The benefit of high-dose melphalan followed by autologous hematopoietic stem cell transplantation (HDM-ASCT) for multiple myeloma (MM) patients with renal insufficiency (RI) is debated. A systematic review and meta-analysis were conducted to assess the safety and efficacy of HDM-ASCT in MM patients with RIs, and the findings were compared with real-world data. The study included 26 articles, 13 of which were pooled for meta-analysis. We compared three different types of MM patients with RI against MM patients with normal renal function (NRF). These patients were: MM patients with RI at the time of transplantation; MM patients with RI at the time of diagnosis; MM patients with RI at diagnosis but with NRF at transplantation. The meta-analysis indicated that MM patients with RIs conditioned with melphalan ≤ 140 mg/m2 followed by ASCT had transplant-related mortality rates comparable to those without RIs. The complete response rates post-ASCT were similar between MM patients with RIs and those with NRF. Although progression-free survival (PFS) was statistically similar between the groups, MM patients with RIs had significantly poorer overall survival (OS) than those with NRF. The real-world data supported these findings. With a reduced dose of melphalan, ASCT is safe and effective for MM patients with RI. MM patients with RI have similar complete response rates and PFS after ASCT compared to MM patients with NRF. The lower OS in MM patients with RI indicates the need for further research to improve OS in these patients.

BACKGROUND: Despite the success of chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory multiple myeloma (RRMM), failure after CAR T-cell therapy remains an unmet medical need. An effective consolidation therapy after CAR T-cell therapy may improve the prognosis of RRMM.
OBJECTIVE: To investigate the effects of consolidation therapy with autologous hematopoietic stem cell transplantation (AHCT) after B-cell maturation antigen (BCMA)-targeted CAR T-cell therapy on the prognosis of RRMM patients.
METHODS: This retrospective study included 39 RRMM patients who received BCMA-targeted CAR T-cell therapy. Basic clinical, therapy, and outcome data were collected, and factors associated with survival were analyzed.
RESULTS: Among the 39 RRMM patients included in the study, 15 had high-risk cytogenetics and 11 had extramedullary disease (EMD). All 39 patients reached peak CAR T-cell expansion within 28 days after infusion. Twenty-six patients developed cytokine release syndrome, including 12 grade 1 and 14 grade 2 cases. Survival analysis revealed that high-risk cytogenetics, high tumor load (International Staging System [ISS] stage III), and EMD were negatively associated with progression-free survival (PFS) and overall survival (OS). Thirteen patients received consolidation AHCT therapy 50-276 days after CAR T-cell therapy, with a median interval of 92 days. No serious complications occurred after consolidation AHCT. Survival analysis showed that consolidation AHCT effectively improved OS and PFS over maintenance chemotherapy. Moreover, Cox regression analysis identified low tumor load (ISS stage I/II) and consolidation AHCT as independent predictors of superior PFS and OS and high-risk cytogenetics as an independent risk factor for poor PFS.
CONCLUSIONS: Consolidation AHCT after CAR T-cell therapy in RRMM patients can improve patient survival.

Multiple myeloma (MM) patients are often accompanied by heightened levels of oxidative stress, even following bone marrow transplantation. Trace mineral supplements have been found to regulate and inhibit the activity of oxidative radicals and inflammatory factors, which are involved in the pathogenesis of MM. The study sought to evaluate the effectiveness of the supplementation by analyzing changes in oxidative, anti-oxidative, and inflammation markers. Patients were randomly assigned to a zinc or placebo group, with the former receiving 30 mg of zinc or placebo tablets daily for 1 month. Blood samples were collected from the patients on the day of transplantation, 15 days, and 30 days post-transplantation. Real-time PCR was employed to measure the expression of oxidative/antioxidative genes. Furthermore, the protein level of oxidative markers in serum samples was assessed. Finally, serum TNF-α concentrations were measured using the ELISA technique. The expression levels of SOD1, SOD2, and NRF2 genes were significantly higher on days 15 and 30 compared to the control group (P < 0.05), with a greater increase on day 30 (P < 0.05). Conversely, the expression levels of Keap1 and NOX2 genes were lower on day 30 than those of the control group (P < 0.05), with a further decrease from day 15 to day 30 (P < 0.05). The experimental group exhibited a notable reduction in TNF-α cytokine levels on day 30 compared to the control and placebo groups (P < 0.05). All findings were coordinated according to the nutritional questionnaire. Our findings suggest a potential benefit of zinc supplementation in managing the adverse effects of chemotherapy in MM patients, warranting further investigation.

OBJECTIVE: The aim was to determine the value of autologous haematopoietic stem cell transplantation (aHSCT) as a therapeutic intervention for progressive multiple sclerosis (PMS) based on a systematic review of the current literature.
METHODS: All studies from the databases PubMed and Google Scholar published in English before February 2024 which provided individual data for PMS patients were systematically reviewed. PICO was defined as population (P), primary progressive MS and secondary progressive MS patients; intervention (I), treatment with aHSCT; comparison (C), none, disease-modifying therapy treated/relapsing-remitting MS cohorts if available; outcome (O), transplant-related mortality, progression-free survival (PFS) and no evidence of disease activity.
RESULTS: A total of 15 studies met the criteria including 665 patients with PMS (74 primary progressive MS, 591 secondary progressive MS) and 801 patients with relapsing-remitting MS as controls. PFS data were available for 647 patients. PMS patients showed more severe disability at baseline than relapsing-remitting MS patients. The average transplant-related mortality for PMS in 10 studies was 1.9%, with 10 deaths in 528 patients. PFS ranged from 0% to 78% in PMS groups 5 years after treatment initiation, demonstrating a high variability. No evidence of disease activity scores at 5 years ranged from 0% to 75%.
CONCLUSIONS: Based on the available data, aHSCT does not halt progression in people with PMS. However, there appears to be evidence of improved outcome in selected patients. Due to the heterogeneity of the available data, more comprehensive clinical trials assessing the efficacy of aHSCT across different patient groups are urgently needed to reduce variability and improve patient stratification.

Adequate stem cell harvesting is required for autologous hematopoietic transplantation. In deficient mobilizer patients, the collection of stem cells can be challenging because of the impossibility of achieving satisfactory CD34 cell counts with GCSF + - chemotherapy. Plerixafor is a potent and expensive drug that promotes the release of stem cells from the medullary niche to the peripheral blood and allows satisfactory harvests. We performed a retrospective analysis of 370 patients with myeloma and lymphoma harvested at our institution. 99 % of patients achieved satisfactory apheresis using Plerixafor in 45 %. Satisfactory harvests were obtained in patients mobilized with GCSF or plerixafor. In patients who used plerixafor, it was necessary to perform fewer apheresis procedures (P = 0.05). In multivariate analysis, the only factor that predicted the need for plerixafor was the presence of less than 30,000 CD34 / ul on the day of apheresis (OR 0.3. p < 0.001). Since we adopted the plerixafor protocol guided by CD34 counts, the number of patients with harvest failure has decreased. In conclusion, the rational and standardized use of plerixafor favors satisfactory harvest in patients who require autologous transplantation in South-American patients.

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDC/ASCT) has been useful in relapsed or refractory classic Hodgkin lymphoma (RRcHL). Furthermore, a ranimustine, cytarabine, etoposide, and cyclophosphamide (MCVAC) conditioning regimen has been effective in diffuse large B-cell lymphoma. However, limited data are available regarding this conditioning regimen for cHL. In this study, we investigated the efficacy and toxicity of MCVAC for RRcHL. We retrospectively analyzed 10 patients with RRcHL who underwent ASCT preceded by the MCVAC conditioning regimen between January 2009 and December 2021 at our institution. A total of 10 patients (median [range] age, 36 [23-64] years), including 5 (50%) men and 5 (50%) women, were treated with the MCVAC regimen followed by ASCT. The median follow-up duration of the 10 patients was 25.0 months. The 36-month PFS and OS rates were 43.8% (95% CI, 11.9%-72.6%) and 64.0% (95% CI, 22.6%-87.5%), respectively. Two patients died because of treatment-related factors, and one patient died because of disease progression. Based on our findings, recognizing the risk factors for adverse events (AEs) associated with this treatment, MCVAC may be a valid treatment option for the management of RRcHL.

Early lymphocyte recovery as manifested by an absolute lymphocyte count at d+15 (ALC-15) ≥ 0.5 × 109/L after autologous hematopoietic stem cell transplantation (AHCT) has been associated with a better outcome. This prospective multicenter study aimed to clarify factors associated with ALC-15 ≥ 0.5 × 109/L after AHCT among 178 patients with non-Hodgkin lymphoma. The mobilization capacity, as manifested by peak blood CD34+ cell numbers > 45 × 106/L correlated with higher ALC-15 levels (p = 0.020). In addition, the amount of CD3+CD4+ T cells > 31.8 × 106/kg in the infused graft predicted ALC-15 ≥ 0.5 × 109/L (p < 0.001). Also, the number of infused graft CD3+CD8+ T cells > 28.8 × 106/kg (p = 0.017) and NK cells > 4.4 × 106/kg was linked with higher ALC-15 (p < 0.001). The two-year progression-free survival after AHCT was significantly better in patients with ALC-15 ≥ 0.5 × 109/L (74 vs. 57%, p = 0.027). The five-year OS in patients with higher ALC-15 was 78% vs. 60% in those with lower ALC-15 (p = 0.136). To conclude, the mobilization capacity of CD34+ cells and detailed measures of graft cellular content mark prognostic tools that predict ALC-15 ≥ 0.5 × 109/L, which is associated with a better outcome in NHL patients after AHCT.

BACKGROUND: To explore the efficiency and safety of recombinant human thrombopoietin (TPO) on the platelet engraftment after autologous stem cell transplantation (ASCT) in patients with aggressive lymphoma.
METHODS: Forty patients were enrolled in a single-center, retrospective clinical trial from July 2019 with rhTPO administration when the platelet count ≤ 75 × 109/L after the reinfusion of stem cells. The hematopoietic reconstitution, platelet transfusion dependence, the cost and length of hospitalization, side effects and survival benefit were compared between the rhTPO group and the control group of 25 historic patients without rhTPO.
RESULTS: The cumulative incidence of platelet engraftment in the rhTPO group was significantly higher since d+ 13 post-transplantation. But no difference of neutrophil engraftment was found. rhTPO was considered to influence the platelet engraftment independently by multivariate analysis. Subgroup analysis demonstrated that when the patients were older than 45 years old, male, at stage-IV as diagnosed and obtained PR after previous treatment, rhTPO was more recommended to facilitate platelet early engraftment after ASCT. Although rhTPO didn\'t relieve the dependency of platelet transfusion, patients had the shorter length of hospitalization. And better OS was shown in the rhTPO group.
CONCLUSIONS: rhTPO improved platelet engraftment after ASCT with aggressive lymphoma, especially the ones older than 45 years old, male, at stage-IV as diagnosed and obtained PR after previous treatment. Although rhTPO didn\'t lessen platelet transfusion dependence, the length and medical cost of hospitalization were reduced when rhTPO was involved. rhTPO was efficacy and safety which could be recommended after ASCT.

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. Results: ① A 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. ③ The 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]. ⑤ All 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). ⑥ The 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.
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: The effect and safety of etoposide combined with G-CSF were compared with those of cyclophosphamide combined with G-CSF in autologous peripheral blood mobilization in patients with multiple myeloma (MM) . Methods: Patients with MM who received autologous peripheral blood stem cell mobilization and collection in the Department of Hematology, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 1, 2020 to July 31, 2023 were included. A total of 134 patients were screened by propensity score matching technology according to a 1∶1 ratio. A total of 67 cases were each treated with ETO combined with G-CSF mobilization scheme (ETO group) and CTX combined with G-CSF mobilization scheme (CTX group). Their clinical data were retrospectively analyzed. Results: ①Collection results: the ETO and CTX groups [2 (1-3) d vs 2 (1-5) d; P<0.001] and CD34(+) cells [7.62×10(6) (2.26×10(6)-37.20×10(6)) /kg vs 2.73×10(6) (0.53×10(6)-9.85×10(6)) /kg; P<0.001] were collected. The success rate of collection was 100.0% (67/67) versus 76.1% (51/67) (P<0.001). Excellent rate of collection was 82.1% (55/67) versus 20.9% (14/67; P<0.001). Two patients in the ETO group switched protocols after 1 day of collection, and 11 patients in the CTX group switched protocols after 1-2 days of collection. ②Adverse reactions: granular deficiency with fever (21.5%[14/65] vs. 10.7%[6/56]; P=0.110), requiring platelet transfusion [10.7% (7/65) vs 1.8% (1/56) ; P=0.047]. ③Until the end of follow-up, 63 cases in the ETO group and 54 cases in the CTX group have undergone autologous transplantation. The median number of CD34(+) cells infused in the two groups was 4.62×10(6) (2.14×10(6)-19.89×10(6)) /kg versus 2.62×10(6) (1.12×10(6)-5.31×10(6)) /kg (P<0.001), neutrophil implantation time was 11 (9-14) d versus 11 (10-14) d (P=0.049), and platelet implantation time was 11 (0-19) d vs. 12 (0-34) d (P=0.035). One case in the CTX group experienced delayed platelet implantation. Conclusion: The mobilization scheme of etoposide combined with G-CSF requires relatively platelet transfusion, but the collection days are shortened. The collection success rate, excellent rate, and the number of CD34(+) cells obtained are high, and the neutrophil and platelet engraftment is accelerated after transplantation.
目的： 比较依托泊苷（ETO）联合G-CSF与环磷酰胺（CTX）联合G-CSF在多发性骨髓瘤（MM）患者中进行自体外周血造血干细胞动员的效果及安全性。 方法： 纳入2020年1月1日至2023年7月31在首都医科大学附属北京朝阳医院血液科接受自体外周血造血干细胞动员、采集的MM患者，利用倾向性评分按照1∶1匹配比例筛选出134例患者，ETO联合G-CSF动员方案（ETO组）、CTX联合G-CSF动员方案（CTX组）各67例，对其临床资料进行回顾性分析。 结果： ①ETO组、CTX组采集天数分别为2（1~3）d、2（1~5）d（P<0.001），CD34(+)细胞采集量分别为7.62（2.26~37.20）×10(6)/kg、2.73（0.53~9.85）×10(6)/kg（P<0.001），采集成功率分别为100.0%（67/67）、76.1%（51/67）（P<0.001）、采集优良率分别为82.1%（55/67）、20.9%（14/67）（P<0.001）。ETO组有2例患者在采集1 d后进行方案转换，CTX组有11例患者在采集1~2 d后进行方案转换。②ETO组、CTX组粒缺伴发热发生率分别为21.5%（14/65）、10.7%（6/56）（P=0.110），血小板输注患者占比分别为10.7%（7/65）、1.8%（1/56）（P=0.047）。③至随访截止，ETO组63例、CTX组54例患者接受了自体造血干细胞移植，中位CD34(+)细胞回输量分别为4.62（2.14~19.89）×10(6)/kg、2.62（1.12~5.31）×10(6)/kg（P<0.001），中性粒细胞植入时间分别为11（9~14）d、11（10~14）d（P=0.049），血小板植入时间分别为11（0~19）d、12（0~34）d（P=0.035）。CTX组有1例患者发生血小板延迟植入。 结论： 依托泊苷联合G-CSF的动员方案可能有较多的患者需要输注血小板，但采集天数缩短，采集成功率、优良率及CD34(+)细胞采集量较高，移植后中性粒细胞和血小板植入较快。.