Long-Term Results in Multiple Myeloma After High-Dose Melphalan and Autologous Transplantation According to Response Categories in the Era of Old Drugs

BackgroundThe aim of this study was to investigate the correlation between the long-term prognosis of multiple myeloma (MM) and the quality of response to therapy in a cohort of 173 patients treated with high-dose melphalan (HDM) and autologous transplantation in the era of old drugs.Patients and MethodsA total of 173 patients with de novo MM who received a transplant between 1994 and 2010 were analyzed. VAD (vincristine, doxorubicin [Adriamycin], dexamethasone) was used as front-line regimen before auto-HPCT. The conditioning was HDM 200 mg/m². Patients were evaluated for clinical response using the criteria from the European Group for Blood and Marrow Transplantation, modified to include near complete remission (nCR) and very good partial remission (VGPR).ResultsThe response distribution after transplantation in our series was complete remission (CR) in 33 cases (19%), nearly complete remission (nCR) in 38 cases (22%), VGPR in 30 cases (17%), partial remission (PR) in 65 cases (38%), and stable disease (SD) in 7 cases (4%). Patients were followed for 48 ± 36 months. Median overall survival (OS) was not reached for the CR group. Progression-free survival (PFS) was 122 months for CR, 55 months for nCR, 56 months for VGPR, 32 months for PR, and 22 months for SD. Significant differences in PFS and OS were found between the CR and nCR groups (P = .003 and P = .001, respectively), between the CR and VGPR groups (P = .002 and P = .001, respectively), and between the CR and PR groups (P = .000 and P = .001, respectively). Responses were clustered in 3 main categories, ie, CR, nCR + VGPR + PR, and SD. The respective 10-year PFS and OS values were 58% and 70% for CR, 15% and 18% for nCR + VGPR + PR, and 0% and 0% for SD.ConclusionThe achievement of depth and prolonged response represents the most important prognostic factor. The relapse rate is low for patients in CR after 10 years of follow-up, possibly signifying a cure.     

PAD序贯自体造血干细胞移植治疗难治多发性骨髓瘤（附22例）

目的：多发性骨髓瘤（multiple myeloma,MM）至今仍不可治愈,几乎所有病人均会出现复发或难治,本文初步探讨硼替佐米应用于难治性MM患者PAD化疗并序贯自体外周血造血干细胞移植（autologous pe-ripheral blood stem cell t ransplantation,APBSCT）的可行性和疗效。方法：采用PAD（硼替佐米＋阿霉素＋地塞米松）方案治疗复发或难治性MM。结果：22例中3例难治MM患者给予PAD方案化疗4-6个疗程后,2例达到接近完全缓解（nCR）,1例达到部分缓解（VGPR）,并随后行APBSCT,动员方案PAD＋CTX（PAD,环磷酰胺1.5g/m2,d15）联合G-CSF。预处理方案为马法兰140mg/m2。移植后采用沙利度胺100mg/天。所有患者在移植前均达到CR或VGPR,干细胞采集充分,安全有效,移植后造血功能均快速顺利重建。无1例死亡。移植后采用沙利度胺维持,随访3-12个月,病情稳定。结论：PAD用于难治MM患者的治疗达CR后,继续序贯进行APBSCT不仅可行,而且PAD不影响正常造血干细胞动员,故采用PAD和序贯用PAD＋CTX动员方案的APBSCT的治疗手段,为难治MM患者的治疗提供新的治疗手段。但对长期生存的改善作用需进一步研究。     

PAD序贯自体造血干细胞移植治疗难治多发性骨髓瘤(附22例)

目的:多发性骨髓瘤(multiple myeloma,MM)至今仍不可治愈,几乎所有病人均会出现复发或难治,本文初步探讨硼替佐米应用于难治性MM患者PAD化疗并序贯自体外周血造血干细胞移植(autologous pe-ripheral blood stem cell t ransplantation,APBSCT)的可行性和疗效。方法:采用PAD(硼替佐米+阿霉素+地塞米松)方案治疗复发或难治性MM。结果:22例中3例难治MM患者给予PAD方案化疗4-6个疗程后,2例达到接近完全缓解(nCR),1例达到部分缓解(VGPR),并随后行APBSCT,动员方案PAD+CTX(PAD,环磷酰胺1.5g/m2,d15)联合G-CSF。预处理方案为马法兰140mg/m2。移植后采用沙利度胺100mg/天。所有患者在移植前均达到CR或VGPR,干细胞采集充分,安全有效,移植后造血功能均快速顺利重建。无1例死亡。移植后采用沙利度胺维持,随访3-12个月,病情稳定。结论:PAD用于难治MM患者的治疗达CR后,继续序贯进行APBSCT不仅可行,而且PAD不影响正常造血干细胞动员,故采用PAD和序贯用PAD+CTX动员方案的APBSCT的治疗手段,为难治MM患者的治疗提供新的治疗手段。但对长期生存的改善作用需进一步研究。     

Serum C-reactive protein at diagnosis and response to therapy is the most powerful factor predicting outcome of multiple myeloma treated with thalidomide/ anthracycline-based therapy

BackgroundFew studies have focused on factors affecting outcome in patients with multiple myeloma (MM) treated with thalidomide-based therapy. We investigated factors affecting response, progression-free survival (PFS), and overall survival (OS) in patients with MM treated with the thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) regimen with the aim to select patients benefiting more from this therapy.Patients and MethodsSixty-six patients with MM were treated first line with the ThaDD regimen. We analyzed demographics and disease-related characteristics to search for factors affecting response (≥ very good partial remission [VGPR] vs. < VGPR], PFS, and OS.ResultsOverall, 45 patients (68%) showed response ≥ VGPR; median TTP and OS were 23.5 months and 35.5 months, respectively. Multivariate analysis selected only serum C-reactive protein (sCRP) as a predictive factor for response (P < .0001). By multivariate analysis, normal sCRP level (P = .001) and response to treatment ≥ VGPR (P = .007) were found to be associated with longer PFS. The factors that remained significantly associated with a longer OS when assessed by multivariate analysis were normal sCRP level (P = .005) and response to therapy ≥ VGPR (P = .019).ConclusionSerum C-reactive protein before therapy and response after therapy are the only factors useful in identifying patients benefiting from anthracycline/thalidomide—based therapy.     

Induction Treatment With Cyclophosphamide,Thalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma: A Phase II Study

Background:Thalidomide has alternative mechanisms of action; it can be combined with dexamethasone or alkylating agents for the treatment of multiple myeloma (MM); however, the optimal doses and appropriate intervals of thalidomide continue to be debated.Patients and Methods:We assessed the clinical efficacy and toxicity of thalidomide in patients with newly diagnosed MM; 68 patients were treated with pulsed cyclophosphamide, thalidomide, and dexamethasone (CTD) chemotherapy for induction treatment.Results:After a median of 28 months' follow-up, the overall response rate was 79.4%, with a 42.6% complete response (CR) or very good partial response (VGPR). Patients with cytogenetically high-risk disease had poor CR/VGPR rates (27.3%) at a median of 11.5 months of time to progression (TTP) compared with patients with standard-risk disease who achieved CR/VGPR rates (50%) at a median of 20.3 months of TTP. The major adverse events included peripheral sensory neuropathy (14.3%), infection (10.2%), and thromboembolic complications (5.9%). Thirty-two patients who achieved more than a PR proceeded to peripheral blood stem cell collection with a median number of 5.0 × 10⁶ CD34⁺ cells/kg collected.Conclusion:CTD resulted in a favorable response with tolerable toxicity in patients with MM and did not affect the yield of the stem cell collection.     

Outcomes After Salvage Autologous Hematopoietic Cell Transplant for Patients With Relapsed/Refractory Multiple Myeloma: A Single-Institution Experience

BackgroundThe role of salvage autologous hematopoietic cell transplantation (sAHCT2) for patients with relapsed/refractory multiple myeloma (RRMM) in the era of modern therapeutics is unclear. As prospective data is limited, we conducted a retrospective analysis to determine the outcomes of sAHCT2.Patients and methodsWe conducted a single-institution, retrospective analysis of patients who received sAHCT2 at The Ohio State University from 2000 to 2018. Patients who received a second transplant as part of a planned tandem or autologous-allogeneic transplant were excluded.ResultsFifty-seven patients were treated with sAHCT2. Patients had a median of 2 lines of therapy after AHCT1 prior to their sAHCT2; 70% had prior immunomodulatory imide drugs, 82% had prior proteasome inhibitor, and 20% had prior anti-CD38 monoclonal antibodies as part of re-induction therapy. Forty-two percent of patients attained ≥VGPR prior to sAHCT2. Seventy-four were treated with melphalan 200 mg/m² as conditioning regimen before infusion of a median of 3.8 × 10⁶ CD34+ cells/kg. Fifty-eight percent patients had maintenance therapy and 81% patients attained CR/VGPR as the best response after sAHCT2. The median PFS and OS after sAHCT2 were 1.6 and 3.6 years, respectively. On multivariable analysis, high-risk cytogenetics, not having attained CR/VGPR, and having more than 2 lines of therapy post-AHCT1 were associated with inferior PFS. Melphalan 140 mg/m² compared to melphalan 200 mg/m² and no maintenance therapy compared to maintenance therapy were not associated with inferior PFS. There was no transplant-related mortality in this patient cohort.ConclusionsFor MM patients deriving durable remission after their AHCT1, sAHCT2 was safe and resulted in deep and durable remissions.     

硼替佐米对多发性骨髓瘤CLC-3表达的影响

目的:研究接受硼替佐米化疗的多发性骨髓瘤（MM）患者在化疗前后CLC-3蛋白表达的变化,探讨硼替佐米对MM患者CLC-3的影响及疗效的变化。方法:流式细胞技术分离12例初发、及复发难治的多发性骨髓瘤患者的浆（瘤）细胞,检测其CLC-3蛋白表达情况。然后所有观察病例均予以硼替佐米为主的化疗方案治疗至少4（4-6）个疗程,检测其CLC-3蛋白表达的水平,了解该指标与临床疗效的关系。结果:12例MM患者治疗前的CLC-3均存在高表达。经硼替佐米为主的化疗方案治疗后,其表达水平呈下降趋势。6例完全缓解（CR）及4例非常好的部分缓解（VGPR）的患者,CLC-3表达水平恢复接近正常。结论:硼替佐米可以对多发性骨髓瘤患者的CLC-3的表达情况产生影响,CLC-3表达水平与硼替佐米疗效呈负相关性。硼替佐米直接能否下调CLC-3水平,以及氯通道可否作为治疗该病的新靶点值得进一步研究。     

Randomized,double-blind,dose-ranging trial of the oral neurokinin-1 receptor antagonist casopitant mesylate for the prevention of cisplatin-induced nausea and vomiting

BackgroundCasopitant mesylate is a novel, oral neurokinin-1 receptor antagonist with demonstrated antiemetic efficacy. We conducted a randomized, double-blind, controlled phase II trial to evaluate three casopitant doses as part of a triple-therapy regimen for the prevention of nausea and vomiting associated with high-dose cisplatin. The aim of the study was to detect a dose response.Patients and methodsA total of 493 patients with solid tumors receiving a first cycle of cisplatin ≥70 mg/m² were randomly assigned among six treatment arms. The primary analysis compared a control arm [ondansetron/dexamethasone (Ond/Dex)] with three investigational treatments (Ond/Dex plus oral casopitant 50, 100, or 150 mg administered daily for 3 days). Two exploratory arms were included: one evaluating a single oral casopitant dose of 150 mg added to standard Ond/Dex and another with 3-day oral aprepitant-based therapy (Ond/Dex plus aprepitant 125 mg day 1, 80 mg days 2–3).ResultsThe complete response (CR) rate (defined as no vomiting, retching, rescue therapy, or premature discontinuation) was significantly increased in each casopitant arm relative to control over the 120-h evaluation period: 76% (50 mg), 86% (100 mg), 77% (150 mg), and 60% with control (P = 0.0036). The CR rate for the single oral dose regimen was similar to the CR rate reported for the 3-day regimens. No differences were observed in the incidence of nausea or significant nausea among groups in the primary analysis. The most common adverse events related to treatment included headache (n = 10) and hiccups (n = 14).ConclusionAll doses of oral casopitant as a 3-day regimen (and likely as a 150-mg single oral dose) in combination with Ond/Dex provided significant improvement in the prevention of cisplatin-induced emesis.     

Autologous Stem Cell Transplantation for Multiple Myeloma: Identification of Prognostic Factors

IntroductionThe purpose of this study was to evaluate the effect of prognostic factors on the outcome of patients with MM after ASCT.Patients and MethodsWe analyzed results of 170 consecutive patients (121 male and 49 female) of MM who underwent ASCT. Patients' median age was 52 years (range, 26-68 years). High dose melphalan (200 mg/m²) was used for conditioning. One hundred thirty-two patients (77.6%) had evidence of chemosensitive disease before transplant. Response was assessed using European Group for Blood and Bone Marrow Transplantation criteria.ResultsPost ASCT 44.7% of patients achieved CR, 24.7% had very good partial response (VGPR), and 21.2% had partial response (PR). Presence of pretransplant chemosensitive disease (CR, VGPR, and PR) and transplant within 12 months of diagnosis for years before 2006 were associated with higher response rates on multivariate analysis. At a median follow-up of 84 months, median overall (OS) and event-free survival (EFS) is 85.5 and 41 months, respectively. Estimated OS and EFS at 60 months is 62 ± 0.04% and 41 ± 0.04%, respectively. Patients who responded to transplant (CR, VGPR, and PR) had a longer OS (P < .001) and EFS (P < .001). Additionally, patients who achieved CR post transplant had a longer OS (P < .001) and EFS (P < .001). Patients who received novel agents for induction pretransplant had a longer OS (P < .001) and EFS (P < .002).ConclusionOutcome after ASCT is better for myeloma patients with pretransplant chemosensitive disease and those who achieve CR after transplant.     

雷利度胺为主方案治疗多发性骨髓瘤25例疗效分析

 目的　观察雷利度胺为主方案治疗多发性骨髓瘤（MM）患者的疗效及不良反应。方法　MM患者25例,其中5例为初治患者,13例为含沙利度胺方案治疗后难治、复发患者,7例为治疗后达平台期维持治疗患者。初治MM患者均采用R-PAD方案,难治、复发患者选用R-MD方案,维持治疗MM患者由于出现Ⅱ级伴疼痛以上的周围神经炎（PN）,采用雷利度胺单药治疗。结果　初治组5例,经过2个疗程的治疗均达到完全缓解（CR）（100 %）;难治、复发组13例,CR率为23.08 %（3／13）,非常好的部分缓解（VGPR）率为15.38 %（2／13）,部分缓解（PR）率为38.46 %（5／13）,总反应率（ORR）为76.92 %（10／13）;其余3例无反应患者中,2例疾病稳定（SD）,1例疾病进展（PD）。维持治疗组7例在平均38周的随访期内均维持缓解;改用雷利度胺后,PN获得不同程度的缓解。结论　对于初治MM患者,R-PAD方案缓解率高,起效快;对于难治、复发患者,特别是伴严重PN的MM患者,R-MD是值得选择的方案;雷利度胺还可用于伴PN的MM患者的维持治疗。     

Primary Amyloidosis With Renal Involvement: Outcomes in 77 Consecutive Patients at a Single Center

BackgroundOutcomes in primary amyloid renal patients are of interest as the era of monoclonal antibody therapies begins.Patients and MethodsWe studied 77 consecutive primary amyloid renal patients (58% men) for renal progression (end stage renal disease [ESRD]), renal response (RR), and overall survival (OS).ResultsAt diagnosis median age was 63 (range, 35-81) years, estimated glomerular filtration rate 70 mL/min (range, 5-114), difference between involved and uninvolved free light chains 127 mg/L (range, 1-9957), ESRD 4%, renal stage 2 and 3 78%, and cardiac stage 2 and 3 56%. Ninety-six percent received bortezomib and 44% stem cell transplantation as well as bortezomib, 68% achieved complete or very good partial hematologic response (CR/VGPR), 34% had ESRD, and 39% RR. Median times to ESRD and RR were 18 (range, 3-81) and 12 (range, 2-30) months, respectively. Median OS was not reached in this cohort and was not reached from onset of ESRD. More than two-thirds of patients with ESRD also achieved CR/VGPR. In those without ESRD at diagnosis, baseline creatinine and absent RR predicted progression to ESRD in multivariate Cox regression analysis, whereas CR/VGPR predicted RR. In multivariate Cox regression analysis, cardiac stage and achievement of CR/VGPR predicted OS, enabling construction of a prognostic model.ConclusionAnti-plasma cell therapies provide a definite albeit limited benefit and new approaches to amyloid-related organ dysfunction are needed.     

PAD及VAD样-T方案治疗多发性骨髓瘤126例效果比较

目的：探讨多发性骨髓瘤（MM）行 PAD 方案（硼替佐米、多柔比星、地塞米松）及 VAD 方案（长春新碱、多柔比星／多柔比星衍生物、地塞米松）联合沙利度胺（VAD 样-T 方案）治疗效果的差异。方法回顾性分析54例接受 VAD 样-T 方案及72例接受 PAD 方案治疗的 MM 患者的疗效,包括完全缓解（CR）率、非常好的部分缓解（VGPR）率、总有效率（ORR）、总生存（OS）、无进展生存（PFS）及不良反应发生情况。结果 PAD 组 CR 率高于 VAD 样-T 组,差异有统计学意义[31.5%（23／72）比9.3%（5／54）,χ2＝0.30,P＝0.002],但是 VGPR 率及 ORR 两组相比差异无统计学意义[16.7%（12／72）比16.6%（9／54）,P＝0.180;82.2%（65／72）比81.5%（44／54）,P＝0.190]。 PAD 组中位 PFS 时间长于 VAD 样-T 组[（38.2±2.2）个月比（28.0±7.6）个月,P＝0.017];PAD 组3年 PFS 率和5年 OS 率高于 VAD 样-T 组,但差异均无统计学意义（均 P＞0.05）。 PAD 组末梢神经损害发生率高于 VAD 样-T 组,差异有统计学意义[31.5%（23／72）比14.5%（8／54）,P＝0.03]。结论虽然 VAD 样-T 方案的 CR 率低于 PAD 方案,中位PFS 时间短于 PAD 方案,但 VGPR 率、ORR、3年 PFS 率、5年 OS 率与 PAD 方案相当,且相对安全,末梢神经损害的发生率相对较低。对于国内无法使用硼替佐米及骨髓移植的初发 MM 患者,可选择 VAD 样-T作为一线诱导化疗方案。     

Prognostic factors for the efficacy of thalidomide in the treatment of multiple myeloma: a clinical study of 110 patients in China

Thalidomide (Thal) has been used for a few years as salvage treatment for patients with multiple myeloma (MM). However, the response rate in Chinese patients treated with Thal has not been determined and the prognostic factors for response rate (RR), progression-free survival (PFS) and overall survival (OS) not yet well identified. This study enrolled 110 Chinese patients with MM who received either Thal alone, Thal plus dexamethasone (Thal + Dex) or Thal plus conventional chemotherapy (Thal + CC). Their laboratory and clinical parameters were retrospectively analysed. The overall RR was 63.6% (complete response rate 6.4%, partial response rate 57.3%). Patients aged < 65 years, time from diagnosis to the start of Thal treatment < 6 months or combined therapy had a significantly higher RR (p < 0.05). In univariate analysis, age < 65years predicted a longer PFS (p = 0.008). Age < 65 years, serum creatinine < 176.8 micromol L-1 and serum beta 2 microglobulin (beta2M) < 3.5 mg L-1 were associated with longer OS (p = 0.028, 0.045 and 0.019, respectively). Multi-factor analysis suggested that serum beta2M was the only independent prognostic factor for OS (p = 0.025).     

Clinical Study of Thalidomide Combined with Dexamethasone for the Treatment of Elderly Patients with Newly Diagnosed Multiple Myeloma

Objective: To investigate the relationship between the efficacy and safety of different doses of thalidomide(Thal) plus dexamethasone (Dex) as the initial therapy in elderly patients with newly diagnosed multiplemyeloma (MM). Methods: Clinical data of 28 elderly patients with newly diagnosed MM who underwent theTD regimen as the initial therapy were analyzed retrospectively. The patients were divided into two groupsaccording to the maximal sustained dose of Thal: lower dose (group A) and higher dose (group B). The overallresponse rate (ORR), progression free survival (PFS), overall survival (OS), and adverse events (AES) werecompared between the two groups. Results: A total of 28 patients were followed up with a median of 18 months.The ORR was 60.1%. The median response time and PFS were 2.0 and 17.0 months, respectively. The meansustained dose of Thal in group B was significantly higher than group A (292.9 mg v 180.4 mg, P=0.01). Therewas no significantly difference in ORR (57.1% v 64.3%, P=1.00) and PFS (9.63months v 17.66 months, P=0.73)between groups A and B. During the follow up, only five patients died (<40%) and, therefore, median OS valueswere not available. It is estimated, however, that the mean survival time in the two groups was 35.6 and 33.4months (P>0.05), respectively. All of the patients tolerated the treatment well. The incidence of AES in patientswith a grading above 3 in group B was significantly higher than in group A (P=0.033). Conclusions: The TDregimen results in a high response rate and manageable AES as the initial therapy in elderly patients with MM.TD should be considered as the front line regimen for the treatment of elderly patients with MM in areas withfinancial constraints. The clinical response can be achieved at a low dose Thal with minimal toxicity.     

小剂量环磷酰胺联合泼尼松持续应用治疗伴有严重并发症的多发性骨髓瘤

目的探讨小剂量环磷酰胺（CTX）联合泼尼松（Pred）（cP方案）持续口服治疗伴有严重并发症的多发性骨髓瘤（MM）的疗效和毒副作用。方法小剂量CTX（50mg／d）联合Pred（15mg／d）持续口服,6个月无效或进展则退出研究,如完全缓解（CR）后维持6周则停药随访。23例患者中18例伴有严重并发症,5例患者因接受常规化疗疗效差且反复出现严重感染不愿接受常规化疗。既往方案1。4个。结果23例患者中CR1例,非常好的部分缓解（VGPR）4例,部分缓解（PR）9例,微小反应（MR）3例,进展（PD）6例,生活质量及体力状况明显改善。结论小剂量CTX联合Pred持续口服治疗伴有严重并发症的MM是可行的。     

A Clinical and Correlative Study of Elotuzumab,Carfilzomib, Lenalidomide,and Dexamethasone (Elo-KRd) for Lenalidomide Refractory Multiple Myeloma in First Relapse

IntroductionTreatment of patients with multiple myeloma (MM) in first relapse remains a challenge. This phase II study combined elotuzumab (Elo) with carfilzomib, lenalidomide, and dexamethasone (KRd) for treatment of MM in first relapse with the aim of improving efficacy.MethodsEnrolled patients received Elo-KRd induction for 4 cycles, and Elo-lenalidomide maintenance until progression. The primary endpoint was VGPR or better (≥VGPR) postinduction. Secondary endpoints were MRD by flow cytometry, OS, PFS, and safety. Correlatives included characterization of the impact of Elo-KRd on NK and T cell subsets via flow cytometry. Target accrual of 40 patients was not met due to COVID-19 pandemic.ResultsOf 15 patients enrolled, 10 (67%) had high-risk features (del17p, t[4;14], t[14;16], 1q gain/amplification, plasma cell leukemia, extramedullary MM, or functional high risk), 12 (80%) were lenalidomide-refractory, and 5 (33.3%) bortezomib-refractory. Postinduction ≥VGPR was 7/15 (46.7%) and MRD-negative (10⁻⁵) rate 20%. Overall response during study was 80%, including ≥VGPR as best response of 53.3%. At median follow-up of 28.2 (range, 3.8 to 44.2) months, the median PFS was 11.5 months (95% CI 1.9, 18), and median OS not reached (95% CI 10.1, NA). No new safety concerns were reported. Elo-KRd treatment did not augment NK cell distribution or activity in blood or bone marrow. Effector CD4+ and CD8+ T cells significantly decreased postinduction, with concomitant acquisition of T central memory phenotype, particularly at a high rate in ≥VGPR group.ConclusionA short course of Elo-KRd induction followed by Elo-lenalidomide maintenance demonstrated activity in predominantly lenalidomide-refractory and / or high-risk MM. The results with this well-tolerated combination are comparable to other contemporary approved triplet combinations.     

硼替佐米联合异环磷酰胺、甲泼尼龙、沙利度胺方案治疗多发性骨髓瘤

 目的　观察硼替佐米联合异环磷酰胺、甲泼尼龙、沙利度胺（V-CMPT方案）治疗多发性骨髓瘤（MM）的临床疗效和患者不良反应。方法　回顾性分析应用V-CMPT方案进行治疗的24例初治和复发难治MM患者资料,3周为1个周期,治疗2个周期。应用骨髓细胞学检查、M蛋白鉴定以及其他血液学指标评价病情及疗效。结果　初治的9例患者中,完全缓解（CR）3例、部分缓解（PR）5例、轻微缓解（MR）1例;复发难治的15例患者中,CR2例、接近完全缓解（nCR）2例、PR 3例、MR 6例、无变化（NC）2例;两组间总缓解率（ORR）（P＝0.511）及CR／nCR率（P＝1.000）差异无统计学意义。总的CR／nCR率29.2 %（7／24）,ORR达到91.7%（22／24）。2个周期V-CMPT化疗后,患者的血红蛋白、血清清蛋白及血清β2微球蛋白得到明显改善。不良反应包括胃肠道反应、血小板减少、周围神经病变等,经对症处理或间歇期停药多好转,不影响化疗的继续进行。结论　V-CMPT方案对初治和复发难治性MM临床疗效明显,能够明显改善血液学指标,药物耐受性良好。     

Familial Disease Predisposition Impacts Treatment Outcome in Patients With Waldenström Macroglobulinemia

BackgroundWe examined the impact of familial predisposition on treatment outcome in 135 patients with Waldenström macroglobulinemia (WM), 26.7% of whom had first- or second-degree relatives with a B-cell lymphoproliferative disorder.Patients and MethodsAll patients were rituximab naive and received a rituximab-containing regimen. There were no significant differences in baseline characteristics between cohorts.ResultsOverall response (93.9% vs. 75.0%; P = .029) and complete response/very good partial response (CR/VGPR) (23.2% vs. 16.7%; P < .0001), time to progression (TTP) (45.5 vs. 21 months; P = .015) and time to next therapy (TTNT) (50.0 vs. 33.0 months; P = .024) favored patients with sporadic WM. By multivariate analysis, familial predisposition was an independent marker for disease progression (hazard ratio, 0.554). Patients with familial but not sporadic disease exhibited better responses, including CR/VGPR attainment (P = .0006) and a trend for longer progression-free survival (> 33 vs. 20.6 months; P = .08), with bortezomib-containing therapy.ConclusionThe findings convey that familial predisposition is an important determinant of treatment outcome in WM. Prospective studies to confirm these observations are needed.     

30例自体外周造血干细胞移植治疗多发性骨髓瘤的疗效及预后因素评价

目的:对30例多发性骨髓瘤（multiple myeloma,MM）患者经自体外周造血干细胞移植（autologous hematopoietic stem cell transplantation ,APBSCT）治疗后的临床疗效进行评估,并分析可能影响预后的因素。方法:30例MM患者有2 例复发行2 次APBSCT,因此共计移植32例次。移植前予常规联合化疗（11例含万珂）,化疗联合G-CSF 动员APBSC ,选择以马法兰为基础的预处理方案,d0 天回输。结果:动员后患者采集的单个核细胞（MNC）中位数为6.41× 108/kg,CD34+细胞4.75× 106/kg。APBSCT后中位中性粒细胞和血小板重建时间分别为9.5 天和11天。APBSCT后CR和VGPR 率分别为37.5% 和34.4% ,中位生存期（overallsurvival ,OS）为67.27个月,中位无进展生存期（progression-freesurvival ,PFS）为29.77个月,其中CR组、PR组中位PFS 分别为29个月、20个月,VGPR 组中位PFS 未达到,CR+VGPR组与PR组PFS 比较P=0.025。万珂组和非万珂组CR率分别为63.6% 和23.8%（P=0.034）,万珂组中位OS及PFS 均未达到,非万珂组中位PFS 为22个月（P=0.045）。 结论:硼替佐米诱导序贯APBSCT可获得更长的无病生存。APBSCT作为MM诱导缓解后的强化治疗,缓解率高,且移植后获得VGPR 以上反应的患者PFS 获益。      

沙利度胺联合地塞米松治疗复发和(或)难治及平台期多发性骨髓瘤疗效分析

目的观察沙利度胺联合地塞米松（TD方案）治疗多发性骨髓瘤（MM）的疗效。方法62例MM患者,其中复发和（或）难治组25例,平台期组37例。复发和（或）难治组治疗方案为：TD方案3个疗程后无效或进展者更换方案;有效者,继续使用TD方案,3个疗程后停用地塞米松,单独使用沙利度胺直到复发。平台期组的患者仅使用3个疗程的TD方案,再单独使用沙利度胺维持治疗。结果25例复发和（或）难治的患者,前3个疗程TD方案的25例中20例总有效[非常好的部分缓解（VGPR）＋部分缓解（PR）＋进步（MR）]率为80％,但无完全缓解（CR）或接近完全缓解（nCR）。有效者,经后3个疗程TD治疗后,1例获得nCR,而2例PR患者回到MR,无患者发展到NR或进展;对13例VGPR＋PR＋nCR患者,单独使用沙利度胺4～12个月（中位时间6．8个月）后复发。37例平台期的患者经上述方案治疗8～26个月（中位时间17．5个月）后复发。明显优于难治和（或）复发组的治疗效果（P〈0．001）。结论沙利度胺联合地塞米松是难治和（或）复发MM有效治疗方案,也可作为平台期患者的维持治疗。