Page 1552 - Williams Hematology ( PDFDrive )

1527

CHAPTER 92 DEFINITION AND EPIDEMIOLOGY

CHRONIC LYMPHOCYTIC Chronic lymphocytic leukemia (CLL) is one of the most common leu-
kemias in the Western hemisphere. CLL is a malignant lymphoid neo-
LEUKEMIA plasm that is characterized by the accumulation of a population of small
mature B cells. The diagnosis of CLL requires the presence of at least
5000 circulating B cells/μL with clonality demonstrated by flow cytom-
etry according to International Workshop on Chronic Lymphocytic
1
Farrukh T. Awan and John C. Byrd Leukemia (IWCLL) criteria. Over the last 2 centuries, significant strides
have been made in the understanding of the disease pathophysiology,
clinical features, and complications arising from CLL. CLL was initially
described by Virchow in the 1840s when he described patients with
SUMMARY lymph node enlargement and leukocytosis. Subsequent studies revealed
the involvement of the spleen and marrow and led to the introduction
Chronic lymphocytic leukemia is a malignancy of mature B cells character- of the term “lymphosarcoma.” Ensuing natural history studies estab-
ized by progressive lymphocytosis, lymphadenopathy, splenomegaly, and lished the malignant and clonal nature of the disease and categorized
cytopenias. The progressive accumulation of leukemic B cells is a consequence patients based on clinical presentation. Surveillance, Epidemiology, and
of defective apoptosis and survival signals derived from the microenviron- End Results Program (SEER) data from 2013 estimate the prevalence of
ment. Progressive disease results in dysregulation of the cellular and humoral CLL in the United States at 126,553 patients, of whom 72,569 are males.
components of the effector immune system with a resultant increase in the The American Cancer Society estimates 15,720 new cases of CLL in 2014
incidence of infectious complications, which constitutes the leading cause with a median age of diagnosis of 72 years. This cancer is more common
2
of morbidity and mortality in this disease. Significant therapeutic advances in men, uncommon in patients younger than the age of 40 years, and
have been realized in recent years, especially with the development of well- extremely rare in children. The risk also increases progressively with
age and decreases with increasing parity in women. It is also relatively
3
4
tolerated targeted antibodies and kinase inhibitors. Although not curative, uncommon in Asians, even in Asian immigrants to the Western hemi-
5
these therapies have resulted in significant improvements in patient outcomes sphere, suggesting a possibility of a genetic predisposition. In the last
6
with substantial increases in progression-free and overall survival intervals. few years there has been a tremendous growth in the understanding of
Multiple novel agents are also in development with the potential to alter the the disease biology, which has resulted in the development of numerous
treatment paradigms for this disease and ultimately to affect a cure. new therapeutic options with resultant transformation in the manage-
ment of this illness. Despite the significant improvement in the progno-
sis of this disease, cure currently remains elusive.

Acronyms and Abbreviations: ABC, activated B cell; ABVD, Adriamycin, bleomycin, MBL, monoclonal B-cell lymphocytosis; MCL-1, myeloid cell leukemia-1; MHC, major his-
vinblastine, and dacarbazine; ADCC, antibody-dependent cell-mediated cytotoxicity; tocompatibility complex; miRNA, microRNA; MMP, matrix metalloproteinase; MMR, mea-
ADP, adenosine diphosphate; AIHA, autoimmune hemolytic anemia; ALL, acute lympho- sles, mumps, and rubella; MRD, minimal residual disease; MYD88, myeloid differentiation
blastic lymphoma; ARLTS1, ADP-ribosylation factor-like tumor-suppressor gene 1; ATM, primary response gene 88; NAD, nicotinic acid adenine; NCCN, National Comprehensive
ataxia-telangiectasia mutated; BAK, Bcl-2 homologous antagonist/killer; BCL-2, B-cell Cancer Network; NFAT, nuclear factor of activated T cells; NF-κB, nuclear factor kappa B;
lymphoma-2; BCR, B-cell receptor; BiTE, Bi-specific T-cell engaging; BR, bendamustine NK, natural killer; NOTCH1, Notch homologue 1, translocation-associated; NRM, nonrelapse
and rituximab; BTK, Bruton tyrosine kinase; CALGB, Cancer and Leukemia Group B; CAP, mortality; OFAR, oxaliplatin, fludarabine, and rituximab; ORR, overall response rate; OS,
cyclophosphamide, doxorubicin, and prednisone; CAR-T, chimeric antigen receptor T cell; overall survival; PCR, pentostatin, cyclophosphamide, and rituximab; PCV-13, pneumococ-
CD, cluster of differentiation; CDC, complement-dependent cytotoxicity; CDK, cyclin- cal 13-valent conjugate vaccine; PFS, progression-free survival; PI3K, phosphatidylinosi-
dependent kinase; CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; tol-4,5-bisphosphate 3-kinase; PLCγ , phospholipase C-gamma-2; PLL, prolymphocytic
2
CIRS, cumulative illness rating scale; CLL, chronic lymphocytic leukemia; CMP, cyclophos- leukemia; PR, partial response; PR+L, partial response with lymphocytosis; PRCA, pure
phamide, melphalan, and prednisone; CMV, cytomegalovirus; CR, complete response; red cell aplasia; RB, retinoblastoma; R-CHOP, rituximab, cyclophosphamide, doxorubicin,
CRi, complete response with incomplete count recovery; CT, computed tomography; CVP, vincristine, and prednisone; R-EPOCH, rituximab, etoposide, prednisone, vincristine, cyclo-
cyclophosphamide, vincristine, and prednisone; CXCR4, C-X-C chemokine receptor type phosphamide, and doxorubicin; R-hyperCVXD, fractionated cyclophosphamide, vincristine,
4; DAPK, death-associated protein kinase; ERK1, extracellular signal-regulated kinase 1; liposomal daunorubicin, and dexamethasone; RS, Richter syndrome; SCT, stem cell trans-
FC, fludarabine and cyclophosphamide; FCR, fludarabine, cyclophosphamide, and ritux- plantation; SDF-1, stromal cell–derived factor-1; SF3B1, splicing factor 3B subunit 1; SLL,
imab; FDG-PET, fluorodeoxyglucose positron emission tomography; FISH, fluorescent in small lymphocytic B-cell lymphoma; SNP, single nucleotide polymorphism; STAT3, signal
situ hybridization; FR, fludarabine and rituximab; G-CSF, granulocyte colony-stimulating transducer and activator of transcription 3; SUV, standardized uptake value; SYK, spleen
factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; GVL, graft-versus- tyrosine kinase; TCL1, T-cell leukemia/lymphoma protein 1A; TGF-β, transforming growth
leukemia; HCL, hairy cell leukemia; HLA, human leukocyte antigen; Ig, immunoglobulin; factor-β; T-LGL, T-cell large granular lymphoma; TNF-α, tumor necrosis factor-α; TP53,
IGH, immunoglobulin heavy chain; IGHV, immunoglobulin heavy-chain variable region; tumor protein p53; T-PLL, T-cell prolymphocytic lymphoma; TRAP, tartrate-resistant acid
IL, interleukin; ITK, IL-2–inducible T-cell kinase; ITP, immune thrombocytopenia; IVIG, phosphatase; TRM, transplant-related mortality; VCAM, vascular cell adhesion molecule;
intravenous immunoglobulins; IWCLL, International Workshop on Chronic Lymphocytic XIAP, X-linked inhibitor of apoptosis protein; XPO1, gene encoding exportin-1; ZAP-70,
Leukemia; KLHL6, Kelch-like protein-6; LDH, lactate dehydrogenase; LYN, Lck/Yes novel; zeta-chain–associated protein kinase of 70 kDa.

Kaushansky_chapter 92_p1527-1552.indd 1527 9/18/15 10:45 AM