RESUMO
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.
Assuntos
Herpesvirus Humano 6/isolamento & purificação , Melfalan/uso terapêutico , Mieloma Múltiplo/terapia , Infecções por Roseolovirus/complicações , Transplante de Células-Tronco/efeitos adversos , Acidente Vascular Cerebral/etiologia , Trombose/etiologia , Ativação Viral/fisiologia , Antineoplásicos Alquilantes/uso terapêutico , Antivirais/uso terapêutico , Terapia Combinada , Feminino , Herpesvirus Humano 6/fisiologia , Humanos , Pessoa de Meia-Idade , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do TratamentoRESUMO
Given the favorable immunologic effects of IL-2 post transplant, we conducted a feasibility study examining rIL-2 1.0x106 IU/m2/day (SQ) beginning on D+14 post-transplant and continuing for 90 days in 12 patients with low-grade lymphoproliferative disorders. Prior to high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDCT), 11 patients underwent cytoreduction with fludarabine and cyclophosphamide (Flu/Cy); 11 were in complete remission (CR) and one was in partial remission at the time of HDCT. All 12 patients were in CR 90 days post-HDCT. At a median follow-up of 30 (range 3-44) months, seven patients (58%) remain in remission, four are alive with disease, and one has died of disease progression, resulting in an overall survival of 92%. Kaplan-Meier estimates of progression-free survival (PFS) for the group demonstrate a median of 31 (range 3-43) months. Five patients required rIL-2 cessation at 8-58 days after starting the therapy due to hematologic toxicity. These results are comparable to those achieved in other published bone marrow and peripheral blood stem cell transplantion (PBSCT) series without the addition of rIL-2. Furthermore, rIL-2 using this schedule following fludarabine-based cytoreduction was associated with excessive hematologic toxicity.