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

Edgardo R. Parrilla Castellar, Elaine S. Jaffe, Jonathan W. Said, Steven H. Swerdlow, Rhett P. Ketterling, Ryan A. Knudson, Jagmohan S. Sidhu, Eric D. Hsi, Shridevi Karikehalli, Liuyan Jiang, George Vasmatzis, Sarah E. Gibson, Sarah Ondrejka, Alina Nicolae, Karen L. Grogg, Cristine Allmer, Kay M. Ristow, Wyndham H. Wilson, William R. Macon, Mark E. LawJames R Cerhan, Thomas Matthew Habermann, Stephen Maxted Ansell, Ahmet Dogan, Matthew J. Maurer, Andrew L Feldman

Research output: Contribution to journalArticle

165 Citations (Scopus)

Abstract

Anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a CD30-positive T-cell non-Hodgkin lymphoma that morphologically resembles ALKpositive 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 3 genetic markers (P < .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 × 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-negativeALCLis 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.

Original languageEnglish (US)
Article number1284
Pages (from-to)1473-1480
Number of pages8
JournalBlood
Volume124
Issue number9
DOIs
StatePublished - Aug 28 2014

Fingerprint

Anaplastic Large-Cell Lymphoma
anaplastic lymphoma kinase
Clinical Pathology
Chemotherapy
T-cells
Genetic Heterogeneity
T-Cell Lymphoma
Anthracyclines
Stem Cell Transplantation
Biomarkers
Pathology
Stem cells
Fluorescence In Situ Hybridization
Genetic Markers
Non-Hodgkin's Lymphoma
Hazards
Survival Rate
Genes
Fluorescence
Immunohistochemistry

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Parrilla Castellar, E. R., Jaffe, E. S., Said, J. W., Swerdlow, S. H., Ketterling, R. P., Knudson, R. A., ... Feldman, A. L. (2014). ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. Blood, 124(9), 1473-1480. [1284]. https://doi.org/10.1182/blood-2014-04-571091

ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. / Parrilla Castellar, Edgardo R.; Jaffe, Elaine S.; Said, Jonathan W.; Swerdlow, Steven H.; Ketterling, Rhett P.; Knudson, Ryan A.; Sidhu, Jagmohan S.; Hsi, Eric D.; Karikehalli, Shridevi; Jiang, Liuyan; Vasmatzis, George; Gibson, Sarah E.; Ondrejka, Sarah; Nicolae, Alina; Grogg, Karen L.; Allmer, Cristine; Ristow, Kay M.; Wilson, Wyndham H.; Macon, William R.; Law, Mark E.; Cerhan, James R; Habermann, Thomas Matthew; Ansell, Stephen Maxted; Dogan, Ahmet; Maurer, Matthew J.; Feldman, Andrew L.

In: Blood, Vol. 124, No. 9, 1284, 28.08.2014, p. 1473-1480.

Research output: Contribution to journalArticle

Parrilla Castellar, ER, Jaffe, ES, Said, JW, Swerdlow, SH, Ketterling, RP, Knudson, RA, Sidhu, JS, Hsi, ED, Karikehalli, S, Jiang, L, Vasmatzis, G, Gibson, SE, Ondrejka, S, Nicolae, A, Grogg, KL, Allmer, C, Ristow, KM, Wilson, WH, Macon, WR, Law, ME, Cerhan, JR, Habermann, TM, Ansell, SM, Dogan, A, Maurer, MJ & Feldman, AL 2014, 'ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes', Blood, vol. 124, no. 9, 1284, pp. 1473-1480. https://doi.org/10.1182/blood-2014-04-571091
Parrilla Castellar ER, Jaffe ES, Said JW, Swerdlow SH, Ketterling RP, Knudson RA et al. ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. Blood. 2014 Aug 28;124(9):1473-1480. 1284. https://doi.org/10.1182/blood-2014-04-571091
Parrilla Castellar, Edgardo R. ; Jaffe, Elaine S. ; Said, Jonathan W. ; Swerdlow, Steven H. ; Ketterling, Rhett P. ; Knudson, Ryan A. ; Sidhu, Jagmohan S. ; Hsi, Eric D. ; Karikehalli, Shridevi ; Jiang, Liuyan ; Vasmatzis, George ; Gibson, Sarah E. ; Ondrejka, Sarah ; Nicolae, Alina ; Grogg, Karen L. ; Allmer, Cristine ; Ristow, Kay M. ; Wilson, Wyndham H. ; Macon, William R. ; Law, Mark E. ; Cerhan, James R ; Habermann, Thomas Matthew ; Ansell, Stephen Maxted ; Dogan, Ahmet ; Maurer, Matthew J. ; Feldman, Andrew L. / ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. In: Blood. 2014 ; Vol. 124, No. 9. pp. 1473-1480.
@article{831581c583a844b481cc1f1202a88c68,
title = "ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes",
abstract = "Anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a CD30-positive T-cell non-Hodgkin lymphoma that morphologically resembles ALKpositive 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 3 genetic markers (P < .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 × 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-negativeALCLis 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.",
author = "{Parrilla Castellar}, {Edgardo R.} and Jaffe, {Elaine S.} and Said, {Jonathan W.} and Swerdlow, {Steven H.} and Ketterling, {Rhett P.} and Knudson, {Ryan A.} and Sidhu, {Jagmohan S.} and Hsi, {Eric D.} and Shridevi Karikehalli and Liuyan Jiang and George Vasmatzis and Gibson, {Sarah E.} and Sarah Ondrejka and Alina Nicolae and Grogg, {Karen L.} and Cristine Allmer and Ristow, {Kay M.} and Wilson, {Wyndham H.} and Macon, {William R.} and Law, {Mark E.} and Cerhan, {James R} and Habermann, {Thomas Matthew} and Ansell, {Stephen Maxted} and Ahmet Dogan and Maurer, {Matthew J.} and Feldman, {Andrew L}",
year = "2014",
month = "8",
day = "28",
doi = "10.1182/blood-2014-04-571091",
language = "English (US)",
volume = "124",
pages = "1473--1480",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "9",

}

TY - JOUR

T1 - ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes

AU - Parrilla Castellar, Edgardo R.

AU - Jaffe, Elaine S.

AU - Said, Jonathan W.

AU - Swerdlow, Steven H.

AU - Ketterling, Rhett P.

AU - Knudson, Ryan A.

AU - Sidhu, Jagmohan S.

AU - Hsi, Eric D.

AU - Karikehalli, Shridevi

AU - Jiang, Liuyan

AU - Vasmatzis, George

AU - Gibson, Sarah E.

AU - Ondrejka, Sarah

AU - Nicolae, Alina

AU - Grogg, Karen L.

AU - Allmer, Cristine

AU - Ristow, Kay M.

AU - Wilson, Wyndham H.

AU - Macon, William R.

AU - Law, Mark E.

AU - Cerhan, James R

AU - Habermann, Thomas Matthew

AU - Ansell, Stephen Maxted

AU - Dogan, Ahmet

AU - Maurer, Matthew J.

AU - Feldman, Andrew L

PY - 2014/8/28

Y1 - 2014/8/28

N2 - Anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a CD30-positive T-cell non-Hodgkin lymphoma that morphologically resembles ALKpositive 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 3 genetic markers (P < .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 × 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-negativeALCLis 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.

AB - Anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a CD30-positive T-cell non-Hodgkin lymphoma that morphologically resembles ALKpositive 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 3 genetic markers (P < .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 × 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-negativeALCLis 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.

UR - http://www.scopus.com/inward/record.url?scp=84907379195&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907379195&partnerID=8YFLogxK

U2 - 10.1182/blood-2014-04-571091

DO - 10.1182/blood-2014-04-571091

M3 - Article

C2 - 24894770

AN - SCOPUS:84907379195

VL - 124

SP - 1473

EP - 1480

JO - Blood

JF - Blood

SN - 0006-4971

IS - 9

M1 - 1284

ER -