ХРОНИЧЕСКИЙ ЛИМФОЛЕЙКОЗ: СОВРЕМЕННЫЕ ВОПРОСЫ ДИАГНОСТИКИ И ЛЕЧЕНИЯ
Ключові слова:
хронический лимфолейкоз, лимфома из малых лимфоцитов, клиникогематологические проявления, критерии лабораторной диагностики, прогностические факторы, таргетная терапия, ингибитор BCL-2, ингибиторы киназ.Анотація
Хронический лимфолейкоз (ХЛЛ)/лимфома из малых лимфоцитов является
наиболее частой формой лимфопролиферативных заболеваний у взрослого населения стран Европы иСеверной Америки. Применяемый в настоящее время
комплексный анализ клинико-лабораторных признаков ХЛЛ позволяет своевременно устанавливать диагноз и определять стадию заболевания, что обусловливает дальнейшую тактику лечения. Выделен ряд критериев, которые
дают возможность с высокой степенью достоверности индивидуально прогнозировать клиническое течение заболевания и результаты лечения больных
ХЛЛ. Доклинические и клинические исследования показали чрезвычайную чувствительность субстратных клеток ХЛЛ ксинтетическим BH3-миметикам
и ингибиторам тирозинкиназы Брутона илиPI3K киназ, которые участвуют
в передаче регуляторных сигналов, опосредуемых B-клеточным рецептором.
В обзоре представлены обобщенные данные о принципах современной диагностики ХЛЛ. Обсуждается стратегия фармакотерапии больных ХЛЛ, в том
числе связанная с использованием новых таргетных препаратов.
Посилання
Diagnosis and treatment of chronic lymphocytic leukemia. Adapted clinical evidence-proved guidance (revised). State Expertise Center of the Ministry of Health of Ukraine. 2016. 84 p. Available from: http://mtd.dec.gov.ua/images/dodatki/2016_439_ HLL/2016_439_AKN_HLL.pdf (in Ukrainian).
Mauro FR, Foa R, Giannarelli D, et al. Clinical characteristics and outcome of young chronic lymphocytic leukemia patients: a single institution study of 204 cases. Blood 1999; 94 (2): 448–54.
Cerhan JR, Slager SL. Familial predisposition and genetic risk factors for lymphoma. Blood 2015; 126: 2265–73.
Ishibe N, Sgambati MT, Fontaine L, et al. Clinical characteristics of familial B-CLL in the National Cancer Institute Familial Registry. Leuk Lymphoma 2001; 42 (1–2): 99–108.
Pang JW, Cook LS, Schwartz SM, Weiss NS. Incidence of leukemia in Asian migrants to the United States and their descendents. Cancer Causes Control 2002; 13 (9): 791–5.
Schinasi LH, De Roos AJ, Ray RM, et al. Insecticide exposure and farm history in relation to risk of lymphomas and leukemias in the Women’s Health Initiative observational study cohort. Ann Epidemiol 2015; 25 (11): 803–10.
Gluzman DF, Abramenko IV, Machilo VM. Large granular lymphocyte leukemia in Chernobyl clean-up workers. Exp Oncol 2000; 22 (1–2): 84–5.
Richardson DB, Wing S, Schroeder J, et al. Ionizing radiation and chronic lymphocytic leukemia. Environ Health Perspect 2005; 113 (1): 1–5.
Schubauer-Berigan MK, Daniels RD, Fleming DA, et al. Chronic lymphocytic leukaemia and radiation: findings among workers at five US nuclear facilities and a review of the recent literature. Br J Haematol 2007; 139 (5): 799–808.
Zablotska LB, Bazyka D, Lubin JH, et al. Radiation and the risk of chronic lymphocytic and other leukemias among Chornobyl cleanup workers. Environ Health Perspect 2013; 121 (1): 59–65.
Philchenkov AA. Molecular epidemiological markers of radiation-induced hematologic malignancies. Radiats Biol Radioecol 2016; 56 (6): 570–82 (in Russian).
Finch SC, Dyagil I, Reiss RF, et al. Clinical characteristics of chronic lymphocytic leukemia occurring in Chornobyl cleanup workers. Hematol Oncol 2017; 35 (2): 215–24.
Royle JA, Baade PD, Joske D, et al. Second cancer incidence and cancer mortality among chronic lymphocytic leukaemia patients: a population-based study. Br J Cancer 2011; 105 (7): 1076–81.
Cheson BD, Vena DA, Barrett J, Freidlin B. Second malignancies as a consequence of nucleoside analog therapy for chronic lymphoid leukemias. J Clin Oncol 1999; 17 (8): 2454–60.
Müller-Hermelink HK, Montserrat E, Catovsky D, et al. Chronic lymphocytic leukemia/small lymphocytic lymphoma. In: WHO classification of tumour of haematopoietic and lymphoid tissues. Lyon: IARC, 2008: 179–82.
Hematology: Modern reference book. Abdulkadyrov KM, ed. Moscow: Eksmo; St Petersburg: Sova, 2004. 928 p. (in Russian).
Jaffe ES, Harris NL, Stein H, Isaacson PG. Classification of lymphoid neoplasms: the microscope as a tool for disease discovery.
Blood 2008; 112 (12): 4384–99.
Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127 (20): 2375–90.
Hallek K, 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 (12): 5546–56.
Volkova MA. Chronic lymphocytic leukemia. In: Clinical Oncohematology: Guide for Physicians. Volkova MA, ed. Moscow: Medicine, 2001: 376–92 (in Russian).
Atlas. Neoplasms of the Lymphatic System. Vorob’ev AI, Kremenetskaya AM, eds. Moscow: Newdiamed, 2007. 294 p. (in Russian).
Rai KR, Sawitsky A, Cronkite EP, et al. Clinical staging of chronic lymphocytic leukemia. Blood 1975; 46 (2): 219–34.
Binet JL, Leporrier M, Dighiero G, et al. A clinical staging system for chronic lymphocytic leukemia: prognostic significance. Cancer 1977; 40 (2): 855–64.
Kipps TJ, Stevenson FK, Wu CJ, et al. Chronic lymphocytic leukaemia. Nat Rev Dis Primers 2017; 3: 16096.
Gluzman DF, Sklyarenko LM, Nadgornaya VA. Diagnosis in Oncohematology. Kyiv: Morion, 2011. 256 p. (in Russian).
Montserrat E, Rozman C. Bone marrow biopsy in chronic lymphocytic leukaemia: a study of 208 cases. Haematologia (Budap) 1983; 16 (1–4): 73–9.
Nikitin EA, Hallek M, Baikov VV, et al. Russian clinical recommendations on diagnosis and management of chronic lymphocytic leukemia (version 2012). Clin Oncohematol 2013; 6 (1): 99–109 (in Russian).
Scarfò L, Ghia P. What does it mean I have a monoclonal B-cell lymphocytosis?: Recent insights and new challenges. Semin Oncol 2016; 43 (2): 201–8.
Bain BJ. Leukemia Diagnosis, 4nd ed. London: WileyBlackwell, 2010. 377 p.
Schwarz J, Mikulenková D, Cermáková M, et al. Prognostic relevance of the FAB morphological criteria in chronic lymphocytic leukemia: correlations with IgVH gene mutational status and other prognostic markers. Neoplasma 2006;
(3): 219–25.
Alapat D, Coviello-Malle J, Owens R, et al. Diagnostic usefulness and prognostic impact of CD200 expression in lymphoid malignancies and plasma cell myeloma. Am J Clin Pathol 2012; 137 (1): 93–100.
Cui B, Ghia EM, Chen L, et al. High-level ROR1 associates with accelerated disease progression in chronic lymphocytic
leukemia. Blood 2016; 128 (25): 2931–40.
Döhner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 2000; 343 (26): 1910–6.
Klein U, Lia M, Crespo M, et al. The DLEU2/miR15a/16-1 cluster controls B cell proliferation and its deletion leads
to chronic lymphocytic leukemia. Cancer Cell 2010; 17 (1): 28–40.
Philchenkov AA. Apoptosis modulators. Biomed Khim 2003; 49 (4): 333–59 (in Russian).
Tobin G, Rosenquist R. Prognostic usage of V(H) gene mutation status and its surrogate markers and the role of antigen selection in chronic lymphocytic leukemia. Med Oncol 2005; 22 (3): 217–28.
Morilla A, Gonzalez de Castro D, Del Giudice I, et al. Combinations of ZAP-70, CD38 and IGHV mutational status as predictors of time to first treatment in CLL. Leuk Lymphoma 2008; 49 (11): 2108–15.
Chen YH, Peterson LC, Dittmann D, et al. Comparative analysis of flow cytometric techniques in assessment of ZAP-70 expression in relation to IgVH mutational status in chronic lymphocytic leukemia. Am J Clin Pathol 2007; 127 (2): 182–91.
Siddon AJ, Rinder HM; Education Committee of the Academy of Clinical Laboratory Physicians and Scientists. Pathology consultation on evaluating prognosis in incidental monoclonal lymphocytosis and chronic lymphocytic leukemia. Am J Clin Pathol 2013; 139 (6): 708–12.
Landau DA, Tausch E, Taylor-Weiner AN, et al. Mutations driving CLL and their evolution in progression and relapse. Nature 2015; 526 (7574): 525–30.
Calin GA, Dumitru CD, Shimizu M, et al.Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 2002; 99 (24): 15524–9.
Cimmino A, Calin GA, Fabbri M, et al. miR-15 and miR16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A
; 102 (39): 13944–9.
Cui B, Chen L, Zhang S, et al. MicroRNA-155 influences B-cell receptor signaling and associates with aggressive disease in chronic lymphocytic leukemia. Blood 2014; 124 (4): 546–54.
Hallek M, Wanders L, Ostwald M, et al. Serum beta(2)-microglobulin and serum thymidine kinase are independent predictors of progression-free survival in chronic lymphocytic leukemia and immunocytoma. Leuk Lymphoma 1996; 22 (5–6): 439–47.
Sagatys EM, Zhang L. Clinical and laboratory prognostic indicators in chronic lymphocytic leukemia. Cancer Control
; 19 (1): 18–25.
Diehl LF, Karnell LH, Menck HR. The American College of Surgeons Commission 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 (12): 2684–92.
Wadhwa PD, Morrison VA. Infectious complications of chronic lymphocytic leukemia. Semin Oncol 2006; 33 (2): 240–9.
Kriachok IA. Chronic lymphocytic leukemia: New in treatment. Approaches to the first-line treatment and their evolution. Clin Oncol (Kyiv) 2013; (3): 121–9 (in Russian).
Nikitin EA, Sudarikov AB. High-risk chronic lymphocytic leukemia: history, definition, diagnosis, and management. Clin Oncohematol 2013; 6 (1): 59–67 (in Russian).
Zenz T, Benner A, Döhner H, Stilgenbauer S. Chronic lymphocytic leukemia and treatment resistance in cancer: the role of the p53 pathway. Cell Cycle 2008; 7 (24): 3810–4.
Dighiero G, Binet JL. When and how to treat chronic lymphocytic leukemia. N Engl J Med 2000; 343 (24): 1799–801.
Fiyas AT, Frenkel BI. Chronic lymphocytic leukemia: Diagnosis and treatment. J Grodno State Med Univer 2011; (4):
–7 (in Russian).
Zagoskina TP. Value of alemtuzumab in therapy of chronic lymphatic leukemia. Bull Sib Branch Russ Acad Med Sci 2011; 31 (2): 48–52 (in Russian).
Keating MJ, O’Brien S, Albitar M, et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol 2005; 23 (18): 4079–88.
Tsujimoto Y, Finger LR, Yunis J, et al. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science 1984; 226 (4678): 1097–9.
Vaux DL, Cory S, Adams JM. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 1988; 335 (6189): 440–2.
Strasser A, Harris AW, Cory S. bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell 1991; 67 (5): 889–99.
Boise LH, González-García M, Postema CE, et al. bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell 1993; 74 (4): 597–608.
Kozopas KM, Yang T, Buchan HL, et al. MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2. Proc Natl Acad Sci U S A 1993; 90
(8): 3516–20.
Gibson L, Holmgreen SP, Huang DC, et al. bcl-w, a novel member of the bcl-2 family, promotes cell survival. Oncogene 1996; 13 (4): 665–75.
Gross A, Katz SG. Non-apoptotic functions of BCL-2 family proteins. Cell Death Differ 2017; 24 (8): 1348–58.
Hanahan D, Weinberg RA. The hallmarks of cancer: The next generation. Cell 2011; 144 (5): 646–74.
Abramenko IV, Philchenkov AA. Prognostic value of apoptotic and proliferative indices in human solid tumors. Oncology (Kyiv) 2002; 4 (3): 165–70 (in Russian).
Luna-Vargas MP, Chipuk JE. The deadly landscape of proapoptotic BCL-2 proteins in the outer mitochondrial membrane. FEBS J 2016; 283 (14): 2676–89.
Oltersdorf T, Elmore SW, Shoemaker AR, et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 2005; 435 (7042): 677–81.
Tse C, Shoemaker AR, Adickes J, et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res 2008; 68 (9): 3421–8.
Kipps TJ, Eradat H, Grosicki S, et al. A phase 2 study of the BH3 mimetic BCL2 inhibitor navitoclax (ABT-263) with or without rituximab, in previously untreated B-cell chronic lymphocytic leukemia. Leuk Lymphoma 2015; 56 (10): 2826–33.
Mason KD, Carpinelli MR, Fletcher JI, et al. Programmed anuclear cell death delimits platelet life span. Cell 2007; 128 (6): 1173–86.
Souers AJ, Leverson JD, Boghaert ER, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med 2013; 19 (2): 202–8.
Jones JA, Mato AR, Coutre S, et al. Preliminary results of a phase 2, open-label study of venetoclax (ABT-199/GDC-0199) monotherapy in patients with chronic lymphocytic leukemia relapsed after or refractory to ibrutinib or idelalisib therapy. Blood 2015; 126 (18): 715.
Stilgenbauer S, Eichhorst B, Schetelig J, et al. Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study. Lancet Oncol 2016; 17 (6): 768–78.
Roberts AW, Davids MS, Pagel JM, et al. Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N Engl J Med 2016; 374 (4): 311–22.
Philchenkov AA. Apoptosis-reactivating agents for targeted anticancer therapy. Biomed Khim 2013; 59 (2): 119–43 (in Russian).
Olin JL, Griffiths CL, Smith MB. Venetoclax: A novel Bcell lymphoma-2 inhibitor for chronic lymphocytic leukemia and
other hematologic malignancies. J Oncol Pharm Pract 2017 [Epub ahead of print].
Woyach JA, Johnson AJ, Byrd JC. The B-cell receptor signaling pathway as a therapeutic target in CLL. Blood 2012; 120 (6): 1175–84.
Burger JA, Chiorazzi N. B cell receptor signaling in chronic lymphocytic leukemia. Trends Immunol 2013; 34 (12): 592–601.
Woyach JA, Bojnik E, Ruppert AS, et al. Bruton’s tyrosine kinase (BTK) function is important to the development and expansion of chronic lymphocytic leukemia (CLL). Blood 2014; 123 (8): 1207–13.
Herman SE, Gordon AL, Wagner AJ, et al. Phosphatidylinositol 3-kinase-delta inhibitor CAL-101 shows promising
preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals. Blood 2010; 116 (12): 2078–88.
Pan Z, Scheerens H, Li SJ, et al. Discovery of selective irreversible inhibitors for Bruton’s tyrosine kinase. Chem Med Chem 2007; 2 (1): 58–61.
Herman SE, Gordon AL, Hertlein E, et al. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI32765. Blood 2011; 117 (23): 6287–96.
Advani RH, Buggy JJ, Sharman JP, et al. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol 2013; 31 (1): 88–94.
Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med 2013; 369 (1): 32–42.
Byrd JC, Furman RR, Coutre SE, et al. Three-year followup of treatment-naïve and previously treated patients with CLL and SLL receiving single-agent ibrutinib. Blood 2015; 125 (16): 2497–50.
O’Brien SM, Furman RR, Coutre SE, et al. Five-year experience with single-agent ibrutinib in patients with previously untreated and relapsed/refractory chronic lymphocytic leukemia/small lymphocytic leukemia. Blood 2016; 128 (16): 233.
Sorokina TV, Goryacheva SR, Spirina VA, et al. Experience with ibrutinib in patients with refractory and recurrent Bcell chronic lymphocytic leukemia. Med Council 2017; (6): 132– 8 (in Russian).
Hoellenriegel J, Meadows SA, Sivina M, et al. The phosphoinositide 3'-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia. Blood 2011; 118 (13): 3603–12.
Brown JR, Byrd JC, Coutre SE, et al. Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110δ, for relapsed/refractory chronic lymphocytic leukemia. Blood 2014; 123 (22): 3390–7.
O’Brien SM, Lamanna N, Kipps TJ, et al. A phase 2 study of idelalisib plus rituximab in treatment-naïve older patients with chronic lymphocytic leukemia. Blood 2015; 126 (25): 2686–94.
Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med 2014; 370 (11): 997–1007.
Jones JA, Robak T, Brown JR, et al. Efficacy and safety of idelalisib in combination with ofatumumab for previously treated chronic lymphocytic leukaemia: an open-label, randomised phase 3 trial. Lancet Haematol 2017; 4 (3): e114–26.
Cheah CY, Fowler NH. Idelalisib in the management of lymphoma. Blood 2016; 128 (3): 331–6.
European Medicines Agency. EMA reviews cancer medicine Zydelig. 11 March 201(http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2016/03/WC500203235.pdf).
