#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Recommendations for chronic lymphocytic leukaemia diagnosis and therapy 2021


Authors: L. Smolej 1;  M. Špaček 2;  Š. Pospíšilová 3;  M. Jarošová 3;  T. Papajík 4;  R. Urbanová 4;  M. Šimkovič 1;  D. Lysák 5;  M. Brejcha 6;  M. Doubek 3
Authors‘ workplace: IV. interní hematologická klinika LF UK a FN Hradec Králové 1;  I. interní klinika – klinika hematologie 1. LF UK a VFN v Praze 2;  Interní hematologická a onkologická klinika LF MU a FN Brno 3;  Hemato-onkologická klinika LF UP a FN Olomouc 4;  Hematologicko-onkologické oddělení, FN Plzeň 5;  Hematologické oddělení, Onkologické centrum Nový Jičín 6
Published in: Transfuze Hematol. dnes,27, 2021, No. 1, p. 91-106.
Category: Best Practices
doi: https://doi.org/10.48095/cctahd202191

Overview

Chronic lymphocytic leukaemia (CLL) is a disease with a remarkably heterogeneous clinical course. The dia­gnostic procedures and therapeutic interventions need to be individually tailored according to patient age, comorbidities and therapeutic aims. We have seen crucial developments in prognostication and therapy in the recent years. The introduction of oral signalling pathway targeted inhibitors (ibrutinib, idelalisib and venetoclax) has resulted in revolutionary improvement of CLL patients’ fate. Results of novel clinical trials with direct impact on clinical practice are accumulating with hitherto unprecedented speed. Therefore, the Czech CLL Study Group, the working group of the Czech Haematological Society, has developed these updated guidelines to facilitate the decision-making process for dia­gnosis and treatment in routine practice. The guidelines are based on a comprehensive analysis of current literature and follow the principles of evidence-based medicine.

Keywords:

chronic lymphocytic leukaemia – dia­gnostics – prognostication – complications – treatment


Sources

1. Hallek M, Cheson BD, Catovsky D, et al. iwCLL guidelines for dia­gnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018; 131: 2745–2760.

2. Doubek M, Špaček M, Pospíšilová Š, et al. Doporučení pro dia­gnostiku a léčbu chronické lymfocytární leukemie (CLL) – 2018. Transfuze Hematol. Dnes 2018; 24: 208–220.

3. Moreau EJ, Matutes E, A‘Hern RP, et al. Improvement of the chronic lymphocytic leukemia scoring system with the monoclonal antibody SN8 (CD79b). Am J Clin Pathol. 1997; 108: 378–382.

4. Rawstron AC, Kreuzer KA, Soosapilla A, et al. Reproducible dia­gnosis of chronic lymphocytic leukemia by flow cytometry: An European Research Initiative on CLL (ERIC) & European Society for Clinical Cell Analysis (ESCCA) Harmonisation project. Cytometry B Clin Cytom. 2018; 94: 121–128.

5. Strati P, Shanafelt TD. Monoclonal B-cell lymphocytosis and early-stage chronic lymphocytic leukemia: dia­gnosis, natural history, and risk stratification. Blood. 2015; 126: 454–462.

6. Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS. Clinical staging of chronic lymphocytic leukemia. Blood. 1975; 46: 219–234.

7. Binet JL, 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.

8. Eichhorst B, Robak T, Montserrat E, et al. Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for dia­gnosis, treatment and follow-up (dagger). Ann Oncol. 2020; S0923-7534 (20) 42469-X.

9. Dohner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000; 343: 1910–1916.

10. Ghia P, Stamatopoulos K, Belessi C, et al. ERIC recommendations on IGHV gene mutational status analysis in chronic lymphocytic leukemia. Leukemia. 2007; 21: 1–3.

11. Malcikova J, Tausch E, Rossi D, et al. ERIC recommendations for TP53 mutation analysis in chronic lymphocytic leukemia-update on methodological approaches and results interpretation. Leukemia. 2018; 32: 1070–1080.

12. Pospisilova S, Gonzalez D, Malcikova J, et al. ERIC recommendations on TP53 mutation analysis in chronic lymphocytic leukemia. Leukemia. 2012; 26: 1458–1461.

13. Brejcha M, Stoklasova M, Brychtova Y, et al. Clonal evolution in chronic lymphocytic leukemia detected by fluorescence in situ hybridization and conventional cytogenetics after stimulation with CpG oligonucleotides and interleukin-2: a prospective analysis. Leuk Res. 2014; 38: 170–175.

14. Malcikova J, Tausch E, Rossi D, et al. ERIC recommendations for TP53 mutation analysis in chronic lymphocytic leukemia-update on methodological approaches and results interpretation. Leukemia 2018; 32 (5): 1070–1080.

15. Pospisilova S, Gonzalez D, Malcikova J, et al. ERIC recommendations on TP53 mutation analysis in chronic lymphocytic leukemia. Leukemia. 2012; 26: 1458–1461.

16. Baliakas P, Hadzidimitriou A, Sutton LA, et al. Recurrent mutations refine prognosis in chronic lymphocytic leukemia. Leukemia. 2015; 29: 329–336.

17. Malcikova J, Pavlova S, Kozubik KS, Pospisilova S. TP53 mutation analysis in clinical practice: lessons from chronic lymphocytic leukemia. Hum Mutat. 2014; 35: 663–671.

18. 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.

19. Stevens-Kroef M, Simons A, Rack K, Hastings RJ. Cytogenetic nomenclature and reporting. Methods Mol Biol. 2017; 1541: 303–309.

20. Hastings RJ, Cavani S, Bricarelli FD, Patsalis PC, Kristoffersson U, Co-ordinators EP. Cytogenetic guidelines and quality assurance: a common European framework for quality assessment for constitutional and acquired cytogenetic investigations. Eur J Hum Genet. 2007; 15: 525–527.

21. Baliakas P, Jeromin S, Iskas M, et al. Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact. Blood. 2019; 133: 1205–1216.

22. International CLLIPIwg. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. Lancet Oncol. 2016; 17: 779–790.

23. Condoluci A, Terzi di Bergamo L, Langerbeins P, et al. International prognostic score for asymptomatic early-stage chronic lymphocytic leukemia. Blood. 2020; 135: 1859–1869.

24. Smolej L, Turcsányi P, Kubová Z, et al. External validation of International Prognostic Score for asymptomatic early-stage chronic lymphocytic leukaemia and proposal of an alternative score. Br J Haematol. 2020; doi: 10.1111/bjh.17074. Online ahead of print.

25. Eichhorst B, Robak T, Montserrat E, et al. Chronic lymphocytic leukaemia: ESMO clinical practice guidelines for dia­gnosis, treatment and follow-updagger. Ann Oncol. 2020; S0923-7534 (20) 42469-X.

26. Furstenau M, Bahlo J, Fink AM, et al. Residual abdominal lymphadenopathy after intensive frontline chemoimmunotherapy is associated with inferior outcome independently of minimal residual disease status in chronic lymphocytic leukemia. Leukemia. 2020; 34: 924–928.

27. Al-Sawaf O, Bazeos A, Robrecht S, et al. Mode of progression after first line treatment correlates with outcome of chronic lymphocytic leukemia (CLL). Am J Hematol. 2019; 94: 1002–1006.

28. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976; 16: 31–41.

29. Thurmes P, Call T, Slager S, et al. Comorbid conditions and survival in unselected, newly dia­gnosed patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2008; 49: 49–56.

30. Extermann M, Overcash J, Lyman GH, Parr J, Balducci L. Comorbidity and functional status are independent in older cancer patients. J Clin Oncol. 1998; 16: 1582–1587.

31. Goede V, Cramer P, Busch R, et al. Interactions between comorbidity and treatment of chronic lymphocytic leukemia: results of German Chronic Lymphocytic Leukemia Study Group trials. Haematologica. 2014; 99: 1095–1100.

32. Parmelee PA, Thuras PD, Katz IR, Lawton MP. Validation of the cumulative illness rating scale in a geriatric residential population. J Am Geriatr Soc. 1995; 43: 130–137.

33. Salvi F, Miller MD, Grilli A, et al. A manual of guidelines to score the modified cumulative illness rating scale and its validation in acute hospitalized elderly patients. J Am Geriatr Soc. 2008; 56: 1926–1931.

34. Cheson BD, Byrd JC, Rai KR, et al. Novel targeted agents and the need to refine clinical end points in chronic lymphocytic leukemia. J Clin Oncol. 2012; 30: 2820–2822.

35. Fischer K, Bahlo J, Fink AM, et al. Long-term remissions after FCR chemoimmu- notherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood. 2016; 127: 208–215.

36. Eichhorst B, Fink AM, Busch R, et al. First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2016; 17 (7): 928–942.

37. Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019; 380: 2225–2236.

38. Woyach JA, Ruppert AS, Heerema NA, et al. Ibrutinib Regimens versus chemoimmunotherapy in older patients with untreated CLL. N Engl J Med. 2018; 379: 2517–2528.

39. Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019; 381: 432–443.

40. Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010; 376: 1164–1174.

41. Farooqui MZ, Valdez J, Martyr S, et al. Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: a phase 2, single-arm trial. Lancet Oncol. 2015; 16: 169–176.

42. Burger JA, Barr PM, Robak T, et al. Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study. Leukemia. 2020; 34: 787–798.

43. Singh M, Mealing S, Baculea S, Cote S, Whelan J. Impact of novel agents on patient-relevant outcomes in patients with previously untreated chronic lymphocytic leukemia who are not eligible for fludarabine-based therapy. J Med Econ. 2017; 20: 1066–1073.

44. Burger JA, Sivina M, Jain N, et al. Randomized trial of ibrutinib vs ibrutinib plus rituximab in patients with chronic lymphocytic leukemia. Blood. 2019; 133: 1011–1019.

45. Wierda WG, Byrd JC, Abramson JS, et al. Chronic lymphocytic leukemia/small lymphocytic lymphoma, version 4.2020, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2020; 18: 185–217.

46. Hillmen P, Skotnicki AB, Robak T, et al. Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia. J Clin Oncol. 2007; 25: 5616–5623.

47. Eichhorst B, Fink AM, Bahlo J, et al. First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2016; 17: 928–942.

48. Zelenetz AD, Gordon LI, Wierda WG, et al. Chronic lymphocytic leukemia/small lymphocytic lymphoma, version 1. 2015. J Natl Compr Canc Netw. 2015; 13: 326–362.

49. Michallet AS, Rossignol J, Cazin B, Ysebaert L. Rituximab-cyclophosphamide-dexamethasone combination in management of autoimmune cytopenias associated with chronic lymphocytic leukemia. Leuk Lymphoma. 2011; 52: 1401–1403.

50. Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020; 395: 1278–1291.

51. Moreno C, Greil R, Demirkan F, et al. Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019; 20: 43–56.

52. Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014; 370: 1101–1110.

53. Goede V, Fischer K, Engelke A, et al. Obinutuzumab as frontline treatment of chronic lymphocytic leukemia: updated results of the CLL11 study. Leukemia. 2015; 29: 1602–1604.

54. Michallet AS, Aktan M, Hiddemann W, et al. Rituximab plus bendamustine or chlorambucil for chronic lymphocytic leukemia: primary analysis of the randomized, open-label MABLE study. Haematologica. 2018; 103: 698–706.

55. Hillmen P, Gribben JG, Follows GA, et al. Rituximab plus chlorambucil as first-line treatment for chronic lymphocytic leukemia: Final analysis of an open-label phase II study. J Clin Oncol. 2014; 32: 1236–1241.

56. Fischer K, Al-Sawaf O, Fink AM, et al. Venetoclax and obinutuzumab in chronic lymphocytic leukemia. Blood. 2017; 129: 2702–2705.

57. Al-Sawaf O, Zhang C, Tandon M, et al. Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2020; 21: 1188–1200.

58. Sinha R, Redekop WK. Cost-effectiveness of ibrutinib compared with obinutuzumab with chlorambucil in untreated chronic lymphocytic leukemia patients with comorbidities in the United Kingdom. Clin Lymphoma Myeloma Leuk. 2018; 18: e131–e142.

59. Smolej L. Therapy of elderly/comorbid patients with chronic lymphocytic leukemia. Curr Pharm Des. 2012; 18: 3399–3405.

60. Simkovic M, Motyckova M, Belada D, et al. Five years of experience with rituximab plus high-dose dexamethasone for relapsed/refractory chronic lymphocytic leukemia. Arch Med Sci. 2016; 12: 421–427.

61. Smolej L, Doubek M, Panovska A, et al. Rituximab in combination with high-dose dexamethasone for the treatment of relapsed/refractory chronic lymphocytic leukemia. Leuk Res. 2012; 36 (10): 1278-82.

62. Ghia P, Pluta A, Wach M, et al. ASCEND: Phase III, randomized trial of acalabrutinib versus idelalisib plus rituximab or bendamustine plus rituximab in relapsed or refractory chronic lymphocytic leukemia. J Clin Oncol. 2020; 38: 2849–2861.

63. Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013; 369: 32–42.

64. Byrd JC, Brown JR, O‘Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014; 371: 213–223.

65. Byrd JC, Furman RR, Coutre SE, et al. Three-year follow-up of treatment-naive and previously treated patients with CLL and SLL receiving single-agent ibrutinib. Blood. 2015; 125: 2497–2506.

66. Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014; 370: 997–1007.

67. Sharman JP, Coutre SE, Furman RR, et al. Final results of a randomized, phase III study of rituximab with or without idelalisib followed by open-label idelalisib in patients with relapsed chronic lymphocytic leukemia. J Clin Oncol. 2019; 37: 1391–1402.

68. Roberts AW, Davids MS, Pagel JM, et al. Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016; 374: 311–322.

69. 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: 768–778.

70. Seymour JF, Mobasher M, Kater AP. Venetoclax-rituximab in chronic lymphocytic leukemia. N Engl J Med. 2018; 378: 2143–2144.

71. Seymour JF, Kipps TJ, Eichhorst BF, et al. Four-year analysis of Murano study confirms sustained benefit of time-limited venetoclax-rituximab (VenR) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Blood. 2019; 134: 355–355.

72. Kater AP, Wu JQ, Kipps T, et al. Venetoclax plus rituximab in relapsed chronic lymphocytic leukemia: 4-year results and evaluation of impact of genomic complexity and gene mutations from the MURANO phase III study. J Clin Oncol. 2020; 38 (34): 4042-4054.

73. Chanan-Khan A, Cramer P, Demirkan F, et al. Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study. Lancet Oncol. 2016; 17: 200–211.

74. Zelenetz AD, Barrientos JC, Brown JR, et al. Idelalisib or placebo in combination with bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukaemia: interim results from a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2017; 18: 297–311.

75. Keating MJ, Flinn I, Jain V, et al. Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood. 2002; 99: 3554–3561.

76. Stilgenbauer S, Zenz T, Winkler D, et al. Subcutaneous alemtuzumab in fludarabine-refractory chronic lymphocytic leukemia: clinical results and prognostic marker analyses from the CLL2H study of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2009; 27: 3994–4001.

77. Fischer K, Cramer P, Busch R, et al. Bendamustine combined with rituximab in patients with relapsed and/or refractory chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2011; 29: 3559–3566.

78. Cuneo A, Follows G, Rigolin GM, et al. Efficacy of bendamustine and rituximab as first salvage treatment in chronic lymphocytic leukemia and indirect comparison with ibrutinib: a GIMEMA, ERIC and UK CLL FORUM study. Haematologica 2018; 103 (7): 1209–1217.

79. Robak T, Dmoszynska A, Solal-Celigny P, et al. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol. 2010; 28: 1756–1765.

80. Badoux XC, Keating MJ, Wang X, et al. Fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy is highly effective treatment for relapsed patients with CLL. Blood. 2011; 117: 3016–3024.

81. Awan FT, Hillmen P, Hellmann A, et al. A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia. Br J Haematol. 2014; 167: 466–477.

82. Durot E, Michallet AS, Lepretre S, Le QH, Leblond V, Delmer A. Platinum and high-dose cytarabine-based regimens are efficient in ultra high/high-risk chronic lymphocytic leukemia and Richter‘s syndrome: results of a French retrospective multicenter study. Eur J Haematol. 2015; 95: 160–167.

83. Wierda WG, Kipps TJ, Mayer J, et al. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2010; 28: 1749–1755.

84. Smolej L, Brychtova Y, Doubek M, et al. Low-dose FCR is a safe and effective treatment option for elderly/comorbid patients with chronic lymphocytic leukemia/small lymphocytic lymphoma. updated results of project Q-Lite by Czech CLL Study Group. Blood. 2014; 124: 4670.

85. Mato AR, Hill BT, Lamanna N, et al. Optimal sequencing of ibrutinib, idelalisib, and venetoclax in chronic lymphocytic leukemia: results from a multicenter study of 683 patients. Ann Oncol. 2017; 28: 1050–1056.

86. Mato AR, Roeker LE, Jacobs R, et al. Assessment of the efficacy of therapies following venetoclax discontinuation in CLL reveals BTK inhibition as an effective strategy. Clin Cancer Res. 2020; 26: 3589–3596.

87. Bottcher S. Minimal residual disease quantification in chronic lymphocytic leukemia: clinical significance and flow cytometric methods. Methods Mol Biol. 2019; 1881: 211–238.

88. Del Giudice I, Raponi S, Della Starza I, et al. Minimal residual disease in chronic lymphocytic leukemia: a new goal? Front Oncol. 2019; 9: 689.

89. Logan AC, Zhang B, Narasimhan B, et al. Minimal residual disease quantification using consensus primers and high-throughput IGH sequencing predicts post-transplant relapse in chronic lymphocytic leukemia. Leukemia. 2013; 27: 1659–1665.

90. Dreger P, Corradini P, Kimby E, et al. Indications for allogeneic stem cell transplantation in chronic lymphocytic leukemia: the EBMT transplant consensus. Leukemia. 2007; 21: 12–17.

91. Dreger P, Schetelig J, Andersen N, et al. Managing high-risk CLL during transition to a new treatment era: stem cell transplantation or novel agents? Blood. 2014; 124: 3841–3849.

92. Dreger P, Michallet M, Bosman P, et al. Ibrutinib for bridging to allogeneic hematopoietic cell transplantation in patients with chronic lymphocytic leukemia or mantle cell lymphoma: a study by the EBMT Chronic Malignancies and Lymphoma Working Parties. Bone Marrow Transplant. 2019; 54: 44–52.

93. Schetelig J, Chevallier P, van Gelder M, et al. Idelalisib treatment prior to allogeneic stem cell transplantation for patients with chronic lymphocytic leukemia: a report from the EBMT Chronic Malignancies Working Party. Bone Marrow Transplant 2020; doi: 10.1038/s41409-020-01069-w. Online ahead of print.

94. Dreger P, Ghia P, Schetelig J, et al. High-risk chronic lymphocytic leukemia in the era of pathway inhibitors: integrating molecular and cellular therapies. Blood. 2018; 132: 892–902.

95. Vitale C, Montalbano MC, Salvetti C, et al. Autoimmune complications in chronic lymphocytic leukemia in the era of targeted drugs. Cancers (Basel). 2020; 12 (2): 282.

96. D‘Arena G, Guariglia R, La Rocca F, et al. Autoimmune cytopenias in chronic lymphocytic leukemia. Clin Dev Immunol. 2013; 2013: 730131.

97. Fattizzo B, Barcellini W. Autoimmune cytopenias in chronic lymphocytic leukemia: focus on molecular aspects. Front Oncol. 2019; 9: 1435.

98. Jeon K, Kim M, Lee J, et al. Immature platelet fraction: A useful marker for identifying the cause of thrombocytopenia and predicting platelet recovery. Medicine (Baltimore). 2020; 99: e19096.

99. Rossi D, Gaidano G. Richter syndrome: molecular insights and clinical perspectives. Hematol Oncol. 2009; 27: 1–10.

100. Parikh SA, Kay NE, Shanafelt TD. How we treat Richter syndrome. Blood. 2014; 123: 1647–1657.

101. Parikh SA, Shanafelt TD. Risk factors for Richter syndrome in chronic lymphocytic leukemia. Curr Hematol Malig Rep. 2014; 9: 294–299.

102. Mauro FR, Chauvie S, Paoloni F, et al. Dia­g­nostic and prognostic role of PET/CT in patients with chronic lymphocytic leukemia and progressive disease. Leukemia. 2015; 29: 1360–1365.

103. Osterborg A, Foa R, Bezares RF, et al. Management guidelines for the use of alemtuzumab in chronic lymphocytic leukemia. Leukemia. 2009; 23: 1980–1988.

104. Smolej L, Prochazka V, Spacek M, et al. Doporučení pro léčbu alemtuzumabem u chronické lymfocytární leukemie. Vnitr Lek 2012; 58: 232–236.

105. Moia R, Diop F, Favini C, Kodipad AA, Gaidano G. Potential of BCL2 as a target for chronic lymphocytic leukemia treatment. Expert Rev Hematol. 2018; 11 (5): 391-402.

106. Gribben JG. Practical management of tumour lysis syndrome in venetoclax-treated patients with chronic lymphocytic leukaemia. Br J Haematol. 2020; 188: 844–851.

107. Tambaro FP, Wierda WG. Tumour lysis syndrome in patients with chronic lymphocytic leukaemia treated with BCL-2 inhibitors: risk factors, prophylaxis, and treatment recommendations. Lancet Haematol. 2020; 7: e168–e176.

108. Oscier D, Dearden C, Eren E, et al. Guidelines on the dia­gnosis, investigation and management of chronic lymphocytic leukaemia. Br J Haematol. 2012; 159: 541–564.

109. Dhalla F, Lucas M, Schuh A, et al. Antibody deficiency secondary to chronic lymphocytic leukemia: should patients be treated with prophylactic replacement immunoglobulin? J Clin Immunol. 2014; 34: 277–282.

110. Shanafelt T. Treatment of older patients with chronic lymphocytic leukemia: key questions and current answers. Hematology Am Soc Hematol Educ Program. 2013; 2013: 158–167.

111. Bokemeyer C, Aapro MS, Courdi A, et al. EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer: 2006 update. Eur J Cancer. 2007; 43: 258–270.

112. Aapro MS, Bohlius J, Cameron DA, et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer. 2011; 47: 8–32.

113. Tsimberidou AM, Wen S, McLaughlin P, et al. Other malignancies in chronic lymphocytic leukemia/small lymphocytic lymphoma. J Clin Oncol. 2009; 27: 904–910.

114. Pospisilova S, Jarosova M, Doubek M. Chronická lymfocytární leukemie – současné využití moderních prognostických a prediktivních faktorů v dia­gnostice. Transfuze Hematol dnes. 2019; 25; 66–71.

115. Flinn IW, Hillmen P, Montillo M, et al. The phase 3 DUO trial: duvelisib vs ofatumumab in relapsed and refractory CLL/SLL. Blood. 2018; 132: 2446–2455.

116. Rogers KA, Huang Y, Ruppert AS, et al. Phase 1b study of obinutuzumab, ibrutinib, and venetoclax in relapsed and refractory chronic lymphocytic leukemia. Blood. 2018; 132: 1568–1572.

117. Banerji V, Anglin P, Christofides A, Doucette S, Laneuville P. Updates from the American Society of Hematology 2019 annual meeting: practice-changing studies in treatment-naive chronic lymphocytic leukemia. Curr Oncol. 2020; 27: e231–e245.

118. Tam CS, Robak T, Ghia P, et al. Zanubrutinib monotherapy for patients with treatment naive chronic lymphocytic leukemia and 17p deletion. Haematologica. 2020; doi: 10.3324/haematol.2020.259432, online ahead of print.

119. Porter DL, Hwang WT, Frey NV, et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015; 7: 303ra139.

120. Mato AR, Thompson MC, Nabhan C, Svoboda J, Schuster SJ. Chimeric antigen receptor T-cell therapy for chronic lymphocytic leukemia: a narrative review. Clin Lymphoma Myeloma Leuk. 2017; 17: 852–856.

121. Scarfo L, Chadzikonstantinou T, Rigolin GM, et al. COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: a joint study by ERIC, the European Research Initiative on CLL, and CLL Campus. Leukemia. 2020; 34 (9): 2354–2363.

122. Mato A, Roeker LE, Lamanna N, et al. Outcomes of COVID-19 in patients with CLL: a multicenter international experience. Blood. 2020; 136 (10): 1134–1143.

123. Rossi D, Shadman M, Condoluci A, et al. How we manage patients with chronic lymphocytic leukemia during the SARS-CoV-2 pandemic. Hemasphere. 2020; 4 (4): e432.

124. NICE 2020. COVID-19 rapid guideline: delivery of systemic anticancer treatments. www.nice.org.uk/guidance/ng161. Last updated 9 November 2020.

125. Jazieh AR, Chan SL, Curigliano G, et al. Delivering cancer care during the COVID-19 pandemic: recommendations and lessons learned from ASCO global webinars. JCO Glob Oncol. 2020; 6: 1461–1471.

126. ASH. COVID-19 and CLL: Frequently Asked Questions. https: //www.hematology.org/covid-19/covid-19-and-cll. Version 4.0; last updated November 17, 2020.

Labels
Haematology Internal medicine Clinical oncology

Article was published in

Transfusion and Haematology Today

Issue 1

2021 Issue 1

Most read in this issue
Topics Journals
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#