自体外周血干细胞移植支持大剂量化疗治疗淋巴瘤的远期疗效

目的：观察自体外周血造血干细胞移植支持大剂量化疗治疗淋巴瘤的远期疗效。方法：我院1997年8月-2005年4月行自体外周血干细胞移植支持大剂量化疗治疗的淋巴瘤患者共16例,其中男性10例,女性6例;年龄12—61岁,中位年龄30．5岁。所有病例均经病理组织学及免疫组化确诊,其中霍奇金淋巴瘤5例,非霍奇金淋巴瘤11例。移植前状态：处于完全缓解（CR）CR17例,CR22例,部分缓解（PR）PR14例,PR21例。结果：移植后CR9例,PR6例,移植相关死亡1例。全部病例随访至2006年5月,中位随访时间44．5个月（13—89个月）,1例干移植后22个月死于高血压脑卒中,2例分别于移植后12个月及38个月死于复发,其余12例存活至今（其中CR15例,CR22例,PR13例,PR21例,耐药1例）,总生存率75％,无事件生存率62．5％。结论：自体外周血1二细胞移植支持大剂量化疗治疗淋巴瘤,刘提高总生存率和无事件生存率可能有益,值得进一步开展临床研究。     

自体外周血造血干细胞移植治疗淋巴瘤效果分析

目的:探讨自体外周血造血干细胞移植治疗淋巴瘤的临床效果。方法:回顾性分析2014年1月至2020年12月济宁医学院附属医院行自体外周血造血干细胞移植治疗的41例淋巴瘤患者临床资料,包括霍奇金淋巴瘤6例,非霍奇金淋巴瘤35例。采用化疗药物+粒细胞集落刺激因子（G-CSF）+血小板生成素（TPO）或化疗药物+G-CSF的动员方案。移植前预处理方案：26例患者采用BEAM方案+地西他滨,12例采用BEAM方案,3例采用BEAM方案+西达苯胺。观察患者无进展生存（PFS）及总生存（OS）、相关并发症、移植后转归,以及临床分期、B症状、国际预后指数（IPI）评分、结外累及部位、血红蛋白、乳酸脱氢酶（LDH）、β 2-微球蛋白（β 2-MG）、移植方案、移植前状态对移植后OS及PFS的影响。 结果:41例患者中自体外周血造血干细胞移植前疾病获得完全缓解37例（90.24%）,部分缓解2例（4.88%）,未评估2例（4.88%）。24例干细胞采集资料完整的患者采集的中位有核细胞计数12.74×10 8/kg[（3.91~22.68）×10 8/kg],中位CD34阳性细胞数为6.74×10 6/kg[（0.91~50.47）×10 6/kg]。全部41例患者均获得造血重建,中位血小板植入时间为11 d（7~32 d）,中位粒细胞植入时间为9 d（8~16 d）。41例患者移植后疾病均获得完全缓解,无一例发生移植相关死亡。至随访结束,无疾病进展33例,死亡8例。患者移植后12、24、72个月OS率分别为93.4%、85.3%和60.9%,PFS率分别为93.3%、84.0%、84.0%。中位PFS及OS时间均为未达到。不同性别、临床分期、B症状、IPI评分、结外累及部位、血红蛋白、LDH、β 2-MG、移植前状态患者OS及PFS差异均无统计学意义（均 P>0.05）,移植前预处理方案为BEAM方案+地西他滨患者PFS及OS均优于单用BEAM方案患者（均 P<0.05）。 结论:自体外周血造血干细胞移植治疗淋巴瘤具有较好的效果。BEAM方案+地西他滨预处理方案较单用BEAM方案可获得更长的生存时间。     

69例恶性淋巴瘤骨髓侵犯后骨髓象与血象分析

目的了解恶性淋巴瘤骨髓侵犯后骨髓与外周血白细胞之间的关系.方法对69例恶性淋巴瘤具有骨髓侵犯的骨髓细胞分类及外周血白细胞检验结果作回顾性分析.结果 69例恶性淋巴瘤骨髓侵犯者外周血白细胞计数异常33例,分类计数异常35例,骨髓增生正常者19例,增生异常者50例.结论当恶性淋巴瘤发展到骨髓侵犯或淋巴瘤细胞白血病时,外周血白细胞计数和分类计数与骨髓象之间没有绝对的对应关系,但如明确诊断为恶性淋巴瘤时则应把骨髓涂片细胞形态学列为常规检查,如其外周血白细胞形态出现异常,则应高度怀疑有淋巴瘤细胞白血病.     

抗CD20单克隆抗体联合自体外周血干细胞移植治疗非霍奇金淋巴瘤的临床研究

 目的　探讨抗CD20单克隆抗体（利妥昔单抗,商品名：美罗华）联合自体外周血干细胞移植（APBSCT）治疗B细胞非霍奇金淋巴瘤（NHL）的疗效。方法　21例CD20阳性的NHL患者,经过前期治疗,5例达完全缓解（CR）,难治性病例为16例,包括11例部分缓解（PR）和5例疾病进展（PD）。在自体造血干细胞动员的第1、8天及预处理的-1、＋7天每天应用利妥昔单抗375 mg／m2。结果　移植前疾病达到CR的5例患者,无一例复发;移植前处于PR的11例患者,仅1例在移植后6个月疾病复发,其余均无病生存;移植前处于PD的5例患者,2例无病生存。21例患者中位随访24（1～68）个月,复发、死亡4例（19 %）,其余17例均无病生存,2年无病生存（EFS）和总生存（OS）率均为81.0 %。未观察到利妥昔单抗对采集所得干细胞的质量和数量以及移植后造血恢复有不良影响。结论　APBSCT联合利妥昔单抗做体内净化治疗B细胞NHL疗效与移植前状态有关,作为巩固治疗,能使移植前达CR的患者获得长期生存,提高治愈率;作为强化治疗,可提高缓解率,延长PR患者的EFS及OS。利妥昔单抗的加入不影响造血干细胞采集和移植后造血重建。     

非霍奇金淋巴瘤患者外周血T细胞亚群及NK细胞检测的临床意义

目的 探讨非霍奇金淋巴瘤(NHL)患者外周血T细胞亚群及NK细胞检测的临床意义.方法 收集病理确诊的初治NHL患者62例,采集静脉血经流式细胞术检测T细胞亚群及NK细胞水平,与30名健康对照者进行比较；并比较不同年龄、性别、病理类型患者之间的表达差异,分析其与临床分期、国际预后指数(IPI)、有无B症状等因素的相关性.结果 NHL组外周血CD3、CD4、NK细胞比例[(64.13±19.83)％、(27.10±8.20)％、(13.51±10.59)％]低于健康对照组[(65.78±10.69)％、(31.95±12.74)％、(18.76±7.36)％](P＜0.05)；CD8、调节性T细胞(Treg细胞)比例[(32.15±13.83)％、(10.44±3.00)％]高于健康对照组[(29.25±12.35)％、(7.51±4.36)％](P＜0.05).NHL患者≤60岁组CD3、NKT细胞比例[(67.06±19.24)％、(4.91±3.69)％]明显高于＞60岁组[(59.18±20.33)％、(4.89±3.05)％](P＜0.05),T细胞NHL组Treg细胞比例明显高于B细胞NHL组[(8.17±6.41)％比(7.11±2.53)％](P＜0.05).NHL患者外周血CD3、CD4、NK、NKT细胞比例与临床分期相关(均P＜ 0.05)；CD8细胞比例与IPI相关(P=0.000)；Treg细胞比例与IPI、B症状相关(均P＜ 0.05).结论 NHL患者存在细胞免疫抑制,其外周血T细胞亚群及NK细胞比例在不同性别、年龄、病理亚型之间存在不同,与临床分期、IPI、有无B症状等的相关性尚需进一步探讨.     

Role of up-front autologous stem-cell transplantation in peripheral T-cell lymphoma for patients in response after induction: an analysis of patients from LYSA centers

BackgroundPeripheral T-cell lymphoma (PTCL) remains a therapeutic challenge. Due to the rarity and the heterogeneity of PTCL, no consensus has been achieved regarding even the type of first-line treatment. The benefit of autologous stem-cell transplantation (ASCT) is, therefore, still intensely debated.Patients and methodsIn the absence of randomized trials addressing the role of ASCT, we performed a large multicentric retrospective study and used both a multivariate proportional hazard model and a propensity score matching approach to correct for sample selection bias between patients allocated or not to ASCT in intention-to-treat (ITT).ResultsAmong 527 patients screened from 14 centers in France, Belgium and Portugal, a final cohort of 269 patients ≤65 years old with PTCL-not otherwise specified (NOS) (N = 78, 29%), angioimmunoblastic T-cell lymphoma (AITL) (N = 123, 46%) and anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK-ALCL) (N = 68, 25%) with partial (N = 52, 19%) or complete responses (N = 217, 81%) after induction was identified and information about treatment allocation was carefully collected before therapy initiation from medical records. One hundred and thirty-four patients were allocated to ASCT in ITT and 135 were not. Neither the Cox multivariate model (HR = 1.02; 95% CI: 0.69–1.50 for PFS and HR = 1.08; 95% CI: 0.68–1.69 for OS) nor the propensity score analysis after stringent matching for potential confounding factors (logrank P = 0.90 and 0.66 for PFS and OS, respectively) found a survival advantage in favor of ASCT as a consolidation procedure for patients in response after induction. Subgroup analyses did not reveal any further difference for patients according to response status, stage disease or risk category.ConclusionsThe present data do not support the use of ASCT for up-front consolidation for all patients with PTCL-NOS, AITL, or ALK-ALCL with partial or complete response after induction.     

A pilot study of a response oriented chemotherapeutic regimen combined with autologous peripheral blood progenitor cell transplantation in aggressive non-Hodgkin's lymphoma.

Fourteen consecutive patients with poor-risk aggressive NHL who at presentation had any one of four risk factors underwent response oriented induction chemotherapy and successive high-dose chemotherapy followed by autologous PBPC transplantation. After treatment with three cycles of conventional CHOP with G-CSF support (CHOP-G), the response was evaluated. For patients who achieved a complete remission (CR), an additional three cycles of CHOP-G were administered, while for partial response patients, another induction regimen including some non-cross-resistant agents was given; three cycles of VIPDexa-G (etoposide, ifosfamide, cisplatinum and dexamethasone) +/- two cycles of ENAP-G (mitoxantrone, etoposide, cytosine arabinoside and prednisone), were given. The scheduled induction chemotherapy, was followed by treatment with a high-dose cytoreductive regimen followed by autologous PBPC transplantation. After three cycles of CHOP-G, four patients (29%) achieved a CR, and 10 (71%) achieved a partial response (PR). When all scheduled induction therapy was completed, 10 patients (71%) had a CR. All 14 patients received high-dose therapy and obtained a complete hematologic recovery, except for one with a bone marrow relapse two months after transplantation. Evaluation of response after high-dose therapy showed 12 CRs (86%) which included three additional CRs, one PR, and one toxicity-related death. With a median follow-up of 12 months (range, 4 to 40), 12 are alive, with 11 in continuous first CR, and one relapse. The 2-year overall survival (OS) rate and event-free survival (EFS) rate are 77% and 79%, respectively, while the disease-free survival (DFS) rate is 92%. In conclusion, this pilot study suggests that response oriented induction chemotherapy and successive high-dose chemotherapy followed by autologous PBPC transplantation is commendable and can be associated with a high rate of remission and DFS for poor risk subjects with aggressive NHL.     

Efficiency of in vivo purging with rituximab prior to autologous peripheral blood progenitor cell transplantation in B-cell non-Hodgkin's lymphoma: a single institution study.

BACKGROUND: Rituximab induces clinical response in advanced B-cell lymphoma and is efficient in removing circulating B-cell from peripheral blood. We therefore postulated that rituximab might be a useful in vivo purging agent before high-dose therapy in this setting. PATIENTS AND METHODS: Fourteen patients with relapsed follicular, marginal zone and mantle cell lymphomas (11, two and one cases, respectively) and a PCR-detectable molecular marker were treated first with rituximab, then a mobilization chemotherapeutic regimen, followed by high-dose therapy with peripheral blood stem cell transplantation. PCR analyses were performed in peripheral blood before rituximab and during follow-up, and in harvest. RESULTS: Harvests were free of PCR-detectable molecular marker in nine of the 11 studied cases (82%). After high-dose therapy, clinical complete remission was obtained in 13 (93%) patients and molecular remission in 11 (79%). With a median follow-up of 3 years, the 14 transplanted patients were alive, 11 of them remaining in clinical complete remission and eight in molecular remission at last follow-up. CONCLUSION: Rituximab treatment followed by high dose therapy appears to be effective in achieving complete clinical and molecular response. In vivo harvest purging is predictive of prolonged clinical and molecular remission.     

自体造血干细胞移植治疗纵隔大B细胞非霍奇金淋巴瘤

目的 探讨高剂量放化疗联合自体外周血造血干细胞移植(APBSCT)治疗原发纵隔的、弥漫大B细胞性非霍奇金淋巴瘤(PMLBL)的疗效和安全性。方法 9例PMLBL接受了高剂量放化疗联合APBSCT的治疗,7例采用高剂量化疗(HDC)联合全身照射(TBI)或全淋巴结照射(TLI)或次全淋巴结照射(STLI)作为预处理方案,2例采用单纯高剂量化疗作为预处理方案。均于移植后进行了原发部位的补量放疗。随访10-84个月,中位24个月。诱导化疗后完全缓解(CR)5例,部分缓解(PR)3例,进展(PD)1例。结果 5例诱导化疗后获CR的患者全部无病存活;3例诱导化疗后PR者中,l例获长期无病生存,2例分别于移植后3个月和5个月死亡;l例PD者移植后6个月死亡。全组无移植相关死亡。根据寿命表法分析,全组7年累积无疾病生存率(DFS)为66．7％,7年累积总生存率(OS)为66．7％。结论 高剂量放化疗联合APBSCT治疗具有不良预后因素的PMLBL,取得较好的疗效,该方法易耐受,安全性好,但其在综合治疗中的价值,有待进一步探讨。     

Five-year results of cyclic semi-high dose neoadjuvant chemotherapy supported by autologous peripheral blood stem-cell transplantation in patients with advanced ovarian cancer

Background To achieve anti-ovarian tumor responses similar to those obtained with high-dose chemotherapy but with milder side effects, we developed a treatment protocol in which semi-high dose multi-cycle neoadjuvant chemotherapy was supported by autologous peripheral blood stem-cell transplantation (auto-PBSCT).Methods Seventeen patients with advanced ovarian cancer were enrolled in this study. Two cycles of semi-high dose neoadjuvant chemotherapy, using carboplatin (AUC, 8.75; average dose, 621mg/m²) and etoposide (average dose, 960mg/m²) were supported by auto-PBSCT and followed by cytoreductive surgery and further chemotherapy. Each patient was followed for at least 5 years.Results This treatment schedule achieved an overall response rate of 70.6% in 17 patients with stage III or stage IV ovarian cancer. The 5-year disease-free survival rate was 52.9% (95% confidence interval, 29.2%–76.6%) and the median survival time was 63 months (95% confidence interval, 16–79 months). Thus, we obtained superior treatment outcomes in these 17 patients in comparison with published conventional protocols.Conclusion Cyclic semi-high dose neoadjuvant chemotherapy supported by auto-PBSCT may be tolerable and favorable for patients with advanced ovarian cancer.     

HIGH DOSE CHEMORADIOTHERAPY WITH AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THE TREATMENT OF ADVANCED HODGKIN‘S LYMPHOMA: A REPORT OF 11 CASES

Objective: High dose therapy (HDT) with autologous hematopoietic stem celltransplantation (ASCT) has become one of the important salvage treatments for the Hodgkin‘s Lymphoma patients with relapsed or resistant disease, but its role as the primary treatment remains indefinite. This study was designed to further evaluate its status in the combined modality treatment, especially, to discuss its value in the primary treatment of the patients who had advanced disease with poor prognostic factors. Methods: Eleven patients who had advanced or relapsed disease with poor prognostic factors were enrolled in this study. Among them, 9 cases had primary treatment, and 2 cases had secondary treatment; one patient received autologous bone marrow transplantation (ABMT), and 10 patients received autologous peripheral blood stem cell transplantation (APBSCT). After induction treatment 4 cases achieved complete response (CR) and 7 cases achieved partial response (PR). High dose chemotherapy combined with total body irradiation (TBI) ortotal lymph node irradiation (TLI)/subtotallymph node irradiation (STLI) were adopted in 7 cases and only high dose chemotherapy were adopted in 4 cases as the transplant preparative regimens. 5 cases received complementary irradiation in the primary sites after transplant. Results:The patients who had CR before transplantation were given consolidative therapy. Among the rest with PR, 2 cases achieved CR, 1 case PR, and 4 cases SD. Furthermore all these patients who maintained SD had bone involvement. With a median follow-up for all patients of 13(1(80) months, all of them are alive currently. Four cases are event-free survival (EFS); 4 cases with bone involvement are progression-free survival (PFS); 3 cases experienced relapse after transplant, one ofthem is EFS for 42 months again after a local relapsed site irradiation; the other two cases are being given further salvaged treatment now. According to the Life Tables method, the cumulative probability of 6-year PFS and OS is 55.68% and100% respectively. The dominating transplant- related toxicity was bone marrow suppression in grades IV. No obvious cardiac, hepatic, and nephritic toxicity was found. No transplant related mortality. Conclusion: HDT combined with ASCT is a method worthwhile to further study for the treatment of the patients with advanced or relapsed Hodgkin‘s Lymphoma with poor prognostic factors.     

Effect of cell determinant (CD)34+ cell dose on the cost and consequences of peripheral blood stem cell transplantation for non-Hodgkin's lymphoma patients in front-line therapy

The aim of this study was to assess the effect of cell determinant (CD)34+ cell dose on the cost and consequences of peripheral blood stem cell transplantation for non-Hodgkin's lymphoma (NHL) patients in front-line therapy. Resource utilisation, length of aplasia, overall (OS) and event-free survival (EFS) were assessed for 63 patients. Economic data were calculated taking into account harvest, hospitalisation, blood product requirements and drugs required until discharge. The point of view of the Hospital Institution was chosen. A significantly earlier haematopoietic engraftment was achieved in patients with a count of more than 5×10⁶ CD34+/kg. There were no differences for OS and EFS. A high CD34+ cell content resulted in a total cost saving of $4210. This was principally related to a significant reduction in the length of hospitalisation (−$3010) and platelet and red blood cell transfusions (−$815), although the latter was not significant. Several sensitivity analyses showed the robustness of our results. A CD34+ cell dose higher than 5×10⁶/kg appeared to be optimal for clinical and economic considerations in NHL patients undergoing transplantation in front-line therapy.