title: Monitoring of the JAK2-V617F mutation by highly sensitive quantitative real-time PCR after allogeneic stem cell transplantation in patients with myelofibrosis.
abstract: The JAK2-V617F mutation occurs in about 50% of patients with myelofibrosis and might be a reliable marker to monitor residual disease after allogeneic stem cell transplantation. We describe a new, highly sensitive (>or= 0.01%) real-time polymerase chain reaction (PCR) to monitor and quantify V617F-JAK2-positive cells after dose-reduced allogeneic stem cell transplantation. After 22 allogeneic stem cell transplantation procedures in 21 JAK2-positive patients with myelofibrosis, 78% became PCR negative. In 15 of 17 patients (88%), JAK2 remained negative after a median follow-up of 20 months. JAK2 negativity was achieved after a median of 89 days after allograft (range, 19-750 days). A significant inverse correlation was seen for JAK2 positivity and donor-cell chimerism (r:-0.91, P<.001). Four of 5 patients who never achieved JAK2 negativity fulfilled during the entire follow-up all criteria for complete remission recently proposed by the International Working Group, suggesting a major role for JAK2 measurement to determine depths of remission. In one case, residual JAK2-positive cells were successfully eliminated by donor lymphocyte infusion. In conclusion, allogeneic stem cell transplantation after dose-reduced conditioning induces high rates of molecular remission in JAK2-positive patients with myelofibrosis, and quantification of V617F-JAK2 mutation by real-time PCR allows the detection of minimal residual disease to guide adoptive immunotherapy.
authors.affiliation: Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, and Department of Hematology/Oncology, University Hospital Regensburg, Germany. nkroeger@uke.uni-hamburg.de
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.forename: Anita
authors.initials: A
authors.lastname: Badbaran
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
authors.forename: Joachim
authors.initials: J
authors.lastname: Hahn
authors.forename: Guido
authors.initials: G
authors.lastname: Kobbe
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.forename: Andreas
authors.initials: A
authors.lastname: Reiter
authors.forename: Tatjana
authors.initials: T
authors.lastname: Zabelina
authors.forename: Axel R
authors.initials: AR
authors.lastname: Zander
authors.forename: Boris
authors.initials: B
authors.lastname: Fehse
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods / Q000401:mortality; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D018365:Neoplasm, Residual / Q000175:diagnosis*; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods* / Q000592:standards; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2