Molecular remission after allo-SCT in a patient with post-essential thrombocythemia myelofibrosis carrying the MPL (W515A) mutation.

Post-essential thrombocythemia myelofibrosis (post-ET MF) may occur as a late event during the course of ET.1 Criteria for diagnosis of post-ET MF have been recently established by the International Working Group on Myelofibrosis Research and Treatment.2 Once ET evolves into post-ET MF, survival is worsened, and in a few instances hemopoietic allo-SCT may be considered as a treatment option.3, 4 Patients with myelofibrosis may carry the JAK2 (V617F) mutation5 or, more rarely, mutations within the MPL gene.6 This allows one to study minimal residual disease after allo-SCT by monitoring these activating molecular mutations in positive patients.7, 8 Herein, we report the clinical course and minimal residual disease in a man with post-ET MF carrying the MPL mutation, who received allo-SCT. The patient gave his written informed consent for DNA studies. At the age of 49 years, the patient developed post-ET MF after 108 months of ET. Diagnosis of disease evolution was based on the International Working Group on Myelofibrosis Research and Treatment criteria.2 When he was referred to our Division of Hematology, he had transfusion-dependent anemia (Hb 7.1 g per 100 ml), leukopenia (WBC 3.4 × 109/l) and splenomegaly. Circulating CD34+ cells were at the upper normal range (49 × 106/l) and the lactate dehydrogenase level was elevated (1085 mU/ml). His BM biopsy showed hypercellularity (90%), megakaryocytic hyperplasia with atypia, grade 2 myelofibrosis according to the European Classification and a 3% CD34+ blast cell count. The patient had a normal diploid karyotype. High-resolution melting and sequencing analyses on circulating granulocytes showed an MPL W515A mutation.9 After failure of conventional treatments, he received a matched unrelated-donor allo-SCT. A fully myeloablative conditioning, including TBI (1200 rad in six doses) and CY (60 mg/kg/day for 2 days), was given. A total of 8.9 × 106/kg peripheral CD34+ cells were infused. Engraftment was achieved on day +16 after transplantation. During the post-transplant period, CMV reactivation occurred and required treatment with ganciclovir. At day +100, a CR was documented on the basis of the International Working Group criteria:10 resolution of splenomegaly, normal peripheral blood counts and leukocyte differential, and normal BM histology without fibrosis. Circulating CD34+ cells were within the normal range (3.1 × 106/l). At day +100, minimal residual disease was assessed by chimerism analysis using microsatellite evaluation (D20S889, D20S117, D19S220, sensitivity 0.1%) and by the MPL mutation analysis using high-resolution melting (sensitivity 1%) and sequencing. Full donor chimerism was achieved (Figure 1a). Absence of the MPL (W515A) mutation was demonstrated by high-resolution melting and by sequencing, thereafter defining a status of molecular remission (Figure 1b). At 9 months after transplantation, the patient is still alive in molecular remission. This is the first report of a patient with MPL-positive post-ET MF who became negative for the MPL mutation with allo-SCT.