Acta Med. 2010, 53: 213-220

https://doi.org/10.14712/18059694.2016.79

How I Treat Elderly or Comorbid Patients with Chronic Lymphocytic Leukemia

Lukáš Smolej

Charles University in Prague, Faculty of Medicine and University Hospital Hradec Králové, 2nd Department of Medicine, Department of Hematology, Czech Republic

Received April 1, 2010
Accepted September 20, 2010

References

1. Abrisqueta P, Pereira A, Rozman C, Aymerich M, Gine E, Moreno C, et al. Improving survival in patients with chronic lymphocytic leukemia (1980–2008): the Hospital Clinic of Barcelona experience. Blood. 2009; 114(10): 2044–50. <https://doi.org/10.1182/blood-2009-04-214346>
2. Altman SJ, Haut A, Cartwright GE, Wintrobe MM. Early experience with p- (N,N-di-2-chloroethyl)-aminophenylbutyric acid (CB 1348), a new chemotherapeutic agent effective in the treatment of chronic lymphocytic leukemia. Cancer. 1956; 9(3): 512–7. <https://doi.org/10.1002/1097-0142(195605/06)9:3<512::AID-CNCR2820090312>3.0.CO;2-O>
3. Bergmann MA, Goebeler ME, Herold M, Emmerich B, Wilhelm M, Ruelfs C, et al. Efficacy of bendamustine in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase I/II study of the German CLL Study Group. Haematologica. 2005; 90(10): 1357–64.
4. Bocchia M, Bigazzi C, Marconcini S et al. Favorable impact of low-dose fludarabine plus epirubicin and cyclophosphamide regimen (FLEC) as treatment for low-grade non-Hodgkin’s lymphomas. Haematologica. 1999; 84(8): 716–20.
5. Bowen DA, Call TG, Jenkins GD et al. Methylprednisolone-rituximab is an effective salvage therapy for patients with relapsed chronic lymphocytic leukemia including those with unfavorable cytogenetic features. Leuk Lymphoma. 2007; 48(12): 2412–7. <https://doi.org/10.1080/10428190701724801>
6. Castro JE, Sandoval-Sus JD, Bole J et al. Rituximab in combination with highdose methylprednisolone for the treatment of fludarabine refractory high-risk chronic lymphocytic leukemia. Leukemia. 2008; 22(11): 2048–53. <https://doi.org/10.1038/leu.2008.214> <PubMed>
7. Catovsky D, Richards S, Matutes E, Oscier D, Dyer MJ, Bezares RF, et al. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet. 2007; 370(9583): 230–9. <https://doi.org/10.1016/S0140-6736(07)61125-8>
8. Cheson BD. Monoclonal antibody therapy of chronic lymphocytic leukemia. Cancer Immunol Immunother. 2006; 55(2): 188–96. <https://doi.org/10.1007/s00262-005-0010-0>
9. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976; 16(1): 31–41. <https://doi.org/10.1159/000180580>
10. Cramer P, Goede V, Jenke P et al. Impact of different chemotherapy regimen in comorbid patients with advanced chronic lymphocytic leukemia: metaanalysis of two phase-III-trials of the German CLL study group. Blood 2006; 108.
11. 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. <https://doi.org/10.1002/(SICI)1097-0142(19991215)86:12<2684::AID-CNCR13>3.0.CO;2-V>
12. Dores GM, Anderson WF, Curtis RE, Landgren O, Ostroumova E, Bluhm EC, et al. Chronic lymphocytic leukaemia and small lymphocytic lymphoma: overview of the descriptive epidemiology. Br J Haematol. 2007; 139(5): 809–19. <https://doi.org/10.1111/j.1365-2141.2007.06856.x>
13. Doubek M, Smolej L, Panovksa A, Brychtova Y, Mayer J. Rituximab in combination with dexamethasone or high-dose methylprednisolone in refractory chronic lymphocytic leukemia. XIII International Workshop on Chronic Lymphocytic Leukemia; Spain, 16–18 October 2009. Haematologica 2009; 94(s3): abstract 7.3.
14. Dungarwalla M, Evans SO, Riley U et al. High dose methylprednisolone and rituximab is an effective therapy in advanced refractory chronic lymphocytic leukemia resistant to fludarabine therapy. Haematologica. 2008; 93(3): 475–6. <https://doi.org/10.3324/haematol.11903>
15. Eichhorst BF, Busch R, Hopfinger G, Pasold R, Hensel M, Steinbrecher C, et al. Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia. Blood. 2006; 107(3): 885–91. <https://doi.org/10.1182/blood-2005-06-2395>
16. Eichhorst BF, Busch R, Schweighofer C, Wendtner CM, Emmerich B, Hallek M. Due to low infection rates no routine anti-infective prophylaxis is required in younger patients with chronic lymphocytic leukaemia during fludarabine-based first line therapy. Br J Haematol. 2007; 136(1): 63–72. <https://doi.org/10.1111/j.1365-2141.2006.06382.x>
17. Eichhorst BF, Busch R, Stilgenbauer S, Stauch M, Bergmann MA, Ritgen M, et al. First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia. Blood. 2009; 114(16): 3382–91. <https://doi.org/10.1182/blood-2009-02-206185>
18. Eichhorst B, Goede V, Hallek M. Treatment of elderly patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2009; 50(2): 171–8. <https://doi.org/10.1080/10428190802688517>
19. 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. <https://doi.org/10.1200/JCO.1998.16.4.1582>
20. Fabbri A, Lenoci M, Gozzetti A, Marotta G, Raspadori D, Forconi F, et al. Lowdose oral fludarabine plus cyclophosphamide in elderly patients with chronic lymphoproliferative disorders. Hematol J. 2004; 5(6): 472–4. <https://doi.org/10.1038/sj.thj.6200563>
21. Fabbri A, Lenoci M, Gozzetti A, Chitarrelli I, Olcese F, Raspadori D, et al. Lowdose oral fludarabine plus cyclophosphamide as first-line treatment in elderly patients with indolent non-Hodgkin lymphoma. Br J Haematol. 2007; 139(1): 90–3. <https://doi.org/10.1111/j.1365-2141.2007.06746.x>
22. Ferrajoli A, O’Brien S, Wierda W et al. Treatment of patients with CLL 70 years old and older: a single center experience of 142 patients. Leuk Lymphoma 2005; 46(Suppl 1): S86 (abstract P95).
23. Ferrajoli A, O’Brien S, Wierda W et al. Lenalidomide as initial treatment of elderly patients with chronic lymphocytic leukemia (CLL). Blood (ASH Annual Meeting Abstracts) 2008; 112: 23 (abstract 45).
24. Ferrajoli A, O’Brien S, Faderl S, Wierda W, Jorgensen J, Keating MJ. The combination of rituximab and GM-CSF as frontline treatment for elderly patients with chronic lymphocytic leukemia. Leuk Lymphoma 2007; 48(Suppl 1): S161 (abstract P 5.03).
25. Fischer K, Stilgenbauer S, Schweighofer CD et al. Bendamustine in Combination with Rituximab (BR) for Patients with Relapsed Chronic Lymphocytic Leukemia (CLL): A Multicentre Phase II Trial of the German CLL Study Group (GCLLSG). Blood (ASH Annual Meeting Abstracts) 2008; 112: Abstract 330.
26. Flinn IW, Neuberg DS, Grever MR, Dewald GW, Bennett JM, Paietta EM, et al. Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997. J Clin Oncol. 2007; 25(7): 793–8. <https://doi.org/10.1200/JCO.2006.08.0762>
27. Foon KA, Boyiadzis M, Land SR et al. Chemoimmunotherapy with low-dose fludarabine and cyclophosphamide and high dose rituximab in previously untreated patients with chronic lymphocytic leukemia. J Clin Oncol. 2009; 27(4): 498–503. <https://doi.org/10.1200/JCO.2008.17.2619>
28. Forconi F, Fabbri A, Lenoci M, Sozzi E, Gozzetti A, Tassi M, et al. Low-dose oral fludarabine plus cyclophosphamide in elderly patients with untreated and relapsed or refractory chronic lymphocytic Leukaemia. Hematol Oncol. 2008; 26(4): 247–51. <https://doi.org/10.1002/hon.868>
29. 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(12): 5446–5456. <https://doi.org/10.1182/blood-2007-06-093906> <PubMed>
30. Hallek M, Fingerle-Rowson G, Fink AM et al. First-Line Treatment with Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Improves Overall Survival (OS) in Previously Untreated Patients (pts) with Advanced Chronic Lymphocytic Leukemia (CLL): Results of a Randomized Phase III Trial On Behalf of An International Group of Investigators and the German CLL Study Group. Blood (ASH Annual Meeting Abstracts) 2009; 114: Abstract 535.
31. Hillmen P, Gribben JG, Follows GA et al. An Open-Label Phase II Study to Investigate the Safety and Efficacy of Rituximab Plus Chlorambucil in Previously Untreated Patients with CD20–Positive B-Cell Chronic Lymphocytic Leukaemia (CLL). Blood (ASH Annual Meeting Abstracts) 2009; 114: abstract 3428.
32. Janssen-Heijnen ML, van Spronsen DJ, Lemmens VE et al. A population-based study of severity of comorbidity among patients with non-Hodgkin’s lymphoma: prognostic impact independent of International prognostic index. Br J Haematol 2005; 129: 597–606. <https://doi.org/10.1111/j.1365-2141.2005.05508.x>
33. Knauf WU, Lissichkov T, Aldaoud A, Liberati A, Loscertales J, Herbrecht R, et al. Phase III randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia. J Clin Oncol. 2009; 27(26): 4378–84. <https://doi.org/10.1200/JCO.2008.20.8389>
34. Lindeman RD. Changes in renal function with aging. Implications for treatment. Drugs Aging. 1992; 2(5): 423–31. <https://doi.org/10.2165/00002512-199202050-00006>
35. Linet MS, Schubauer-Berigan MK, Weisenburger DD, Richardson DB, Landgren O, Blair A, et al. Chronic lymphocytic leukaemia: an overview of aetiology in light of recent developments in classification and pathogenesis. Br J Haematol. 2007; 139(5): 672–86. <https://doi.org/10.1111/j.1365-2141.2007.06847.x>
36. Marotta G, Bigazzi C, Lenoci M, Tozzi M, Bocchia M, Lauria F. Low-dose fludarabine and cyclophosphamide in elderly patients with B-cell chronic lymphocytic leukemia refractory to conventional therapy. Haematologica. 2000; 85(12): 1268–70.
37. Martell RE, Peterson BL, Cohen HJ, Petros WP, Rai KR, Morrison VA, et al. Analysis of age, estimated creatinine clearance and pretreatment hematologic parameters as predictors of fludarabine toxicity in patients treated for chronic lymphocytic leukemia: a CALGB (9011) coordinated intergroup study. Cancer Chemother Pharmacol. 2002; 50(1): 37–45. <https://doi.org/10.1007/s00280-002-0443-5>
38. Muntanola A, Bosch F, Arguis P, Arellano-Rodrigo E, Ayuso C, Gine E, et al. Abdominal computed tomography predicts progression in patients with Rai stage 0 chronic lymphocytic leukemia. J Clin Oncol. 2007; 25(12): 1576–80. <https://doi.org/10.1200/JCO.2006.08.4194>
39. National Cancer Institute: SEER Cancer Statistics Review. Available at http://seer.cancer.gov. Accessed on 10.2.2010.
40. National Cancer Institute: Registry of clinical trials. Available at http://www.cancer. gov/clinicaltrials/search. Accessed on 28.3.2010.
41. Norin S, Kimby E, Lundin J. Tumor burden status evaluated by computed tomography scan is of prognostic importance in patients with chronic lymphocytic leukemia. Med Oncol. 2009 (online early).
42. Piccirillo JF, Tierney RM, Costas I, Grove L, Spitznagel EL Jr. Prognostic importance of comorbidity in a hospital-based cancer registry. JAMA 2004; 291: 2441–2447. <https://doi.org/10.1001/jama.291.20.2441>
43. Plunkett W, Gandhi V, Huang P, Robertson LE, Yang LY, Gregoire V, et al. Fludarabine: pharmacokinetics, mechanisms of action, and rationales for combination therapies. Semin Oncol. 1993; 20(5 Suppl 7): 2–12.
44. Protocol Q-lite of Czech CLL Study Group. Available online at http:// www.cll.cz/studie-granty-projekty/. Accessed on 8.2.2010.
45. Quinn J, Sajir M, Chipperfield K et al. Efficacy of rituximab in combination with steroids in refractory chronic lymphocytic leukaemia. Leuk Lymphoma 2008; 49: 1995–1998. <https://doi.org/10.1080/10428190802340192>
46. Rai KR, Peterson BL, Appelbaum FR, Kolitz J, Elias L, Shepherd L, et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000; 343(24): 1750–7. <https://doi.org/10.1056/NEJM200012143432402>
47. Robak T, Dmoszynska A, Solal-Celigny P, Warzocha K, Loscertales J, Catalano J, 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, ePub online.
48. Robak T, Jamroziak K, Gora-Tybor J, Stella-Holowiecka B, Konopka L, Ceglarek B, et al. Comparison of Cladribine Plus Cyclophosphamide With Fludarabine Plus Cyclophosphamide As First-Line Therapy for Chronic Lymphocytic Leukemia: A Phase III Randomized Study by the Polish Adult Leukemia Group (PALG-CLL3 Study). J Clin Oncol. 2010, ePub online.
49. Robertson LE, O’Brien S, Kantarjian H, Koller C, Beran M, Andreeff M, et al. A 3-day schedule of fludarabine in previously treated chronic lymphocytic leukemia. Leukemia. 1995; 9(9): 1444–9.
50. Shanafelt TD, Lin T, Geyer SM, Zent CS, Leung N, Kabat B, et al. Pentostatin, cyclophosphamide, and rituximab regimen in older patients with chronic lymphocytic leukemia. Cancer 2007; 109: 2291–2298. <https://doi.org/10.1002/cncr.22662>
51. Shvidel L, Shtalrid M, Bairey O et al; Israeli Study Group on CLL. Conventional dose fludarabine-based regimens are effective but have excessive toxicity in elderly patients with refractory chronic lymphocytic leukemia. Leuk Lymphoma. 2003; 44(11): 1947–50. <https://doi.org/10.1080/1042819031000110991>
52. Smolej L. Modern concepts in the treatment of chronic lymphocytic leukemia. Hematology. 2009; 14(5): 249–54. <https://doi.org/10.1179/102453309X446153>
53. Smolej L, Vasova I, Salkova J, et al. Small Lymphocytic Lymphoma (SLL): Retrospective Analysis From the Registry of Czech Lymphoma Study Group. Haematologica 2009; 94 (Suppl 3): S5 (abstract 1.11).
54. Tam CS, O’Brien S, Lerner S, Khouri I, Ferrajoli A, Faderl S, et al. The natural history of fludarabine-refractory chronic lymphocytic leukemia patients who fail alemtuzumab or have bulky lymphadenopathy. Leuk Lymphoma. 2007; 48(10): 1931–9. <https://doi.org/10.1080/10428190701573257>
55. Thurmes P, Call T, Slager S, Zent C, Jenkins G, Schwager S, et al. Comorbid conditions and survival in unselected, newly diagnosed patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2008; 49(1): 49–56. <https://doi.org/10.1080/10428190701724785>
56. Wierda WG, O’Brien S, Wang X, Faderl S, Ferrajoli A, Do KA, et al. Characteristics associated with important clinical end points in patients with chronic lymphocytic leukemia at initial treatment. J Clin Oncol. 2009; 27(10): 1637–43. <https://doi.org/10.1200/JCO.2008.18.1701> <PubMed>
57. Wierda WG, Kipps TJ, Mayer J, Stilgenbauer S, Williams CD, Hellmann A, et al. Ofatumumab As Single-Agent CD20 Immunotherapy in Fludarabine-Refractory Chronic Lymphocytic Leukemia. J Clin Oncol. 2010 (online early).
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