Predicting the survival time for diffuse large B-cell lymphoma using microarray data.

Predicting the survival time for diffuse large B-cell lymphoma using microarray data.

2012

Khoshhali M, Mahjub H, Saidijam M, Poorolajal J, Soltanian AR.

Source

Department of Biostatistics & Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran.

Abstract

The present study was conducted to predict survival time in patients with diffuse large B-cell lymphoma, DLBCL, based on microarray data using Cox regression model combined with seven dimension reduction methods. This historical cohort included 2042 gene expression measurements from 40 patients with DLBCL. In order to predict survival, a combination of Cox regression model was used with seven methods for dimension reduction or shrinkage including univariate selection, forward stepwise selection, principal component regression, supervised principal component regression, partial least squares regression, ridge regression and Losso. The capacity of predictions was examined by three different criteria including log rank test, prognostic index and deviance. MATLAB r2008a and RKWard software were used for data analysis. Based on our findings, performance of ridge regression was better than other methods. Based on ridge regression coefficients and a given cut point value, 16 genes were selected. By using forward stepwise selection method in Cox regression model, it was indicated that the expression of genes GENE3555X and GENE3807X decreased the survival time (P=0.008 and P=0.003, respectively), whereas the genes GENE3228X and GENE1551X increased survival time (P=0.002 and P<0.001, respectively). This study indicated that ridge regression method had higher capacity than other dimension reduction methods for the prediction of survival time in patients with DLBCL. Furthermore, a combination of statistical methods and microarray data could help to detect influential genes in survival.

PubMed

ESMO Guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse large B-cell lymphoma(DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL).

Nov 2012

Ghielmini M, Vitolo U, Kimby E, Montoto S, Walewski J, Pfreundschuh M, Federico M, Hoskin P, McNamara C, Caligaris-Cappio F, Stilgenbauer S, Marcus R, Trneny M, Dreger P, Montserrat E, Dreyling M; On behalf of the Panel Members of the 1st ESMO Consensus Conference on Malignant Lymphoma.

Source

Department of Medical Oncology, Oncology Institute of Southern Switzerland, Ospedale San Giovanni, Bellinzona, Switzerland.

Abstract

To complete the existing treatment guidelines for all tumor types, ESMO organizes consensus conferences to better clarify open issues in each disease. In this setting, a consensus conference on the management of lymphoma was held on 18 June 2011 in Lugano, immediately after the end of the 11th International Conference on Malignant Lymphoma.The consensus conference convened ∼45 experts from all around Europe and selected six lymphoma entities to be addressed; for each of them three to five open questions were to be discussed by the experts. For each question, a recommendation should be given by the panel, supported by the strength of the recommendation based on the level of evidence.This consensus report focuses on the three most common lymphoproliferative malignancies: diffuse large B-cell lymphoma, follicular lymphoma and chronic lymphocytic leukemia. A second report will concentrate on mantle cell lymphoma, marginal zone lymphoma and T-cell lymphomas.

PubMed

Outcome and pathological classification of children and adolescents with mediastinal large B-cell lymphoma treated with FAB/LMB96 mature B-NHL therapy.

Nov 2012

Gerrard M, Waxman IM, Sposto R, Auperin A, Perkins SL, Goldman S, Harrison L, Pinkerton R, McCarthy K, Raphael M,Patte C, Cairo MS.

Source

Sheffield Children's Hospital, Sheffield, United Kingdom;

Abstract

Mediastinal large B-cell lymphoma (MLBL) represents only 2% of mature B-cell non-Hodgkin lymphoma (B-NHL) in patients ≤18 years of age. Gene expression profiling demonstrates that MLBL in adults more closely resembles classical Hodgkinlymphoma than it does diffuse large B-cell lymphoma (DLBCL). We analyzed data from childhood and adolescent patients with Stage III MLBL (N=42) and non MLBL DLBCL (N=69) treated with Group B therapy on the FAB/LMB 96 study. Demographics of MLBL patients: M/F: 26/16; median age 15.7 yrs (12.5-19.7); LDH <2 vs. ≥2 ULN: 23:19. Six MLBL patients (14%) had <20% response to initial COP-therapy. Central pathology classification revealed approximately 50% with classical features of primary mediastinal B-cell lymphoma (PMBL). Five-year event-free survival (EFS) for Stage III MLBL and non-MLBL DLBCL groups were 66% (95% CI: 49-78%) and 85% (95% CI: 71-92%), respectively, p<0.001 (14%). The 5-year overall survival (OS) in the 42 MLBL patients was 73% (95% CI: 56-84%). MLBL in adolescent patients is associated with significantly inferior EFS compared with stage III non-MLBL DLBCL and can be of multiple histologies. Alternate treatment strategies should be investigated in the future taking into account both adult MLBL approaches and more recent biological findings in adult MLBL.

Blood Journal

Primary cutaneous diffuse large B-cell lymphoma (PCDLBCL), leg-type and other: an update on morphology and treatment.

Dec 2012

Paulli M, Lucioni M, Maffi A, Croci GA, Nicola M, Berti E.

Source

Anatomic Pathology Section, Department of Molecular Pathology, University of Pavia and IRCCSFondazione Policlinico "San Matteo", Pavia, Italy - marco.paulli@unipv.it.

Abstract

Primary cutaneous B-cell lymphoma (PCBCL) is an heterogeneous group of lymphoproliferative disorders, which account for 25-30% of all primary cutaneous lymphoma and include three main histotypes: 1) primary cutaneous marginal zone B-cell lymphoma (PCMZL); 2) primary cutaneous follicular center cell lymphoma (PCFCL); 3) primary cutaneous diffuse large B-cell lymphoma (DLBCL), leg type (PCDLBCL-LT). PCMZL and PCFCL are indolent lymphomas, with an excellent prognosis despite an high rate of cutaneous recurrences; in contrast, PCDLBCL-LT is clinically more aggressive and usually requires to be treated with multi-agent chemotherapy and anti-CD20 monoclonal antibodies. PCDLBCL-LT histologically consists of large round cells (centroblasts and immunoblasts), is characterized by strong bcl-2 expression, in the absence of t(14;18) translocation, and resembles the activated B-cell type of nodal DLBCL. Recently, the term primary cutaneous DLBCL-other (PCDLBCL-O) has been proposed to include diffuse lymphomas composed of large transformed B-cells that lack the typical features of PCDLBCL-LT and do not conform to the definition of PCFCL. Some clinical studies suggested that such cases have an indolent clinical course and may be treated in a conservative manner; however, data regarding the actual prognosis and clinical behaviour of these peculiar cases are still too limited. The spectrum of primary cutaneous DLBCL also encompasses some rare morphological variants, such as anaplastic or plasmablastic subtypes and T-cell rich B-cell lymphoma, and some recently described, exceedingly rare DLBCL subtypes, such as intravascular large B-cell lymphoma and EBV-associated large B-cell lymphoma of the elderly, which often present in the skin.

PubMed

Indolent cutaneous B-cell lymphoma: diagnosis and treatment 2012.

Dec 2012

Santucci M, Grandi V, Maio V, Delfino C, Alterini R, Pimpinelli N.

Source

Divisions of Pathological AnatomyDepartment of Critical Care Medicine and SurgeryUniversity of Florence Medical School, Florence, Italy2Division of DermatologyDepartment of Critical Care Medicine and SurgeryUniversity of Florence Medical School, Florence, Italy3Division of HematologyDepartment of Critical Care Medicine and SurgeryUniversity of Florence Medical School, Florence, Italy.

Abstract

Among primary cutaneous B-cell lymphomas (CBCL), two main clinico-pathologic entities are recognized, i.e. marginal zone lymphoma (MZL), otherwise defined as extranodal MZL, MALT (Mucosa-Associated Lymphoid Tissue) type, and follicle center lymphoma (FCL). They are mostly characterized by indolent course (very limited risk of extracutaneous spread), very good response to non-aggressive treatment (radiotherapy is the gold standard), and excellent prognosis (>90% 5-year survival overall). The clinical presentation of MZL and FCL slightly differ concerning site predilection (trunk and upper limbs in the former, head&neck and trunk in the latter) and frequency of cases with multiple, non-contiguous lesions (higher in MZL). Histologically, MZL and FCL share the multiphasic evolution of lesions, while some distinctive features are clues to diagnosis and differential diagnosis: CD5-/CD10-/bcl2+ phenotype of neoplastic cells, "colonization" of reactive lymphoid follicles by neoplastic cells, lymphoplasmacytoid and plasma cells at the periphery of nodular infiltrates in MZL; CD5-, CD10 +/-, bcl6+, MUM-1 neg, FOX-P1 neg, IRF4 neg, IgM neg phenotype of neoplastic cells (centrocytes), and neoplastic follicles (in early lesions) in FCL.

Pub Med

Aggressive B-cell lymphomas: how many categories do we need?

Nov 2012

Said JW.

Source

Department of Pathology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.

Abstract

Aggressive B-cell lymphomas are diverse group of neoplasms that arise at different stages of B-cell development and by various mechanisms of neoplastic transformation. The aggressive B-cell lymphomas include many types, subtypes and variants of diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), mantle cell lymphoma and its blastoid variant, and B lymphoblastic lymphoma. Differences in histology, cytogenetic and molecular abnormalities, as well as the relationship with the tumor microenvironment, help define characteristic signatures for these neoplasms, and in turn dictate potential therapeutic targets. Rather than survey the entire spectrum of aggressive B-cell lymphomas, this report aims to identify and characterize important clinically aggressive subtypes of DLBCL, and explore the relationship of DLBCL to BL and the gray zone between them (B-cell lymphoma unclassifiable with features intermediate between DLBCL and BL).Modern Pathology advance online publication, 16 November 2012; doi:10.1038/modpathol.2012.178.

PubMed

Chromosome abnormalities in diffuse large B-cell lymphomas: analysis of 231 Chinese patients.

Nov 2012

Zhao X, Fan R, Lin G, Wang X.

Source

Department of Haematology, Huashan Hospital of Fudan University, Shanghai, China.

Abstract

Genome instability is a hallmark of cancer. Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkinlymphoma with high levels of chromosomal aberrations. The purpose of this study was to characterize chromosomal aberrations in Chinese DLBCL patients and to compare chromosomal abnormalities between germinal centre B-cell-like (GCB) and non-GCB subgroups. Fluorescence in situ hybridization, G-band cytogenetics and immunohistochemistry were performed in 231 cases of de novo DLBCL. We demonstrated that the rate of abnormal and complex karyotypes was 89.1% (139/156) and 92.8% (129/139), respectively. We found a total of 490 structural chromosomal aberrations, including 96 frequent and recurring structural alterations. 

Most importantly, we identified several rare or novel chromosomal alterations: eight gains (5, 13, 14q, 17, 19p, 20, 21p, Y), one loss (21) and three recurrent translocations [t(7;15)(q22;q22), t(3;20)(p24;q13.1), t(2;3)(q21;q25)]. Moreover, the frequent recurrent genomic imbalance between GCB and non-GCB subgroups was different. Finally, we discovered two cases of concurrent IGH-BCL6 and MYC rearrangements. The rate of abnormal karyotypes in DLBCL patients of Chinese descent was similar to that of Western countries, but some common karyotypes were different, as were the abnormal karyotypes of GCB and non-GCB subgroups. Our discovery of rare and novel abnormal karyotypes may represent unique chromosomal alterations in Chinese DLBCL patients. 

John Wiley & Sons, Ltd.

Prognostic significance of rituximab and radiotherapy for patients with primary mediastinal large B-cell lymphoma receiving doxorubicin-containing chemotherapy.

Nov 2012

Xu LM, Fang H, Wang WH, Jin J, Wang SL, Liu YP, Song YW, Ren H, Zhou LQ, Li YX.

Abstract

The aim of this study was to evaluate the prognostic importance of rituximab and radiotherapy in patients with primary mediastinal large B-cell lymphoma (PMBCL) receiving doxorubicin-containing chemotherapy. Seventy-nine patients with PMBCL received CHOP chemotherapy with (n = 39) or without rituximab (n = 40), and 60 patients received additional radiotherapy. Patients treated with R-CHOP had significantly superior survival rates. The 5-year overall survival (OS) and progression-free (PFS) rates were 83.7% and 76.7% for R-CHOP, compared with 48.3% (P=0.011) and 44.2% (P=0.012) for CHOP, respectively. Similarly, the 5-year OS and PFS rates for early stage patients were 93.8% and 84.6% with R-CHOP, and 52.0% (P=0.002) and 46.6% (P=0.003) with CHOP, respectively. Patients treated with chemotherapy and radiotherapy had better survival and local control (LC) rates compared with chemotherapy alone. The 5-year OS, PFS and LC rates for early stage patients were 73.6%, 69.9% and 92.6% for chemotherapy and radiotherapy, and 50.8% (P = 0.076), 36.9% (P = 0.008) and 56.4% (P<0.001) for chemotherapy alone, respectively. Early stage patients treated with R-CHOP and radiotherapy had 5-year OS, PFS and LC rates of 96.4%, 85.9% and 93.1%. R-CHOP plus consolidation radiotherapy was associated with excellent survival and LC rates.

PubMed

The Absolute Monocyte and Lymphocyte Prognostic Index for Patients With Diffuse Large B-Cell Lymphoma Who Receive R-CHOP.

Nov 2012

Batty N, Ghonimi E, Feng L, Fayad L, Younes A, Rodriguez MA, Romaguera JE, McLaughlin P, Samaniego F, Kwak LW,Hagemeister FB Jr.

Source

Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY.

Abstract

BACKGROUND:

The baseline absolute monocyte count and absolute lymphocyte count were used to generate a prognostic index (the AMLPI) for survival in diffuse large B-cell lymphoma (DLBCL).

METHODS:

Data from 245 patients with DLBCL who were treated with standard R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) were reviewed. By using the values previously reported for the AMLPI, its prognostic value was examined in our population.

RESULTS:

After a median follow-up of 22 months for censored observations, the 3-year progression-free survival (PFS) rates for the international prognostic index (IPI) 0-2 and 3-5 risk groups were 73% and 58%, respectively (P = .0004); comparable overall survival (OS) rates were 88% and 68%, respectively (P < .0001). For patients with IPI scores of 0-2, 1-year PFS rates for AMLPI low-, intermediate-, and high-risk groups were 92%, 89%, and 80%, respectively (P = .022); comparable 1-year OS rates were 96%, 95%, and 80%, respectively (P = .049). By multivariate analysis, with the adjustment of IPI in the model, AMLPI effects (low- vs. high-risk groups) on PFS and OS rates were significant, with P = .046 (hazard ratio [HR] 0.402 [95% CI, 0.164-0.986] and P = .052 (HR 0.325 [95% CI, 0.104-1.011]), respectively.

CONCLUSIONS:

The absolute monocyte and lymphocyte counts prognostic index (the AMLPI) may add prognostic value beyond that of the IPI for patients with DLBCL who receive R-CHOP.

PubMed

Long-term remission of primary bone marrow diffuse large B-cell lymphoma treated with high-dose chemotherapy rescued by in vivo rituximab-purged autologous stem cells.

2012

Kazama H, Teramura M, Yoshinaga K, Masuda A, Motoji T.

Source

Department of Hematology, Tokyo Women's Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.

Abstract

Primary bone marrow diffuse large B-cell lymphoma (DLBCL) is a rare type of extranodal lymphoma with poor prognosis. Here, we report a case of primary bone marrow DLBCL successfully treated with high-dose chemotherapy and rescued by in vivo rituximab-purged autologous stem cells. A 39-year-old woman visited our hospital because of anemia. Bone marrow examination revealed a large B-cell lymphoma invasion. An (18)F-fluorodeoxyglucose positron emission tomography scan revealed disseminated bone marrow uptake without evidence of dissemination at other sites. These findings led to a diagnosis of primary bone marrow DLBCL. Our patient underwent R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy and achieved complete remission. Subsequently, she received high-dose chemotherapy with an in vivo rituximab-purged autologous stem cell transplant. Seven years have passed since the transplantation, and she remains in remission. This suggests that transplantation of an in vivo rituximab-purged autograft is a promising strategy for primary bone marrow DLBCL.

Case Reports in Medicine

Bone marrow involvement is predictive of infusion-related reaction during rituximab administration in patients with B cell lymphoma.

Oct 2012

Hong J, Kim JY, Ahn HK, Lee SM, Sym SJ, Park J, Cho EK, Ahn JY, Park S, Lee SP, Shin DB, Lee JH.

Source

Division of Hematology & Medical Oncology, Department of Internal Medicine, Gachon University School of Medicine, Gachon University Gil Hospital, Incheon, Republic of Korea.

Abstract

PURPOSE:

The purpose of this study is to evaluate risk factors for infusion-related reaction (IRR) following rituximab administration in patients with B cell non-Hodgkin lymphoma.

METHODS:

A retrospective analysis was conducted of patients with newly diagnosed B cell lymphoma who have received rituximab-included immunochemotherapy with appropriate premedication and commonly used schedule of infusion rate. IRRs were graded by review of the patients' electronic medical record according to the Common Terminology Criteria for Adverse Events version 4.0.

RESULTS:

One hundred and sixty-nine patients were included in the analysis and most of the patients (150; 88.8 %) had diffuse large B cell lymphoma (DLBCL). Thirty-six patients (21.3 %) had any grade of IRRs: 23 patients were grade (G) 1 (13.6 %), 13 had ≥G2 IRRs (7.7 %), and only 4 had ≥G3 IRRs (2.4 %). All except one patient had IRR during the first cycle and only two had repetitive IRR thereafter. Bone marrow (BM) involvement was the strongest risk factor for IRR in multivariable analysis (odds ratio 4.06, 95 % confidence interval 1.67-9.89; p = 0.002). A subgroup analysis confined to patients with DLBCL showed very similar results when compared with the entire population, and patients with DLBCL who had ≥G2 IRR showed shorter event-free and overall survival when compared to those who did not.

CONCLUSIONS:

BM involvement is predictive of occurrence of IRR during rituximab administration in patients with B cell lymphoma. More intensive premedication and careful observation for IRR during rituximab administration are required for patients with B cell lymphoma who have BM involvement.

PubMed