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

• Published in: American journal of hematology Vol. 76; no. 2; pp. 156 - 162
• Main Authors: Belford, Amy, Myles, Otha, Magill, Alan, Wang, James, Myhand, Rick C., Waselenko, Jamie K.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.06.2004; Wiley-Liss
• Subjects: Antineoplastic Agents, Alkylating - therapeutic use; Antiviral Agents - therapeutic use; autologous stem cell transplantation; Biological and medical sciences; Combined Modality Therapy; Cytomegalovirus; encephalitis; Female; Hematologic and hematopoietic diseases; Herpes simplex virus 1; Herpesvirus 6, Human - isolation & purification; Herpesvirus 6, Human - physiology; Human herpesvirus 6; Humans; Medical sciences; melphalan; Melphalan - therapeutic use; Middle Aged; Multiple Myeloma - therapy; Neurology; Platelet diseases and coagulopathies; Roseolovirus Infections - complications; Stem Cell Transplantation - adverse effects; stroke; Stroke - etiology; Thrombosis - etiology; thrombotic microangiopathy; Tissue Plasminogen Activator - therapeutic use; Treatment Outcome; TTP; Vascular diseases and vascular malformations of the nervous system; Virus Activation - physiology; Antineoplastic agent; Skin disease; Stem cell; autologous stem cell transplantation; Hematopoietic cell; Cardiovascular disease; Hemopathy; Thrombohemolytic microangiopathy; Vascular disease; TTP; Autograft; Thrombotic thrombocytopenic purpura; Hemolytic anemia; Melphalan; Graft; Adult; thrombotic microangiopathy; Human herpesvirus 6; High dose; human herpesvirus-6; Cerebrovascular disease; Human; Encephalitis; Nervous system diseases; Stroke; Reactivation; Urinary system disease; Vascular disorders of the skin; Cerebral disorder; Alkylating agent; Platelet; Central nervous system disease; Capillary vessel disease; Coagulopathy
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/ajh.20068

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 IgGκ 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°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. Am. J. Hematol. 76:156–162, 2004. © 2004 Wiley‐Liss, Inc.