异基因外周血造血干细胞移植治疗多发性骨髓瘤二例

多发性骨髓瘤(MM)为浆细胞恶性克隆增生性疾病,传统化疗和自体造血干细胞移植虽可使疾病得到暂时缓解,但最终不免复发和进展,患者的中位存活时间仅3～4年。异基因造血干细胞移植是目前惟一可治愈该病的方法,我院采用外周血造血干细胞移植治疗多发性骨髓瘤2例,报告如下。     

自体及非清髓异基因造血干细胞移植治疗多发性骨髓瘤一例

异基因造血干细胞移植是目前可以治愈多发性骨髓瘤(MM)的方法之一。为了降低治疗相关死亡率，减少复发，我们对1例多发性骨髓瘤患者进行了2次移植。第1次为自体外周血造血干细胞移植，第2次为非清髓性异基因外周血造血干细胞移植。现报告如下。     

自体及非清髓性异基因造血干细胞移植治疗多发性骨髓瘤二例

多发性骨髓瘤(multiple myeloma,MM)是浆细胞的恶性肿瘤,大剂量化疗及自体造血干细胞移植(auto-HSCT)使MM的完全缓解率及长期生存有了明显提高,但二者均不能治愈MM.只有接受异基因造血干细胞移植(allo-HSCT)的患者才能够长期无病生存,清髓性allo-HSCT由于其较高的移植相关死亡率,临床应用明显受限.近期我们采用auto-HSCT后序贯给予非清髓性allo-HSCT(NST)治疗2例MM患者,获得较好治疗效果,报道如下.     

福达拉滨、环磷酰胺、美罗华方案进行预处理的非清髓性异基因干细胞移植治疗复发的滤泡性淋巴瘤

异基因造血干细胞移植是治疗滤泡性淋巴瘤的有效方法,大量研究显示接受异基因造血干细胞移植患者的复发率显著低于接受自体造血干细胞移植的患者.非清髓性异基因造血干细胞移植利用其移植物抗淋巴瘤的免疫作用以达到治疗滤泡性淋巴瘤的目的,但是此策略长期的疗效和毒性仍不明确.本项前瞻性研究分析并评价了非清髓性异基因干细胞移植治疗复发的滤泡性淋巴瘤的8年经验.     

自体造血干细胞移植治疗急性髓系白血病的疗效观察

目的观察自体造血干细胞移植对完全缓解期的急性髓系白血病(AML)患者的疗效。方法回顾性分析14例行自体造血干细胞移植的AML患者的临床资料,其中低危7例,中危6例,高危1例。预处理后予回输预先冻存的自体外周血造血干细胞,并予成分输血、升白细胞、预防感染等治疗,观察患者的自体干细胞造血重建情况,并了解移植相关并发症的发生情况;绘制生存曲线并计算术后1年和3年的存活率和无病存活(DFS)率。结果 14例患者均获得造血重建,白细胞植入中位时间为12(9~28)d,血小板植入中位时间为29(8~158)d。2例患者粒细胞缺乏期出现大肠杆菌败血症,1例发生普通变形杆菌败血症,1例患者在移植后29 d出现巨细胞病毒血症,其余患者预处理后出现感染或胃肠道反应,经抗感染及其它对症支持等治疗后均治愈。随访时间29.8(5.3~61.5)个月,14例患者中共有5例复发(35.7%),11例患者存活,3例死于复发。术后1年、3年的存活率分别为86%和79%,术后1年、3年的DFS率分别为64%和57%。结论自体造血干细胞移植是大部分低、中危AML患者的有效治疗方法。     

高危急性髓系白血病异基因造血干细胞移植后复发的防治

急性髓系白血病（AML）是一组高度异质性的克隆性疾病,化学药物治疗和造血干细胞移植均为治疗AML的方法。对于高危AML患者而言,异基因造血干细胞移植为治疗该疾病的有效手段,但部分AML患者造血干细胞移植后仍可能面临疾病复发的问题,大多数复发患者再行化学药物治疗、二次移植等的效果不佳,是导致患者异基因造血干细胞移植后死亡的主要原因。因此,加强对异基因造血干细胞移植后AML患者的随访,并采取一些合适的手段预防移植后复发显得尤为重要。本文就高危AML患者异基因造血干细胞移植后复发的监测、药物治疗和细胞治疗进行综述,以期为改善高危AML患者异基因造血干细胞移植预后提供参考。     

成人急性淋巴细胞白血病治疗的比较性研究

本文综述了异基因造血干细胞移植与自体造血干细胞移植治疗成人急性淋巴细胞白血病的疗效及研究现状,比较了不同治疗方法的差异,提出了今后研究中需要解决的问题。     

成人急性淋巴细胞白血病治疗的比较性研究

本文综述了异基因造血干细胞移植与自体造血干细胞移植治疗成人急性淋巴细胞白血病的疗效及研究现状，比较了不同治疗方法的差异，提出了今后研究中需要解决的问题。     

异基因造血干细胞移植治疗难治性恶性淋巴瘤14例

异基因造血干细胞移植(allo-HSCT)是惟一有可能治愈恶性淋巴瘤的方法,尤其是发生骨髓侵犯或自体造血干细胞移植后复发的晚期难治性恶性淋巴瘤患者,有望再次长期缓解.     

亲缘异基因造血干细胞移植与自体造血干细胞移植治疗弥漫性大B细胞淋巴瘤大宗病例分析

选择自体造血干细胞移植还是异基凶造血干细胞移植治疗弥漫性大B细胞淋巴瘤（diffuse large B cell lymphoma,DLBCL）患者需权衡治疗相关死亡率（treatment—related mortality,TRM）差异、自体移植物被肿瘤污染的可能、干细胞动员失败和异基因移植物抗淋巴瘤效应等因素之间的利弊。     

Effect of melphalan 140 mg/m2 vs 200 mg/m2 on toxicities and outcomes in multiple myeloma patients undergoing single autologous stem cell transplantation—a single center experience

Although melphalan at a dose of 140 mg/m² (MEL140) is an acceptable conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients, very few studies compared it to the most commonly used dose of 200 mg/m² (MEL200). A retrospective review of records of MM patients (2001–2010) identified 33 patients who received MEL140 and 96 patients who received MEL200. As expected, significantly higher percentage of patients in the MEL140 arm were >65 years or had cardiac ejection fraction <50%, had Karnofsky score <80, or had creatinine >2 at the time of ASCT (P≤.01). There were no significant differences in incidence of treatment related mortality and morbidity. At a median follow‐up of 74 months from ASCT, there were no significant differences in relapse free survival (RFS) and overall survival (OS) between the two groups. Similar proportion had myeloma status improve to ≥VGPR at 3 months post‐ASCT. Usage of post‐ASCT maintenance was similar. In multivariate cox proportional hazards model, only disease status of ≥VGPR at the time of ASCT significantly improved RFS (P=.024), but not OS (P=.104). In conclusion, MM patients who received MEL140 had similar long‐term outcomes to MEL200 patients despite their older age and co‐morbidities.     

Retrospective analysis of the efficacy and influencing factors of autologous hematopoietic stem cell transplantation for multiple myeloma

This study aims to review the clinical efficacy and factors affecting the treatment of multiple myeloma (MM) by autologous hematopoietic stem cell transplantation (ASCT). The clinical data of 47 patients with MM from the Department of Hematology of Henan Cancer Hospital from September 2010 to July 2018 were retrospectively analyzed. At pre‐transplantation of autologous cells, 25.5% were in complete remission (CR), 14.9% were in very good partial remission (VGPR) and 59.6% were in partial remission (PR). Among these cases, one case had PR after three recurrences. At post‐transplantation, 51% were in CR, including two cases who received double transplantations, 27.7% were in VGPR, and 21.3% were in PR. The median follow‐up time was 27.6 months (4–96 months). The 3‐year progression free survival (PFS) and overall survival (OS) were 47.9% and 79.6%, respectively. The Analysis of variance (ANOVA) results revealed that factors that affected OS were international staging system (ISS) stage (P = 0.002), CR and VGPR post‐transplantation (P = 0.002), while factors that affected PFS were ISS stage (P = 0.005), pre‐transplant induction therapy (P = 0.032), and disease risk stratification (P = 0.017). The curative effects for PFS were CR and VGPR pre‐transplantation (P = 0.013) and post‐transplantation (P = 0.011). The Cox multivariate regression analysis revealed that ISS stage and CR and VGPR post‐transplantation were independent prognostic factors of OS. At post‐transplantation, CR and VGPR, ISS stage, and pre‐transplant induction therapy were independent prognostic factors for PFS. In conclusion, ASCT can improve the clinical efficacy and survival rate of MM patients. ISS stage, CR and VGPR post‐transplantation are independent prognostic factors of OS and PFS, while pre‐transplant induction therapy is an independent prognostic factor for PFS.     

The Prognostic Significance of Pretransplant Plasma Fibrinogen Levels in Autologous Hematopoietic Stem Cell Transplantation

Elevated plasma fibrinogen is associated with tumor progression and poor outcomes in several cancers. However, no studies have demonstrated the prognostic value of hyperfibrinogenemia in the setting of autologous hematopoietic stem cell transplantation (ASCT). We retrospectively reviewed 104 patients who were diagnosed with malignant lymphoma (ML) or multiple myeloma (MM) and underwent ASCT in our institution between 2007 and 2018. The patients included 63 men and 41 women with a median age of 58 years (range, 24-70 years). Forty-seven patients were diagnosed with ML, and 57 patients were diagnosed with MM. The median follow-up period was 59 months. The median pretransplant plasma fibrinogen levels were 336 mg/dL in ML patients and 320 mg/dL in MM patients. The Kaplan-Meier method revealed that patients with pretransplant hyperfibrinogenemia had a significantly shorter 5-year overall survival (OS) than those without hyperfibrinogenemia (5-year OS: 34.3% vs 81.0%, P < .001). Among 27 patients with diffuse large B cell lymphoma, patients with pretransplant hyperfibrinogenemia (n = 12) had a significantly shorter OS than those without hyperfibrinogenemia (n = 15) (5-year OS: 40.0% vs 80.2%, P = .006). Among 57 MM patients, there was no significant difference in the 5-year OS between the high-fibrinogen group and the low-fibrinogen group (5-year OS: 77.1% vs 50.4%, P = .17). Our study suggested that pretransplant hyperfibrinogenemia was associated with a poor survival in patients with lymphoma who underwent ASCT. Because our results are based on a small-sized analysis, further large-scale prospective studies are warranted to verify this conclusion.     

High complete remission rate and durable remissions achieved with rational use of autologous stem‐cell transplantation,thalidomide maintenance,and non‐myeloablative allogeneic transplantation in patients with multiple myeloma

Abstract: Autologous stem‐cell transplantation (ASCT) has emerged as the standard approach in patients with multiple myeloma, although it is unlikely to achieve cure. Thalidomide maintenance and non‐myeloablative allogeneic transplantation (NST) may increase complete remission (CR) rate and increase overall survival. In this study, 35 ASCT and 10 NST were performed in 33 patients. Patients, who were resistant or relapsed following ASCT, underwent NST if they had an HLA‐matched sibling, otherwise treated with a second ASCT. Thalidomide was started as maintenance after ASCT. After first transplantation, three patients underwent second ASCT and 10 patients underwent NST. Following first transplantation, CR rate was 39% and increased to 60% (overall response 93%) with addition of thalidomide, bortezomib, and second transplantation. CR was durable in 14 (42%) patients. During a median follow‐up of 24 months, 18 patients progressed and nine patients died. The 100‐d transplant‐related mortality was <5%. The four‐yr progression‐free survival (PFS) was 52.4%. In conclusion, ASCT followed by thalidomide and NST in resistant patients can lead to high CR and PFS rates. As a second transplantation has not been performed routinely, patients having durable CR had a chance to avoid or delay a second transplantation without compromising disease control.     

Evaluation of cytokine profile in the different phases of the autologous hematopoietic stem cell transplantation in patients with multiple myeloma

BackgroundThe autologous hematopoietic stem cell transplantation (ASCT) is of fundamental importance in the treatment of patients with multiple myeloma (MM). Nevertheless, due to its toxicity, it decreases the number of bone marrow cells available, altering the cell interactions and causing an imbalance between pro- and anti-inflammatory cytokines.MethodsThus, we determined the serum levels of pro- and anti-inflammatory cytokines in samples of patients with MM obtained from the different phases of ASCT.ResultsIn summary, the cytokines levels varied considering the different phases of ASCT. The levels of IL-1ra tend to increase in the post-apheresis period suggesting an anti-inflammatory role induced by the apheresis process. A response characterized by the increase in the concentrations of IL-5 and IL-8 was observed in the post-conditioning bone marrow aplasia phase. The rise in IL-5 levels was not correlated with any clinical or laboratory event in this framework; IL-8 was associated with positive blood cultures and seems to have an effect against microbial agents. The increase in the levels of IL-10 and IL-12 suggests a possible regulatory effect of the inflammatory response in the period of bone marrow recovery and IL-12 seems to be inversely associated with the presence of minimal residual disease.ConclusionsApheresis process seems to induce an anti-inflammatory response, followed by a pro-inflammatory response and a stimulus for granulocytes differentiation.     

Continuous Infusion Cyclophosphamide and Low-Dose Total Body Irradiation Is a Safe and Effective Conditioning Regimen for Autologous Transplant in Multiple Myeloma

We present the results of a novel conditioning regimen in multiple myeloma (MM) patients undergoing tandem autologous stem cell transplant (ASCT). MM patients were enrolled in a prospective phase II clinical trial. After initial ASCT, disease response was assessed by day +100. Patients achieving very good partial remission (VGPR) were offered maintenance therapy. If patients achieved VGPR, they were offered a second ASCT using continuous intravenous cyclophosphamide (CICy) 6 g/m² over 4 days and low-dose total body irradiation (ldTBI) 600 rads over 2 days. Total body irradiation was replaced by melphalan 140 mg/m² if patients had received prior radiation. Twenty-one patients received tandem ASCT. Three patients received CICy and melphalan. Median duration of neutropenia with CICy/ldTBI was 11 days. Fifteen patients (71.4%) developed febrile neutropenia while grade 1 to 2 diarrhea was the next most common adverse event (42.9%). There was no treatment-related mortality. Four patients had entered complete remission (19%) and 6 achieved VGPR (28.6%). In conclusion, this conditioning regimen is safe and effective and may be useful in patients who do not benefit from first ASCT using more traditional conditioning regimen.     

Delayed autologous stem cell transplantation following cardiac transplantation experience in patients with cardiac amyloidosis

This study sought to retrospectively investigate the outcomes of patients with light‐chain amyloidosis (AL) with advanced cardiac involvement who were treated with a strategy of heart transplantation (HT) followed by delayed autologous stem cell transplantation (ASCT) at 1‐year posttransplant. Patients with AL amyloidosis with substantial cardiac involvement have traditionally had very poor survival (eg, several months). A few select centers have reported their outcomes for HT followed by a strategy of early ASCT (ie, 6 months) for CA. The outcomes of patients undergoing a delayed strategy have not been reported. All patients with AL amyloidosis at a single institution undergoing evaluation for HT from 2004‐2018 were included. Retrospective analyses were performed. Sixteen patients underwent HT (including two combined heart‐kidney transplant) for AL amyloidosis. ASCT was performed in a total of nine patients to date at a median 13.5 months (12.8‐32.9 months) post‐HT. Survival was 87.5% at 1 year and 76.6% at 5 years, comparable to institutional outcomes for nonamyloid HT recipients. In addition to these 16 patients, two patients underwent combined heart‐lung transplantation. A strategy of delayed ASCT 1‐year post‐HT for patients with AL amyloidosis is feasible, safe, and associated with comparable outcomes to those undergoing an earlier ASCT strategy.     

我国2004年至2009年自体干细胞移植治疗糖尿病足文献计量分析

目的 用文献计量法总结我国2004年至2009年自体干细胞移植(ASCT)治疗糖尿病足的文献,介绍其发展、术式,预测发展趋势等.方法 以"糖尿病足"为检索词,从中文生物医学期刊文献数据库和中国生物医学文献数据库获取题录,再获取原文,按作者、手术方式、刊文期刊、发文机构、地区等行计量分析.结果 共检获104篇,主要发文期刊、发文机构、作者、地区发文数量及术式分别是中国组织工程研究与临床康复杂志(6篇),北京首都医科大学(10篇),谷涌泉(9篇),北京(17篇),手术方式以外周血干细胞移植(ABMSCT)和骨髓干细胞移植(APBSCT)为主.结论 概括性介绍我国发表的ASCT治疗糖尿病足的文献,为深入研究提供了可靠资料.阐述此课题的研究现状并预测主要发展趋势:在严格量化适应证前,ABMSCT及APBSCT为ASCT的主要手术方式;量化ASCT的适应证,与其他药物联用使ASCT更好地发挥作用必将是这一课题的研究热点.     

Prognostic impact of natural killer cell recovery on minimal residual disease after autologous stem cell transplantation in multiple myeloma

IntroductionNatural killer cells are a potent effector lymphocyte subset that can induce cytotoxicity without the need for antigen sensitization or presentation. NK cells are a tempting target –for immune therapy, monoclonal antibody, or genetic engineering-to enhance immune surveillance mechanisms against myeloma cells.Materials and methodsWe hypothesized an association between natural killer cell recovery after autologous stem cell transplantation (ASCT) and disease outcomes in multiple myeloma patients.We concluded a prospective study that started enrolling patients in January 2020 to identify the association between absolute NK cell count two to three after ASCT and disease outcomes after autologous stem cell transplantation in multiple myeloma using univariate and multivariate analysis.ResultsNatural killer cell recovery was evaluated during the third month after ASCT, day +60 to +90 post-ASCT. Our patients had a mean NK cell count of 90.53, ranging from 14 to 282 Cell/μL (Std Dev 84.64 Cell/μL). The odds of having a minimal residual disease (MRD-positivity) among patients with partial remission before transplantation is four times higher than patients with very good partial response or better (95% confidence interval 0.45–35.79). Our patients were classified into two groups based on MRD status after ASCT, an MRD-negative group of eight participants and an MRD-positive group of seven participants. The mean absolute NK cell count was significantly higher in the MRD-negative cohort, 131.38 Cell/μL, versus 43.86 Cell/μL in the MRD-positive group (p = 0.049).ConclusionWe conclude that for multiple myeloma patients treated with ASCT, high absolute NK cell counts two to three months after ASCT is an independent predictor for MRD negativity.     

Successful treatment of nephrotic syndrome due to systemic AL amyloidosis after autologous stem cell transplantation: renal response is an important therapeutic end point

Primary systemic (AL) amyloidosis involves vital organs from the early phase of illness, resulting in poor prognosis. Today, high-dose melphalan followed by autologous peripheral blood stem cell transplantation is an effective treatment for systemic AL amyloidosis. We report a patient with nephrotic syndrome due to systemic AL amyloidosis, who was successfully treated with autologous peripheral blood stem cell transplantation. At follow-up 36 months from ASCT, the patient showed a significant improvement in the signs of peripheral neuropathy and reduction in proteinuria without further organ involvement. Due to poor prognosis with conventional therapy, autologous stem cell transplantation should be considered for treatment in patients with systemic AL amyloidosis, and favorable outcome is ensured with achievement of renal response after ASCT.