美法仑等药物治疗系统性淀粉样变的临床疗效分析

目的:分析系统性淀粉样变临床特点及不同方案治疗情况下的临床疗效,提高对淀粉样变的治疗认识。方法:回顾分析哈医大一院及大庆油田总医院近10年43例淀粉样变药物治疗的临床资料,总结不同临床特点下药物疗效和预后。结果:2组药物有效率分别为54.90%、48.57%,组间无差异性(P0.05)。原发性淀粉样变和继发性淀粉样变总有效率分别为32.72%、74.19%,组间具有差异性(P0.05)。不同年龄组间有效率具有差异性(P0.05)。不同治疗周期有效率无差异性(P0.05)。不同病变系统有效率分别为单系统75.00%,2个系统45.00%,3个系统29.41%,4个及以上系统5.88%,组间具有差异性(P0.05)。器官功能代偿期与失代偿期的有效率分别为61.76%、30.76%,组间具有差异性(P0.05)。结论:药物治疗系统性淀粉样变性具有确切的临床疗效,对继发性淀粉样变的临床疗效优于原发性淀粉样变。药物治疗的最佳周期为6个月以内,延长治疗时间不能提高临床疗效而会增加副作用。随着病变器官和系统的增加及器官功能失代偿,药物疗效降低。     

华蟾素联合MPT方案治疗多发性骨髓瘤疗效观察

目的观察华蟾素联合MPT方案治疗多发性骨髓瘤初治患者近期疗效。方法回顾性分析了45例多发性骨髓瘤初治患者,以应用华蟾素与否分为两组。对照组采用MPT方案化疗,治疗组在对照组基础上加用华蟾素注射液,4周为1疗程,3个疗程后观察疗效。结果治疗组有效率为80%,略高于对照组（70%）,但无统计学意义（P〉0.05）。治疗后治疗组卡氏评分高于对照组（P〈0.05）,骨痛评分明显低于对照组（P〈0.05）。治疗前两组患者CD3＋/HLA-DR＋表达比例接近,治疗1疗程后CD3＋/HLA-DR＋水平降低,但两组差异无统计学意义（P〉0.05）,治疗3疗程后CD3＋/HLA-DR＋表达有上升趋势,治疗组恢复较快,优于对照组（P〈0.05）。华蟾素的副作用主要表现为血管刺激,两组其余不良反应相当,差异无统计学意义（P〉0.05）。结论华蟾素对多发性骨髓瘤初治患者的近期疗效无明显提高,但在改善患者生活质量及免疫功能方面具有较好的效果。     

Isolated limb perfusion for the management limb threatening soft tissue sarcomas: The role of histological type on clinical outcomes

Background

Hyperthermic isolated limb perfusion (HILP) is an effective neoadjuvant treatment to avoid amputation in patients with locally advanced extremity soft tissue sarcomas (STS). We aimed to investigate whether STS histological type plays a role in predicting clinical outcomes.

Superior Survival in African American Patients Who Underwent Autologous Stem Cell Transplantation for Multiple Myeloma

Introduction/BackgroundAfrican American (AA) individuals have a twofold higher incidence of multiple myeloma (MM) compared with other racial groups. Outcomes are affected by factors such as disparate access to care as well as differences in disease biology.Patients and MethodsWe conducted a single-institution analysis to evaluate the effect of AA race on outcomes of MM patients who underwent autologous stem cell transplantation (ASCT) in the pre-novel and novel agent era.ResultsSixty-one (47%) patients were AA and 69 (53%) were non-AA. Overall, 78 (60%) patients received any novel agent before transplantation and 52 (40%) received only chemotherapy. More non-AA patients received initial induction with a proteasome inhibitor (40 [60%] vs. 17 [28%]; P = .0007), and were treated with post-ASCT maintenance therapy (28 [41%] vs. 14 [23%]; P = .04). Time from diagnosis to ASCT in AA patients was 10 (range, 4-144) versus 8 (range, 3-54) months in non-AA patients (P = .01). Despite this, treatment-free survival (TFS) was equivalent between the 2 groups (x vs. y). Furthermore, AA patients had greater median overall survival (OS) compared with non-AA patients (not reached vs. 108 months; P = .03) and significantly improved OS in multivariable Cox proportional hazards models (adjusted hazard ratio, 0.30; 95% confidence interval, 0.11-0.81; P = .017). Median OS, landmarked at the time of relapse, was improved in AA patients (not reached vs. 68 months for P = .05).ConclusionOur study showed with long follow-up, equivalent TFS after ASCT in AA and non-AA patients yet improved OS. Post relapse survival is improved in AA patients suggesting a better response to salvage therapy.     

Isolated limb perfusion with tumor necrosis factor and melphalan for nonresectable Stewart-Treves lymphangiosarcoma

Background Cutaneous Stewart-Treves lymphangiosarcomas represent a rare group of tumors characterized by a high grade of vascularization and by localization in an extremity with lymphedema. The multifocality and the localization makes these tumors eligible for treatment with isolated limb perfusion (ILP). ILP with tumor necrosis factor (TNF) and melphalan is a safe and highly effective procedure that can achieve limb salvage in ≥80% of all patients with nonresectable extremity soft tissue sarcoma or melanoma. Methods In 10 patients with multifocal Stewart-Treves lymphangiosarcoma of the extremities, 16 ILPs with TNF plus melphalan were performed. All patients would have been candidates for exarticulation of the extremity. Results We observed an 87% overall response rate (complete and partial responses); one patient had a mixed response, and one patient did not respond to the therapy. In nine perfusions (56%), a complete response was achieved, and five perfusions (31%) resulted in a partial response. Limb salvage was achieved in eight patients (80%), with a mean follow-up duration of 34.8 months (range, 3 to ≥115 months). Regional toxicity was limited and systemic toxicity minimal to moderate, with no toxic deaths. Conclusions Multifocal Stewart-Treves lymphangiosarcomas in extremities with chronic lymphedema can be successfully treated by ILP with TNF and melphalan.     

Factors Affecting Survival After Complete Response to Isolated Limb Perfusion in Patients With In-Transit Melanoma

Background: Isolated limb perfusion ILP results in complete response CR rates of 60% to 90% in patients with regionally advanced melanoma. Survival after a CR may be influenced by various factors, particularly out-of-field disease in iliac lymph nodes ILN identified during lower-extremity ILP. We examined clinical and pathological parameters, including ILN status and outcome, for patients with in-transit melanoma who had a CR to ILP.Methods: From May 1992 to July 1997, 50 patients 16 men and 34 women; median age, 57 years with stage IIIA or IIIAB melanoma had a CR to a 90-minute hyperthermic iliac ILP with melphalan 10 mg/L limb volume, n = 20 or melphalan and tumor necrosis factor 4–6 mg ± 200 g interferon; n = 30. Clinical and pathological parameters were analyzed by univariate and Cox proportional hazards models to determine which were associated with survival or in-field recurrence.Results: The median in-field recurrence–free survival in the cohort of 50 patients after a CR to ILP was 1.4 years, and the actuarial 5-year in-field recurrence–free survival was 30%. By univariate analysis, there was a trend for improved outcome with female sex and stage IIIA vs. IIIAB at initial diagnosis was associated with improved survival after a CR to ILP P = .056 and .012, respectively. Eleven 22% of 50 patients had positive ILNs identified and resected at ILP. The probability of overall in-field recurrence was 70% after 4 years, and there was no difference between those with or without positive ILNs; median time to in-field recurrence was 13 and 19 months, respectively P = .62. Similarly, overall survival was not influenced by positive ILN status median [months]: +ILN, 69 vs. –ILN, 58; P = .68. Of note, Cox models identified that the risk of death was significantly greater in those with a history of prior systemic therapy hazard ratio: 2.67 [95% confidence interval, 1.17–6.11]; P = .02 and those with an in-transit lesion size l.4 cm² hazard ratio, 3.12 [95% confidence interval, 1.30–7.5]; P = .011. When these two variables were combined, there was a highly significant association with shortened survival P = .002 by log-rank test.Conclusions: These data indicate that for patients undergoing ILP and in whom positive ILNs are found and resected, ILP is justified. In addition, patients who have a CR after ILP and have a history of prior treatment or larger lesions should be considered for adjuvant systemic therapy.Presented at the 54th Annual Meeting of the Society of Surgical Oncology, Washington, DC, from March 15–18, 2001.     

Neuromuscular damage after hyperthermic isolated limb perfusion in patients with melanoma or sarcoma treated with chemotherapeutic agents

Purpose: To evaluate the incidence and entity of muscle damage after hyperthermic limb perfusion (HLP) with doxorubicin or melphalan, two widely used chemotherapeutic agents. Methods: We collected muscle biopsies from eleven patients with lower limb sarcoma or melanoma immediately before and at a variable time after the chemotherapeutic procedure (mean= 49.4 days). Biopsy specimens were stained with standard histochemical and immunohistochemical methods on cryostat sections and the grade of fiber atrophy was calculated. Results: Clear neurogenic alterations were present in pre-HLP biopsies of seven patients related to age and previous therapy. In six patients, the comparison between biopsies before and after HLP demonstrated worsening of preexisting neurogenic condition and appearance of mitochondrial-related damage. Reduction in type I or type II fiber diameter was present in nine patients, but no relation to doxorubicin or melphalan treatment was clear. An unexpected, large accumulation of desmin was detected in the muscle biopsy of one patient receiving doxorubicin, probably related to the mechanism of doxorubicin-induced myotoxicity. Conclusions: The observed neuromuscular toxic effects could be related to the physical or chemical conditions of HLP, in particular perfusion temperature; in addition, the present study demonstrates that preexisting neuromuscular changes, i.e. neuropathy, modulates the degree of further damage following HLP. Received: 16 March 2000 / Accepted: 26 June 2000     

Feasibility and Safety of Treosulfan,Melphalan, and Thiotepa-Based Megachemotherapy with Autologous or Allogeneic Stem Cell Transplantation in Heavily Pretreated Children with Relapsed or Refractory Neuroblastoma

The prognosis of resistant or relapsing children with neuroblastoma remains very poor, and the search for new therapies is ongoing. In this analysis, we assessed the toxicity of a treosulfan, melphalan, and thiotepa (TMT) regimen in 17 children with recurrent or refractory neuroblastoma who underwent stem cell transplantation (SCT). For allogeneic SCT, fludarabine and antithymocyte globulin were added. The stem cell source was autologous in 8 patients, haploidentical in 8 patients, and a matched unrelated donor in 1 patient. The reported nonhematologic toxicities included grade 3 mucositis, grade 1 to 3 hypertransaminasemia, and in 3 patients, veno-occlusive disease. No neurologic, cardiac, or dermatologic toxicities were observed. The probability of overall survival (OS) in patients with primary resistance was superior to that in patients with relapsed disease (100% versus 22.6%; P = .046). Post-transplantation dinutuximab beta immunotherapy was associated with superior 5-year OS (66.7% versus 11.4%; P = .0007). The use of an allogeneic donor, previous autologous SCT with busulfan and melphalan, and pretreatment with high-dose metaiodobenzylguanidine therapy demonstrated no effect on outcomes. In 4 patients, TMT megatherapy alone was enough to achieve complete remission. The TMT conditioning regimen was well tolerated in heavily pretreated patients with neuroblastoma. The manageable toxicity and addition of new anticancer drugs with optional post-SCT immunotherapy or chemotherapy support further trials with the TMT regimen in patients with neuroblastoma.     

Choosing a Reduced-Intensity Conditioning Regimen for Allogeneic Stem Cell Transplantation,Fludarabine/Busulfan versus Fludarabine Melphalan: A Systematic Review and Meta-Analysis

Fludarabine with busulfan (FB) or melphalan (FM) are 2 more commonly used reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (HCT).We present a systematic review and meta-analysis of studies comparing these 2 RIC regimens. We searched electronic databases from inception through November 1, 2017 for literature searches to identify relevant studies. A DerSimonian random effects model was used to measure efficacy outcomes; hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) are reported. Seven studies, including a total of 1955 patients, met criteria for inclusion, of which 6 were included in the overall pooled analysis because of repetition of some patients in 2 studies. Three studies were included in the subgroup analysis of acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS) and 2 in the subgroup analysis of lymphoid malignancies. Overall survival (OS) and progression-free survival were not statistically significantly different between the 2 RIC regimens in analysis of all studies. However, OS was better with FM in subgroup analysis of AML/MDS studies (HR, .83; 95% CI, .73 to .95). Nonrelapse mortality was lower with FB (HR, .64; 95% CI, .46 to .89), whereas relapse was lower with FM (HR, 1.52; 95% CI, 1.13 to 2.06) in the analysis of all studies. This meta-analysis shows that FB and FM are associated with a similar OS in patients undergoing HCT. Relapse rates are lower with FM but at the cost of higher nonrelapse mortality.