Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) - all the aspects
Main Article Content
Abstract
B-chronic lymphocytic leukemia (B-CLL)/Small lymphocytic lymphoma (SLL) is a neoplastic, lymphoproliferative disease, characterized by accumulation of small, mature lymphocytes of the B- cell line in the blood, bone marrow and lymphoid tissues. CLL and SLL are different manifestations of the same disease. The major difference is that in CLL a significant number of the abnormal lymphocytes are also found in the bone marrow and blood, while in SLL the abnormal lymphocytes are predominantly found in the lymph nodes and bone marrow. B-CLL is the commonest leukaemia in adults in the Western countries. The mean age of occurrence is in the range of 64-70 years. The clinical course of the disease is highly variable. Approximately 2-10% of patients with CLL/SLL will develop histologic transformation to diffuse large B-cell lymphoma or Hodgkin lymphoma. This transformation is called Richter's syndrome and involves a much more aggressive disease and a fatal outcome. Adequate immunophenotyping of peripheral blood is essential for establishing the diagnosis of CLL/SLL. The typical immunophenotype for CLL/SLL is CD5+, CD10-, CD19+, and CD20 dim, surface immunoglobulin dim, CD23+, CD43 +/-, and cyclin D1-. During the past decade, numerous prognostic factors were identified and include serum markers such as thymidine kinase and beta-2 microglobulin, genetic markers including IGHV mutational status and cytogenetic abnormalities detected by FISH (e.g., del(13q), del(11q), del(17p), CD38 expression, CD49d and ZAP-70 expression/methylation). During the last few years, recurrent mutations in NOTCH1, SF3B1 and BIRC3 genes with prognostic implications in CLL were also identified. Minimal residual disease (MRD) negativity determined in the peripheral blood after the end of treatment is emerging as an important predictor of treatment efficacy. Ongoing preclinical and clinical studies will unravel newer therapeutic targets and keep on improving patient outcomes and the quality of life.
Article Details
How to Cite
JAHIC, Azra; HASIC CUSTENDIL, Samira.
Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) - all the aspects.
Medical Research Archives, [S.l.], v. 5, n. 3, mar. 2017.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/1043>. Date accessed: 18 nov. 2024.
Keywords
B-chronic lymphocytic leukemia (B-CLL)/Small lymphocytic lymphoma (SLL), immunophenotype, prognostic factors
Section
Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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Ahn Jo, Koo HH, Park BJ, et al. Incidence estimation of leukemia among Koreans. J Korean Med Sci 1991; 6:299-307.
Austen B, Skowronska A, Baker C, et al. Mutation status of the residual ATM allele is an important determinant of the cellular response to chemotherapy and survival in patients with chronic lymphocytic leukemia containing an 11q deletion. J Clin Oncol 2007;25:5448-5457.
Baliakas P, Iskas M, Gardiner A, et al. Chromosomal translocations and karyotype complexity in chronic lymphocytic leukemia: a systematic reappraisal of classic cytogenetic data. Am J Hematol 2014;89:249-255.
Bartal A, Bentwich Z, Manny N, Izak G. Ethnical and clinical aspects of chronic lymphocytic laeukemia in Israel: A survey on 288 patients. Acta Haematol 1978; 60:161-171.
Binet J, Auquier A, Dighiero G, et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer 1981;48:198-206.
Cartwright RA, Gurney KA, Moorman AV. Sex ratios and the risks of haemathologic malignancies. Br J Haematol 2002; 118: 1071-1077.
Crespo M, Bosch F, Villamor N, et al. ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med 2003;348:1764-1775.
Cuttner J. Increased incidence of hematologic malignancies in first-degree relatives of patients with chronic lymphocytic leukemia. Cancer Invest 1992; 10:103-109.
Damle RN, Wasil T, Fais F, et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 1999;94:1840-1847.
Del Poeta G, Maurillo L, Venditti A, et al. Clinical significance of CD38 expression in chronic lymphocytic leukemia. Blood 2001;98:2633-2639.
Del Principe MI, Del Poeta G, Buccisano F, et al. Clinical significance of ZAP-70 protein expression in B-cell chronic lymphocytic leukemia. Blood 2006;108:853-861.
Dick FR, Maca RD. The lymph node in chronic lymphocytic lymphoma leukemia. Cancer 1978; 41:283-292.
Dicker F, Schnittger S, Haferlach T, et al. Immunostimulatory oligonucleotide-induced metaphase cytogenetics detect chromosomal aberrations in 80% of CLL patients: A study of 132 CLL cases with correlation to FISH, IgVH status, and CD38 expression. Blood 2006 (108):3152-3160.
Diehl LF, Karnell LH, Menck HR: The American College of Surgeons Commision on Cancer and the American Cancer Society. The National Cancer Data Base report on age, gender, treatment, and outcomes of patients with chronic lymphocytic leukemia. Cancer 1999; 86:2684.
Dohner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 2000;343:1910-1916.
Elliott MA, Letendre L, Li Cy, et al. Chronic lymphocytic leukaemia with symptomatic diffuse central nervous system infiltration responding to therapy with systemic fludarabine. Br J Haemathology 1999; 104:689-694.
Fabbri G, Rasi S, Rossi D, et al. Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation. J Exp Med 2011;208:1389-1401.
Gentile M, Mauro FR, Calabrese E, et al. The prognostic value of CD38 expression in chronic lymphocytic leukaemia patients studied prospectively at diagnosis: a single institute experience. Br J Haematol 2005;130:549-557.
Gonzalez D, Martinez P, Wade R, et al. Mutational status of the TP53 gene as a predictor of response and survival in patients with chronic lymphocytic leukemia: results from the LRF CLL4 trial. J Clin Oncol 2011;29:2223-2229.
Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008;111:5446-5456.
Hisada M, Biggar RJ, Greene MH, Fraumeni JF Jr, Travis LB. Solid tumors after chronic lymphocytic leukemia. Blood 2001; 98(6):1979–1981.
Ibrahim S, Keating M, Do KA, et al. CD38 expression as an important prognostic factor in B-cell chronic lymphocytic leukemia. Blood 2001;98:181-186.
Inskip PD, Kleinerman RA, Stovall M, et al. Leukemia, lymphoma and multiple myeloma after pelvic radiotherapy for benign disease. Radiat Res 1993; 135:108-125.
Jahic A, Iljazovic E, Arnautovic-Custovic A, Halilbasic A, Simendic V, Zabic A. Prognostic significance of bone-marrow pattern and immunophenotypic score in B-chronic lymphocytic leukemia at diagnosis. Med Arh. 2011; 65(3):132-136.
Krober A, Bloehdorn J, Hafner S, et al. Additional genetic high-risk features such as 11q deletion, 17p deletion, and V3-21 usage characterize discordance of ZAP-70 and VH mutation status in chronic lymphocytic leukemia. J Clin Oncol 2006;24:969-975.
Krober A, Seiler T, Benner A, et al. V(H) mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood 2002;100:1410-1416.
Kipps TJ, Robbins BA, Tefferi A, et al. CD5-positive B-cell malignancies frequently express cross-reactive idiotypes associated with IgM autoantibodies. Am J Pathol 1990; 136:809-816.
Kovacs G, Boettcher S, Bahlo J, et al. Value of Minimal Residual Disease (MRD) Negative Status at Response Evaluation in Chronic Lymphocytic Leukemia (CLL): Combined Analysis of Two Phase III Studies of the German CLL Study Group (GCLLSG). Blood 2014;124:Abstract 23.
Kuppers R, Klein U, Hansmann ML, Rajewsky K. Cellular origin of human B-cell lymphomas. N Engl J Med 1999; 341(20):1520–1529.
Kuppers, R. Mechanisms of B-cell lymphoma pathogenesis. Nat Rev Cancer 2005; 5(4):251–262.
Mao Z, Leticia Q-M, Mark R, et al. IgVH mutational status and clonality analysis of Richter’s transformation: diffuse large B-cell lymphoma and Hodgkin lymphoma in association with B-cell chronic lymphocytic leukemia (B-CLL) represent 2 different pathways of disease evolution. Am J Surg Path 2007; (32):1605–1614.
Montserrat E, Moreno C. Chronic lymphocytic leukaemia: a short overview. Ann Oncol 2008; 19(7):320–325.
Nakamura Naoya, Masafumi Abe. Richter syndrome in B-cell chronic lymphocytic leukemia. Pathology International 2003; 53 (4): 195–203.
Oscier D, Wade R, Davis Z, et al. Prognostic factors identified three risk groups in the LRF CLL4 trial, independent of treatment allocation. Haematologica 2010;95:1705-1712.
Oscier DG, Gardiner AC, Mould SJ, et al. Multivariate analysis of prognostic factors in CLL: clinical stage, IGVH gene mutational status, and loss or mutation of the p53 gene are independent prognostic factors. Blood 2002;100:1177-1184.
Orchard JA, Ibbotson RE, Davis Z, et al. ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet 2004;363:105-111.
Oscier DG, Rose-Zerilli MJ, Winkelmann N, et al. The clinical significance of NOTCH1 and SF3B1 mutations in the UK LRF CLL466, trial. Blood 2013;121:468-475.
Puente XS, Pinyol M, Quesada V, et al. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature 2011;475:101-105.
Quesada V, Conde L, Villamor N, et al. Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat Genet 2012;44:47-52.
Rai KR, Sawitsky A, Cronkite EP, et al. Clinical staging of chronic lymphocytic leukemia. Blood 1975;46:219-234.
Rawstron AC. Monoclonal B-cell lymphocytosis. Hematology Am Soc Hematol Educ Program 2009:430-439.
Redaelli A, Laskin BL, Stephens JM, et al. The clinical and epidemiological burden of chronic lymphocytic leukaemia. Eur J Cancer Care (Engl) 2004; 13(3):279–287.
Rossi D, Fangazio M, Rasi S, et al. Disruption of BIRC3 associates with fludarabine chemorefractoriness in TP53 wild-type chronic lymphocytic leukemia. Blood 2012;119:2854-2862.
Rossi D, Rasi S, Spina V, et al. Different impact of NOTCH1 and SF3B1 mutations on the risk of chronic lymphocytic leukemia transformation to Richter syndrome. Br J Haematol 2012;158:426-429.
Rushton L, Romaniuk H. A case-control study to investigate the risk of leukaemia associated with exposure to benzene in petroleum marketing and distribution workers in the United Kingdom. Occup Environ Med 1997; 54:152-166.
Simonsson B, Wibell L, Nilsson K. Beta 2-microglobulin in chronic lymphocytic leukaemia. Scand J Haematol 1980; 24: 174-180.
Sivakumaran M, Qureshi H, Chapman CS. Chylous effusions in CLL. Leuk Lymphoma 1995; 18:365-366.
Stilgenbauer S, Schnaiter A, Paschka P, et al. Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. Blood 2014;123:3247-3254.
Swerdlow S, Campo E, Harris NL, et al (2008). WHO Classification of Tumours of Haematopoietic and Lymphoid Tisues. 4th ed. Lyon: IARC.
Tam CS, O'Brien S, Wierda W, et al. Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. Blood 2008;112:975-980.
Tamura K, Sawada H, Izumi Y, et al. Chronic lymphocytic leukaemia (CLL) is rare, but proportion of T-CLL is high in Japan. Eur J Haematol 2001; 67:152-157.
Thompson PA, Wierda WG, Ferrajoli A, et al. Complex Karyotype, Rather Than Del(17p), Is Associated with Inferior Outcomes in Relapsed or Refractory CLL Patients Treated with Ibrutinib-Based Regimens. Blood 2014;124:Abstract 229.
Tsimberidou AM, Tam C, Wierda W, et al. Beta-2 microglobulin (B2M) is an independent prognostic factor for clinical outcomes in patients with CLL treated with frontline fludarabine, cyclophosphamide, and rituximab (FCR) regardless of age, creatinine clearance (CrCl) [abstract]. J Clin Oncol 2007;25:Abstract 7034.
Tsimberidou AM, Tam C, Abruzzo LV, O'Brien S, Wierda WG, Lerner S,. Kantarjian HM, Keating MJ.
Chemoimmunotherapy may overcome the adverse prognostic significance of 11q deletion in previously untreated patients with chronic lymphocytic leukemia. Cancer 2009. 115(2): 373–380.
Tsimberidou AM, Wen S, O'Brien S, et al. Assessment of chronic lymphocytic leukemia and small lymphocytic lymphoma by absolute lymphocyte counts in 2,126 patients: 20 years of experience at the University of Texas M.D. Anderson Cancer Center. J Clin Oncol 2007;25:4648-4656.
Villamor N, Conde L, Martinez-Trillos A, et al. NOTCH1 mutations identify a genetic subgroup of chronic lymphocytic leukemia patients with high risk of transformation and poor outcome. Leukemia 2013;27:1100-1106.
Wang L, Lawrence MS, Wan Y, et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med 2011;365:2497-2506.
Wierda WG, O'Brien S, Wang X, et al. Characteristics associated with important clinical end points in patients with chronic lymphocytic leukemia at initial treatment. J Clin Oncol 2009;27:1637-1643.
Woyach JA, Ruppert AS, Lozanski G, et al. Association of disease progression on ibrutinib therapy with the acquisition of resistance mutations: A single-center experience of 267 patients [abstract]. J Clin Oncol 2014;32 (15_suppl):Abstract 7010.
Yuille MR, Matutes E, Marossy A, et al. Familial chronic lymphocytic leukemia: A survey and review on of published studies. Br J Haematol 2000; 109(4):794-799.
Zenz T, Eichhorst B, Busch R, et al. TP53 Mutation and Survival in Chronic Lymphocytic Leukemia. J Clin Oncol 2010;28:4473-4479.
Ahn Jo, Koo HH, Park BJ, et al. Incidence estimation of leukemia among Koreans. J Korean Med Sci 1991; 6:299-307.
Austen B, Skowronska A, Baker C, et al. Mutation status of the residual ATM allele is an important determinant of the cellular response to chemotherapy and survival in patients with chronic lymphocytic leukemia containing an 11q deletion. J Clin Oncol 2007;25:5448-5457.
Baliakas P, Iskas M, Gardiner A, et al. Chromosomal translocations and karyotype complexity in chronic lymphocytic leukemia: a systematic reappraisal of classic cytogenetic data. Am J Hematol 2014;89:249-255.
Bartal A, Bentwich Z, Manny N, Izak G. Ethnical and clinical aspects of chronic lymphocytic laeukemia in Israel: A survey on 288 patients. Acta Haematol 1978; 60:161-171.
Binet J, Auquier A, Dighiero G, et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer 1981;48:198-206.
Cartwright RA, Gurney KA, Moorman AV. Sex ratios and the risks of haemathologic malignancies. Br J Haematol 2002; 118: 1071-1077.
Crespo M, Bosch F, Villamor N, et al. ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med 2003;348:1764-1775.
Cuttner J. Increased incidence of hematologic malignancies in first-degree relatives of patients with chronic lymphocytic leukemia. Cancer Invest 1992; 10:103-109.
Damle RN, Wasil T, Fais F, et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 1999;94:1840-1847.
Del Poeta G, Maurillo L, Venditti A, et al. Clinical significance of CD38 expression in chronic lymphocytic leukemia. Blood 2001;98:2633-2639.
Del Principe MI, Del Poeta G, Buccisano F, et al. Clinical significance of ZAP-70 protein expression in B-cell chronic lymphocytic leukemia. Blood 2006;108:853-861.
Dick FR, Maca RD. The lymph node in chronic lymphocytic lymphoma leukemia. Cancer 1978; 41:283-292.
Dicker F, Schnittger S, Haferlach T, et al. Immunostimulatory oligonucleotide-induced metaphase cytogenetics detect chromosomal aberrations in 80% of CLL patients: A study of 132 CLL cases with correlation to FISH, IgVH status, and CD38 expression. Blood 2006 (108):3152-3160.
Diehl LF, Karnell LH, Menck HR: The American College of Surgeons Commision on Cancer and the American Cancer Society. The National Cancer Data Base report on age, gender, treatment, and outcomes of patients with chronic lymphocytic leukemia. Cancer 1999; 86:2684.
Dohner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 2000;343:1910-1916.
Elliott MA, Letendre L, Li Cy, et al. Chronic lymphocytic leukaemia with symptomatic diffuse central nervous system infiltration responding to therapy with systemic fludarabine. Br J Haemathology 1999; 104:689-694.
Fabbri G, Rasi S, Rossi D, et al. Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation. J Exp Med 2011;208:1389-1401.
Gentile M, Mauro FR, Calabrese E, et al. The prognostic value of CD38 expression in chronic lymphocytic leukaemia patients studied prospectively at diagnosis: a single institute experience. Br J Haematol 2005;130:549-557.
Gonzalez D, Martinez P, Wade R, et al. Mutational status of the TP53 gene as a predictor of response and survival in patients with chronic lymphocytic leukemia: results from the LRF CLL4 trial. J Clin Oncol 2011;29:2223-2229.
Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008;111:5446-5456.
Hisada M, Biggar RJ, Greene MH, Fraumeni JF Jr, Travis LB. Solid tumors after chronic lymphocytic leukemia. Blood 2001; 98(6):1979–1981.
Ibrahim S, Keating M, Do KA, et al. CD38 expression as an important prognostic factor in B-cell chronic lymphocytic leukemia. Blood 2001;98:181-186.
Inskip PD, Kleinerman RA, Stovall M, et al. Leukemia, lymphoma and multiple myeloma after pelvic radiotherapy for benign disease. Radiat Res 1993; 135:108-125.
Jahic A, Iljazovic E, Arnautovic-Custovic A, Halilbasic A, Simendic V, Zabic A. Prognostic significance of bone-marrow pattern and immunophenotypic score in B-chronic lymphocytic leukemia at diagnosis. Med Arh. 2011; 65(3):132-136.
Krober A, Bloehdorn J, Hafner S, et al. Additional genetic high-risk features such as 11q deletion, 17p deletion, and V3-21 usage characterize discordance of ZAP-70 and VH mutation status in chronic lymphocytic leukemia. J Clin Oncol 2006;24:969-975.
Krober A, Seiler T, Benner A, et al. V(H) mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood 2002;100:1410-1416.
Kipps TJ, Robbins BA, Tefferi A, et al. CD5-positive B-cell malignancies frequently express cross-reactive idiotypes associated with IgM autoantibodies. Am J Pathol 1990; 136:809-816.
Kovacs G, Boettcher S, Bahlo J, et al. Value of Minimal Residual Disease (MRD) Negative Status at Response Evaluation in Chronic Lymphocytic Leukemia (CLL): Combined Analysis of Two Phase III Studies of the German CLL Study Group (GCLLSG). Blood 2014;124:Abstract 23.
Kuppers R, Klein U, Hansmann ML, Rajewsky K. Cellular origin of human B-cell lymphomas. N Engl J Med 1999; 341(20):1520–1529.
Kuppers, R. Mechanisms of B-cell lymphoma pathogenesis. Nat Rev Cancer 2005; 5(4):251–262.
Mao Z, Leticia Q-M, Mark R, et al. IgVH mutational status and clonality analysis of Richter’s transformation: diffuse large B-cell lymphoma and Hodgkin lymphoma in association with B-cell chronic lymphocytic leukemia (B-CLL) represent 2 different pathways of disease evolution. Am J Surg Path 2007; (32):1605–1614.
Montserrat E, Moreno C. Chronic lymphocytic leukaemia: a short overview. Ann Oncol 2008; 19(7):320–325.
Nakamura Naoya, Masafumi Abe. Richter syndrome in B-cell chronic lymphocytic leukemia. Pathology International 2003; 53 (4): 195–203.
Oscier D, Wade R, Davis Z, et al. Prognostic factors identified three risk groups in the LRF CLL4 trial, independent of treatment allocation. Haematologica 2010;95:1705-1712.
Oscier DG, Gardiner AC, Mould SJ, et al. Multivariate analysis of prognostic factors in CLL: clinical stage, IGVH gene mutational status, and loss or mutation of the p53 gene are independent prognostic factors. Blood 2002;100:1177-1184.
Orchard JA, Ibbotson RE, Davis Z, et al. ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet 2004;363:105-111.
Oscier DG, Rose-Zerilli MJ, Winkelmann N, et al. The clinical significance of NOTCH1 and SF3B1 mutations in the UK LRF CLL466, trial. Blood 2013;121:468-475.
Puente XS, Pinyol M, Quesada V, et al. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature 2011;475:101-105.
Quesada V, Conde L, Villamor N, et al. Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat Genet 2012;44:47-52.
Rai KR, Sawitsky A, Cronkite EP, et al. Clinical staging of chronic lymphocytic leukemia. Blood 1975;46:219-234.
Rawstron AC. Monoclonal B-cell lymphocytosis. Hematology Am Soc Hematol Educ Program 2009:430-439.
Redaelli A, Laskin BL, Stephens JM, et al. The clinical and epidemiological burden of chronic lymphocytic leukaemia. Eur J Cancer Care (Engl) 2004; 13(3):279–287.
Rossi D, Fangazio M, Rasi S, et al. Disruption of BIRC3 associates with fludarabine chemorefractoriness in TP53 wild-type chronic lymphocytic leukemia. Blood 2012;119:2854-2862.
Rossi D, Rasi S, Spina V, et al. Different impact of NOTCH1 and SF3B1 mutations on the risk of chronic lymphocytic leukemia transformation to Richter syndrome. Br J Haematol 2012;158:426-429.
Rushton L, Romaniuk H. A case-control study to investigate the risk of leukaemia associated with exposure to benzene in petroleum marketing and distribution workers in the United Kingdom. Occup Environ Med 1997; 54:152-166.
Simonsson B, Wibell L, Nilsson K. Beta 2-microglobulin in chronic lymphocytic leukaemia. Scand J Haematol 1980; 24: 174-180.
Sivakumaran M, Qureshi H, Chapman CS. Chylous effusions in CLL. Leuk Lymphoma 1995; 18:365-366.
Stilgenbauer S, Schnaiter A, Paschka P, et al. Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. Blood 2014;123:3247-3254.
Swerdlow S, Campo E, Harris NL, et al (2008). WHO Classification of Tumours of Haematopoietic and Lymphoid Tisues. 4th ed. Lyon: IARC.
Tam CS, O'Brien S, Wierda W, et al. Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. Blood 2008;112:975-980.
Tamura K, Sawada H, Izumi Y, et al. Chronic lymphocytic leukaemia (CLL) is rare, but proportion of T-CLL is high in Japan. Eur J Haematol 2001; 67:152-157.
Thompson PA, Wierda WG, Ferrajoli A, et al. Complex Karyotype, Rather Than Del(17p), Is Associated with Inferior Outcomes in Relapsed or Refractory CLL Patients Treated with Ibrutinib-Based Regimens. Blood 2014;124:Abstract 229.
Tsimberidou AM, Tam C, Wierda W, et al. Beta-2 microglobulin (B2M) is an independent prognostic factor for clinical outcomes in patients with CLL treated with frontline fludarabine, cyclophosphamide, and rituximab (FCR) regardless of age, creatinine clearance (CrCl) [abstract]. J Clin Oncol 2007;25:Abstract 7034.
Tsimberidou AM, Tam C, Abruzzo LV, O'Brien S, Wierda WG, Lerner S,. Kantarjian HM, Keating MJ.
Chemoimmunotherapy may overcome the adverse prognostic significance of 11q deletion in previously untreated patients with chronic lymphocytic leukemia. Cancer 2009. 115(2): 373–380.
Tsimberidou AM, Wen S, O'Brien S, et al. Assessment of chronic lymphocytic leukemia and small lymphocytic lymphoma by absolute lymphocyte counts in 2,126 patients: 20 years of experience at the University of Texas M.D. Anderson Cancer Center. J Clin Oncol 2007;25:4648-4656.
Villamor N, Conde L, Martinez-Trillos A, et al. NOTCH1 mutations identify a genetic subgroup of chronic lymphocytic leukemia patients with high risk of transformation and poor outcome. Leukemia 2013;27:1100-1106.
Wang L, Lawrence MS, Wan Y, et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med 2011;365:2497-2506.
Wierda WG, O'Brien S, Wang X, et al. Characteristics associated with important clinical end points in patients with chronic lymphocytic leukemia at initial treatment. J Clin Oncol 2009;27:1637-1643.
Woyach JA, Ruppert AS, Lozanski G, et al. Association of disease progression on ibrutinib therapy with the acquisition of resistance mutations: A single-center experience of 267 patients [abstract]. J Clin Oncol 2014;32 (15_suppl):Abstract 7010.
Yuille MR, Matutes E, Marossy A, et al. Familial chronic lymphocytic leukemia: A survey and review on of published studies. Br J Haematol 2000; 109(4):794-799.
Zenz T, Eichhorst B, Busch R, et al. TP53 Mutation and Survival in Chronic Lymphocytic Leukemia. J Clin Oncol 2010;28:4473-4479.