Cerebral venous sinus thrombosis after allogeneic stem cell transplantation

Abstract

Neurological complications are an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT) [1]. Complications that affect the central nervous system (CNS) can include infection in immunocompromised hosts, cerebrovascular events such as subdural hematoma or stroke, calcineurin-induced CNS neuropathy, and leukoencephalopathy resulting from intrathecal chemotherapy or cranial irradiation [2]. Cerebral venous sinus thrombosis (CVST) is a relatively rare complication after allogeneic HSCT [3, 4] and its pathogenesis is still unclear. Here, we describe a patient who developed CVST during immunosuppressive therapy for chronic graft-versus-host disease (GVHD) after allogeneic HCST. In August 2007, a 42-year-old Japanese woman was diagnosed as having acute myeloid leukemia. She was transferred to our hospital for allogeneic HSCT in January 2008, after achieving complete remission with combination chemotherapy. In March 2008, the patient underwent allogeneic HSCT from her HLA-identical brother. The pretransplant conditioning regimen consisted of intravenous busulfan (0.8 mg/m 9 4/day on days -7, -6, -5, and -4) and cyclophosphamide (60 mg/kg/day on days -3 and -2). She received GVHD prophylaxis with short-term methotrexate (15 mg/m on day 1; and 10 mg/m on days 3 and 6) plus cyclosporin A (CsA) as a continuous infusion at a dose of 3 mg/kg/day. She also received 250 lg/day of granulocyte colony-stimulating factor by continuous infusion from day 1 to promote granulocyte recovery. Her granulocyte count was more than 0.5 9 10/L on day 19 and the platelet count exceeded 20 9 10/L on day 26. Complete engraftment was confirmed on day 22 by fluorescence in situ hybridization analysis using Xand Y-chromosome probes. She developed acute GVHD (grade II) involving the skin on day 26 and was treated with a topical corticosteroid preparation. She was discharged on day 87 without any evidence of GVHD. However, she was re-admitted on day 120 after HSCT because of skin lesions and a decrease of the platelet count. A diagnosis of chronic GVHD with skin lesions (maculopapular rash, sclerotic changes, and abnormal pigmentation) and thrombocytopenia (21 9 10/L) was made, and prednisolone (PSL) was started at a dose of 0.5 mg/kg daily from day 126. Although her skin lesions improved, recovery of the platelet count was not obtained. Bone marrow smear on day 135 revealed hypocellular marrow and a few megakaryocytes. Examination of the clotting profile on day 141 showed the following: her prothrombin time was 65% (normal range 70–130%), the fibrinogen level was 85 mg/dL (normal range 150–450 mg/dL), the FDP level was 31.1 lg/dL (normal range 0–5.0 lg/dL), the D-dimer level was 11.1 lg/dL (normal range 0–1.0 lg/dL), and the thrombomodulin level was 4.0 FU/mL (normal range 0–1.0 FU/mL). Lactate dehydrogenase level was within normal limits and fragmented red cells were not observed. Thrombosis was suspected from the laboratory findings, but deep vein thrombosis was not detected by screening tests. On day 153, she suddenly developed a severe K. Motohashi (&) T. Tachibana H. Takasaki M. Tanaka A. Maruta H. Kanamori Department of Hematology, Kanagawa Cancer Center, 1-1-2 Nakao, Asahi-ku, Yokohama 241-0815, Japan e-mail: motohashik@kcch.jp