Characteristics and prognosis of KI-1 positive anaplastic large cell lymphoma in Asians

Background : Ki-1 positive anaplastic large cell lymphoma is a rare type of non-Hodgkin's lymphoma (NHL), and has not been extensively described in Asian patients.
Aim : To evaluate the clinical characteristics, prognostic factors and treatment outcome of Ki-1 positive lymphoma in an Asian community.
Methods : A retrospective analysis of all patients with CD30 antigen positive anaplastic large cell lymphoma from 1987 to 1996 in a single institution.
Results : Of 218 patients with NHL, ten (5%) were identified with Ki-1 positive anaplastic large cell lymphoma. Eight were Chinese, two Indians. The male: female ratio was 1.5:1, and the median age was 32 years. Seven patients presented with B-symptoms, and five had stage III/IV disease. The majority (seven of ten) was low-or low-intermediate risk according to the International Prognostic Index (IPI). Four out of five cases immunophenotyped showed a T-cell origin. Five out of eight patients who received first-line combination chemotherapy achieved a complete remission. Two relapsed, with one being re-induced into a durable second remission. One patient with recurrent cutaneous lymphoma received solely radiotherapy and was disease-free at 20+ years from diagnosis. At analysis, two patients had died, five were disease-free at four, 27, 78, 89 months and 20 years respectively, and three were alive with disease. The IPI appears to have prognostic significance.
Conclusion : Incidence and clinical characteristics in our Asian patients were similar to those described in Western populations. The IPI appears to have prognostic relevance. In approximately one-third of patients, long term survival can be achieved with standard treatment.     

Prognostic factors in childhood anaplastic large cell lymphoma: results of a large European intergroup study

To study prognostic factors of progression/relapse, data concerning 225 children enrolled between 1987 and 1997 in Berlin-Frankfurt-Münster, Société Fran?aise d'Oncologie Pédiatrique and United Kingdom Children's Cancer Study Group prospective studies for the treatment of anaplastic large cell lymphoma (ALCL) were merged. Median follow-up was 9.3 years. Five-year overall survival and event-free survival of the whole population was 81% (95% confidence interval, 76%-86%) and 69% (63%-74%), respectively. B symptoms, mediastinal involvement, skin lesions, visceral involvement, St Jude stage 3-4, Ann Arbor stage 3-4, and elevated lactate dehydrogenase increased the risk of progression/relapse in the univariate analysis. In the multivariate analysis, 3 factors remained significant: mediastinal involvement (relative risk [RR] = 2.1 [1.2-3.5]), visceral involvement defined as lung, liver, or spleen involvement (RR = 2.1 [1.3-3.6]), and skin lesions (RR = 1.9 [1.1-3.2]). Five-year progression-free survival (PFS) of the 81 patients with none of these risk factors was 89% [82%-96%], contrasting with a 5-year PFS of 61% [53%-69%] in the 144 patients with at least 1 risk factor (RR = 4.4 [2.2-8.9; P < .001). In conclusion, 3 factors associated with an increased risk of failure in childhood ALCL have been defined: mediastinal involvement, visceral involvement, and skin lesions.     

Recurrent childhood anaplastic large cell lymphoma: a retrospective analysis of registered cases in Japan

This report presents a retrospective study of 26 Japanese children with recurrent anaplastic large cell lymphoma. The first relapses were documented at a median of 10.5 months after the initial diagnosis. Twenty-four patients achieved a second remission. After a median follow-up period of 47 months, 18 patients are still alive: 15 patients are in second complete remission (CR), three patients are in third CR or later. The 5 year overall and relapse-free survival rates were 61 +/- 12% and 51 +/- 12% respectively. The patients who received allogeneic haematopoietic stem cell transplantation during second CR showed a superior outcome to other patients.     

Expression of CD8 is associated with non-common type morphology and outcome in pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma

Anaplastic lymphoma kinase-positive anaplastic large T-cell lymphoma is characterized by morphological variability. Morphological variants (non-common subtype) are associated with a poor outcome. They display abundant reactive bystander cells admixed with the lymphoma cells. So far, the difficulty in distinguishing lymphoma cells from bystander cells by visual inspection has prevented detailed and reliable immunophenotypic analysis using conventional immunohistochemistry. To overcome these limitations, we analyzed 124 cases of pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma treated within clinical trials using immunofluorescence multi-staining and digital image analysis combining antibodies against anaplastic lymphoma kinase to specifically identify lymphoma cells with antibodies against CD30, CD3, CD5, CD8, Ki67 and phosphorylated STAT3. Non-common type anaplastic lymphoma kinase-positive anaplastic large cell lymphomas express CD8 more frequently than common type anaplastic lymphoma kinase-positive anaplastic large cell lymphomas (35.4% and 5.6%, respectively; P=0.0002). CD8 expression was associated with a poorer outcome. Importantly, in a multivariate analysis including clinical risk factors, histological subtype and CD8 expression, CD8-positivity proved to be an independent prognostic predictor of worse outcome (hazard ratio for survival 3.38, P=0.042).     

Cardiac presentation of ALK positive anaplastic large cell lymphoma

Cardiac involvement as an initial presentation of malignant lymphoma is a rare occurrence. We report the case of an immunocompetent 29-year-old male who presented with syncope and arrythmias secondary to a ventricular cardiac mass. Transcutaneous cardiac biopsy was non-diagnostic, therefore an open cardiac biopsy was performed from which a provisional diagnosis of a cardiac inflammatory pseudotumour was made. Six months after presentation, he developed several subcutaneous lesions with systemic symptoms. Histological and immunophenotypic review of the initial cardiac biopsy revealed features consistent with a diagnosis of CD30, ALK1 positive anaplastic large cell lymphoma (ALCL). Despite intensive treatment with combination chemotherapy, there was significant progression of disease, and he died 11 months after diagnosis. The overall prognosis of cardiac lymphoma remains poor, which may be due to the often late presentation of the tumour. To our knowledge, this is the first reported case of a cardiac ALK positive ALCL. Although rare, cardiac presentation of ALCL should be added to the list of differential diagnoses of cardiac lymphomas.     

ALK-negative anaplastic large cell lymphoma and Hodgkin's disease of nodular sclerosing type in 2 siblings

Familial clustering of Hodgkin's disease (HD) and increased risk of developing the disease among the siblings of affected patients suggest that both environmental and genetic factors may play an important role in its pathogenesis. An association between Epstein-Barr virus (EBV) and HD has been widely demonstrated. Recently, latent membrane protein of EBV has also been detected in CD30-positive anaplastic large cell lymphoma. Familial aggregation of HD and a three- to seven-fold-increased risk among the siblings of affected patients suggest increased genetically determined susceptibility. No data about genetic factors are available for anaplastic large-cell lymphoma. In this study, the authors report the case of a woman with anaplastic-lymphoma-kinase (ALK)-negative CD30-positive anaplastic large cell lymphoma, whose brother had developed HD 11 years previously. The clinical, histologic, and immunohistochemical features of the 2 lymphomas were studied. Both siblings showed bulky mediastinal involvement, effacement of normal lymph node architecture by large, atypical cells, resembling Reed-Sternberg cells, expression of EBV latent membrane protein-1 in the lymph node specimens, concordance of both HLA classes I and II. The clinical presentations and immunological studies disclose numerous similarities between the 2 cases and can suggest that their association is not fortuitous. At present, in problematic cases, a combination of morphologic, immunophenotypic and genetic studies may contribute to better define the tumour type.     

Isolation of differentially expressed genes in NPM-ALK-positive anaplastic large cell lymphoma

In this study, we used subtractive suppression hybridization to compare gene expression between an ALK-positive anaplastic large cell lymphoma (ALCL)-derived cell line and a clinical case of ALK-negative ALCL. Construction and screening of a subtracted library resulted in the cloning of 29 cDNAs which were differentially expressed. Most of these clones corresponded to novel genes with unknown function (EST) or to genes implicated in the differentiation, activation or signalling of T cells such as Ran/TC4, interleukin 1-receptor, thymosin beta4, thymosin beta10, moesin and cytohesin-1. Other genes involved in the regulation of apoptosis, such as human inhibitor of apoptosis-1 (HIAP-1), Bax inhibitor-1 and MCL-1, or DNA repair, such as poly (ADP-ribose) polymerase 1 (PARP-1), X-associated protein-1 (XAP-1), SUMO-1 (sentrin-1) and RanGTPase-activating protein 1 (RanGAP-1), were isolated. Interestingly, we found that both RNA and protein levels of human sterol isomerase (hSI), also referred to as emopamil binding protein (EBP), were overexpressed in ALK+ tumours. This protein is involved in the biosynthesis of cholesterol and may be activated by NPM-ALK. Overall, our results suggest that all the genes described above are upregulated in the NPM-ALK-driven transformation process, and that moesin and cytohesin-1 may be more specifically implicated in a signalling pathway involving PLCgamma and PI3K.     

Prognostic significance of anaplastic lymphoma kinase (ALK) protein expression in adults with anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL) is an aggressive lymphoma that is frequently associated with the t(2;5)(p23;q35), resulting in expression of a fusion protein, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), which can be detected by either monoclonal or polyclonal antibodies to the ALK protein. The clinical features of adults with ALCL are incompletely described, and the prognostic factors that are useful for predicting survival remain unclear. This report describes the clinical and laboratory findings in 70 adults with systemic ALCL who were treated with curative intent. We attempted to identify the clinical and pathological factors of prognostic importance, including the International Prognostic Index (IPI), immunophenotype, and expression of the ALK protein. The median age of the patients was 49 years (range, 15 to 75). There were 26 women and 44 men with a median follow-up of 50 months for living patients. Advanced stage was present in 56% and B symptoms were noted in 70% of the patients. Immunostains showed that 46% of the cases had a T-cell phenotype, 36% a null phenotype, and 18% a B-cell phenotype. The expression of ALK protein was found in 51% of the cases. The IPI factors were evenly distributed between the ALK+ and ALK- groups, except that the ALK+ patients were younger (median age, 30 v 61 years; P <.002). The ALK+ cohort included cases with null (44%), T-cell (42%), and B-cell (14%) phenotypes. All 10 cases with cytogenetic or molecular evidence of a t(2;5) were ALK+. The 5-year overall survival (OS) of the entire cohort was 65%. The 5-year OS of the ALK+ and ALK- cases was 79% and 46%, respectively (P <.0003). Analysis of only the T-cell/null cases (n = 57) showed a 5-year OS of 93% for the ALK+ cases and only 37% for the ALK- cases (P <.00001). Univariate analysis of the clinical features showed that age 相似文献   

CD30/Ki-1-positive anaplastic large cell lymphoma preceded by Hodgkin's disease.

A 59-year-old man was initially diagnosed as having Hodgkin's disease, nodular sclerosis type, and complete remission was achieved after combination chemotherapy. One year later, he developed a high fever and recurrence of the Hodgkin's disease was diagnosed. Salvage chemotherapy was ineffective, and the patient died. Autopsy specimens showed infiltration of lymphoma cells into multiple organs. Lymph nodes showed characteristics of non-Hodgkin's lymphoma, with expansion of anaplastic large cells; this differed from the histological features at initial diagnosis. Immunohistochemical staining was positive for CD30/Ki-1, but negative for CD15 (LeuM1). These findings were compatible with Ki-1 lymphoma, suggesting that this may be a case of CD30/Ki-1 lymphoma preceded by Hodgkin's disease and that a certain proportion of Ki-1 lymphomas and Hodgkin's disease may share the same cellular origin.