Significance of Minimal Residual Disease in Pediatric Mixed Phenotype Acute Leukemia: A Multi-Center Cohort Study
The rarity of mixed phenotype acute leukemia (MPAL) has precluded adequate data to incorporate minimal residual disease (MRD) monitoring into therapy. Fluidity in MPAL classification systems further complicates understanding its biology and outcomes; this includes uncertainty surrounding the impact...
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| Published in | Leukemia Vol. 34; no. 7; pp. 1741 - 1750 |
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| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
14.02.2020
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| Online Access | Get full text |
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| Abstract | The rarity of mixed phenotype acute leukemia (MPAL) has precluded adequate data to incorporate minimal residual disease (MRD) monitoring into therapy. Fluidity in MPAL classification systems further complicates understanding its biology and outcomes; this includes uncertainty surrounding the impact of shifting diagnostic requirements even between iterations of the World Health Organization (WHO) classification. Our primary objective was to address these knowledge gaps. To do so, we analyzed clinicopathologic features, therapy, MRD, and survival in a centrally-reviewed, multi-center cohort of MPAL uniformly diagnosed by the WHO classification and treated with acute lymphoblastic leukemia (ALL) regimens. ALL induction therapy achieved an EOI MRD negative (<0.01%) remission in most patients (70%). EOI MRD positivity was predictive of 5-year EFS (HR=6.00, p<0.001) and OS (HR=9.57, p=0.003). Patients who cleared MRD by EOC had worse survival compared to those EOI MRD negative. In contrast to adults with MPAL, ALL therapy without transplantation was adequate to treat most pediatric patients. Earlier MRD clearance was associated with better treatment success and survival. Prospective trials are now necessary to validate and refine MRD thresholds within the pediatric MPAL population and to identify salvage strategies for those with poor predicted survival. |
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| AbstractList | The rarity of mixed phenotype acute leukemia (MPAL) has precluded adequate data to incorporate minimal residual disease (MRD) monitoring into therapy. Fluidity in MPAL classification systems further complicates understanding its biology and outcomes; this includes uncertainty surrounding the impact of shifting diagnostic requirements even between iterations of the World Health Organization (WHO) classification. Our primary objective was to address these knowledge gaps. To do so, we analyzed clinicopathologic features, therapy, MRD, and survival in a centrally-reviewed, multi-center cohort of MPAL uniformly diagnosed by the WHO classification and treated with acute lymphoblastic leukemia (ALL) regimens. ALL induction therapy achieved an EOI MRD negative (<0.01%) remission in most patients (70%). EOI MRD positivity was predictive of 5-year EFS (HR=6.00, p<0.001) and OS (HR=9.57, p=0.003). Patients who cleared MRD by EOC had worse survival compared to those EOI MRD negative. In contrast to adults with MPAL, ALL therapy without transplantation was adequate to treat most pediatric patients. Earlier MRD clearance was associated with better treatment success and survival. Prospective trials are now necessary to validate and refine MRD thresholds within the pediatric MPAL population and to identify salvage strategies for those with poor predicted survival. |
| Author | Punia, Jyotinder N. Guinipero, Terri Cahen, Viviane C. Rabin, Karen R. Luca, Dragos C. Seif, Alix E. Schore, Reuven J. Woods, William G. Malvar, Jemily Oberley, Matthew J. Wertheim, Gerald B. Raikar, Sunil S. O'Gorman, Maurice R.G. Orgel, Etan Sposto, Richard |
| AuthorAffiliation | 1 Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA 4 Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania & the Children’s Hospital of Philadelphia, Philadelphia, PA 6 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 8 Department of Pathology and Immunology, Baylor College of Medicine/Texas Children’s Hospital 7 Texas Children’s Cancer Center, Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX 11 Department of Pediatrics, The Ohio State University & Nationwide Children's Hospital , Columbus, OH 5 Children’s Center for Cancer and Blood Diseases, Children’s Hospital Los Angeles, Los Angeles, CA 9 Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA 10 Children's National Medical Center & George Washington University School of Medicine and Health Sciences, Washi |
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Keck School of Medicine, University of Southern California, Los Angeles, CA |
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| Notes | E.O: study conception & research design; M.J.O. and G.W. conducted the hematopathology central review; J.M. and R.S. performed the statistical analysis; M.J.O, S.S.R., and E.O. wrote the manuscript first draft; All authors contributed case data, interpreted the analysis, and reviewed/edited manuscript. Authorship Contributions M.J.O. and S.S.R. contributed equally to this work |
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| Snippet | The rarity of mixed phenotype acute leukemia (MPAL) has precluded adequate data to incorporate minimal residual disease (MRD) monitoring into therapy. Fluidity... |
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| Title | Significance of Minimal Residual Disease in Pediatric Mixed Phenotype Acute Leukemia: A Multi-Center Cohort Study |
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