Cytomegalovirus pneumonitis, activated prothrombin time prolongation and subacute thyroiditis after unrelated allogeneic bone marrow transplantation

Abstract

Summary:A 22-year-old female with acute myeloid leukemia (AML) in complete remission received a conditioning regimen containing antithymocyte globulin for an unrelated bone marrow transplant (BMT). After BMT, the patient suffered from cytomegalovirus (CMV) pneumonitis with markedly high levels of CMV antigenemia, activated prothrombin time (APTT) prolongation, and subacute thyroiditis. Recovery of CD4؉ cells was delayed as long as 1 year after BMT. An association between these three episodes and viral infection due to the delayed recovery of CD4 ؉ cells is suggested. Bone Marrow Transplantation (2000) 26, 1347-1349. Keywords: bone marrow transplantation; antithymocyte globulin; viral infection; CD4 ϩ cells Viral infections are major causes of mortality and morbidity in patients who receive an allogeneic BMT. During the early and late post-transplant periods, herpes and other viruses cause localized and systemic disease. Of these viruses, CMV infection is the most common, and patients may present with pneumonitis, enteritis or myelosuppression. 1-4 CMV reactivation can be measured by detecting the CMV pp65 antigen (CMV antigenemia). 5,6We describe a patient with AML who received an unrelated allogeneic BMT and developed CMV pneumonitis, APTT prolongation and subacute thyroiditis. CMV pneumonitis and subacute thyroiditis were successfully treated with ganciclovir and prednisolone, respectively. Case reportA 22-year-old female with AML (FAB M6) in first complete remission underwent an allogeneic BMT. The patient was seropositive for CMV and Epstein-Barr (EB) viruses and had normal coagulation parameters. On 5 June 1997, she received an allogeneic BMT from an unrelated HLAidentical male donor (A2, A24, B7, B54, Cw1, Cw7, DR1 and DR4). Conditioning was with total body irradiation at 1200 cGy in six fractions from days Ϫ9 to Ϫ7; cytarabine, 1000 mg/m 2 twice a day from days Ϫ6 to Ϫ4; and cyclophosphamide, 60 mg/kg on days Ϫ3 and Ϫ2. In addition, 2.5 mg/kg of antithymocyte globulin (ATG) was administered from days Ϫ5 to Ϫ2. On day 0, 4.1 ϫ 10 8 /kg of untreated nucleated bone marrow cells was infused. Graftversus-host disease (GVHD) prophylaxis was short-term methotrexate and cyclosporine. CMV hyperimmuneglobulin was given at a dose of 12.5 g every 2 weeks to prevent CMV infection, between days ϩ7 and ϩ120. Granulocyte colony-stimulating factor was given from day ϩ1.Regimen-related toxicities were mild; the patient complained of slight nausea and diarrhea. Bone marrow engraftment was confirmed on day ϩ15 using karyotypic and fluorescence in situ hybridization analyses. On day ϩ54, the patient developed a dry cough and low-grade fever. Computed tomography of the chest showed pneumonitis in both lungs. At this time, markedly high levels of CMV antigenemia were noticed (Figure 1). CMV pneumonitis was diagnosed and 5 mg/kg of ganciclovir twice a day was initiated. Following the therapy, CMV antigenemia levels dropped and the interstitial infiltrates in both lungs resolved. No acute GVHD occurred. On day ϩ118, she complaine...

Development of a secondary autoimmune disorder after hematopoietic stem cell transplantation for autoimmune diseases: role of conditioning regimen used

“…41 There was a case of a patient who developed asymptomatic factor XII inhibitors after allogeneic HSCT with an ATG-containing regimen for acute myeloid leukemia. 42 To our knowledge, the only other report of acquired hemophilia secondary to factor VIII inhibitors after ATG involved a patient with MS who underwent auto-HSCT after busulfan and ATG conditioning. 22 Alemtuzumab is a monoclonal antibody directed against CD52 which is expressed on virtually all T and B lymphocytes (although preferentially on T lymphocytes) 43 and monocytes.…”

Rare Presentations of Cytomegalovirus Infection in Renal Allograft Recipients

“…Concomitant CMV pneumonitis and subacute thyroiditis were reported in a case study of a recipient of a bone-marrow transplant. The condition successfully responded to treatment with ganciclovir and prednisolone (58). CMV-induced adrenal insufficiency is a known condition in HIV-infected patients and has also been reported in one renal-transplant recipient, whose condition improved after increasing his corticosteroid dosage (59).…”