The CD52 and CD20 antigens are ubiquitously expressed on CLL B cells and are important therapeutic targets for the monoclonal antibodies alemtuzumab and rituximab, respectively. Circulating soluble CD52 (sCD52) and CD20 (sCD20) have been shown to have prognostic value in CLL, non-Hodgkin’s lymphoma and Hodgkin’s disease (

Blood 101:2507, 2003
;
Br J Haem 123:850, 2003
). The pharmacokinetics and therapeutic efficacy of these mAbs may be adversely affected by circulating sCD52 and sCD20. Using the previously described ELISAs, we measured levels of sCD52 and sCD20 at various time points in blood (PB) and bone marrow (BM) of chemotherapy-naïve patients treated with FCR. Treatment consisted of fludarabine 25 mg/m2 d1-3, cyclophosphamide 250mg/m2 d1-3, and rituximab 375–500mg/m2 d1 as previously described (
JCO 23:4079, 2005
). Courses were repeated every 4 weeks for a total of 6 courses. Univariate and multivariate Cox proportional hazards models were fit to evaluate the correlations of sCD52 and sCD20 and baseline characteristics with progression free survival (PFS) and overall survival (OS). A total of 291 patients were included, pretreatment characteristics [median (range)] were as follows: age=57yrs (17–86); WBC=76.9K/μL(2.1–619.5); ALC=66.7K/μL(0.8–558); HGB=12.4g/dL(6.1–18.7); PLT=155K/μL(8–406); ß2M= 3.7mg/L(1.6–16.4); LDH=550 IU/L(103–1828). Patients with Rai stage 0=8; I–II=186; and III–IV=97. The median follow-up time for all patients is 56 months. Of the 278 responding patients, 88 (31.7%) have progressed; the median time to progression has not been reached. To date, the median survival time for the 291 patients has not been reached; 57 (19.6%) patients have died. Pretreatment characteristics analyzed included age, gender, PS, WBC, ALC, HGB, PLT, ß2M, and RAI stage; post-treatment factors included PCR for IgVH in BM, and sCD52 and sCD20 (BM and PB) levels at response. Univariate analyses identified the following predictors for PFS (p < .05): age, HGB, ß2M, PCR for IgVH at response, and PB sCD20 at response. Independent predictors for PFS identified in multivariate analysis included PCR for IgVH and PB sCD20 level at response. For OS, significant (p < .05) factors in univariate analyses included: age, HGB, ß2M, PCR for IgVH at response, and BM sCD52 at response. Independent predictors for OS identified in multivariate analysis included age and BM sCD52 level at response. Residual sCD52 at response may reflect residual disease, therefore correlating with shorter OS. We are currently evaluating sCD52 and sCD20 as prognostic factors for clinical outcomes in previously treated patients that received FCR as salvage therapy.

Topics:
alemtuzumab, cd20 antigens, cyclophosphamide, fludarabine, rituximab, polymerase chain reaction, hemoglobin, chemotherapy regimen, follow-up, heme

Disclosure: No relevant conflicts of interest to declare.

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2006, The American Society of Hematology
2006
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