Classification of non-Hodgkin lymphoma in Central and South America: a review of 1028 cases

Abstract The distribution of non-Hodgkin lymphoma (NHL) subtypes differs around the world but a systematic study of Latin America has not been done. Therefore, we evaluated the relative frequencies of NHL subtypes in Central and South America (CSA). Five expert hematopathologists classified consecutive cases of NHL from 5 CSA countries using the WHO classification and compared them to 400 cases from North America (NA). Among the 1028 CSA cases, the proportions of B- and T-cell NHL and the sex distribution were similar to NA. However, the median age of B-cell NHL in CSA (59 years) was significantly lower than in NA (66 years; P < .0001). The distribution of high-grade (52.9%) and low-grade (47.1%) mature B-cell NHL in CSA was also significantly different from NA (37.5% and 62.5%; P < .0001). Diffuse large B-cell lymphoma was more common in CSA (40%) than in NA (29.2%; P < .0001), whereas the frequency of follicular lymphoma was similar in Argentina (34.1%) and NA (33.8%), and higher than the rest of CSA (17%; P < .001). Extranodal NK/T-cell NHL was also more common in CSA (P < .0001). Our study provides new objective evidence that the distribution of NHL subtypes varies significantly by geographic region and should prompt epidemiologic studies to explain these differences.

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A Phase II Clinical Study of Rituximab and High-Dose Biweekly THP-COP (Pirarubicin, Cyclophosphamide, Vincristine and Predonisolone) with G-CSF for Non-Hodgkin Lymphoma: Results of a Multicentric Study of NMLSG (Niigata Malignant Lymphoma Study Group).

Blood ◽

10.1182/blood.v106.11.4734.4734 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4734-4734

Author(s):

Jun Takizawa ◽

Sadao Aoki ◽

Kazue Takai ◽

Tohri Kurasaki ◽

Keiichiro Honma ◽

...

Keyword(s):

Clinical Study ◽

T Cell ◽

B Cell ◽

Hodgkin Lymphoma ◽

Phase Ii ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

High Dose ◽

Histological Subtypes ◽

Non Hodgkin Lymphoma

Abstract Introduction CHOP chemotherapy has been accepted as the standard treatment for patients with non-Hodgkin lymphoma (NHL), but in some histological or clinical subtypes the results are not satisfactory. We have shown the efficacy and safety of high-dose biweekly THP-COP with G-CSF support (HDBW-TCOP(G)) for NHL. In this regimen, we choose pirarubicin in stead of doxorubicin because it was proven high efficacy against NHL and the lower toxicity than doxorubicin. Recently, the combination of rituximab and standard CHOP has been shown to have a synergistic effect for NHL. We performed a phase II multicentric clinical study to assessed the feasibility and toxicity of the combination chemotherapy of rituximab and HDBW-TCOP(G) (HDBW-R-TCOP(G)) compared with those of HDBW-TCOP(G). Patients and methods Between August 1998 and December 2004, Forty-one Japanese patients with previously untreated NHL from whom informed consent was obtained were included in this study. Median age was 45 (range 19–63) years. There were 19 males and 22 females. According to WHO-classification diagnoses, histological subtypes included follicular lymphoma (FL) 15(37%); nodal marginal zone B-cell lymphoma (NMZBCL) 2(5%); mantle cell lymphoma (MCL) 3(7%); anaplastic large cell lymphoma (ALCL) 1(2%), diffuse large B-cell lymphoma (DLBCL) 18(44%); peripheral T-cell lymphoma (PTCL) 1(2%), angioimmunoblastic T-cell lymphoma (AILT) 1(2%). Of 41 patients, one patient was stage 1, stage 2, 11 stage 3 and 16 stage 4. International prognostic index (IPI) included L 6; LI 22; HI 7; H 6. HDBW-TCOP(G) consisted of pirarubicin 70 mg/m2 on day 1; cyclophosphamide 1000 mg/m2 on day 1; vincristine 1.4 mg/m2 on day 1; predonisolone 50 mg/m2 orally from day 1 to 5; lenograstim 2.0 μg/kg/day from day 3. Fifteen patients who enrolled after rituximab was approved in Japan received therapy combined HDBW-TCOP(G) with rituximab 375mg/ m2 on day -2 (HDBW-R-TCOP(G)). Six cycles were administered at intervals of two weeks. Results Of the 41 patients treated, 32 (78.0%) achieved a complete remission (CR) and nine (22.0%) achieved a partial remission (PR), for an overall response rate of 100%. After median follow-up of 36 months (range 2.9– 81.8), progression free survival (PFS) and overall survival (OS) were 68.2% and 97.5%, respectively. PFS was 90.9% for HDBW-R-TCOP(G), and 69.5% for HDBW-TCOP(G), but no significant differences was found among two regimen. There was no significant difference in the PFS and OS between aggressive and indolent histological subtypes. 76% of patients developed Grade4 leukopenia (according to NCI criteria) but no patients experienced febrile neutropenia. 15% of patients developed G4 anemia and 17% of patients G4 thrombocytopenia. Other adverse effects were minimal. Conclusion Both HDBW-TCOP(G) and HDBW-R-TCOP(G) are feasible for NHL with acceptable toxicity. The excellent result suggests they are effective for aggressive NHL patients with poor prognostic factors and advanced stage indolent NHL.

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Clinical Outcome of 119 Children with Non-Hodgkin Lymphoma Treated in a Single Center in China

Blood ◽

10.1182/blood.v112.11.5299.5299 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5299-5299

Author(s):

Yonghong Zhang ◽

Ling Jin ◽

Jing Yang ◽

Yanlong Duan ◽

Chunjv Zhou ◽

...

Keyword(s):

Bone Marrow ◽

T Cell ◽

B Cell ◽

Hodgkin Lymphoma ◽

Nk Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Lymphoblastic Lymphoma ◽

Non Hodgkin Lymphoma ◽

Pathologic Classification

Abstract One hundred and nineteen children with non-Hodgkin lymphoma were treated between February 2003 and December 2006 in Beijing Children’s Hospital on BCH-2003-NHL protocol. The diagnosis was made by histopathology of the biopsied tissue and/or bone marrow, and disease was classified according to WHO-2001 pathologic classification. We applied modified LMB89 protocol to cases with B-cell lymphoma; modified BFM90-ALL protocol for lymphoblastic lymphoma and cutaneous T-cell/NK cell lymphoma; and modified BFM90-ALCL protocol for anaplastic large-cell lymphoma (ALCL). There were 50 cases (42%) of B cell lymphoma including 32 cases of Burkitt¡’s lymphoma, 10 cases of Burkitt-like lymphoma and 8 cases of diffuse large B cell lymphoma; 44 cases (37%) of lymphoblastic lymphoma; 19 cases (16%) of ALCL; and 6 cases (5%) of cutaneous T-cell/NK cell lymphoma. The 85 boys and 34 girls (ratio, 2.5:1) ranged in age from 2 to 15 years (median, 7.8 years) at diagnosis. B cell lymphoma typically presented as abdomen mass and acute abdomen; nasopharynx and tonsil were also common sites of involvement. Lymphoblastic lymphoma generally presented with mediastinal mass and bone marrow involvement. There was no typical presentation for ALCL. According to the St. Jude staging system, 19 cases had stage I–II, and 94 cases stage III–VI diseases (exclude 6 cases of cutaneous T-cell/NK cell lymphoma). Seven cases had CNS involvement and 25 cases involved bone marrow. The treatment duration was 2 to 8 months for B-cell lymphoma, 2.5 to 3 years for lymphoblastic lymphoma and 1 to 1.5 years for ALCL. The follow-up rate was 100% and median observation period was 23 months. The overall survival (OS) at 3 years was 90.7% and the 3-year event-free survival (EFS) estimate was 82.3%. For B-cell lymphoma, 3-year OS was 88.68% and 3-year EFS was 81.8%. For lymphoblastoma lymphoma, the rates were 89.3% and 69.4%, respectively. All cases of ALCL are alive with on undergoing treatment for relapse. Patients with ALCL achieved the best 3-year OS (100%) and had 3-year EFS of 94.2%. Grade 3 or 4 bone marrow suppression occurred in 97.5% of patients with B-cell lymphoma, 100% of those with lymphoblastic lymphoma and 89.5% of cases with ALCL. As of to date, 11 patients have died, the causes of death include infection (n=4), abandonment of therapy (n=6) and relapse (n=1). Univarate analysis showed that stage IV disease, failure to achieve complete remission after 3 months of treatment, and bulky mass are were associated with poor prognosis £all P values <0.05£©. In summary, we have achieved excellent treatment results using modified international protocols. Infection and financial problem remained the main reasons of treatment failure.

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Clinicopathologic features and treatment outcome of primary intestinal non-Hodgkin lymphoma: A single center experience.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e19523 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e19523-e19523

Author(s):

Wei-Hsun Hsu ◽

Kun-Huei Yeh ◽

Chung-Wu Lin ◽

Chih-Hung Hsu ◽

Ann-Lii Cheng ◽

...

Keyword(s):

Small Intestine ◽

Treatment Outcome ◽

T Cell ◽

B Cell ◽

Hodgkin Lymphoma ◽

Cell Lymphoma ◽

Univariate Analysis ◽

B Cell Lymphoma ◽

Clinicopathologic Features ◽

Non Hodgkin Lymphoma

e19523 Background: Primary intestinal non-Hodgkin lymphoma (NHL) is a rare but heterogeneous disease in East Asia. However, the benefit of multidisciplinary treatment is still in debate. We characterized the clinicopathologic features, and treatment outcome in a single institute database. Methods: Patients with NHL primarily involving the intestine and treated during 1992 to 2008 were selected from the Cancer Registry of National Taiwan University Hospital. The medical charts and pathology records were carefully reviewed. Results: There were 64 men and 17 women with a median age of 51.5 years. Sites involved were colon/rectum (53.2%), small intestine (30.9%), and duodenum (13%). Histopathology subclassification included diffuse large B-cell lymphoma (DLBCL) (61.7%), mucosa-associated lymphoid tissue lymphoma (11.1%), Burkitt’s lymphoma (8.6%), T cell lymphoma (6.2%), follicular lymphoma (2.5%), mantle cell lymphoma (1.2 %) and others (8.6%). Ann Arbor stage IE to IIE accounted for 61.7%, whereas lower IPI score (1-2) were 54.8%. Among them, 27 patients received surgery plus chemotherapy, 60 received chemotherapy, and 4 had radiotherapy. At average follow-up of 48.7 months, 5 year survival rate were 59%, 43% and 51% for colon/rectum, small intestine, and duodenal NHL, respectively (p=0.45). Surgery plus chemotherapy versus chemotherapy alone showed no survival benefit in lower IPI group (p=0.682) nor in higher IPI (3-5) group (p=0.939). A trend of better median overall survival (mOS) was seen in rituximab group than in non-rituximab group in DLBCL subtypes (not reach vs. 39.8mo, p=0.075). In univariate analysis, stage III/IV (p=0.008), IPI score greater than 2 (p=0.011), and T cell histology (p<0.001) were significant prognostic factors for poor OS. In multivariate analysis, T cell histology remained the independent prognostic factor for inferior OS (p<0.001, HR: 20.3, 95% CI: 5.1-80.4). Conclusions: Although B cell NHL was the majority of primary intestinal NHL in our institute, T cell histology has significant inferior survival. Chemotherapy is still the backbone of treatment for primary intestinal NHL. The benefit of rituximab to intestinal DLBCL needs further confirmation.

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Imaging of Chemokine Receptor-4 Targeted PET/CT with 68Ga-Pentixafor in Non-Hodgkin Lymphoma: Comparison to 18F-FDG

10.21203/rs.3.rs-34553/v1 ◽

2020 ◽

Author(s):

Qingqing Pan ◽

Yaping Luo ◽

Yan Zhang ◽

Long Chang ◽

Ji Li ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Hodgkin Lymphoma ◽

Marginal Zone ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

T Cell Lymphoma ◽

Lymphoplasmacytic Lymphoma ◽

Non Hodgkin Lymphoma ◽

Pet Ct

Abstract Background: In order to study the CXCR4 expression with 68Ga-Pentixafor PET in different types of non-Hodgkin lymphoma, we performed a retrospective study to describe the 68Ga-Pentixafor PET/CT imaging in a spectrum of lymphomas and to compare it with 18F-FDG PET/CT. Results: Twenty-seven patients with newly diagnosed non-Hodgkin lymphoma were recruited retrospectively. 68Ga-Pentixafor PET showed increased radioactivity in lymphoplasmacytic lymphoma (n = 8), marginal zone lymphoma (n = 4), diffuse large B cell lymphoma (n = 3), follicular lymphoma (n = 2), mantle cell lymphoma (n = 1), unclassified indolent B cell lymphoma (n = 3) and enteropathy associated T cell lymphoma (n = 3). However, peripheral T cell lymphoma, not otherwise specified (n = 1), and NK/T cell lymphoma (n = 2) were not avid for 68Ga-Pentixafor. In comparison to 18F-FDG PET, 68Ga-Pentixafor PET demonstrated more extensive disease and higher radioactivity in lymphoplasmacytic lymphoma and marginal zone lymphoma. Conclusion: CXCR4 expression varies in different types of non-Hodgkin lymphoma. Overexpression of CXCR4 was detected with 68Ga-Pentixafor PET/CT in lymphoplasmacytic lymphoma, marginal zone lymphoma, diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma, unclassified indolent B cell lymphoma, and enteropathy associated T cell lymphoma.

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Flow Cytometric Detection of the Double-Positive (CD4+CD8+)/PD-1bright T-Cell Subset Is Useful in Diagnosing Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2020-0726-oa ◽

2021 ◽

Author(s):

Zhongchuan Will Chen ◽

Juanita Wizniak ◽

Chuquan Shang ◽

Raymond Lai

Keyword(s):

Flow Cytometry ◽

T Cells ◽

T Cell ◽

B Cell ◽

Hodgkin Lymphoma ◽

B Cell Lymphoma ◽

The Other ◽

Non Hodgkin Lymphoma ◽

Flow Cytometric ◽

Large B Cell

Context.— Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is characterized by neoplastic lymphocyte-predominant cells frequently rimmed by CD3+/CD57+/programmed death receptor-1 (PD-1)+ T cells. Because of the rarity of lymphocyte-predominant cells in most cases, flow cytometric studies on NLPHL often fail to show evidence of malignancy. Objective.— To evaluate the diagnostic utility of PD-1 in detecting NLPHL by flow cytometry, in conjunction with the CD4:CD8 ratio and the percentage of T cells doubly positive for CD4 and CD8. Design.— Flow cytometric data obtained from cases of NLPHL (n = 10), classical Hodgkin lymphoma (n = 20), B-cell non-Hodgkin lymphoma (n = 22), T-cell non-Hodgkin lymphoma (n = 5), benign lymphoid lesions (n = 20), angioimmunoblastic T-cell lymphomas (n = 6) and T-cell/histiocyte–rich large B-cell lymphomas (n = 2) were analyzed and compared. Results.— Compared with the other groups, NLPHL showed significantly higher values in the following parameters: CD4:CD8 ratio, percentage of T cells doubly positive for CD4 and CD8, percentage of PD-1–positive T cells, and median fluorescence intensity of PD-1 expression in the doubly positive for CD4 and CD8 subset. Using a scoring system (0–4) based on arbitrary cutoffs for these 4 parameters, all 10 NLPHL cases scored 3 or higher, as compared with only 3 cases from the other groups, producing an overall sensitivity of 100% and a specificity of 96% (72 of 75). Two of the 3 outliers were non-Hodgkin lymphoma, and both showed definitive immunophenotypic abnormalities leading to the correct diagnosis. The remaining outlier was a case of T-cell/histiocyte–rich large B-cell lymphoma. Conclusions.— The inclusion of anti–PD-1 in flow cytometry is useful for detecting NLPHL in fresh tissue samples, most of which would have otherwise been labeled as nondiagnostic or reactive lymphoid processes.

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Clinical Applications of the Genomic Landscape of Aggressive Non-Hodgkin Lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2016.71.7603 ◽

2017 ◽

Vol 35 (9) ◽

pp. 955-962 ◽

Cited By ~ 25

Author(s):

Andrea B. Moffitt ◽

Sandeep S. Dave

Keyword(s):

T Cell ◽

B Cell ◽

Hodgkin Lymphoma ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large Cell ◽

T Cell Lymphoma ◽

Adult T Cell Leukemia ◽

Non Hodgkin Lymphoma ◽

T Cell Lymphomas

In this review, we examine the genomic landscapes of lymphomas that arise from B, T, and natural killer cells. Lymphomas represent a striking spectrum of clinical behaviors. Although some lymphomas are curable with standard therapy, the majority of the affected patients succumb to their disease. Here, the genetic underpinnings of these heterogeneous entities are reviewed. We consider B-cell lymphomas, including Burkitt lymphoma, diffuse large B-cell lymphoma, Hodgkin lymphoma, and primary mediastinal B-cell lymphoma. We also examine T-cell lymphomas, including anaplastic large-cell lymphoma, angioimmunoblastic T-cell lymphoma, cutaneous T-cell lymphoma, adult T-cell leukemia/lymphoma, and other peripheral T-cell lymphomas. Together, these malignancies make up most lymphomas diagnosed around the world. Genomic technologies, including microarrays and next-generation sequencing, have enabled a better understanding of the molecular underpinnings of these cancers. We describe the broad genomics findings that characterize these lymphoma types and discuss new therapeutic opportunities that arise from these findings.

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Comparison of Autologous Vs. Allogeneic Stem Cell Transplantation for Non-Hodgkin Lymphoma

Blood ◽

10.1182/blood.v120.21.2036.2036 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2036-2036

Author(s):

Nishitha M. Reddy ◽

Olalekan O Oluwole ◽

John P Greer ◽

David S Morgan ◽

Stacey Goodman ◽

...

Keyword(s):

Stem Cell ◽

T Cell ◽

Stem Cell Transplantation ◽

B Cell ◽

Hodgkin Lymphoma ◽

Cell Lymphoma ◽

Conditioning Regimen ◽

B Cell Lymphoma ◽

T Cell Lymphoma ◽

Non Hodgkin Lymphoma

Abstract Abstract 2036 Background: Stem cell transplantation (SCT) is a common indication for patients with Non-Hodgkin lymphoma (NHL). Auto-SCT is recommended for patients with relapsed NHL or as consolidative therapy in first remission. Allo-SCT is reserved for pts with either relapsed or primary refractory disease. The outcomes of these pts in large prospective studies are lacking and current recommendations and timing of selection of auto vs. allo-SCT are influenced by variety of factors including physician bias. Transplant outcomes of auto or allo-SCT have not been elucidated as a single cohort. Methods: We report a retrospective analysis of 270 pts with NHL who underwent auto-SCT or allo-SCT between January 2000- December 2010 after obtaining institutional IRB approval. Data were analyzed using SPSS.19. Results: Of the 270 pts, 238 patients underwent SCT for B-cell lymphoma (178 auto, 60 allo-SCT), and 32 for T-cell lymphoma (21 auto and 11 allo-SCT). Fifteen pts (6%) received prior auto-SCT. The median age of transplant was 52 years for the entire group. For those who underwent allo-SCT, median age was 47 (range 22–65 yrs) and 54 yrs (range 22–77) for auto-SCT. One hundred seventy (62%) were male. Majority of pts (76%) had advanced stage disease (stages III and IV). Fifty four (20%) received radiation therapy either before or after transplantation. The median number of prior regimens for allo-SCT were 3 (range 1–5) and 2 for auto-SCT (range 1 to 4). Within the allo-SCT group (n=71), 45 received matched-related donor transplants, and 26 unrelated donor transplants; majority of pts (n=47) received reduced intensity conditioning regimen. The auto-SCT group predominantly received CBV as their conditioning regimen. Median time from diagnosis to allo-SCT or auto-SCT was 1.4 yrs (range 0.32–13.1 yrs) and 1.69 (range 0.38–13.7 yrs), respectively. The median follow up time for the entire cohort was 6.2 yrs. The overall survival (OS) rates for the B- cell and T-cell NHL were 58% and 50% respectively (allo-SCT 51% vs. 54% for B and T-cell NHL, and auto-SCT 60% vs. 47% for B and T-cell lymphoma, respectively) (p=0.26). Within the allo-SCT group the relapse and non-relapse mortalities were 45% and 16%, respectively. In the auto-SCT group, the relapse and non-relapse mortality were 46% and 7% respectively. In B-cell lymphoma the relapse rate was 48% and 45% for auto and allo-SCT respectively (p=0.80). In T-cell lymphoma the relapse rate was 40% and 45% for auto and allo-SCT (p=0.67). Multivariate analysis of pts receiving auto vs. allo-SCT in NHL will be presented. Conclusions: We conclude that in this highly selected patient population with otherwise minimal comorbidities but chemo-sensitive aggressive lymphomas, about 50% of patients achieve long term survival after either an auto or allo-SCT approach. Despite recent evidence, there are intricate difficulties in patient selection for allo vs. auto-SCT and outcome of either approach is not satisfactory. Post transplant relapse is the most common cause of post-SCT failure. Tandem auto followed by allo-SCT and maintenance strategies need to be explored. We propose a larger prospective analysis on transplant outcomes in both B and T-cell lymphoma and improve strategies to prevent relapses after SCT. Disclosures: No relevant conflicts of interest to declare.

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Safety and Clinical Activity of a Combination Therapy Comprising Two Antibody-Based Targeting Agents for the Treatment of Non-Hodgkin Lymphoma: Results of a Phase I/II Study Evaluating the Immunoconjugate Inotuzumab Ozogamicin With Rituximab

Journal of Clinical Oncology ◽

10.1200/jco.2012.42.7211 ◽

2013 ◽

Vol 31 (5) ◽

pp. 573-583 ◽

Cited By ~ 97

Author(s):

Luis Fayad ◽

Fritz Offner ◽

Mitchell R. Smith ◽

Gregor Verhoef ◽

Peter Johnson ◽

...

Keyword(s):

Phase I ◽

B Cell ◽

Hodgkin Lymphoma ◽

Single Agent ◽

Objective Response ◽

B Cell Lymphoma ◽

Response Rates ◽

Low Grade ◽

Inotuzumab Ozogamicin ◽

Non Hodgkin Lymphoma

Purpose Inotuzumab ozogamicin (INO) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. We performed a phase I/II study to determine the maximum-tolerated dose (MTD), safety, efficacy, and pharmacokinetics of INO plus rituximab (R-INO) for treatment of relapsed/refractory CD20+/CD22+ B-cell non-Hodgkin lymphoma (NHL). Patients and Methods A dose-escalation phase to determine the MTD of R-INO was followed by an expanded cohort to further evaluate the efficacy and safety at the MTD. Patients with relapsed follicular lymphoma (FL), relapsed diffuse large B-cell lymphoma (DLBCL), or refractory aggressive NHL received R-INO every 4 weeks for up to eight cycles. Results In all, 118 patients received one or more cycles of R-INO (median, four cycles). Most common grade 3 to 4 adverse events were thrombocytopenia (31%) and neutropenia (22%). Common low-grade toxicities included hyperbilirubinemia (25%) and increased AST (36%). The MTD of INO in combination with rituximab (375 mg/m2) was confirmed to be the same as that for single-agent INO (1.8 mg/m2). Treatment at the MTD yielded objective response rates of 87%, 74%, and 20% for relapsed FL (n = 39), relapsed DLBCL (n = 42), and refractory aggressive NHL (n = 30), respectively. The 2-year progression-free survival (PFS) rate was 68% (median, not reached) for FL and 42% (median, 17.1 months) for relapsed DLBCL. Conclusion R-INO demonstrated high response rates and long PFS in patients with relapsed FL or DLBCL. This and the manageable toxicity profile suggest that R-INO may be a promising option for CD20+/CD22+ B-cell NHL.

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CD19 CAR T cells following autologous transplantation in poor-risk relapsed and refractory B-cell non-Hodgkin lymphoma

Blood ◽

10.1182/blood.2018883421 ◽

2019 ◽

Vol 134 (7) ◽

pp. 626-635 ◽

Cited By ~ 17

Author(s):

Craig S. Sauter ◽

Brigitte Senechal ◽

Isabelle Rivière ◽

Ai Ni ◽

Yvette Bernal ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

B Cell ◽

Hodgkin Lymphoma ◽

B Cell Lymphoma ◽

Car T Cells ◽

Poor Risk ◽

Car T Cell ◽

Non Hodgkin Lymphoma ◽

Car T

Abstract High-dose chemotherapy and autologous stem cell transplantation (HDT-ASCT) is the standard of care for relapsed or primary refractory (rel/ref) chemorefractory diffuse large B-cell lymphoma. Only 50% of patients are cured with this approach. We investigated safety and efficacy of CD19-specific chimeric antigen receptor (CAR) T cells administered following HDT-ASCT. Eligibility for this study includes poor-risk rel/ref aggressive B-cell non-Hodgkin lymphoma chemosensitive to salvage therapy with: (1) positron emission tomography–positive disease or (2) bone marrow involvement. Patients underwent standard HDT-ASCT followed by 19-28z CAR T cells on days +2 and +3. Of 15 subjects treated on study, dose-limiting toxicity was observed at both dose levels (5 × 106 and 1 × 107 19-28z CAR T per kilogram). Ten of 15 subjects experienced CAR T-cell–induced neurotoxicity and/or cytokine release syndrome (CRS), which were associated with greater CAR T-cell persistence (P = .05) but not peak CAR T-cell expansion. Serum interferon-γ elevation (P < .001) and possibly interleukin-10 (P = .07) were associated with toxicity. The 2-year progression-free survival (PFS) is 30% (95% confidence interval, 20% to 70%). Subjects given decreased naive-like (CD45RA+CCR7+) CD4+ and CD8+ CAR T cells experienced superior PFS (P = .02 and .04, respectively). There was no association between CAR T-cell peak expansion, persistence, or cytokine changes and PFS. 19-28z CAR T cells following HDT-ASCT were associated with a high incidence of reversible neurotoxicity and CRS. Following HDT-ASCT, effector CD4+ and CD8+ immunophenotypes may improve disease control. This trial was registered at www.clinicaltrials.gov as #NCT01840566.

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The Feature of Distribution and Clonality of TCRγ/δSubfamilies T Cells in Patients with B-Cell Non-Hodgkin Lymphoma

Journal of Immunology Research ◽

10.1155/2014/241246 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 6

Author(s):

Liang Wang ◽

Meng Xu ◽

Chunyan Wang ◽

Lihua Zhu ◽

Junyan Hu ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

B Cell ◽

Hodgkin Lymphoma ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Distribution Patterns ◽

Cell Receptor ◽

Non Hodgkin Lymphoma ◽

Clonal Proliferation

Restricted T-cell receptor (TCR) Vα/Vβrepertoire expression and clonal expansion ofαβT cells especially for putative tumor-associated antigens were observed in patients with hematological malignancies. To further characterize theγδT-cell immune status in B-cell non-Hodgkin lymphoma (B-NHL), we investigated the distribution and clonality of TCR Vγ/Vδrepertoire in peripheral blood (PB), bone marrow (BM), and lymph node (LN) from patients with B-NHL. Four newly diagnosed B-NHL cases, including three with diffuse large B-cell lymphoma (DLBCL) and one with small lymphocytic lymphoma (SLL), were enrolled. The restrictive expression of TCR Vγ/Vδsubfamilies with different distribution patterns could be detected in PB, BM, or LN from all of four patients, and partial subfamily T cells showed clonal proliferation. At least one clonally expanded Vδsubfamily member was found in PB from each patient. However, the expression pattern and clonality of TCR Vγ/Vδchanged in different immune organs and showed individual feature in different patients. The clonally expanded Vδ5, Vδ6, and Vδ8 were detected only in PB but neither in BM nor LN while clonally expanded Vδ2 and Vδ3 could be detected in both PB and BM/LN. In conclusion, the results provide a preliminary profile of distribution and clonality of TCRγ/δsubfamilies T cells in PB, BM, and LN from B-NHL; similar clonally expanded Vδsubfamily T cells in PB and BM may be related to the same B-cell lymphoma-associated antigens, while the different reactive clonally expanded Vγ/VδT cells may be due to local immune response.

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