Download PDF
Open Access
CC BY 4.0 · Brazilian Journal of Oncology 2018; 14(49): 1-6
DOI: 10.5935/1806-6054.20180002
REVIEW ARTICLES

Chronic Lymphocytic Leukemia and solid and hematological second neoplasms: a real association?

Leucemia Linfóide Crônica e segundos neoplasmas sólidos e hematológicos: uma associação real?

Authors

  • Arthur Youssif Mota Arabi

    1   University Hospital of Brasilia, Internal Medicine - Brasilia - Federal District - Brazil

  • Vitória Espíndola Leite Borges

    1   University Hospital of Brasilia, Internal Medicine - Brasilia - Federal District - Brazil

  • Fernando Sérgio Blumm Ferreira

    1   University Hospital of Brasilia, Internal Medicine - Brasilia - Federal District - Brazil
    2   Hospital Sírio Libanês, Center of Oncology - Brasília - Federal District - Brazil

  • Flávia Dias Xavier

    1   University Hospital of Brasilia, Internal Medicine - Brasilia - Federal District - Brazil
    2   Hospital Sírio Libanês, Center of Oncology - Brasília - Federal District - Brazil

Financial support: none to declare.
Further Information
  Permissions and Reprints All articles of this category

ABSTRACT

The Chronic Lymphocytic Leukemia is the most common cause of Leukemia in adults, corresponding to 30% of the total amount of the cases of leukemia diagnosed nowadays. One of the greatest challenges regarding its clinical management is related to the greater risk of developing secondary diseases, in especial the appearance of hematological and solid neoplasms. It is thought that the immunosuppression induced by the leukemia and by the chemotherapeutic treatments, the genetic features intrinsic to each individual, and some risk factors (such as smoking and solar exposure) have a key role in facilitating the appearance of those secondary malignancies. The patients with leukemia need to go through a more careful follow-up, intending to monitor the emergence and treatment of those possible secondary malignancies, in order to achieve a better prognosis and a better quality of life.

RESUMO

A Leucemia Linfóide Crônica (LLC) constitui a forma leucêmica mais comum em adultos, correspondendo a 30% do total de casos de leucemia diagnosticados atualmente. Um dos grandes desafios relacionados a seu manejo clínico diz respeito ao maior risco de desenvolvimento de doenças secundárias, dentre as quais se destacam os neoplasmas sólidos e hematológicos. Estima-se que a imunossupressão induzida pela própria leucemia e pelos tratamentos quimioterápicos, as características genéticas intrínsecas a cada indivíduo e alguns fatores de risco (como tabagismo e exposição solar) tenham papel atuante na facilitação do aparecimento desses segundos neoplasms. Os pacientes portadores de LLC precisam passar por um acompanhamento clínico mais próximo e cauteloso, na intenção de monitorar o aparecimento e tratamento de eventuais segundas malignidades, a fim de se obter um melhor prognóstico e uma qualidade de vida mais adequada.

Keywords:

Leukemia - Lymphocytic - Chronic - B-Cell - Hematologic Neoplasms - Neoplasms - Secondary Primary

Descritores:

Leucemia - Linfocítica - Cronica - Célula B - Neoplasias Hematológicas - Neoplasias - Primária Secundária


Publication History

Received: 28 October 2018

Accepted: 06 December 2018

Article published online:
07 March 2025

© 2022. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

 

  • REFERENCES

  • Rossi D, Gaidano G.. The clinical implications of gene mutations in chronic lymphocytic leukaemia. Br J Cancer 2016; 114 (08) 849-854
    PubMedSearch in Google Scholar
  • Robak T, Stilgenbauer S, Tedeschi A.. Front-line treatment of CLL in the era of novel agents. Cancer Treat Rev 2017; 53: 70-78
    PubMedSearch in Google Scholar
  • Melton MF, Pearlman AN.. Chronic lymphocytic leukemia of the oropharyngeal cavity and paranasal sinuses: a case series and literature review. Int Forum Allergy Rhinol 2015; 5 (11) 1055-1058
    PubMedSearch in Google Scholar
  • Visentin A, Imbergamo S, Gurrieri C, Frezzato F, Trimarco V, Martini V. et al Major infections, secondary cancers and autoimmune diseases occur in different clinical subsets of chronic lymphocytic leukaemia patients. Eur J Cancer 2017; 72: 103-111
    PubMedSearch in Google Scholar
  • Tsimberidou AM, Wen S, McLaughlin P, O'Brien S, Wierda WG, Lerner S. et al Other malignancies in chronic lymphocytic leukemia/ small lymphocytic lymphoma. J Clin Oncol 2009; 27 (06) 904-910
    PubMedSearch in Google Scholar
  • Maurer C, Langerbeins P, Bahlo J, Cramer P, Fink AM, Pflug N. et al Effect of first-line treatment on second primary malignancies and Richter's transformation in patients with CLL. Leukemia 2016; 30 (10) 2019-2025
    PubMedSearch in Google Scholar
  • Morton LM, Curtis RE, Linet MS, Bluhm EC, Tucker MA, Caporaso N. et al Second malignancy risks after non-Hodgkin's lymphoma and chronic lymphocytic leukemia: differences by lymphoma subtype. J Clin Oncol 2010; 28 (33) 4935-4944
    PubMedSearch in Google Scholar
  • Molica S.. Second neoplasms in chronic lymphocytic leukemia: incidence and pathogenesis with emphasis on the role of different therapies. Leuk Lymphoma 2005; 46 (01) 49-54
    PubMedSearch in Google Scholar
  • Kyasa MJ, Hazlett L, Parrish RS, Schichman SA, Zent CS.. Veterans with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) have a marked ly increased rate of second malignancy, which is the most common cause of death. Leuk Lymphoma 2004; 45 (03) 507-513
    PubMedSearch in Google Scholar
  • 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 (08) 2454-2460
    PubMedSearch in Google Scholar
  • Royle JA, Baade PD, Joske D, Girschik J, Fritschi L.. Second cancer incidence and cancer mortality among chronic lymphocytic leukaemia patients: a population-based study. Br J Cancer 2011; 105 (07) 1076-1081
    PubMedSearch in Google Scholar
  • Falchi L, Vitale C, Keating MJ, Lerner S, Wang X, Elhor Gbito KY. et al Incidence and prognostic impact of other cancers in a population of longterm survivors of chronic lymphocytic leukemia. Ann Oncol 2016; 27 (06) 1100-1106
    PubMedSearch in Google Scholar
  • Robak T.. Second malignancies and Richter's syndrome in patients with chronic lymphocytic leukemia. Hematology 2004; 9 (5-6): 387-400
    PubMedSearch in Google Scholar
  • Robak E, Robak T.. Skin lesions in chronic lymphocytic leukemia. Leuk Lymphoma 2007; 48 (05) 855-865
    PubMedSearch in Google Scholar
  • Solomon BM, Rabe KG, Slager SL, Brewer JD, Cerhan JR, Shanafelt TD.. Overall and cancer-specific survival of patients with breast, colon, kidney, and lung cancers with and without chronic lymphocytic leukemia: a SEER population-based study. J Clin Oncol 2013; 31 (07) 930-937
    PubMedSearch in Google Scholar
  • Hisada M, Biggar RJ, Greene MH, Fraumeni Jr JF, Travis LB. Solid tumors after chronic lymphocytic leukemia. Blood 2001; 98 (06) 1979-1981
    PubMedSearch in Google Scholar
  • Benjamini O, Jain P, Trinh L, Qiao W, Strom SS, Lerner S. et al Second cancers in patients with chronic lymphocytic leukemia who received frontline fludarabine, cyclophosphamide and rituximab therapy: distribution and clinical outcomes. Leuk Lymphoma 2015; 56 (06) 1643-1650
    CrossrefPubMedSearch in Google Scholar
  • Hisada M, Biggar RJ, Greene MH, Fraumeni Jr JF, Travis LB. Solid tumors after chronic lymphocytic leukemia. Blood 2001; 98 (06) 1979-1981
    PubMedSearch in Google Scholar
  • Tabuteau S, Garidi R, Fernandes J, Vaida I, Capiod JC, Legrand S. et al Fludarabine (FAMP) and risk of occurrence of Richter's syndrome among B-CLL. Blood 2000; 96: 295B
    Search in Google Scholar
  • Thornton PD, Bellas C, Santon A, Shah G, Pocock C, Wotherspoon AC. et al Richter's transformation of chronic lymphocytic leukemia: The possible role of fludarabine and the Epstein-Barr virus in its pathogenesis. Leuk Res 2005; 29 (04) 389-395
    PubMedSearch in Google Scholar
  • Mauro FR, Foa R, Giannarelli D, Cordone I, Crescenzi S, Pescarmona E. et al Clinical characteristics and outcome of young chronic lymphocytic leukemia patients: a single institution study of 204 cases. Blood 1999; 94 (02) 448-454
    PubMedSearch in Google Scholar
  • Maddocks-Christianson K, Slager SL, Zent CS, Reinalda M, Call TG, Habermann TM. et al Risk factors for development of a second lymphoid malignancy in patients with chronic lymphocytic leukaemia. Br J Haematol 2007; 139 (03) 398-404
    PubMedSearch in Google Scholar
  • Morrison VA, Rai KR, Peterson BL, Kolitz JE, Elias L, Appelbaum FR. et al Therapy-related myeloid leukemias are observed in patients with chronic lymphocytic leukemia after treatment with fludarabine and chlorambucil: results of an intergroup study, cancer and leukemia group B 9011. J Clin Oncol 2002; 20 (18) 3878-3884
    PubMedSearch in Google Scholar
  • Dighiero G, Maloum K, Desablens B, Cazin B, Navarro M, Leblay R. et al Chlorambucil in indolent chronic lymphocytic leukemia. French Cooperative Group on Chronic Lymphocytic Leukemia. N Engl J Med 1998; 338 (21) 1506-1514
    PubMedSearch in Google Scholar
  • Fischer K, Bahlo J, Fink AM, Goede V, Herling CD, Cramer P. et al Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood 2016; 127 (02) 208-215
    CrossrefPubMedSearch in Google Scholar
  • Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J. et al International Group of Investigators, German Chronic Lymphocytic Leukaemia Study Group. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 2010; 376 (9747) 1164-1174
    PubMedSearch in Google Scholar
  • Brown J, O'Brien S, Kingsley CD, Eradat H, Pagel JM, Lymp J. et al Obinutuzumab plus fludarabine/ cyclophosphamide or bendamustine in the initial therapy of CLL patients: the phase 1b GALTON trial. Blood 2015; 125 (18) 2779-2785
    PubMedSearch in Google Scholar
  • Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM. et al Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med 2014; 370 (12) 1101-1110
    PubMedSearch in Google Scholar
  • Al-Sawaf O, Fischer K, Engelke A, Pflug N, Hallek M, Goede V.. Obinutuzumab in chronic lymphocytic leukemia: design, development and place in therapy. Drug Des Devel Ther 2017; 11: 295-304
    PubMedSearch in Google Scholar
  • Tobinai K, Klein C, Oya N, Fingerle-Rowson G. A. Review of Obinutuzumab (GA101), a Novel Type II Anti- CD20 Monoclonal Antibody, for the Treatment of Patients with B-Cell Malignancies. Adv Ther 2017; 34 (02) 324-356
    PubMedSearch in Google Scholar
  • Jain P, O'Brien S.. Richter's transformation in chronic lymphocytic leukemia. Oncology (Williston Park) 2012; 26 (12) 1146-1152
    PubMedSearch in Google Scholar
  • Jamroziak K, Tadmor T, Robak T, Polliack A.. Richter syndrome in chronic lymphocytic leukemia: updates on biology, clinical features and therapy. Leuk Lymphoma 2015; 56 (07) 1949-1958
    PubMedSearch in Google Scholar
  • Giles FJ, O'Brien SM, Keating MJ.. Chronic lymphocytic leukemia in (Richter's) transformation. Semin Oncol 1998; 25 (01) 117-125
    PubMedSearch in Google Scholar
  • Schöllkopf C, Rosendahl D, Rostgaard K, Pipper C, Hjalgrim H. et al Risk of second cancer after chronic lymphocytic leukemia. Int J Cancer 2007; 121 (01) 151-156
    PubMedSearch in Google Scholar
  • Nakamura N, Abe M.. Richter syndrome in B cell chronic lymphocytic leukemia. Pathol Int 2003; 53 (04) 195-203
    PubMedSearch in Google Scholar
  • Lazzarino M, Orlandi E, Baldanti F, Furione M, Pagnucco G, Astori C. et al The immunosuppression and potential for EBV reactivation of fludarabine combined with cyclophosphamide and dexamethasone in patients with lymphoproliferative disorders. Br J Haematol 1999; 107 (04) 877-882
    PubMedSearch in Google Scholar
  • Kanzler H, Küppers R, Helmes S, Wacker HH, Chott A, Hansmann ML. et al Hodgkin and ReedSternberg-like cells in B-cell chronic lymphocytic leukemia represent the outgrowth of single germinal-center B-cell-derived clones: potential precursors of Hodgkin and Reed-Sternberg cells in Hodgkin's disease. Blood 2000; 95 (03) 1023-1031
    PubMedSearch in Google Scholar
  • Robak T, Blonski JZ, Gora-Tybor J, Kasznicki M, Konopka L, Ceglarek B. et al Second malignancies and Richter's syndrome in patients with chronic lymphocytic leukaemia treated with cladribine. Eur J Cancer 2004; 40 (03) 383-389
    PubMedSearch in Google Scholar
  • Ito S, Fujiwara SI, Mashima K, Umino K, Minakata D, Nakano H. et al Development of acute myeloid leukemia in patients with untreated chronic lymphocytic leukemia. Ann Hematol 2017; 96 (05) 719-724
    PubMedSearch in Google Scholar