Accuracy of Pathologic Diagnosis in Patients With Lymphoma and Survival: A Prospective Analysis From Botswana

PURPOSE With intense HIV epidemics, southern African countries have a high burden of classic Hodgkin lymphoma (CHL) and non-Hodgkin lymphoma (NHL). However, suboptimal access to pathology resources limits subtype classification. We sought to assess the diagnostic accuracy of specimens classified as lymphoma and to determine association between discordant pathologic diagnosis and overall survival. METHODS Seventy patients with CHL or NHL and treated at three Botswana hospitals from 2010 to 2016 were analyzed. Local pathologic assessment relied primarily on morphology. All cases underwent secondary US hematopathology review, which is considered gold standard. RESULTS The median follow-up was 58 months. The overall reclassification rate was 20 of 70 cases (29%). All 20 CHL cases were correctly classified in Botswana, and mixed cellularity was the most common subtype, diagnosed in 11 (55%) cases. Of 47 confirmed NHL cases, diffuse large B-cell lymphoma was the final US diagnosis in 28 cases (60%), another aggressive B-cell NHL in nine (19%), an indolent B-cell NHL in six (13%), and T-cell NHL in four (9%). Common types of diagnostic discordance included NHL subtype reclassification (11 of 20, 55%) and CHL reclassified as NHL (7 of 20, 35%). Concordant versus discordant diagnosis after secondary review was associated with improved 5-year overall survival (60.1% v 26.3%, P = .0066). Discordant diagnosis was independently associated with increased risk of death (adjusted hazard ratio 2.733; 95% CI, 1.102 to 6.775; P = .0300) even after stratifying results by CHL versus NHL. CONCLUSION In this single prospective cohort, discordant pathologic diagnosis was associated with a nearly three-fold increased risk of death. Limited access to relatively basic diagnostic techniques impairs treatment decisions and leads to poor patient outcomes in low-resource countries.

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Transformation and outcome of nodular lymphocyte predominant Hodgkin lymphoma: a Finnish Nationwide population-based study

Blood Cancer Journal ◽

10.1038/s41408-021-00586-1 ◽

2021 ◽

Vol 11 (12) ◽

Author(s):

Ilja Kalashnikov ◽

Tomas Tanskanen ◽

Janne Pitkäniemi ◽

Nea Malila ◽

Sirkku Jyrkkiö ◽

...

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Relative Survival ◽

B Cell Lymphoma ◽

Population Based ◽

Population Based Study ◽

Entire Study ◽

Risk Of Death ◽

Increased Risk ◽

Histological Transformation

AbstractNodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare B-cell malignancy associated with excellent survival. However, some patients experience histological transformation into aggressive large B-cell lymphoma. Population-based data on transformation in patients with NLPHL is limited. We conducted a nationwide population-based study to estimate the risk of transformation and relative survival in patients diagnosed with NLPHL in Finland between 1995 and 2018. We identified a total of 453 patients (median age, 48 years; 76% males) with the incident NLPHL from the Finnish Cancer Registry. The cumulative incidence of transformation was 6.3% (95% CI, 4.2-9.6) at 10 years. After adjusting for sex, age and year of diagnosis, transformation was associated with a substantially increased risk of death (HR 8.55, 95% CI 4.49−16.3). Ten-year relative survival was 94% (95% CI, 89%‒100%). The patients diagnosed at a later calendar year had lower excess risk of death (HR, 0.38 per 10-year increase; 95% CI, 0.15‒0.98). We conclude that while the 10-year relative survival for the patients with NLPHL was excellent in this large population-based cohort for the entire study period, transformation resulted in a substantially increased mortality compared with the patients without transformation. Our results also suggest a reduction in excess mortality over time.

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Cytokine polymorphisms in Th1/Th2 pathway genes, body mass index, and risk of non-Hodgkin lymphoma

Blood ◽

10.1182/blood-2010-07-295097 ◽

2011 ◽

Vol 117 (2) ◽

pp. 585-590 ◽

Cited By ~ 26

Author(s):

Yingtai Chen ◽

Tongzhang Zheng ◽

Qing Lan ◽

Francine Foss ◽

Christopher Kim ◽

...

Keyword(s):

Body Mass Index ◽

B Cell ◽

Hodgkin Lymphoma ◽

Body Mass ◽

Significant Interaction ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Lymphocytic Leukemia ◽

Non Hodgkin Lymphoma ◽

Increased Risk

Abstract We conducted a population-based, case-control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes modify the relationship between body mass index (BMI) and risk of non-Hodgkin lymphoma (NHL). Compared with those with BMI less than 25 kg/m2, women with BMI more than or equal to 25 kg/m2 had 50% to 90% increased risk of NHL among women who carried IFNGR2 (rs9808753) AA, IL5 (rs2069812) CT/TT, IL7R (rs1494555) AA, and TNF (rs1799724) CC genotypes, but no increased risk among women with IFNGR2 AG/GG, IL5 CC, IL7R AG/GG, and TNF CT/TT genotypes. A significant interaction with BMI was only observed for IFNGR2 (rs9808753 Pforinteraction = .034) and IL7R (rs1494555 Pforinteraction = .016) for NHL overall; IL7R (rs1494555 Pforinteraction = .016) and TNF (1799724 Pforinteraction = .031) for B-cell lymphoma; and IL5 (rs2069812 Pforinteraction = .034) for T-cell lymphoma. After stratification by common B-cell lymphoma subtypes, a significant interaction was observed for IFNGR2 (rs9808753 Pforinteraction = .006), IL13 (rs20541 Pforinteraction = .019), and IL7R (rs1494555 Pforinteraction = .012) for marginal zone B-cell lymphoma; IL7R (rs1494555 Pforinteraction = .017) for small lymphocytic lymphoma/chronic lymphocytic leukemia; and IL12A (rs568408 Pforinteraction = .013) and TNF (1799724 Pforinteraction = .04) for follicular lymphoma. The results suggest that common genetic variation in Th1/Th2 pathway genes may modify the association between BMI and NHL risk.

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Improved Outcome of Relapsed or Refractory Pediatric B-Cell Non-Hodgkin Lymphoma in Japan

Blood ◽

10.1182/blood.v126.23.5078.5078 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5078-5078

Author(s):

Tomoo Osumi ◽

Tetsuya Mori ◽

Naoto Fujita ◽

Akiko M. Saito ◽

Atsuko Nakazawa ◽

...

Keyword(s):

Overall Survival ◽

Survival Rate ◽

B Cell ◽

Hodgkin Lymphoma ◽

Salvage Therapy ◽

Combined Treatment ◽

B Cell Lymphoma ◽

Overall Survival Rate ◽

Hematopoietic Stem ◽

Non Hodgkin Lymphoma

Abstract Introduction Relapsed or refractory pediatric B-cell non-Hodgkin lymphoma (B-NHL) has been reported to be extremely difficult to cure. We previously conducted a retrospective study of pediatric relapsed or refractory B-NHL in Japan between 1996 and 2004 and found that the four-year overall survival rate was only 20.5% (Fujita N. e al. PBC. 2008). Rituximab, a chimeric anti-CD20 monoclonal antibody, is expected to be effective in improving the prognosis of pediatric relapsed or refractory B-NHL and was approved for use in 2003 in Japan. Here, we retrospectively assessed the treatment and prognosis of pediatric relapsed or refractory pediatric B-NHL in the rituximab era in Japan. Methods We collected relapsed pediatric B-NHL cases from patients enrolled in our current study, JPLSG B-NHL03 study, which was the first nationwide multicenter trial for newly diagnosed pediatric B-NHL. We collected information on treatment and outcome after induction failure or relapse. Results In 33 patients enrolled this study, the median age at diagnosis was 9.7 years and male predominance was observed. Nine cases were pathologically subclassified initially as diffuse large B-cell lymphoma, 11 as Burkitt lymphoma, 11 as Burkitt Leukemia and two as others. According to initial Murphy staging, most cases were in the advanced stage. The most common site of relapse was abdomen (8 cases), followed by bone marrow (8 cases) and central nervous system (7 cases). Twenty-three cases relapsed in one site while 10 did so in multiple sites. Among them, 20 relapsed within six months after initial diagnosis. Among them, 28 patients received some rituximab combined treatment as salvage therapy. R-ICE (rituximab, ifosfamide, carboplatin and etoposide) regimen was the most popular and used in 22 patients as first-line salvage therapy. As a result, 22 patients (66.7%) achieved complete remission (CR) by some salvage therapy. 23 received hematopoietic stem cell transplantation (HSCT). Their 5-year overall survival rate was 48.5%, which was far more superior to both our previous study (Figure 1) and another on relapsed or refractory B-NHL in childhood. In risk factor analysis for survival, rituximab combined treatment and HSCT did not influence the outcome, but achievement of CR after salvage treatment resulted in significantly better survival (68.2% vs 9.1%, p=0.001). These results suggest that the advent of rituximab induced an improvement of CR rate for relapsed paediatric B-NHL, which resulted in an improvement of the survival rate. Conclusion In conclusion, the prognosis of the pediatric relapsed or refractory B-NHL in a Japanese cohort remained poor but is showing improvement in the rituximab era. Disclosures No relevant conflicts of interest to declare.

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The role of radiotherapy and intrathecal CNS prophylaxis in extralymphatic craniofacial diffuse large B-cell lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.8566 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 8566-8566

Author(s):

Niels Murawski ◽

Samira Zeynalova ◽

Gerhard Held ◽

Marita Ziepert ◽

Barbara Kempf ◽

...

Keyword(s):

Overall Survival ◽

B Cell ◽

Cell Lymphoma ◽

Multivariable Analysis ◽

Cumulative Risk ◽

B Cell Lymphoma ◽

Risk Groups ◽

Cns Disease ◽

Increased Risk

8566 Background: The role of radiotherapy and intrathecal prophylaxis in extralymphatic craniofacial involvement of aggressive B-cell lymphoma remains to be determined in the rituximab era. Methods: In a retrospective subgroup analysis of 9 consecutive prospective DSHNHL trials covering all DLBCL risk groups from 18 to 60 years of age, patients with and without craniofacial involvement were compared with respect to clinical presentation, event-free and overall survival. Results: 336 sites of extralymphatic craniofacial involvement were observed in 284/3840 (7.4%) patients (orbita: 30, paranasal sinuses: 90; main nasal cavity: 38, tongue: 26, remaining oral cavity: 99, salivary glands: 53). In a multivariable analysis adjusting for IPI risk factors the addition of rituximab improved EFS and OS in both patients with and without craniofacial involvement. The 141 responding patients who received radiotherapy to sites of craniofacial involvement had a similar 3-year event-free (79% vs 79%; p=0.835) and 3-year overall survival (88% vs. 85%; p=0.311) when compared with the 56 patients who did not receive radiotherapy. Without rituximab, the 2-year-rate of cumulative risk of CNS disease was increased in 205 patients with compared to 2586 patients without craniofacial involvement (4.2% vs. 2.8%; p=0.038), while this difference disappeared in patients who received CHOP(like) chemotherapy in combination with rituximab (1.7% in 77 patients with compared to 2.9% in 946 patients without craniofacial involvement; p=0.868). Of 85 patients with craniofacial involvement who received intrathecal prophylaxis with methotrexate, the 2-year-rate of cumulative risk of CNS disease was 4.3% compared to 2.3% in 189 patients who did not (p=0.995). Conclusions: Rituximab eliminates the increased risk for CNS disease in patients with craniofacial involvement. As a practical consequence intrathecal prophylaxis and radiotherapy to sites of craniofacial involvement should not be given any more.

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Lymphdx: A Custom Microarray for Molecular Diagnosis and Prognosis in Non-Hodgkin Lymphoma.

Blood ◽

10.1182/blood.v104.11.701.701 ◽

2004 ◽

Vol 104 (11) ◽

pp. 701-701 ◽

Cited By ~ 1

Author(s):

Sandeep S. Dave ◽

G. Wright ◽

B. Tan ◽

A. Rosenwald ◽

W. C. Chan ◽

...

Keyword(s):

Gene Expression ◽

Overall Survival ◽

B Cell ◽

Hodgkin Lymphoma ◽

Molecular Diagnosis ◽

Cell Lymphoma ◽

Diagnostic Algorithm ◽

B Cell Lymphoma ◽

Response To Therapy ◽

Non Hodgkin Lymphoma

Abstract Clinical management differs significantly for the various types of non-Hodgkin lymphoma (NHL), and the diagnosis of these lymphomas can be challenging in some cases. Further, existing NHL categories include subgroups that can differ substantially in gene expression, response to therapy and overall survival. We have created a custom oligonucleotide microarray, named LymphDx, which could prove clinically useful for molecular diagnosis and outcome prediction in NHL. Biopsy specimens were obtained from 559 patients with a variety of lymphomas and lymphoproliferative conditions. Gene expression profiles of these samples were obtained using Affymetrix U133 A and B microarrays. The 2653 genes on LymphDx were chosen to include:(1)Genes most differentially expressed among NHL types based on Affymetrix U133 or Lymphochip microarrays (2)Genes predicting length of survival in diffuse large B cell lymphoma(DLBCL), follicular lymphoma(FL) and mantle cell lymphoma(MCL) (3)Genes encoded in the EBV and HHV-8 viral genomes (4)Genes encoding all known surface markers, kinases, cytokines and their receptors, as well as oncogenes, tumor suppressors, and other genes relevant to lymphoma. The LymphDx microarray was used to profile gene expression in 434 biopsy samples. These data were used to create a diagnostic algorithm that can distinguish various NHL types and benign follicular hyperplasia(FH) based on gene expression. The algorithm classifies a sample into one of the following categories: Burkitt’s lymphoma(BL), DLBCL, FL, MCL, small lymphocytic lymphoma(SLL) or FH. The algorithm further distinguishes the 3 recognized DLBCL subgroups: germinal center B cell-like, activated B cell-like or primary mediastinal lymphoma. Using a leave one out, cross validation strategy, the algorithm was found to agree well with the pathology diagnosis (see Figure). Some samples were deemed unclassified when their gene expression did not adequately match with that of any of the NHL categories. For a few samples, the gene expression-based diagnosis and the pathology diagnosis were discordant. Pathology review showed that two NHL types coexisted (eg FL and DLBCL) in many of these cases, potentially explaining the results of the diagnostic algorithm. LymphDx could also reliably predict the overall survival of patients with DLBCL, FL and MCL. Prospective evaluation of the LymphDx microarray is warranted since it could be used to provide objective molecular diagnostic, and prognostic information for patients with NHL. Figure Figure

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Characteristics and Outcome Among 116 Patients with HIV Associated Lymphoma Included in the French ANRS CO16 Lymphovir Cohort Study.

Blood ◽

10.1182/blood.v120.21.2147.2147 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2147-2147

Author(s):

Caroline Besson ◽

Sophie Prevot ◽

Houria Chavez ◽

Selma Trabelsi ◽

Michele Genin ◽

...

Keyword(s):

Hiv Infection ◽

B Cell ◽

Disease Progression ◽

Hodgkin Lymphoma ◽

B Cell Lymphoma ◽

World Health ◽

Second Cancer ◽

Anaplastic Lymphoma ◽

Increased Risk

Abstract Abstract 2147 Background: Human Immunodeficiency Virus (HIV) infection is associated with an increased risk of Hodgkin lymphoma (HL) and B-cell non-Hodgkin lymphoma (NHL). Increased risk of NHL is strongly correlated to the severity of the underlying immunodeficiency. Introduction of combined antiretroviral therapy (cART) has reduced the incidence of NHL -but not of HL's- among HIV-infected individuals. Outcomes are reported to be poorer among HIV-infected patients with HL or NHL than among non-HIV-infected patients. We carry out a cohort with the aim to study the characteristics and outcome of HIV-related lymphomas. Methods: The multicentric prospective Cohort of HIV related lymphomas (ANRS-CO16 Lymphovir cohort) enrolled 116 adult patients in 32 centers between October 2007 and April 2012. Investigations were performed after approval of the ethic committee. Patients were included at diagnosis of lymphoma (n=108) or at first relapse (1 HL, 7 NHL). Data collection concerned HIV infection history, clinical, biological and histological presentation, treatment and evolution of lymphoma. Pathological materials were centralized and 91 cases were reviewed. Diagnoses were based on World Health Organization criteria. Each patient was followed every 6 months during 5 years. Results: Among the 116 patients, 39.7% (46) were diagnosed with HL and 60.3% (70) with NHL. Median age was 43.5 years (ranging from 20 to 61) among patients with HL and 47 years (23 to 67) among those with NHL. Gender (male/female) ratio was 8.2 (41/5) among patients with HL, 1.7 (44/26) among those with NHL. The histological distribution of NHL were diffuse large B-cell lymphoma (DLBCL) 54.3% (38), Burkitt lymphomas (BL) 18.6% (13), plasmablastic lymphoma 10% (7), marginal zone/lymphoplasmocytic lymphoma 7.1% (5), others 10%: PTLD- like lymphoma (2), primary effusion lymphoma (1), follicular lymphoma (1), anaplastic lymphoma (1), unclassified (2). There was a predominance of clinical stages III/IV versus I/II among HL (76.7%, 33/43) and NHL patients (73.5%, 50/68). Among patients with DLBCL, LDH level was elevated in 68.4% (26/38) and performance status altered (2–4 versus 0–1) in 38.5% (15/39). HIV infection had been diagnosed for a median of 151 months (0 to 312) among HL patients and 117 (0 to 327) among those with NHL. The interval between diagnoses of HIV infection and lymphoma was shorter than 3 months for 2 patients with HL and 13 with NHL. All other patients except 6 NHL patients had been treated with ART at diagnosis of lymphoma. Median durations of ARV were 128 months (2 to 238) among HL patients and 119 months (1 to 236) among those with NHL. Patients with HL had a median CD4 T-cell count at diagnosis of lymphoma of 353/mm3 (range 37–1120), those with NHL, 261/mm3 (range 7–1322)]. The median interval between lymphoma occurrence and last follow-up was 21 months (range 0–41). During follow-up, all patients were treated with ARV. Among first-line HL patients, 39 out of 40 were treated with ABVD. Out of 40 patients with DLBCL or BL, 30 received chemotherapies combined with rituximab. At 24 months, overall survival is 95% among patients with HL and 78% among those with NHL (Figure 1). Two HL patients died during follow-up: one HL patient included in relapse from progression, another from a second cancer. Sixteen NHL patients died during follow-up: there were 10 early deaths (<6 months) from complications of treatment (9) or disease progression (1) and 6 later deaths from disease progression (4), second cancer (1), unknown (1). None of the patients who died during the first 6 months following diagnosis had received rituximab. Conclusions: The present study points out the high proportion of HL among HIV infection with lymphoma in the cART era and their favourable outcome compared to previous reports. This study also strengthens the heterogeneity of HIV-related lymphomas and the frequency of early deaths among patients with NHL. Disclosures: No relevant conflicts of interest to declare.

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Intensive Immunochemotherapy In Patients With B-Cell Lymphoma, Unclassifiable (B-UCL), With Features Intermediate Between Diffuse Large B-Cell Lymphoma (DLBCL) and Burkitt Lymphoma (BL): A Comparison With BL Patients Treated With The Same Protocol In The Pethema-Burkimab-04 Trial

Blood ◽

10.1182/blood.v122.21.1793.1793 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1793-1793

Author(s):

Pere Barba ◽

Albert Oriol ◽

Carlos Grande ◽

Pau Abrisqueta ◽

José González-Campos ◽

...

Keyword(s):

Overall Survival ◽

B Cell ◽

Clinical Characteristics ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

World Health ◽

Hiv Positive ◽

Risk Of Death ◽

Grade 3

Abstract B-UCL is a new category of lymphomas that comprises a heterogeneous group of tumors from a morphological, phenotypic and genetic perspective with features intermediate between DLBCL and BL. This entity has been included as a new category in the 2008 World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues. The outcome of patients with B-UCL is generally considered very poor. However, the number of series analyzing the prognosis of B-UCL is scarce and they include small number of patients not homogeneously treated. Against this background, herein we present a series of patients diagnosed with B-UCL (WHO 2008) or Burkitt-like variant (WHO 2001) homogeneously treated according to the PETHEMA-Burkimab-04 trial. This trial was designed for the treatment of BL, including both HIV positive and negative patients. Patients with B-UCL were allowed to be treated following the same protocol and were considered separately. The main clinical characteristics and outcome were compared to those obtained from classical BL patients in the same trial (Ribera et al. Cancer 2013). Diagnosis of B-UCL was made in each center based on morphological, phenotypic and genetic characteristics and centrally reviewed by two pathologists. Patients received 6 courses of chemotherapy including continuous methotrexate infusion, cytarabine, vincristine and dexametasone among other drugs. A single dose of rituximab (375mg/m2) before each cycle was administered. Patients with non-bulky stage I-II disease received only 4 courses of treatment, whereas patients with advanced stage (II bulky-IV) received 2 additional doses of rituximab at the end of the chemotherapy. A total of 30 patients with B-UCL were included and were compared with the 118 patients with BL. Median follow-up for survivors was 24 months (range 3-93). Considering B-UCL, 8 (27%) patients were HIV positive and 10 (33%) had an ECOG performance status ≥ 2. Four (13%) and 6 (20%) patients had CNS involvement and bulky (>10 cm) disease, respectively. Serum LDH level was > UNL in 25 (83%) patients. These and other clinical characteristics were similar between patients with B-UCL and BL, except for the median age at diagnosis (57 years in B-UCL vs. 44 years in BL, p=0.001). In B-UCL patients, death during induction occurred in 5 patients (17%) and 2 patients experienced treatment failure. Twenty-three (77%) patients achieved complete remission. Relapse after CR and death in remission were observed in one patient, each. All these outcomes were comparable with BL patients except for a trend to a higher risk of death during induction in patients with B-UCL (17% in B-UCL, vs. 8% in BL, p= 0.1). A total of 104 consolidation cycles were evaluable for patients with B-UCL. Most frequent grade 3-4 toxicities were neutropenia (n=57, 54%), thrombocytopenia (n=44, 42%) and infection (n=21, 20%). Grade 3-4 gastrointestinal, renal and hepatic toxicities were seen in <5% of the cycles. Overall survival at 2 years for patients with B-UCL and BL was 68% (95% CI 59-77) vs. 78% (95% CI 74-82), p=0.2, respectively. Probability of disease-free survival from CR1 for B-UCL and BL patients was 84% (95% CI 76-92) vs. 80% (95% CI 69-91), p=0.6. In conclusion, the Burkitt-type chemotherapy included in the PETHEMA-Burkimab-04 trial was able to achieve an important number of complete and durable responses in patients with B-UCL with an acceptable toxicity. As a consequence, the outcome of patients with B-UCL treated with this intensive immunochemotherapy seems similar to that obtained in the treatment of classical BL.Figure 1Overall survival from diagnosis in patients with B-UCL and BL treated with Burkimab-04.Figure 1. Overall survival from diagnosis in patients with B-UCL and BL treated with Burkimab-04.Table 1Baseline characteristics of all patients according to definitive diagnosis.CharacteristicsBurkitt (n = 118)LDCG-B/Burkitt (n=30)pGender, male n (%)85 (72)21 (70)0.8Age, median [min -max]44 [15 - 83]57 [16-77]0.001Stage, n (%)Non bulky I – II26 (22)10 (33)0.8II (bulky), III - IV92 (78)20 (67)ECOG ≥2, n (%)55 (47)10 (33)0.3HIV infection39 (33)8 (27)0.4Extranodal involvement (≥2 sites), n (%)55 (47)11 (37)0.5CNS involvement, n (%)14 (12)4 (13)0.6Bulky disease, n (%)31 (26)6 (20)0.3LDH level above normal, n (%)106 (90)25 (83)0.5Age-adjusted IPI, n (%)Low6/116 (5)2 (7)1Low-intermediate17/116 (15)6 (20)Intermediate-high46/116 (40)11 (37)High47/116 (40)11 (37)Follow-up [all patients] (months)19 (0-92)16 (0-93)0.9 Disclosures: No relevant conflicts of interest to declare.

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Distinct CD30 Expression Patterns In Germinal Center B-Cell (GCB) and Non-GCB Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽

10.1182/blood.v122.21.5064.5064 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5064-5064

Author(s):

Shipra Gandhi ◽

Vishala T. Neppalli ◽

George Deeb ◽

Myron S. Czuczman ◽

Francisco J Hernandez-Ilizaliturri

Keyword(s):

Overall Survival ◽

B Cell ◽

Hodgkin Lymphoma ◽

Germinal Center ◽

Molecular Subtypes ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Complete Response ◽

Therapeutic Strategies ◽

Germinal Center B Cell

Abstract Background DLBCL is the most common type of non-Hodgkin lymphoma, which demonstrates morphologic, immunophenotypic, molecular, and clinical heterogeneity. Gene expression profiling studies define two molecular subtypes of DLBCL, namely germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL. Hans' algorithm was developed to provide an immunohistochemical correlation to the molecular subtypes of DLBCL. In the pre and post-rituximab era, ABC subtype of DLBCL is known to demonstrate poor overall survival when compared to GCB subtype. In addition, relapsed or primary refractory DLBCL responds poorly to current therapeutic strategies. These findings underscore the necessity to identify novel therapeutic targets in DLBCL to achieve better clinical outcomes. Recent data suggests that CD30, a member of the tumor necrosis factor receptor family, is a potential therapeutic target in DLBCL. CD30 is widely expressed in classical Hodgkin lymphoma (cHL) and anaplastic large cell lymphoma (ALCL) thus serving as an attractive target of immunotherapy for cHL and ALCL. In this study we conducted a retrospective evaluation of CD30 expression in GCB and non-GCB DLBCL, treated at our Institution with standard front-line chemo-immunotherapy (i.e. R+CHOP or R+ DA-EPOCH). Materials and Methods We identified 60 patients with confirmed DLBCL for which archived formalin fixed paraffin embedded tissue was available in the form of a tissue micro-array (39 Cases) or diagnostic biopsy material (21 Cases). Immunohistochemical detection of CD30 was performed using routine methods (Biocare #PM031, ready to use aliquots). Demographic, clinical and pharmacological parameters were obtained for each patient. DLBCL cases were subtyped as GCB or non-GCB using immunohistochemistry-based Hans' algorithm. Membranous and Golgi pattern of CD30 expression in the tumor cells was designated as positive. Results 21 patients (48.8%) were classified as GCB, 22 patients (51.2%) non-GCB. CD30 expression was detected in 13.3% of all DLBCL patients. Differences in CD30 expression were noted between GCB- and non-GCB DLBCL. CD30 expression was detected in 9.5% and 23% of the GCB- and non-GCB DLBCL subtypes respectively. Demographics and clinical characteristics were equally distributed between GCB- and non-GCB and between CD30 positive or negative DLBCL. Patients received either R+CHOP (82%) or R+DA-EPOCH (18%). The complete response (CR) rate of the entire cohort was 67% and no differences were observed between GCB- or non-GCB DLBCL. CD30 (+) DLBCL had a higher CR (complete response) rate than CD30 (-) DLBCL (88% vs 63.4%). However, the numbers were too small to reach statistical significance. No significant differences were observed between CD30 (+) or (-) DLBCL in terms of progression free survival (PFS) (CD30[-]37m vs. CD30[+]16.5m, P =0.785) or overall survival (OS) (CD30[-]86m vs. CD30[+]57.4m, P =0.99). In contrast to previously reported by other investigators, there was no difference in the clinical outcome between GCB vs. non-GCB DLBCL treated with R+CHOP or R+DA-EPOCH. Conclusions Our data suggests that CD30 expression is more prevalent in non-GCB DLBCL patients based on our small cohort. While CD30 expression may not confer a prognostic value in newly diagnosed DLBCL (Table 1), routine testing for it may identify a group of patients that may benefit from CD30-targeted therapeutic strategies (i.e. antibody-drug conjugates) in the relapsed/refractory setting. (Research, in part, supported by The Eugene and Connie Corasanti Lymphoma Research Fund) Disclosures: Czuczman: Genetech, Onyx, Celgene, Astellas, Millennium, Mundipharma: Advisory Committees Other. Hernandez-Ilizaliturri:Seattle Genetics: Consultancy, Honoraria.

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Primary lymphoma of bone: a population-based study of 2558 patients

Therapeutic Advances in Hematology ◽

10.1177/2040620720958538 ◽

2020 ◽

Vol 11 ◽

pp. 204062072095853

Author(s):

Chen-Xin Liu ◽

Tian-Qi Xu ◽

Li Xu ◽

Pan-Pan Wang ◽

Chun Cao ◽

...

Keyword(s):

Prognostic Factors ◽

B Cell ◽

Hodgkin Lymphoma ◽

Primary Tumor ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Primary Lymphoma ◽

Anatomic Site ◽

Risk Of Death ◽

Ann Arbor

Background: Primary lymphoma of bone (PLB) is an extremely rare malignancy arising in the skeletal system. There is no consensus over the best definition of PLB. Most of the published articles are single-institutional retrospective studies with a limited sample size. The rarity of PLB and discrepancies on diagnostic criteria has resulted in a vague understanding of PLB. Methods We retrospectively analyzed the clinical characteristics and prognostic factors of 2558 PLB patients who were registered in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2016. Survival rates were calculated using the Kaplan–Meier method. The effects of various factors on survival outcomes were analyzed by using the log-rank test. Univariate and multivariate analyses were conducted by using the Cox proportional hazards model to determine independent prognostic factors. Results: The median follow-up time of all eligible patients was 58 months. There seemed no sex preponderance in PLB incidence. The most involved sites are axial skeletons. The most common histological subtype was diffuse large B-cell lymphoma. The 3-, 5-, 10-, and 20-year overall survival (OS) rates were 70.70%, 65.70%, 54.40% and 39.50%, respectively. PLB patients whose primary tumor sites were appendicular and craniofacial skeletons had a significant survival advantage [hazard ratio (HR) = 0.694, 95% confidence interval (CI) 0.552–0.872; HR = 0.729, 95% CI 0.597–0.889, respectively] over those with axial skeletons as primary tumor sites. Patients with Hodgkin lymphoma, non-Hodgkin lymphoma (NHL)–mature B-cell lymphoma, and NHL-precursor-cell lymphoblastic lymphoma also had a significant OS advantage (HR = 0.392, 95% CI 0.200–0.771; HR = 0.826, 95% CI 0.700–0.973; and HR = 0.453, 95% CI 0.223–0.923, respectively). Patients with Ann Arbor stage III–IV at diagnosis were at higher risk of death than those with stage I–II (HR = 1.348, 95% CI 1.107–1.641). Chemotherapy was an independent favorable prognostic factor (HR = 0.734, 95% CI 0.605–0.890). Conclusions: Primary anatomic site, histology type, higher Ann Arbor stage and chemotherapy were independent prognostic factors. Chemotherapy played a pivotal role in PLB treatment.

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Is Absolute Lymphocyte Count at Time of Diagnosis a Predictor of Overall Survival in Non-Hodgkin Lymphoma Patients?

Blood ◽

10.1182/blood-2020-138571 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 32-32

Author(s):

Mallak Zatreh ◽

Anahat Kaur ◽

Anas Albawaliz ◽

Sheetal Bulchandani ◽

Ghazal Khan

Keyword(s):

Overall Survival ◽

Follicular Lymphoma ◽

B Cell ◽

Hodgkin Lymphoma ◽

Lymphocyte Count ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Absolute Lymphocyte Count ◽

Histopathological Diagnosis ◽

Non Hodgkin Lymphoma

Introduction:The prognostic significance of absolute lymphocyte count (ALC) has been an area of debate in non-Hodgkin-lymphoma (NHL). Several studies have reported that lymphocyte count during and after chemotherapy independently predict outcome in patients with acute myelocytic lymphoma (AML), follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). Furthermore, lymphocytopenia is a poor prognostic marker in initial staging of NHL and in relapsed DLBCL. Therefore, we aimed to investigate whether ALC at time of diagnosis is an independent predictor of overall survival (OS) in NHL. Methods:We retrospectively reviewed patients with aggressive NHL who were seen at hospitals affiliated with Saint Luke's Health System from January 2000 to December 2017 with at least 2 year longitudinal follow up after diagnosis. We retrieved 447 patients with histopathological diagnosis of DLBCL, Burkitt's Lymphoma, Follicular Lymphoma Grade IIIB, primary Effusion Lymphoma, B-cell Lymphoma unclassifiable, and high-grade B cell lymphoma. Through chart review we determined pathological and clinical characteristics of these patients, calculated the ALC at time of diagnosis, studied the treatment patterns, response to therapy and survival in our center. ALC at time of diagnosis was obtained on 358 patients based on data availability. Results:A multivariate analysis was conducted to see if ALC at time of diagnosis is a predictor of OS by correcting for age at diagnosis, gender, race, stage at diagnosis, international prognostic index (IPI), central nervous system involvement, histopathological diagnosis and type of chemotherapy. ALC at diagnosis after controlling all variables was not a significant predictor of OS (P: 0.7126). Conclusion:We found that ALC at time of diagnosis did not have a statistically significant effect on OS. We believe that prospective large-scale studies are needed to determine whether ALC at time of diagnosis affects OS in NHL patients. Table Disclosures No relevant conflicts of interest to declare.

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