Splenic marginal zone lymphoma: Clinical characteristics and prognostic factors in a series of 52 patients

Abstract Splenic marginal zone lymphoma (SMZL) is generally an indolent disorder which has a median survival of 10 – 13 years, but a minority of patients pursue a more aggressive clinical course. A number of adverse prognostic factors including the level of haemoglobin, lymphocyte count and platelet count, B2 microglobulin, presence of a paraprotein, IgVH gene mutational status and p53 loss or mutation have been identified, but these have not been consistent among recent series. We have studied 89 patients with SMZL, diagnosed on the basis of lymphocyte morphology, immunophenotype and marrow and splenic histology, when available, and have evaluated the impact of presenting Hb, lymphocyte count, spleen size, presence of a paraprotein, cytogenetic abnormalities and IgVH gene mutational status on both the need for treatment and on overall survival. In 43 patients the diagnosis was made following a routine blood count performed for an incidental reason. The M:F ratio was 1:1.78, median age at presentation was 67.5 years (range; 49 – 91) and mean follow-up was 78.1 months. 63/89 (71%)patients presented with palpable splenomegaly, and a further 5 developed splenomegaly during the course of their disease. 42/89 (47%) patients required treatment of whom 29 (32%) underwent splenectomy. 36 patients have not required treatment, 25 have received an alkylating agent, 12 have received fludarabine and 4 were treated with rituximab.15/29 (17%) received chemotherapy for progressive disease post splenectomy. In six patients there was transformation to a high grade lymphoma. 14 patients (16%) died, 11 of whom had a disease-related death. 24/83 patients (29%) had a paraprotein, 67/87 (77%) had an abnormal karyotype of whom 39 (45%) had an abnormality of 7q. Using interphase FISH, 7/78((9%) showed trisomy 3 and 7/74(9%) had p53 loss. Of the patients with high grade transformation, 3/6 had p53 loss. 47/67 patients (70%) had mutated IgVH genes, and 15 cases utilised the VH1-02 gene segment. Only spleen size >10cm (p=0.0002) and Hb <100 gm/l (p=0.008) correlated with the need for treatment. Only unmutated IgVH genes (p=0.032) and the need for further therapy following initial treatment with splenectomy (p=0.034) correlated with overall survival.The median survival of unmutated cases was 113 months and was not reached for mutated cases.The median survival of patients for whom splenectomy has been their only treatment has not been reached, but was 110 months for patients requiring additional treatment post splenectomy. There is a need for larger, multi-centre studies to identify poor risk patients with SMZL.

Download Full-text

Clinical Characteristics and Outcome in Dogs with Splenic Marginal Zone Lymphoma

Journal of Veterinary Internal Medicine ◽

10.1111/jvim.12116 ◽

2013 ◽

Vol 27 (4) ◽

pp. 949-954 ◽

Cited By ~ 18

Author(s):

D. O'Brien ◽

P.F. Moore ◽

W. Vernau ◽

J.R. Peauroi ◽

R.B. Rebhun ◽

...

Keyword(s):

Clinical Characteristics ◽

Marginal Zone ◽

Marginal Zone Lymphoma ◽

Splenic Marginal Zone Lymphoma

Download Full-text

Gene Expression Profiling Analysis in Splenic Marginal Zone Lymphoma Allows To Predict Survival and Histological Transformation.

Blood ◽

10.1182/blood.v104.11.1125.1125 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1125-1125

Author(s):

C. Thieblemont ◽

B. Ballester ◽

V. Nasser ◽

S. Gazzo ◽

G. Doucet ◽

...

Keyword(s):

Gene Expression ◽

Cell Proliferation ◽

Prognostic Factors ◽

Marginal Zone ◽

Marginal Zone Lymphoma ◽

Matched Pair ◽

Splenic Marginal Zone Lymphoma ◽

Term Survival ◽

Disease Evolution ◽

Histological Transformation

Abstract Splenic Marginal Zone Lymphoma (MZL) is described as an indolent lymphoma with a long term survival. However classical prognostic factors can not distinguish between patients who are likely to have good or poor outcomes. Moreover histological progression occurs in 10–20% of cases at the time of recurrence, but may be present at diagnosis, inducing a shorter survival with a median around 2 years. New model based on molecular understanding are needed to better discriminate these patients for their prognosis and disease evolution. Biopsy samples of splenic MZL from 43 patients treated in one institution and 8 with transformed splenic MZL were examined for gene expression using a nylon cDNA microarray consisting of 7, 000 human genes. Two of them came from a group of matched pair of splenic MZL and the transformed counterpart. An additional group comprising 4 transformed follicular lymphomas and 1 transformed small lymphocytic lymphoma were also analysed. Hierarchical clustering realized with all samples allowed to visualized patterns of gene expression already described in our previous work1 and corresponding to precise functions (proliferation, early response...), cell or tissue subtype (T cells, stroma …) or lymphoma subtype (MZL, MCL, SLL). The ability of individual genes to distinguish 1/ MZL and transformed-MZL subtypes, and 2/ alive patients and dead patients was calculated using a supervised method (discriminating score and bootstrap resampling). This allowed us to construct molecular predictors of survival and histological transformation. Transformation discriminating genes regrouped 73 genes related to cell proliferation such as CDC10, CDK4, PRKDC, PLCG2, LDHA, MCL2, and NPM1. P53 was down-expressed in all the transformed samples. Survival discriminating genes regrouped 26 genes from a unique cluster related to cell proliferation such as LDHA, NME1, MYC, ENO1. Although these genes seem to participate to the same function, only one gene was found discriminating the 2 parameters (LDHA). Gene ontology analysis using GOminer showed that the histological transformation was more related to cyclin-dependent protein kinase and that the survival was more related to metabolism. We used 26 genes to construct a predictor for survival in MZL patients. This gene-based predictor allowed predicting survival (p <0.00001) in MZL patients better than with classical prognostic factors (age, performance status, stage, LDH, monoclonal component, IPI…), but also in transformed MZL patients. In conclusion, genes involved in histological transformation and survival in MZL patients are implicated in independent but complementary functions leading to cell proliferation.

Download Full-text

Splenic marginal zone lymphoma: Prognostic factors, role of watch and wait policy, and other therapeutic approaches in the rituximab era

Leukemia Research ◽

10.1016/j.leukres.2016.03.005 ◽

2016 ◽

Vol 44 ◽

pp. 53-60 ◽

Cited By ~ 13

Author(s):

Salvatore Perrone ◽

Gianna Maria D’Elia ◽

Giorgia Annechini ◽

Antonietta Ferretti ◽

Maria Elena Tosti ◽

...

Keyword(s):

Prognostic Factors ◽

Marginal Zone ◽

Marginal Zone Lymphoma ◽

Splenic Marginal Zone Lymphoma ◽

Watch And Wait ◽

Therapeutic Approaches

Download Full-text

Splenic marginal zone lymphoma: clinical characteristics and prognostic factors in a series of 60 patients

Blood ◽

10.1182/blood.v100.5.1648.h81702001648_1648_1654 ◽

2002 ◽

Vol 100 (5) ◽

pp. 1648-1654 ◽

Cited By ~ 129

Author(s):

Jose I. Chacón ◽

Manuela Mollejo ◽

Enriqueta Muñoz ◽

Patricia Algara ◽

Marisol Mateo ◽

...

Keyword(s):

Prognostic Factors ◽

Marginal Zone ◽

Performance Status ◽

Univariate Analysis ◽

Bone Marrow Involvement ◽

Eastern Cooperative Oncology Group ◽

Marginal Zone Lymphoma ◽

Response To Therapy ◽

Splenic Marginal Zone Lymphoma ◽

P53 Overexpression

A precise description of clinical features at presentation and analysis of clinical and biologic prognostic factors in splenic marginal zone lymphoma (SMZL) are still lacking. Here we describe the clinical and biologic features of a series of 60 SMZL patients diagnosed after splenectomy. Analysis for overall survival (OS), failure-free survival (FFS), and the probability of obtaining a response was performed using univariate and multivariate tests. The median age of the patient was 63 years (range, 35-84 years). Performance status according to the Eastern Cooperative Oncology Group (ECOG scale) was 0 = 16%, 1 = 58%, and 2 = 25%. Of the 60 patients, 53 (86.6%) were at Ann Arbor stage IV. All 60 patients received splenectomies, 29 of 60 also received chemotherapy, and 2 received spleen radiotherapy. A complete response (CR) was achieved by 38.3% of patients, and a partial response (PR) was achieved by 55%. Mean OS of the series was 103 months (range, 2-164 months); mean FFS was 40 months (range, 3-164 months). At 5 years from diagnosis, 39 patients (65%) were alive. Patients dying from the disease had a relatively aggressive clinical course, with a short survival (17.5 months [range, 2-72 months]). Significant prognostic factors in multivariate analysis were (1) (for OS and FFS) lack of response to therapy (CR versus noncomplete response [nCR]) and involvement of nonhematopoietic sites, and (2) (for the probability of obtaining CR) bone marrow involvement. Chemotherapy did not influence OS or FFS. p53 overexpression predicted a shorter OS in the univariate analysis. These data confirm the relative indolence of this disease, indicating the existence of a subset of more aggressive cases, which should stimulate the search for predictive biologic factors and alternative therapies.

Download Full-text