Plerixafor strategies for autologous hematopoietic cell transplant mobilization: A comparison of efficacy and cost

Addition of plerixafor (P) to granulocyte colony stimulating factor (G-CSF) during peripheral blood mobilization of hematopoietic stem cells (HSC) increases the number of patients meeting collection goals prior to autologous stem cell transplant (aSCT). However, use of P is not universal among transplant centers due to cost. This study aims to compare clinical and financial impacts of using an algorithm-based P mobilization strategy versus use in all patients. This was a single center, retrospective analysis of adult patients with myeloma or amyloidosis receiving aSCT who received apheresis of their HSC between 3/1/2017 and 3/1/2019. Patients prior to 3/1/2018 were classified as receiving P “per algorithm” and those after this date were classified as “up-front” P. For the per-algorithm group, P was given for a pre-apheresis CD34+ cell count of <20 cells/μL on mobilization day 5 and patients returned on day 6 for apheresis. Of the 129 patients included, 55 received P per-algorithm and 74 received up-front P. There was a reduction in median number of apheresis days (1.5 vs 1 day, p < 0.001) and an increase in median number of CD34+ cells collected (6.6 vs 8.5 × 10⁶ cells/kg, p < 0.001) with up-front P. Up-front P increased drug cost but reduced apheresis costs, which resulted in a net savings of $121 per patient in total mobilization costs. These findings suggest that use of up-front P for mobilization significantly reduces apheresis days and increases HSC collection yield without increasing overall cost per patient.     

Plerixafor combined with G-CSF for stem cell mobilization in children qualified for autologous transplantation- single center experience

Failure of autologous peripheral blood CD34⁺ stem cells collection can adversely affect the treatment modality for patients with hematological and nonhematological malignant diseases where high dose chemotherapy followed by hematopoietic stem cell transplantation has become part of their treatment. Plerixafor in conjunction with G-CSF is approved for clinical use as a mobilization agent. The clinical efficacy of Plerixafor in CD34⁺ cells collection was analyzed in our institution. A total of 13 patients aged 1–15,5 years received Plerixafor in combination with G-CSF: 7 with neuroblastoma, 2 with Ewing’s sarcoma and single patients with Hodgkin’s lymphoma, germ cell tumor, retinoblastoma and Wilms tumor. Twelve patients (923%) achieved CD34+ cell counts of ≥ 20 × 10⁶/L after 1–7 doses of Plerixafor. The average 9,9 - fold increase in number of CD34⁺ cells were achieved following the first dose and 429 - fold after second dose of plerixafor. Among the 13 patients, 12 yielded the minimum required cell collection of 2 × 10⁶/kg within an average of 2 doses of Plerixafor. The mean number of apheresis days was 1.75. The median total number of collected CD34⁺ cells was 982 × 10⁶/kg. Plerixafor enables rapid and effective mobilization, and collection of sufficient number of CD34⁺ cells.     

The effect of comorbidity on survival and collected CD34 + cell counts in autologous hematopoietic stem cell transplant patients

ObjectiveIn this study, we aimed to report the effectiveness of hematopoietic cell transplantation–specific comorbidity index (HCT-CI) and GATMO scores in predicting overall survival (OS) who underwent autologous stem cell transplantation (ASCT).Material and methodsThe data of 263 MM and 204 lymphoma patients who underwent ASCT in the last 11 years were retrospectively analyzed.ResultsNeutrophil engraftment time, thrombocyte engraftment time and collected CD34+ cell counts were similar in MM patients with HCT-CI>2 and HCT-CI≤2 (all p>0.05). Although the estimated median OS of MM patients with HCT-CI ≤2 tended to be higher than those with HCT-CI>2, this difference was not statistically significant (52.8 vs 45 months, p=0.172). No effect of GATMO score on CD34 + count, engraftment times and OS in MM patients was detected (p>0.05). The effect of HCT-CI score on lymphoma patients was examined, it was found that the neutrophil engraftment time was longer (p=0.039) and the number of collected CD34+ cells was lower (p=0.02) in patients with HCT-CI>2 than those with HCT-CI≤2. While the estimated median OS of lymphoma patients with HCT-CI≤2 was 51.5 months, the estimated median OS of patients with HCT-CI>2 was 9.5 months (p=0.012). When lymphoma patients were divided into four groups according to their GATMO scores, the OS of the four groups was found to be different from each other (p<0.001).ConclusionHCT-CI and GATMO scores predict OS in lymphoma patients but not MM patients.     

Usefulness of hematopoietic progenitor cell monitoring to predict autologous peripheral blood stem cell harvest timing: A single-center retrospective study

IntroductionIn autologous peripheral blood stem cell harvest (APBSCH), CD34-positive cells have been measured to assess the numbers of hematopoietic stem cells, but measurement requires specialized equipment. Recently, there was a report that peripheral blood hematopoietic progenitor cells (HPCs) are useful indicators of the presence of hematopoietic stem cells. We examined the usefulness of HPC monitoring to predict APBSCH timing.MethodsWe retrospectively analyzed the relationship between HPC and collected CD34-positive cells in 84 consecutive patients who underwent APBSCH.ResultsAccording to the receiver operating characteristics curve for the collection of ≥2 × 106 CD34-positive cells/kg, the HPC cut-off value on the day before collection was 21/μL, while that on the day of collection was 41/μL. No significant factors were found in the univariate analysis except for the HPC count on the day before collection (p < 0.001) and the day of collection (p < 0.001). According to the multivariate analysis, the HPC count on the day before collection (p < 0.001) and the day of collection (p < 0.001) were also factors that strongly influenced the quantity of CD34-positive cells collected.ConclusionOur results suggest that the HPC count on not only the day of collection but also the day before collection is a good indicator for appropriate APBSCH timing.     

Plerixafor as a salvage mobilization strategy for haploidentical peripheral blood allogeneic stem cell transplantation

In allogeneic stem cell mobilization, peripheral blood stem cell mobilization with filgrastim can be considered standard of care. Poor mobilizers may be at risk for inadequate stem cell collection during apheresis. He we present a successful case of salvage plerixafor use with filgrastim in a haploidentical identical transplant patient.     

造血干细胞移植治疗间变大细胞淋巴瘤的临床分析

目的探讨造血干细胞移植治疗间变大细胞淋巴瘤(ALCL)的疗效及预后。方法回顾性分析全国八家三甲医院2005年1月至2017年12月收治的33例接受造血干细胞移植(HSCT)的ALCL患者临床资料,评价自体造血干细胞移植(auto-HSCT)和异基因造血干细胞移植(allo-HSCT)治疗ALCL的生存率、复发率和影响预后的相关因素。结果33例接受HSCT的ALCL患者的中位发病年龄为31(12~57)岁,男23例,女10例,间变性淋巴瘤激酶阳性(ALK+)和阴性(ALK-)分别为24例(72.7%)和9例(27.3%)。25例患者接受auto-HSCT(ALK+患者19例,ALK-患者6例),8例患者接受allo-HSCT(ALK+患者5例,ALK-患者3例)。移植后中位随访时间18.7(4.0~150.0)个月。移植前疾病缓解状态:完全缓解6例(均行auto-HSCT),部分缓解16例(auto-HSCT组14例,allo-HSCT组2例),复发难治11例(auto-HSCT组5例,allo-HSCT组6例)。疾病进展死亡7例,其中auto-HSCT组5例(20.0%),allo-HSCT组2例(25.0%)。移植相关死亡(TRM)5例,其中auto-HSCT组2例(8.0%),allo-HSCT组3例(37.5%)。auto-HSCT后中位无进展生存(PFS)和总生存(OS)时间均为15个月,allo-HSCT后中位PFS时间为3.7(1.0~90.0)个月,中位OS时间为4.6(1.0~90.0)个月,两组生存曲线差异无统计学意义(OS及PFS P值分别为0.247和0.317)。auto-HSCT和allo-HSCT组的2年OS率分别为72%和50%,5年OS率分别为36%和25%。结论ALCL化疗反应率高,有不良预后因素的情况下化疗后序贯auto-HSCT为重要治疗措施,高危患者或可从allo-HSCT中获益。     

适时护理推送模式在自体造血干细胞移植患者中的应用

目的观察适时护理推送模式在自体造血干细胞移植患者中的应用效果。方法选择适时护理推送模式实施前2018年1—10月我院行自体造血干细胞移植患者43例作为对照组,将实施后2018年11月至2019年8月于我院行自体造血干细胞移植患者43例为试验组,对照组接受自体造血干细胞移植术常规护理,试验组接受适时护理模式干预,对两组干预后的各观察指标进行比较。结果试验组患者焦虑抑郁自评分值、消化道并发症发生率显著低于对照组,护理满意度评定分值显著高于对照组,(P<0.05)。结论采用适时护理推送模式对自体造血干细胞移植患者实施干预,可明显改善患者心理困扰,降低并发症风险,提高护理满意度。     

Erythropoiesis-stimulating agents in allogeneic and autologous hematopoietic stem cell transplantation

Introduction: Erythropoiesis-stimulating agents (ESAs) are used in treating cancer- and chemotherapy-induced anemia with the aim of accelerating the recovery of red blood cells (RBCs), reduce the risks associated with RBC transfusions and improve quality of life.

Areas covered: A systematic review has been conducted to examine the current evidence for the efficacy and safety of using ESAs in hematopoietic stem cell transplants (HSCTs).

Expert opinion: Despite the international recommendations for the use of ESAs in treating different malignancies, there is a lack of guidelines for their use in patients undergoing HSCT. An evaluation of published clinical trials shows that there are no available powerful studies concerning the use of ESAs in this setting, with only heterogeneous and small numbers of patients reported so far. Nevertheless, the more robust and intriguing of these data suggest that the ESA’s administration at an appropriate time after the infusion of stem cells may be effective both in autologous and allogeneic HSCTs. New guidelines are required, overseen by an expert in the in the field of stem cell transplantation.     

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.     

造血干细胞移植患者腹部超声特点

目的 探讨血液病患者造血干细胞移植治疗后腹部超声特点及相关临床意义.方法 对51例接受造血干细胞移植患者进行常规腹部超声检查,观察腹腔脏器声像图变化.结果 同移植前比较,患者在移植后发生弥漫性肝实质损害、肝静脉纤细、胆囊壁增厚、胆汁淤积、脾体积缩小、肠蠕动异常及腹水等一系列变化,差异有显著性意义（P〈0.05）;而肝大小、肾实质损害、脾内部回声及胰腺变化则差异无显著性意义（P〉0.05）.结论 造血干细胞移植后患者常发生一系列腹腔脏器超声特征性变化,常规腹部超声检查能为移植相关并发症早期诊断提供及时、可靠的诊断依据.     

异基因造血干细胞移植后供者外周血造血干细胞输注预防高危白血病复发

目的评估重组人粒细胞集落刺激因子(G-CSF)动员的供者外周血造血干细胞输注 (GPBSCI)作为一种早期过继性免疫治疗方法的有效性和安全性。方法 12例高危白血病患者同胞配型相合异基因造血干细胞移植(allo-HSCT)后接受了G-CSF动员的预防性GPBSCI。allo-HSCT前患者的诊断包括2例Ph 急性淋巴细胞白血病首次完全缓解(ALL-CR1),1例ALL-CR2,1例ALL合并顽固中枢神经系统白血病(CNSL),1例急性髓系白血病(AML)复发,1例AML合并CNSL,1例 AML-CR3,4例进展期慢性粒细胞白血病(CML)及1例骨髓增生异常综合征-难治性贫血伴幼稚细胞增多型(MDS-RAEB)。结果 12例患者共接受了16次GPBSCI,其中移植后90天( 90天)前接受 GPBSCI 5次,输注的单个核细胞(MNC)及CD3 细胞中位数分别为1．00(0．95-1．24)×108/kg和 0．53(0．39-0．63)×108/kg。 90天后接受GPBSCI 11次,输注两类细胞中位数分别为2．27(1．00- 4．30)×108/kg和1．15(0．55-2．10)×108/kg。输注后4例患者发生了Ⅰ或Ⅱ度急性移植物抗宿主病(GVHD),1例患者发生Ⅲ度急性GVHD。7例患者发生了慢性GVHD,其中4例为广泛型。2例患者未发生输注相关GVHD。未观察到GPBSCI相关的全血细胞减少。中位随访563(415-728)d,12 例高危白血病患者中有10例无病存活,2例死于白血病复发。结论预防性GPBSCI可以增强移植物抗白血病作用,相关不良反应小,可能成为改善高危白血病allo-HSCT预后的安全有效的手段。     

多发性硬化患者造血干细胞移植后Th、Tc细胞亚型的变化

目的观察多发性硬化(MS)患者自体造血干细胞移植(AHSCT)前后外周血中辅助性T细胞(Th)、细胞毒性T细胞(Tc)亚型的变化,及其在AHSCT后诱导MS缓解中的作用。方法用流式细胞仪(FCM)检测患者移植前1周及移植后1月外周血中Th、Tc细胞亚型,及其分别占CD3+T淋巴细胞的百分比。结果MS患者外周血Th1和Tc1细胞百分比高于健康对照组(P<0.01及P<0.05),移植后Th1和Tc1显著低于移植前及对照组(P<0.01)。移植前MS患者Th2细胞与健康对照组差异无显著性(P>0.05),Tc2细胞低于对照组(P<0.05)。移植前后相比,移植前组Th2细胞下降(P<0.05),而Tc2差异无显著性(P>0.05)。结论MS患者体内存在高水平的Th1和Tc1。AHSCT可使其逆转,从而有利于MS病情的缓解。     

多发性硬化患者造血干细胞移植后Th、Tc细胞亚型的变化

目的 观察多发性硬化（MS）患者自体造血干细胞移植（AHSCT）前后外周血中辅助性T细胞（Th）、细胞毒性T细胞（Tc）亚型的变化,及其在AHSCT后诱导MS缓解中的作用.方法 用流式细胞仪（FCM）检测患者移植前1周及移植后1月外周血中Th、Tc细胞亚型,及其分别占CD3＋T淋巴细胞的百分比.结果 MS患者外周血Th1和Tc1细胞百分比高于健康对照组（P〈0.01及P〈0.05）,移植后Th1和Tc1显著低于移植前及对照组（P〈0.01）.移植前MS患者Th2细胞与健康对照组差异无显著性（P〉0.05）,Tc2细胞低于对照组（P〈0.05）.移植前后相比,移植前组Th2细胞下降（P〈0.05）,而Tc2差异无显著性（P〉0.05）.结论 MS患者体内存在高水平的Th1和Tc1.AHSCT可使其逆转,从而有利于MS病情的缓解.     

Cutaneous Mycobacterium chelonae infection following autologous peripheral blood stem cell transplantation for POEMS syndrome

Although hematopoietic stem cell transplantation (HSCT) may increase the curability of refractory hematologic diseases, it requires complication management due to a long-term immunocompromised state. We experienced a case who received an autologous peripheral blood stem cell transplantation (Auto-PBSCT) for POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) and developed cutaneous Mycobacterium chelonae infection. It is clear that attention needs to be paid to prevent bacterial, fungal and viral infection after HSCT. It is also important to keep in mind that tuberculous and nontuberculous mycobacteria (NTM), in rare cases, lead to lethal complications.     

急性白血病患者第一次完全缓解期自体和异基因造血干细胞移植疗效的比较

目的　对急性白血病 (AL) (不包括急性髓系白血病M3 型 )患者第 1次完全缓解 (CR1)期自体造血干细胞移植 (auto HSCT)和异基因造血干细胞移植 (allo HSCT)的疗效进行比较。方法　AL CR1期HSCT患者 14 0例 ,其中HLA相合同胞供者allo HSCT 4 6例 ,auto HSCT 94例 ,预处理方案包括全身照射 环磷酰胺 (TBICy)、白消安 环磷酰胺 (BuCy)以及马法兰 阿糖胞苷 环磷酰胺(MAC)方案。allo HSCT组予以环孢菌素A(CsA)或联合甲氨蝶呤 (MTX)或FK5 0 6预防移植物抗宿主病 (GVHD) ,auto HSCT组自体骨髓净化 39例 ,移植后免疫治疗和 (或 )维持化疗 38例。结果　 14 0例患者移植后均获髓系造血重建 ,中位随访时间 70 0 (18～ 5 5 6 3)d ,auto HSCT组与allo HSCT组比较 :移植后 5年无白血病生存 (LFS)率 [分别为 (5 1.5± 5 .4 ) %和 (5 2 .8± 7.6 ) % ]相近 (P >0 .0 5 ) ;累积移植相关死亡率 [分别为 (14 .4± 4 .1) %和 (37.6± 7.8) % ]后者显著增高 (P <0 .0 5 ) ;累积复发率 [分别为 (5 2 .0± 5 .5 ) %和 (2 6 .3± 6 .9) % ]前者明显增加 ,但无显著性差异 (P >0 .0 5 )。auto HSCT组中自体骨髓净化和移植后治疗患者与未经相应处理患者比较 ,5年LFS率显著提高 ,分别为 (6 2 .8± 6 .8) %和 (38.4± 8.4 ) % ,P <     

Autologous stem cell transplantation and stem cell mobilization kinetics in elderly patients with B cell non-Hodgkin lymphoma

As known, the world population is aging and as the life span increases the number of advanced-age lymphomas also shows an upward trend. Autologous hematopoietic stem cell transplantation (HSCT) is the standard treatment modality in chemotherapy-sensitive relapsed or refractory aggressive lymphomas. Increased morbidity and mortality related to both the transplant itself and comorbid diseases can be observed in elderly lymphoma patients. Patients who are 65 years or older and underwent autologous HSCT with B-cell non-Hodgkin lymphoma were retrospectively included in our study. In terms of survival analysis, median follow-up was 34.5 months (8–159) while the overall survival (OS) was 58%. In the univariate analysis of prognostic data in OS, patients who were referred to transplantation with complete response had a statistically significant survival advantage (p = 0.043). In terms of the effect of pre-transplant conditioning regimens on survival, BEAM regimen yielded better results, though not statistically significant. Age, number of chemotherapy cycles received before mobilization and radiation therapy had no significant effect on the CD34 (+) cell count in the final product (p = 0.492, 0.746 and 0.078 respectively). In conclusion, autologous HSCT is a practicable treatment modality that provides survival advantage in suitable advanced-age patients with a diagnosis of B-cell non-Hodgkin lymphoma.     

普乐沙福联合G-CSF在浆细胞疾病自体造血干细胞动员中的有效性及安全性

目的:分析普乐沙福联合G-CSF在浆细胞疾病自体造血干细胞中动员的效果及安全性。方法:回顾性分析2018年1月至2019年12月在北京大学人民医院使用普乐沙福联合G-CSF进行自体造血干细胞动员的浆细胞疾病患者的基线临床资料、采集成功率及不良反应。结果:共纳入49例浆细胞疾病患者,多发性骨髓瘤（MM）39例（79.6%...     

儿童造血干细胞移植后的生存质量研究进展

随着造血干细胞移植（HSCT）技术、造血干细胞来源体系的不断完善及支持治疗的不断改进,移植成功率也在逐年上升,越来越多的儿童从 HSCT 中获得长期生存,造血干细胞移植后患儿的生存质量在近年来也逐渐被重视。针对 HSCT 患儿生存质量的研究在国内仍为空白,而国外学者通过各种量表研究发现：（1）HSCT患儿远期总体的生存质量（QOL）良好;（2）移植前后患儿QOL变化规律：移植前患儿的QOL已经下降,且预处理后会立即进一步下降,但移植4～24个月后会提高;（3）与非移植治疗的白血病患儿相比,HSCT白血病患儿有更多的晚期不良事件,QOL低于非HSCT患儿及正常儿童;（4） HSCT患儿QOL较公认的影响因素主要包括患儿的家庭功能、患儿本身的能力（如社会功能）以及是否存在慢性移植物抗宿主病（cGVHD）,而多数研究显示移植时的年龄、性别、原发病、身高等不影响患儿的生存质量。需要指出的是,以上结论均是由国外研究得出,而我国HSCT治疗后患儿的QOL情况有待进一步研究。     

Peripheral blood stem cell collection for allogeneic hematopoietic stem cell transplantation: Practical implications after 200 consequent transplants

Background

Proper stem cell mobilization is one of the most important steps in hematopoietic stem cell transplantation (HSCT). The aim of this paper is to share our 6 years’ experience and provide practical clinical approaches particularly for stem cell mobilization and collection within the series of more than 200 successive allogeneic HSCT at our transplant center.

自身免疫病患者造血干细胞移植后Ts及Tc细胞的变化

目的检测严重自身免疫病(SAID)患者自体造血干细胞移植(AHSCT)前后外周血中抑制性T(Ts)细胞、杀伤性T(Tc)细胞亚群的变化,探讨Ts、Tc细胞在AHSCT诱导自身免疫病缓解中的作用。方法使用流式细胞术(FCM)检测对照组及SAID患者AHSCT前1周及AHSCT后1~3月外周血中Ts、Tc细胞亚群。Ts细胞表型为CD3 CD8 CD28-,Tc表型为CD3 CD8 CD28 。分析各细胞亚群占T淋巴细胞的百分率,并比较AHSCT前后Ts、Tc的变化。结果SAID患者AHSCT前Ts与对照组比较差异无统计学意义(P>0.05),Tc高于对照组(P<0.05)。AHSCT前后比较,患者外周血中Ts细胞显著增高(P<0.05);Tc虽有下降,但差异无统计学意义(P>0.05)。AHSCT后与对照组比较,Ts显著增高(P<0.05),Tc差异无统计学意义。结论AHSCT治疗SAID患者,能显著提高患者Ts细胞,降低Tc细胞的比例,是AHSCT诱导SAID缓解的机制之一。