Cancer Therapy-associated Lymphoproliferative Disorders: An Under-recognized Type of Immunodeficiency-associated Lymphoproliferative Disorder

Abstract

We describe the clinicopathologic features of 17 patients who had a hematologic malignancy of various types, were treated, and subsequently developed a lymphoproliferative disorder (LPD). There were 10 men and 7 women with a median age of 59 years (range, 36 to 83 y). The primary hematologic neoplasms included: 5 chronic lymphocytic leukemia/small lymphocytic lymphoma, 3 plasma cell myeloma, 2 acute monoblastic leukemia, and 1 case each of mixed-phenotype acute leukemia, chronic myeloid leukemia, splenic marginal zone lymphoma, follicular lymphoma, mantle cell lymphoma, T-cell prolymphocytic leukemia, and peripheral T-cell lymphoma. All patients were treated with chemotherapy with or without therapeutic antibodies; 3 also underwent autologous stem cell transplantation. The mean interval from initiation of therapy for initial hematologic malignancy to onset of LPD was 66 months (range, 3 to 299 mo). Ten (59%) LPDs were extranodal and 7 (41%) involved nodal tissues. The histologic diagnoses included: 8 diffuse large B-cell lymphoma, 4 classical Hodgkin lymphoma, 3 polymorphic LPD, 1 lymphomatoid granulomatosis, and 1 Epstein-Barr virus (EBV) mucocutaneous ulcer. Fourteen cases were EBV. Following the onset of LPD, chemotherapy was administered to 10 (59%) patients. With a median follow-up of 100 months (range, 5 to 328 mo), 8 (47%) patients are alive and 9 (53%) died. One (6%) patient with lymphomatoid granulomatosis underwent spontaneous remission. On the basis of the clinicopathologic features and high prevalence of EBV infection in this cohort, we believe that these LPDs show similarities with other types of immunodeficiency-associated LPDs. We suggest that cancer therapy-associated LPD be included in future classification systems for immunodeficiency-associated LPDs.