The prognosis of chronic lymphocytic leukemia (CLL) depends on different markers, including cytogenetic aberrations, oncogenic mutations, and mutational status of the immunoglobulin (Ig) heavy-chain variable (IGHV) gene. The number of IGHV mutations distinguishes mutated (M) CLL with a markedly superior prognosis from unmutated (UM) CLL cases. In addition, B cell antigen receptor (BCR) stereotypes as defined by IGHV usage and complementarity-determining regions (CDRs) classify ∼30% of CLL cases into prognostically important subsets. Subset 2 expresses a BCR with the combination of IGHV3-21–derived heavy chains (HCs) with IGLV3-21–derived light chains (LCs), and is associated with an unfavorable prognosis. Importantly, the subset 2 LC carries a single-point mutation, termed R110, at the junction between the variable and constant LC regions. By analyzing 4 independent clinical cohorts through BCR sequencing and by immunophenotyping with antibodies specifically recognizing wild-type IGLV3-21 and R110-mutated IGLV3-21 (IGLV3-21R110), we show that IGLV3-21R110–expressing CLL represents a distinct subset with poor prognosis independent of IGHV mutations. Compared with other alleles, only IGLV3-21*01 facilitates effective homotypic BCR–BCR interaction that results in autonomous, oncogenic BCR signaling after acquiring R110 as a single-point mutation. Presumably, this mutation acts as a standalone driver that transforms IGLV3-21*01–expressing B cells to develop CLL. Thus, we propose to expand the conventional definition of CLL subset 2 to subset 2L by including all IGLV3-21R110–expressing CLL cases regardless of IGHV mutational status. Moreover, the generation of monoclonal antibodies recognizing IGLV3-21 or mutated IGLV3-21R110 facilitates the recognition of B cells carrying this mutation in CLL patients or healthy donors.

Intravascular large B-cell lymphoma (IVLBCL) is a rare variant of extranodal diffuse large B-cell lymphoma (DLBCL). It is characterized by proliferation of blastic, neoplastic B cells within the lumina of small-or intermediate-sized blood vessels and capillaries. 1 IVLBCL may potentially involve any organ and is often widely disseminated. Two major patterns have been recognized. In Western patients, predominantly the skin and the central nervous system (CNS) are involved, whereas in Asian countries, the disease often involves multiple other organs and is accompanied by hemophagocytosis. 2 Additionally, a cutaneous variant, with skin-limited disease at time of diagnosis, has been described in younger, Western women. 3 Standard treatment of IVLBCL consists of rituximab-containing chemotherapeutic regimens, demonstrating an estimated 3-year overall survival (OS) of 60% to 81%. 4,5

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Purpose: Targeted radiotherapy with 131 iodine-metaiodobenzylguanidine ( 131 I-MIBG) is effective for neuroblastoma (NBL), although optimal scheduling during high-risk (HR) treatment is being investigated. We aimed to evaluate the feasibility of stem cell apheresis and study hematologic reconstitution after autologous stem cell transplantation (ASCT) in patients with HR-NBL treated with upfront 131 I-MIBG-therapy.Experimental Design: In two prospective multicenter cohort studies, newly diagnosed patients with HR-NBL were treated with two courses of 131 I-MIBG-therapy, followed by an HR-induction protocol. Hematopoietic stem and progenitor cell (e.g., CD34 þ cell) harvest yield, required number of apheresis sessions, and time to neutrophil (>0.5 Â 10 9 /L) and platelet (>20 Â 10 9 /L) reconstitution after ASCT were analyzed and compared with "chemotherapy-only"-treated patients. Moreover, harvested CD34 þ cells were functionally (viability and clonogenic capacity) and phenotypically (CD33, CD41, and CD62L) tested before cryopreservation (n ¼ 44) and/or after thawing (n ¼ 19).Results: Thirty-eight patients (47%) were treated with 131