ABSTRACT
Background: Gray zone lymphoma (GZL) is a rare lymphoma subtype characterized by features intermediate between diffuse large B-cell lymphoma (DLBCL) and classic Hodgkin lymphoma (cHL). The optimal first-line treatment for GZL remains undefined, particularly for patients with poor performance status or baseline organ impairment. Brentuximab vedotin (BV), a targeted therapy that binds to CD30, a TNFR superfamily member involved in NF-kB signaling, has shown promise in the treatment of CD30-positive lymphomas. However, its use in GZL, especially in patients with severe liver impairment, has not been reported previously. Case description: We present a case of a 37-year-old male with GZL and severe liver impairment at initial presentation. The patient initially received monotherapy with BV, which resulted in a marked improvement in liver enzymes and bilirubin levels. Subsequently, combination cytotoxic chemotherapy consisting of dose-adjusted etoposide, prednisone, cyclophosphamide, and doxorubicin (DA-EP_CH) was added. Repeat imaging revealed near complete resolution of lymphadenopathy and significant reduction in hepatosplenomegaly. The patient completed a full course of chemotherapy and achieved a complete response. Follow-up examinations showed no evidence of recurrent disease, and the patient resumed full-time work. Discussion: GZL poses diagnostic challenges due to its overlapping features with DLBCL and cHL. Accurate diagnosis relies on comprehensive histopathological evaluation, immunophenotyping, and molecular analysis. The optimal first-line treatment for GZL remains uncertain. BV shows promise as an addition to chemotherapy in GZL, even in the presence of severe liver impairment. The molecular pathogenesis of GZL is complex and heterogeneous, frequently involving aberrant NF-kB signaling and impaired apoptosis regulation via loss of TP53 expression. Understanding the underlying molecular mechanisms is essential for developing targeted therapies and identifying predictive biomarkers for treatment response. Conclusion: This case demonstrates the successful use of BV as a bridge to cytotoxic chemotherapy in a GZL patient with severe liver impairment, highlighting its potential safety and efficacy even in the setting of end-organ failure. Further investigation is warranted to define optimal treatment strategies, identify predictive biomarkers, and improve outcomes for patients with this rare and challenging lymphoma subtype.
ABSTRACT
A 49-year-old male presented to his physician with three weeks of dyspnea, dry cough, and fever. He did not respond to antibiotics and corticosteroids. He presented to the emergency department with worsening symptoms, where blood work revealed severe anemia, leukocytosis, thrombocytopenia, and 61% blasts on peripheral smear. Bone marrow biopsy showed acute myeloid leukemia (AML). While the results of other studies were awaited, treatment was begun with 7+3 induction (cytarabine and daunorubicin). Karyotyping returned positive for the BCR-ABL1 fusion gene (Philadelphia chromosome), near-tetraploidy, and 5q deletion. Follow-up bone marrow biopsy revealed residual disease (12% blasts). Re-induction was initiated with 5+2 cytarabine and daunorubicin with the addition of dasatinib. Subsequent bone marrow biopsies revealed minimal residual disease and BCR-ABL on polymerase chain reaction (PCR). The patient was placed on dasatinib maintenance and later switched to nilotinib. This case demonstrates the simultaneous presence of rare cytogenetic abnormalities in AML. It also discusses the successful utilization of tyrosine kinase inhibitors (TKIs) in the treatment of BCR-ABL-positive AML, as there are no established guidelines.
