改良Hyper-CVAD方案治疗27例淋巴母细胞性淋巴瘤疗效分析

淋巴母细胞性淋巴瘤(lymphoblastic lymphoma,LBL)是较为少见的高度侵袭性淋巴瘤,约占非霍奇金淋巴瘤的4%以及儿童和青少年非霍奇金淋巴瘤发病率的35%,是危害青少年生命的主要恶性肿瘤之一。LBL具有恶性程度高、进展速度快、死亡率高、易侵犯骨髓和神经系统等特点。LBL来源于前体的T淋巴细胞或B淋巴细胞,LBL与急性淋巴细胞白血病是同一疾病的不同表现形式,2者在细胞生物学特征(如形态学、免疫表型、细胞和分子遗传学等)以及治疗策略和转归上具有高度的一致性。     

多参数流式细胞术在淋巴细胞白血病和非霍奇金淋巴瘤骨髓侵犯诊断的应用

背景与目的：骨髓形态学检查可诊断淋巴细胞白血病,结合淋巴结活检可诊断非霍奇金淋巴瘤(non—Hodgkin‘s lymphoma,NHL)侵犯骨髓,但形态学仅是初步的诊断,采用免疫分型而获得肿瘤细胞来源及发育阶段的资料是目前诊治淋巴系统恶性肿瘤所必需的。本研究探讨多参数流式细胞术(flow cytometry,FCM)在淋巴细胞白血病、NHL骨髓侵犯的诊断和免疫分型方面的应用价值。方法：取初治白血病患者骨髓标本11例和NHL患者骨髓侵犯的骨髓标本41例,以及2例分别表现为巨大纵隔肿块和腹部巨大肿块的患者因无法取得病理标本而取骨髓检测的骨髓标本2例。采用B细胞系列抗体、T细胞系列抗体、粒细胞系列抗体,按常规行FCM免疫表型检测,CD45结合两个系列单抗或阶段特异性单抗进行三色免疫荧光染色,CD45／SSC设门后可将骨髓细胞清晰地分出成熟细胞和幼稚细胞群,然后行FSC、SSC、McAb1-FITC、McAb2-PE、CD45-Cychrome五参数分析。结果：11例白血病患者骨髓形态学经FCM的免疫分型获得进一步确诊和分型。41例NHL骨髓侵犯标本免疫表型与其淋巴结病理免疫组化相符合的为80．5％(33／41),不相符的有19．5％(8／41),结合临床、病理、骨髓形态学诊断和骨髓FCM的结果,最终获得明确诊断。2例分别为巨大纵隔肿块和腹块的患者仅靠骨髓形态学和骨髓FCM确诊为T—NHL和B—NHL。结论：多参数FCM能进一步明确白血病和NHL骨髓侵犯的诊断,对急性淋巴细胞白血病和NHL的病例还可同时获得T或B细胞来源和细胞分化早期或后期的参数,有助于临床诊断、鉴别诊断和治疗方案的确定。     

急性T淋巴细胞白血病/淋巴瘤分子遗传学研究进展

急性T淋巴细胞白血病/淋巴瘤(T-cell acute lymphoblastic leukemia/lymphoma,T-ALL/LBL)是定向于T细胞系的淋巴母细胞恶性肿瘤,具有高度侵袭性.近年来,许多研究致力于了解T-ALL/LBL的发病机制,寻找新的治疗靶点,开发毒性更小、效果更强、更加有针对性的药物.本文将从...     

弥漫性大B细胞淋巴瘤侵犯骨髓的病理学观察

 目的　探讨弥漫性大B细胞淋巴瘤（DLBCL）侵犯骨髓的病理学特点、诊断与鉴别诊断。方法　对24例DLBCL侵犯骨髓的骨髓活检HE染色切片进行形态学观察,20例免疫组化（IHC）法进行免疫表型分析。将其中10例髓外部位原发的NHL患者的骨髓与髓外部位瘤细胞的形态学进行对比观察。结果　DLBCL侵犯骨髓的方式依次为：弥漫型14 例,间质型 6例,混合型2例,结节型1 例,窦内型1例。侵犯程度为重度15例,中度4例,轻度5例。瘤细胞形态学类型为中心母细胞型21 例,免疫母细胞型3例。瘤细胞表达CD20、CD45RA、Pax5等一种或多种B细胞的标记。不表达CD3、CD45RO、CD5、CD10、TdT、CyclinD1、CD38、CD68、MPO。10例髓外原发淋巴瘤患者的骨髓与其髓外部位瘤细胞形态一致。结论　DLBCL侵犯骨髓多具有特殊的骨髓病理学特点。少数轻度、间质型浸润以及混有较多小淋巴细胞者, 免疫组化有助于鉴别诊断。骨髓活检对于DLBCL侵犯骨髓的诊断具有重要意义。     

64例淋巴瘤细胞白血病患者的病理免疫组化及骨髓流式免疫分型分析及临床意义

目的 分析淋巴瘤细胞白血病(LCL)患者骨髓流式免疫及病理免疫组化分型及临床意义。方法 64例LCL患者,均行病理免疫组化及流式细胞术(FC)检查。分析免疫组化及骨髓流式免疫分型各抗原表达情况,同时进行随访,分析LCL患者生存周期特点。结果 免疫组化及骨髓流式免疫分型均显示,25例T淋巴细胞型,39例B淋巴细胞型;免疫组化各抗原表达结果显示,T淋巴细胞型表达率最高的抗原为CD7,占比100.00%,其次为CD3,占比60.00%;B淋巴细胞型表达率最高的抗原为CD19,占比94.87%,其次为CD20,占比56.41%;骨髓流式免疫各抗原表达结果显示,T淋巴细胞型表达率最高的抗原为CD7,占比100.00%,其次为CD3,占比60.00%;B淋巴细胞型表达率最高的抗原为CD19,占比94.87%,其次为CD20,占比56.41%;25例T淋巴细胞型患者生存周期为1～40个月不等,中位生存周期为19.78个月,伴CD3表达缺失中位生存期为12.98个月,不伴CD3表达缺失中位生存期为9.55个月;39例B淋巴细胞型患者生存周期为3～60个月不等,中位生存周期为27.75个月,伴CD20表...     

华氏巨球蛋白血症的骨髓病理特点与鉴别

 目的　探讨华氏巨球蛋白血症（WM）的骨髓病理特点、诊断与鉴别。方法　19例WM患者行骨髓穿刺（BMA）及骨髓活组织检查（BMB）进行形态学观察,用流式细胞术（FCM）及免疫组织化学（IHC）方法进行免疫表型分析。结果　11例BMA示浆细胞样淋巴细胞增生。BMB示19例均见瘤细胞侵犯,其中17例主要为小淋巴细胞增生,2例主要为浆细胞样淋巴细胞增生。4例未见典型的浆细胞样淋巴细胞。骨髓侵犯呈弥漫型12例,结节型4例,间质型3例。FCM示14例瘤细胞CD+19、CD+20、CD+22、CD-5、CD-10。IHC示小淋巴细胞及浆细胞样淋巴细胞CD+20、Pax5+,浆细胞CD+38、CD+138、CD-20、Pax5-。结论　小淋巴细胞增生伴有浆细胞样分化是WM的典型骨髓病理组织学改变,IHC有利于识别淋巴细胞及浆细胞两种不同的细胞成分,形态学与FCM、IHC相结合有助于WM的诊断与鉴别。     

流式细胞术联合形态学检查对淋巴瘤骨髓累犯的诊断价值

目的 探讨流式细胞术(FCM)联合形态学检查对淋巴瘤骨髓累犯的诊断价值.方法 对52例淋巴瘤患者的骨髓标本行FCM、涂片及活组织病理切片检查,观察骨髓受累率、免疫表型数据和检查前后临床分期(CS)、国际预后指数(IPI)的变化.结果 6例霍奇金淋巴瘤(HL)切片法仅发现1例骨髓受累;46例非霍奇金淋巴瘤(NHL)中,骨髓受累FCM检出3l例,涂片法检出5例,切片法检出12例.FCM发现的3l例受累患者中,21例为早期浸润(瘤细胞＜5%);12例为小细胞淋巴瘤(SLL);6例同时表达T、B细胞抗原,1例弥漫大B细胞性淋巴瘤同时表达髓系抗原CD13、CD33;检查后,19例由原分期Ⅰ、Ⅱ、Ⅲ期升至Ⅳ期,18例进展型NHL的IPI提高.结论FCM联合形态学检查提高了骨髓受累的检出率,并能了解骨髓增生程度,提供免疫表型数据,尤对早期浸润和SLL声重要鉴别价值.准确的骨髓检查提高了患者CS和IPI.     

髓系／NK前体细胞急性白血病1例的诊断分析

目的 分析1例髓系／NK前体细胞急性白血病（M／NKPAL）的诊断过程,提高对M／NKPAL的认识。方法 对1例M/NKPAL采用细胞涂片染色、细胞化学染色方法和流式细胞术进行细胞形态学和免疫表型分析,并应用细胞遗传学和PCR技术进行染色体核型分析及T细胞受体、白血病融合基因的检测,同时结合相关文献进行分析。结果骨髓原始细胞为90.4％,绝大部分白血病细胞形态学类似急性淋巴细胞白血病L2型,过氧化物酶染色阴性,偶见Auer小体。免疫表型为CD34、HLA-DR、CD33、CD7、CD56、CD38阳性和cyCD3弱表达,而cyMPO、CD3、CD4等阴性。存在染色体核型异常,未检测到克隆性T细胞受体基因重排和白血病相关的融合基因。结论M/NKPAL临床少见,诊断复杂,仅依据形态学难以诊断,应注意与伴有髓系抗原表达的T淋巴细胞白血病、急性髓细胞白血病微分化型、T／髓系混合表型急性白血病和母细胞性NK细胞白血病／淋巴瘤等相鉴别。     

抗T淋巴细胞单克隆抗体治疗骨髓增生异常综合征

用抗T淋巴细胞单克隆抗体SMU3(抗CD3)和SMU8(抗CD8)治疗10例骨髓增生异常综合征(MDS),结果表明:2例明显进步,5例进步,白细胞和血红蛋白显著升高。治疗前CD4~ 细胞少,CD8~ 细胞多,CD4/CD8比值降低或倒置,HLA-DR抗原高表达,与对照组比较均有显著差异,治疗后T淋巴细胞亚群比例恢复,HLA-DR表达降低。T淋巴细胞各亚群比例失调和功能异常是MDS的诱发因素之一。     

流式细胞术在侵袭性NK细胞白血病诊断中的价值:一例报道并文献复习

 目的　分析侵袭性NK细胞白血病的临床特征及诊治方法,探讨流式细胞术（FCM）对其诊断的价值。方法　分析1例侵袭性NK细胞白血病患者的临床特征,并进行文献复习。结果　患者持续高热、肝脾进行性增大、血三系细胞减少,骨髓中可见不典型细胞,FCM检查示骨髓中NK细胞约占淋巴细胞的83.3 %,免疫表型为CD34-、CD2+、CD7+、CD3-、CyCD3+、CD5-、CD16+、CD56+、CD30-、CD4-、CD8-、CD117-、CD11c-、CD19-、CD45++、SSC+～++,TCR、IgH基因重排阴性,染色体正常,诊断为侵袭性NK细胞白血病。结论　侵袭性NK细胞白血病是一种少见的血液系统恶性疾病,临床表现多样、疾病进展迅速,早期容易误诊,FCM免疫分型结合骨髓细胞学涂片具有简便、快捷、可行、创伤性小的优势,在一些特殊情况下可作为首选检测手段。     

急性髓细胞白血病微分化型流式细胞术免疫分型分析

目的探讨流式细胞术（FCM）检测免疫表型在诊断急性髓细胞白血病微分化型（AML—M0）中的意义。方法采用多色FCM分析14例AML—M0病例的各相关抗原表达情况。结果14例AML—M0中,仅1例依据骨髓细胞形态学作出诊断,其余13例均依靠FCM作出明确诊断。在AML—M0中,髓系抗原CD33 14例（100％）表达阳性,CD13和CD117 9例（64％）表达阳性,CD34和HLA—DR12例（86％）表达阳性,一般成熟髓系相关抗原如CD16、CD10、CD14等均阴性,B和T淋巴细胞特异抗原如CD79a和CD3均为阴性,少数原始细胞表达细胞内髓过氧化物酶（MPO）、TdT。常常表达一些淋系但并不特异的抗原如CD7、CD2或CD19,但比淋巴细胞白血病表达的荧光强度弱。结论FCM免疫分型在AML—M0诊断中至关重要。     

The soluble form of CD83 is present at elevated levels in a number of hematological malignancies

Recombinant forms of soluble CD83 (sCD83) inhibit anti-tumor responses. In this analysis of circulating sCD83 levels we report that although >95% of acute myeloid leukemia (AML) and multiple myeloma (MM) patients have normal or only weakly elevated sCD83 levels, 20% of chronic lymphocytic leukemia (CLL) and 5/7 mantle cell lymphoma (MCL) patients have significantly elevated levels (>1 ng/ml). Isolated CLL cells both weakly expressed membrane CD83 (mCD83), and released sCD83 during in vitro culture. We conclude that malignant cells are a potential source of sCD83 and that it may have functional and/or prognostic significance in hematological malignancies, particularly CLL and MCL.     

Correlation between histology and immunophenotype in a series of 322 cases of non-Hodgkin's lymphoma

The non-Hodgkin's lymphomas (NHL) are a heterogeneous group of lymphoid neoplasms displaying a wide variation in cell morphology, histological patterns, immunological phenotype and prognosis. In this paper we compare the results of phenotypic investigation of 322 tissue biopsies with the histology based on the Kiel classification. Immunological analysis revealed that 81 per cent of these tumours were of B cell origin, 12 per cent of T cell origin and the remaining 7 per cent could not be characterized as representing either cell lineage. This last group included a number of cases which had received a histological diagnosis of true histiocytic lymphoma. The original morphological diagnosis, based on routine haematoxylin and eosion sections correlated with the immunologically determined phenotype in 86 and 93 per cent of the T- and B-cell cases respectively. The B cell tumours were phenotypically heterogenous with respect to immunoglobulin (Ig) heavy chain and B lymphocyte subset marker expression. IgG was most often found associated with NHL of cb/cc histology and a small subgroup of lymphocytic NHL. IgA expression was uncommon and occurred in combination with IgD and G in three cases and alone in two cases of NHL. The most common immunoglobulin isotype expressed was IgM this isotype occurred with IgD most often in lymphocytic and centrocytic NHL and less often in tumours of cb/cc histology. Whilst greater than 90 per cent of the lymphocytic NHLs expressed the CD5 antigen, between 20 and 75 per cent of B-cell tumours of other histologies also expressed this epitope. The CD10 antigen and the epitope recognized by the monoclonal reagent FMC7 were widely distributed on tumour cells from all histologies. TdT expression commonly regarded as a marker for immature cells was found in one case of follicle centre cell lymphoma. All cases of T cell NHL displayed marked heterogeneity for both pan T and T subset antigens which is significant in terms of the routine diagnosis of T NHL and with regard to the rational classification of node based T NHL. Unlike resting peripheral blood T cells, MHC class II, OKT 10 and CD25 epitopes were expressed reflecting activation of tumour populations.(ABSTRACT TRUNCATED AT 400 WORDS)     

恶性淋巴瘤骨髓受累的免疫表型特征

目的:探讨淋巴瘤骨髓受累的免疫表型特征。方法:采用流式细胞仪CD45/SSC设门方法对34例恶性淋巴瘤患者的骨髓标本进行检测,以骨髓涂片细胞学检查作阳性对照。收集骨髓受累患者的CD分子表达数据。结果:①对34例恶性淋巴瘤患者的骨髓应用流式细胞仪进行检测,发现23例阳性,阳性率67.65%(23/34),95%可信区间(51.92%,83.37%)。②该23例阳性患者中,非霍奇金淋巴瘤(NHL)19例,霍奇金淋巴瘤(HL)4例。NHL患者中B细胞来源免疫荧光单克隆抗体标记抗原出现频率最高的为CD19,CD20;T细胞来源标记抗原出现频率最高的为CD7。而在HL患者中出现频率最高的为CD9。结论:采用流式细胞仪CD45/SSC设门方法,发现非霍奇金淋巴瘤骨髓受累患者免疫表型特征为:B细胞来源:CD19、CD20;T细胞来源:CD7。霍奇金淋巴瘤为:CD9。     

ROR1 is expressed on hematogones (non-neoplastic human B-lymphocyte precursors) and a minority of precursor-B acute lymphoblastic leukemia

ROR1 is a receptor tyrosine kinase expressed during embryogenesis, on chronic lymphocytic leukemia (CLL) and in other malignancies. Hematogones (non-neoplastic B-lymphocyte precursors) express surface ROR1 at an intermediate stage of maturation that lacks CD34 or TdT. The neoplastic counterpart to hematogones is precursor-B acute lymphoblastic leukemia (B-ALL), but less than 10% of B-ALL express surface ROR1, and these ROR1+ B-ALL cases have an unusually high frequency of lacking CD34 and/or having t(1;19), a chromosomal translocation that defines a specific subtype of B-ALL.     

Expression of 1D8—A novel non-sialylated B-cell-associated carbohydrate epitope in lymphoproliferative disorders

The expression of a novel B-cell-associated carbohydrate epitope (1 D8) was studied by means of flow cytometry in 153 well defined cases of leukemias and lymphomas and 19 cases of lymphadenopathy used as controls. The 1D8 epitope was detected preferentially in proliferations of mature B-lymphocytes (11/15 CD20⁺ acute lymphoblastic leukemia (ALL), 14/ 16 chronic lymphocytic leukemia (CLL), 4/7 mantle cell non-Hodgkins lymphoma (NHL), 3/8 follicle cell NHL. However its expression did not appear lineage- or differentiation stage-restricted. Intensive expression on in vivo and in vitro-activated lymphocytes as well as in some high grade malignancies indicated a relationship to the functional state of cells. Bearing in mind the enhanced detection of 1D8 upon desialylation, the epitope might be involved in the regulation of adhesion/migration potential of normal leukocytes and their malignant counterparts.     

Incidence of phenotypic aberrations in a series of 467 patients with B chronic lymphoproliferative disorders: basis for the design of specific four-color stainings to be used for minimal residual disease investigation.

Multiparameter immunophenotypic analysis of neoplastic cells has proven to be of great help for the investigation of minimal residual disease in acute leukemias; however, its utility has not been systematically explored in B cell chronic lymphoproliferative disorders. The aim of the present study was to investigate the incidence of phenotypic aberrations in a series of 467 consecutive leukemic B cell chronic lymphoproliferative disorders through the comparison of the phenotypic characteristics of tumor vs normal peripheral blood (n = 10) and bone marrow (n = 10) B cells, in order to explore the applicability of this strategy for minimal residual disease monitoring. An additional goal of our study was to evaluate the sensitivity of multiparameter flow cytometry for the detection of minimal residual disease in leukemic B cell chronic lymphoproliferative disorders through dilutional experiments (n = 19). From the patients analyzed 382 corresponded to B cell chronic lymphocytic leukemia/small lymphocytic lymphoma (353 typical and 29 atypical); five to prolymphocytic leukemia; 13 to hairy cell leukemias; 12 to lymphoplasmacytic lymphomas; 14 to splenic marginal zone lymphomas; 22 were follicular lymphomas; and 19 mantle cell lymphomas. The following triple stainings were systematically applied to both normal and leukemic samples: FMC7/CD5/CD19, CD22/CD23/CD19, CD103/CD25/CD19, CD10/CD11c/CD19 and sIg/sIg(lambda)/CD19. Overall, 98% of the leukemic B cell chronic lymphoproliferative disorders cases displayed aberrant phenotypes at diagnosis with no significant differences being found between cases analyzed in peripheral blood vs bone marrow samples. The most common types of aberrant criteria detected included asynchronous antigen expression (92%) and antigen over-expression (54%); abnormally light scatter characteristics were found in 17% of the cases. Most of the cases studied (90%) displayed four or more phenotypic aberrations. Once patients were divided according to the different diagnostic subgroups, the overall incidence of aberrant phenotypes ranged from 79 to 80% among atypical B cell chronic lymphocytic leukemia/small lymphocytic lymphoma and prolymphocytic leukemia to 97% of follicular lymphoma and 100% of typical B cell chronic lymphocytic leukemia/small lymphocytic lymphoma, hairy cell leukemia, lymphoplasmacytic lymphomas, splenic marginal zone lymphomas and mantle cell lymphomas. Based on the aberrant phenotypes detected unique four-color stainings could be built for the specific identification of aberrant phenotypes. These include CD22/CD23/CD19/CD5 and sIg(kappa)/sIg(lambda)/CD19/CD5 for lymphocytic leukemia/small lymphocytic lymphoma and prolymphocytic leukemia, CD103/CD25 or CD22/CD19/CD11c for hairy cell leukemia, FMC7/CD22/CD19/CD103 and sIg(kappa)/sIg(lambda)/CD22/CD19 for splenic marginal zone lymphomas, CD22/CD23/CD19/CD10 for follicular lymphomas and CD10/CD22/CD19/CD5 for mantle cell lymphomas. Serial dilutional experiments showed that the sensitivity level of immunophenotyping ranges between 10(-4) and 10(-5). In summary, the present study shows that immunophenotypic analysis allows the identification of aberrant phenotypes in 98% of leukemic B cell chronic lymphoproliferative disorders and these phenotypes can be used for minimal residual disease monitoring with a sensitivity limit of 10(-4)-10(-5).     

Prediagnostic serum sCD27 and sCD30 in serial samples and risks of non-Hodgkin lymphoma subtypes

Elevated prediagnostic serum levels of the immune activation markers sCD27 and sCD30 have been associated with non-Hodgkin lymphoma (NHL). However, the use of a single sample per participant in these studies has limited etiologic inferences. We report findings, overall and by NHL subtype, from a case–control analysis (422 cases, 434 controls) within the Janus Serum Bank with two samples per subject collected on average 5 years apart. Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) was associated with elevated sCD27 in the later, but not earlier, prediagnostic sample (odds ratio [OR] 4.2, 95% confidence interval [CI] 1.5–11.6 and 1.7, 0.7–4.7 per log increase, respectively) in analyses adjusting for both analytes, while follicular lymphoma (FL) was associated with elevated sCD30 in both the later and earlier samples (OR 2.9, 95% CI 1.4–4.4 and 2.3, 1.2–4.4, respectively). CLL/SLL cases were significantly more likely than controls to have higher sCD27 in the later vs. earlier sample (OR 1.4, 95% CI 1.1–1.9 per standard deviation increase); no such difference in sCD30 was apparent for FL. In a joint analysis, NHL cases were more likely than controls to have below-median sCD27 in the earlier sample and above-median sCD27 in the later sample (OR 1.5, 95% CI 1.0–2.3). For sCD30, the association between sCD30 and FL was confined to subjects with above-median analyte levels in both samples (OR 2.5, 95% CI 1.1–5.9). Our findings are compatible with elevated sCD27 representing a disease-induced effect and sCD30 representing a marker of increased FL susceptibility.     

Expression of inhibitor of apoptosis proteins in B-cell non-Hodgkin and Hodgkin lymphomas

BACKGROUND: Inhibitor of apoptosis proteins (IAPs) inhibit apoptosis by binding specific caspases, and possibly by other mechanisms. Eight IAPs have been identified in humans, of which cIAP1, cIAP2, and XIAP are well known. IAPs are being investigated as potential treatment targets in cancer patients. METHODS: cIAP1, cIAP2, and XIAP were assessed in lymphoma cell lines, 240 B-cell non-Hodgkin lymphoma (NHL) tumors, and 40 Hodgkin lymphoma (HL) tumors. RESULTS: All IAPs were expressed in most NHL and all HL cell lines. In NHL tumors, cIAP1 was expressed in 174 (73%), cIAP2 in 115 (48%), and XIAP in 37 (15%). cIAP1 was positive in all precursor B-cell lymphoblastic lymphoma/leukemia (LBL) and nodal marginal zone B-cell lymphoma (MZL), over 90% of follicular lymphoma and diffuse large B-cell lymphoma (DLBCL), and approximately 50% to 60% of myeloma, Burkitt lymphoma (BL), lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM), small lymphocytic lymphoma/ chronic lymphocytic leukemia (SLL/CLL), extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue (MALT-lymphoma), splenic MZL, and mantle cell lymphoma. cIAP2 was positive in all MALT-lymphoma, over 90% of precursor B-cell LBL (94%), most BL (75%), LPL/WM (71%), and SLL/CLL (67%), and approximately 40% to 60% of follicular lymphoma, myeloma, and DLBCL. XIAP was positive most cases of precursor B-cell LBL (57%) and approximately 30% to 40% of nodal MZL, BL, and DLBCL. In HL tumors, cIAP1 was positive in 30 (75%), cIAP2 in 27 (68%), and XIAP in 23 (58%), and did not correlate with histologic type. CONCLUSIONS: Differential expression of IAPs in B-cell lymphomas suggests differences in pathogenesis that may have implications for novel treatment strategies targeting IAPs.     

Rituximab Therapy of B-Cell Neoplasms

The development of rituximab, an anti-CD20 monoclonal antibody, represents a revolutionary advance in the therapy of hematological malignancies. Rituximab was approved in 1997 by the Food and Drug Administration for the treatment of relapsed or refractory, CD20+, B-cell, low-grade or follicular non-Hodgkin's lymphoma (NHL). Recent studies have documented activity of rituximab in other CD20- expressing hematological malignancies including mantle cell lymphoma, small lymphocytic lymphoma, aggressive NHL, chronic lymphocytic leukemia, and Waldenstrom's macroglobulinemia. When used in combination with cytotoxic chemotherapy, rituximab achieves response rates of 90%–95% in low-grade follicular and aggressive NHL patients. Currently, rituximab is undergoing intensive investigation in several large phase II and III trials, both as a single agent and in combination with chemotherapy. Clinical research will help define the ultimate role of this agent and its potential impact on survival of patients with B-cell neoplasms. This article describes current clinical trials with rituximab and discusses their significance.