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Blood, 1 February 2007, Vol. 109, No. 3, pp. 1316-1321.
Prepublished online as a Blood First Edition Paper on October 3, 2006; DOI 10.1182/blood-2006-08-039909.
Previous Article | Next Article 
Submitted August 7, 2006
Accepted September 7, 2006
Monitoring of V617F-JAK2-mutation by highly sensitive quantitative real-time PCR after allogeneic stem cell transplantation in patients with myelofibrosis
Nicolaus Kroger*, Anita Badbaran, Ernst Holler, Joachim Hahn, Guido Kobbe, Martin Bornhauser, Andreas Reiter, Tatjana Zabelina, Axel R Zander, and Boris Fehse
Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Department of Hematology/Oncology, University Hospital Regensburg, Regensburg, Germany
Department of Hematology/Oncology, University Hospital Duesseldorf, Duesseldorf, Germany
Department of Hematology/Oncology, University Hospital Dresden, Dresden, Germany
Department of Hematology/Oncology, University Hospital Mannheim, Mannheim, Germany
* Corresponding author; email: nkroeger{at}uke.uni-hamburg.de.
The V617F-JAK2-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 ( 0.01 %) real-time 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 out 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 post allograft (range, 19 750 days). A significant inverse correlation was seen for JAK2 positivity and donor cell chimerism (r:-0.91, p<0.001). Four of five 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 myelofibrosis-patients, and quantification of V617F-JAK2 mutation by real-time PCR allows detecting minimal residual disease to guide adoptive immunotherapy.

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