Abstract 2847

Chronic lymphocytic leukemia (CLL) is frequently complicated by autoimmune disorders, primarily autoimmune hemolytic anemia and immune thrombocytopenia (ITP). In order to investigate biological features related to ITP development, we retrospectively analyzed 463 CLL patients characterized for immunoglobulin heavy-chain variable (IGHV) gene mutational status, cytogenetic features and B-cell receptor (BCR) configuration (HCDR3) at the time of diagnosis. Thirty-six patients (7.7%) had developed ITP, according to our previously reported criteria (Visco et al, Blood 2008): i) an otherwise unexplained rapid (< 2 weeks) and severe fall (at least half of the initial level and below 100*109/L) of the platelet count; ii) normal or augmented number of megakaryocytes in the bone marrow; iii) no or limited (not palpable) splenomegaly and iv) no cytotoxic treatment in the last month. Stereotyped BCR configuration was defined by means of pair-wise alignment with known stereotyped sequences available from different public databases (Stamatopoulos et al, Blood 2007; Bomben et al, Br J Hematol 2009; Murray et al, Blood 2008), specifically excluding pairs of sequences whose length differed more than 3 amino acids and sharing more than 60% identity on alignments showing less than 3 gaps, as described by others and by our group (Stamatopoulos et al, Blood 2007; Maura et al, Plos One, in press). Our results indicated that the occurrence of ITP was strongly associated with unmutated (UM) IGHV (p<0.0001), unfavorable cytogenetic lesions (P =0.005), and interestingly, the occurrence of stereotyped HCDR3 (P =0.006). Additionally, the UM IGHV mutational status, unfavorable cytogenetic lesions, or stereotyped BCR were significantly associated with shorter time to ITP development (P <0.0001, P =0.02 and P =0.005 respectively) compared to other patients. As regards to the most represented HCDR3 subsets, we observed that subsets #1 (IGHV1-5-7/IGHD6-19/IGHJ4; 16/16 UM) and #7 (IGHV1-69 or IGHV3-30/IGHD3-3/IGHJ6; 13/13 UM) were significantly associated with ITP development (P =0.003 and P =0.001, respectively). Moreover, restricting the analysis to UM patients, subset #7 retained a significant association with the occurrence of ITP (P =0.02). Time to ITP development was also significantly shorter in subsets #1 and #7 patients than in all others patients (P =0.0076 and P <0.0001, respectively). Overall, our data suggest that patients with CLL and peculiar BCR conformations are at higher risk of developing secondary ITP, and that stereotyped BCR may be involved in the pathogenesis of this complication.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.

Sign in via your Institution