Monitoring of the JAK2-V617F mutation by highly sensitive quantitative real-time PCR after allogeneic stem cell transplantation in patients with myelofibrosis

Kroeger, Nicolaus and Badbaran, Anita and Holler, Ernst and Hahn, Joachim and Kobbe, Guido and Bornhaeuser, Martin and Reiter, Andreas and Zabelina, Tatjana and Zander, Axel R. and Fehse, Boris (2007) Monitoring of the JAK2-V617F mutation by highly sensitive quantitative real-time PCR after allogeneic stem cell transplantation in patients with myelofibrosis. BLOOD, 109 (3). pp. 1316-1321. ISSN 0006-4971, 1528-0020

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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 (>= 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 realtime PCR allows the detection of minimal residual disease to guide adoptive immunotherapy.

Item Type: Article
Uncontrolled Keywords: AGNOGENIC MYELOID METAPLASIA; TYROSINE KINASE JAK2; MYELOPROLIFERATIVE DISORDERS; POLYCYTHEMIA-VERA; ESSENTIAL THROMBOCYTHEMIA; PROGNOSTIC-FACTORS; SURVIVAL; LEUKEMIA; CRITERIA; SYSTEM;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 22 Dec 2020 09:38
Last Modified: 22 Dec 2020 09:38
URI: https://pred.uni-regensburg.de/id/eprint/33199

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