Sequential Lymphoma Research Articles

A Twist of Fate: A Case of Sequential Lymphoma

A Twist of Fate: A Case of Sequential Lymphoma

Survival among patients with composite and sequential lymphoma between primary mediastinal lymphoma/diffuse large B-cell lymphoma and classical Hodgkin lymphoma: A population-based study

BackgroundData on composite and sequential lymphoma between primary mediastinal lymphoma/diffuse large B-cell lymphoma (LBCL) and classical Hodgkin lymphoma (cHL) are rare. MethodsWe identified 25 cases with composite lymphoma (CL), 116 cases developing LBCL as a second primary cancer after cHL (cHL-LBCL), and 74 cases developing cHL as a second primary cancer after LBCL (LBCL-cHL) from the Surveillance, Epidemiology, and End Results (SEER) 18 database. Comparisons of overall survival (OS) and lymphoma cause-specific survival (CSS) between patients with cHL-LBCL or cHL-LBCL and their de novo counterparts were performed. ResultsThe 5-year OS of patients with CL was 74.8 %. No significant difference in unadjusted OS and lymphoma CSS were observed between patients with de novo LBCL (LBCL-1 group) and patients with cHL-LBCL. However, the age- and stage-adjusted cHL-LBCL group had inferior OS and lymphoma CSS compared with that in the LBCL-1 group. The unadjusted and adjusted OS and lymphoma CSS in the LBCL-cHL group were significantly worse than patients with de novo cHL. ConclusionsCL between LBCL and cHL may have good outcomes. cHL survivors had poorer outcomes after a LBCL diagnosis versus patients with LBCL-1. Significantly poor outcomes were observed in patients with LBCL-cHL compared with patients with de novo cHL.

Sequential Lymphoma between Classical Hodgkin Lymphoma and Diffuse Large B Cell Lymphoma: Clinicopathological Characteristics and Outcome of 18 Patients from Lysa Center

Sequential Lymphoma between Classical Hodgkin Lymphoma and Diffuse Large B Cell Lymphoma: Clinicopathological Characteristics and Outcome of 18 Patients from Lysa Center

Incidence Patterns of Sequential or Composite Lymphoma: A Population-Based Cancer Registry Study.

The development of multiple histologic types of lymphoma in a single patient has been sporadically reported as sequential or composite lymphoma. However, the incidence pattern of such patients has been rarely evaluated in a large population-based setting. We investigated the incidence of sequential or composite lymphoma based on 11,174 lymphoma records from a population-based cancer registry between 1985-2012 in Nagasaki Prefecture, Japan. We identified 99 lymphoma records were of 49 independent patients other than relapse. The prevalence of the sequential or composite lymphomas in a single patient was 0.44% (95% confidence interval [95% CI], 0.32-0.56%) without sex difference. Among the 49 patients, five (10.2%) were composite/discordant lymphoma. The most frequent "composite lymphoma" was a combination of diffuse large B-cell lymphomas (DLBCL) and adult T-cell leukemia (n = 3). A case of "discordant lymphoma" was a combination of follicular lymphoma on spleen and Waldenström macroglobulinemia on bone marrow. The rest of the patients (n = 44, 89.8% of all composite lymphoma) were "sequential lymphoma" with various combination of lymphoma subtypes on different dates. The major combination of the sequential lymphoma was DLBCL after marginal zone lymphomas (n = 4). In the era of improved survival of lymphoma patients, hematologists should be aware of the development of additional lymphomas.

CD28.OX40 co-stimulatory combination is associated with long in vivo persistence and high activity of CAR.CD30 T-cells.

The prognosis of many patients with chemotherapy-refractory or multiply relapsed CD30+ non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) still remains poor, and novel therapeutic approaches are warranted to address this unmet clinical need. In light of this consideration, we designed and pre-clinically validated a chimeric antigen receptor (CAR) construct characterized by a novel anti-CD30 single- chain variable-fragment cassette, linked to CD3ζ by the signaling domains of two co-stimulatory molecules, namely CD28.4-1BB or CD28.OX40. We found that CAR.CD30 T cells exhibit remarkable cytolytic activity in vitro against both HL and NHL cell lines, with sustained proliferation and pro-inflammatory cytokine production, even after multiple and sequential lymphoma-cell challenges. CAR.CD30 T cells also demonstrated anti-lymphoma activity in two in vivo xenograft immune-deficient mouse models of metastatic HL and NHL. We observed that administration of CAR.CD30 T cells, incorporating the CD28.OX40 co-stimulatory domains and manufactured in the presence of interleukin 7 and interleukin 15, were associated with the best overall survival in the treated mice, along with establishment of a long-term immunological memory able to protect mice from further tumor re-challenge. Our data indicate that, in the context of in vivo systemic metastatic xenograft mouse models, the co-stimulatory machinery of CD28.OX40 is crucial for improving persistence, in vivo expansion and proliferation of CAR.CD30 T cells upon tumor encounter. The CD28.OX40 co-stimulatory combination is ultimately responsible for the anti-tumor efficacy of the approach, paving the way to translate this therapeutic strategy into clinical use for patients with CD30+ HL and NHL.

Lung cancer and concurrent or sequential lymphoma: Two case reports with hypersensitivity to bevacizumab and a review of the literature.

Non-small cell lung cancer (NSCLC) accounts for ~80% of all cases of lung cancer, and is the leading cause of cancer-related mortality worldwide. The majority of NSCLC cases of are diagnosed at an advanced stage. The outcome of patients with advanced NSCLC is poor with a median survival time of ~12 months in European and American populations. Lymphoproliferative disorders (LPDs) represent a heterogeneous group of expanding lymphoid cells, which occurs as a result of immune dysfunction. LPDs are often associated with primary solid cancers. We report two cases of LPD diagnosed concurrently and successively to NSCLC. The first case presents a 65-year-old female patient with advanced IV stage lung cancer, according to the International Association for the Study of Lung Cancer TNM staging system. The patient developed a concurrent lymphoma and was treated with first-line therapy including six cycles of gemcitabine and cisplatin, however, the patient experienced an adverse drug reaction to bevacizumab, which was administered after gemcitabine and prior to cisplatin. The second case presented a 74-year-old male patient diagnosed with large B cell lymphoma. The patient acheived remission of the illness, however, after one year the patient was diagnosed with squamous cell lung cancer. After three years, the patient underwent surgery, however disease recurrence was identified. Subsequently, the patient was treated with sterotactic radiotherapy and oral chemotherapy. A review of the associated literature was also conducted.

Mediastinal Gray Zone Lymphoma

In recent years, overlap in biologic and morphologic features has been identified between classic Hodgkin lymphoma (cHL) and B-cell non-Hodgkin lymphoma. Nevertheless, the therapeutic approaches for these diseases remain different. We undertook a study of "mediastinal gray zone lymphomas" (MGZL), with features transitional between cHL nodular sclerosis (NS) and primary mediastinal large B-cell lymphoma (MLBCL) to better understand the morphologic and immunophenotypic spectrum of such cases. Twenty-one MGZL cases were identified over a 20-year period. We also studied 6 cases of composite or synchronous lymphoma with two distinct components at the same time (cHL-NS and MLBCL) and 9 sequential cases with MLBCL and cHL-NS at different times. All patients had a large mediastinal mass. Immunohistochemical studies focused on markers known to discriminate between cHL and MLBCL, including B-cell transcription factors. VJ-PCR was performed in 8 cases to look at clonality of the immunoglobulin heavy chain gene (IgH). Of the gray zone cases, 11 had morphology reminiscent of cHL-NS, but with unusual features, including a large number of mononuclear variants, diminished inflammatory background, absence of classic Hodgkin phenotype, and strong CD20 expression (11 of 11). Ten cases had morphology of MLBCL, but with admixed Hodgkin/Reed-Sternberg and lacunar cells, absent (3 of 10) or weak (7 of 10) CD20 expression, and positivity for CD15 in 7 cases. B-cell transcription factor expression in the gray zone cases more closely resembled MLBCL than cHL with expression of Pax5, Oct2, and BOB.1 in all but 1 case studied (14 of 15). MAL staining was found in 7 of 10 MGZL, and in at least one component of 6 of 7 evaluable composite or sequential MLBCL/cHL cases. Two cases of sequential lymphoma showed rearrangements of the IgH gene of identical size: one in which MLBCL was the first diagnosis and one in which MLBCL was diagnosed at relapse, indicating clonal identity for the two components of cHL and MLBCL. There is accumulating evidence that MLBCL and cHL are related entities. Further support for a relationship between MLBCL and cHL-NS is provided by composite and metachronous lymphomas in the same patient, as well as the existence of MGZL with transitional morphology and phenotype.

Utility of flow cytometry in subtyping composite and sequential lymphoma

Composite lymphoma (CL) is defined as more than one distinct lymphoma variant occurring in the same anatomic site, and sequential lymphoma (SL) is defined as different lymphoma variants occurring at different sites or at different times in the same patient. The utility of flow cytometry immunophenotyping in evaluating CL and SL has only been investigated in a few single-case studies. To further define the utility of flow cytometry in evaluating these tumors, records were searched at two institutions. Cases representing high-grade progression of low-grade lymphoma were excluded. For each CL/SL, clinical data was obtained and morphology was evaluated in routinely processed H&E-stained tissue sections. Tumor components were subtyped using revised European-American classification (REAL) criteria. Follicle center components were graded using modified Rappaport criteria. Immunophenotype was determined using two-color flow cytometry and paraffin-section immunostains. Four cases were identified. Case 1, nodal follicle center, follicular, grade III plus marginal zone CL, showed two discrete populations of monoclonal B-cells that differed in their expression of CD10. Case 2, cutaneous lymphoplasmacytoid lymphoma followed by mesenteric non-Hodgkin's lymphoma (lymphoplasmacytoid plus follicle center, follicular, grade III) plus Hodgkin's disease CL, showed CD5-/CD10-/CD19+/kappa+ cells by flow cytometry in both tissue samples. The Hodgkin's disease component showed CD3-/CD15-/CD20-/CD30+ Reed-Sternberg cell variants in paraffin-section immunostains. Case 3 represented nodal follicle center lymphoma, follicular, grade I (CD3-/CD5-/CD10-/CD19+/kappa+) followed by cutaneous anaplastic large T-cell lymphoma (CD2+/CD4+/CD5+/CD19- cells with partial expression of CD3 and CD7). Case 4 represented cutaneous follicle center lymphoma, follicular, grade I (CD5-/CD10+/CD19+/CD23+/lambda+) followed by bone marrow B-cell small lymphocytic lymphoma (CD5+/CD10-/CD19+/CD23+/kappa+). Results show that flow cytometry is a potentially useful adjunct in characterizing CL and SL.