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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.
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TRANSPLANTATION
Monitoring of the JAK2-V617F mutation by highly sensitive quantitative real-time PCR after allogeneic stem cell transplantation in patients with myelofibrosis
Nicolaus Kröger1,
Anita Badbaran1,
Ernst Holler2,
Joachim Hahn2,
Guido Kobbe3,
Martin Bornhäuser4,
Andreas Reiter5,
Tatjana Zabelina1,
Axel R. Zander1, and
Boris Fehse1
1 Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Germany;
2 Department of Hematology/Oncology, University Hospital Regensburg, Germany;
3 Department of Hematology/Oncology, University Hospital Düsseldorf, Germany;
4 Department of Hematology/Oncology, University Hospital Dresden, Germany;
5 Department of Hematology/Oncology, University Hospital Mannheim, Germany
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 ( 0.01%) real-time polymerase chain reaction (PCR) to monitor and quantify V617F-JAK2positive 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.

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