IGH translocations in chronic lymphocytic leukemia

Clinicopathologic features and clinical outcomes

Hong Fang, Kaaren K. Reichard, Kari G. Rabe, Curtis A. Hanson, Timothy G. Call, Wei D Ding, Saad Kenderian, Eli Muchtar, Susan M. Schwager, Jose F. Leis, Asher A Chanan Khan, Susan L Slager, Esteban D Braggio, Stephanie A. Smoley, Neil Elliot Kay, Tait D. Shanafelt, Daniel L. Van Dyke, Sameer A Parikh

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Hematology
DOIs
StateAccepted/In press - Jan 1 2019

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B-Cell Chronic Lymphocytic Leukemia
Survival
Therapeutics
Databases

ASJC Scopus subject areas

  • Hematology

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IGH translocations in chronic lymphocytic leukemia : Clinicopathologic features and clinical outcomes. / Fang, Hong; Reichard, Kaaren K.; Rabe, Kari G.; Hanson, Curtis A.; Call, Timothy G.; Ding, Wei D; Kenderian, Saad; Muchtar, Eli; Schwager, Susan M.; Leis, Jose F.; Chanan Khan, Asher A; Slager, Susan L; Braggio, Esteban D; Smoley, Stephanie A.; Kay, Neil Elliot; Shanafelt, Tait D.; Van Dyke, Daniel L.; Parikh, Sameer A.

In: American Journal of Hematology, 01.01.2019.

Research output: Contribution to journalArticle

Fang, Hong ; Reichard, Kaaren K. ; Rabe, Kari G. ; Hanson, Curtis A. ; Call, Timothy G. ; Ding, Wei D ; Kenderian, Saad ; Muchtar, Eli ; Schwager, Susan M. ; Leis, Jose F. ; Chanan Khan, Asher A ; Slager, Susan L ; Braggio, Esteban D ; Smoley, Stephanie A. ; Kay, Neil Elliot ; Shanafelt, Tait D. ; Van Dyke, Daniel L. ; Parikh, Sameer A. / IGH translocations in chronic lymphocytic leukemia : Clinicopathologic features and clinical outcomes. In: American Journal of Hematology. 2019.
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abstract = "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.",
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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 D

AU - Kenderian, Saad

AU - Muchtar, Eli

AU - Schwager, Susan M.

AU - Leis, Jose F.

AU - Chanan Khan, Asher A

AU - Slager, Susan L

AU - Braggio, Esteban D

AU - Smoley, Stephanie A.

AU - Kay, Neil Elliot

AU - Shanafelt, Tait D.

AU - Van Dyke, Daniel L.

AU - Parikh, Sameer A

PY - 2019/1/1

Y1 - 2019/1/1

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.

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