Ongoing Monoclonal B-Cell Proliferation Is Not Common in Gastric B-Cell Lymphoma After Combined Radiochemotherapy

2004 ◽  
Vol 22 (15) ◽  
pp. 3039-3045 ◽  
Author(s):  
Birgit Alpen ◽  
Rolf Kuse ◽  
Radzak Parwaresch ◽  
Hans Konrad Müller-Hermelink ◽  
Manfred Stolte ◽  
...  

Purpose Gastric marginal-zone B-cell lymphoma (MZBCL) of the mucosa-associated lymphoid tissue (MALT) is associated with chronic Helicobacter pylori gastritis. Stable complete remission (CR) can be induced by H pylori eradication. Whether this is paralleled by cure of the lymphoma remains unclear. Persisting monoclonal bands for immunoglobulin heavy chain variable region (VH) representing the lymphoma clone have been described in up to 50% of patients in CR. This retrospective study investigated whether this phenomenon also occurs after radiochemotherapy. Patients and Methods Biopsy samples of 20 patients receiving chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone and irradiation were analyzed before and after therapy. Study patients had Ann Arbor stage I/II primary gastric cancer, including four cases of MZBCL of MALT type, 12 cases of diffuse large-cell lymphomas (DLCL), and four cases of mixed MALT type/DLCL. Polymerase chain reaction (PCR) for VH rearrangement was performed. Monoclonal PCR products were cloned and sequenced. Results Fourteen of 20 patients had a monoclonal or oligoclonal band distribution at diagnosis converted into polyclonal pattern after radiochemotherapy. Of the remaining six patients, two were lost to follow-up. One patient did not respond and died of progressive disease. PCR in this patient showed persistent B-cell clonality. In three patients, the initial PCR showed a polyclonal pattern and thus could not be evaluated during follow-up. Conclusion In contrast with H pylori eradication alone, radiochemotherapy results in clearing of monoclonal cells during follow-up. This may result in better elimination of residual lymphoma cells. Further study is needed to determine whether this translates into lower risk of relapse.

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1601-1601 ◽  
Author(s):  
Jeremy S. Abramson ◽  
Matthew D Hellmann ◽  
Yang Feng ◽  
Jeffrey A. Barnes ◽  
Tak Takvorian ◽  
...  

Abstract Abstract 1601 Introduction: Primary Mediastinal B-cell Lymphoma (PMBCL) is an uncommon variant of Diffuse Large B-cell Lymphoma (DLBCL). Given the rarity of this disease, data guiding management is extrapolated from DLBCL trials, or from small retrospective analyses limited to PMBCL. Prospective evaluation of R-CHOP in the MiNT trial showed excellent results in PMBCL, but this trial was limited to young low risk patients. We present the largest retrospective series to date of R-CHOP for PMBCL in all risk groups. Methods: We identified cases of PMBCL at our institution using a comprehensive clinicopathologic database derived from tumor registry data. Natural language processing software was used to search pathology reports for terms of “mediastinal lymphoma,” “mediastinal large cell lymphoma,” “mediastinal large B-cell lymphoma,” as well as “lymphoma” in mediastinal biopsy specimens. Cases were included if they met clinicopathologic criteria for PMBCL, defined as a large B-cell lymphoma with typical features for PMBCL presenting with a dominant anterior mediastinal mass. All patients had to have been treated with R-CHOP. Progression-free survival (PFS) and overall survival (OS) are calculated by the Kaplan-Meier method and univariate analysis is performed to assess predictors of outcome. Results: Fifty-eight cases from 2000–2011 met inclusion criteria and are included in the analysis. The median age was 38 years (range 20–82) and 60% were male. Forty-four patients (76%) presented at limited Ann Arbor stage and 12 patients (21%) at advanced stage; presenting stage could not be discerned in 2 patients. Fifty-five percent of patients presented with mediastinal bulk ≥10cm in size; median size was 11cm (range 5–17cm). LDH was elevated at diagnosis in 60% of patients, normal in 21%, and unknown in 19%. By revised IPI score, 19% were low-risk (0 risk factors), 60% were intermediate risk (1–2 risk factors) and 12% were high-risk (≥3 risk factors). R-CHOP was given for a median of 6 cycles (range 1–8); 51 of 58 patients received 6 or 8 cycles. Among patients who achieved initial remission, 78% underwent consolidative radiotherapy and the remainder were observed after chemotherapy alone. The overall response rate was 81% (90%CI [71%–89%]) with 72% complete responses and 9% partial responses. Ten patients (17%) had primary refractory disease defined as progression on treatment or within 3 months of completion of therapy. Among 46 patients who achieved a response, 5 (11%) subsequently relapsed. Two patients, both elderly, died during treatment. Among the 10 patients with primary refractory disease, 6 have died from progressive lymphoma, 2 patients are alive with active disease undergoing salvage therapy, 1 is alive and free of disease greater than 8 years from diagnosis, and 1 was lost to follow-up. Among 5 patients with relapsed disease, 2 are alive without disease at last follow-up, while 3 have died of progressive lymphoma. Median follow-up for the entire series is 58 months. Five-year PFS is 68% (95% CI, 55% to 80%) and 5-year OS is 76% (95% CI, 65% to 88%). On univariate analysis, advanced Ann Arbor stage and high R-IPI score were associated with inferior PFS and OS. (p=0.006 and p<0.001, respectively for PFS, p=0.005 and p<0.001 for OS, log-rank test). Conclusion: PMBCL treated with R-CHOP carries an overall favorable prognosis, though primary refractory disease occurs in a significant number of patients, and is rarely curable with second line therapy. Advanced stage disease and high R-IPI scores are associated with inferior outcome. Novel treatment approaches warrant evaluation in high-risk patients. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 94-101
Author(s):  
LF Bertoli ◽  
H Kubagawa ◽  
GV Borzillo ◽  
PD Burrows ◽  
MT Schreeder ◽  
...  

To search for precursors of the neoplastic B cells in a patient with a nodular lymphoma, we produced a monoclonal antibody to a variable region idiotope on the lymphoma IgM heavy chain. Clonal ancestors of the lymphoma cells were identified by this marker among bone marrow pre- B cells (5% to 26%). A second antiidiotype (anti-Id) antibody specific for the complete lymphoma IgM kappa recognized 10% of B cells in bone marrow and blood and greater than 95% of B cells in lymphomatous lymph nodes, including one obtained after tumor conversion to a diffuse large cell lymphoma. Immunoglobulin gene analysis surprisingly revealed expansion of multiple clones of early B lineage cells in bone marrow, including members of the neoplastic clone. The data suggest that this lymphoma arose through a progression of transformational events beginning in bone marrow: first, creation of an oligoclonal pre- neoplastic pool of pre-B cells, subsequent conversion of a single subclone into low grade neoplastic B cells that homed to the lymph node follicles, and later progression to a more invasive form of the B-cell lymphoma.


2021 ◽  
Vol 20 (1) ◽  
pp. 162-167
Author(s):  
M. A. Senchenko ◽  
D. S. Abramov ◽  
A. E. Rudneva ◽  
E. V. Volchkov ◽  
G. A. Nasirdinova ◽  
...  

Nodular lymphocyte predominant Hodgkin lymphoma (NLHLP) – B-cell lymphoma, which has been historically added to the group of Hodgkin's lymphomas, despite the peculiarities of the clinical course, treatment and prognosis, as well as morphological and immunophenotypical differences. In 75% of cases, the disease is detected at early stages (I–II according to Ann Arbor classification), has an indolent course and a favorable prognosis with 10-years an overall survival rate, more than 80%. Despite this, with long-term follow-up and the development of frequent relapses, transformation into diffuse large-cell B-cell lymphoma (DCBCL) or T-lymphocyte/histiocyte-rich DCBCL can occur, isolated cases in children. In the world literature, there are isolated cases of the development of NLHLP after treatment of DCBKL in adults, while among the pediatric population, cases have not been described. This article presents a clinical case of DCBKL in a 10-year-old child who, 5 years after the end of treatment, developed nodular Hodgkin's lymphoma with lymphocytic predominance. The patient's parents agreed to use the information, including the child's photo, in scientific research and publications. 


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3590-3590 ◽  
Author(s):  
Kieron Dunleavy ◽  
Stefania Pittaluga ◽  
Nicole Grant ◽  
Seth Steinberg ◽  
Margaret Shovlin ◽  
...  

Abstract Gray zone lymphomas (GZL) are diseases with transitional morphology and immunophenotypic features between Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Their pathological and clinical characteristics are not well studied and the best treatment strategy (using HL or DLBCL regimens) has not been defined. Small previous series of HL-like ALCL, which would include GZL, suggest they have a poor outcome with HL treatments. We present GZL’s treated on studies of DA-EPOCH-R at the National Cancer Institute and describe their clinical and histological features and outcome. Overall, 14 patients with GZL were identified. Characteristics included median (range) age 30 (12–51) years; male sex 10 (71%); stage III/IV 2 (14%) and; elevated LDH 7 (50%). These cases could be divided into three Gray zone groups: classical HL (cHL) and primary mediastinal B-cell lymphoma (PMBL) in 9 (64%) patients; cHL and DLBCL in 2 (14%) and; lymphocyte predominant HL (LPHL) and T-cell histiocyte-rich large cell lymphoma (TCRBCL) in 2 (14%). Pathological characteristics are shown below. All but one case was CD 10 negative. Markers of cHL included CD15 in 33–50% and CD30 in 66–100% of cases. Morphologically, Reed-Sternberg like cells were typically seen in GZL with cHL features. Thirteen newly diagnosed patients received DA-EPOCH-R. Of 11 patients evaluable for response (2TE), 10 (91%) achieved CR and 1 PR. At a median follow-up time of 4 years, OS and PFS are is 86% and 57%, respectively. Of 9 patients with GZL between cHL and PMBL, 4 (44%) also required radiation therapy compared to only 3/31 (10%) patients with PMBL to achieve durable remissions. Gray zone lymphomas represent a biological and clinical continuum between HL and B-cell lymphomas. Clinically, they appear to be more resistant to treatment than either HL or DLBCL and may require aggressive treatment strategies including radiation. Accrual continues. Gray Zone Total 14 CD 20 CD 15 CD 30 cHL- PMBL 9 8 (89%) 7 (50%) 9 (100%) cHL-DLBCL 2 2 (100%) 1 (50%) 2(100%) LPHL-TCRBCL 3 3 (100%) 1 (33%) 2 (66%)


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5099-5099
Author(s):  
Jose Carlos Revilla Lopez ◽  
Jorge A Benavides vasquez ◽  
Lina P Huerta Saenz

Abstract Abstract 5099 Non-Gastric Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue in a Peruvian Referral Cancer Center (Instituto Nacional de Enfermedades Neoplasicas) Jose C. Revilla, MD1, Jorge A. Benavides, MD, Lina Huerta-Saenz, MD*,2. 1Oncological Medicine Deparment, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru,2Albert Einstein Medical Center, Philadelphia, PA, USA Historically, non-gastric marginal zone MALT lymphomas have been difficult to characterize because of their wide anatomical distribution. Previous studies have shown broad distribution patterns with different clinical courses and responses to therapy. There are still questions regarding which could be the best clinical management and this remains without a conclusive answer. A retrospective 10-year study from 1997 to 2007 of patients with diagnosis of non-gastric marginal zone B-cell lymphoma of mucosa-associated lymphoma tissue (MALT) was performed in a Peruvian referral cancer center. To be eligible for the study, all patients had to have pathological confirmation of diagnosis with a clinically dominant non-gastric site of localization. Disease stage was defined according to the Ann Arbor staging criteria, Zubrod performance status scale and location of extranodal disease. Serum lactate dehydrogenase (LDH) and β2-microglobulin levels were used for laboratory monitoring. Bone marrow compromise was also evaluated. All data regarding medical treatment, response to treatment, failure, death and disease status at last follow-up were obtained. The results showed 23 patients with confirmed diagnosis, 74% of whom were female, and the mean age at time of diagnosis was 52 years old. The clinical predominant disease stages at the time of diagnosis were Ann Arbor stage I or II (76%). B-symptoms were present in 35% of the patients and only 13% of them had increased LDH levels. Bone marrow compromise was not present in the majority of patients (96%) and 75% of them had a low international prognostic index (IPI) score. The predominant anatomical location was the conjunctiva (39.1%) followed by the lung (13.1%). These findings were different from previous studies in European and North American populations where the salivary glands were the most common location. Ethnicity may be proposed as a factor related to these differences in anatomical location patterns. Regarding medical management, chemotherapy was the first-line of treatment and anthracyclines were the agents predominantly used (47.8% of patients). Radiotherapy alone was given to 18.2% of patients during the study and combinations of chemotherapy and radiotherapy were used in 4.6% of patients. Follow-up was completed for an average of 25.1 months (range=14.3-35.9 mo), with a complete response to the treatment in 56.6% of patients. Hashimoto's thyroiditis and hepatitis C were the only concomitant medical conditions reported for one patient each, respectively. The survival curve did not show significant differences by gender (p<0.05). In this study, non-gastric B-cell lymphoma of mucosa-associated lymphoma tissue (MALT) showed an indolent clinical course with female predominance and early stages at time of diagnosis. Ocular conjunctiva was the most common location and most of the patients showed good clinical response to the first-line chemotherapy treatment; additionally, there was a low associated mortality rate. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 94-101 ◽  
Author(s):  
LF Bertoli ◽  
H Kubagawa ◽  
GV Borzillo ◽  
PD Burrows ◽  
MT Schreeder ◽  
...  

Abstract To search for precursors of the neoplastic B cells in a patient with a nodular lymphoma, we produced a monoclonal antibody to a variable region idiotope on the lymphoma IgM heavy chain. Clonal ancestors of the lymphoma cells were identified by this marker among bone marrow pre- B cells (5% to 26%). A second antiidiotype (anti-Id) antibody specific for the complete lymphoma IgM kappa recognized 10% of B cells in bone marrow and blood and greater than 95% of B cells in lymphomatous lymph nodes, including one obtained after tumor conversion to a diffuse large cell lymphoma. Immunoglobulin gene analysis surprisingly revealed expansion of multiple clones of early B lineage cells in bone marrow, including members of the neoplastic clone. The data suggest that this lymphoma arose through a progression of transformational events beginning in bone marrow: first, creation of an oligoclonal pre- neoplastic pool of pre-B cells, subsequent conversion of a single subclone into low grade neoplastic B cells that homed to the lymph node follicles, and later progression to a more invasive form of the B-cell lymphoma.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5494-5494 ◽  
Author(s):  
Jana Konstantinovna Mangasarova ◽  
Sergey Kirillovich Kravchenko ◽  
Aminat Umaraskhabovna Magomedova ◽  
Anna Misyurina ◽  
Elena Baryakh ◽  
...  

Abstract Introduction. Primary mediastinal B-cell lymphoma (PMBCL) amounts from 0,9 to 4% of Non-Hodgkin Lymphomas. Predominantly suffer young women. All relapses in PMBCL occur as early events. Taking into account unfavorable prognosis in case of relapse or progression of PMBCL (2-year overall survival (OS) is about 15% [Kurvilla J., 2008]), it's necessary to achieve a complete remission (CR) in first line treatment. Aim. To compare an efficacy of R-DA-EPOCH followed by R-DHAP and autologous peripheral blood stem cell transplantation (autoSCT) with BEAM conditioning regimen with modified (m) NHL-BFM-90 chemotherapy protocol in pts with partial remission (PR) of PMBCL. Patients and Methods. In 107 pts (34 males, 73 females) diagnosis of PMBCL was established according to WHO criteria. All pts had stage II of disease according to Ann Arbor classification. 30 pts received R-DA-EPOCH, 77 pts - m-NHL-BFM-90 ± R. Median age of pts in R-DA-EPOCH group was 28 years old (from 20 to 67 years old); in m-NHL-BFM-90 ± R-group - 77 years old. Increased LDH concentration was revealed in 24 from 30 (80%) pts in R-DA-EPOCH group and in 75/77 (97%) pts from m-NHL-BFM-90 ± R group. Bulky mediastinal disease was in 30/30 (100%) pts in R-DA-EPOCH group and in 59/77 (76%) - m-NHL-BFM-90 ± R group. In case of CR after 6 courses according to computer tomography and PET scanning treatment was completed. In case of PR pts underwent 2 R-DHAP courses with autoSCT (BEAM conditioning regimen). All pts from m-NHL-BFM-90 ± R group independently from PET-results stopped treatment. All cases of treatment failure occurred till one year of observation. Kaplan-Meier method was used to calculate OS and relapse-free survival (RFS). OS was defined as time from diagnosis to death from any reason; RFS was defined as time from diagnosis until relapse or death from any cause. Results: After 6 R-DA-EPOCH therapy CR was achieved in 24/30 (80%) pts, 6/30 (20%) pts had PR and underwent 2 R-DHAP courses followed by auto-SCT (BEAM). 2- RFS and OS was 100%. Median follow up was 16 months. In m-NHL-BFM-90 ± R group 10-year RFS and OS were 85% and 92%, respectively. Median follow up was 53 months. Conclusion: High dose pulsed m-NHL-BFM-90-chemotherapy as well as R-DA-EPOCH allows getting high efficacy of primary mediastinal B-cell lymphoma therapy. Although future analysis will show more distant results of R-DA-EPOCH chemotherapy. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1790-1790 ◽  
Author(s):  
Ho-Young Yhim ◽  
Jae-Yong Kwak ◽  
Hye Jin Kang ◽  
Seok Jin Kim ◽  
Won Seog Kim ◽  
...  

Abstract Abstract 1790 Introduction The addition of rituximab to standard chemotherapy has substantially improved the survival in patients with diffuse large B cell lymphoma (DLBCL). Previous studies in the pre-rituximab era have identified the worse outcomes in primary extranodal DLBCL compared with nodal DLBCL. However, there have been reported conflicting datas about outcomes of primary extranodal DLBCL compared with nodal DLBCL in the rituximab era. Primary breast DLBCL is one of the extremely rare extranodal lymphoma. As in other primary extranodal lymphoma, few clinical studies have been reported for investigating the efficacy of rituximab in patients with primary breast DLBCL. For clarifying this, a large randomized trial comparing survival in patients with primary breast DLBCL is required. However, the rarity of primary breast DLBCL makes large trial virtually difficult in single center or study group. Additionally, retrospective studies for evaluating the role of rituximab in primary breast DLBCL had bias according to the difference of treatment period between CHOP and R-CHOP era. Thus, to investigate the impact of rituximab in primary breast DLBCL, we performed a matched pair analysis following strict matching criteria in patients with primary breast and nodal DLBCL treated with R-CHOP. Materials and methods Primary breast DLBCL patients treated with R-CHOP was identified from 11 hospitals in Korea between May 2004 and August 2009. The eligibility criteria included: (1) histologically confirmed DLBCL, (2) Ann Arbor stage I or II of primary breast DLBCL, defined as isolated breast involvement with or without nodal disease, (3) received front-line treatment with R-CHOP. Each primary breast DLBCL patient was matched to three nodal DLBCL patients treated with R-CHOP during the same period from the data registry of Korean Lymphoma Working Party. The patients were matched for 5 known prognostic factors: age (<60 vs. ≥60), Ann Arbor stage (I vs. II), Eastern Cooperative Oncology Group (ECOG) performance status (PS) (0-1 vs. 2–3), serum LDH level (normal vs. elevated), and B symptom (absent vs. present). All factors should be matched between the four matched patients. Results Twenty-five patients with primary breast DLBCL were identified. The median age at diagnosis was 56 (range, 21–79) years and all patients were female. The Ann Arbor stage was I in 13 patients (52%) and II in 12 patients (48%). ECOG PS was 0 or 1 in 23 patients (92%), B symptom was present in 1 patient (4%), and serum LDH level was elevated in 9 patients (36%). Thus, stage-modified international prognostic index (IPI) was 0 or 1 in 20 patients (80%). Eight patients (32%) were received 3 or 4 cycles of R-CHOP followed by involved field radiotherapy and 17 patients (68%) were treated with 6 to 8 cycles of R-CHOP. After matching process, stage-modified IPI, treatment strategy, radiation dose, and follow-up duration as well as 5 matching factors were not significantly different between primary breast and nodal DLBCL groups. With a median follow-up of 34.3 (range, 4.4–76.2) months, 3-year progression-free survival (PFS; 70.0% [59.9-80.1] vs. 85.2% [79.9-90.5], p=0.145) and overall survival (OS; 82.2% [72.6-92.8] vs. 90.0% [86.0-94.0], p=0.528) was not statistically different between primary breast and nodal DLBCL groups. In multivariate analysis, 2 or 3 risk factors of stage-modified IPI were independent prognostic factor for worse PFS (hazard ratio [HR], 3.18; 95% CI, 1.22–8.30) and OS (HR, 4.88; 95% CI, 1.55–15.33). Comparing 3-year cumulative incidence of progression between primary breast and nodal DLBCL, extranodal progression in the breast or central nervous system (CNS) was significantly higher in the primary breast DLBCL than nodal DLBCL (23.6 ± 9.3% vs. 1.4 ± 1.3%, p<0.001, respectively). Conclusions In the post rituximab era, the survival outcomes of primary breast DLBCL were not significantly inferior to those of nodal DLBCL. These results suggest adding rituximab improve survival in primary breast DLBCL as in nodal DLBCL, so that the results provide evidence to add rituximab in this rare extranodal DLBCL. However, even including rituximab, extranodal progression in the breast or CNS was observed still high. Thus, further larger studies of international collaboration to confirm these results are warranted. Disclosures: No relevant conflicts of interest to declare.


Praxis ◽  
2016 ◽  
Vol 105 (1) ◽  
pp. 47-52 ◽  
Author(s):  
Andreas Lohri

Zusammenfassung. Maligne Lymphome unterteilen sich zwar in über 60 Entitäten, das grosszellige B-Zell-Lymphom, das follikuläre Lymphom, der Hodgkin und das Mantelzell-Lymphom machen aber mehr als die Hälfte aller Lymphome aus. Im revidierten Ann Arbor staging system gelten die Suffixe «A» und «B» nur noch für den Hodgkin. «E» erscheint nur noch bei Stadien I und II. Eine Knochenmarksuntersuchung wird beim Hodgkin nicht mehr verlangt, beim DLBCL (Diffuse large B cell lymphoma) nur, falls das PET keinen Knochenmark-Befall zeigt. Der PET-Untersuchung, speziell dem Interim-PET, kommt eine entscheidende Bedeutung zu. PET-gesteuerte Therapien führen zu weniger Toxizität. Gezielt wirkende Medikamente mit eindrücklicher Wirksamkeit wurden neu zugelassen. Deren Kosten sind hoch. Eine strahlen- und chemotherapiefreie Behandlung maligner Lymphome wird in Zukunft möglich sein.


Sign in / Sign up

Export Citation Format

Share Document