Ruxolitinib combined with TCP therapy for treatment of myelofibrosis:A real world study
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摘要: 目的:为了减轻芦可替尼对骨髓纤维化(MF)患者的血液学毒副反应,我们开展了一项小剂量芦可替尼联合TCP方案的探索性治疗,并呈现该研究方案的真实数据。方法:于2019-02-01—2020-03-31对就诊于我院血液科的19例MF患者,给予小剂量芦可替尼联合TCP方案治疗(芦可替尼5 mg Bid;沙利度胺50 mg QN,骨化三醇25 mg Bid,泼尼松10 mg QD)。治疗过程中每个月复查血常规和肝肾功能,每3个月复查肝脾超声和MF症状评估表(MPN-SAF-TSS)。结果:共19例患者纳入研究,男10例,女9例;中位年龄63(31~82)岁,<60岁和60~74岁患者各7例(各36.84%),≥75岁5例(26.32%);有1例高白细胞(WBC≥25×109/L),5例贫血(Hb<100 g/L),3例血小板减少(PLT<100×109/L);PMF患者13例(68.42%),post-ET MF和post-PV MF患者各3例(各15.79%)。DIPSS预后分组:中危-1组9例(47.37%),中危-2组10例(52.63%);MIPSS70积分:中危组13例(68.42%),高危组6例(31.58%);染色体核型:极高危核型1例(5.26%),有利核型16例(84.21%),不良核型2例(10.53%);二代基因检测:JAK2V617F突变阳性14例(73.68%),CARL突变阳性2例(10.53%),JAK2、CALR、MPL三阴性3例(15.79%),5例(26.32%)患者有1个高危突变,1例(5.26%)患者有2个高危突变。治疗前MPN-SAF-TSS评分33(11~60)分;15例(78.95%)患者B超证实有脾肿大。中位治疗时间6(3~13)个月。19例患者经治疗后,高白细胞、贫血、血小板减少患者各减少1例。19例患者经治疗后最低MPN-SAF-TSS评分17(8~35)分,评分下降幅度13(3~45)分;有4例(21.05%)患者症状评分降低≥50%(最大75%)。15例脾肿大患者治疗后13例(86.67%)有不同程度的脾脏缩小,缩小比例38.67%(4.36%~53.26%),缩小比例≥35%者有8例(53.33%)。接受该治疗方案的19例患者目前均未停药,有1例在用药1个月时出现血红蛋白和血小板计数下降(治疗2个月后恢复正常),另1例用药2个月时贫血加重(治疗3个月后血红蛋白回升),其余17例患者均未见血液学不良反应;未出现Ⅲ/Ⅳ级非血液学不良反应;Ⅰ/Ⅱ级非血液学不良反应包括便秘1例、腹胀2例,经胃肠道调节治疗后好转。没有患者因不良反应中断治疗或者用药剂量调整。结论:小剂量芦可替尼联合TCP方案的治疗方案,对于MF患者安全有效,不仅能减少常规剂量芦可替尼引发的贫血和血小板减少的发生率,而且对于老年MF患者,甚至是>75岁的超高龄患者,也可以作为一种治疗选择。然而,该方案也存在脾脏缩小不敏感的患者,有待于调整芦可替尼剂量。Abstract: Objective:To reduce the hematologic toxicity and adverse reactions of ruxolitinib on myelofibrosis(MF)patients,a pilot study of low dose ruxolitinib combined with TCP therapy was conducted and the results were presented as follows.Method:A total of 19 patients with MF,who were treated in the Department of Hematology,Shanghai No.6 People's Hospital,were given low dose of ruxolitinib combined with TCP(ruxolitinib 5 mg,Bid;thalidomide 50 mg QN;calcitriol 25 mg,Bid;prednisone 10 mg QD)from February 1,2019 to March 31,2020.Ordinary blood test and hepatic and renal functions were tested monthly,liver and spleen ultrasound and myeloproliferative neoplasm symptom assessment form total symptom score(MPN-SAF-TSS)were checked every three months during the study.Result:Among 19 patients,10 cases were male and 9 cases were female;the median age was 63(31-82),7 cases(36.84%)were<60 years old,7 cases(36.84%)were 60-74 years old and 5 cases(26.32%)were ≥75 years old.There was 1 case with hyperleukocytosis(WBC≥25×109/L),5 cases with anemia(Hb<100 g/L),and 3 cases with thrombocytopenia(PLT<100×109/L).Thirteen patients(68.42%)were with PMF,3 patients(15.79%)with post-ET MF and 3 patients(15.79%)with post-PV MF.DIPSS prognostic grading group:9 cases(47.37%)in the intermediate-risk-1 group and 10 cases(52.63%)in the intermediate-risk-2 group.MIPSS70 score:13 cases(68.42%)in the middle-risk group and 6 cases(31.58%)in the high-risk group.Karyotype:1 case(5.26%)with very-high-risk karyotype,16 cases(84.21%)with favorable karyotype and 2 cases(10.53%)with unfavorable karyotype.Second-generation sequencing:14 cases(73.68%)were positive for JAK2 V617 F mutation,2 cases(10.53%)were positive for CARL mutation,3 cases(15.79%)were triple negative for JAK2,CALR and MPL,5 cases(26.32%)had one high risk mutation,1 case(5.26%)had two high-risk mutations.Before treatment,the MPN-SAF-TSS score was 33(11-60)points and 15 patients(78.95%)were confirmed to have splenomegaly by ultrasound.The median treatment time was 6(3-13)months.There was 1 case of alleviated hyperleukocytosis,anemia and thrombocytopenia after treatment,respectively.After treatment of 19 patients,the lowest MPN-SAF-TSS score was 17(8-35)points,and the score decreased by 13(3-45)points,4 patients(21.05%)had a score reduction of ≥50%(maximum 75%).Thirteen cases(86.67%)out of 15 patients with splenomegaly achieved different degrees of spleen response,with a shrinkage ratio of 38.67%(4.36%-53.26%),and 8 cases(53.33%)achieved a ≥35% reduction from baseline in spleen size.The 19 patients receiving this treatment had not withdrawn at present.One case showed a decrease in hemoglobin and platelet counts during the first month of treatment(returned to normal after 2 months of treatment),and another case showed severer anemia during the second month of treatment(rebounded after 3 months of treatment),and the remaining 17 patients had no hematological adverse events.No grade Ⅲ/Ⅳ non-hematological adverse event was observed.Grade Ⅰ/Ⅱ non-hematological adverse events,including 1 case of constipation and 2 cases of abdominal distension,were improved after gastrointestinal treatment.No patients discontinued or adjusted the dosage of therapies due to adverse events.Conclusion:Low dose ruxolitinib combined with TCP therapy appears to be a safe and effective treatment for MF patients.It reduces incidence of anemia and thrombocytopenia compared with conventional doses of ruxotinib and offers a treatment option for elderly MF patients,even for those super elderly patients over 75 years old.For cases of insensitivity to spleen reduction,the dose of ruxotinib needs to be adjusted.
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Key words:
- myelofibrosis /
- ruxolitinib /
- TCP therapy /
- real world study /
- low dose
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