Survival Among Lymphoma Patients Over the Past Three Decades: A Single Institution Based Retrospective Review From 1976 to 2006.

Abstract Abstract 4527 Background The incidence of lymphoma has doubled in the past 3 decades in the US and most western countries. Since the advent of multi-drug chemotherapy, studies have shown improvement in survival in specific diagnostic groups such as diffuse large B-cell lymphomas. However, there have been few studies showing the impact of evolving therapies on survival for the total burden of lymphoma patients. We assessed survival for an aggregate population of all patients presenting with lymphoma to a regional tertiary university hospital over the past 3 decades. Goal To assess the magnitude of improvement in survival for patients with lymphoma over the past 3 decades. Methods We analyzed data from the Penn State Hershey Medical Center Cancer Registry, selecting all cases diagnosed with lymphoma by ICD-0-3 codes from Jan 1st 1976 to Dec 31st 2006. Five and ten year (yr) absolute survival rates during five time periods [group (gp) 1: 1976-1980, gp 2: 1981-1985, gp 3: 1986-1990, gp 4: 1996-2000, gp 5: 2001-2006] were obtained by using conventional period analysis (PA). In addition, a period Cox Proportional Model (CPH) was fit to the data, allowing for survival risk estimates of 5 yr survival, statistical testing of time periods, and adjustments for age at diagnosis. SAS v 9.1 was used to obtain estimates, with Brenner's PERIOD macro used for PA and PHREG used for CPH. Results Of 2843 patients, Hodgkin's lymphoma accounted for 17%, high grade lymphoma 4%, intermediate grade lymphoma 29%, low grade lymphoma 17%, cutaneous T-cell lymphoma 6%, chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) 13%, malignant lymphoma not otherwise specified (NOS) 14%. Median age was 56 yr and mean was 52 yr with a standard deviation (SD) of 20.9 yr. Median follow up was 4 yr and mean was 6 yr with SD 6.5 yr. Approximately 25% (N=700) survived beyond 10 yr. CPH adjusted for age demonstrated a 5 yr improvement among all lymphomas of 8%, Hazard Ratio (HR)=1.31, 95%, p=0.0192, between gp 5 and gp 1. Consistent improvements in 5 yr survival were detected for intermediate grade lymphoma (15%, HR=1.5, p=0.0219), high grade lymphoma (40%, HR=12.83, p<0.0001), and malignant lymphoma NOS (19%, HR=1.8, p=0.069) comparing gp 5 to gp 1. Changes in survival rates for Hodgkin's lymphoma, low grade lymphoma, CLL/SLL, and cutaneous T-cell lymphoma were not significant. Results for conventional PA were similar. There was a 7% improvement in 5 yr survival between gp 5 and gp 1 for all patients with lymphoma. However, improvement in 10 yr survival between available time intervals was minimal. For the PA, significant improvement in 5 yr survival was seen for intermediate grade lymphoma (24%), high grade lymphoma (28%), malignant lymphoma NOS (19%) comparing gp 5 to gp 1. Interestingly, cutaneous T-cell lymphoma showed a descriptive decline in both 5 yr and 10 yr survival of 29% and 14% respectively. Conclusion There has been a significant improvement of 8% in overall 5 yr survival in lymphoma patients over the past 3 decades after adjusting for age. There was an improvement in survival in both intermediate and high grade groups. There was a trend towards declining survival in cutaneous T cell lymphoma. This could be attributed to diagnostic drift with changing classification and to the fewer number of cases diagnosed in the earlier years as compared to later years. Disclosures: No relevant conflicts of interest to declare.

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Epidemiology, clinical and cytological features of lymphoma in Boxer dogs

Acta Veterinaria Hungarica ◽

10.1556/004.2019.024 ◽

2019 ◽

Vol 67 (2) ◽

pp. 224-240

Author(s):

Urszula Jankowska ◽

Dariusz Jagielski ◽

Michał Czopowicz ◽

Rafał Sapierzyński

Keyword(s):

T Cell ◽

B Cell ◽

Cell Lymphoma ◽

Clinical Stage ◽

T Cell Lymphoma ◽

Low Grade ◽

High Grade ◽

Kiel Classification ◽

Cytological Features ◽

Boxer Dogs

The aim of this study was to evaluate the epidemiology, clinical and laboratory characteristics of canine lymphomas as well as some aspects of treatment outcomes. The study was conducted on Boxer dogs with lymphoma diagnosed by cytology and immunocytochemistry (CD3 and CD79 alpha). During the study period, lymphoma was diagnosed in 63 Boxers; 86.8% were T-cell (based on the Kiel classification: small clear cell lymphoma, pleomorphic small cell lymphoma, pleomorphic mixed T-cell lymphoma, pleomorphic large T-cell lymphoma, lymphoblastic lymphoma/acute lymphoblastic leukaemia) and 13.2% were B-cell lymphomas (according to the Kiel classification: B-cell chronic lymphocytic leukaemia, centroblastic/centroblastic polymorphic lymphoma). Overall survival (OS) was significantly longer in dogs with low-grade than with high-grade lymphoma (median OS of 6.8 and 4.7 months, respectively; P = 0.024). OS was not influenced by WHO clinical stage, WHO clinical substage, presence of splenomegaly, early administration of glucocorticoids or the time from the first presentation to the beginning of chemotherapy. There are no significant differences in clinical and laboratory parameters between low-grade and high-grade lymphomas. Boxer dogs are predisposed to T-cell lymphoma, with a predominance of high-grade tumour, especially pleomorphic, mixed small and large T-cell subtype. It is possible that Boxer dogs may respond less favourably to chemotherapy than patients of other breeds.

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Clinical efficacy of zanolimumab (HuMax-CD4): two phase 2 studies in refractory cutaneous T-cell lymphoma

Blood ◽

10.1182/blood-2006-12-062877 ◽

2007 ◽

Vol 109 (11) ◽

pp. 4655-4662 ◽

Cited By ~ 138

Author(s):

Youn H. Kim ◽

Madeleine Duvic ◽

Erik Obitz ◽

Robert Gniadecki ◽

Lars Iversen ◽

...

Keyword(s):

T Cell ◽

Clinical Efficacy ◽

Response Rate ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Low Grade ◽

Cutaneous T Cell Lymphoma ◽

Phase 2 ◽

Two Phase ◽

Median Response

Abstract The efficacy and safety of zanolimumab in patients with refractory cutaneous T-cell lymphoma (CTCL) have been assessed in two phase 2, multicenter, prospective, open-label, uncontrolled clinical studies. Patients with treatment refractory CD4+ CTCL (mycosis fungoides [MF], n = 38; Sézary syndrome [SS], n = 9) received 17 weekly infusions of zanolimumab (early-stage patients, 280 and 560 mg; advanced-stage patients, 280 and 980 mg). The primary end point was objective response (OR) as assessed by composite assessment of index lesion disease activity score. Secondary end points included physician's global assessment (PGA), time to response, response duration, and time to progression. ORs were recorded for patients in both CTCL types (MF, 13 ORs; SS, 2 ORs). In the high-dose groups (560 and 980 mg dose groups), a response rate of 56% was obtained with a median response of 81 weeks. Adverse events reported most frequently included low-grade infections and eczematous dermatitis. Zanolimumab showed marked clinical efficacy in the treatment of patients with refractory MF, with early onset of response, high response rate, and durable responses. The treatment was well tolerated with no dose-related toxicity other than the targeted depletion of peripheral T cells. A pivotal study has been initiated based on these findings.

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Differential Expression of the Homeobox Gene MIXL1 in Non Hodgkin (NHL) and Hodgkin Lymphomas (HL).

Blood ◽

10.1182/blood.v106.11.3014.3014 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3014-3014

Author(s):

Elias Drakos ◽

George Z. Rassidakis ◽

Wei Guo ◽

L. Jeffrey Medeiros ◽

Lalitha Nagarajan

Keyword(s):

T Cell ◽

Protein Expression ◽

B Cell ◽

Tumor Cells ◽

Cell Lymphoma ◽

Lymphoblastic Leukemia ◽

T Cell Lymphoma ◽

High Grade ◽

Intermediate Grade ◽

Aberrant Expression

Abstract The gene MIXL1 (Mix1 homeobox-like) encodes a paired class homeobox transcription factor involved in early hematopoietic specification during embryogenesis. Previous studies have shown that MIXL1 gene is expressed in hematopoietic cells during adult life (Guo et al. Blood100;1;89–96, 2002). Furthermore 5′ MIXL1 sequences are a target of retroviral insertion in murine T-cell lymphoma (http:RTCGD.ncifcrf.gov), suggesting a selection advantage for aberrant expression of this gene. However, the status of MIXL1 expression in human lymphomas has not been examined. Using a highly specific antibody, we assessed for MIXL1 protein expression in 14 lymphoma cell lines (9 B-cell and 5 T-cell) by immunobloting. MIXL1 was detected predominantly in nuclear extracts of lysates of all cell lines tested, although at a variable level. We also assessed for MIXL1 protein expression in 126 B-cell and 21 T-cell NHLs of various types, as well as 14 Hodgkin lymphomas using immunohistochemical methods. The results of the immunohistochemical studies are summarized in table 1. Once again, MIXL1 immunoreactivity was primarily nuclear in the tumor cells. Based on distribution data (histogram), a 50% cutoff was selected for high versus low MIXL1 expression. Among B-cell tumors, high expression levels of MIXL1 protein were more frequently detected in high-grade NHL and HL compared with low/intermediate grade NHL (p<0.0001, chi-square test). As a continuous variable, the percentage of MIXL1-positive tumor cells was also significantly higher in high-grade B-cell NHL and HL compared with low/intermediate grade NHL (p<0.0001, Kruskal Wallis test). All Hodgkin lymphomas expressed high levels of MIXL1 with 60% to 100% of neoplastic cells being positive for MIXL1. Most T-cell NHLs also expressed high levels of MIXL1. In contrast, most low/intermediate-grade B-cell NHL and multiple myelomas expressed low levels of MIXL1. Frequent overexpression of MIXL1 gene product in most high-grade B-cell NHLs, HL and T-cell NHLs suggests that aberrant expression of MIXL1 may play a role in proliferation, block of differentiation or both. Table 1. HL (n=14) B-NHL (n =126) T-NHL (n =21) N (%) Low/intermediate grade N (%) N (%) Classical HL 12/12(100%) Chronic lymphocytic leukemia /small lymphocytic lymphoma 0/8 (0% T-precursor lymphoblastic leukemia/lymphoma 2/2 (0%) Nodular lymphocyte predominance HL 2/2 (100%) MALT-lymphoma 0/8 (0%) Mycosis fungoides/Sezary syndrome 2/2 (0%) Follicular lymphoma 9/24 (38%) Extranodal NK/T-cell lymphoma, nasal type 3/3 (100%) Mantle cell lymphoma 5/34 (15%) Peripheral T-cell lymphoma, unspecified 6/9 (66% High grade Anaplastic large cell lymphoma 5/5 (100%) B-precursor lymphoblastic leukemia/lymphoma 1/3 (33%) Burkitt lymphoma/leukemia 2/2 (100%) Diffuse large B-cell lymphoma 30/31 (97%) Plasma cell myeloma/plasmacytoma 0/16 (0%)

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Inactivation of the p16 Cyclin-Dependent Kinase Inhibitor in High-Grade Canine Non-Hodgkin's T-Cell Lymphoma

Veterinary Pathology ◽

10.1354/vp.44-4-467 ◽

2007 ◽

Vol 44 (4) ◽

pp. 467-478 ◽

Cited By ~ 32

Author(s):

S. P. Fosmire ◽

R. Thomas ◽

C. M. Jubala ◽

J. W. Wojcieszyn ◽

V. E. O. Valli ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

T Cell Lymphoma ◽

World Health ◽

Low Grade ◽

High Grade ◽

Chromosome 11 ◽

Rb Phosphorylation

The significance of p16/Rb tumor suppressor pathway inactivation in T-cell non-Hodgkin's lymphoma (NHL) remains incompletely understood. We used naturally occurring canine NHL to test the hypothesis that p16 inactivation has specific pathologic correlates. Forty-eight samples (22 T-cell NHL and 26 B-cell NHL) were included. As applicable, metaphase- or array-based comparative genomic hybridization, Southern blotting, promoter methylation, and Rb phosphorylation were used to determine the presence, expression, and activity of p16. Fisher's exact test was used to test for significance. Deletion of p16 (or loss of dog chromosome 11) was restricted to high-grade T-cell NHL (lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified). These were characterized by a concomitant increase of tumor cells with Rb phosphorylation at canonical CDK4 sites. Rb phosphorylation also was seen in high-grade B-cell NHL (diffuse large B-cell lymphoma and Burkitt-type lymphoma), but in those cases, it appeared to be associated with c-Myc overexpression. The data show that p16 deletion or inactivation occurs almost exclusively in high-grade T-cell NHL; however, alternative pathways can generate functional phenotypes of Rb deficiency in low-grade T-cell NHL and in high-grade B-cell NHL. Both morphologic classification according to World Health Organization criteria and assessment of Rb phosphorylation are prognostically valuable parameters for canine NHL.

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A Rare Presentation of Transformed, CD30+ High-Grade Cutaneous T-Cell Lymphoma of the Hallux

Journal of the American Podiatric Medical Association ◽

10.7547/13-103.1 ◽

2015 ◽

Vol 105 (6) ◽

pp. 550-556

Author(s):

Brant L. McCartan ◽

Bang Tang ◽

Allyson Berglund ◽

John Giurini ◽

German Pihan

Keyword(s):

T Cell ◽

Lymphatic System ◽

Cell Lymphoma ◽

Treatment Protocol ◽

T Cell Lymphoma ◽

High Grade ◽

Cutaneous T Cell Lymphoma ◽

Rare Presentation ◽

Molecular Defects

Cutaneous T-cell lymphoma is a type of non-Hodgkin's lymphoma, which is a neoplasm affecting the lymphatic system. Mycosis fungoides is the most common subset of cutaneous T-cell lymphoma and is often treated conservatively. This neoplasm is most common in adults older than 60 years and does not regularly manifest in the toes. A case is reported of a 70-year-old man seen for a nonhealing hallux ulceration leading to amputation. Histopathologic examination revealed a rare transformed CD30+ high-grade cutaneous T-cell lymphoma. The morbidity of lymphomas is highly dependent on type and grade. Pharmaceutical precision therapies exist that target specific molecular defects or abnormally expressed genes, such as high expression of CD30. This article focuses on treatment protocol and emphasizes the importance of early diagnosis, determination of cell type, and proper referral of atypical dermatologic lesions.

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