Tamar Tadmor1,2, Andrei Braester3,4, Dally Najib5, Ariel Aviv6, Yair Herishanu7,8, Mona Yuklea9, Lev Shvidel10, Naomi Rahimi-Levene11, Rosa Ruchlemer12, Ariela Arad13, Claudia Fogl14, Clara Henig15, Mira Barak15, Lee Magal16, Aaron Polliack13, Kelly Townsend14. 1. Bnai Zion Medical Center, Haifa, Israel. 2. The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel. 3. Western Galilee Hospital, Nahariya, Israel. 4. Bar Ilan University, Ramat Gan, Israel. 5. Ziv Medical Center, Safed, Israel. 6. Emek Medical Center, Afula, Israel. 7. Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel. 8. Tel-Aviv University, Tel Aviv, Israel. 9. Meir Medical Center, Kfar Saba, Israel. 10. Kaplan Medical Center, Rehovot, Israel. 11. Assaf Harofeh Medical Center, Be'er Ya'akov, Israel. 12. Shaare Zedek Medical Center, Jerusalem, Israel. 13. Department of Hematology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 14. The Binding Site Group Ltd, Birmingham, UK. 15. Haifa and Western Galilee Laboratory, Nesher, Israel. 16. Almog Diagnostic, Park Shoham, Israel.
Abstract
BACKGROUND: Chronic lymphocytic leukemia (CLL) is frequently accompanied by immune dysregulation. AIMS: In this multicenter prospective study, we investigated whether heavy + light chains (HLC: IgGκ, IgGλ, IgAκ, IgAκ, IgMκ, IgMλ) and IgG subclasses (IgG1, IgG2, IgG3, and IgG4) could be used as novel prognostic markers of immunoparesis in 105 treatment-naïve patients with CLL. RESULTS: Heavy + light chains immunoparesis of ≥1, ≥2, and ≥3 isotypes was evident in 74 (70%), 58 (55%), and 36 (34%) patients, respectively. Severe HLC immunoparesis was identified in 40 (38%) patients. Of the IgG subclasses, IgG1 and IgG2 were most frequently suppressed, affecting 46 (44%) and 36 (34%) patients, respectively; 63 (60%) patients had low levels of at least one IgG subclass. In multivariate analysis, severe HLC immunoparesis (hazard ratio [HR]: 36.5; P = .010) and ΣFLC ≥ 70 mg/L (HR: 13.2; P = .004) were the only factors independently associated with time to first treatment (TTFT). A risk model including these variables identified patients with 0, 1, and 2 risk factors and significantly different TTFT (P < .001). Patients with two factors represented an ultra-high-risk group with a median TTFT of only 1.3 months. CONCLUSION: The above findings demonstrate the potential for the use of HLC immunoparesis, together with sFLC measurements, as future prognostic biomarkers in CLL.
BACKGROUND:Chronic lymphocytic leukemia (CLL) is frequently accompanied by immune dysregulation. AIMS: In this multicenter prospective study, we investigated whether heavy + light chains (HLC: IgGκ, IgGλ, IgAκ, IgAκ, IgMκ, IgMλ) and IgG subclasses (IgG1, IgG2, IgG3, and IgG4) could be used as novel prognostic markers of immunoparesis in 105 treatment-naïve patients with CLL. RESULTS: Heavy + light chains immunoparesis of ≥1, ≥2, and ≥3 isotypes was evident in 74 (70%), 58 (55%), and 36 (34%) patients, respectively. Severe HLC immunoparesis was identified in 40 (38%) patients. Of the IgG subclasses, IgG1 and IgG2 were most frequently suppressed, affecting 46 (44%) and 36 (34%) patients, respectively; 63 (60%) patients had low levels of at least one IgG subclass. In multivariate analysis, severe HLC immunoparesis (hazard ratio [HR]: 36.5; P = .010) and ΣFLC ≥ 70 mg/L (HR: 13.2; P = .004) were the only factors independently associated with time to first treatment (TTFT). A risk model including these variables identified patients with 0, 1, and 2 risk factors and significantly different TTFT (P < .001). Patients with two factors represented an ultra-high-risk group with a median TTFT of only 1.3 months. CONCLUSION: The above findings demonstrate the potential for the use of HLC immunoparesis, together with sFLC measurements, as future prognostic biomarkers in CLL.
Authors: Namrata Singh; Sarah L Mott; Grerk Sutamtewagul; Ashley McCarthy; Susan L Slager; James R Cerhan; Zuhair Ballas; Brian K Link Journal: EJHaem Date: 2020-09-01