Histologic Transformation in Marginal Zone Lymphomas

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1571-1571
Author(s):  
Silvia Franceschetti ◽  
Annarita Conconi ◽  
Kathrin Aprile Von Hohenstaufen ◽  
Gloria Margiotta Casaluci ◽  
Anastasios Stathis ◽  
...  
Keyword(s):  
B Cell ◽  
Marginal Zone ◽  
Cell Lymphoma ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Off Label ◽  
Clinical Variables

Abstract Abstract 1571 Background. Information concerning histologic transformation (HT) of marginal zone lymphomas (MZL) into aggressive entities is scant. We retrospectively analyzed the clinical variables at diagnosis and outcome, with special reference to HT, in a population of consecutive patients (pts) with confirmed diagnosis of MZL, including extranodal MZL (MALT lymphoma), splenic MZL (SMZL) and nodal MZL (NMZL). Patients and methods. The database of the Oncology Institute of Southern Switzerland (IOSI, Bellinzona) and of the Hematology Division of the Amedeo Avogadro University of Eastern Piedmont (Novara) includes 373 cases of MZL diagnosed and treated since 1979 to 2012: 186 MALT lymphomas (50%), 88 SMZL (23%), 36 NMZL (10%). Sixty-three patients (17%) could not be properly classified (uMZL): they presented with bone marrow infiltration with or without detectable involvement of peripheral blood but without splenomegaly and with apparently no other extranodal or nodal involved site. Results. Incidence was not significantly different according to sex (male: 47; female: 53%), median age at diagnosis was 68 years (20–94 years); 244 pts (65%) had stage III-IV disease. LDH was elevated in 45/212 (21%) tested pts, beta2-microglobulin in 108/205 (53%) tested pts. B symptoms were reported in 27/368 pts (7%). Five percent of pts had an ECOG performance status higher than 1. Serologic evidence of hepatitis C virus (HCV) infection was reported in 45/243 (19%) pts for whom the data was available. Among the 186 MALT lymphomas, 91 pts (49%) had a gastric localization, and 54 (29%) had multiple extranodal sites of disease involvement. Median overall survival (OS) and progression-free survival of the whole population were 15 years and 8 years, respectively. After a median follow-up of 5 years, HT was observed in 14 cases (4%, 95%CI:2%-6%). A diagnosis of diffuse large B cell lymphoma was documented in 12 pts (85.7% of patients undergoing HT), while in two cases the diagnosis was of classical Hodgkin lymphoma and mantle cell lymphoma, respectively. HT occurred after a median interval of 3 years (range: 1–12 years) after diagnosis. With respect to MZL type, HT occurred in 6% SMZL, 4% MALT lymphomas, 3% NMZL, and 2% uMZL (P=0.635). Risk of HT was 4% (95%CI, 2–8%) at 5 years, 6% (95%CI:3%-11%) at 10 years and 9% (95%CI, 5–16%) at 15 years; the rate of transformation tended to plateau from that point onward. At the time of HT, most pts had high LDH serum levels (8/11, 73%) and presence of B symptoms (6/10, 60%). After transformation, nine pts received anthracycline-containing regimens, and four pts were treated with high dose cytarabine regimens; in a single patient only supportive measures were adopted. In four pts, autologous stem cell transplantation was performed after induction. At a median follow-up of 12 months after HT, five of 14 pts died, all for lymphoma-related causes, with a 2-year post-transformation survival rate of 38% (95%CI:5%-74%). There was no significant association between the risk of HT and any of the clinical variables at diagnosis or frontline treatment strategies. Conclusions. This large retrospective series documents that the risk of HT is low across all MZL types. The incidence of HT in MZL is apparently lower than that of other indolent B cell malignancies, namely follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). As also observed in FL and CLL, HT in MZL occurs relatively early during the clinical course, pointing to putative biological differences at diagnosis in MZL patients destined to transform. Disclosures: Off Label Use: Trial partially supported by a research grant by Celgene. Lenalidomide was provided free by Celgene. The use of Lenalidomide is off-label in untreated DLBCL. Bertoni:OncoEthix SA: Research Funding.

An unusual case of indolent B-cell lymphoma with distinct chronic lymphocytic leukemia and marginal zone differentiation according to the site of involvement

2005 ◽  
Vol 46 (9) ◽  
pp. 1369-1374 ◽  
Author(s):  
Lucile Baseggio ◽  
Sophie Gazzo ◽  
Evelyne Callet-Bauchu ◽  
Alexandra Traverse-Glehen ◽  
Catherine Thieblemont ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Unusual Case ◽  
Marginal Zone ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia

scholarly journals Extranodal marginal zone non Hodgkin's lymphoma of the lung: A ten-year experience

2011 ◽  
Vol 68 (2) ◽  
pp. 150-154 ◽  
Author(s):  
Violeta Milosevic ◽  
Andrija Bogdanovic ◽  
Snezana Jankovic ◽  
Maja Perunicic-Jovanovic ◽  
Biljana Mihaljevic
Keyword(s):  
B Cell ◽  
Marginal Zone ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
Chop Regimen ◽  
Female Ratio ◽  
Balt Lymphoma

Background/Aim. Bronchus-associated lymphoid tissue (BALT) lymphoma is a rare subtype of low grade marginal zone B cell lymphoma representing 10% of all MALT lymphomas. The purpose of this study was to analyze the outcome of this group of patients comparing prognostic parameters and therapy modalities. Methods. A total of eight patients with BALT lymphoma had diagnosed between January 1998 - April 2008 at the Institute of Hematology, Clinical Center of Serbia, Belgrade, and they were included in this retrospective analysis. Results. Male/female ratio was 2/6, the median age was 64 years (range 37-67 years). Six patients had nonspecific respiratory symptoms and all of them had B symptoms. The patients were seronegative for HIV, HCV and HBsAg. Three patients had Sjogren's syndrome, rheumatoid arthritis and pulmonary tuberculosis, respectively. Seven patients were diagnosed by transbronchial biopsy and an open lung biopsy was done in one patient. Patohistological findings revealed lymphoma of marginal zone B cell lymphoma: CD20+/CD10-/CD5-/CyclinD1- /CD23-/IgM- with Ki-67+<20% of all cells. According to the Ferraro staging system, five patients had localized disease (CS I-IIE) and three had stage IVE; bulky tumor mass had 3 patients. All patients had Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. Five patients received monochemotherapy with chlorambucil and 3 were treated with CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone). A complete response (CR) was achieved in 5 patients and a partial response (PR) in 3 of them, treated with chlorambucil monotherapy and CHOP regimen. All patients were alive during a median follow-up period of 49 months (range 6- 110 months). Three patients relapsed after monochemotherapy into the other extranodal localization. They were treated with CHOP regimen and remained in stable PR. Conclusion. BALT lymphoma tends to be localised disease at the time of diagnosis, responds well to monochemotherapy with chlorambucil and has a favourable prognosis.

Treatment of Diffuse Large B-Cell Lymphoma with Rituximab, Intensive Induction and High-Dose Consolidation: The Final Analysis of the Czech Lymphoma Study Group (CLSG) R-MegaCHOP-ESHAP-BEAM (R-MEB) Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 21-21
Author(s):  
Marek Trneny ◽  
Robert Pytlik ◽  
David Belada ◽  
Katerina Kubackova ◽  
Ingrid Vasova ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background. Combined immunochemotherapy with CHOP and rituximab have improved the outcome of patients with diffuse large B-cell lymphoma (DLBCL). and related diseases. However, the cure rate of patients with IPI 3–5 or aaIPI 3 is still only about 50% with this regimen. Given the feasibility of previous CLSG regimens based on high-dose CHOP-ESHAP induction and BEAM consolidation, we have conducted a phase II trial combining this approach with rituximab immunotherapy. Patients and methods. Patients aged 18–65 years with DLBCL and age-adjusted IPI (aaIPI) 2–3 were treated with three cycles of high-dose CHOP (MegaCHOP - cyclophosphamide, 3 g/m2, vincristine 2 mg, adriamycin, 75 mg/m2, and prednisone, 300 mg/m2) with G-CSF every 3 weeks, followed by three cycles of ESHAP (etoposide, 240 mg/m2, cisplatin, 100 mg/m2, methylprednisolone, 2000 mg and Ara-C 2000 mg/m2) every 3 weeks. Four to six doses of rituximab 375 mg/m2 were administered on day 1 of each cycle of induction therapy. High-dose therapy (BEAM) followed by autologous stem cell transplant (ASCT) was used as consolidation. Radiotherapy was given to residual masses or sites of bulky disease. Primary endpoint was progression-free survival (PFS), while secondary endpoints were overall survival (OS) and feasibility of the treatment. Results. From April 2002 to October 2006, 105 consecutive patients from 10 centers were recruited. 58% were men and 42% women with median age 46 years (19–63 years). 74% of patients had stage IV disease, 92% had elevated LDH, 53% had performance status &gt;1, 55% had B symptoms and 19% had bone marrow involvement. aaIPI was 2 in 62% of patients and 3 in 38% of patients. 68% of patients received the whole treatment according to the protocol, including ASCT and radiotherapy. Stem cells mobilization according to the protocol was performed in 90% of patients and was successful in 86% of mobilized patients (77% of all patients). 73% of patients ultimately received ASCT (including 3 patients transplanted after ammended treatment) and 51% of patients received planned radiotherapy. Complete remission (CR) was achieved in 83% of all patients and partial remission (PR) in 2%. Early toxic death rate was 6% and 9% patients had primary refractory disease. Of patients who achieved CR or PR, only 6 subsequently relapsed (7%) and two suffered late toxic death (2%). With a median follow-up of 32 months for living patients, the estimated 2-year PFS is 77% and 2-year OS is 81%. Age less than median (46 years) was strongest predictor of favorable outcome (p = 0,00006 for PFS and p = 0,00013 for OS), while there was no effect of stage, LDH, performance status or aaIPI (2-year PFS 79% for aaIPI 2 and 77% for aaIPI 3, 2-year OS 81% for aaIPI 2 and 80% for aaIPI 3). Delivery of ASCT or radiotherapy did not significantly affected PFS in patients who did not suffered early progression or early toxic death, but radiotherapy modestly improved OS of these patients (p = 0,03). Conclusion. R-MEB has proved to be an effective treatment strategy for younger patients with high-risk aggressive B-cell lymphoma. Currently, CLSG is testing whether utilization of early PET scan may decrease toxicity and improve treatment tolerance while maintaining the efficacy of this regimen.

scholarly journals Numbers of early CD34+ progenitors of bone marrow hematopoiesis in patients with diffuse large B-cell lymphoma

2017 ◽  
Vol 89 (1) ◽  
pp. 43-48
Author(s):  
E I Dorokhina ◽  
A U Magomedova ◽  
I V Galtseva ◽  
V N Dvirnyk ◽  
S A Glinkina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Late Period ◽  
Large B Cell Lymphoma ◽  
Relationship Of ◽  
Large B Cell

Aim. To estimate the number of early progenitors of bone marrow (BM) hematopoiesis in patients with diffuse large B-cell lymphoma (DLBCL) in the late period after high-dose chemotherapy (HDCT) according to the mNHL-BFM-90 program. Subjects and methods. The investigators analyzed the results of BM immunophenotypic and histological studies in 40 patients (median age, 57 years) with DLBCL who received HDCT according to the mNHL-BFM-90 program at the Hematology Research Center (HRC), Ministry of Health of the Russian Federation (MHRF), in the period 2002 to 2009. A comparison group consisted of 19 patients (median age, 70 years) treated according to the CHOP/R-CHOP program at HRC, MHRF, in the same period. The median follow-up period was 6 years. The results of BM examination were analyzed before and 5—10 years after the end of HDCT. Immunophenotypic study determined the number of early CD34+ hematopoietic progenitors. BM cellularity, the size of erythroid, granulocytic and megakaryocytic lineages, their ratio, the presence of dysplasia signs, and secondary stromal changes were histologically determined. The BM toxic injury signs found for the first time were evaluated as manifestations of late myelotoxicity. Results. At 5-to-10-year follow-ups after the end of HDCT according to the mNHL-BFM-90 program, the patients showed a smaller number of early CD34+ progenitors of BM hematopoiesis in 31 (78%) cases than those treated according to the CHOP/R-CHOP-21 program (n=8 (2%)) (p=0.005). Myelopoiesis with decreased CD34+ cell count was characterized by hypocellularity in 8 (26%) patients (p=0.07), the narrowing of megakaryocytic lineage in 14 (45%) (p=0.006), erythroid one in 7 (23%) (p=0.01), and granulocytic one in 8 (26%) (p=0.92), pronounced secondary stromal changes in 15 (48%) (p=0.03), and grade 1 thrombocytopenia in 13 (42%); p=0.02). Conclusion. There is evidence that the number of early CD34+ progenitors of BM hematopoiesis decreased in patients with DLBCL in the late period after HDCT. The investigation shows the relationship of the reduction in the number of early CD34+ progenitors of BM hematopoiesis in the late follow-up period to the presence of pronounced secondary changes in the BM stroma (p=0.02). There was no statistically significant relationship of the decreased number of CD34+ cells to the age younger or older than 60 years, to the period after the end of chemotherapy, to gender or presence of specific BM injury.

The chemokine receptor CXCR3 is expressed in a subset of B-cell lymphomas and is a marker of B-cell chronic lymphocytic leukemia

Blood ◽  
2000 ◽  
Vol 95 (2) ◽  
pp. 627-632 ◽  
Author(s):  
Dan Jones ◽  
Richard J. Benjamin ◽  
Aliakbar Shahsafaei ◽  
David M. Dorfman
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Chemokine Receptor ◽  
Marginal Zone ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Marginal Zone Lymphoma ◽  
Lymphocytic Leukemia ◽  
Splenic Marginal Zone Lymphoma ◽  
Flow Cytometric

Chemotaxis in leukocytes is mediated through binding of soluble chemokines to transmembrane G-protein coupled receptors. The chemokine receptor CXCR3 has been previously shown to be widely expressed on activated T cells and to mediate T-cell chemotaxis on binding to various ligands, including Mig, IP-10, and ITAC. By using immunohistochemical and flow cytometric analysis, we report that CXCR3 is also expressed on a subset of peripheral blood B cells and in distinct subtypes of B-cell lymphoma. CXCR3 immunohistochemical or flow cytometric expression was seen in 37 of 39 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (diffusely positive in 33 cases), whereas mantle cell lymphoma (30 cases), follicular lymphoma (27 cases), and small noncleaved cell lymphoma (8 cases) were negative in all but 2 cases. Strong CXCR3 expression was also seen in splenic marginal zone lymphoma (14 of 14 cases) and in the monocytoid and plasmacytic cells in extranodal marginal zone lymphoma (15 of 16 cases). This differential expression of CXCR3 in B-cell tumors contrasts with that of another B-cell–associated chemokine receptor, BLR1/CXCR5, which we show here is expressed on all types of B-cell lymphoma tested. We also report that the CXCR3 ligand, Mig, is coexpressed on tumor cells in many cases of CLL/SLL (10 of 13 cases examined) with Mig expression less frequently seen in other B-cell lymphoma subtypes. Coexpression of CXCR3 and its ligand, Mig, may be an important functional interaction in B-CLL, as well as a useful diagnostic marker for the differential diagnosis of small cell lymphomas.

Lisocabtagene maraleucel (liso-cel) for treatment of second-line (2L) transplant noneligible (TNE) relapsed/refractory (R/R) aggressive large B-cell non-Hodgkin lymphoma (NHL): Updated results from the PILOT study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8040-8040 ◽  
Author(s):  
Alison R. Sehgal ◽  
Gerhard Hildebrandt ◽  
Nilanjan Ghosh ◽  
John E. Godwin ◽  
Nina D. Wagner-Johnston ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Car T Cells ◽  
Car T ◽  
Grade 3 ◽  
Large B Cell

8040 Background: Patients (pts) with aggressive large B-cell NHL who are R/R after first-line immunochemotherapy and not eligible for high-dose chemotherapy and HSCT have a poor prognosis and no established standard of care. The ongoing, open-label phase 2 PILOT study is the first to assess the safety and efficacy of liso-cel, an investigational, CD19-directed, defined composition, 4-1BB CAR T cell product infused at equal target doses of CD8+ and CD4+ CAR+ T cells, as 2L therapy in TNE pts (NCT03483103). Methods: Eligible pts had aggressive R/R diffuse large B-cell lymphoma NOS (de novo or transformed follicular lymphoma [FL]), high-grade B-cell lymphoma, or FL grade 3B with 1 line of prior therapy containing an anthracycline and anti-CD20 agent. Pts were deemed TNE by meeting ≥1 criteria: age ≥70 y, ECOG PS 2, or impaired organ function (DLCO ≤60% [but SaO2 ≥92% and CTCAE ≤1 dyspnea], LVEF ≥40% to < 50%, creatinine clearance > 30 to < 60 mL/min, or AST/ALT > 2 to ≤5 × ULN). Liso-cel (100 × 106 CAR+ T cells) was administered 2–7 days after lymphodepletion (LD) with fludarabine/cyclophosphamide. The primary endpoint is ORR; key secondary endpoints are AEs and CR rate. Results: At data cutoff, 25 pts had LD followed by liso-cel infusion. Pt characteristics are summarized in the Table. Overall, 48% (n = 12) had high tumor burden and 48% were primary refractory. 18/25 (72%) pts had grade ≥3 treatment-emergent AEs, 40% of which were cytopenias. No grade 5 AEs occurred within the first 30 days after liso-cel. Five pts (20%) had cytokine release syndrome (CRS) and 3 (12%) had neurological events (NEs). No grade 3/4 CRS was observed; 2 pts (8%) had grade 3/4 NEs. Five pts (20%) received tocilizumab and/or dexamethasone for CRS/NEs. At a median follow-up of 3.5 mo, the ORR was 80% (95% CI, 59–93; n = 20); 48% of pts (n = 12) achieved CR. Conclusions: These interim data suggest that elderly and/or comorbid pts with R/R aggressive large B-cell NHL, who are not eligible for high-dose chemotherapy and HSCT, can receive 2L liso-cel with similar safety and efficacy to 3L+ pts as previously reported (Abramson, ASH 2019 #241). Updated data with longer follow-up will be presented. Clinical trial information: NCT03483103 . [Table: see text]

Chlamydia Psittaci-Eradicating Antibiotic Therapy as a Potential Therapeutic Strategy Against Marginal Zone B-Cell Lymphoma of the Ocular Adnexa.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3274-3274 ◽  
Author(s):  
Andres J. Ferreri ◽  
Maurilio Ponzoni ◽  
Massimo Guidoboni ◽  
Antonia A. Lettini ◽  
Laura Caggiari ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
B Cell ◽  
Marginal Zone ◽  
Mononuclear Cells ◽  
Cell Lymphoma ◽  
Objective Response ◽  
B Cell Lymphoma ◽  
Chlamydia Psittaci ◽  
Ocular Adnexa

Abstract Background: Chlamydia psittaci (Ch.ps.) DNA has been detected in tumor tissue of 80% of patients with ocular adnexal lymphoma (OAL) and in peripheral blood mononuclear cells (PBMCs) of 40% of them [Ferreri AJM, et al. J Natl Cancer Inst 96:586, 2004]. Chronic antigenic stimulation provided by Ch.ps. persistent infection may favor the development and sustaining of OAL. Removal of this stimulation with antibiotic therapy could result in lymphoma regression. Aim: To assess the rate of Ch.ps. eradication and anti-lymphoma activity of antibiotic therapy in OAL patients. Methods: Twelve patients with Ch.ps.-positive marginal zone B-cell lymphoma of the ocular adnexa, at diagnosis (n=5) or relapse, were treated with doxycycline 100 mg, bid orally, for three weeks. The presence of Ch.ps. DNA in lymphoma samples was assessed by multiplex touchdown PCR. Specificity of the amplified PCR fragments was confirmed by direct sequencing of both sense and anti-sense strands. The presence of Ch.ps. DNA in PBMCs collected before and one and 12 months after antibiotic therapy was evaluated in 11 cases. Six of these patients had Ch.ps.-positive PBMCs and were assessable for bacterial eradication rate. Nine patients had measurable disease at the time of therapy and were evaluable for objective response; a lymphomatous lesion of ocular adnexa was detected in all 9 evaluable patients: unilateral in three, bilateral in three, associated with regional lymphadenopathies in two, and with multiple subcutaneous nodules in one. Objective response was assessed one, three and six months after therapy conclusion and every six months during follow-up. Observation period after doxycycline ranged from 1 to 29 months (median 25). Results: All patients but one completed antibiotic therapy, with excellent tolerability. At one month from doxycycline assumption, Ch.ps. DNA was no longer detectable in PBMC of the six positive patients; these results were confirmed at one year of fw-up in all the three assessable cases. Objective response was complete in two patients (26+ and 9+ months), partial in two (29+ and 6+ m.) and lower than 50% in two (3+ and 5+ m.), whereas one patient had stable disease at one month of fw-up. Two patients experienced progression and received salvage treatment. Importantly, two patients showed lymphoma regression in previously irradiated orbit, and the two patients with regional lymphadenopathies achieved complete response; doxycycline was the 4th-line treatment in one of them. Time to the best response ranged from 3 to 24 months. All patients are alive and well (median fw-up: 54 m.). Conclusions: Ch.ps.-eradicating antibiotic therapy is followed by tumor regression in OAL patients, even after multiple relapses. Estimation of response rate requires a longer follow-up. A large phase II trial is warranted to confirm whether this fast, cheap and well-tolerated therapy may be a valid alternative to conventional, more aggressive strategies against OAL.

Sign in / Sign up

Export Citation Format

Share Document