Malignant Lymphomas in Pakistan According to the WHO Classification of Lymphoid Neoplasms

Objective: To determine the spectrum of malignant lymphomas in our set up, according to the WHO classification. Methods: All the cases diagnosed as malignant lymphoma, during the year 2005, were retrieved from the institution based tumour registry record and classified according to WHO criteria depending on the immunohistochemical results of a panel of lymphoma markers. Results: The male to female ratio was 2.5:1 for almost all types of malignant lymphomas. The age range was 3 to 80 years. The frequency of Hodgkin's lymphoma, Burkitt's lymphoma and lymphoblastic lymphoma were higher amongst the children, whereas follicular lymphomas, mantle cell lymphoma and CLL/SLL were more frequently reported in 5th, 6th and 7th decades. Of the total cases 62% were nodal and 38% extranodal (majority in the GI tract). Non Hodgkin's lymphoma was more (73%) frequent than Hodgkin's disease. Mixed cellularity and nodular sclerosis were the main histological variants of Hodgkin's disease. Conclusions: Immunohistochemistry is not very frequently used in our set up and also at very few other centres. Therefore, its application should be encouraged to raise the quality of data on lymphoid neoplasms and contribute to their control.     

The Association of c-myc Rearrangements with Specific Types of Human Non-Hodgkin's Lymphomas

The function of c-myc in physiology is only partially known. Its product has DNA binding properties and plays a role in the control of proliferation and differentiation. In general, increased c-myc expression leads to proliferation and abolishment of differentiation. The involvement of c-myc in mouse plasmacytomas and human Burkitt's lymphoma is well known: due to chromosomal translocation c-myc comes under the influence of regulatory elements of immunoglobulin genes, leading to increased expression of the gene and proliferation of the cells. In man, the chromosomal translocations may occur within the increased pool of (pre) B-cells due to Epstein Barr virus (EBV) and malaria infection with subsequent immunosuppression. Apart from these early (primary?) events in lymphomagenesis, c-myc is also often involved in tumour progression, probably by a similar mechanism.

Different types of c-myc involvement are associated with specific types of lymphoma: there are differences between endemic, sporadic and ileocecal Burkitt's lymphoma as well as between those and primary extranodal large cell lymphoma and large cell lymphoma which has progressed. These differences are associated with the differentiation of the involved lymphoid cells and may point to the stage of differentiation in which the oncogenic event occurred.     

Non-Hodgkin's Lymphomas in Elderly Patients

Based on population statistics and institutional reviews, the median age of patients developing non-Hodgkin's lymphomas (NHL's) is around 65 years. A review of retrospective studies suggesting that increasing age imparts an adverse prognosis in patients with NHL's is presented. Interpretation of this data is often confounded by referral bias of patients to specialized centres, multiple other NHL-related risk factors and inadequate chemotherapy administration due to age and toxicity related dose reductions. These factors, as well as alterations in tumour-host biology and comorbid diseases which result in changes in pharmacokinetics and pharmacodynamics, are discussed as possible reasons for poorer outcome in the elderly. In an effort to develop better tolerated and thus more effective combination chemotherapy for older patients, a number of prospective single arm and randomized clinicaltrials of novel regimens have been undertaken. Improved rates of disease remission and overall survival appear often to have been achieved at the expense of greater morbidity and mortality. Ongoing attempts to improve the therapeutic index include the application of chronic oral chemotherapy, brief duration intensive therapy and fractionation of standard drug doses as well as incorporation of myelo-preserving haematopoietic growth factors. The possibility of developing flexible, “customized” therapy for elderly patients is discussed.     

Clinicopathological evaluation of the Revised European-American Classification of Lymphoid Neoplasms (REAL) in Japan.

After the publication of a Revised European-American Classification of Lymphoid Neoplasms (REAL classification) in 1994, there have been reports from Europe and America regarding its practical utility and clinical significance. However, no studies have been published from Eastern countries including Japan. It has been well recognized that the distribution of malignant lymphoma in Japan is quite different from that seen in Western countries. In addition, some new entities have also been described in the REAL classification. Therefore, it seems important to examine its practical utility and clinical significance in Japan. Of the 579 cases reviewed, approximately 68% were B-cell non-Hodgkin's lymphoma (NHL) followed by 27% T-cell lymphomas. Hodgkin's disease (HD) comprised only 5% of all cases, making the ratio of NHL to HD 20.6. The most common type was diffuse large B-cell lymphoma which represented about 37% of all cases. Peripheral T-cell lymphomas, unspecified (PTCL), occurred in 15% whereas marginal zone B-cell lymphoma followed (14.9%). However, follicle center lymphoma (FCL) was less common (4.4%) as has been previously reported. We evaluated the clinical significance of the new REAL classification in 244 cases. International Prognostic Index (IPI) was a powerful predictor of survival (p<0.0001), and the immunophenotype was significant (p<0.05). Furthermore, here, we also attempt to establish a prognostic scheme based on the histologic type. In conclusion, the REAL classification appears to be useful and clinically significant in Japan.     

Non-Hodgkin's Lymphomas in Turkey: Eighteen Years'Experience at the Hacettepe University

In this retrospective study, 470 patients with non-Hodgkin's lymphoma (NHL) who had been followed in the Hacettepe University Medical Oncology Department between 1973 and 1990, were evaluated to establish their epidemiologic, clinical and therapeutic characteristics. Out of 470 patients, 302 (62.2%) were male and 168 (37.8%) were female. The ages ranged from 16 to 85, with a median of 44 years. Constitutional symptoms were present in 46.4% of the patients. According to the Working Formulation, low, intermediate, and high-grade lymphomas comprised 33.4%, 54.9%, and 12.7%, respectively. The most common extranodal presentation was gastrointestinal. The chemotherapy regimens most commonly used were CVP (cyclophosphamide, vincristine, prednisone), BCNOP (bleomycin, cyclophosphamide, mitoxantrone, vincristine, prednisone), CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and CHOP-Bleo (cyclophosphamide, doxorubicin, vincristine, prednisone, bleomycin). The response rates and the survival figures attained with these regimens were not statistically significantly different ( P > 0.05). In the Cox multivariate model, pathologic grade, leukopenia, responsiveness to chemotherapy, bone marrow involvement and age were the important factors influencing the disease-free survival, while responsiveness to chemotherapy, age, presence of constitutional symptoms, pathologic grade, extranodal presentation and stage were the important factors influencing the overall survival. The distribution of NHL according to grade and stage was similar to that in western societies, while constitutional symptoms and lymphomas of the small intestine including immunoproliferative small intestinal disease were more common in Turkey.     

Familial Lymphomas A review of the literature with report of cases in Jerusalem

Non-Hodgkin's lymphoma Although non-Hodgkin's lymphoma (NHL) is a common disorder, there are relatively few reports occurring in family groups. Extensive review of the literature by Ladish et al. in 1978¹ revealed 38 multiple-case families with NHL, most of whom were sibpairs, either sibs alone (6.3%) or sibs plus other relatives (13%), including a pair of monozygotic twins². The mean age of diagnosis in these cases was 23.5 years compared with 42.3 years for the general population with NHL. About half of the familial cases were extranodal (44 cases), primarily involving the gastro-intestinal tract in 26 cases, with the distal small bowel and cecum being most frequently affected. No histologic type was predominant in the affected families³. As described for Hodgkin's disease (HD)^4,5 increased incidence with small family size has been observed for NHL; however, no change in risk has been seen with increasing family size⁶.     

MACOP-B vs F-MACHOP Regimen in the Treatment of High-Grade Non-Hodgkin's Lymphomas

A prospective randomized study on aggressive non-Hodgkin's lymphomas was conducted by investigators at several Italian institutions with the intent of comparing two third-generation conceptually different regimens: the regimen containing methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B), a short-term continuous twelve-week therapy, and F-MACHOP (5-fluorouracil, methotrexate with leucovorin rescue, cytarabine, cyclophosphamide, doxorubicin, vincristine, and prednisone), a monthly intensive cyclic treatment combining prednisone with six active non-cross-resistant cytotoxic drugs. The goals of this study were the response rate, relapse-free survival, and incidence of hematologic and nonhematologic toxicities.

Two hundred-eighty-six patients included between 15 and 60 years fulfilled the criteria for entry to the study; 140 patients were treated with MACOP-B and 146 with F-MACHOP. The minimum follow-up was 24 months. Clinical characteristics of all patients were similar and known prognostic factors were equally distributed between the two groups. Complete remission (CR) was achieved by 61% and 67% of the patients treated with MACOP-B and F-MACHOP, respectively; 4% and 6% were primarily resistant, 2% and 5%, respectively, died of causes directly related to therapy. At 50 months, 74% of all CR patients were alive without disease and there were no significant differences in relapse-free survival between the two groups: 75% in the F-MACHOP group and 73% in the MACOP-B group at 50 months. There was a higher incidence of mucositis among patients treated with MACOP-B than among those given F-MACHOP (11% vs 3.5%). Higher incidences of severe cytopenia (51% vs 21%) and of fatal sepsis (5% vs 2%) were recorded among patients treated with F-MACHOP than with MACOP-B.

The third-generation regimens, F-MACHOP and MACOP-B, are as effective as other regimens. A prognostic analysis taking into account the principal covariates (age, symptoms, stage, serum lactate dehydrogenase, mediastinum involvement, bulky disease, histology, therapy, and dose intensity) was assessed for their impact on complete response rate incidence and on relapse rate from complete response by multivariate analysis. The linear logistic model showed that symptoms, advanced stage, mediastinum involvement, and bulky disease are prognostic factors that increase the risk of a lower rate of complete response. These data confirm the important role of a pretreatment selection for the poor-risk patients and, on the basis of these parameters, it will probably be possible to consider these patients for high-dose therapy with autologous bone marrow transplantation or autologous hematopoietic stem-cell support.     

CTVP方案治疗侵袭性B细胞非霍奇金淋巴瘤85例临床疗效分析

评估含吡喃阿霉素（THP）及长春地辛（VDS）的CTVP方案治疗非霍奇金淋巴瘤（NHL）的近期疗效、远期生存及不良反应。方法：收集2000年1月至2005年12月间应用CTVP方案治疗的资料完整的侵袭性B细胞NHL患者85例,分析其近期疗效、远期生存及不良反应。结果：85例患者中初治74例,复治11例,全部病例均可评价疗效,一线治疗CR 55.4%,有效率68.9%,临床受益率86.0%,二线治疗有效率45.5%,临床受益率63.6%。随访至2009年12月,中位随访时间为69个月（6～102个月）,1、3、5年生存率分别为82.4%、71.5%和60.7%,中位生存期75个月（6～99个月）,骨髓抑制、胃肠道反应、乏力、外周神经毒性和脱发为主要不良反应。结论：采用含THP和VDS的CTVP方案治疗NHL疗效较好,毒性较低,远期生存率较高,值得临床进一步研究。     

CDK1 and Cyclin A Expression is Linked to Cell Proliferation and Associated with Prognosis in Non-Hodgkin's Lymphomas

Cellular proliferation is regulated by several kinasic complexes associating cyclins and their catalytic subunits cyclin-dependent kinases (CDKs). In order to gain insight into the mechanisms underlying proliferation in non-Hodgkin's lymphoma (NHL), we examined the expression of certain cell cycle regulatory proteins normally expressed in lymphoid cells, cyclins A, B, D3 and E and cdkl, 2, 4, and 6. In 70 patients presenting a previously untreated lymphoma, cyclins and CDKs were studied by Western blotting and quantified by densitomerry. Flow cytometry study of DNA content was canied out for all patients in order to study cell proliferation and level of ploidy. The results were analysed according to the histological types, the immunological phenotypes of the lymphomas and the outcome of the patients.

Cdk1 and cyclin A were correlated with the percentage of cells in S and S+G2/M phases, and significantly different according to the grade of malignancy, with the lowest expression in low-, and the highest in high-grade NHL according to the Working Formulation. In B-NHLs, cdkl, cyclin A, as well as cdk2, cyclin D3 and E expression was higher in the aneuploid than in the euploid group. Our results point to some particularities of cell cycle regulation in two lymphoma sub-types: I) a low expression of cyclin D3 and cdk6 in mantle cell lymphomas and 2) a discrepancy between the high proliferative activity and the level of protein expression in Burkitt's lymphomas. CDKl and cyclin A showed a significant prognostic value for achievement of complete remission (Cdk 1) and for both disease free (cyclin A) and overall survival (cyclin A and cdkl): low protein level was associated with the best prognosis in B-NHLs.

Our results show that differential cell cycle regulating protein expression may be associated with different biological and clinical behaviour of NHLs and confirm the usefulness of the study of cell cycle regulation as a tool for understanding lymphoid malignancies.     

Expression of P-Glycoprotein in Non-Hodgkin's Lymphomas

Drug resistance has been shown to be associated with the expression of P-glycoprotein (P-gp), the product of the mdr-1 gene. In the present study the expression of P-gp in 57 cases B-cell non Hodgkin lymphoma NHL was assessed before chemotherapy. Six cases of reactive lymphoid tissue and 11 cases of solid tumors were also studied. The expression of P-gp was evaluated by immunocyto- and histochemical methods, using three different Monoclonal Antibodies C219, JSB-1 and MRK16 directed against separate epitopes of P-gp.

Comparable frequencies of cases positive for P-gp were found in low grade (6/40) and high grade (3/17) lymphomas. The pattern of staining was predominantly cytoplasmic, although a Golgi-associated dot like pattern of staining was also seen, mostly with JSB-1 MAb. Both cases of Hairy cell leukemia were P-gp positive. P-gp expression was also found in the endothelium of small capillaries and some high endothelial venules, as well as in macrophages, in both lymphomas and reactive lymphoid tissues. P-gp expression was found in a low frequency in NHL, suggesting that clinical drug resistance may already be predicted at the time of diagnosis and thus may serve as a guide in the choice of chemotherapeutical regiment.     

Non-Hodgkin's lymphoma in the Netherlands: results from a population-based registry

The Comprehensive Cancer Centre West (CCCW) population based non-Hodgkin's lymphoma (NHL) registry contains information on all newly diagnosed NHL patients living in the region covered by the CCCW. Patients were entered from June 1st 1981 to December 31st 1989. Follow-up is still ongoing, median follow-up is 113 months (1-191 months) for patients alive. In this study, patient and tumor characteristics, data on patterns of care, response and (relative) survival are described. As follicular lymphomas and diffuse large B-cell lymphomas are the most frequently occurring NHL subtypes in the database, a separate analysis is performed to characterize the clinical picture of these disease entities in the CCCW population. Our data illustrate that NHL patients in the general population are substantially older than patients included in trials and hospital based series. Due to older age, treatment is withheld or adapted for a substantial number of patients. The resulting survival and relative survival rates are a reflection of these choices.     

原发骨非霍奇金淋巴瘤临床分析

目的:探讨原发骨非霍奇金淋巴瘤的临床特点、诊断、治疗及预后。方法:选择1970年11月～2003年2月我院收治的21例原发于骨的非霍奇金淋巴瘤,其中Ⅰ期14例(66.7%),Ⅱ期2例(9.5%),Ⅳ期5例(23.8%)。弥漫性大B细胞型12例(57.1%),混合细胞型4例(19.0%),小淋巴细胞型1例(4.8%),T细胞型1例(4.8%),未分型3例(14.3%)。采用单纯放疗6例(28.6%),放疗和化疗综合治疗15例(71.4%)。结果:中位随访86个月,2例(9.5%)局部复发,9例(42.9%)出现远处受侵,3年、5年、10年无进展生存率分别为56.7%、38.9%、29.1%;3年、5年、10年总生存率分别为69.1%、42.2%、42.2%。结论:原发于骨的非霍奇金淋巴瘤首选放疗和化疗的综合治疗;放疗剂量推荐45Gy～46Gy。     

大肠原发非何杰金氏恶性淋巴瘤

本文报告23例大肠原发非何杰金氏恶性淋巴瘤。其特点如下;1.本病少见,占同期收治大肠恶性肿瘤的1.9％。2.男∶女=1.9∶1;平均43.6岁(>41岁占65.3％)。3.升结肠发病多(69.6％)。全组均为B细胞源性NHL。4.本组除1例直肠经咬检术前获明确诊断外,余均为术后病理证实。5.本组5年生存率为31.6％,比大肠癌差。而手术切除率为100％, 又比大肠癌要好。6.浆膜受累,淋巴结转移,病期早晚直接影响预后。7.术后放疗 化疗可使术后单纯化疗的5年生存率从25％提高到50％。     

Fine-Needle Aspiration Cytology and Immunocytochemistry of Abdominal Non-Hodgkin's Lymphomas

The cytomorphology and immunologic characteristics of cells obtained by fine-needle aspiration biopsy of 34 consecutive patients with abdominal lymphomas were analyzed. Nineteen patients had no previous diagnosis, while 15 had previously known or suspected lymphomas. On cytology 21 high-grade and 13 low-intermediate-grade lymphomas were diagnosed. Immunologic characterization of aspirated cells identified one T-cell and 33 B-cell neoplasms. A monoclonal light chain expression was detected in 27 of the B-cell lymphomas. The results were in good agreement with those from histologic (n = 19) and immunohistochemical (n = 5) evaluations. The value and accuracy of fine-needle aspiration cytology in conjunction with immunocytochemistry are detailed.     

CHVmP-VB方案治疗恶性非霍奇金淋巴瘤

〔目的〕评价CHVmP-VB方案治疗中、高度恶性非霍奇金林巴瘤（NHI）的疗效和毒性。[方法]22例中、高度恶性非霍奇金淋巴瘤接受CHVmP-VB方案（环磷酰胺,阿霉素,鬼臼噻吩甙,泼泥松,长春新碱,博莱霉素）化疗。［结果］2例仅化疗1周期而剔除。可评价疗效18例,CR15例,PR3例,有效率1000％（18／18）,CR率833％（15／18）。复治1例,获PR。可评价毒性20例,3－4度白细胞减少50.0％（按病例数）和21．8％（按周期数）;3度血红蛋白减少15.0％（按病例数）和2．7％（按周期数）;血小板减少均为1－2度。非血液学毒性有恶心、呕吐85．0％,3度5．0％;肝功能异常45．0％,多为1度;脱发100．0％,3度25％。[结论]CHVmP－VB方案治疗中、高度恶性NHL疗效较好,主要毒性为血液学毒性、恶心呕吐和脱发,均可耐受。值得与常用的CHOP方案进一步比较。     

18例原发性结外型非何杰金淋巴瘤临床分析

恶性淋巴瘤有少部分患者可首发于淋巴结外，本文报告18例原发于结外的非何杰金淋巴瘤，其中发生于胃肠道的9例，头颈部6例，其他部位少见。病理学特点多为弥漫型。手术在结外非何杰金淋巴瘤的诊断和治疗中占首要地位。本组结外非何杰金淋巴瘤首选手术16例，首选化疗2例，总的完全缓解（CR）为13例，占72％。     

培美曲塞为主的化疗方案治疗中老年非霍奇金淋巴瘤回顾性分析CSCD

目的回顾性分析培美曲塞为主的化疗方案治疗中老年非霍奇金瘤患者的安全性及有效性。方法回顾性收集2016年11月至2018年10月中国医学科学院肿瘤医院收治的以培美曲塞为主的化疗方案治疗的非霍奇金淋巴瘤患者临床资料,并对相关文献进行系统性综述。结果共纳入10例非霍奇金淋巴瘤患者,7例为弥漫大B细胞淋巴瘤,2例为血管免疫母T细胞淋巴瘤,1例为结外NK/T细胞淋巴瘤。肿瘤复发或一线治疗进展后接受培美曲塞为主的化疗方案,弥漫大B细胞淋巴瘤有4例达到部分缓解,3例疾病进展,出现的不良反应主要为Ⅰ~Ⅱ度骨髓抑制及胃肠道反应。结论培美曲塞为主的化疗方案治疗弥漫大B细胞淋巴瘤患者,尤其是原发性中枢神经系统淋巴瘤,可能有一定的有效性,且安全性可控。     

Mutations of the Retinoblastoma Gene in Human Lymphoid Neoplasms

The inactivation or loss of tumor suppressor genes (anti-oncogenes) has been implicated as a mechanism central to the pathogenesis of many solid tumors. More recently, we and others have identified a role of one rumor suppressor gene, the retinoblastoma gene, in the development of human lymphoid lymphoma and leukemia. Here we review the involvement of the retinoblastoma gene in the control of normal lymphocyte cell division and the consequences of inactivation of the retinoblastoma gene for the development of lymphoid neoplasia. Our survey has disclosed a broad involvement of retinoblastoma gene inactivation in a wide variety of non-Hodgkin's lymphomas and lymphocytic leukemia. Based on these early findings, it appears likely that tumor suppressor genes may well be involved in many hematopoietic neoplasma.     

美罗华联合CTOP方案治疗B 细胞非霍奇金淋巴瘤35例临床分析

目的:评价美罗华联合环磷酰胺、吡柔比星、长春新碱、泼尼松（R-CTOP 方案）治疗B 细胞非霍奇金淋巴瘤的疗效及不良反应,分析影响疗效的相关因素。方法:回顾性分析我院35例经病理证实为CD20+ 的B 细胞非霍奇金淋巴瘤患者的临床资料,评估R-CTOP 方案化疗的疗效及不良反应,分析性别、年龄、疾病分期、病理类型、LDH 水平及IPI 评分等影响疗效的相关因素。结果:35例患者中33例可评价疗效,其中完全缓解（CR）17例（51.5%）,部分缓解（PR）11例（33.3%）,有效率（CR+PR）84.8% 。23例初治患者中,CR13例（56.5%）,PR8 例（34.8%）,有效率（CR+ PR）91.3% ;10例复发难治患者中,CR4 例（40%）,PR3 例（30%）,有效率70% 。疗效与性别、疾病分期、病理类型、LDH 水平及IPI 评分等因素无显著相关,年龄对疗效有一定影响（P=0.012 ）。 35例患者中无治疗相关死亡,不良反应主要为骨髓抑制（Ⅲ～Ⅳ度白细胞下降32.1%）,心脏毒性和脱发较轻,主要为Ⅰ～Ⅱ级反应。其它不良反应经对症处理后均可耐受。结论:R-CTOP 方案治疗B 细胞非霍奇金淋巴瘤有效率高且不良反应轻微,可作为治疗B 细胞非霍奇金淋巴瘤特别是老年非霍奇金淋巴瘤患者的优先选择。      

108 例非霍奇金淋巴瘤预后因素分析

目的:分析非霍奇金淋巴瘤（NHL ）的预后相关因素,探讨NHL 患者入院时外周血淋巴细胞绝对计数的预后价值。方法:回顾性分析2000年1 月至2008年1 月间108 例非霍奇金淋巴瘤患者的临床特征,结合随访资料,应用SPSS14.0 软件进行统计分析,采用Kaplan-Meier 法对生存概率进行评估,进一步采用Cox 回归模型对单因素分析中有统计学意义的参数进行多因素分析。结果:108 例非霍奇金淋巴瘤患者中,男女比例约为1. 5:1,中位年龄48岁。治疗前,61.1% 的患者为Ann ArborⅠ～Ⅱ期,ECOG 体力状态（performance status）评分0～1 的患者约占总数的93% ,乳酸脱氢酶升高见于19.2% 的患者,80.6% 的患者属于IPI低危组。入院时外周血淋巴细胞绝对计数减少（ALC ≤1 × 109/L ）见于35.2% 的患者,29.6% 的患者有贫血（Hb≤110g/L）,26.9% 的患者伴有B 症状。ALC>1 × 109/L 患者70例,平均Hb为129.2 ± 17.5g/L,而ALC ≤1 × 109/L 患者38例,平均Hb为98.1 ± 20.6g/L（P<0.05）。 全组患者中位随访时间2 年,中位生存时间2.3 年,2 年和 5 年的总生存率分别为73.2%和39.6%。单因素生存分析显示,ALC ≤1 × 109/L、Hb≤110g/L、B 症状及国际预后指数（IPI）≥2 是NHL 的不良预后因素。多因素分析显示,ALC ≤1 × 109/L 、B 症状及IPI≥2是NHL 的独立不良预后因素。结论:外周血淋巴细胞绝对计数及B 症状是独立于国际预后指数之外的非霍奇金淋巴瘤预后指标。临床上,根据IPI 及简单的临床参数ALC 和B 症状判断NHL 预后,对实施个体化治疗可能具有更大实用价值。