Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, Germany.
Blood. 2010 Nov 4;116(18):3572-81. doi: 10.1182/blood-2009-12-260588. Epub 2010 May 20.
Allogeneic stem cell transplantation (ASCT) after reduced-intensity conditioning has become a reasonable treatment option for patients with advanced myelofibrosis. The role of characteristic molecular genetic abnormalities, such as JAK2V617F on outcome of ASCT, is not yet elucidated. In 139 of 162 myelofibrosis patients with known JAK2V617F mutation status who received ASCT after reduced-intensity conditioning, the impact of JAK2 genotype, JAK2V617F allele burden, and clearance of mutation after ASCT was evaluated. Overall survival was significantly reduced in multivariate analysis in patients harboring JAK2 wild-type (hazard ratio = 2.14, P = .01) compared with JAK2 mutated patients. No significant influence on outcome was noted for the mutated allele burden analyzed either as continuous variable or after dividing into quartiles. Achievement of JAK2V617F negativity after ASCT was significantly associated with a decreased incidence of relapse (hazard ratio = 0.22, P = .04). In a landmark analysis, patients who cleared JAK2 mutation level in peripheral blood 6 months after ASCT had a significant lower risk of relapse (5% vs 35%, P = .03). We conclude that JAK2V617F-mutated status, but not allele frequency, resulted in an improved survival and rapid clearance after allografting reduces the risk of relapse.
异基因造血干细胞移植（ASCT）在减低强度预处理后已成为治疗骨髓纤维化的合理选择。特征性分子遗传学异常，如 JAK2V617F 对 ASCT 结果的影响尚不清楚。在 162 例已知 JAK2V617F 突变状态的骨髓纤维化患者中，有 139 例接受了减低强度预处理后的 ASCT，评估了 JAK2 基因型、JAK2V617F 等位基因负担和 ASCT 后突变清除对结果的影响。多因素分析显示，与 JAK2 突变患者相比，携带 JAK2 野生型的患者总生存率显著降低（风险比=2.14，P=.01）。分析连续变量或分为四分位数后，突变等位基因负担对结果无显著影响。ASCT 后 JAK2V617F 阴性的获得与复发发生率降低显著相关（风险比=0.22，P=.04）。在一个里程碑分析中，ASCT 后 6 个月外周血清除 JAK2 突变水平的患者复发风险显著降低（5% vs 35%，P=.03）。我们得出结论，JAK2V617F 突变状态而不是等位基因频率与改善生存相关，同种异体移植后快速清除可降低复发风险。
