Human Cancer Biology Immune Thrombocytopenia in Patients with Chronic Lymphocytic Leukemia IsAssociatedwithStereotypedB-cell Receptors

Purpose: To assess biologic features related to the development of immune thrombocytopenia (ITP) in patients with chronic lymphocytic leukemia (CLL). Experimental Design:We retrospectively analyzed 463 patients with CLL with available immunoglobulin heavy-chain variable (IGHV) gene status and B-cell receptor (BCR) configuration [heavy-chain complementary-determining region 3 (HCDR3)], of whom thirty-six developed ITP, according to previously defined criteria. Most of them had available cytogenetic analysis. Results:We observed a significant association between ITP occurrence and IGHV unmutated gene status (P < 0.0001), unfavorable cytogenetic lesions (P1⁄4 0.005), and stereotyped HCDR3 (P1⁄4 0.006). The more frequent stereotyped HCDR3 subsets were #1 (IGHV1-5-7/IGHD6-19/IGHJ4; 16 of 16 unmutated) and #7 (IGHV1-69 or IGHV3-30/IGHD3-3/IGHJ6; 13 of 13 unmutated), both being significantlymore represented among patients developing ITP (P1⁄4 0.003 and P1⁄4 0.001, respectively).Moreover, restricting the analysis to unmutated patients, subset #7 confirmed its independent significant association with the occurrence of ITP (P1⁄4 0.013). Both unmutated IGHVmutational status, del(11)(q23) and stereotyped BCRwere significantly associated with shorter time to ITP development (P < 0.0001, P 1⁄4 0.02, and P 1⁄4 0.005, respectively) than