Adult Lymphoma-Associated Hemophagocytic Lymphohistiocytosis: A Clinical Case Series in a Predominantly Hispanic Cohort

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a systemic inflammation disorder secondary to immune dysregulation. Patients may present with fevers, splenomegaly, bone marrow failure and hemophagocytosis, among other clinical and laboratory findings. Lymphoma-associated HLH (LA-HLH) is a puzzling diagnosis given both conditions overlapping presentation. There are currently no established treatment guidelines for LA-HLH. We conducted a retrospective search of the tumor registry and pathology database at the University of Miami/Jackson Memorial Hospital using Pathology Laboratory Information System (LIS) and natural language search. We identified adult patients with a combined diagnosis of lymphoma and HLH between January 2008 and July 2018. Data from nine LA-HLH patients were identified and reviewed. The median age was 53 years (range 19 - 73), with 78% of cases of Hispanic origin. Lymphoma subtypes consisted of six T-cell/NK-cell neoplasms: two peripheral T-cell lymphoma (PTCL), not otherwise specified (NOS); two Epstein-Barr virus (EBV)+ extranodal NK-/T-cell lymphomas; one EBV+, CD8⁺, PTCL, NOS; one EBV+, post-transplant lymphoproliferative disorder-anaplastic large cell lymphoma, anaplastic lymphoma kinase negative (PTLD ALCL ALK-); and three B-cell neoplasms: one EBV+ diffuse large B-cell lymphoma (DLBCL); two DLBCL, NOS. HLH and lymphoma were diagnosed simultaneously in six out of nine cases. Hemophagocytosis phenomena were demonstrated in seven out of nine cases. Treatment consisted of combined HLH and lymphoma therapies in four cases, while lymphoma-directed therapy was applied to four patients; another case was treated with a modified version of the HLH-1994 protocol. Overall, a total of five cases were exposed to HLH-directed regimens (HLH-1994/2004). Three patients had refractory LA-HLH and entered hospice care, whereas another three cases succumbed to treatment-related complications. Of the seven cases that were evaluable for lymphoma response, four cases (57%) achieved complete response (CR), and three of them (43%) were alive with no evidence of recurrence at 10, 16 and 52 months as of the last contact. Herein, we describe our unique experience of an LA-HLH case series in a predominantly Hispanic population in South Florida. The diagnosis is challenging, often delayed, and the prognosis is dismal in refractory cases despite currently available rescue therapies. Furthermore, we describe for the first time the association between HLH and PTLD ALCL.

Keywords: HLH-200; Hemophagocytic lymphohistiocytosis; Hyperferritinemia; Lymphoma; NK cell; Phagocytosis.