title: Thrombotic microangiopathy (TMA) and stroke due to human herpesvirus-6 (HHV-6) reactivation in an adult receiving high-dose melphalan with autologous peripheral stem cell transplantation.
abstract: We report an adult autologous stem cell transplant (ASCT) patient who developed transplant-associated thrombotic microangiopathy (TMA) due to human herpesvirus-6 (HHV-6) reactivation. A 58-year-old female with Stage IIIA IgGkappa multiple myeloma received a melphalan (200 mg/m2) ASCT with discharge home after resolution of ASCT-related toxicities. She presented on D+20 with dyspnea, rash, and fever to 105 degrees F, followed by worsening dyspnea, hypotension, and capillary leak. Mental status (MS) changes were noted on D+23, but head CT and EEG were unremarkable. On D+29, a generalized seizure occurred with decline in platelet count and haptoglobin. TMA was noted on peripheral blood smear and therapeutic plasma exchange (TPE) was initiated on D+31. Lumbar puncture (LP) revealed CSF protein 74 mg/dL and white blood count 7,000/mm3 with 74% lymphocytosis. TPE was continued without improvement in her MS or thrombocytopenia despite improvement in microangiopathy. An MRI of the brain showed a left hippocampus abnormality, and an EEG was consistent with encephalopathy. Serum polymerase chain regimen (PCR) was negative for CMV, HSV1, and HSV2 but was strongly positive for HHV-6. Repeat LP protein was 597 mg/dL. Foscarnet was initiated, and cerebrospinal fluid (CSF) PCR for HHV-6 revealed 1,400 DNA copies/mL. Her MS greatly improved within 48 hr of antiviral therapy, serum HHV-6 became negative, and TPE was tapered without recurrence of her TMA. TMA with HHV-6 reactivation is likely an underdiagnosed entity. Given its fulminant course and favorable response to therapy, HHV-6 reactivation should be considered a potential etiology in patients with TMA after ASCT.
authors.affiliation: Department of Hematology/Oncology, Walter Reed Army Medical Center, Washington, DC 20307, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Belford
authors.forename: Otha
authors.initials: O
authors.lastname: Myles
authors.forename: Alan
authors.initials: A
authors.lastname: Magill
authors.forename: James
authors.initials: J
authors.lastname: Wang
authors.forename: Rick C
authors.initials: RC
authors.lastname: Myhand
authors.forename: Jamie K
authors.initials: JK
authors.lastname: Waselenko
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005260:Female; D015654:Herpesvirus 6, Human / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D008558:Melphalan / Q000627:therapeutic use*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D019349:Roseolovirus Infections / Q000150:complications*; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D020521:Stroke / Q000209:etiology*; D013927:Thrombosis / Q000209:etiology*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D016896:Treatment Outcome; D014775:Virus Activation / Q000502:physiology*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000998:Antiviral Agents; D010959:Tissue Plasminogen Activator; D008558:Melphalan