Blood Journal
Leading the way in experimental and clinical research in hematology

ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes

  1. Edgardo R. Parilla Castellar1,
  2. Elaine S. Jaffe2,
  3. Jonathan W. Said3,
  4. Steven H. Swerdlow4,
  5. Rhett P. Ketterling1,
  6. Ryan A. Knudson1,
  7. Jagmohan S. Sidhu5,
  8. Eric D. Hsi6,
  9. Shridevi Karikehalli7,
  10. Liuyan Jiang8,
  11. George Vasmatzis9,
  12. Sarah E. Gibson4,
  13. Sarah Ondrejka6,
  14. Alina Nicolae2,
  15. Karen L. Grogg1,
  16. Cristine Allmer10,
  17. Kay M. Ristow11,
  18. Wyndham H. Wilson12,
  19. William R. Macon1,
  20. Mark E. Law1,
  21. James R. Cerhan10,
  22. Thomas M. Habermann11,
  23. Stephen M. Ansell11,
  24. Ahmet Dogan1,
  25. Matthew J. Maurer10, and
  26. Andrew L. Feldman1,*
  1. 1 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States;
  2. 2 Hematopathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD, United States;
  3. 3 Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA, United States;
  4. 4 Division of Hematopathology, University of Pittsburgh Medical Center, Pittsburgh, PA, United States;
  5. 5 Department of Pathology and Laboratory Medicine, United Health Services Hospitals, Johnson City/Binghamton, NY, United States;
  6. 6 Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH, United States;
  7. 7 Department of Pathology and Laboratory Medicine, Centrex Clinical Laboratories, Utica, NY, United States;
  8. 8 Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL, United States;
  9. 9 Center for Individualized Medicine, Mayo Clinic, Rochester, MN, United States;
  10. 10 Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States;
  11. 11 Division of Hematology, Mayo Clinic, Rochester, MN, United States;
  12. 12 Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States
  1. * Corresponding author; email: feldman.andrew{at}mayo.edu

Key points

  • ALK-negative ALCLs have chromosomal rearrangements of DUSP22 or TP63 in 30% and 8% of cases, respectively.

  • DUSP22-rearranged cases have favorable outcomes similar to ALK-positive ALCLs, while other genetic subtypes have inferior outcomes.

Abstract

ALK-negative anaplastic large cell lymphoma (ALCL) is a CD30-positive T-cell non-Hodgkin lymphoma that morphologically resembles ALK-positive ALCL but lacks chromosomal rearrangements of the ALK gene. The genetic and clinical heterogeneity of ALK-negative ALCL has not been delineated. We performed immunohistochemistry and fluorescence in situ hybridization on 73 ALK-negative ALCLs and 32 ALK-positive ALCLs and evaluated the associations among pathology, genetics, and clinical outcome. Chromosomal rearrangements of DUSP22 and TP63 were identified in 30% and 8% of ALK-negative ALCLs, respectively. These rearrangements were mutually exclusive and were absent in ALK-positive ALCLs. Five-year overall survival rates were 85% for ALK-positive ALCLs, 90% for DUSP22-rearranged ALCLs, 17% for TP63-rearranged ALCLs, and 42% for cases lacking all three genetic markers (p<0.0001). Hazard ratios for death in these 4 groups after adjusting for International Prognostic Index and age were 1.0 (reference group), 0.58, 8.63, and 4.16, respectively (p=7.10 x 10-5). These results were similar when restricted to patients receiving anthracycline-based chemotherapy as well as to patients not receiving stem-cell transplantation. Thus, ALK-negative ALCL is a genetically heterogeneous disease with widely disparate outcomes following standard therapy. DUSP22 and TP63 rearrangements may serve as predictive biomarkers to help guide patient management.

  • Submitted April 21, 2014.
  • Accepted May 26, 2014.