Evaluation of patients diagnosed with psoriasis and multiple myeloma after autologous stem cell transplantation

IntroductionThe secretion of monoclonal immunoglobulins increase in chronic inflammatory disorders such as chronic infections and autoimmune diseases. This risk is further increased by the biological agents used in the treatment of autoimmune diseases such as psoriasis. Hematological malignancies occurring in patients with psoriasis provides an opportunity to evaluate the effect of autologous or allogeneic stem cell transplantation in this immune-mediated disease.CasesFour patients diagnosed with psoriasis are presented, having undergone autologous bone marrow transplantation (ABMT), and eventually having remission of their psoriasis, after developing multiple myeloma during follow up. Psoriasis history of the patients was 20, 23, 2 and 2 years, respectively. All of them received peroral methotrexate or topical corticosteroid therapy. Time until myeloma diagnosis were 220, 144, 25, 18 months and follow-up after ABMT were 26, 19, 15, 22 months, respectivelyConclusionPsoriasis can be effectively treated with stem cell transplantation that is used in the treatment of malignancies. For this reason, stem cell transplantation can be considered as a treatment option in these patients, considering the benefit-to-harm ratio. However, uncertainty continues regarding the autologous or allogeneic application of stem cell transplantation     

Characteristics of unexpected protein bands in multiple myeloma patients after autologous stem cell transplantation

ObjectivesThe aim of this study is to investigate the characteristics of unexpected protein bands (UPBs) in patients with multiple myeloma (MM).Design and methodsIndividuals diagnosed with MM (n = 193) were enrolled. Their medical records and IFE patterns were reviewed.ResultsOf the patients that underwent ASCT, 54% developed UPBs. The median time for UPB appearance and duration was 1.8 and 5.7 months, respectively. IFE revealed 74.1% of UPBs to be of the immunoglobulin G type and 72.2% to be of the κ-type. At UPB appearance, 42.6% of patients were defined as sCR or CR, and 50.0% of the patients satisfying the CR criteria had an abnormal FLC ratio. Of the patients who developed UPBs, five relapsed. Among these, four patients showed disappearance of the previous IFE oligoclonality and reappearance of the original paraprotein at relapse.ConclusionsClose follow-up of UPBs is critical for evaluating MM therapeutic response and disease progression. The presence of monoclonal bands may indicate relapse of disease, but in the vast majority of cases with UPBs, it does not; instead, it most likely represents a transient phenomenon caused by the immune response.     

自体造血干细胞移植治疗多发性骨髓瘤的新进展

背景：自体造血干细胞移植是治疗多发性骨髓瘤的有效手段,诱导化疗后行自体造血干细胞移植已成为多发性骨髓瘤的标准治疗方案,多单位、多中心进行了大规模的研究报道。如何减少药物毒副反应、移植相关并发症及改善长期生存是目前关注的重点。
　　目的：综述自体造血干细胞移植治疗多发性骨髓瘤的新进展。
　　方法：应用计算机检索2006年1月至2012年11月PubMed、CNKI数据库、维普数据库、万方数据库、free medicaljournals.com网络资源关于自体造血干细胞移植治疗多发性骨髓瘤的文献。英文检索词“Autologous hematopoietic stem cel transplantation, multiple myeloma”;中文检索词“自体造血干细胞移植,多发性骨髓瘤”。选中相关性强的46篇进行综述。
　　结果与结论：大剂量化疗联合自体造血干细胞移植治疗多发性骨髓瘤的疗效优于传统化疗。但单次自体造血干细胞移植后仍有许多患者不能得到很好的缓解,疾病最终难免复发;异基因造血干细胞移植受到供体来源限制,且治疗相关病死率高,运用受到限制。因此目前的新发展方向包括：在单次自体造血干细胞移植的基础上进行2次自体造血干细胞移植、自体联合减低预处理强度的异体移植以及药物巩固维持治疗。新型药物蛋白酶体抑制剂及免疫调节剂在诱导缓解、预处理、尤其是巩固维持阶段的使用,使多发性骨髓瘤的治疗总体反应率及长期生存得到显著改善。     

新药时代自体造血干细胞移植在多发性骨髓瘤治疗中的问题与展望

自体造血干细胞移植(auto-HSCT)自20世纪80年代初开始应用于多发性骨髓瘤(MM)的治疗,一直在国际上被认为是年龄≤65岁初诊MM(NDMM)患者的首选或一线治疗选择。随着新药的不断涌现,MM的疗效得到很大的提高,auto-HSCT在MM治疗中的地位曾几度被质疑。auto-HSCT是一个整体治疗过程,auto-HSCT的每个环节也随治疗药物或手段的增加而发生了或多或少的改变。本文就新药时代auto-HSCT在MM治疗中的地位和进展作一综述。     

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.     

Role of stem cell transplantation in treatment of multiple myeloma

The role of stem cell transplantation in the treatment of multiple myeloma (MM) is described. High-dose chemotherapy (HDT) followed by autologous stem cell transplantation (SCT) is routinely recommended for most patients with newly diagnosed MM under 65 years of age. However, recently published meta-analysis of randomized controlled trials indicated PFS benefit but not OS benefit for HDT with autologous SCT performed early in MM. Tandem autologous SCT is superior to single transplantation in terms of event-free survival. Survival in recipients of autologous SCT followed by reduced-intensity conditioning allogeneic transplantation is superior to that in recipients of tandem autologous SCT. Recently developed new drugs including thalidomide, lenalidomide or bortezomib in combination with SCT might improve survival of myeloma patients.     

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.     

Disseminated adenovirus infection in a patient with relapsed refractory multiple myeloma undergoing autologous stem cell transplantation and pomalidomide/dexamethasone as salvage regimens

Background

Disseminated adenovirus (ADV) infection is a fatal complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), however, it is rare following autologous peripheral blood stem cell transplantation (auto-PBSCT) or chemotherapy alone.

T cell repertoire following autologous stem cell transplantation for multiple sclerosis

Autologous hematopoietic stem cell transplantation (HSCT) is commonly employed for hematologic and non-hematologic malignancies. In clinical trials, HSCT has been evaluated for severe autoimmunity as a method to “reset” the immune system and produce a new, non-autoimmune repertoire. While the feasibility of eliminating the vast majority of mature T cells is well established, accurate and quantitative determination of the relationship of regenerated T cells to the baseline repertoire has been difficult to assess. Here, in a phase II study of HSCT for poor-prognosis multiple sclerosis, we used high-throughput deep TCRβ chain sequencing to assess millions of individual TCRs per patient sample. We found that HSCT has distinctive effects on CD4⁺ and CD8⁺ T cell repertoires. In CD4⁺ T cells, dominant TCR clones present before treatment were undetectable following reconstitution, and patients largely developed a new repertoire. In contrast, dominant CD8⁺ clones were not effectively removed, and the reconstituted CD8⁺ T cell repertoire was created by clonal expansion of cells present before treatment. Importantly, patients who failed to respond to treatment had less diversity in their T cell repertoire early during the reconstitution process. These results demonstrate that TCR characterization during immunomodulatory treatment is both feasible and informative, and may enable monitoring of pathogenic or protective T cell clones following HSCT and cellular therapies.     

Thalidomide for patients with relapsed multiple myeloma after high-dose chemotherapy and stem cell transplantation: results of an open-label multicenter phase 2 study of efficacy, toxicity, and biological activity

OBJECTIVES: To determine the progression-free survival at 12 weeks, to evaluate the toxic effects, and to analyze the biological activity of thalidomide in patients with relapsed multiple myeloma (MM) after high-dose chemotherapy and stem cell transplantation. PATIENTS AND METHODS: From 1999 to 2001, we performed a multicenter prospective phase 2 study in patients with MM that relapsed after high-dose chemotherapy and stem cell transplantation to evaluate the efficacy of oral thalidomide, with dose escalation from 200 to 600 mg/d over 12 weeks and a subsequent maintenance phase of 200 mg/d for up to 1 year. Outcome was correlated with serum and plasma levels of vascular endothelial growth factor and serum levels of tumor necrosis factor alpha, soluble intercellular adhesion molecule 1, interferon gamma, interleukin (IL) 2, and IL-6 during treatment. RESULTS: Thirty patients were treated (19 men and 11 women; median age, 58 years). The median number of prior therapies was 5, and the median duration from diagnosis of MM to study enrollment was 4.3 years. The 12-week progression-free survival rate was 67% (95% confidence interval [CI], 48%-86%). The observed response rate (partial response plus minor response) was 43% (95% CI, 28%-60%) with a median duration of 6 months. Attributable toxicities included constipation, fatigue, rash, and neuropathy, which was dose limiting in 8 patients (27%). Dose escalation from 200 to 600 mg/d was achieved in 50% of patients. Although responses were observed with lower doses, possibly eliminating the need to escalate the dose, responses were also seen in patients who completed the dose escalation. Some patients had disease progression while receiving the maintenance dose of 200 mg/d. Analysis of biomarker assays did not identify any biomarker associated with greater response, but a significant increase in levels of soluble intercellular adhesion molecule 1, IL-2, and interferon gamma was seen with thalidomide therapy. CONCLUSION: The optimal thalidomide dose varies, and adverse effects can be dose limiting. The dose of thalidomide therapy should be based on the individual patient to ensure that it is well tolerated and that a response is achieved.     

自体造血干细胞移植治疗多发性骨髓瘤的研究进展

自体造血干细胞移植治疗多发性骨髓瘤的研究进展张茂宏孙恺综述自体造血干细胞移植（ＡＨＳＣＴ）包括自体骨髓移植（ＡＢＭＴ）和自体外周血干细胞移植（ＡＰＢＳＣＴ），自８０年代中期开始应用于血液系统恶性肿瘤包括多发性骨髓瘤（ＭＭ）的治疗。近年来的临床研究资料...     

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。     

Development of an oral care guide for patients undergoing autologous stem cell transplantation.

Nurses identified oral mucositis as a recurring issue in clinical practice. To meet this challenge, a group of nurses took a leadership role in developing an oral care guide. The University Health Network Nursing Research Utilization Model and the Neuman Systems Model served as conceptual frameworks. A flowchart was developed to ensure a coordinated and continuous provision of oral care. Educational presentations were conducted to familiarize nurses and members of the multidisciplinary team of the practice changes. The introduction of the oral care regimen as primary prevention, plus systematic oral assessment and monitoring had the potential to reduce the occurrence and severity of oral mucositis in patients undergoing autologous stem cell transplantation.     

The current status of hematopoietic stem cell transplantation for multiple myeloma

Multiple myeloma is often successfully controlled with conventional chemotherapy, but complete remissions are uncommon and cure is rare. High-dose therapy followed by autologous or allogeneic stem cells, employed for the treatment of multiple myeloma in the past 20 years, is promising as a means to increase remission rates and improve survival. Autologous transplants have not always demonstrated survival benefits in randomized studies because most of the patients transplanted relapse, while patients given conventional therapy can receive salvage transplants when they relapse. Efforts to improve the results of autologous transplant include targeted radiation, cytoprotective agents, tandem transplants, or post-transplant immunotherapy. Only allogeneic hematopoietic stem cell transplantation is potentially curative, due to a graft-versus-myeloma effect. While patients who receive either allogeneic or autologous stem cell transplants for multiple myeloma have similar 3-5 year survival, only allograft recipients appear to enjoy long-term disease-free survival. High transplant-related mortality associated with allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative modality. Strategies designed to improve the therapeutic index of allografts include the use of nonablative conditioning regimens, peripheral blood cells rather than bone marrow, graft engineering, and targeted conditioning therapies such as bone-seeking radioisotopes.     

Hospital in the home (HITH) care following autologous stem cell transplantation for lymphoma and multiple myeloma.

BACKGROUND: Advances in outpatient and supportive care and increased pressure on hospital bed usage has led to the investigation of hospital in the home (HITH) management following autologous haematologous stem cell transplantation (AutoHSCT) for patients with multiple myeloma or lymphoma. DESIGN: The Newcastle Mater Hospital Haematology Unit together with the Mater Acute Care Community Service (MACCS) developed a protocol for HITH care following AutoHSCT. OUTCOMES: Clinical outcomes of the protocol were audited: 40% (13) of patients were suitable candidates for HITH care post transplantation. Of these 84.6% (11) were readmitted to the haematology unit within seven days of discharge from hospital. CONCLUSION: Our preliminary experience suggests that with adequate infrastructure support and rigorous patient selection this model of care is both safe and feasible.