Life-Threatening Fungal Infection in Richter Transformation of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Case Report and Brief Review of Literature

Abstract

Chronic lymphocytic leukemia/small lymphocytic lymphoma is an indolent B cell lymphoproliferative malignancy typically affecting the elderly. Clinical outcomes of this condition have steadily improved as a result of advances in therapy. However, an increase in survival is accompanied by increased incidence of Richter transformation into an aggressive lymphoma. We present one such case and delve into its risk factors and associated complications. Exposure to increased lines of treatment appears to be a contributing factor in transformation, such that those with fewer than two lines of treatment are considered to have a lower risk of transformation. Fever, rapid lymph node involvement and drastic increases in lactate dehydrogenase, as seen in our patient, are concerning for transformation and treatment options include chemotherapy versus novel agent therapy. However, patients receiving therapy are at risk for adverse outcomes such as invasive infections, particularly in those receiving consolidation chemotherapy. Fungal infections such as Aspergillus and Candida are gaining prominence in the setting of neutropenia which adversely impact survival, but are underreported. Efforts to improve outcomes may include consideration of growth factor therapy in neutropenic patients and continuing to be vigilant for early signs of infection.

A Systematic Review on the Prevention and Control of Opportunistic Infections in Patients With Chronic Lymphocytic Leukemia Complicated by Richter’s Transformation

“…CLL patients are regularly at risk for infection and related complications by the immunodeficiency that is inherent in the disease itself. Immunosuppression relative to the development of CLL can be attributed to different causative factors, one of the most prominent of which is hypogammaglobulinemia, which is a marker of the immune system’s inability to produce immunoglobulin, the antibodies that are vital to fighting both viral and bacterial infections [ 5 , 11 ]. Infections that impact patients with “early, untreated CLL” are those that are related to hypogammaglobulinemia (HGG) and generally confined to “infections by encapsulated bacteria” [ 16 ].…”

“…At the same time, however, they have contributed to adverse outcomes. Consider, for example, that therapeutic advances and enhancements have improved clinical outcomes, including an increase in survival rates but the increase in longevity has allowed some CLL patients to live long enough to experience the development of RT in the form of aggressive lymphomas [ 5 ]. What is especially compelling about the manner in which the therapies used to treat CLL/CLL-RT contribute to the frequency and type of infections that can affect this patient population.…”

“…Treatment, however, is critical if and when the CLL patient progresses to RT [ 5 ]. It should be noted as well that, once a therapeutic option is initiated, for example, ibrutinib, even a temporary pause in its course can work to instigate the “release of inhibition of B-cell receptor signaling” and induce RT [ 5 ].…”

“…Treatment, however, is critical if and when the CLL patient progresses to RT [ 5 ]. It should be noted as well that, once a therapeutic option is initiated, for example, ibrutinib, even a temporary pause in its course can work to instigate the “release of inhibition of B-cell receptor signaling” and induce RT [ 5 ]. Nevertheless, CLL patients are in an immunosuppressed state regardless of stage and incidence of RT, with any difference in how the prevention and control of infection are meted out in its progression being dependent on the initiation of cytotoxic therapies and the incidence of RT, which diminishes immune-competence even further [ 6 ].…”

“…Table 1 enumerates the individual characteristics of the final included reports for this review article [ 5 , 8 - 15 ].…”