title: Rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin in the treatment of secondary hemophagocytic lymphohistiocytosis with classical Hodgkin lymphoma: a case report and review of the literature.
abstract: BACKGROUND
  Hemophagocytic lymphohistiocytosis is becoming an increasingly recognized disorder in adults. Classical Hodgkin lymphoma is a relatively uncommon etiology of hemophagocytic lymphohistiocytosis and may complicate treatment options. Rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin are discussed here as a treatment regimen.
  
  
  METHODS
  A 66-year-old Hispanic man previously in good health presented with a 1-month history of recurrent fevers, chills, and night sweats and a 3-week history of new onset jaundice. A bone marrow biopsy revealed a normocellular bone marrow with increased histiocytes with areas of hemophagocytic activity. He met five out of eight criteria for hemophagocytic lymphohistiocytosis diagnosis including fevers, pancytopenia, hemophagocytosis, ferritin of 23,292 ng/mL (>500 ng/mL), and soluble-CD25 of 15,330 pg/mL (>1033 pg/mL). A right cervical lymph node biopsy revealed CD15, CD30, MUM-1, and Epstein-Barr virus-encoded small ribonucleic acid-positive cells with morphologic findings of classical Hodgkin lymphoma, lymphocyte-rich subtype. He completed 2 weeks of hemophagocytic lymphohistiocytosis-directed therapy with etoposide and dexamethasone, but then was switched to rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin due to minimal improvement in his pancytopenia and hepatic impairment. He completed one full cycle of rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin with notable improvement in serial hepatic function panels and had an undetectable Epstein-Barr virus viral load. However, he eventually died due to complications of Enterococcus faecalis bacteremia and colonic microperforation in the setting of persistent pancytopenia.
  
  
  CONCLUSIONS
  This case discusses the challenges facing treatment of adult malignancy-associated hemophagocytic lymphohistiocytosis. Rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin may be a viable option for patients with secondary hemophagocytic lymphohistiocytosis and Hodgkin lymphoma who cannot tolerate standard therapies due to hepatic impairment. Targeted therapy and immunotherapy are promising new areas of developing treatments.
authors.affiliation: Department of Internal Medicine, University of New Mexico, MSC10 5550, 1 University of New Mexico, 87131, Albuquerque, NM, USA. sthu@salud.unm.edu.
authors.forename: Steve
authors.identifier: http://orcid.org/0000-0001-6391-6962
authors.initials: S
authors.lastname: Hu
authors.affiliation: University of New Mexico Comprehensive Cancer Center, 1201 Camino de Salud NE, Room 3618, 87131, Albuquerque, NM, USA.
authors.forename: Pranshu
authors.initials: P
authors.lastname: Bansal
authors.affiliation: Department of Pathology, University of New Mexico, MSC08 4640, 1 University of New Mexico, 87131, Albuquerque, NM, USA.
authors.forename: David
authors.initials: D
authors.lastname: Lynch
authors.affiliation: University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1464, 77030, Houston, TX, USA.
authors.forename: Cristhiam Mauricio
authors.initials: CM
authors.lastname: Rojas Hernandez
authors.affiliation: University of New Mexico Comprehensive Cancer Center, 1201 Camino de Salud NE, Room 3618, 87131, Albuquerque, NM, USA.
authors.forename: Zoneddy
authors.initials: Z
authors.lastname: Dayao
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor; D001853:Bone Marrow / Q000473:pathology*; D002945:Cisplatin / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use; D013293:Enterococcus faecalis / Q000302:isolation & purification; D005047:Etoposide / Q000627:therapeutic use; D017809:Fatal Outcome; D005334:Fever / Q000382:microbiology*; D016908:Gram-Positive Bacterial Infections / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology; D006689:Hodgkin Disease / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D007565:Jaundice / Q000382:microbiology*; D051359:Lymphohistiocytosis, Hemophagocytic / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D010198:Pancytopenia / Q000150:complications / Q000188:drug therapy*; D000069283:Rituximab / Q000627:therapeutic use
chemical_list: D014408:Biomarkers, Tumor; D003561:Cytarabine; D000069283:Rituximab; D005047:Etoposide; D002945:Cisplatin; D008775:Methylprednisolone
keywords: Case report; EBER; ESHAP; Epstein–Barr virus; Hemophagocytic lymphohistiocytosis; Hodgkin lymphoma; Pancytopenia; Rituximab