Low-grade non-Hodgkin lymphoma at advanced stage: a case successfully treated with cyclophosphamide plus somatostatin, bromocriptine, retinoids, and melatonin

Low-grade non-Hodgkin lymphomas (NHLs) at advanced stage are still incurable, and treatment may include chemotherapy with a single drug or a combination of different drugs. With a combination of cyclophosphamide, somatostatin, bromocriptin, retinoids, melatonin, and adrenocorticotropic hormone, we already reported 100% of global response (50% complete response and 50% partial response) in 12 patients with low-grade NHL at advanced stage: 4 previously untreated patients and 8 with relapse of disease after single or combined chemotherapy and therapy free time >or=6 months. This provided the rationale to treat a patient affected by low-grade NHL stage 4, with cyclophosphamide, somatostatin, bromocriptin, retinoids, and melatonin (adrenocorticotropic hormone was not administered for high blood pressure). The patient was treated for at least 2 months. After this period, if he had stable or responding disease, he received an additional 3 months of treatment, and if he was stable or responding after 5 months he was treated for 3 months and more. After 2 months the patient had a partial response, and after 5 months he achieved a complete response. Today, 18 months after the beginning of treatment, the patient is in complete remission. Treatment had very good tolerance, and the patient carried on at home doing his normal activities.     

自体外周血造血干细胞移植治疗恶性淋巴瘤的生存预后分析

目的回顾性分析自体外周血造血干细胞移植(APBSCT)治疗恶性淋巴瘤的临床相关指标,以及影响预后的因素。方法收集2012年1月至2013年12月在该院确诊的31例恶性淋巴瘤患者的临床资料进行回顾性分析,采用Kaplan-Meier法进行生存分析,Log-Rank法进行单因素分析患者预后。结果 31例患者移植成功,无移植相关死亡;截至随访时间,移植后3年及5年总生存率分别为85.1%和78.5%,3年及5年无进展生存率分别为84.9%和75.5%。单因素预后分析结果显示,年龄≥60岁、IPI评分>2~5分、肝脾肿大患者3年生存率明显低于年龄<60岁、IPI评分1~2分,无肝脾肿大患者,差异有统计学意义(P <0.05)。结论恶性淋巴瘤患者行APBSCT安全有效,APBSCT可改善患者长期生存率,而年龄、IPI评分、肝脾肿大影响患者预后。     

Higher infused CD34+ hematopoietic stem cell dose correlates with earlier lymphocyte recovery and better clinical outcome after autologous stem cell transplantation in non-Hodgkin's lymphoma

BACKGROUND: Lymphocyte recovery after autologous stem cell transplantation (ASCT) has been shown to be associated with positive clinical outcome in non-Hodgkin's lymphoma (NHL). This study sought to identify variables that affect lymphocyte recovery and survival after ASCT.
STUDY DESIGN AND METHODS: A retrospective analysis of outcomes in 97 consecutive patients with NHL who underwent ASCT in a single center from August 1999 to January 2008 was conducted.
RESULTS: A significant relationship was not observed between infused lymphocyte count and days to recovery of absolute lymphocyte count 500 × 10⁶/L or greater after ASCT (ALC500; r = 0.139, p = 0.176), but there was a significant inverse correlation between infused CD34+ cell count and days to ALC500 (r = −0.333, p = 0.001). Univariately, infused CD34+ cell count and recovery of ALC500 by 20th day after ASCT were significant predictors of survival. The median overall survival (OS) and event-free survival (EFS) were significantly longer in patients who received 8.2 × 10⁶ CD34+ cells/kg or more than in those who received fewer than 8.2 × 10⁶ CD34+ cells/kg (OS, not reached vs. 11.6 months, p = 0.001; EFS, not reached vs. 4.8 months, p = 0.003). Multivariate analysis confirmed that infused CD34+ cell count was an independent prognostic factor for OS (p = 0.017) and EFS (p = 0.002).
CONCLUSION: These data suggest that infused CD34+ cell count is predictive of kinetics of lymphocyte recovery after ASCT and is an independent prognostic factor for OS and EFS after ASCT in patients with NHL.     

自体外周血干细胞移植治疗非霍奇金淋巴瘤的外周血干细胞动员方案临床分析

本研究比较CEP+G-CSF与CVP+G-CSF动员方案对非霍奇金淋巴瘤(NHL)患者外周血造血干细胞动员采集及造血恢复的效果。回顾性分析我科收治的57例NHL患者。分组采用CEP+G-CSF与CVP+G-CSF动员方案进行外周血干细胞动员采集,并于预处理结束后回输外周血干细胞,分析动员效果、不良反应及自身移植后造血恢复情况。结果表明:动员期间所有患者外周血白细胞(WBC)计数均降至1.0×109/L以下,血小板(Plt)数降至40×109/L以下。57例患者均采集成功,CEP+G-CSF动员方案组采集单个核细胞(MNC)数和CD34+细胞数明显高于CVP+G-CSF动员方案组(p=0.002和p=0.019)。预处理后所有病例均达到骨髓抑制,CEP+G-CSF和CVP+G-CSF动员方案组WBC数恢复到≥1.0×109/L的平均时间分别为11.4和12.3天(p﹥0.05),Plt数恢复到≥50×109/L的平均时间分别为18.6和19.3天(p﹥0.05)。结论:自体外周血干细胞移植治疗NHL疗效显著,CEP或CVP联合G-CSF方案行外周血干细胞动员均安全有效,临床效果满意,CEP+G-CSF方案动员外周血干细胞效果更好。     

恶性淋巴瘤患者自体造血干细胞移植前后淋巴细胞绝对数与预后的关系

目的 分析非霍奇金淋巴瘤(NHL)患者自体外周血造血干细胞移植前后淋巴细胞绝对数(ALC)、输注CD34+细胞数与NHL疾病复发、无病生存(DFS)期、总生存(OS)时间的关系.方法 回顾性分析40例行自体外周血造血干细胞移植术的NHL患者的临床资料和实验室检查结果,对预处理前淋巴细胞绝对数(ALC-Pro)、移植后第15天淋巴细胞绝对数(ALC-15)以及输注CD34+细胞数与NHL疾病复发、DFS和OS的关系,进行统计学处理和多因素线性回归分析.结果 ALC-Pro和ALC-15与NHL复发密切相关,ALC-Pro和ALC-15水平高的患者,复发率较低;通过Kaplan-Meier生存曲线和COX多因素回归分析,发现ALC-Pro和ALC-15均为影响患者DFS的重要因素;输注的CD34+细胞数虽然与ALC-15无关,但与患者DFS有关,输注CD34+细胞数多的患者其DFS期更长;ALC-Pro、ALC-15、CD34+细胞均与NHL患者的OS有密切关系,移植前后ALC水平高、输注CD34+细胞数量多的患者,其OS时间较长.结论 NHL患者自体外周血造血干细胞移植前后ALC水平和输注的CD34+细胞数,对于判断NHL复发、DFS、OS有一定参考意义,有可能成为NHL患者自体移植后预后判断的有价值的指标.     

造血干细胞移植治疗间变大细胞淋巴瘤的临床分析

目的探讨造血干细胞移植治疗间变大细胞淋巴瘤(ALCL)的疗效及预后。方法回顾性分析全国八家三甲医院2005年1月至2017年12月收治的33例接受造血干细胞移植(HSCT)的ALCL患者临床资料,评价自体造血干细胞移植(auto-HSCT)和异基因造血干细胞移植(allo-HSCT)治疗ALCL的生存率、复发率和影响预后的相关因素。结果33例接受HSCT的ALCL患者的中位发病年龄为31(12~57)岁,男23例,女10例,间变性淋巴瘤激酶阳性(ALK+)和阴性(ALK-)分别为24例(72.7%)和9例(27.3%)。25例患者接受auto-HSCT(ALK+患者19例,ALK-患者6例),8例患者接受allo-HSCT(ALK+患者5例,ALK-患者3例)。移植后中位随访时间18.7(4.0~150.0)个月。移植前疾病缓解状态:完全缓解6例(均行auto-HSCT),部分缓解16例(auto-HSCT组14例,allo-HSCT组2例),复发难治11例(auto-HSCT组5例,allo-HSCT组6例)。疾病进展死亡7例,其中auto-HSCT组5例(20.0%),allo-HSCT组2例(25.0%)。移植相关死亡(TRM)5例,其中auto-HSCT组2例(8.0%),allo-HSCT组3例(37.5%)。auto-HSCT后中位无进展生存(PFS)和总生存(OS)时间均为15个月,allo-HSCT后中位PFS时间为3.7(1.0~90.0)个月,中位OS时间为4.6(1.0~90.0)个月,两组生存曲线差异无统计学意义(OS及PFS P值分别为0.247和0.317)。auto-HSCT和allo-HSCT组的2年OS率分别为72%和50%,5年OS率分别为36%和25%。结论ALCL化疗反应率高,有不良预后因素的情况下化疗后序贯auto-HSCT为重要治疗措施,高危患者或可从allo-HSCT中获益。     

自体外周血干细胞移植治疗重症天疱疮的护理

报告了1例自体造血干细胞移植治疗天疱疮的护理。通过移植前的评估,有针对性地做好心理护理,落实各项护理措施,防止并发症的发生,保证了移植的成功。     

Prospective randomized comparative observation of single- versus split-dose lenograstim to enhance engraftment after autologous stem cell transplantation in patients with multiple myeloma or non-Hodgkin's lymphoma

BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF) is used to enhance hematopoietic recovery after autologous stem cell transplantation (ASCT). Recommendations for administration of G-CSF during the engraftment phase of ASCT have recently changed. This study sought to compare the early engraftment profile between groups receiving single-dose versus split-dose lenograstim to enhance engraftment after ASCT. STUDY DESIGN AND METHODS: A prospective, randomized study was performed with 40 patients (14 with non-Hodgkin's lymphoma, 26 with multiple myeloma) undergoing ASCT. Patients were randomly assigned to receive 5 microg per kg lenograstim once daily (single dose) or 2.5 microg per kg lenograstim twice daily (split dose) starting 1 day after transplantation (Day +1). A minimum of 3 x 10(6) per kg CD34+ cells per kg was required for the autograft. RESULTS: The median time to neutrophil engraftment was 10 days for both groups. Platelet (PLT) engraftment was achieved in 11 days for the single-dose group and 14 days for the split-dose group. Episodes of clinically documented infection were low and similar in both groups (18 during 392 patient-days in the single-dose group and 22 during 556 patient-days in the split-dose group). There were no significant differences in requirements for red blood cell or PLT transfusion between the two groups. The duration of hospitalization after stem cell infusion was 18 days for the single-dose group and 22 days for the split-dose group. CONCLUSION: Administration of split doses of lenograstim is not associated with superior clinical efficacy compared with conventional daily single-dose administration for immediate hematopoietic recovery after ASCT.     

Simultaneous acute myeloid leukemia and multiple myeloma successfully treated with allogeneic stem cell transplantation

We present a case of concurrent diagnosis of acute myeloid leukemia (AML) with multiple myeloma with complex karyotype, which was successfully treated with allogeneic stem cell transplantation. A 51-year-old man with no past medical history presented with fatigue and anemia with blasts on peripheral smear. Bone marrow biopsy confirmed the simultaneous diagnosis of myeloma and AML. The patient received bortezomib and the myeloma responded well, but induction chemotherapy for the AML failed twice. He underwent an allogeneic stem cell transplant from his human lymphocyte antigen (HLA)-matched sibling, and is now disease-free approximately one year since the transplant. He has mild graft-versus-host disease (GVHD). To our knowledge, this is the first case of a patient with simultaneous AML and multiple myeloma who has undergone successful treatment with allogeneic stem cell transplantation.     

恶性淋巴瘤患者自体造血干细胞移植治疗后感染特点及治疗对策探讨

造血干细胞移植(HSCT)是人类治疗恶性肿瘤所取得的重要突破之一.随着HSCT的广泛开展,感染作为主要并发症及移植相关死亡的重要原因日益受到重视.     

Severe bleeding symptoms in refractory idiopathic thrombocytopenic purpura: a case successfully treated with melatonin

The prognosis of patients with idiopathic thrombocytopenic purpura refractory to corticosteroids and splenectomy (refractory ITP) is poor; these patients present high morbidity from disease and its treatment and have a mortality rate of approximately 16%. A patient is reported with severe bleeding symptoms related to refractory ITP successfully treated with melatonin.     

Weekly cyclophosphamide and alternate-day prednisone: an effective, convenient, and well-tolerated oral treatment for relapsed multiple myeloma after autologous stem cell transplantation

OBJECTIVE: To assess the efficacy and tolerability of weekly oral cyclophosphamide in combination with alternate-day prednisone (CP) as salvage therapy for patients with relapsed multiple myeloma (MM) after autologous stem cell transplantation (ASCT). PATIENTS AND METHODS: We retrospectively reviewed the medical records of all patients identified in our clinical database as having received CP as treatment for relapsed MM after ASCT at Princess Margaret Hospital between July 1998 and May 2004. The CP regimen consisted of oral cyclophosphamide at 500 mg once weekly and oral prednisone at 100 mg on alternate days. RESULTS: A total of 66 patients received the CP regimen, with a median of 2.0 prior therapies (range, 1.0-5.0) from time of diagnosis to initiation of CP. The median time from relapse after ASCT to start of CP therapy was 1.5 months (range, 0.0-23.5 months). Because of nonsecretory disease in 7 patients, only 59 patients were evaluable for response. The median duration of CP treatment was estimated at 5.8 months (95% confidence interval [CI], 4.6-7.8 months). With a median follow-up of 15.9 months (range, 1.4-67.2 months), 36 patients (61%) responded to treatment, 24 (41%) of whom had a partial response. The 1-year progression-free survival of all evaluable patients was estimated at 66% (95% CI, 54%-80%), with a median progression-free survival of 18.6 months (95% CI, 13.9-29.9 months). The median overall survival from time of initiation of CP was estimated at 28.6 months (95% CI, 22.1-not available months). CONCLUSION: Our data show that CP is an effective, well-tolerated, and convenient regimen as salvage therapy for MM after ASCT.     

Haploidentical allogeneic haematopoietic stem cell transplantation as salvage therapy for engraftment failure after unrelated and autologous stem cell transplantation: a case report and review of the literature

Engraftment failure is a rare but life-threatening complication of haematopoietic stem cell transplantation (HSCT) and treatment of this condition is often challenging. This case report describes a patient with acute myeloid leukaemia and engraftment failure after unrelated donor allogeneic stem cell transplantation. Rescue treatment with granulocyte-colony stimulating factor and reinfusion of autologous 'back-up' stem cells failed, but transplantation of haploidentical donor stem cells following a fludarabine and antithymocyte globulin (ATG)-based conditioning regimen resulted in haematological reconstitution and long-term disease-free survival. The use of haploidentical donor stem cell transplantation as salvage therapy after engraftment failure in adult patients has not, to the authors' knowledge, been previously reported. Additionally, a review of the relevant literature is presented. This case report and literature review suggest that reinfusion of cryopreserved 'back-up' haematopoietic stem cells is a safe and effective salvage therapy for engraftment failure after allogeneic HSCT. Haploidentical donor stem cell transplantation after a fludarabine and ATG-based conditioning regimen could provide effective second-line therapy in adult patients.     

Impact of autologous stem cell transplantation on survival outcomes in patients with peripheral T cell lymphoma

Data about the timing of autologous stem cell transplantation (ASCT) in peripheral T cell lymphoma (PTCL) are conflicting. We aimed to investigate the impact of the sequence of ASCT on the survival outcomes in patients with PTCL. Analyzes were performed retrospectively in a total of 81 patients, 16 of whom underwent upfront ASCT and 12 received salvage ASCT. In univariate analysis, upfront ASCT reduced the risk of progression and death by 77% (Hazard ratio (HR): 0.23, 95% confidence interval (CI): 0.09–0.60) (p = 0.003) and by 84% (HR: 0.16, 95% CI: 0.5–0.55) (p = 0.003), respectively. However, in multivariate analysis, only salvage ASCT predicted a more favorable progression-free and overall survival (HR: 0.17, 95% CI: 0.06–0.48, p = 0.001 and HR: 0.20, %95 GA: 0.06–0.62, p = 0.005, respectively). In conclusion, regardless of first-line therapy, patients have more favorable outcomes if they receive salvage ASCT. Upfront ASCT does not add clinically significant benefit to survival outcomes.     

自体骨髓干细胞移植治疗扩张型心肌病的护理

扩张型心肌病所致心力衰竭是心肌细胞舒缩功能减弱,心肌细胞失去增值能力或增值能力极低[1]。增加具有舒缩功能的心肌细胞数目是改善心功能的关键。干细胞是具有自我更新、多分化潜能的早期未分化细胞[2]。骨髓干细胞(MSCs)移植可分化成心肌细胞,增加有功能的细胞,新生的血管内皮细胞形成的侧支循环改善了供血及心脏局部和整体收缩功能[3]。我科于2004年8月开展MSCs移植术治疗心力衰竭病人12例,均采用导管介入移植手术,在病人同意下行自体MSCs冠状动脉内注射,MSCs移植与经皮冠状动脉成形术一并进行,现将其护理总结报道如下。1临床资料…     

自体骨髓干细胞移植治疗心肌梗死6例报告

目的:观察自体骨髓干细胞移植治疗急性心肌梗死的临床可行性、安全性和有效性。方法:选择2003-11/2004-06在北京同仁医院住院的急性ST抬高性心肌梗死患者6例,年龄18～75岁,急性ST抬高性心肌梗死患者6例。患者接受自体骨髓干细胞移植治疗前签署同意书。患者入院后行经皮冠状动脉介入治疗使梗死相关血管再通后,即开始使用粒细胞集落刺激因子10μg(kg·d)进行干细胞动员,6d后进行患者外周血单个核细胞分离,进一步纯化后经球囊导管输入梗死相关冠状动脉内。治疗后对患者进行6个月的随访。结果:心肌梗死患者6例均进入结果分析。①经单光子断层发射扫描和正电子断层发射扫描等检查证实,6例患者治疗后3个月,梗死面积平均下降42.7%;其中2例患者治疗后6个月,梗死面积下降68%,另外4例患者治疗后3个月,梗死面积下降31.5%。②治疗后3个月患者左室射血分数由平均35.6%增加到50.8%,增加了15.2%。③移植手术过程中患者无不适,术后随访观察过程中无异常发现。结论:自体骨髓干细胞经动员后,再分离纯化外周血单个核细胞治疗心肌梗死,可改善心肌梗死患者心功能,减小梗死面积,且较为安全。     

自体骨髓干细胞移植治疗心肌梗死6例报告

目的：观察自体骨髓干细胞移植治疗急性心肌梗死的临床可行性、安全性和有效性。 方法：选择2003-11／2004-06在北京同仁医院住院的急性ST抬高性心肌梗死患者6例，年龄18-75岁，急性ST抬高性心肌梗死患者6例。患者接受自体骨髓干细胞移植治疗前签署同意书。患者入院后行经皮冠状动脉介入治疗使梗死相关血管再通后，即开始使用粒细胞集落刺激因子10μg（kg&;#183;d）进行干细胞动员，6d后进行患者外周血单个核细胞分离，进一步纯化后经球囊导管输入梗死相关冠状动脉内。治疗后对患者进行6个月的随访。 结果：心肌梗死患者6例均进入结果分析。①经单光子断层发射扫描和正电子断层发射扫描等检查证实，6例患者治疗后3个月，梗死面积平均下降42．7％；其中2例患者治疗后6个月，梗死面积下降68％，另外4例患者治疗后3个月，梗死面积下降31．5％。②治疗后3个月患者左室射血分数由平均35．6％增加到50．8％，增加了15．2％。③移植手术过程中患者无不适，术后随访观察过程中无异常发现。 结论：自体骨髓干细胞经动员后，再分离纯化外周血单个核细胞治疗心肌梗死，可改善心肌梗死患者心功能，减小梗死面积，且较为安全。     

Peripheral blood stem cell mobilization with cyclophosphamide in combination with G-CSF, GM-CSF, or sequential GM-CSF/G-CSF in non-Hodgkin's lymphoma patients: a randomized prospective study

We designed a randomized, prospective three-arm mobilization study to determine the kinetics of peripheral blood stem cell (PBSC) mobilization in 60 non-Hodgkin's lymphoma (NHL) patients primed with cyclophosphamide (CTX) in combination with granulocyte colony-stimulating factor (G-CSF) (arm A), granulocyte-macrophage (GM)-CSF (arm B) or GM-CSF/G-CSF (arm C). We also compared mobilization and transplant-related toxicities, pre- and post-transplant support and the probability of survival among the three arms. To date, 35 patients have been enrolled in the study; 13 patients have been enrolled in arm A, 10 patients in arm B, and 13 patients in arm C. Successful collection of the target of > or = 2 X 10(6) CD34+ cells/kg in one to four apheresis collections was 10/13, 6/10, and 7/12 in arms A, B, and C, respectively. The differences between arms were not statistically significant. The median time to achieve the target CD34+ cells in patients who successfully mobilized the target CD34+ cells was 3 days, 2 days, and 1 day, in patients in arms A, B, and C, respectively. The time for neutrophil engraftment was 11, 10, and 10 days in arms A, B, and C, respectively. The time for platelet engraftment was 11 days for patients in all arms of the study. Most importantly, no significant differences were observed among the three arms in the duration of neutropenic fever, the extent of mucositis, diarrhea, and nausea/vomiting, or in the number of units of platelets or red cells transfused after transplantation. Risk factors associated with poor mobilization were > or = 3 regimens of chemotherapy prior to mobilization, older age, and disease histology (follicular versus diffuse). Therefore, we conclude that the type of growth factor used for mobilization did not play a major role in the outcome of mobilization and recommend mobilizing NHL patients before they receive multiple regimens of chemotherapy.