Jones, Amy V., Higley, Katherine, Curtis, Claire, Kreil, Sebastien, Zoi, Katerina, Hochhaus, Andreas, Reiter, Andreas, Oscier, David, Merber, Alec, Silver, Richard T. and Cross, Nicholas C.P.
No significant molecular response in polycythemia vera patients treated with imatinib or interferon alpha
Blood, 106, (11), .
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Imatinib mesylate and interferon alpha (rIFNa) have both been reported to induce remission in patients with polycythemia vera (PV), but until recently it has not been possible generally to gauge the depth of these responses due to the absence of a specific cytogenetic or molecular marker of the disease. Here we have used ARMS and pyrosequencing assays to detect and quantify the V617F JAK2 mutation in granulocytes or mononuclear cells from 111 PV patients, of whom 14 were undergoing treatment with imatinib (300–800 mg/day; median follow up 17 months; range 5–31), seven were undergoing treatment with rIFNa (dose range from 2MU three times/week to 3MU/day; median follow up 60 months; range 13–132), and 90 were untreated or treated only by phlebotomy, hydroxyurea or anagrelide (control group). Clinical responses in the 14 imatinib treated cases were none (NR; n=3), partial (PR; n=9) or complete (CR; n=2); responses in the seven rIFNa treated cases were PR (n=1) or CR (n=6). The V617F mutation was detected in all cases undergoing treatment with imatinib or rIFNa and in 82 (91%) of the control PV cases. The median percentage of mutated JAK2 alleles (%V617F) did not differ significantly between the imatinib treated cases (median 59%, range 8–91), the rIFNa treated cases (median 27%, range 19–87) or the V617F positive cases from the control group (median 53%, range 5–100). In the imatinib group, the median %V617F for cases with NR, PR and CR were 72% (44–89; n=3), 60% (30–91; n=9) and 15% (8 and 21; n=2), respectively. In the rIFNa treated group the single case with a PR had 87% V617F compared to a median of 26% (19–39) for the six cases in CR. Pretreatment samples were available for 9 of the imatinib treated cases. Of these, all seven of the NR or PR cases showed a marginal increase (median 1.2 fold, range 1.0–1.5) in the percentage of V617F alleles on treatment. In contrast, the two CR patients showed a 2–3 fold reduction in %V617F on treatment. We conclude that although PV patients may benefit from treatment with imatinib or rIFNa, molecular analysis indicates that responses are modest.
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