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Chronic lymphocytic leukemia is a malignancy of mature B cells characterized by progressive lymphocytosis, lymphadenopathy, splenomegaly, and cytopenias. The progressive accumulation of leukemic B cells is a consequence of defective apoptosis and survival signals derived from the microenvironment. Progressive disease results in dysregulation of the cellular and humoral components of the effector immune system with a resultant increase in the incidence of infectious complications, which constitutes the leading cause of morbidity and mortality in this disease. Significant therapeutic advances have been realized in recent years, especially with the development of well-tolerated targeted antibodies and kinase inhibitors. Although not curative, these therapies have resulted in significant improvements in patient outcomes with substantial increases in progression-free and overall survival intervals. Multiple novel agents are also in development with the potential to alter the treatment paradigms for this disease and ultimately to affect a cure.

Acronyms and Abbreviations

ABC, activated B cell; ABVD, Adriamycin, bleomycin, vinblastine, and dacarbazine; ADCC, antibody-dependent cell-mediated cytotoxicity; ADP, adenosine diphosphate; AIHA, autoimmune hemolytic anemia; ALL, acute lymphoblastic lymphoma; ARLTS1, ADP-ribosylation factor-like tumor-suppressor gene 1; ATM, ataxia-telangiectasia mutated; BAK, Bcl-2 homologous antagonist/killer; BCL-2, B-cell lymphoma-2; BCR, B-cell receptor; BiTE, Bi-specific T-cell engaging; BR, bendamustine and rituximab; BTK, Bruton tyrosine kinase; CALGB, Cancer and Leukemia Group B; CAP, cyclophosphamide, doxorubicin, and prednisone; CAR-T, chimeric antigen receptor T cell; CD, cluster of differentiation; CDC, complement-dependent cytotoxicity; CDK, cyclin-dependent kinase; CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; CIRS, cumulative illness rating scale; CLL, chronic lymphocytic leukemia; CMP, cyclophosphamide, melphalan, and prednisone; CMV, cytomegalovirus; CR, complete response; CRi, complete response with incomplete count recovery; CT, computed tomography; CVP, cyclophosphamide, vincristine, and prednisone; CXCR4, C-X-C chemokine receptor type 4; DAPK, death-associated protein kinase; ERK1, extracellular signal-regulated kinase 1; FC, fludarabine and cyclophosphamide; FCR, fludarabine, cyclophosphamide, and rituximab; FDG-PET, fluorodeoxyglucose positron emission tomography; FISH, fluorescent in situ hybridization; FR, fludarabine and rituximab; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; GVL, graft-versus-leukemia; HCL, hairy cell leukemia; HLA, human leukocyte antigen; Ig, immunoglobulin; IGH, immunoglobulin heavy chain; IGHV, immunoglobulin heavy-chain variable region; IL, interleukin; ITK, IL-2–inducible T-cell kinase; ITP, immune thrombocytopenia; IVIG, intravenous immunoglobulins; IWCLL, International Workshop on Chronic Lymphocytic Leukemia; KLHL6, Kelch-like protein-6; LDH, lactate dehydrogenase; LYN, Lck/Yes novel; MBL, monoclonal B-cell lymphocytosis; MCL-1, myeloid cell leukemia-1; MHC, major histocompatibility complex; miRNA, microRNA; MMP, matrix metalloproteinase; MMR, measles, mumps, and rubella; MRD, minimal residual disease; MYD88, myeloid differentiation primary response gene 88; NAD, nicotinic acid adenine; NCCN, National Comprehensive Cancer Network; NFAT, nuclear factor of activated T cells; NF-κB, nuclear factor kappa B; NK, natural killer; NOTCH1, Notch homologue 1, translocation-associated; NRM, nonrelapse mortality; OFAR, oxaliplatin, fludarabine, and rituximab; ORR, overall response rate; OS, overall survival; PCR, pentostatin, cyclophosphamide, and rituximab; PCV-13, pneumococcal 13-valent conjugate vaccine; PFS, progression-free survival; PI3K, phosphatidylinositol-4,5-bisphosphate 3-kinase; PLCγ2, phospholipase C-gamma-2; PLL, prolymphocytic leukemia; PR, partial response; PR+L, partial response with lymphocytosis; PRCA, pure red cell aplasia; RB, retinoblastoma; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, ...

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