CD49d associates with nodal presentation and subsequent development of lymphadenopathy in patients with chronic lymphocytic leukaemia

Paolo Strati, Sameer A Parikh, Kari G. Chaffee, Sara J. Achenbach, Susan L Slager, Timothy G. Call, Wei D Ding, Diane F Jelinek, Curtis A. Hanson, Neil Elliot Kay, Tait D. Shanafelt

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Summary: CD49d is a surface integrin that is expressed on chronic lymphocytic leukaemia (CLL) cells, and strongly correlates with more aggressive disease. Given its association with cell-cell adhesion and leucocyte trafficking, we hypothesized that patients with high CD49d expression would experience a clinical course dominated by lymphadenopathy. CD49d expression was measured by flow cytometry and considered positive if expressed by ≥30% of CLL cells. The study included 797 newly diagnosed CLL/small lymphocytic leukaemia patients; 279 (35%) were CD49d positive. CD49d-positive patients were more likely to present with lymphadenopathy (P < 0·001); a finding that persisted after adjusting for fluorescence in situ hybridisation (FISH) and IGHV mutation status [odds ratio (OR) 2·51; 95% confidence interval (CI) 1·64-3·83; P < 0·001]. Among CLL Rai 0 patients, CD49d positivity was associated with shorter time to development of lymphadenopathy (3·2 years vs not reached, P < 0·01). This association was maintained after adjusting for either FISH [hazard ratio (HR) 2·18; 95% CI 1·25-3·81; P = 0·006) or IGHV status (HR 2·02; 95% CI 1·11-3·69; P = 0·02) individually, but was attenuated when adjusting by both (HR 1·72; 95% CI 0·88-3·38; P = 0·11).These data demonstrate that CD49d-positive CLL patients experience a disease course dominated by lymphadenopathy. These findings could have implications for therapy selection and disease monitoring.

Original languageEnglish (US)
JournalBritish Journal of Haematology
DOIs
StateAccepted/In press - 2017

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B-Cell Chronic Lymphocytic Leukemia
Confidence Intervals
Fluorescence In Situ Hybridization
Lymphoid Leukemia
Cell Adhesion
Integrins
Flow Cytometry
Leukocytes
Odds Ratio
Lymphadenopathy
Mutation

Keywords

  • CD49d
  • Chronic lymphocytic leukaemia
  • Lymphadenopathy
  • Small lymphocytic lymphoma

ASJC Scopus subject areas

  • Hematology

Cite this

CD49d associates with nodal presentation and subsequent development of lymphadenopathy in patients with chronic lymphocytic leukaemia. / Strati, Paolo; Parikh, Sameer A; Chaffee, Kari G.; Achenbach, Sara J.; Slager, Susan L; Call, Timothy G.; Ding, Wei D; Jelinek, Diane F; Hanson, Curtis A.; Kay, Neil Elliot; Shanafelt, Tait D.

In: British Journal of Haematology, 2017.

Research output: Contribution to journalArticle

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AU - Strati, Paolo

AU - Parikh, Sameer A

AU - Chaffee, Kari G.

AU - Achenbach, Sara J.

AU - Slager, Susan L

AU - Call, Timothy G.

AU - Ding, Wei D

AU - Jelinek, Diane F

AU - Hanson, Curtis A.

AU - Kay, Neil Elliot

AU - Shanafelt, Tait D.

PY - 2017

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AB - Summary: CD49d is a surface integrin that is expressed on chronic lymphocytic leukaemia (CLL) cells, and strongly correlates with more aggressive disease. Given its association with cell-cell adhesion and leucocyte trafficking, we hypothesized that patients with high CD49d expression would experience a clinical course dominated by lymphadenopathy. CD49d expression was measured by flow cytometry and considered positive if expressed by ≥30% of CLL cells. The study included 797 newly diagnosed CLL/small lymphocytic leukaemia patients; 279 (35%) were CD49d positive. CD49d-positive patients were more likely to present with lymphadenopathy (P < 0·001); a finding that persisted after adjusting for fluorescence in situ hybridisation (FISH) and IGHV mutation status [odds ratio (OR) 2·51; 95% confidence interval (CI) 1·64-3·83; P < 0·001]. Among CLL Rai 0 patients, CD49d positivity was associated with shorter time to development of lymphadenopathy (3·2 years vs not reached, P < 0·01). This association was maintained after adjusting for either FISH [hazard ratio (HR) 2·18; 95% CI 1·25-3·81; P = 0·006) or IGHV status (HR 2·02; 95% CI 1·11-3·69; P = 0·02) individually, but was attenuated when adjusting by both (HR 1·72; 95% CI 0·88-3·38; P = 0·11).These data demonstrate that CD49d-positive CLL patients experience a disease course dominated by lymphadenopathy. These findings could have implications for therapy selection and disease monitoring.

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KW - Chronic lymphocytic leukaemia

KW - Lymphadenopathy

KW - Small lymphocytic lymphoma

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