Tumor Lysis Syndrome Caused by Unrecognized Richter’s Transformation of Chronic Lymphocytic Leukemia: Treatment With Venetoclax for Suspected Disease Progression

Abstract

Richter's transformation (RT) is defined as the transition of chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) into an aggressive lymphoma. The conversion generally leads to diffuse large B-cell lymphoma (DLBCL), but more aggressive forms such as Hodgkin lymphoma (HL) can also occur. RT is a rare complication of CLL. RT can be confused with CLL progression. Its identification is crucial because the management of lymphoma and CLL differ from each other. Furthermore, the use of certain agents for CLL such as venetoclax increases the risk of tumor lysis syndrome (TLS) in neoplasms with rapid replication such as DLBCL or CLL with hyperleukocytosis (blast crisis). We present the case of a 76-year-old man with a history of CLL on chemotherapy who developed fatigue, malaise, night sweats, chills, and unintentional weight loss for which he was started on treatment with venetoclax due to suspected clinical progression of his disease. The patient developed TLS, requiring hospitalization, and he was found to have an acute blast crisis. Also, his CLL was found to have been transformed into an aggressive DLBCL. This case highlights the importance of differentiating a true progression of CLL from RT into an aggressive lymphoma given that treatment would be different for the two and the prognosis with the transformation is worse.

Tumor Lysis Syndrome: Introduction of a Cutaneous Variant and a New Classification System

“…Systemic tumor lysis syndrome b [1,2, Spontaneous (idiopathic) c [1,2,[6][7][8][10][11][12][13][14][15][16][17][18][19][20][21][22][23] Hematologic malignancies [1,6,10,[12][13][14][15] Solid tumors [2,7,8,10,11,[15][16][17][18][19][20][21][22][23] Therapy-associated d [1,2,[9][10][11]15,17,20,21,[23]…”

“…There is lysis of the tumor cells following the initiation of malignancy-directed therapy. The treatments associated with the subsequent development of systemic tumor lysis syndrome include chemotherapy, corticosteroids, embolization, immunotherapy, interferon, monoclonal antibodies, radiotherapy, surgery, and tamoxifen [1,2,[9][10][11]15,17,20,21,[23][24][25][26].…”

“…Subsequently, in 1977, the first patient with solid tumor-associated tumor lysis syndrome was described [ 8 ]. In both settings, tumor lysis syndrome is typically associated with a rapidly proliferating malignancy in which there is widespread disease and marked sensitivity to antineoplastic therapy [ 1 , 2 , 9 , 10 ].…”

“…Indeed, the reported incidence has ranged from 42% to 4%. However, an increased awareness by oncologists of therapy-associated systemic tumor lysis syndrome and their use of preventative measures resulted in a significant decrease in the incidence of this subtype of systemic tumor lysis [ 1 , 2 , 9 , 10 ].…”

“…Hence, patients with either high-grade, aggressive, and bulky lymphomas (such as Burkitt lymphoma and acute lymphoblastic lymphoma) or acute leukemias (such as acute lymphocytic leukemia or acute myelogenous leukemia with white blood cell counts greater than 100,000/µL) are more susceptible to therapy-associated systemic tumor lysis syndrome. In addition, dehydration and diminished kidney function (which may be more common in older individuals) have also been associated with an increased risk of systemic tumor lysis syndrome developing after malignancy-directed therapy has been initiated [ 1 , 2 , 9 , 10 ].…”