TY - JOUR
T1 - IGH translocations in chronic lymphocytic leukemia
T2 - Clinicopathologic features and clinical outcomes
AU - Fang, Hong
AU - Reichard, Kaaren K.
AU - Rabe, Kari G.
AU - Hanson, Curtis A.
AU - Call, Timothy G.
AU - Ding, Wei
AU - Kenderian, Saad S.
AU - Muchtar, Eli
AU - Schwager, Susan M.
AU - Leis, Jose F.
AU - Chanan-Khan, Asher A.
AU - Slager, Susan L.
AU - Braggio, Esteban
AU - Smoley, Stephanie A.
AU - Kay, Neil E.
AU - Shanafelt, Tait D.
AU - Van Dyke, Daniel L.
AU - Parikh, Sameer A.
N1 - Funding Information:
Sameer A. Parikh and Saad S. Kenderian are recipients of the K12 CA090628 grant from the National Cancer Institute (Paul Calabresi Career Development Award for Clinical Oncology). Tait D. Shanafelt and Neil E. Kay are supported by R01CA197120. Daniel Van Dyke is supported by UO1 CA 81534 (NIH, CRC - CLL Research Consortium - Core C).
Publisher Copyright:
© 2018 Wiley Periodicals, Inc.
PY - 2019/3
Y1 - 2019/3
N2 - The prevalence, clinicopathologic correlates, and outcomes of previously untreated chronic lymphocytic leukemia (CLL) patients with IGH-BCL2 and IGH-BCL3 translocations are not well known. Using the Mayo Clinic CLL database, we identified patients seen between March 1, 2002 and September 30, 2016 who had FISH testing performed within 3 years of CLL diagnosis. The prognostic profile, time to first therapy (TTT), and overall survival (OS) of patients with IGH-BCL2 and IGH-BCL3 translocation were compared to patients without these abnormalities (non-IGH group). Of 1684 patients who met the inclusion criteria, 38 (2.2%) had IGH-BCL2, and 16 (0.9%) had IGH-BCL3 translocation at diagnosis. Patients with IGH-BCL3 translocation were more likely to have high and very-high CLL-International Prognostic Index, compared to patients with IGH-BCL2 translocation and the non-IGH group. The 5-year probability of requiring therapy was significantly higher for IGH-BCL3 compared to IGH-BCL2 and non-IGH groups (84% vs 33% vs 29%, respectively, P < 0.0001). The 5-year OS was significantly shorter for IGH-BCL3 compared to IGH-BCL2 and non-IGH groups (45% vs 89% vs 86%, respectively, P < 0.0001). On multivariable analyses, IGH-BCL3 translocation was associated with a shorter TTT (hazard ratio [HR] = 2.7; P = 0.005) and shorter OS (HR = 5.5; P < 0.0001); IGH-BCL2 translocation did not impact TTT and OS. In conclusion, approximately 3% of all newly diagnosed CLL patients have either an IGH-BCL2 or IGH-BCL3 translocation. Patients with IGH-BCL3 translocations have a distinct prognostic profile and outcome. These results support the inclusion of an IGH probe during the routine evaluation of FISH abnormalities in newly diagnosed CLL.
AB - The prevalence, clinicopathologic correlates, and outcomes of previously untreated chronic lymphocytic leukemia (CLL) patients with IGH-BCL2 and IGH-BCL3 translocations are not well known. Using the Mayo Clinic CLL database, we identified patients seen between March 1, 2002 and September 30, 2016 who had FISH testing performed within 3 years of CLL diagnosis. The prognostic profile, time to first therapy (TTT), and overall survival (OS) of patients with IGH-BCL2 and IGH-BCL3 translocation were compared to patients without these abnormalities (non-IGH group). Of 1684 patients who met the inclusion criteria, 38 (2.2%) had IGH-BCL2, and 16 (0.9%) had IGH-BCL3 translocation at diagnosis. Patients with IGH-BCL3 translocation were more likely to have high and very-high CLL-International Prognostic Index, compared to patients with IGH-BCL2 translocation and the non-IGH group. The 5-year probability of requiring therapy was significantly higher for IGH-BCL3 compared to IGH-BCL2 and non-IGH groups (84% vs 33% vs 29%, respectively, P < 0.0001). The 5-year OS was significantly shorter for IGH-BCL3 compared to IGH-BCL2 and non-IGH groups (45% vs 89% vs 86%, respectively, P < 0.0001). On multivariable analyses, IGH-BCL3 translocation was associated with a shorter TTT (hazard ratio [HR] = 2.7; P = 0.005) and shorter OS (HR = 5.5; P < 0.0001); IGH-BCL2 translocation did not impact TTT and OS. In conclusion, approximately 3% of all newly diagnosed CLL patients have either an IGH-BCL2 or IGH-BCL3 translocation. Patients with IGH-BCL3 translocations have a distinct prognostic profile and outcome. These results support the inclusion of an IGH probe during the routine evaluation of FISH abnormalities in newly diagnosed CLL.
UR - http://www.scopus.com/inward/record.url?scp=85059673326&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85059673326&partnerID=8YFLogxK
U2 - 10.1002/ajh.25385
DO - 10.1002/ajh.25385
M3 - Article
C2 - 30575108
AN - SCOPUS:85059673326
VL - 94
SP - 338
EP - 345
JO - American Journal of Hematology
JF - American Journal of Hematology
SN - 0361-8609
IS - 3
ER -