Impact of the Conditioning Regimen Dose Intensity Before Autologous Stem Cell Transplantation on the Pulmonary Function Test Abnormalities in Patients With Lymphoma and Multiple Myeloma: Single Center Experience

BackgroundMost studies addressing the impact of hematopoietic stem cell transplantation (SCT) on pulmonary function test (PFT), and the various factors affecting that impact have been performed on the allogenic type. Few have addressed PFT changes in autologous SCT. This study describes PFT changes seen in autologous SCT recipients and addresses the various factors impacting these changes.Patients and MethodsWe reviewed the medical records of 223 consecutive adult autologous SCT recipients. We collected pre-transplant and post-transplant data, as well as PFT data and long-term mortality.ResultsA total of 123 patients with lymphoma receiving the BEAM (carmustine, etoposide, aracytin, and melphalan) conditioning regimen had a significant 5% drop in mean forced vital capacity and total lung capacity but no significant change in forced expiratory volume in one second/forced vital capacity ratio nor in diffusion lung capacity of carbon monoxide adjusted to volume. Fifteen percent of the patients with lymphoma had a clinically significant drop of 15% in their lung volume parameters. The patients with multiple myeloma receiving the melphalan conditioning regimen had no significant change in any of the PFT parameters. Smoking, baseline PFT parameters, and radiation did not affect lung function or mortality.ConclusionsAutologous SCT impact on lung function depends on the disease and conditioning regimen. It leads to a drop in lung volumes but no obstruction or decrease in diffusion in patients with lymphoma receiving the BEAM regimen. Autologous SCT did not affect lung functions in patients with multiple myeloma, and these patients may not need screening PFTs.     

Autologous Stem Cell Transplant in Lymphoma Using a Noncryopreserved Platform: An Adapted Sequential Conditioning Maintaining Dose Intensity Does not Affect Transplantation Outcomes

BackgroundHematopoietic autologous stem cell transplantation (ASCT) is a validated therapeutic strategy for lymphoma treatment and precise well-tolerated conditioning. Several conditioning methods are available, but the most commonly used are CVB, BEAM, and ICE, which are conventionally administered in 6 to 7 days. Since 2015, our program has moved toward noncryopreserved platforms that require concise times; therefore, we have modified the conditioning by reducing it to 4 to 5 days. In this study, we show our experience.MethodsWe compared ASCT performed in our program before and after 2015 in lymphoma patients. Between 2000 and 2014 and from 2015 to 2022, we performed 46 and 61 ASCT procedures, respectively.ResultsSince 2015, we observed a greater number of infused stem cells, fewer episodes of febrile neutropenia (60% vs. 37% P = .008), shorter hospitalizations (30 vs. 18 days P = .001), faster engraftment (20 vs. 14 days P = .001) and better progression-free survival (72 vs. 44 months P = .002). Additionally, a prolonged overall survival was observed at these results, and this prolonged survival is difficult to interpret due to the short follow-up.ConclusionIn conclusion, conditioning adjusted for a noncryopreserved strategy offers at least similar or even better results than the cryopreserved strategy. Prospective studies are warranted.     

A Comparison of the BEAM and MITO/MEL Conditioning Regimens for Autologous Hematopoietic Stem Cell Transplantation in Hodgkin Lymphoma: An Analysis of Efficiency and Treatment-Related Toxicity

BackgroundApproximately half of patients with relapsed chemosensitive disease achieve robust responses with BEAM (BCNU, etoposide, cytarabine, and melphalan) and autologous stem cell rescue. The scarcity of comparative studies further limits alternative treatment protocols, such as the MITO/MEL (mitoxantrone, melphalan) protocol.Patients and MethodsIn this retrospective multicenter study, we compared the BEAM and MITO/MEL regimens used before autologous hematopoietic stem cell transplantation (ASCT) in terms of efficacy and side effects in patients with Hodgkin lymphoma. Data met international accreditation rules. Before ASCT, 108 patients received the MITO/MEL, and 34 patients received the BEAM.ResultsThe median follow-up time was 36 months in the MITO/MEL group (range, 3-178) and 23 months in the BEAM group (range, 4-99). After ASCT, the 3-year expected overall survival and disease-free survival rates were 86.1% and 86.1% for the MITO/MEL group and 91.3% and 76.5% for the BEAM group, respectively. Although 50% of patients developed febrile neutropenia attacks in the MITO/MEL group, this rate was 91.1% in the BEAM group. The grade II and higher rates of hepatic, renal, gastrointestinal, and cardiac toxicities were similar in both groups. However, the rate of pulmonary toxicity was determined to be 1.9% in the MITO/MEL group and 29.4% in the BEAM group (P < .001).ConclusionThe MITO/MEL conditioning regimen seems to be as effective as the BEAM regimen but has better tolerability in terms of pulmonary toxicity and may be used as an alternative option if necessary, depending on the comorbidity status of the patient.     

含氟达拉滨的预处理行异基因造血干细胞移植治疗恶性血液病的远期疗效

目的：观察含氟达拉滨的预处理方案进行异基因造血干细胞移植治疗恶性血液病的长期疗效。方法：选取2003年2 月至2004年12月间厦门大学附属中山医院收治的15例恶性血液病患者,其中急性髓性白血病3 例,急性淋巴细胞白血病5 例,慢性粒细胞白血病6 例,骨髓增生异常综合症（RAEB）1 例。供受者HLA 配型同胞全相合6 例,同胞或亲缘不相合8 例,非亲缘全相合1 例。预处理方案采用氟达拉滨（Flu 30mg/m2·d,共5d）、马利兰（BU4mg/kg·d,共2～3d）、环磷酰胺（CTX 50mg/kg·d,共2d）,其中8 例加用阿糖胞苷（Ara-c 1.0～2.0g/m2·d,共2d）,9 例HLA 不全相合及非血缘移植者加用兔抗胸腺细胞球蛋白（ATG 3.0～5.0mg/kg·d,共3d）。 预防移植物抗宿主病（GVHD）均采用骁悉（MMF）+ 环孢素（CsA）+ 短程甲氨喋呤（MTX）方案。利用SPSS11.5 统计软件及Kaplan-Meier 方法进行生存分析。结果：15例患者移植后均获得快速完全的植入,无严重的预处理相关毒性。46.7% 发生急性GVHD ,85.7% 发生慢性GVHD ;带状疱疹7.1% 。5 年总生存率为53.5% ,其中移植时处于第一次完全缓解（CR1）和慢性期患者11例,5 年生存率为72.7% ,复发率9.1% ,移植时处于第二次完全缓解（CR2）、复发、加速期及急变期的患者4 例,2 年生存率为0,复发率75,两者有统计学差异（P=0.000 3 和P<0.05）,主要死亡原因为疾病复发和GVHD 。结论：对于移植时处于CR1 和慢性期患者,采用含Flu并适当减低放化疗剂量的预处理方案是有效的移植预处理方案,毒副作用较少,未增加机会性感染,复发率较低;预处理中加入Flu对GVHD 发生率无明显影响。     

自体外周血造血干细胞移植治疗非霍奇金淋巴瘤的临床疗效分析

目的 探讨自体外周血造血干细胞移植(auto-PBSCT)治疗非霍奇金淋巴瘤(NHL)的疗效和安全性.、方法 行自体造血干细胞移植的16例NHL患者,其中移植前达到完全缓解状态8例(治疗组),男性3例,女性5例,平均年龄29.6岁(6～42岁);移植前为复发难治性8例(对照组).预处理均采用经典的BEAM方案(卡莫司汀、依托泊苷、阿糖胞苷、马法兰).移植后观察全部患者移植相关并发症发生情况和生存情况.结果 治疗组全部患者均获造血重建,随访至2015年10月,中位随访时间为32.1个月(0.8～67个月),治疗组除1例死于严重肺部感染外,其余7例全部处于完全缓解状态,总生存率(OS)达87.5％;对照组中1例死于多器官功能衰竭,1例死于肺部感染,2例死于败血症,2例复发死亡,2例患者存活,OS达25.0％.两组OS相比,差异有统计学意义(x2=6.349,P=0.012).结论 Auto-PB-SCT对于移植前完全缓解的患者有效、安全,对于复发难治性非霍奇金淋巴瘤,可作为挽救性治疗,在临床广泛开展.     

自体造血干细胞移植支持下BEAC方案治疗晚期复发恶性淋巴瘤

目的：报告 20例恶性淋巴瘤在自体造血干细胞移植支持下接受超大剂量化疗的初步治疗经验 ,评价所用外周血造血干细胞 (peripheral blood progenitors,PBPC )动员方案的动员效果,预处理方案的远期疗效和耐受性,以及回输后造血重建情况。方法： 20例复发、晚期恶性淋巴瘤中, 1例复发霍奇金病 (Hodgkin s disease,HD),19例非霍奇金淋巴瘤 (non- Hodgkin s lymphoma,NHL）。经常规化疗获缓解后, 3例采用自体骨髓移植 (autologous bone marrow transplantation,ABMT), 17例采用自体外周血干细胞移植 (autologous peripheral blood stem cell transplantation,APBSCT);动员方案为环磷酰胺 (CTX)3 500 mg/m2＋ G- CSF 3.5～ 5μ g/kg＋地塞米松 10 mg,预处理方案为 BEAC(CTX 3 600～ 4 000 mg/m2,Vp- 16 1 200 mg/m2,BCNU 300 mg/m2和 Ara- C 1 500～ 2 000 mg/m2),化疗结束后 24～ 48 h回输自体造血干细胞。结果： ABMT病人回输单核细胞 (MNC)1.3(1.0～ 1.7)× 108/kg, APBSCT病人回输 MNC 1.8(1.0～ 4.4)× 108、 CFU- GM 5.1 (1.9～ 9.6 )× 105/kg和 CD34＋细胞 2.9(1.9～ 8.7)× 106/kg。回输造血干细胞后均获快速造血功能重建,中性粒细胞 (ANC)≥ 0.5× 109/L时间为 9(6～ 17)天,血小板≥     

两日预处理方案自体造血干细胞移植治疗恶性实体瘤

目的：探索应用两日预处理方案自体造血干细胞移植治疗实体瘤的疗效与安全性。方法：13例实体瘤患者,中位年龄50岁（14-65岁）,预处理方案9例采用60Co全身照射7.9-8.3Gy加联合化疗,4例不含全身照射。化疗方案组合包括环磷酰胺、顺铂、5-氟脲嘧啶（CDF）,环磷酰胺、阿糖胞苷、足叶乙甙（CAE）,环磷酰胺、阿霉素、顺铂、足叶乙甙（CADE）。全部预处理在48小时内完成,评价疗效及相关毒性反应。结果：13例完全缓解8例（61.5%）,部分缓解2例（15.4%）,总体治疗反应率76.9%;移植相关死亡2例（15.4%）,未缓解或复发4例（30.8%）。中位随访时间14个月,最长无病生存期26个月。结论：两日预处理方案自体造血干细胞移植可有效杀伤肿瘤组织,疗效与非两日预处理方案近似,不增加预处理相关危险因素。     

自体造血干细胞移植相关肝损伤的临床研究

目的探讨自体造血干细胞移植相关肝损伤的临床特点。方法回顾性分析109例接受自体造血干细胞移植的淋巴瘤患者的临床资料。结果109例淋巴瘤患者接受预处理方案化疗后,肝脏生化学的异常改变主要是氨基转移酶、总胆红素的升高,其中30.3%出现丙氨酸氨基转移酶升高,14.7%出现天门冬氨酸氨基转移酶升高,11.0%出现总胆红素升高,Ⅲ～Ⅳ度肝损伤的发生率仅为1.8%。与CBV方案比较,BEAM方案更可能导致总蛋白降低、白蛋白/球蛋白比值异常、总胆红素和间接胆红素升高。10例HBsAg阳性的淋巴瘤患者给予拉米夫定预防治疗,均未发生乙型肝炎病毒再激活。结论自体造血干细胞移植治疗淋巴瘤相关重度肝损伤的发生率低,合并乙型肝炎病毒感染者给予拉米夫定预防治疗可以有效防止乙型肝炎病毒再激活。     

异基因造血干细胞移植FBC预处理14例

[目的]探讨FBC预处理方案在异基因造血干细胞移植中的可行性.[方法]以FBC预处理对14例恶性血液病患者进行异基因造血干细胞移植.FBC预处理方案组成:磷酸氟达拉滨30mg/(m2·d),静滴,-5d～-1d;白消安0.6mg/(kg·d),口服,q6h,-7d～-4d;环磷酰胺30 mg/(kg·d),静滴,-3d～-2d.[结果]14例患者移植后均安全通过骨髓抑制期,顺利重建造血功能,白细胞升至1×109/L为 11d( 9d～ 15d),血小板上升至20×109/L为 12d( 9d～ 21d).8例(57.1%)出现急性移植物抗宿主病,5例(35.7%)出现慢性移植物抗宿主病.至今仍存活11例(78.6%),3例(21.4%)死亡.[结论]用FBC预处理方案进行异基因造血干细胞移植治疗恶性血液病安全、有效.     

造血干细胞支持下大剂量LACE方案对27例难治复发性淋巴瘤疗效观察

目的:评价在造血干细胞支持下,LACE预处理方案对难治性、复发性淋巴瘤临床疗效.方法:自2001年3月至2003年7月对27例难治性、复发性淋巴瘤在造血干细胞支持下,应用LACE预处理方案:罗氮芥(L)200mg/m2,1次口服(移植前第7天),足叶乙甙(E)1g/m2,静脉点滴(移植前第7天),阿糖胞苷(A)2g/m2×d-1,静脉点滴(移植前第6、5天),环磷酰胺(C)1.8/m2×d-1,静脉点滴(移植前第4、3、2天),0天进行自体干细胞输注并进行随访观察.结果:27例患者均可耐受化疗,无移植相关死亡病例,并对移植后的患者进行随访观察,随访中位期14个月(7～35),6例复发,21例缓解.统计分析2年无瘤生存率可达70%,预计5年生存率可达55%.结论:对难治性复发性淋巴瘤,在造血干细胞支持下,LACE方案是较好的一种预处理方案.     

Salvage High-dose Melphalan With Autologous Stem cell Transplantation as Bridge to Consolidation Therapy for Chemoresistant Aggressive B-cell Lymphoma

BackgroundPatients suffering from refractory aggressive B-cell lymphoma not responding to salvage chemotherapy have a dismal prognosis. CAR T-cells or allogeneic stem cell transplantation (SCT) are potentially curative approaches. However, obtaining a remission, and lowering tumor burden before consolidation seems crucial for long-term efficacy of both treatment modalities.Materials and MethodsIn this retrospective analysis, we reviewed patients with chemoresistant aggressive B-cell lymphoma, defined as being refractory or progressive to at least second line salvage chemotherapy including the regimen immediately preceding autologous stem cell transplantation (ASCT), treated at 2 tertiary centers, who were eligible for intensive treatment using single agent high-dose (HD) melphalan to obtain a remission before consolidating therapy.ResultsWe identified 36 patients that received single agent HD melphalan and ASCT as remission induction followed by CAR T-cells or allogeneic stem cell transplantation (SCT). Thirteen of the evaluable patients (39.4%) achieved a partial remission and 9 patients (27.73%) a complete remission, resulting in an overall response rate (ORR) of 66.7%. High remission rates were seen across all subgroups including patients with primary refractory lymphoma (ORR 58.3%), uncontrolled disease and high tumor burden as indicated by increased LDH levels (ORR 66.7% for patients with elevated LDH above 2 times upper limit of norm). 22 patients proceeded to allogeneic SCT and 5 to CAR T-cell therapy. Treatment related mortality of ASCT was 5.5% (2 patients, both due to infections). Two-year overall survival of all patients was 15.8%, primarily due to a high non–relapse mortality (45.5%) of allogeneic SCT patients treated with myeloablative conditioning chemotherapy.ConclusionSingle agent HD melphalan produces high remission rates in patients with chemoresistant, uncontrolled aggressive B-cell lymphoma and provides a window of opportunity for consolidation therapy.MicroabstractPatient with refractory/relapsed aggressive B-cell lymphoma after salvage therapy are an unmet medical need because of their very poor prognosis. In our retrospective analysis of 36 patients we showed that single agent high-dose melphalan can achieve high response rates (ORR 66.7%) even in uncontrolled disease enabling consolidation therapy e.g. with allogeneic stem cell transplantation or CAR T-cell therapy.     

Durable Survival Outcomes in Primary and Secondary Central Nervous System Lymphoma After High-dose Chemotherapy and Autologous Stem Cell Transplantation Using a Thiotepa,Busulfan, and Cyclophosphamide Conditioning Regimen

BackgroundHigh-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) has been investigated in patients with primary central nervous system lymphoma (PCNSL) and non-Hodgkin lymphoma (NHL) with CNS involvement and has shown promising results.Patients and MethodsA retrospective analysis was performed of 48 consecutive patients who had undergone HDC/ASCT with TBC (thiotepa, busulfan, cyclophosphamide) conditioning for PCNSL (27 patients), secondary CNS lymphoma (SCNSL) (8 patients), or relapsed disease with CNS involvement (13 patients) from July 2006 to December 2017. Of the 27 patients with PCNSL, 21 had undergone ASCT at first complete remission (CR1).ResultsThe 2-year progression-free survival (PFS) rate was 80.5% (95% confidence interval [CI], 69.9-92.9) and the 2-year overall survival (OS) rate was 80.1% (95% CI, 69.2%-92.7%) among all patients. The 2-year PFS and OS rate for patients with PCNSL in CR1 was 95.2% (95% CI, 86.6%-100%) and 95.2% (95% CI, 86.6%-100%), respectively. On univariate analysis of the patients with PCNSL, ASCT in CR1 was the only variable statistically significant for outcome (P = .007 for PFS; P = .008 for OS). Among patients with SCNSL or CNS relapse, the 2-year PFS and OS rate were comparable at 75.9% (95% CI, 59.5%-96.8%) and 75.3% (95% CI, 58.6%-98.6%), respectively. The most common side effects were febrile neutropenia (89.6%; of which 66.7% had an infectious etiology identified), nausea/vomiting (85.4%), diarrhea (93.8%), mucositis (89.6%), and electrolyte abnormalities (89.6%). Four patients (8.3%) died of treatment-related overwhelming infection; of these patients, 3 had SCNSL.ConclusionHDC and ASCT using TBC conditioning for both PCNSL and secondary CNS NHL appears to have encouraging long-term efficacy with manageable side effects.     

Nutrition-Related Outcomes for Autologous Stem Cell Transplantation Patients

IntroductionAutologous stem cell transplantation (ASCT) patients are at risk for malnutrition before transplantation admission as well as malnutrition acquired during their transplantation admission.Patients and MethodsIn this retrospective, observational study we examined data related to consecutive adults (n = 330) admitted for ASCT between 2014 and 2016 at the Hospital of the University of Pennsylvania. Malnutrition risk on admission (identified by the Malnutrition Screening Tool) and transplantation-associated weight loss were analyzed for independent associations with hospital length of stay, nosocomial infection, intensive care unit transfer, deconditioning, time to platelet and neutrophil engraftment, 30-day readmission, and 1-year mortality.ResultsAdults with high malnutrition risk (n = 60) had a longer median hospital stay (P = .004), longer median time to platelet engraftment (P = .022), increased nosocomial infections (P = .047), and increased 1-year mortality (P = .036). Adults with high transplantation-associated weight loss (n = 100) experienced longer hospital stays (P < .001) and more intensive care unit transfers (P = .001). Outcomes for deconditioning, time to neutrophil engraftment, and 30-day readmission did not differ significantly on the basis of nutrition risk or weight loss.ConclusionFurther research is needed to determine whether early nutrition intervention would improve these outcomes.     

自体外周血干细胞移植治疗难治复发性恶性淋巴瘤

[目的]探讨自体外周血干细胞移植治疗难治、复发性恶性淋巴瘤的疗效.[方法]3例复发难治恶性淋巴瘤患者(其中霍奇金病2例,非霍奇金淋巴瘤1例)接受自体外周血干细胞移植.[结果]3例患者采集干细胞CD34 细胞数为3.20×106/kg～7.8×106/kg.3例自体外周血干细胞移植后均获造血重建,移植后中性粒细胞上升至＞0.5×109/L的时间为7～14d,血小板上升至＞50×109/L为10～16d.2例HD患者移植后随访18～48个月持续缓解,1例6个月后复发.[结论]自体外周血干细胞移植安全、可靠,对复发、难治恶性淋巴瘤仍有较好的疗效.     

Ofatumumab,Etoposide, and Cytarabine Intensive Mobilization Regimen in Patients with High-risk Relapsed/Refractory Diffuse Large B-Cell Lymphoma Undergoing Autologous Stem Cell Transplantation

BackgroundMore than one-half of high-risk patients with relapsed/refractory (rr) diffuse large B-cell lymphoma (DLBCL) relapse after autologous hematopoietic cell transplantation (auto-HCT). In this phase II study, we investigate the long-term outcomes of high-risk patients with rrDLBCL receiving intensive consolidation therapy (ICT) with OVA (ofatumumab, etoposide, and high-dose cytarabine) prior to auto-HCT.Patients and MethodsThe primary endpoints were the ability of OVA to mobilize peripheral stem cells and the 2-year progression-free survival (PFS) rate following OVA. Secondary endpoints included safety, 2-year overall survival (OS), impact of cell of origin (COO), and the prognostic utility of next-generation sequencing minimal residual disease (MRD) testing. We simultaneously retrospectively assessed the outcomes of DLBCL patients who underwent ICT with a similar regimen at our institution.ResultsTwenty-seven patients received salvage chemotherapy, with a response rate of 25% in patients with germinal center B-cell (GCB)-DLBCL versus 92% in patients with non-GCB-DLBCL (P = .003). Nineteen responding patients underwent ICT with OVA (100% successful stem cell mobilization). The 2-year PFS and OS rate was 47% and 59%, respectively, with no difference based on COO. Similar findings were observed when the study and retrospective cohorts were combined. Neutropenia was the most common toxicity (47%). MRD-negative patients at the completion of salvage had a median OS of not reached versus 3.5 months in MRD-positive patients (P = .02).ConclusionsOVA followed by auto-HCT is effective and safe for high-risk rrDLBCL. Patients with GCB-DLBCL had a lower response to salvage chemotherapy, but no difference in outcomes based on COO was seen after auto-HCT. MRD testing in the relapsed setting was predictive of long-term survival.     

自体干细胞移植治疗T细胞淋巴瘤31例临床分析

目的 探讨自体干细胞移植治疗T细胞淋巴瘤的疗效和其预后因素.方法 回顾性分析31例给予自体干细胞移植治疗的T细胞淋巴瘤的临床资料,观察3年总生存率和无进展生存率,分析一般状况(PS)、乳酸脱氢酶(LDH)、移植前状况、分期、外周T细胞淋巴瘤预后指数(PIT)评分对生存的影响.结果 全组中位随访时间为28(5～68)个月...     

Feasibility and Efficacy of High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation for HIV-Associated Lymphoma: A Single-Institution Experience

Background

HIV-associated lymphomas (HAL) remain an important cause of morbidity and mortality in HIV patients, especially in the setting of treatment-refractory disease. Hematopoietic cell transplantation (HCT) is considered a curative option for patients with refractory HAL.