Hodgkin transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma

  • Miodrag Vučić University Clinical Center Niš, Hematology, Allergology, and Clinical Immunology Clinic, Niš, Serbia ; University of Niš, Faculty of Medicine, Niš, Serbia
  • Božidar Lilić University Clinical Center Niš, Hematology, Allergology, and Clinical Immunology Clinic, Niš, Serbia
  • Slavica Stojnev University of Niš, Faculty of Medicine, Niš, Serbia
  • Miljan Krstić University of Niš, Faculty of Medicine, Niš, Serbia
Keywords: antineoplastic combined chemotherapy protocols;, immunohistochemistry;, histological techniques;, hodgkin disease;, leukemia, lymphocytic, chronic, b-cell;, multidetector computed tomography;, treatment outcome

Abstract


Introduction. In rare cases, chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma may transform into Hodgkin lymphoma, with about a hundred cases reported in the literature so far. We present a case of the Hodgkin variant of Richter transformation. Case report. After a one-year watch and wait period, a 60-year-old male with CLL developed B symptoms, generalized lymphadenopathy, and splenomegaly. Upon initial staging (Binet B/Rai 3), he was started on fludarabine, cyclophosphamide, and rituximab (FCR) regimen. After the third cycle of treatment, the right-sided axillary lymphadenopathy persisted and became painful, while the dimensions of the remaining organs affected by the disease decreased. Upon the finalization of the final sixth FCR cycle, the painful right-sided axillary lymphadenopathy persisted (though partially decreasing in size), with the development of local redness and swelling. A biopsy of the residual axillary node was performed, which revealed disease transformation into Hodgkin lymphoma. Upon multislice computed tomography-based staging (IV E clinical stage) and prognostic assessment (unfavorable prognosis), it was decided that the treatment be continued with doxorubicin, vinblastine, dacarbazine (AVD) regimen. The presented patient died two months after the diagnosis of Hodgkin transformation (HT) was established during the initial cycle of AVD. Conclusion. Although CLL is an indolent malignancy, in rare cases of HT, the prognosis is largely dismal. The available treatment strategies demonstrate suboptimal results, although novel immunotherapies may change the landscape of HT therapy in the near future.

Author Biographies

Miodrag Vučić, University Clinical Center Niš, Hematology, Allergology, and Clinical Immunology Clinic, Niš, Serbia ; University of Niš, Faculty of Medicine, Niš, Serbia

First author of the case report "Hodgkin Transformation of Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma - A Case Report"

Božidar Lilić, University Clinical Center Niš, Hematology, Allergology, and Clinical Immunology Clinic, Niš, Serbia

Second author and the corresponding author of the case report "Hodgkin Transformation of Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma - A Case Report"

References

Eichhorst B, Robak T, Montserrat E, Ghia P, Niemann CU, Kater AP, et al. Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2021; 32(1): 23–33.

Wadhwa PD, Morrison VA. Infectious complications of chronic lymphocytic leukemia. Semin Oncol 2006; 33(2): 240–9.

Zent CS, Kay NE. Autoimmune complications in chronic lymphocytic leukaemia (CLL). Best Pract Res Clin Haematol 2010; 23(1): 47–59.

Kósa F, Nečasová T, Špaček M, Giannopoulos K, Hus I, Jurková T, et al. Secondary malignancies and survival of FCR-treated patients with chronic lymphocytic leukemia in Central Europe. Cancer Med 2023; 12(2): 1961–71.

Condoluci A, Rossi D. Biology and Treatment of Richter Transformation. Front Oncol 2022; 12: 829983.

Tsimberidou AM, Keating MJ. Richter syndrome: biology, incidence, and therapeutic strategies. Cancer 2005; 103(2): 216–28.

Parikh SA, Habermann TM, Chaffee KG, Call TG, Ding W, Leis JF, et al. Hodgkin transformation of chronic lymphocytic leukemia: Incidence, outcomes, and comparison to de novo Hodgkin lymphoma. Am J Hematol 2015; 90(4): 334–8.

Gupta N, Mittal A, Duggal R, Dadu T, Agarwal A, Handoo A. Hodgkin Variant of Richter΄s Transformation in Chronic Lymphocytic Leukemia (CLL): An Illustrative Case Report and Literature Review. Int J Hematol Oncol Stem Cell Res 2021; 15(4): 249–54.

Richter MN. Generalized Reticular Cell Sarcoma of Lymph Nodes Associated with Lymphatic Leukemia. Am J Pathol 1928; 4(4): 285–92.7.

Briski R, Taylor J. Treatment of richter transformation of chronic lymphocytic leukemia in the modern era. Cancers 2023; 15(6): 1857.

Janjetovic S, Bernd HW, Bokemeyer C, Fiedler W. Hodgkin΄s lymphoma as a rare variant of Richter΄s transformation in chronic lymphocytic leukemia: A case report and review of the literature. Mol Clin Oncol 2016; 4(3): 390–2.

Arruga F, Gyau BB, Iannello A, Vitale N, Vaisitti T, Deaglio S. Immune Response Dysfunction in Chronic Lymphocytic Leukemia: Dissecting Molecular Mechanisms and Microenvironmental Conditions. Int J Mol Sci 2020; 21(5): 1825.

Olivier M, Hollstein M, Hainaut P. TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb Perspect Biol 2010; 2(1): a001008.

Mata E, Fernández S, Astudillo A, Fernández R, García-Cosío M, Sánchez-Beato M, et al. Genomic analyses of microdissected Hodgkin and Reed-Sternberg cells: mutations in epigenetic regulators and p53 are frequent in refractory classic Hodgkin lymphoma. Blood Cancer J 2019; 9(3): 34.

Weniger MA, Küppers R. Molecular biology of Hodgkin lymphoma. Leukemia 2021; 35(4): 968–81.

Stephens DM, Boucher K, Kander E, Parikh SA, Parry EM, Shadman M, et al. Hodgkin lymphoma arising in patients with chronic lymphocytic leukemia: outcomes from a large multi-center collaboration. Haematologica 2021; 106(11): 2845–52.

King RL, Gupta A, Kurtin PJ, Ding W, Call TG, Rabe KG, et al. Chronic lymphocytic leukemia (CLL) with Reed-Sternberg-like cells vs Classic Hodgkin lymphoma transformation of CLL: does this distinction matter? Blood Cancer J 2022; 12(1): 18.

Mouhssine S, Gaidano G. Richter syndrome: from molecular pathogenesis to druggable targets. Cancers 2022; 14(19): 4644.

Buckley T, Inamdar A, Mikhail NH, Loo A, Cohen S. Rare Richter Transformation of Chronic Lymphocytic Lymphoma to Hodgkin Lymphoma. Am J Case Rep 2021; 22: e932904.

Khan A, Hill JM, MacLellan A, Loeb E, Hill NO, Thaxton S. Improvement in delayed hypersensitivity in Hodgkin's disease with transfer factor: lymphapheresis and cellular immune reac-tions of normal donors. Cancer 1975; 36(1): 86–9.

Eichenauer DA, Aleman BMP, André M, Federico M, Hutchings M, Illidge T, et al. Hodgkin lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2018; 29(Suppl 4): iv19–29.

Mauro FR, Galieni P, Tedeschi A, Laurenti L, Del Poeta G, Reda G, et al. Factors predicting survival in chronic lymphocytic leukemia patients developing Richter syndrome transformation into Hodgkin lymphoma. Am J Hematol 2017; 92(6): 529–35.

Taneja A, Jones J, Pittaluga S, Maric I, Farooqui M, Ahn IE, et al. Richter transformation to Hodgkin lymphoma on Bruton's ty-rosine kinase inhibitor therapy. Leuk Lymphoma 2019; 60(2): 519–22.

Republic Fund for Health Insurance. The rulebook on the list of medicines that are prescribed and issued at the expense of compulsory health insurance fund. Official Gazette of the Republic of Serbia 2022; p. 378. (Serbian)

Tsimberidou AM, O΄Brien S, Kantarjian HM, Koller C, Hagemeister FB, Fayad L, et al. Hodgkin transformation of chronic lymphocytic leukemia: the M. D. Anderson Cancer Center experience. Cancer 2006; 107(6): 1294–302.

Hasenclever D, Diehl V. A prognostic score for advanced Hodgkin's disease. International Prognostic Factors Project on Advanced Hodgkin's Disease. N Engl J Med 1998; 339(21): 1506–14.

Reinert T, Baldotto CS, Nunes FAP, Scheliga AA. [Internet] Bleomycin-Induced Lung Injury [cited on 2024 Apr 15]. J Cancer Res 2013; 9. Available from: https://www.hindawi.com/journals/jcr/2013/480608/

Evens AM, Hong F, Gordon LI, Fisher RI, Bartlett NL, Connors JM, et al. The efficacy and tolerability of adriamycin, bleomy-cin, vinblastine, dacarbazine and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American intergroup trial E2496. Br J Haematol 2013; 161(1): 76–86.

Published
2024/08/02
Section
Case report