Allogeneic hematopoietic stem cell transplant overcomes the adverse survival effect of very high risk and unfavorable karyotype in myelofibrosis
Allogeneic hematopoietic stem cell transplant overcomes the adverse survival effect of very high risk and unfavorable karyotype in myelofibrosis
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DOI：
10.1002/ajh.25053
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发表时间：
2018-05-01
影响因子：
12.8
通讯作者：
Patnaik, Mrinal M.
中科院分区：
文献类型：
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作者：
Tefferi, Ayalew;Partain, Daniel K.;Patnaik, Mrinal M.
遗传信息在原发性骨髓纤维化（PMF）中的预后重要性最近在一项超过1000例细胞遗传学注释患者的研究中得到强调;极高危（VHR）的5年生存率为8%，27%“不利”和45%“有利”核型。目前的研究解决了异基因造血干细胞移植（HCT）是否可以克服VHR或不利的核型的不利生存影响的实践相关的问题。该研究纳入了67例PMF或继发性MF患者，这些患者在马约诊所接受了HCT，并且可获得移植前细胞遗传学信息。动态国际预后评分系统（DIPSS）风险分布为13%高，66%中间-2和21%中间-1。细胞遗传学风险分布为11% VHR，34%不利，55%有利。存活患者（范围34-170）中位HCT后随访60个月时，记录了28例（42%）死亡。5年生存率为62%，不受VHR或不利核型的影响（P = 0.68）。在对383例PMF患者的非移植队列的联合数据集进行分析时，HCT对VHR或不良核型患者的有益作用也很明显;联合数据集（n = 450）的多变量分析得出HR（95% CI）为2.4（1.6-3.6），VHR核型为3.3（2.2-4.8），不利核型为1.6（1.2-2.1），DIPSS高为2.9（2.0-4.2），DIPSS中间-2为1.7（1.4-2.2）。通过分析更严格匹配的病例对照亚组队列进一步证实了这些观察结果，并为细胞遗传学高风险MF患者中HCT的治疗偏好提供了证据。
The prognostic importance of genetic information in primary myelofibrosis (PMF) was recently highlighted in a study of over 1000 cytogenetically-annotated patients; 5-year survival rates were 8% for very high risk (VHR), 27% "unfavorable" and 45% "favorable" karyotype. The current study addresses the practice-relevant question of whether or not allogeneic hematopoietic stem cell transplant (HCT) can overcome the detrimental survival effect of VHR or unfavorable karyotype. The study included 67 patients with PMF or secondary MF who received HCT at the Mayo Clinic and in whom pretransplant cytogenetic information was available. Dynamic international prognostic scoring system (DIPSS) risk distribution was 13% high, 66% intermediate-2 and 21% intermediate-1. Cytogenetic risk distribution was 11% VHR, 34% unfavorable and 55% favorable. At median post-HCT follow-up of 60 months for living patients (range 34-170), 28 (42%) deaths were recorded. Five-year survival was 62% and was not affected by VHR or unfavorable karyotype (P = .68). The salutary effect of HCT in patients with VHR or unfavorable karyotype was also apparent during analysis of a combined dataset that included a nontransplant cohort of 383 patients with PMF; multivariable analysis of the combined dataset (n = 450) resulted in HRs (95% CI) of 2.4 (1.6-3.6) for absence of transplant, 3.3 (2.2-4.8) for VHR karyotype, 1.6 (1.2-2.1) for unfavorable karyotype, 2.9 (2.0-4.2) for DIPSS high and 1.7 (1.4-2.2) for DIPSS intermediate-2. These observations were further confirmed by analysis of more stringently matched case-control subset cohorts and provide the evidence for the therapeutic preference of HCT in cytogenetically high risk patients with MF.