时辰高剂量化疗联合白体骨髓移植治疗非霍奇金淋巴瘤的长期随访

目的 探讨在自体骨髓(造血干细胞)移植技术支持下应用时辰高剂量的环磷酰胺、足叶乙甙、阿糖胞苷和表阿霉素等组成COAE预处理化疗方案治疗预后差的中高度恶性非霍奇金淋巴瘤(NHL)的疗效。方法 观察11例NHL患者应用该项治疗后造血与免疫功能重建、长期无病生存率、毒副作用及移植相关死亡等．选用C0X回归模型分析性别、年龄、预处理方案、分期、移植时状态等对无病生存时间的影响。结果 所有患者均获得造血与免疫功能重建。随访1、3、5年，无病生存率分别为81．8％、63．6％、54．5％．最长存活9年。5例复发(45．4％)。无移植相关死亡。结论 该法在给药时间上进行了创新，提高了疗效，减低了高剂量化疗的毒副作用。该法作为有不良预后因素的中高度恶性NHL患者诱导化疗达完全缓解后强化治疗手段的远期疗效显著，优于常规化疗，能够改善生存率。     

自体外周血干细胞移植、生物治疗、长间歇维持化疗序贯治疗恶性血液病的临床研究

目的评价自体外周血干细胞移植治疗高龄恶性血液病的疗效。方法将60例老年患者分为移植组与非移植组,其中移植组的34例高龄恶性血液病患者首次缓解并经3~4个周期强化治疗后,行自体外周血干细胞移植,预处理方案采用MAC、M及CY TBI,造血重建后予以大剂量IL-2行生物治疗4个疗程,之后每3~4个月予以长间歇维持化疗1次,常用方案包括TA、MA、MP、CTOD等;非移植组的26例患者采用常规的化疗治疗。结果34例患者移植后均成功重建造血,无一例移植相关死亡。移植后维持化疗满2年的患者有20例,有10例复发(50%),其中6例死亡。34例患者中16例复发(47.1%),其中死亡8例。3年无病生存率为(43.0±7.1)%。26例常规化疗的患者中20例复发(76.9%),其中有12例死亡,3年无病生存率为(19.2±6.2)%。结论自体外周血干细胞移植、生物治疗、长间歇维持化疗序贯治疗高龄恶性血液病,治疗相关死亡率低,无病生存率较高,可作为改善高龄恶性血液病治疗效果的重要措施。     

激活骨髓自体移植治疗白血病和淋巴瘤的疗效分析

目的 探讨激活骨髓自体移植治疗恶性血液病的疗效及影响因素。方法 ４４例为白血病和非霍奇金淋巴瘤（ＮＨＬ）患者进行激活骨髓自体移植,观察移植后造血与免疫功能重建,移植后完全缓解（ＣＲ）,移植后相关死亡、肿瘤复发率和长期无病生存率及移植物抗宿主产产表现及毒副作用。选用Ｋａｐｌａｎ－Ｍｅｉｅｒ生存曲线评估一３、５年无病生存率、ＣＯＸ回归模型分析性别、年龄、疾病种类、移植前状态（ＣＲ与未ＣＲ）,预处理方案     

自体造血干细胞移植+BEAC方案治疗预后不良非霍奇金淋巴瘤疗效观察

用自体外周血造血干细胞移植（APBSCT）＋大剂量BEAC方案治疗预后不良非霍奇金淋巴瘤（NHL）患者10例,均获快速造血功能重建,其中7例高危初治者完全缓解（CR）,3例复发者中CR2例、PR1例;无移植相关死亡。提示APBSCT＋大剂量化疗对预后不良或复发NHL安全有效,能改善患者生存率。     

大剂量烷化剂为主的预处理方案在造血干细胞移植中的相关毒性与疗效

目的 观察烷化剂为主的化疗作预处理，并进行造血干细胞移植治疗12例恶性血液病的相关毒性和疗效。方法 毒性分级用Bearman等制订的标准，并统计分析完全缓解（CR）率、复发率和无病生存期。结果 1例无任何毒性发生。以烷化剂为主的大剂量化疗预处理方案的髓外毒性（RRT）主要表现在口腔粘膜和胃肠道。BU／CY方案发生了多脏器Ⅲ级RRT。移植后全部患者造血功能获得重建，无1例发生移植相关死亡，9／12例移植后持续CR，生存期最长达46个月。结论 烷化剂为主的大剂量化疗预处理对急性白血病和淋巴瘤有良好疗效，且髓外RRT轻。BY／CY方案剂量需调整或对方案进行改良。     

自体外周造血干细胞移植对侵袭性非霍奇金淋巴瘤疗效及生活质量影响

<正>自CHOP方案成为非霍奇金淋巴瘤(NHL)患者的标准方案后,预后不良侵袭性NHL患者中44%可经过CHOP方案化疗获完全缓解,但5年总生存率仅为26%[1-2]。造成复发率仍居高不下的原因可能与肿瘤细胞对化疗药物的敏感性降低有关[3]。自体外周造血干细胞移植(APBSCT)联合大剂量放化疗(HDC)治疗侵袭性NHL,可提高缓解率及降低复发率,但APBSCT是否能改善侵袭性NHL患者预     

异基因造血干细胞移植治疗MDS临床研究

目的探讨HLA配型相合异基因造血干细胞移植（allo—HSCT）治疗骨髓增生异常综合征（MDS）的可行治疗方案和疗效。方法以HLA配型相合的骨髓移植治疗MDS患者6例,预处理方案为非清髓性预处理方案1例,清髓性预处理方案5例;以霉酚酸酯、环孢菌素A加短疗程的甲氨喋呤预防移植物抗宿主病（GVHD）。结果6例患者均造血重建。5例清髓性预处理方案仍然无病存活,非清髓性预处理方案1例移植后出现MDS,于移植后17个月死亡。移植后最长无病存活时间已达8a。移植期间发生Ⅰ、Ⅱ°急性移植物抗宿主病（aGVHD）4例。结论allo-HSCT治疗MDS可行、有效,清髓性预处理方案可能对于长期稳定植入有利。     

自体外周血造血干细胞移植治疗非霍奇金淋巴瘤182例临床分析

目的　评价自体外周血造血干细胞移植 (APBSCT)治疗非霍奇金淋巴瘤 (NHL)患者的疗效。方法　全国 34家单位采用APBSCT治疗NHL 182例。其中第一次完全缓解 (CR1)移植 112例 ,部分缓解 (PR)或复发期移植 70例。外周血造血干细胞 (APBSC)动员方案分为四组 :1组为大剂量环磷酰胺 (HD CY)联合粒细胞 集落刺激因子 (G CSF) 5 5例 ;2组为大剂量阿糖胞苷 (HD Ara C)联合G CSF7例 ;3组为增大环磷酰胺剂量的针对性化疗方案联合G CSF 10 2例 ;4组为单独应用G CSF 18例。预处理方案 :移植前处于CR1状态的 112例中 ,含有全身照射 (TBI)的预处理方案 39例 ,不含TBI的 73例 ;PR或复发的 70例中 ,含有TBI的预处理方案 2 9例 ,不含TBI的 4 1例。结果　四组所采集到的APBSC均可达到临床所需数量。四组间采集的单个核细胞数与采集次数之间无统计学差别。移植后WBC≥ 1 0× 10 9/L的中位数时间为 12 (10～ 30 )d ;血小板≥ 2 0× 10 9/L的中位数时间为 12 (0～ 181)d。患者移植后平均随访时间为 2 4个月。预期 3年无病生存率 (DFS)移植前达CR1期者 6 9 7% ;PR和复发期为 4 4 9%。在移植前达CR1期患者中 ,含有TBI和不含TBI的预处理方案的 3年DFS无统计学差别 (70 1%、6 8 0 % )。而对于PR或复发期患者 ,前者优于后者 (5 7     

自体造血干细胞移植治疗恶性血液病及实体瘤的临床研究

目的探讨自体造血干细胞移植(AHSCT)治疗恶性血液病及实体瘤的疗效。方法1996年5月至2005年2月广州医学院第一附属医院肿瘤血液中心用AHSCT治疗的白血病及恶性淋巴瘤患者共20例,年龄18～50岁。预处理化疗方案选用以下药物中任意2种或3种联合:阿糖胞苷3～4g/m2,环磷酰胺4～6g/m2,依托泊苷(VP-16)0.5～1.0g/m2,司莫司汀300mg/m2,马法兰140mg/m2,塞替哌600mg/m2,卡铂1.0g/m2,白消安(Bu)16mg/kg。除2例ALL联合全身照射(剂量为8Gy)外,其余均单用化疗。结果所有患者移植后均重建造血,无移植相关死亡;随访中位值39.5(2～109)个月,无病生存者15例,占全部移植患者的75.0%。其中无病生存1年12例(60%),2年8例(40%),3年8例(40%),最长存活9年余。结论自体造血干细胞移植可明显提高完全缓解肿瘤患者的治愈率;对于复发或难治者,可以提高完全缓解率,延长生存期,提高生活质量。     

自体外周血造血干细胞移植治疗恶性淋巴瘤

目的 :报告 7例恶性淋巴瘤在自体外周血造血干细胞移植 (APBSCT)支持下接受超大剂量放、化疗的治疗经验 ,评价所用外周血造血干细胞 (PBSC)动员方案的动员效果 ,预处理方案的疗效和耐受性 ,以及移植后造血重建情况。方法 :7例淋巴瘤患者中 ,1例霍奇金病 ,6例非霍奇金淋巴瘤。动员方案为MOEP/CMOP化疗联合rhG -CSF ,预处理采用经典的超大剂量环磷酰胺 (CTX)化疗联合全身放疗 (TBI)。结果 :APBSCT动员后获得到单个核细胞 4.2 (2 .7～ 6 .1)× 10 8/kg,回输单个核细胞 3.7(2 .5～ 5 .3)× 10 8/kg ,中性粒细胞计数恢复到 >0 .5× 10 9/L的时间和血小板 >5 0× 10 9/L的时间分别平均为第 11.6天和第 14.6天。毒副作用主要为消化道反应。结论 :APBSCT治疗恶性淋巴瘤效果肯定 ,采用MOEP/CMOP联合rhG -CSF动员以及经典CTX加TBI方案预处理 ,安全可靠 ,治疗效果良好。     

High-dose therapy and autologous stem cell transplant does not result in long-term disease-free survival in patients with recurrent chemotherapy-sensitive ALK-negative anaplastic large-cell lymphoma

Primary systemic anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALCL) has a poor prognosis. This study sought to determine if high-dose therapy and ASCT results in long-term disease-free survival (DFS) in patients with recurrent, chemotherapy-sensitive ALK-negative ALCL. All patients with non-Hodgkin's lymphoma (NHL) who underwent ASCT at Wake Forest University and Upstate Medical University from 1 January 1990 to 12 December 2002 were reviewed to determine if they had T-, B- or null-cell NHL that was CD30+/CD15-/ALK negative. In all, 16 patients were thus identified as having ALK-negative ALCL. All 16 patients underwent ASCT at the time of first relapse and form the basis of this report. Median age of the 16 patients was 51 years. There were 11 males and five females. International prognostic index scores in 12 patients at the time of relapse were: low 3, LI 6 and HI 3. Of 15 patients, 13 relapsed after ASCT; one patient was lost to follow-up. Median progression-free survival for the 15 patients was 12 weeks (3-212+ weeks). Of 15 patients, 10 have died; nine of recurrent disease. Median overall survival for the 15 evaluable patients was 72 weeks. In our experience, high-dose therapy and ASCT does not produce long-term DFS in patients with recurrent chemotherapy-sensitive ALK-negative ALCL.     

Ifosfamide,mitoxantrone and etoposide (VIM) as salvage therapy of low toxicity in non-Hodgkin's lymphoma

Abstract: Patients with non-Hodgkin's lymphoma (NHL) who fail to respond to first-line treatment or relapse after having shown complete or partial remission have a poor prognosis, especially in high-grade NHL. Several salvage regimens show considerable toxicity and a poor long-term outcome. In this retrospective study we analyzed data of 55 patients (34 men and 21 women) with a median age of 66 years (range: 18–89). The combination chemotherapy (VIM) consisted of VP-16 (etoposide) 65 mg/m², ifosfamide 650 mg/m² and mitoxantrone 3 mg/m² and was administered on 3 consecutive days along with mesna as uroprotection. Patients were treated for refractory disease or relapse and did not qualify for high-dose chemotherapy and ABMT. Stages according to the An Arbor classification were: stage I/16, II/4, III/8 and IV/37 patients. Thirty-three patients suffered from high-grade and 22 from low-grade NHL. Toxicity (WHO recommendations) was very mild. High-grade NHL showed a better response rate (18/33, 46%) than low-grade NHL (7/22, 36%). Overall response was 41% (12 CR and 11 PR) with a median duration of 36 months (range: 6–57 months). The combination therapy investigated exhibits mild toxicity even in extensively pretreated or elderly patients. The overall response rate of 41% might be improved by increased dosage and growth factor support.     

Serum interleukin-10 in non-Hodgkin's lymphoma: a prognostic factor

Serum interleukin-10 (IL-10) was measured retrospectively in 153 patients with a fully documented history of non-Hodgkin's lymphoma (NHL) using an enzyme-linked immunosorbent assay (ELISA) detecting both human IL-10 and the Epstein-Barr virus (EBV) molecule BCRF1/viral IL- 10. IL-10 was detectable in 47 (46%) of the 101 patients with active NHL, 3 of 52 (6%) patients in first partial or complete response, and none of the 60 healthy blood donors. Serum IL-10 was detectable with a similar frequency in all subtypes of NHL and in all clinical stages, as well as in EBV-seropositive and EBV-negative patients. In patients with intermediate or high-grade NHL, the presence of detectable serum IL-10 at diagnosis was correlated to a significantly shorter overall (P = .025) and progression-free (P = .030) survival. Patients with stage IV disease and detectable serum IL-10 had a particularly poor prognosis (4 years of survival: 0%). Multivariate analysis showed that IL-10 was an independent prognosis factor. These results indicate that IL-10 is detectable in a subgroup of patients with active NHL and correlates to a poor survival in patients with intermediate or high-grade NHL.     

Autologous bone marrow transplantation in 69 patients with a history of low-grade B-cell non-Hodgkin's lymphoma

Sixty-nine patients with a history of low-grade B-cell non-Hodgkin's lymphoma (NHL) in sensitive relapse or incomplete first remission underwent high-dose chemoradiotherapy and anti-B-cell monoclonal antibody (MoAb)-treated autologous bone marrow transplantation (ABMT). At ABMT, 51 patients had low-grade histology and 18 patients had a history of low-grade NHL that had undergone histologic transformation to a higher-grade NHL. Before ABMT, only 20 of the 51 low-grade patients and 10 of the 18 patients with transformed histologies were in complete remission. Moreover, at the time of marrow harvest, 24 of the low-grade and eight of the transformed histology patients had histologic evidence of lymphoma cells infiltrating the marrow. Following high-dose therapy, only one acute, in-hospital death was observed. There was no significant difference in the disease-free survival (DFS) between patients with low-grade and patients with transformed histologies. Among patients with low-grade NHL, the patients in complete remission before ABMT experienced significantly longer DFS than those in partial remission (P less than .05). This preliminary study suggests that some patients with relapsed low-grade NHL may experience prolonged DFS following high-dose ablative therapy.     

Autologous peripheral blood stem cell transplantation with granulocyte colony-stimulating factor combined conditioning regimen as a postremission therapy for acute myelogenous leukemia in first complete remission

We retrospectively analyzed the outcomes of 81 patients with non-M3 acute myelogenous leukemia (AML) in first complete remission (CR1) who were treated with high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation (Auto-PBSCT) by the Fukuoka Blood and Marrow Transplantation Group between 1989 and 2005. Cytogenetically, 16 patients were defined as good risk, 56 as intermediate risk, and nine as poor risk, following the Southwest Oncology Group criteria. The pre-transplant conditioning regimen consisted of high-dose busulfan, etoposide, and cytarabine (BEA regimen), combined with priming by granulocyte colony-stimulating factor (G-CSF). Disease-free survival (DFS) and overall survival at 5 years were 64.0 % (95 % CI 52.5–73.4) and 66.4 % (95 % CI 54.9–75.6) after Auto-PBSCT at a median follow-up time of 103 months (range 3–240 months), respectively. Two patients died of transplant-related pulmonary complications 6 months after Auto-PBSCT without relapse. The 5-year DFS rates of patients in the genetically good-, intermediate-, and poor-risk groups were 80.8, 64.3, and 33.3 %, respectively, but there was no significant difference statistically among the risk groups (log-rank p = 0.0579). These observations suggest that HDCT supported by Auto-PBSCT with the BEA regimen combined with G-CSF priming is a therapeutic option for postremission therapy of AML in CR1.     

Fludarabine‐mitoxantrone‐rituximab regimen in untreated intermediate/high‐risk follicular non‐Hodgkin's lymphoma: Experience on 142 patients

There is no international consensus on front‐line optimal chemotherapy regimen for advanced stage follicular lymphoma (FL) patients, or a clear definition of cure for this disease. Aim of this study was to test the degree of effectiveness and the safety of the regimen containing fludarabine, mitoxantrone, and rituximab in a subset of poor prognosis FL patients with particular focus on the long‐term disease‐free survival. A retrospective study was conducted on 142 intermediate/high‐risk FL patients treated in first‐line with fludarabine, mitoxantrone, and rituximab regimen. Responses, safety, and survival were evaluated. The prognostic value of positron emission tomography (PET) was also investigated in a 56‐patients subset. Overall response rate was 95.5% including 88% of complete responses. With a median follow‐up of 48 months, 18% of patients had disease relapse, yielding an estimated 12‐year disease‐free survival (DFS) of 72%. All cases showed the lymphoma recurrence within 40 months: after this timing the DFS curve presented a plateau. Overall survival was 73% at 12 years. Post‐treatment PET positivity remains a highly significant predictor of disease progression. The observed high rate of complete responses following the use of fludarabine, mitoxantrone‐based regimen in combination with rituximab seems to be the first step to improve DFS. Our study could be the starting point to consider DFS as a potential alternative endpoint of future clinical trials on FL patients. Am. J. Heamtol. 88:E273–E276, 2013. © 2013 Wiley Periodicals, Inc.     

Autologous stem cell transplantation for anaplastic large-cell lymphomas: results of a prospective trial

Autologous stem cell transplantation (ASCT) in the front line treatment of non-Hodgkin's lymphoma (NHL) remains controversial. Anaplastic large-cell lymphoma (ALCL) is known to have its own clinical and biological features. The outcome of ALCL patients treated with high-dose chemotherapy and ASCT as part of their first-line therapy was analysed in 202 intermediate or high-grade NHL patients in a prospective randomized trial. First-line chemotherapy comprised two alternating anthracycline-containing regimens. Responding patients were autografted after a BEAM (BCNU, cytarabine, etoposide and melphalan) regimen. Patients with bulky or residual masses were irradiated. Fifteen patients with ALCL were identified by morphological and immunological features (CD30 was expressed in 14 out of 15 patients, three patients expressed B-cell markers, five patients expressed T-cell markers and seven patients did not express cell markers). Anaplastic lymphoma kinase (ALK) expression was confirmed in seven cases. The median age was 39 years with a predominant male sex ratio (2.75). Thirteen patients were stage >/= III and six presented with two or more adverse prognostic factors. According to the international age-adjusted prognostic index, the expected complete remission (CR), event-free survival (EFS) and overall survival (OS) rates were 69%, 71% and 69%. Two deaths were observed (one due to interstitial pneumonitis, one due to pulmonary carcinoma). All patients entered CR, no relapse occurred and EFS and survival reached 87% with a follow-up of more than 5 years. These results differ significantly from those observed in the other 176 lymphoma patients: event-free survival was only 53 +/- 5% and OS reached 60 +/- 4% with a median follow-up of 56 months (P = 0.006). Intensified chemotherapy with autologous stem cell support appeared effective in the treatment of ALCL, offering patients the real chance of a cure.     

Autologous stem cell transplantation for acute myelogenous leukemia in first complete remission: a 6-year follow-up study of 101 patients from a single institution

The objective of the study was to assess the long-term outcome and impact of stem cell source in patients with acute myelogenous leukemia (AML) who received ASCT in first complete remission (CR). A total of 101 patients (median age 46 years) were included in the study. Cytogenetic categories distribution was: favorable: 18%, intermediate: 42%, and unfavorable: 7%. More than one induction course was needed for CR in 21% of patients. In all, 78% of patients had received at least one course of high-dose ara-C before autologous stem cell transplantation (ASCT). Bone marrow (n=58) or peripheral blood stem cells (PBSC) (n=43) transplantation was performed at a median of 3.5 months from CR. Hematologic recovery and hospitalization duration were significantly reduced in the PBSC group. No toxic death was recorded in this group. The median follow-up of survivors is 67 months (range: 15-183). The 6-year survival, disease-free survival (DFS), and relapse probabilities are 44%, 38%, and 54%, respectively. The presence of a favorable karyotype and the use of PBSC are independently associated to better survival, and DFS by multivariate analysis. Our results confirm that long-term DFS can be achieved with high-dose chemotherapy and ASCT in patients with AML. They show that use of PBSC is associated to very low mortality rate and acceptable morbidity and contributes to an improvement of autotransplant results.     

Impact of intensive PBSC mobilization therapy on outcomes following auto-SCT for non-Hodgkin's lymphoma

The best method to mobilize PBSCs in patients with non-Hodgkin's Lymphoma (NHL) is uncertain. We hypothesized that PBSC mobilization using an intensive chemotherapy regimen would improve outcomes after autologous hematopoietic stem cell transplantation (ASCT) in NHL patients at high risk for relapse. Fifty NHL patients were prospectively allocated to intense mobilization with high-dose etoposide plus either high-dose cytarabine or CY if they were 'high risk' for relapse, whereas 30 patients were allocated to nonintense mobilization with CY if they were 'standard risk' (all patients, +/-rituximab). All intensely mobilized patients were hospitalized compared with one-third of nonintensely mobilized patients. The EFS after ASCT was the same between the two groups, but overall survival (OS) was better for intensely mobilized patients (<0.01), including the diffuse large B-cell subgroup (P<0.04). We conclude that the intense mobilization of PBSCs in patients with NHL is more efficient than nonintense mobilization, but with greater toxicity. The equalization of EFS and superiority of OS in patients intensely mobilized to those nonintensely mobilized suggests that a treatment strategy using intensive chemotherapy for mobilization may be improving NHL outcomes after ASCT.