多发性骨髓瘤肾功能损伤的研究进展

 多发性骨髓瘤（MM）是浆细胞的恶性肿瘤,肾功能损伤是多发性骨髓瘤的常见并发症。轻链蛋白在肾小管内沉积,形成骨髓瘤管型肾病被认为是重要的病理基础。针对MM患者,应评估肾小球滤过率,评价其肾功能损伤程度。硼替佐米联合大剂量地塞米松可用于治疗伴发肾功能损伤的骨髓瘤,可改善大多数患者的肾功能。尽管沙利度胺治疗经验有限,但可以对伴发肾衰竭的患者使用标准剂量的治疗。根据肾功能情况减量使用雷利度胺,对骨髓瘤患者是有效的,可逆转部分骨髓瘤患者的肾功能损伤。     

自体干细胞移植治疗伴有严重肾功能不全的多发性骨髓瘤

 肾衰竭是多发性骨髓瘤（MM）患者常见的临床表现。伴有肾衰竭的MM患者对传统化疗的总缓解率为35 %～50 %（完全缓解少见）,中位生存期为4个月～1年,均显著低于肾功能正常患者。有许多中心应用大剂量美法仑以及自体干细胞移植（ASCT）治疗伴有严重肾衰竭的MM患者。目前研究发现,患者肾功能严重程度以及是否接受透析对干细胞动员以及干细胞植入无明显影响。大剂量美法仑以及ASCT后,伴有肾衰竭MM患者的完全缓解率、无事件生存率以及总生存率,分别增加到30 %、20个月以及40个月左右。相当一部分患者脱离透析。但是,该领域存在的问题仍然相当多,如APBSCT导致较高的移植相关死亡率。另外,在沙利度胺、硼替佐米以及雷利度胺等新药应用于临床之后,对于ASCT治疗伴有肾衰竭MM患者的影响如何,也需要进一步探讨。     

多发性骨髓瘤治疗中值得关注的几个问题

多发性骨髓瘤(multiple myeloma,MM)的治疗主要包括传统化疗、自体造血干细胞移植(autologous stem cell transplanration,ASCT)和新型靶向治疗3种方式.新的靶向治疗的联合或与传统抗骨髓瘤药物的联合已经能够获得与ASCT相当的完全缓解(complete remission,CR)率,并可延长患者生存期.取得CR是长期控制疾病的关键,但仍有部分患者虽未取得CR,但生存期却可超过5年甚至10年.本文就CR在MM治疗中的临床意义以及ASCT的地位和作用进行综述.     

新诊断的多发性骨髓瘤的治疗选择

根据国际骨髓瘤工作组（IMWG）关于骨髓瘤的最新分类可以将多发性骨髓瘤（MM）大致分为两类：无症状骨髓瘤（冒烟型骨髓瘤）和有症状的MM。前者相当于Durie-Salmon（DS）I期,此类患者不需要治疗,只需定期复查和观察;后者相当于DSⅡ、Ⅲ期,需要立即进行治疗。2007年美国国家综合癌症网络协会（NCCN）建议Ⅱ期或Ⅲ期、机体状态良好的MM患者行自体干细胞移植（ASCT）。因此应根据是否适合行ASCT对新诊断MM患者选择不同的诱导治疗方案。     

造血干细胞移植治疗16例多发性骨髓瘤疗效分析

目的：评价造血干细胞移植（SCT）治疗多发性骨髓瘤（MM）患者的疗效。方法：回顾性分析我院SCT治疗16例D-S分期Ⅲ期MM患者。自体造血干细胞移植（ASCT）13例。2例原发耐药、2例ASCT后复发和1例高危患者接受HLA匹配同胞供者异基因造血干细胞移植（allo-SCT）;其中4例应用清髓性预处理。采用NCI/SWOG（2004年前）和EBMT标准分析治疗反应。结果：共完成ASCT20例次,无移植相关死亡（TRM）。ASCT后均有效,9例获得完全缓解（CR）,4例部分缓解（PR）。10例移植前CR/PR者,中位随访35（6～126）个月,3例复发/进展,中位总生存（OS）尚未达到[已超过35（6～119）个月],中位无进展生存（PFS）27（1～50）个月。3例ASCT前处于疾病稳定状态（SD）者分别于移植后11、7和5个月后复发/进展。Allo-SCT组1例预处理后早期TRM,余3例CR,1例PR。1例患者移植后4个月死于急性移植物抗宿主病（GVHD）合并严重肺感染;余3例生存分别已达39、41和14个月,其中仅后者仍持续PFS。结论：ASCT治疗MM耐受性好,能明显延长PFS和OS;原发难治患者ASCT仍有效,但PFS持续时间短暂。沙利度胺联合治疗用于移植前/后可能提高疗效。allo-SCT有效提高高危及复发/难治患者的治疗反应率。     

靶向新药时代自体造血干细胞移植在多发性骨髓瘤治疗中的作用

多发性骨髓瘤（MM）是浆细胞恶性克隆性疾病,自体干细胞移植（ASCT）的加入,增加了大剂量化疗在MM治疗中的优势,使部分患者达到长期生存.即使在靶向新药时代ASCT仍可以明显提高治疗的反应率.靶向新药在ASCT前后联合应用,可辅助提高ASCT的疗效,这是目前使用靶向新药的趋势,但其仍不能取代ASCT在MM治疗中的地位.研究更为合理、有效、低毒的治疗方案是今后的方向.     

VD方案联合自体造血干细胞移植治疗难治性不分泌型多发性骨髓瘤一例并文献复习

 目的　观察硼替佐米+地塞米松（VD）方案联合自体造血干细胞移植（ASCT）治疗一例难治性不分泌型多发性骨髓瘤（MM）患者的疗效。方法　通过对1例难治性不分泌型MM患者给予VD方案化疗4个周期,在疾病得到有效控制、临床体征改善后,进行ASCT（预处理方案为美法仑200 mg／m2）,并对国内外相关文献复习。结果　患者经过化疗达到接近完全缓解（nCR）,之后联合ASCT后达到完全缓解（CR）。结论　VD方案联合ASCT可明显改善难治性不分泌型MM患者的临床预后。     

多发性骨髓瘤维持治疗的研究进展

多发性骨髓瘤(multiple mfeloma,MM)是第二常见的血液肿瘤病,目前仍无法治愈。诱导治疗后序贯自体干细胞移植（ASCT）已经成为一种标准化治疗,但依然可能存在复发。使用维持治疗的目的是通过增加无进展生存期（PFS）,加深缓解,进而增加总生存期(OS)。本文主要对新药时代MM的维持治疗的进展作一综述。     

以腕管综合征为首发症状的多发性骨髓瘤合并淀粉样变2例并文献复习北大核心

轻链型淀粉样变又称原发性系统性淀粉样变性,是一种由具有反向β-折叠结构的单克隆免疫球蛋白轻链沉积在器官组织内引起的临床症候群。10%~20%的多发性骨髓瘤患者可出现继发性轻链型淀粉样变[1]。淀粉样物质常沉积在肾脏、心脏、肝脏、周围神经和自主神经、胃肠道以及软组织。以腕管综合征为首发症状的淀粉样变临床少见,本文报道2例我院诊治的以腕管综合征为首发症状的MM伴AL患者,本研究项目设计及实施计划符合伦理基本准则,符合我国《涉及人的生物医学研究伦理审查办法》,并取得受试对象知情同意。     

微小残留病检测在多发性骨髓瘤移植后患者中的应用现状与思考

多发性骨髓瘤（multiple myeloma,MM）患者的治疗疗效在近十年来不断提高,特别是在新药联合移植治疗后,其无进展生存期（progression free survival,PFS）和总生存期（overall survival,OS）均大幅延长。对于患者的疗效而言,传统意义的评效标准完全缓解（complete response,CR）已经不能满足其对预后的指导,微小残留病（minimal residual disease,MRD）的评估应运而生,其检测方法发展较快。血清游离轻链（serum free light chain,sFLC）、流式细胞术、聚合酶链式反应（polymerase chain reaction,PCR）、二代测序（next-generation sequencing,NGS）和PET-CT等各项技术层出不穷。本文就上述各检测手段在MM移植后患者中的应用现状予以综述。      

Manifestations rénales au cours du myélome

Nephropathy associated with myeloma is frequent, sometimes revealing the disease and making the prognosis worse. Histological exam has become, thus, one of the principal keys of the diagnostic of the different lesions and so of the drawing up of the disease prognosis. This study aimed to characterize the histological lesions of kidney during myeloma, in the Academic Hospital Center of Ibn-Rochd of Casablanca (Morocco), and to indicate the immunoglobulin chains, most blamed in their occurrence. It was a retrospective study covering a period of 9 years (2005–2013) and collecting 18 histological reports of kidney biopsy realized in the pathologic anatomy laboratory of the academic hospital center. The patients had a means age of 59.18 ± 9.83 years [39–73 years] with an equal repartition according to the sex (8 women/10 men). The clinical symptomatology was dominated by a proteinuria superior to 1 g/24 h (82.35%), a renal failure (76.47%), and a high blood pressure (52.94%). The most frequent histological diagnosis of nephropathy associated with myeloma in this cohort was cast nephropathy, AL amyloidosis, and light chain deposition disease. One case of Fanconi syndrome with an aspect of proximal tubulopathy was diagnosed. Nephropathy associated with myeloma is frequent and serious. Kidney biopsy should be directed earlier by the clinical and biological follow-up of patients in order to reduce the occurrence of these complications and to increase the patients’ survival.     

The clinical picture of multiple myeloma

Diagnosis of multiple myeloma is based on the triad paraproteinemia, osteolytic bone lesions and bone marrow plasma cell infiltration. Clinically, rheumatoid-like pain induced by osteolytic skeletal lesions often prevails. Occasionally, foudroyant bacterial infections - the most frequent cause of death in myelomatosis - or acute/subacute renal failure or rarely, acute hemi- or paraparesis precede diagnosis. Establishment of diagnosis early in the course of the disease and improved cytostatic and symptomatic treatment has led to a decrease in episodes of hyperviscosity-syndromes. Severe renal insufficiency due to Bence-Jones proteinuria prevails in 20% of patients already at time of diagnosis. With increasing duration of the disease, frequency of renal insufficiency further increases. Hypercalcemia with consecutive dehydration and renal insufficiency usually is a complication of long-standing disease. Anemia, leukopenia and thrombo-cytopenia are not only side effects of cytostatic treatment, but also consequences of tumor-induced suppression of hematopoiesis. Polyneuropathies are common in myelomatosis. They probably are the result of specific and/or unspecific binding of paraproteins to myelin sheaths. Effective treatment for this complication is not available at present. Thrombohemorrhagic complications are more frequent in patients with myeloma than in the control group of other hospitalized patients. Non-secretory myeloma, osteoblastic myeloma and Takatsuki syndrome are variants of myelomatosis. Solitary and extramedullary plasmocytoma are different, potentially curable entities. Prognosis is especially poor in patients with plasma cell leukemia and poor in primary amyloidosis.     

Nonamyloidotic monoclonal immunoglobulin deposition disease. Light-chain, heavy-chain, and light- and heavy-chain deposition diseases

In 1990 and 1992, in previous reviews of the literature and in reports of their experience with both amyloid and non-amyloid monoclonal immunoglobulin deposition diseases, the authors proposed a classification scheme encompassing all the forms of non-antibody-mediated monoclonal immunoglobulin deposition. The premise underlying the proposal was that the mode of pathogenesis of each of the various disorders is similar. Monoclonal expansion of a B-cell and plasma-cell population producing an excess immunoglobulin polypeptide with structural characteristics predisposing to tissue deposition in either the fibrillar or nonfibrillar state would be associated with organ-compromising deposits in tissue. At that time it appeared that LCDD and LHCDD were more likely to occur in the course of myeloma in which the other features of the neoplastic cells (i.e., marrow suppression, lytic lesions, recurrent infections) were also clearly evident. At this time, the authors' additional experience suggests that this judgment may have been premature, based in part on too small an initial sample and in part on the use of diagnostic criteria for multiple myeloma that may have not been sufficiently precise. The authors now believe that the nodular glomerulopathic form of NAMIDD is similar in both course and prognosis to AL amyloidosis occurring in the absence of multiple myeloma (primary amyloidosis). The primarily tubular basement-membrane form of the disease usually seen with concurrent myeloma kidney with BJCN, is associated with more aggressively proliferative plasma-cell neoplasms. The authors believe that these associations relate to the size of the malignant clone which, in turn, determines the amount of depositionogenic protein available and the rate of its presentation to the target organ (primarily the kidney). The distinction is not trivial, for if the authors are correct, their data suggest that not all forms of renal disease occurring in the course of plasma-cell dyscrasias have the same bleak prognosis. The outlook for nodular glomerular disease, as an indirect marker of clone size, may be intrinsically better than that of a renal biopsy showing cast nephropathy and tubular basement membrane LCDD deposits and clinical renal failure. Since 1992, it has also become less certain that there are general structural differences between light chains forming amyloid and those producing non-Congophilic tissue deposits. The current data suggest that light-chain proteins with the capacity to form pathogenic tissue deposits may exist in a spectrum, with one end represented by those only capable of forming amylord, the other by those depositing in a more amorphous, nonfibrillar manner, and a group in the center capable of either or both, depending on circumstances that are presently not understood. An alternative view suggests that all or most proteins depositing as fibrils pass through a non-Congophilic, nonfibrillar phase, of a length varying according to their primary structure, which is not detected in vivo because of the vagaries imposed by clinical sampling. More structural analyses of material extracted from deposits in tissue may resolve this issue.     

以肾功能不全为首发症状MM患者的免疫球蛋白三系和IgM水平特征

目的:分析多发性骨髓瘤并发肾功能不全患者的临床特征.方法:回顾性分析我院收治的70例多发性骨髓瘤患者的临床资料,按照GFR取值,分为肾功能不全组和肾功能正常组.分别对性别、年龄、血红蛋白、白蛋白、血钙、校正血钙、尿酸、乳酸脱氢酶、免疫球蛋白(IgA、IgG、IgM)参数进行统计学分析.对多发性骨髓瘤患者合并肾功能不全患者采用多元Logistic回归分析,确定各因素的关联性.结果:在免疫分型方面,IgM型和轻链型多发性骨髓瘤更容易发生肾功能不全,伴有肾功能不全的多发性骨髓瘤患者具有更低的血红蛋白,更高的血钙、校正钙浓度及血尿酸,均显著高于肾功能正常组(P<0.05).而肾功能不全与健全组患者在性别、年龄、白蛋白、乳酸脱氢酶比例方面并无显著统计学差异.IgM水平与肾功能不全有较强的内在关联性.结论:伴有肾功能不全首发症状的多发性骨髓瘤患者通常与IgM的水平高低有一定的关联性.     

意义未明的单克隆免疫球蛋白血症的病程演变、鉴别诊断及其干预策略:第54届美国血液学会年会报道

 【摘要】　意义未明的单克隆免疫球蛋白血症（monoclonal gammopathy of undetermined significances,MGUS）被界定为癌前克隆性疾病。其在50岁以上人群中的发病率达到4.2 %,且以每年1 %的高风险向多发性骨髓瘤（multiple myeloma,MM）和相关的恶性疾病转化。确定其病程演变将指导临床诊断和治疗。大多数MGUS患者仅需随访观察。而少部分患者则经过冒烟型骨髓瘤（smoldering multiple myeloma,SMM）阶段进展为MM,或者因M蛋白导致终末器官损害,发展为轻链型疾病,如轻链型淀粉样变性、轻链沉淀病等,需要启动药物干预措施。2012年第54届美国血液学会（ASH）年会进行了这部分内容的详细报道。     

Lack of Renal Recovery Predicts Poor Survival in Patients of Multiple Myeloma With Renal Impairment

BackgroundRenal impairment (RI) confers a poor prognosis in multiple myeloma. Reversibility of renal function is associated with improved survival in such patients. Patients in developing countries often present at an advanced stage and renal impairment is present in up to 40% of patients at diagnosis. We studied the renal outcome and survival of these patients with bortezomib-based induction therapy.Materials and MethodsIt was a single-center prospective study in a tertiary care multi-specialty institute in patients of newly diagnosed multiple myeloma (NDMM) who presented with RI from July 2018 to December 2019. The diagnosis of multiple myeloma was made based on IMWG14 criteria. All patients received bortezomib and or immunomodulatory drug-based triplet or quadruplet induction therapy. Hematological and renal outcomes were assessed as per IMWG 2016 criteria.ResultsAmong 216 consecutive patients of NDMM, RI was seen in 91 (42.2%) patients. The median age of 91 patients was 60 years. (range- 32-80 years). Light chain myeloma was seen in 26% (n = 24) of patients. The median estimated glomerular filtration rate (eGFR) was 15.36 mL/min (3.1-38 mL/min) and a majority of patients were in the advanced ISS stage. (ISS III = 85.7%). Thirty-six (39.5%) patients received hemodialysis at presentation. Renal response was seen in 67 (73%) patients and 20 (out of 36; 55%) became dialysis independent over a median time of 38 days (Range 15-160 days). At a median follow-up of 14.7 months, 30 (33%) patients had died, of which, 14 (15.4%) patients had early mortality (within 2 months of diagnosis). Presence of light chain myeloma and cast nephropathy (definite or probable) were identified as independent predictors of poor renal recovery on multivariate analysis. (HR = 2.841; 95% CI [1.471-5.486], P = .002 for light chain myeloma; HR = 1.859; 95% CI (1.087-3.180); P = .024 for cast nephropathy) Patients with low eGFR at presentation (<12.5 mL/min) were more likely to have persistent renal insufficiency. (HR-3.521; 95% CI (1.856-6.679), P = .000). Patients who attained sustained renal recovery had improved survival as compared to patients in whom renal function failed to improve. (median OS- not reached vs. 8.3 months, P = .000) Achievement of hematological response and independence from hemodialysis was associated with improved survival on multivariate analysis.ConclusionRenal impairment was reversible in almost three-fourths of NDMM patients. achievement of hematological response and hemodialysis independence were independent predictors of improved overall survival in NDMM patients with RI.     

Percentage of urinary albumin excretion and serum-free light-chain reduction are important determinants of renal response in myeloma patients with moderate to severe renal impairment

Reversal of renal dysfunction significantly affects the prognosis of multiple myeloma (MM) with renal impairment (RI). There is no reliable test for predicting reversibility of RI in MM patients. We postulated that MM with high albuminuria may reflect glomerular disease that is difficult to reverse. Here, we examined the impact of urinary albumin excretion. We retrospectively analyzed 279 patients admitted to our hospital from April 2000 to December 2013. Clinical variables and laboratory data that may affect myeloma treatment response were extracted. The results were examined for relationship to renal response by univariate and multivariate analysis. RI (estimated glomerular filtration rate ≦50 ml/min per 1.73 m²) was observed in 116 patients (46%) and renal responses of renal complete response, renal partial response, renal minor response and no response were obtained in 46 (40%), 15 (13%), 13 (11%) and 42 (36%) patients, respectively. Although renal recovery was significantly associated with Durie–Salmon 1 or 2 (P=0.02), myeloma response better than very good partial response (P=0.03), involved free light-chain (iFLC) reduction from baseline 80% at day 12 (P=0.005), ≧95% at day 21 (P<0.001) and urinary albumin ≦25% on admission (P<0.001) on univariate analysis, only reduction of iFLC 95% at day 21 (P=0.015) and urinary albumin ≦25% (P=0.007) remained significant for any renal response. Our observation indicates that increased urinary albumin excretion >25% and reduction of iFLC ≦95% on day 21 were associated with favorable renal recovery in MM patients with RI, and were considered as negative predictors for renal response.Renal impairment (RI) is a major cause of morbidity and mortality in patients with multiple myeloma (MM) and approximately 50 and 20% of patients have RI and acute renal failure depending of its definition.^{1, 2, 3, 4} The presence of RI limits the use of antimyeloma agents and eligibility for stem cell transplantation, and, therefore, places these patients at higher risk for disease progression and myeloma-related complications. RI is also associated with an increased risk of early death,^5,6 although the recent introduction of effective novel agents, such as thalidomide, bortezomib and lenalidomide, has led to the improved survival even in patients with RI.^7,8The most common cause of RI in MM is cast nephropathy, which may be seen in up to 30% of patients;⁹ other causes of RI include monoclonal immunoglobulin (Ig) deposition disease and amyloidosis. It should be noted that non-paraprotein-associated renal lesions are also seen in 25% of patients. As most patients with MM are elderly, age-related comorbidities such as hypertension and diabetes may also be associated with the decline of renal function.As the reversibility of renal function may be dependent on the pathogenesis of renal disease,¹⁰ correct renal pathology is necessary for successful treatment. Use of bortezomib-based regimens in combination with or without plasma exchange has been reported to yield high rates of renal recovery in patients with cast nephropathy.^{11, 12, 13, 14} However, reversibility of renal function in cases other than cast nephropathy is largely unknown. Kidney biopsy cannot be performed in all patients with MM and RI because of its various limitations and possible complications. Recently, Nasr et al.⁹ reported the clinicopathologic correlations in MM patients with kidney biopsy; they reported the highest levels of albuminuria in patients with amyloidosis and lowest levels in those with cast nephropathy.Despite the heterogeneity of renal pathology, urine albuminuria is thought to reflect glomerular injury, and patients with cast nephropathy usually show tubulointerstitial injury and lack heavy albuminuria. Therefore, we postulated that renal response may be different according to urinary albumin excretion. In this study, we retrospectively analyzed the clinical variables that may affect renal response in 116 MM patients with RI at our hospital. We also examined the predictive capacity of urinary albumin and serum-free light-chain (FLC) reduction on renal recovery of RI patients with MM.     

The implication of compromised renal function at presentation in myeloma

The purpose of the study was to determine the role of sequential therapy (ST) in new patients with myeloma presenting with renal dysfunction (RD): serum creatinine >140 μmol/L (1.6 mg/dL). Between April 1985 and June 1998, 251 patients, 59 (23%) with RD were entered into a ST program comprised of infusional chemotherapy (IC) with VAMP/C-VAMP (vincristine, doxorubicin, and methylprednisolone with/without cyclophosphamide) followed by autologous transplantation and interferon maintenance. The median overall survival (OS) of 251 patients from the start of IC was 4.2 yr with the RD group faring significantly poorer (median 2.5 yr) than those with no renal dysfunction (NRD; median 4.6 yr; p=0.0025). Mortality during the first 100 d of IC was significantly higher in patients with RD (11/59; p=0.01) compared to patients with NRD. In patients consolidated with high-dose therapy, the OS and event-free survival (EFS) were not significantly different between the two groups. Cox analysis of the variables at presentation failed to show RD as a factor influencing outcome, but it showed that patients with beta-2-microglobulin (β₂M)≥3.7 (p<0.0001), age ≥52.5 yr (p=0.002), performance status (PS) ≥2 (p=0.005) and patients with light-chain myeloma (p=0.03) had a significantly shorter OS, β₂M≥3.7, PS≥2, and light-chain myeloma were predictive of shorter EFS. The study shows that with modern intensive schedules of treatment, renal disease at presentation in isolation does not compromise outcome.     

Primary (AL) amyloidosis in plasma cell disorders

Primary (AL) amyloidosis is the most common form of systemic amyloidosis. The morbidity arises from extracellular deposition of immunoglobulin light chain (LC) fibrils in major organs, such as the kidneys, heart, and bowel. Organ dysfunction contributes to a high mortality and poor prognosis, with a median survival time of 1-2 years from diagnosis. Here, we present a 46-year-old man with an exceptional clinical course of an LC multiple myeloma with generalized amyloidosis, causing renal insufficiency, congestive heart failure, and complete intestinal necrosis. We have summarized recent knowledge on AL amyloidosis, its association with monoclonal gammopathies, clinical presentations, diagnostic tools, and treatment strategies. Our comprehensive overview of this rare and often fatal disease aims to increase the awareness of AL amyloidosis. This may facilitate earlier diagnosis, and thus allow initiation of prompt and specific therapies, which are indispensable in order to improve disease prognosis.     

硼替佐米联合地塞米松治疗24例多发性骨髓瘤的疗效分析

背景及目的:硼替佐米(bortezomib)是一种有效、可逆性的蛋白酶体抑制剂,通过诱导骨髓瘤细胞的凋亡,在骨髓瘤患者的治疗中发挥持久的疗效。本研究旨在观察硼替佐米联合地塞米松治疗初治、难治/复发多发性骨髓瘤(multiple myeloma,MM)患者的疗效和毒副作用,及该方案在肾功能不全患者中应用的安全性。方法:24例MM患者接受硼替佐米联合地塞米松方案治疗,每3周为一个疗程。所有患者共接受中位3个疗程(1～8个疗程)的化疗。采用EBMT疗效评价标准评价疗效,按国立癌症研究所的常规毒性判定标准评价不良反应。结果:全组中位随访4个月,总有效率79.2%(19/24)。轻链型患者CR率57.1%(4/7),明显高于非轻链型患者5.9%(1/17),差异有统计学意义(P=0.014)。7例合并肾功能不全的患者与肾功能正常患者的疗效相近,差异无统计学意义(P=0.272)。Ⅲ～Ⅳ级不良反应包括白细胞减少(2/24,8.3%)、血小板减少(8/24,33.3%)、腹泻(2/24,8.3%)和乏力(1/24,4.2%),经对症治疗或推迟化疗后均可恢复。结论:硼替佐米联合地塞米松方案治疗MM患者有明显疗效,在轻链型患者疗效更加显著。副作用可以耐受,在合并肾功能不全的患者可安全应用。