异基因外周血干细胞移植治疗急性和慢性白血病52例临床观察

目的:评价异基因外周血干细胞移植(Allo-PBSCT)治疗血液肿瘤的疗效。方法:用Allo-PBSCT治疗血液肿瘤患者52例[急性淋巴细胞白血病(ALL)11例,急性髓系白血病(AML)12例,慢性粒细胞白血病(CML)29例]。预处理方案为含TBI(21例)与不含TBI的高剂量化疗方案(31例),采用环孢素加骁悉加甲氨喋呤(MTX)常规预防性控制移植物抗宿主病,非亲缘关系移植加用抗胸腺细胞球蛋白(ATG)。结果:52例患者移植后造血功能均重建,急性移植物抗宿主病(aGVHD)发生率23.1%,慢性移植物抗宿主病(cGVHD)发生率21.2%,其中局限型占15.4%;9例患者于移植后1～16月分别死于移植物抗宿主病、感染和疾病复发或进展,35例患者已PFS3～46个月,ALL-首次完全缓解(CR1)9例,无病存活(DFS)5例,带病生存2例,死亡2例,ALL-不缓解(NR)2例,死亡2例;AML-CR18例,DFS6例,带病生存2例,AML-CR24例,DFS2例,带病生存1例,死亡1例;CML(慢性期)22例,DFS19例,带病生存2例,死亡1例,CML(加速期)4例,DFS2例,带病生存1例,死亡1例,CML(急变期)3例,DFS1例,死亡2例。结论:异基因外周血干细胞移植是目前有可能治愈血液肿瘤的惟一方法。CML慢性期和急性白血病CR1后尽早选择异基因造血干细胞移植。     

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。     

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     

老年人恶性淋巴瘤82例临床分析

恶性淋巴瘤( ML ,简称淋巴瘤) ,是原发于淋巴结或其他淋巴组织的恶性实体瘤,根据病理组织学的不同,ML可分为霍奇金淋巴瘤( HD)和非霍奇金淋巴瘤( NHL )。我国NHL比例明显高于HD,ML死亡率占恶性肿瘤的第11位,而老年患者相对预后差,死亡率高。许多预后因素影响老年ML的生存率。为了客观及正确估计老年ML的病情发展及确定治疗策略,提高缓解率及生存率,现对我院近5年收治并经病理证实的82例ML的临床资料进行回顾性分析。1　临床资料1.1　对象　82例老年ML中HD 2 6例( 31.7% ) ,NHL 5 6例( 6 8.3% )。男5 2例,女30例;男∶女为1.7∶1,…     

淋巴瘤

恶性淋巴瘤（ML）是一组高度异质性的淋巴系统恶性增殖性疾病,分为霍奇金病（HD）和非霍奇金淋巴瘤（NHL）。放、化疗技术的进步使约60％的HD和近30％的NHL患者长期存活,但复发或持续未达缓解者（特别是中、高度恶性NHL）的长期生存改善不明显。大剂量放、化疗联合ASCT为ML提供了一种有效治疗手段。     

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     

大剂量化疗自体外周血干细胞移植生物治疗序贯疗法对67例非霍奇金淋巴瘤的疗效观察

目的评价大剂量化疗、自体外周血干细胞移植、生物治疗序贯疗法对非霍奇金淋巴瘤的疗效。方法2003年6月至2007年3月在第三军医大学新桥医院对67例中、高度恶性非霍奇金淋巴瘤(NHL)患者采用大剂量化疗、自体外周血干细胞移植、白介素-2(IL-2)生物治疗序贯治疗,观察其治疗效果和相关并发症。结果67例患者中,41例完全缓解期患者(NHL-CR),经上述序贯治疗,36例持续CR(87.8%),5例复发(RE,12.2%),其中1例死亡(2.4%);26例部分缓解患者(NHL-PR),达CR15例(57.7%),RE11例(42.3%),其中死亡5例(19.2%)。结论该序贯疗法治疗非霍奇金淋巴瘤安全有效,治疗前达到CR患者疗效更好。     

难治性淋巴母细胞性淋巴瘤治疗后长期无病生存1例

淋巴母细胞性淋巴瘤（LBL）是一种少见但高度恶性的非霍奇金淋巴瘤（NHL），常进展为急性淋巴细胞白血病（ALL），如不及时和正确治疗，则患者生存期很短。我们报道1例难治性LBL患者经过治疗后长期缓解的病例，并结合文献，探讨LBL的治疗。     

PCR—SSCP方法研究血液系统肿瘤的p53d基因突变

目的：探讨p53基因突变在血液系统肿瘤发病及进展中的作用。方法：采用PCR－SSCP方法对34例血液系统肿瘤患者p53基因第5、8显子进行研究。结果：从1例急性粒细胞白血病（AML）（1／12,8．33％）,1例急性淋巴细胞白血病（ALL）（1／5,20％）,2例非霍奇金淋巴瘤（NHL）（2／5,40％）,2例多发性骨髓瘤（MM）（2／8,25％）中发现了p53基因突变。其中1例AML,1例NHL及1例MM,均在检测后3个月内死亡。结论：p53基因突变在血液系统肿瘤的发病及疾病发展中起着一定的作用。     

以腹部包块起病的恶性淋巴瘤35例临床研究

目的总结以腹部包块起病的恶性淋巴瘤患者的临床表现、病理及治疗反应等临床特点。方法对1998~2003年解放军总医院收治的35例以腹部包块起病的恶性淋巴瘤患者的病例及随访资料进行回顾性分析。随访时间16~96个月。结果男性患者占74·3%;以腹膜后淋巴结肿大最多(71·4%);非霍奇金淋巴瘤(NHL)占91·4%(32/35),霍奇金病占8·6%(3/35);非霍奇金淋巴瘤患者中40~50岁发病占15/32(46·9%);NHL中B细胞来源非霍奇金淋巴瘤(B-NHL)比例65·6%(21/32),T细胞来源非霍奇金淋巴瘤(T-NHL)占28·1%(9/32),2例未分型占6·3%;3例霍奇金病患者中1例死于复发,非霍奇金淋巴瘤患者死亡9例,其中常规化疗组6例,移植组3例;起病时伴有肝功能异常及腹水的患者4例中2例死亡。结论以腹部包块起病的恶性淋巴瘤男性多见;B-NHL多见;临床表现以腹部症状为主,包块巨大、有腹水及肝功异常者预后差。     

The efficacy of VAD chemotherapy for refractory lymphoid malignancies

Thirty patients with refractory lymphoid malignancies [multiple myeloma (MM): 8, plasma cell leukemia (PCL): 2, acute lymphocytic leukemia (ALL): 5, chronic myelogenous leukemia in blast crisis: 1, chronic lymphocytic leukemia in blast crisis: 1, adult T-cell leukemia: 1, non-Hodgkin lymphoma (NHL): 9, Hodgkin's disease (HD): 3] were treated with VAD regimen (vincristine, doxorubicin, dexamethasone). Of 28 evaluable patients, 4 patients achieved complete response or remission [MM1, ALL1, NHL1, HD1], 10 attained partial response or remission [MM5, PCL1, NHL3, HD1], and 2 patients with MM attained minor response. The remission duration ranged from 1 month to over 14 months. The response rate was high in patients with MM (75%) and lymphoma (60%), however 4 patients with T-cell malignancies achieved no response except one with NHL. In three patients who showed resistance to VAD, diltiazem was administered in addition to VAD and one patient with MM had response. Atrio-ventricular block was also observed in one patient during the period of diltiazem administration. Nine patients developed documented infections, 5 of which suffered from candida infections. From these observations, we concluded that VAD regimen might be useful as a salvage therapy especially in patients with MM and lymphoma.     

Prolonged subcutaneous administration of 852A, a novel systemic toll-like receptor 7 agonist, to activate innate immune responses in patients with advanced hematologic malignancies

The toll‐like receptor (TLR) 7 agonist 852A, a small‐molecule imidazoquinoline, stimulates plasmacytoid dendritic cells to produce multiple cytokines. We conducted a Phase II study of 852A in patients with recurrent hematologic malignancies. The primary objective was assessing the activity of 852A administered subcutaneously twice weekly for 12 weeks. Secondary objectives were assessing the safety of 852A and its ability to activate the immune system with prolonged dosing. Patients with relapsed hematologic malignancies of any age with adequate organ function were eligible. Patients initiated dosing at 0.6 mg/m² twice weekly and escalated by 0.2 mg/m² after every two doses as tolerated to a target dose of 1.2 mg/m². Patients with responses or stable disease were eligible for additional cycles. Seventeen patients (15 males) entered the study: 6 with AML, 5 ALL, 4 NHL, 1 Hodgkin's lymphoma, and 1 multiple myeloma. The mean age was 41 years (12–71 years). The median number of prior chemotherapy regimens was 5 (range = 1–14). Thirteen patients completed all 24 injections. Grade 3‐4 toxicities included nausea, dyspnea, fever, myalgia, malaise, and cough. Responses included one complete response (ALL), one partial response (AML), two stable disease (AML and NHL), and 9 progressive disease. This is the first in‐human hematologic malignancy trial of a subcutaneously (SC) delivered TLR7 agonist using a prolonged dosing schedule. 852A was safely administered up to 1.2 mg/m² twice weekly with evidence of sustained tolerability and clinical activity in hematologic malignancies. Systemic TLR agonists for the treatment of hematologic malignancies warrant further study. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.     

血液肿瘤患者FLT3/ITD基因突变的检测及临床意义

目的检测血液肿瘤患者FLT3/ITD基因突变,探讨其突变的临床意义。方法2001—2005年对南方医科大学南方医院血液科332例血液肿瘤患者,采用聚合酶链反应(PCR)方法检测FLT3/ITD基因突变。结果FLT3/ITD基因突变阳性率分别为急性髓性白血病(AML)22.3%(23/103)、慢性髓性白血病急变期(CML-BC)6.5%(2/31)、骨髓增生异常综合征(MDS)5.6%(2/36)和急性淋巴细胞白血病(ALL)2.6%(2/76)。而慢性髓性白血病慢性期(CML-CP)、慢性淋巴细胞白血病(CLL)、多发性骨髓瘤(MM)和非霍奇金淋巴瘤(NHL)均未发现FLT3/ITD基因突变。FLT3/ITD基因突变阳性AML患者外周血WBC计数及骨髓白血病细胞比例显著高于FLT3/ITD基因突变阴性AML患者(P<0.05),FLT3/ITD基因突变阳性AML患者完全缓解后18个月内累计复发率(63.6%)显著高于FLT3/ITD基因突变阴性AML组(27.7%)(P<0.05)。结论FLT3/ITD基因突变检测对血液肿瘤预后有一定意义;FLT3/ITD基因突变AML患者预后差。     

Hypermethylation of calcitonin gene in adult acute leukemia at diagnosis and during complete remission

Hypermethylation of the calcitonin gene has been described in various hematologic malignancies. In order to assess its frequency and potential usefulness as a marker for leukemic cells and to detect potential clinical correlations, 180 adult patients (aged > 15 years) with newly diagnosed acute leukemia including 133 cases of acute myeloid leukemia (AML) and 47 cases of acute lymphoblastic leukemia (ALL) were tested for its presence in leukemic blasts at diagnosis by Southern blot technique and polymerase chain reaction (PCR) using 3 sets of primers (P550, P566, P1400), amplifying the most frequent sites of hypermethylation upstream or within the gene. In AML, 92 patients (69%) had hypermethylation detected by Southern blot at diagnosis. This hypermethylation could be confirmed by PCR in 18 of 36 tested cases (50%). Hypermethylation was not significantly associated to any clinical or hematological characteristic of the disease. In ALL, 44 patients (94%) had hypermethylation detected by Southern blot at diagnosis. This hypermethylation could be confirmed by PCR in 33 of the 43 tested cases (77%). Sensitivity of PCR assessed by dilution was 1 to 0.1%. Hypermethylation was not either significantly related to any clinical or hematologic characteristics of the disease. Seven ALL cases which were positive by PCR at diagnosis and achieved cytological CR could be tested during CR. Five cases were negative and did not relapse after 3 to 27 months in CR. One case was positive at the beginning of CR and became negative after autologous transplant. However, he relapsed after 9 months in CR, 3 months after the last negative test. PCR for Bcr/Abl was also negative at this time. We conclude that hypermethylation of the calcitonine gene is frequent at diagnosis in adult acute leukemia, particularly in ALL.     

Effects of low dose Ara-C regimen in acute leukemias and RAEB

Recent increase of leukemia among elderly patients prompted us to investigate the types of leukemia which can be induced into remission by low-dose Ara-C (LDAC) regimen. LDAC regimen was performed in 30 cases with overt acute leukemia (A), hypoplastic leukemia (B), and RAEB (C); Group A consists of M1 (1 case), M2 (4 cases), M3 (1 case), M4 (4 cases), M6 (1 case), and ALL (2 cases), Group B AML (8 cases), ALL (2 cases), and null (1 case), Group C RAEB (2 cases), and RAEB-T (4 cases). Complete remission (CR) rate was 23% (3/13) in group A, 64% (7/11) in group B, 0% (0/6) in group C. Partial remission rate was 33% (2/6) in group C. In group A, patients with M2 were induced into CR. In group B, both AML and ALL were induced into CR. Hypocellular marrow indicating low leukemic burden related to good sensitivity to Ara-C. Duration of CR was rather short; mean duration being 5.3 months. In group C, 2 PR cases of RAEB showed partial hematological recovery. LDAC regimen is effective especially for most of hypoplastic leukemia and some of M2. Side effects were tolerable, but all CR cases passed through bone marrow hypoplasia and needed supportive cares.     

Non-Hodgkin's lymphoma and other nonhepatic malignancies in Swedish patients with hepatitis C virus infection

The aim of this study was to evaluate the association between hepatitis C virus (HCV) infection and non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), thyroid cancer (TC), chronic lymphatic leukemia (CLL), acute lymphatic leukemia (ALL), and Hodgkin's lymphoma (HL). A Swedish cohort of 27,150 HCV-infected persons notified during 1990-2000 was included in the study. The database was linked to other national registers to calculate the observation time, expressed as person-years, and to identify all incident malignancies in the cohort. The patients were stratified according to assumed time of previous HCV infection. The relative risk of malignancy was expressed as a standardized incidence ratio (SIR)-the observed number compared to the expected number. During 1990-2000 there were 50 NHL, 15 MM, 14 ALL, 8 TC, 6 CLL, and 4 HL diagnoses in the cohort. Altogether, 20 NHL, 7 MM, 5 TC, 4 CLL, 1 ALL, and 1 HL patient fulfilled the criteria to be included in the statistical analysis. The observation time was 122,272 person-years. The risk of NHL and MM was significantly increased in the stratum with more than 15 years of infection (SIR 1.89 [95% CI, 1.10-3.03] and 2.54 [95% CI, 1.11-5.69], respectively). The association was not significant in TC or CLL. In conclusion, we report the incidence of several malignancies in a nationwide cohort of HCV-infected persons. Although the delayed diagnosis of HCV probably has resulted in an underestimation of the risk, this study showed a significantly increased risk of NHL and MM.     

Infectious complications after autologous hematopoietic stem cell transplantation: comparison of patients with acute myeloid leukemia,malignant lymphoma,and multiple myeloma

It is yet undetermined whether patients with different hematological malignancies have different propensities to infectious complications after high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (HSCT). We retrospectively analyzed 136 cycles of HDC and autologous HSCT in 114 patients with acute myeloid leukemia (AML, 24 cycles), non-Hodgkin's lymphoma/Hodgkin's disease (NHL/HD, 55 cycles), and multiple myeloma (MM, 57 cycles) with respect to early infectious complications. Median duration of neutropenia was longer in patients with AML and NHL/HD than in patients with MM (11 days vs 8 days) and after conditioning including total body irradiation (TBI) compared with chemotherapy only preparative regimens (11 days vs 7 days). Fever requiring antimicrobial therapy was observed in 88 percent of cycles, with fever of unknown origin (FUO) accounting for 60 percent of febrile episodes. There was no proven fungal infection, but one case of probable invasive pulmonary aspergillosis. Microbiologically documented infections were seen in 29 percent and clinically documented infections in 11 percent. Response to first-line empirical antibiotic therapy was better for FUO than for documented infections (70 percent vs 40 percent). Patients with TBI as part of their conditioning regimen had more overall infections than patients without TBI (96 percent vs 82 percent). There were no differences with respect to the type or incidence of infections between patients with AML, NHL/HD, and MM. Patients with different hematological malignancies have similar rates of early infectious complications after HDC and autologous HSCT. TBI may be associated with an increased risk for infections in the early post-transplant period.     

Refined mapping of genomic rearrangements involving the short arm of chromosome 9 in acute lymphoblastic leukemias and other hematologic malignancies

Deletions of chromosomal band 9p21 have been detected in various tumor types as well as in more than 20% of acute lymphoblastic leukemia (ALL). These deletions frequently include the entire interferon (IFN) gene cluster as well as the methylthioadenosine phosphorylase (MTAP) gene. Recently, the CDKN2 gene (p16INK4A, MTS I, CDK41) was proposed as a candidate tumor-suppressor gene on 9p21 because it is frequently deleted in cell lines derived from multiple tumor types. To determine if CDKN2 or another closely related gene on 9p is the target of 9p deletions in ALL and other hematologic malignancies, we analyzed 20 primary patient samples (13 ALL, 2 acute myeloid leukemias [AML], and 5 non-Hodgkin's lymphomas [NHL]) with 9p rearrangements using Southern blot analysis, fluorescence in situ hybridization (FISH), and single- strand conformation polymorphism (SSCP) for alterations of CDKN2. Homozygous deletions of the CDKN2/CDKN2B (p15) region were detected in 10 cases (50%; 6 ALL, 2 AML, and 2 NHL). In 1 additional case, the intensity of the Southern blot band was significantly reduced, suggesting a CDKN2 deletion in a subpopulation of the malignant cells. No CDKN2 or CDKN2B rearrangements were seen. The IFN gene cluster was homozygously deleted in 2 of 15 (13%) analyzed cases, whereas the MTAP gene was deleted in 6 of 15 cases (40%). In addition, hemizygous deletions of the CDKN2 region were identified in 6 ALL cases using interphase FISH. No point mutation of the coding region of CDKN2 was detected by SSCP in these cases. We conclude that CDKN2 is the most frequently homozygously deleted marker on 9p. The absence of point mutations in the coding region of CDKN2 in cases with hemizygous 9p deletions and the frequent codeletion of MTAP, CDKN2B, and other yet unidentified neighboring genes suggest that the simultaneous deletion of these genes may be necessary for the selective growth advantage of malignant cells.