The Utility of Gemcitabine and Vinorelbine in Patients with Blastic NK Lymphoma (CD4+/CD56+ Hematodermic Neoplasm).
Authors: Ellis Leslie R. , Horwitz Steven M. 
Published: October 2019

Background: Blastic NK lymphoma, provisionally renamed CD4+/CD56+ hematodermic neoplasm in the latest WHO-EORTC classification of cutaneous lymphomas, is a rare, recently described malignancy. The derivation of these neoplasms is not completely understood, but it is felt to arise from either an NK or plasmacytoid dendritic cell precursor. Nonetheless, treatments for this aggressive malignancy have generally been in the form of intensive combination chemotherapy adapted from high-grade lymphoma or acute leukemia regimens. Despite initial responses to treatment, patients frequently relapse, with overall survival measured in months. Moreover, the high toxicity of these approaches limits their use in certain patients. Gemcitabine and vinorelbine are two chemotherapy agents with relatively mild side effect profiles and activity against cutaneous and T cell lymphomas. Here we describe two patients with blastic NK lymphoma who, because of advanced age and multiple comorbidities, received treatment with a combination of gemcitabine and vinorelbine (GN). For both patients, complete responses (CRs) were obtained.

Patients and Methods: The first patient was a 73 year-old man with hypertension, recent hemorrhagic stroke with residual hemiparesis, and stable angina who presented with multiple cutaneous nodules along his face, trunk, and extremities. CT and PET scans were negative. Laboratories revealed pancytopenia, and bone marrow biopsy was negative although flow cytometry on the bone marrow aspirate showed increased CD56+ cells. The second patient was a 71 year-old male with poorly controlled diabetes and hypercholesterolemia; he also presented with extensive cutaneous nodules. CT and PET scans showed diffuse hypermetabolic lymphadenopathy; bone marrow was replaced by lymphoma. Skin biopsies from both patients showed large lymphoid cells expressing CD4, CD56, and HLA-DR; neither tumor expressed CD3, CD45RO, or TdT. Cytogenetics were normal for both patients.

Results: Both patients received treatment with gemcitabine 800 mg/m2 and vinorelbine 15 mg/m2 given every two weeks with growth factor support. Both patients experienced significant improvement in their cutaneous lesions after the first cycle of treatment and subsequently obtained a CR by the fifth course. Once in CR, both patients had their chemotherapy schedules reduced to every four weeks to minimize side effects. The first patient had GN discontinued after 13 cycles and remained in CR for 10 months off therapy. He subsequently recurred in the skin, lymph nodes, and bone marrow. He was retreated with GN for an additional 14 cycles to date; he remains in CR nine months later on monthly therapy. The second patient developed recurrent disease in the skin at five months and was switched to alternate therapy.

Conclusion: Blastic NK lymphoma (CD4+/CD56+ hematodermic neoplasm) is an aggressive lymphoma characterized by a poor prognosis and brief responses to intensive combination chemotherapy. Here we report two elderly patients with multiple comorbidities who responded to a mild chemotherapy regimen of GN given every two to four weeks. This regimen was well-tolerated and both patients attained a CR. The high activity in both patients and durability of response in one suggests GN should be considered for elderly patients with blastic NK lymphoma. Moreover, this report raises the possibility of incorporating these agents into other regimens for this rare disease.