无冻存一体化自体造血干细胞移植模式治疗新诊断多发性骨髓瘤的回顾性临床研究

Retrospective clinical study on cryopreservation-free integrated autologous hematopoietic stem cell transplantation model for newly diagnosed multiple myeloma

目的探讨无冻存一体化自体造血干细胞移植模式在多发性骨髓瘤(MM)患者中的疗效和安全性。方法纳入2020年7月31日至2022年12月31日在电子科技大学附属医院四川省人民医院接受自体造血干细胞移植的新诊断多发性骨髓瘤(NDMM)患者96例, 对其临床资料进行回顾性分析。41例患者接受无冻存一体化移植模式(观察组), 造血干细胞动员采集后冷藏于医用输血冰箱(4 ℃)并立即启动美法仑预处理, 预处理结束24 h后回输自体造血干细胞;55例患者接受传统移植模式(对照组), 造血干细胞动员采集后液氮冷冻保存, 择期启动移植流程。两组患者均采用G-CSF联合普乐沙福进行自体造血干细胞动员。结果①观察组移植前疾病状态为非常好的部分缓解(VGPR)及完全缓解(CR)患者占比显著高于对照组[82.9%(34/41)对60.0%(33/55), P=0.016]。②与对照组相比, 观察组1级口腔黏膜炎的发生率较高(P<0.001), 但2、3级口腔黏膜炎的发生率较低(P=0.004, P=0.048), 两组均未发生≥4级口腔黏膜炎;观察组1级腹泻的发生率较高(P=0.002), 3级腹泻的发生率较低(P=0.007), 4级腹泻的发生率差异无统计学意义(P=0.506), 两组均未发生5级腹泻。③观察组细菌感染发生率低于对照组(34.1%对65.5%, P=0.002), 真菌感染(29.3%对31.4%, P=0.863)、病毒感染(4.88%对3.64%, P=0.831)发生率差异无统计学意义。④观察组与对照组粒细胞植入时间和血小板植入时间差异无统计学意义[10(8~20)d对11(8~17)d, P=0.501;13(10~21)d对15(10~20)d, P=0.245]。⑤移植后100 d前所有患者均未使用来那度胺治疗。移植后30 d, 观察组CTL、NK、Th细胞计数低于对照组(P<0.001, P=0.049, P=0.002), NKT细胞计数高于对照组(P=0.024)。移植后100 d, 观察组CTL、NKT、Th细胞计数高于对照组(P=0.025, P=0.011, P=0.007), NK细胞计数两组差异无统计学意义(P=0.396)。⑥中位随访18(4~33)个月, 观察组和对照组移植后2年总生存率分别为91.5%、78.2%(P=0.337), 无复发生存率分别为85.3%、77.6%(P=0.386), 累积复发率分别为9.8%、16.9%(P=0.373)。结论无冻存一体化自体造血干细胞移植模式在NDMM中可获得与传统移植模式相似的疗效, 重度黏膜炎和感染的发生率低于传统移植模式。

Objective To explore the efficacy and safety of cryopreservation-free integrated autologous hematopoietic stem cell transplantation(HSCT)model for patients with multiple myeloma.Methods A total of 96 patients with newly diagnosed multiple myeloma(NDMM)between July 31,2020,and December 31,2022,were retrospectively analyzed,of which 41 patients in the observation group received integrated non-cryopreserved transplantation mode.After hematopoietic stem cells were mobilized and collected,melphalan was started immediately for pre-transplant conditioning,and non-cryopreserved grafts from the medical blood transfusion refrigerator were directly injected intravenously into the patient within 24-48 h after the melphalan conditioning.The control group consisted of 55 patients who received traditional transplantation mode.After hematopoietic stem cells were collected,stem cell cryopreservation was performed in liquid nitrogen,and then the transplant plans were started at the right time.All patients received mobilization of autologous hematopoietic stem cells using the G-CSF combined with the plerixafor.Results①A total of 34 patients(82.9%)with VGPR plus CR in the observation group were significantly higher than 33 patients(60.0%)in the control group(P=0.016).②Compared with the control group,the incidence of grade 1 oral mucosal inflammation was higher in the observation group(P<0.001);however,the incidence of grades 2 and 3 oral mucosal inflammation was lower(P=0.004,P=0.048),and neither group experienced grade 4 or above oral mucosal inflammation.The incidence of grade 1 diarrhea was higher in the observation group(P=0.002),whereas the incidence of grade 3 diarrhea was lower(P=0.007).No statistically significant difference was observed in the incidence of grade 4 diarrhea(P=0.506),and neither group experienced grade 5 diarrhea.③The incidence of bacterial infection in the observation group was lower than that in the control group(34.1%vs 65.5%,P=0.002),whereas no statistically significant difference was observed in the incidence of fungal infection(29.3%vs 31.4%,P=0.863)and viral infection(4.88%vs 3.64%,P=0.831).④No statistically significant difference was observed in the implantation time of granulocytes and platelets between the observation and control groups[10(8-20)days vs 11(8-17)days,P=0.501;13(10-21)days vs 15(10-20)days,P=0.245].⑤All patients did not receive lenalidomide treatment 100 days post-transplantation.At 30 days post-transplantation,the CTL,NK,and Th cell counts in the observation group were lower than those in the control group(P<0.001,P=0.002,P=0.049),and the NKT cell counts were higher than those in the control group(P=0.024).At 100 days post-transplantation,the CTL,NKT,and Th cell counts in the observation group were higher than those in the control group(P=0.025,P=0.011,P=0.007),and no statistically significant difference in NK cell counts was observed between the two groups(P=0.396).⑥The median follow-up was 18(4-33)months.The overall 2-year survival rates of the observation and control groups post-transplantation were 91.5%and 78.2%,respectively(P=0.337).The recurrence-free survival rates were 85.3%and 77.6%,respectively(P=0.386),and the cumulative recurrence rates were 9.8%and 16.9%,respectively(P=0.373).Conclusion In NDMM,the cryopreservation-free integrated autologous HSCT model can achieve similar therapeutic effects as traditional transplantation models,with lower rates of severe mucosal inflammation and infection compared with traditional transplantation models.