Summary:Allogeneic transplant recipients are at high risk of developing secondary malignancies as a late complication of therapy. We report a case of essential thrombocythemia occurring 8 years following bone marrow transplantation (BMT) for chronic myelogenous leukemia. Keywords: essential thrombocythemia; marrow transplantation; long-term complication Allogeneic bone marrow transplantation (BMT) is a frequently used and efficacious therapeutic modality for selected hematologic malignancies. However, development of secondary neoplasms following BMT is emerging as a serious late complication for long-term survivors.1 The spectrum of secondary hematologic complications includes EBV-associated B cell lymphoproliferative disorders and acute leukemia/myelodysplastic syndromes.
2Essential thrombocythemia post-BMT has not been reported. We describe a case of essential thrombocythemia occurring 8 years following allogeneic BMT.
Case reportA 43-year-old man with chronic phase Philadelphia chromosome positive CML underwent allogeneic BMT 3 years after diagnosis from his HLA-identical brother in 1988. The preparative regimen included total body irradiation (12 Gy), cyclophosphamide and etoposide. Methotrexate and cyclosporin A were given for graft-versus-host disease (GVHD) prophylaxis. The post-transplant period was uncomplicated, and cyclosporine was subsequently discontinued.The patient presented in October 1996 with asymptomatic thrombocytosis (platelet count 1 674 000/mm acute or a chronic inflammatory disorder was found. Hemoglobin was 15.2 g/l and white blood count was 8900/mm 3 , of which 70% were neutrophils and 22% were lymphocytes. Basophils and a leukoerythroblastic picture were not observed on the peripheral blood smear, but large platelets were present. Serum ferritin was normal. Platelet aggregation studies revealed reduced platelet response to collagen, ADP and arachidonic acid, and complete absence of aggregation with epinephrine stimulation. With an enzyme immunoassay using polyclonal antibodies raised against recombinant human thrombopoietin (TPO) for capture and signal generation (material kindly provided by Amgen, Thousand Oaks, CA, USA), endogenous TPO level was 208 pg/ml (serum TPO levels from 90 normal controls: 51-407 pg/ml). Computerized tomography of the chest, abdomen and pelvis were normal.Bone marrow aspirate and core biopsy showed a normocellular marrow with increased megakaryocytes. Karyotypic analysis of 16 metaphases was normal (46,XY). The bcr/abl fusion cDNA was not detected by nested reversetranscriptase polymerase chain reaction performed as previously described.3 Granulomas and fibrosis were absent, and cultures were sterile. Stainable iron was present.To assess hematopoietic chimerism, genomic DNA was isolated, digested with HinfI restriction endonuclease and subjected to agarose gel electrophoresis. HinfI-digested DNA was then transferred to a nylon membrane (ZetaProbe, BioRad, Hercules, CA, USA), and hybridized to radiolabelled hypervariable minisatellite repeat probe D1S7.4 Filte...