目的 观察聚乙二醇化重组人粒细胞刺激因子(PEG-rhG-CSF)与重组人粒细胞刺激因子(rhG-CSF)在造血干细胞移植后促进造血恢复的疗效对比。方法 回顾分析2016年1月—2020年12月以来在深圳市第二人民医院血液科进行造血干细胞移植的恶性血液疾病患者共 100例,随机分为2组,分别在造血干细胞回输后给与聚乙二醇化重组人粒细胞刺激因子与重组人粒细胞刺激因子。结果 PEG-rhG-CSF组与rhG-CSF组中性粒细胞植入时间分别为(18.7±3.4)天、(18.0±3.1)天,P=0.281,无统计学差异。粒细胞缺乏伴发热在PEG-rhG-CSF组与rhG-CSF组分别发生26例、29例,发生率分别为53.06%、56.86%,P=0.89,无差异。用药次数分别为2.6次(2~5次)、18.1次(11~31次),P<0.05,差异有统计学意义。不良反应主要为骨痛、肌肉疼痛。结论 PEG-rhG-CSF组与rhG-CSF组结果相似,PEG-rhG-CSF具有用药次数少的优势。

Objective The efficacy of pegylated recombinant human granulocyte stimulating factor (PEG-rhG-CSF) and recombinant human granulocyte stimulating factor(rhG-CSF) in promoting hematopoiesis recovery after hematopoietic stem cell transplantation.Methods The data of 100 patients with malignant blood diseases who underwent hematopoietic stem cell transplantation in the Hematology Department of Shenzhen Second People's Hospital from January 2016 to December 2020 were retrospectively analyzed.They were randomly assigned to two groups,which accepted PEG-rhG-CSF and rhG-CSF respectively after hematopoietic stem cell transfusion.Results The time of neutrophil implantation in PEG-rhG-CSF group and rhG-CSF group were (18.7±3.4) days and (18.0±3.1) days respectively,P=0.281,showing no statistical difference.There were 26 cases of neutropenia with fever in PEG-rhG-CSF group and 29 cases in rhG-CSF group,with incidence of 53.06% and 56.86% (P=0.89),showing no statistical difference.The times of medication were 2.6 times (2-5 times) and 18.1 times (11-31 times),P<0.05,with significant statistical difference.The main adverse reactions were bone pain and muscle pain.Conclusions The outcomes of PEG-rhG-CSF group and rhG-CSF group were similar,PEG-rhG-CSF had the advantage of fewer times of medication.

目的 探讨PAD方案治疗初发多发性骨髓瘤(MM)有效性及安全性。方法 统计54例接受PAD方案治疗的初发MM患者临床资料,采用回顾性分析方法。PAD方案:P(硼替佐米)1.3 mg/m²,第1、4、8、11天皮下注射,A(脂质体阿霉素)25～30 mg/m²,第1天静脉滴注,D(地塞米松)40 mg,第1～4 天静脉滴注或口服,每21天为1个疗程。采用IMWG疗效标准判定疗效,按NCICTCAE(第3版)标准判断不良反应。结果 ①总体疗效:平均4(2~8)个疗程后,47例(87.0%)患者获部分缓解(PR)以上疗效,其中完全缓解(CR)20例(37.0%),很好的部分缓解(VGPR)19例(35.2%),部分缓解(PR)8例(14.9%),疾病稳定(SD)5例(9.3%),病情进展率(PD)2例(3.7%)。②亚组疗效:54例患者中,35例治疗4个以上疗程,19例小于4个疗程,ORR分别为97.1%(34/35)、68.4%(13/19)(P=0.003)。按照年龄、肾功能、骨破坏数目、骨髓浆细胞比例、ALB、LDH、β2-MG、细胞遗传学、ISS分期、临床分型进行队列亚组疗效比较,结果提示亚组疗效差异无统计学意义(P＞0.05);③总体安全性:中性粒细胞减少8例(14.8%),血小板减少8例(14.8%),周围神经病变16例(29.6%),腹泻2例(3.7%),便秘2例(3.7%),带状疱疹4例(7.4%),细菌感染5例(9.3%),以上不良反应经对症治疗后症状减轻或消失。④亚组安全性:按照年龄和疗程数进行亚组比较,年龄大于60岁患者和年龄小于60岁患者总不良反应发生率和3/4级不良反应发生率分别是47.4% vs 60.0% 和15.8% vs 20.1%,(P=0.404和P=1.00);治疗4个以上疗程患者和小于4个疗程患者总不良反应发生率和3/4级不良反应发生率分别是57.9% vs 54.3%和21.2% vs 17.1%,(P=1.00和P=0.728)。结论 PAD方案治疗初发MM效果显著,缓解率和疗程数有相关性,疗效与传统的生存预后因素无关,可作为MM诱导治疗的一线方案。脂质体阿霉素心脏毒性小,替代传统蒽环类药物阿霉素,不良反应可控,耐受性良好,更适用于老年MM患者。

Objective To investigate the efficacy and safety of PAD regimen in previously untreated patients with multiple myeloma(MM). Methods We retrospectively analyzed 54 patients with newly-diagnosed MM,who were treated with PAD regimen: Bortezomib 1.3mg/m² subcutaneously on day 1,4,8,11. Liposomal doxorubicin 25～30 mg/m² intravenously on the first day. Dexamethasone 40 mg/d intravenously or orally on days 1～4. Treatment was repeated every 21 days. Response was evaluated according to the International Uniform Response Criteria for MM.Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria,version 3.0. Results ①Overall response:after median 4(2～8) courses of PAD,47patients(87.0%)responsed,including complete response (CR) in 20 (37.0%),very good partial response (VGPR) in 19 (35.2%),partial response (PR) in 8 (14.9%),stable disease (SD) in 5 (9.3%) and progressive disease (PD) in 2 (3.7%). ②Subgroups efficacy: among the 54 patients,35 patients received more than 4 therapeutic courses,and 19 patients received less than 4 courses.The ORR was 97.1% (34/35) and 68.4% (13/19) respectively (P=0.003). Subgroups efficacy were compared according to age,renal function,number of bone destruction,proportion of bone marrow plasma cells,ALB,LDH,β2-MG,cytogenetics,ISS staging and clinical classification. The results indicated that there was no statistical difference(P>0.05). ③Overall safety: adverse events included neutropenia in 8 (14.8%),thrombocytopenia in 8 (14.8%),peripheral neuropathy in 16 (29.6%),diarrhea in 2 (3.7%),constipation in 2 (3.7%),herpes zoster in 4 (7.4%) and bacterial infection in 5 (9.3%). The adverse events relieved or disappeared after symptomatic treatment. ④Subgroups safety: compared by age and courses of treatment,the incidence of overall adverse events and grade 3/4 adverse events in patients older than 60 years and ones younger than 60 were 47.4% vs 60.0% and 15.8% vs 20.1% respectively,(P=0.404,P=1.00). The incidence of overall adverse events and grade 3/4 adverse events in patients with more than 4 therapeutic courses and ones with less than 4 courses were 57.9% vs 54.3% and 21.2% vs 17.1% respectively,(P=1.00和P=0.728). Conclusion PAD regimen has really curative effect in treating patients with newly diagnosed MM. There is a correlation between remission rate and therapeutic courses. It can be used as the first selected protocol for the induction therapy of MM. Its efficacy is independent of traditional prognostic factors.Liposomal doxorubicin has almost no cardiotoxicity. Replacing traditional anthracycline doxorubicin,the adverse events are controllable and the tolerance is generally well. PAD regimen is more proper to be applied to older patients with MM.

目的 比较一线伊马替尼疗效欠佳的慢性髓性白血病慢性期(CML-CP)患者,继续伊马替尼原方案或转换为尼洛替尼治疗后的疗效及安全性。方法 收集伊马替尼疗效欠佳的 45 例患者,分为伊马替尼组22例及尼洛替尼转换组23例,22例伊马替尼组患者继续接受原方案伊马替尼治疗,剂量均为400 mg qd,又将尼洛替尼转换组分为早期尼洛替尼转换组7例,晚期尼洛替尼组转换有16例。尼洛替尼转换组的23例患者接受尼洛替尼的剂量均为400 mg,q12h。所有入组患者首诊时测定 Sokal 评分,在治疗过程中随访观察定期监测血液学、细胞遗传学及分子学缓解情况(FISH 和 RQ-PCR),并对患者用药后的基本情况、临床表现及不良反应进行记录。结果 转换尼罗替尼治疗3个月时,早期尼洛替尼转换组中国际标准化 BCR-ABL1融合基因转录本水平(BCR-ABL1^IS)＜10%的患者有 5 例(71.4%),晚期尼洛替尼转换组BCR-ABL1^IS＜10%的患者有6例(37.5%),差异无统计学意义(P＞0.05)。中位观察6(3～12)个月,尼罗替尼组中有17例(73.9%)获得部分细胞遗传学反应,9例(39.1%)患者获得主要分子学反应。伊马替尼组中有9例(40.9%)获得部分细胞遗传学反应,2例(9.1%)患者获得主要分子学反应,尼洛替尼组部分细胞遗传学反应、主要分子学反应患者优于伊马替尼组(P值分别为0.027、0.020)。45例患者中达到完全细胞遗传学反应的患者与未达到完全细胞遗传学反应相比,Sokal 评分偏低(P=0.032)。结论 尼洛替尼可使伊马替尼疗效欠佳的 CML-CP 患者达到更好的疗效,因此需要及时对伊马替尼疗效欠佳的 CML-CP 患者进行评估后及时更换为尼洛替尼等二代酪氨酸激酶抑制剂。

Objective To assess the clinical efficacy and safety of original scheme or switching to nilotinib in patients with chronic myeloid leukemia in chronic phase(CML-CP)with suboptimal response of first-line imatinib. Methods 45 patients with suboptimal response of imatinib were collected and divided into 22 patients who continued to use original scheme and 23 patients who switched to nilotinib therapy. All the 22 patients of imatinib group received imatinib 400 mg once a day. And the 23 patients of nilotinib group were divided into early switch group and late switch group. Early switch group had 7 patients, late switch group had 16 patients. Both early and late switch to nilotinib group were subsequently to nilotinib 400 mg q12h. Sokal scores of all the enrolled patients were measured at the first diagnosis. Hematology, cytogenetics and molecular remission (FISH and RQ-PCR)were monitored, and the patients' basic information, clinical manifestations and adverse reactions were recorded regularly during the treatment. Results After switching to nilotinib for 3 months,there were 5 patients (71.4%)whose BCR-ABL1^IS<10% in the early nilotinib switch group, while 6 patients (37.5%)in the late nilotenib switch group.There was no statistical difference(P>0.05).With a median observation period of 6(3～12)months,there were 17 (73.9%)patients achieved partial cytogenetic response and 9 (39.1%)patients achieved major molecular response in the nilotinib group,there were 9 patients (40.9%)achieved partial cytogenetic response and 2 patients (9.1%)achieved major molecular response in the imatinib group. Patients who achieved partial cytogenetic response and major molecular response in the nilotinib group were more than those in the imatinib group (P values were 0.027 and 0.020, respectively).Sokal scores of 45 patients who had achieved complete cytogenetic response were lower than those who had achieved it (P=0.032). Conclusion Early switch to nitotinib is feasible and effective to patients who didn't have optimal response to imatinib. It is necessary to assess patients regularly in order to have the proper timing switching patients to nilotinib therapy.