Advanced lytic lesion is a poor mobilization factor in peripheral blood stem cell collection in patients with multiple myeloma

This study examined the incidence and predictors of peripheral blood stem cell (PBSC) mobilization failure in patients with multiple myeloma (MM). Retrospective data for 104 patients who received granulocyte colony‐stimulating factor (G‐CSF) alone or with cyclophosphamide as mobilization regimens were analyzed. The rates of mobilization failure using two definitions of failure (< 2 × 10⁶ and < 4 × 10⁶ CD34⁺ cells/kg) following the first collection attempt were 16.3 and 33.7%, respectively. Predictors of mobilization failure were evaluated using logistic regression analysis which included age, advanced osteolytic lesions, bone marrow cellularity before mobilization, platelet count, body mass index before mobilization, and mobilization method. Lytic bone lesions were assessed using a conventional skeletal survey, and advanced osteolytic lesions were defined as lytic lesions in more than three skeletal sites regardless of the number of lytic lesions. On multivariate analysis, advanced osteolytic lesions [hazard ratio (HR) = 10.95, P = 0.001] and age ≥60 years (HR = 5.45, P = 0.016) were associated with a PBSC yield < 2 × 10⁶ CD34⁺ cells/kg, and advanced osteolytic lesions (HR = 5.08, P = 0.006), white blood cell count ≤4,000/µL before mobilization (HR = 4.72, P = 0.005), and G‐CSF only mobilization (HR 10.52, P < 0.001) were associated with PBSC yield < 4 × 10⁶ CD34⁺ cells/kg. The data suggest that an advanced osteolytic lesion is a significant predictor of mobilization failure in MM patients. J. Clin. Apheresis 29:305–310 2014. © 2014 Wiley Periodicals, Inc.     

硼替佐米联合自体外周血造血干细胞移植治疗多发性骨髓瘤

本研究探讨硼替佐米联合自体外周血造血干细胞移植(APBSCT)治疗多发性骨髓瘤(MM)的疗效。对5例MM患者行自体外周血造血干细胞移植,在APBSCT前和预处理中以及移植后的维持治疗中均应用硼替佐咪治疗。选择预处理方案为:硼替佐米(bortezomib)+马法兰(melphalan)。输注的外周血单个核细胞(PBMNC)数为4.06×108(4.09×108-4.37×108)/kg,CD34+细胞数为3.98×106(2.49×106-8.2×106)/kg。结果表明:5例患者造血完全重建,中性粒细胞(ANC)大于0.5×109/L中位时间为14(13-25)天,Plt大于50×109/L中位时间为28(21-58)天。无移植相关死亡病例,5例患者均无病生存。结论:硼替佐米联合自体外周血造血干细胞移植是治疗MM的有效方法,移植后给予硼替佐米维持治疗可能是患者延长生存时间、提高生活质量的较好方法。     

Cyclophosphamide plus granulocyte‐colony stimulating factor for hematopoietic stem cell mobilization in patients with multiple myeloma

We retrospectively reviewed the results of cyclophosphamide (3 g/m²), doxorubicin and dexamethasone plus granulocyte‐colony stimulating factor (G‐CSF) (ID‐CY/DOX group), low‐dose cyclophosphamide (2 g/m²) plus G‐CSF (LD‐CY group) and G‐CSF alone (G‐CSF group) for stem cell mobilization in patients with multiple myeloma. A total of 89 patients with 93 mobilizations were included. Apheresis was started when total white blood cell (WBC) count >10 × 10⁹/L for ID‐CY/DOX and LD‐CY groups and after eight doses of G‐CSF (5 μg/kg twice daily) for G‐CSF group. For five mobilizations in ID‐CY/DOX group, the rate of successful mobilization (≥4.0 × 10⁶/kg CD34+ cells) was 80%. For 78 mobilizations in LD‐CY group, the successful rate was 80.8%. For 10 mobilizations in the G‐CSF group, the successful rate was 50%. The mean yield of CD34+ cells was higher in ID‐CY/DOX and LD‐CY groups as compared with that in G‐CSF group (P = 0.026 and 0.020, respectively). There was no difference in the yield of CD34+ cells between ID‐CY/DOX and LD‐CY groups (P = 0.831). After autologous stem cell transplantation, the days to neutrophil and platelet engraftment were similar in these three groups (P = 0.713 and 0.821, respectively). In conclusion, we observed that ID‐CY/DOX and LD‐CY plus G‐CSF for stem cell mobilization resulted in a higher successful rate and higher stem cell yields than G‐CSF alone and their engraftment time were similar. Total WBC count >10 × 10⁹/L can be used as a guide to start apheresis in CY‐based stem cell mobilization. J. Clin. Apheresis 31:423–428, 2016. © 2015 Wiley Periodicals, Inc.     

Cyclophosphamide‐based hematopoietic stem cell mobilization before autologous stem cell transplantation in newly diagnosed multiple myeloma

High‐dose cyclophosphamide (Cy) is frequently employed for peripheral blood mobilization of hematopoietic stem cells before high‐dose chemotherapy with autologous stem cell transplantation (ASCT) in multiple myeloma (MM). The benefit of mobilization with Cy over filgrastim (granulocyte colony‐stimulating factor; G‐CSF) alone is unclear. Between 2000 and 2008, 167 patients with newly diagnosed MM underwent single ASCT after melphalan conditioning at our institution. Seventy‐three patients were mobilized with G‐CSF alone, and 94 patients with Cy plus G‐CSF (Cy+G‐CSF). We retrospectively analyzed Cy's impact on both toxicity and efficacy. Mobilization efficiency was augmented by Cy; a mean total of 12 versus 5.8 × 10⁶ CD34+ cells/kg were collected from patients mobilized with Cy+G‐CSF versus G‐CSF, respectively, (P < 0.01), over a mean of 1.6 versus 2.2 days of peripheral blood apheresis (p = 0.001). Mobilization‐related toxicity was also, however, augmented by Cy; 14% of Cy+G‐CSF patients were hospitalized because of complications versus none receiving G‐CSF (P < 0.0001). Toxicity, including death, related to ASCT was similar between cohorts. Regarding long‐term outcomes, multivariate analysis revealed no difference for Cy+G‐CSF versus G‐CSF (hazard ratio 0.8 for event‐free survival [95% confidence interval {CI} 0.57–1.25] and 0.96 for overall survival [95% CI 0.61–1.54]). In summary, we show that mobilization with Cy increases toxicity without positively impacting long‐term outcomes in MM. Our findings place into question Cy's benefit as a routine component of stem cell mobilization regimens in MM. Randomized trials are needed to elucidate the risks and benefits of Cy more definitively. J. Clin. Apheresis 30:176–182, 2015. © 2014 Wiley Periodicals, Inc.     

自体外周血干细胞移植治疗非霍奇金淋巴瘤的外周血干细胞动员方案临床分析

本研究比较CEP+G-CSF与CVP+G-CSF动员方案对非霍奇金淋巴瘤(NHL)患者外周血造血干细胞动员采集及造血恢复的效果。回顾性分析我科收治的57例NHL患者。分组采用CEP+G-CSF与CVP+G-CSF动员方案进行外周血干细胞动员采集,并于预处理结束后回输外周血干细胞,分析动员效果、不良反应及自身移植后造血恢复情况。结果表明:动员期间所有患者外周血白细胞(WBC)计数均降至1.0×109/L以下,血小板(Plt)数降至40×109/L以下。57例患者均采集成功,CEP+G-CSF动员方案组采集单个核细胞(MNC)数和CD34+细胞数明显高于CVP+G-CSF动员方案组(p=0.002和p=0.019)。预处理后所有病例均达到骨髓抑制,CEP+G-CSF和CVP+G-CSF动员方案组WBC数恢复到≥1.0×109/L的平均时间分别为11.4和12.3天(p﹥0.05),Plt数恢复到≥50×109/L的平均时间分别为18.6和19.3天(p﹥0.05)。结论:自体外周血干细胞移植治疗NHL疗效显著,CEP或CVP联合G-CSF方案行外周血干细胞动员均安全有效,临床效果满意,CEP+G-CSF方案动员外周血干细胞效果更好。     

Predicting hematopoietic stem cell mobilization failure in patients with multiple myeloma: a simple method using day 1 CD34+ cell yield

Early and reliable prediction of the likelihood of achieving adequate stem cell collection for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) would improve collection efficiency, prevent unnecessary aphereses, and permit appropriate treatment alterations. No previous study has reported a threshold CD34+ cell collection quantity on Day 1 or 2 of leukapheresis that could predict successful stem cell collection. We performed a retrospective analysis of all MM patients undergoing first attempt of stem cell collection at our institution from 2001 through 2008. Recursive partitioning analysis was used to identify Day 1 or Day 1+2 CD34+ collection quantity that predicted failure to reach target ≥ 2 × 10(6) CD34+ cells/kg within five days of collection. Totally, 172 patients were included in the analysis. Patients underwent mobilization with G-CSF or G-CSF+ chemotherapy. 23 of 172 patients (13.4%) failed to collect sufficient (≥ 2 × 10(6) CD34+ cells/kg) CD34+ cells after five days of apheresis: 22 of 29 who collected ≤ 0.70 × 10(6) CD34+ cells/kg and 1 of 143 who collected > 0.70 × 10(6) CD34+ cells/kg (75.9% vs. 0.7%, P < 0.001) on Day 1. Collection failure occurred in 23 of 30 patients who collected ≤ 1.54 × 10(6) CD34+ cells/kg and 0 of 142 who collected >1.54 × 10(6) CD34+ cells/kg (76.7% vs. 0%, P < 0.001) on Days 1 + 2. Day 1 CD34+ cell collection quantity identifies patients unlikely to achieve adequate collection for ASCT. Patients who collect ≤ 0.70 × 10(6) CD34+ cells/kg on day 1 could be considered for treatment modifications to improve CD34+ collection, such as early administration of plerixafor or large volume apheresis.     

Predictive factors for stem cell mobilization failure in multiple myeloma patients: A single center experience

Background and aimHigh-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has been considered the standard of treatment care for patients with multiple myeloma (MM). Insufficient mobilization and harvest of peripheral stem cells can be a major obstacle for performing ASCT. This is resulting in a lacking opportunity of cure in patients with MM. The aim of this study was to evaluate the factors which influence mobilization failure in patients with MM.Materials and methodsThis study has been performed in a retrospective manner. Two hundred and thirty-four patients with diagnosed MM who underwent stem cell mobilization after induction chemotherapy at Hacettepe University Hospital between the years of 2003 and 2018 were evaluated.ResultsA total of 234 patients were included in this study. The median age was 54 (32–76) years at the time of diagnosis. In 209 of 234 patients (89.3%) first mobilization trial was successful. At univariate analysis, among parameters identifiable before mobilization, male gender (p = 0.03), number of chemotherapy cycle before stem cell mobilization (p < 0.001), second ASCT (p < 0.001) and immunomodulatory treatment before stem cell mobilization (p < 0.001) predicted mobilization failure. At multivariate analysis, number of chemotherapy cycle before stem cell mobilization (p = 0.03), second ASCT (p < 0.001) and immunomodulatory treatment before stem cell mobilization (p = 0.02) retained independent predictive power.ConclusionDetectable different clinical characteristics of MM patients before initiating mobilization may be predictors of poor mobilization. Therefore, the mobilization protocol should be evaluated on a patient basis. Minimization of exposure to chemotheraputic agents in MM patients, especially immunomodulatory agents, may increase CD34+ cell harvest yields.     

同胞异基因外周血干细胞移植治疗多发性骨髓瘤10例疗效观察

目的 观察同胞HLA配型相合的异基因外周血干细胞移植(allo-PBSCT)治疗多发性骨髓瘤(MM)的疗效.方法 10例MM患者采用氟达拉滨联合马法兰和环磷酰胺等为主的预处理方案行allo-PBSCT.其中8例患者采用环孢素加霉酚酸酯和短程甲氨蝶呤,2例采用普乐可复(FK506)加短程甲氨蝶呤预防移植物抗宿主病(GVHD).结果 所有患者造血细胞均成功植入,中性粒细胞＞0.5×109/L的中位时间为移植后16(12～24)d,PLT＞20×109/L的中位时间为移植后23( 16～102)d.发生急性GVHD5例,其中仅1例发生了Ⅲ度以上急性GVHD.9例MM患者中7例发生慢性GVHD.100 d内移植相关死亡1例,死因为心、肾功能衰竭和严重感染.1年预期存活率为67.5％,1年无病生存率为55.56％,复发率为11.11％.至今存活6例患者,其中1例已无病生存达99个月.结论 allo-PBSCT在MM中的作用尚需进一步评估,但对于年轻有合适供者的MM患者,以氟达拉滨为基础的allo-PBSCT预处理方案,耐受性好,有可能通过降低移植相关死亡率提高总体生存率.     

自体造血干细胞移植对多发性骨髓瘤患者预后的影响

目的 探讨自体造血干细胞移植(ASCT)在多发性骨髓瘤(MM)治疗中的地位以及对预后的影响.方法 回顾分析1998年10月至2007年2月接受ASCT治疗的28例MM患者(A组)的临床和随访资料,并与同期未行ASCT的MM患者,包括接近完全缓解(nCR)或以上缓解的23例(B组)和仅获得部分缓解(PR)的25例(C组)患者进行比较.分析 ASCT对缓解程度的影响并采用Kaplan-Meier法比较3组患者的缓解持续时间(DOR)、疾病进展时间(TTP)和生存(OS)时间.结果 移植前未达到nCR的8例患者[7例PR和1例轻微缓解(MR)]移植后均达到nCR或以上缓解(3例CR,5例nCR),A组完全缓解(CR)率由移植前的10.7%(3例)提高到42.9%(12例).A组中位DOR(33个月)较B组(17个月)和C组(18个月)延长,差异有统计学意义;A组中位TTP(45个月)较C组(28个月)延长,差异有统计学意义,但与B组(43个月)无明显差异;中位随访时间为30(4～79)个月,A组和B组OS时间较C组长,但随访结束时未显示出差异有统计学意义.结论 ASCT可进一步增强患者的缓解程度,延长患者的DOR和TTP,并可能延长OS时间,改善生存质量;ASCT对TTP的延长得益于更好程度的缓解,因此对其他治疗不能达到很好缓解的MM患者可以通过ASCT改善预后.     

Increment of hematopoietic progenitor cell count as an indicator of efficient autologs stem cell harvest in patients with multiple myeloma

We previously showed that hematopoietic progenitor cell (HPC) count is a useful surrogate for the timing of autologs stem cell collection (ASCC). We investigated the role of HPC count increment in predicting the time for optimal ASCC in patients with multiple myeloma (MM). Between May 2002 and January 2011, 138 patients with MM who underwent ASCC after mobilization with cyclophosphamide (4 g/m²) and granulocyte‐colony stimulating factor at Asan Medical Center. HPC monitoring was started on the 10th day of cyclophosphamide administration and ASCC was performed when HPC count reached at least 10/mm³. Velocity of HPC increment (/mm³/day) was calculated as HPC count on the first day of ASCC/number of days from cyclophosphamide infusion to the first day of ASCC. A total of 422 leukapheresis were performed in 136 patients (median per patient: 3; range: 2–8). Of these patients, 131 (94.9%) successfully achieved optimal ASCC (≥5 × 106 CD34+ cells/kg). The median velocity of HPC increment was 2.17/mm³/day (range: 0.07–144.2/mm³/day). The mean ± standard error numbers of apheresis procedures in patients with velocity of HPC increment ≤2.0/mm³/day and >2.0/mm³/day were 3.43 ± 0.17 and 2.70 ± 0.11, respectively, and their median times to optimal ASCC were 15 and 13 days, respectively, with a hazard ratio of 0.47 (95% confidence interval, 0.32–0.68; P < 0.001) on multivariate analysis. Therefore, a slower increase of HPC of ≤2.0/mm³/day is associated with larger number of apheresis procedures for optimal ASCC. J. Clin. Apheresis 27:229–234, 2012. © 2012 Wiley Periodicals, Inc.     

自体外周血干细胞移植病人的健康教育

[目的]为56例进行自体外周血造血干细胞移植(APB-SCT)的病人提供全程的健康教育,使病人在层流病房中很好地配合治疗及护理,减少并发症,顺利转出层流病房。[方法]采取一对一交谈法、病人现身说法等形式,从病人心理、层流室环境、无菌观念、化疗、回输造血干细胞过程、Ⅳ度骨髓抑制期、转出层流室和出院进行全面的健康教育。[结果]56例病人在干细胞移植的各个阶段都能积极配合医护工作,平均15.2d就完成整个自体外周血造血干细胞移植过程,顺利转出层流病房。[结论]56例病人经过全程健康教育,能正确认识自体外周血干细胞移植的过程及在层流室中配合医护工作,心身协调地完成治疗。     

The efficacy of residual plerixafor for second-day stem cell mobilization in multiple myeloma patients

BackgroundGranulocyte colony-stimulating factor (G-CSF) plus plerixafor has been shown to improve the efficacy of peripheral blood stem cell (PBSC) mobilization, however, due to its high price, the use of plerixafor is limited in China. The purpose of this study was to assess the efficacy of residual plerixafor for second-day stem cell mobilization in multiple myeloma (MM) patients.Materials and methodsIn this single-center retrospective study, 69 MM patients received G-CSF + plerixafor to mobilize PBSCs, which were collected from 28 patients only for one day and 41 patients for two days. Some of the patients received residual plerixafor, and PBSCs were collected on the second day. The data on the characteristics, different doses of plerixafor and efficacy of PBSC mobilization were collected and analyzed.ResultsAfter 1 or 2 apheresis procedures, 85.5% of patients collected more than 2 × 10⁶ cells/kg PBSCs. There was no statistically significant difference in the success rate of CD34 + PBSC mobilization with the different doses of plerixafor on the first day, but the higher residual plerixafor dose resulted in better success rates on the second day (P＜0.001). Among the patients who collected PBSCs for two days, the level of the CD34 + cell yield of 24 patients (58.5%) changed better, which was significantly correlated with the dose of residual plerixafor on the second day (P = 0.001).DiscussionThese results suggested that the administration of residual plerixafor to mobilize stem cells on the second day is an economical, efficient and clinically feasible method.     

Plerixafor for mobilization of blood stem cells in autologous transplantation: an update

Introduction: About 99% of all autologous transplants are now performed with blood stem cells. G-CSF alone or combined with chemotherapy have been used to mobilize CD34⁺ cells. Plerixafor is a novel drug used for mobilization purposes.

Areas covered: We have evaluated recent data in regard to plerixafor use in predicted or proven poor mobilizers. In addition, we have looked for preemptive strategies to optimize the use of this expensive drug. Also cost-efficacy issues and effects of plerixafor on graft composition and post-transplant outcomes will be discussed.

Expert opinion: Plerixafor added to G-CSF is superior than G-CSF alone for mobilization of CD34⁺ cells. This combination is also efficient in patients who have failed a previous mobilization attempt with other methods or in patients with risk factors for poor mobilization. Addition of plerixafor to G-CSF or chemotherapy plus G-CSF mobilization in patients who appear to mobilize poorly is under active investigation and algorithms for a preemptive use of this expensive agent have been proposed. Grafts collected after plerixafor appear to contain more lymphoid cells than the grafts collected without it. Whether this affects post-transplant outcomes such as immune reconstitution and risk of relapse needs to be evaluated.     

进展型多发性硬化患者行自体外周造血干细胞移植的护理

目的总结进展型多发性硬化(PMS)患者行自体外周造血干细胞移植(APBSCT)治疗的护理经验。方法本研究包括20例进展型多发性硬化的护理特点,除了应按照一般自体外周造血干细胞移植的护理常规外,应着重于患者的生活护理。结果19例患者均未发生皮肤感染,1例患者出现腹股沟处破溃皮肤的破溃;10例全瘫患者均未发生褥疮、尿潴留及泌尿系感染。结论护理重点是保持无菌环境、加强各种并发症的预防及护理、做好心理护理及生活护理,是保证移植成功的关键。     

Predictors of unsuccessful mobilization with granulocyte colony‐stimulating factor alone in patients undergoing autologous hematopoietic stem cell transplantation

Mobilization of hematopoietic stem cells is achieved with hematopoietic growth factors with or without chemotherapy or other agents. Although studies comparing granulocyte colony‐stimulating factor (G‐CSF) alone to combined regimens demonstrate an increase in stem cell yield in the latter, mobilization with G‐CSF alone is still effective and has been widely practiced. We conducted a retrospective cohort study of consecutive patients at our institution who underwent at least one mobilization attempt with G‐CSF between January 2000 and December 2008 to identify the proportion of patients failing one or more mobilization attempts and the potential predictors of mobilization failure with this regime. Out of 293 patients, 251 (86.6%) were successfully mobilized and 244 (83.6%) underwent hematopoietic stem cell transplantation. Median yield was 3.55 × 10⁶ CD34⁺ cells/kg. On univariate analysis, mobilization success was influenced by degree of previous treatment and underlying diagnosis (P < 0.001 each) but not by age (P = 0.114), sex (P = 0.860), or radiotherapy (P = 0.454). A diagnosis of non‐Hodgkin's lymphoma (NHL) and number of previous chemotherapy regimens were predictors of failure on multivariate analysis. CD34⁺ yield was influenced by diagnosis and previous chemotherapy (P < 0.001 each). Mobilization with G‐CSF alone yields adequate collections for most patients; however, heavily pretreated NHL patients with one failed attempt had high rates of remobilization failure and should be considered for alternative regimens. J. Clin. Apheresis 28:285–292, 2013. © 2013 Wiley Periodicals, Inc.     

Improved peripheral blood stem cell collection following plasma exchange in a patient with elevated viscosity and coagulopathy

We report a case of improved CD34+ cell yields from peripheral blood stem cell (PBSC) collection following therapeutic plasma exchange (TPE) in a patient with elevated viscosity and coagulopathy. The patient was a 46-year-old male diagnosed with IgM lambda multiple myeloma that was largely unresponsive to standard chemotherapy. He had coagulopathy due to lymphoproliferative disease-associated acquired von Willebrand Factor (vWF) deficiency. The patient underwent two rounds of PBSC collections over 3 consecutive weeks (five total collections) prior to planned tandem transplant for multiple myeloma. Both rounds resulted in poor collections due to processing difficulties. It was decided to perform three TPEs daily immediately prior to attempting additional PBSC collections, to treat the patient's elevated viscosity and thereby potentially improve the efficiency of collections. Immediately following the three TPEs, two additional PBSC collections resulted in sufficient CD34+ cells to proceed to transplant. Lower IgM and/or viscosity levels present after the three TPEs likely permitted successful collection of stem cells.