Dai: Investigation, methodology, data curation, formal analysis, writing review/editing. All other authors: investigation, methodology, writing- review/editing. |
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Optimal chemotherapy for treating mixed‐phenotype acute leukemia (MPAL) and the role of hematopoietic stem cell transplantation (HSCT) remain... Optimal chemotherapy for treating mixed-phenotype acute leukemia (MPAL) and the role of hematopoietic stem cell transplantation (HSCT) remain uncertain. Major... Acute lymphoblastic leukemia–directed chemotherapy without hematopoietic stem cell transplantation may be sufficient therapy for most children with World... BackgroundOptimal chemotherapy for treating mixed‐phenotype acute leukemia (MPAL) and the role of hematopoietic stem cell transplantation (HSCT) remain... BACKGROUNDOptimal chemotherapy for treating mixed-phenotype acute leukemia (MPAL) and the role of hematopoietic stem cell transplantation (HSCT) remain... ALL-directed chemotherapy without hematopoietic stem cell transplantation may be sufficient therapy for most children with WHO2016-defined MPAL. The proposed... |
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| SubjectTerms | acute leukemia of ambiguous lineage Acute lymphoblastic leukemia Acute myeloid leukemia Adolescent Adult biphenotypic acute leukemia Chemotherapy Child Child, Preschool Children Clinical trials Clinical Trials as Topic Disease-Free Survival Female hematopoietic stem cell transplantation Hematopoietic Stem Cell Transplantation - methods Hematopoietic stem cells Humans Immunophenotyping - methods Infant Leukemia Leukemia, Biphenotypic, Acute - epidemiology Leukemia, Biphenotypic, Acute - pathology Leukemia, Biphenotypic, Acute - therapy Literature reviews Lymphatic leukemia Male Medical treatment Minimal residual disease mixed‐phenotype acute leukemia Myeloid leukemia Oncology pediatric leukemia Pediatrics Pediatrics - trends Phenotypes Prognosis Remission Research methods Stem cell transplantation Stem cells Survival Task forces Transplantation World Health Organization Young Adult |
| Title | Mixed‐phenotype acute leukemia: A cohort and consensus research strategy from the Children’s Oncology Group Acute Leukemia of Ambiguous Lineage Task Force |
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