title: Epstein-Barr virus-positive B-cell lymphoproliferative disorders arising in immunodeficient patients previously treated with fludarabine for low-grade B-cell neoplasms.
abstract: We describe five patients with treated low-grade B-cell neoplasms who subsequently developed Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disorders (BLPDs). The low-grade B-cell neoplasms were B-cell chronic lymphocytic leukemia in four patients and splenic marginal zone lymphoma in one patient. All patients had received treatment with fludarabine for the low-grade B-cell neoplasm, and three had also received Campath-1H. The EBV-BLPDs arose 2-12 months after completion of fludarabine therapy and morphologically resembled the EBV-BLPDs that occur in the setting of iatrogenic immunodeficiency. Molecular genetic studies showed that these lesions were clonally distinct from the low-grade B-cell neoplasm in three of four cases assessed. Two patients did not receive therapy for the EBV-BLPD. The lesions regressed spontaneously in both patients but recurred in one. One patient underwent surgical excision and remains without evidence of the EBV-BLPD. One patient received aggressive multiagent chemotherapy with a complete response initially, but the EBV-BLPD recurred after 12 months. One patient received antiviral therapy and responded completely but died 2 months later of an opportunistic infection. We conclude that patients with low-grade B-cell neoplasms treated with fludarabine, possibly in combination with other immune suppressive agents, may subsequently develop EBV-BLPDs that morphologically resemble other iatrogenic immunodeficiency-associated BLPDs. Most are clonally distinct from the underlying low-grade B-cell neoplasm. A subset of these lesions may regress without systemic therapy.
authors.affiliation: Department of Hematopathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. labruzzo@mdanderson.org
authors.forename: Lynne V
authors.initials: LV
authors.lastname: Abruzzo
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Rosales
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Francisco
authors.initials: F
authors.lastname: Vega
authors.forename: Rajyalakshmi
authors.initials: R
authors.lastname: Luthra
authors.forename: John T
authors.initials: JT
authors.lastname: Manning
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D020031:Epstein-Barr Virus Infections / Q000139:chemically induced* / Q000473:pathology / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008232:Lymphoproliferative Disorders / Q000139:chemically induced* / Q000473:pathology / Q000821:virology; D008297:Male; D016601:RNA-Binding Proteins / Q000032:analysis; D012269:Ribosomal Proteins; D014740:Vidarabine / Q000009:adverse effects* / Q000031:analogs & derivatives
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; C067169:RPL22 protein, human; D014740:Vidarabine; C024352:fludarabine