8099 Background: An evaluation of clinical characteristics and potential risk factors affecting o... more 8099 Background: An evaluation of clinical characteristics and potential risk factors affecting outcome in patients with MALT lymphoma was performed at our institution. Patients and Methods: As of 1997, a total of 170 consecutive patients with histologically verified MALT lymphoma (99 female/71 male) underwent uniform staging and assessment of clinical characteristics including assessment of genetic changes, presence of autoimmune disease (AD), Helicobacter pylori (HP)-status, monoclonal immunoglobulins (MG) and plasmacytic differentiation (PD). All patients with follow-up at our institution were analysed, and influence of various parameters on dissemination and outcome were evaluated. Sixty-four patients (38%) had gastric MALT-lymphoma (GML) and 106 (62%) extragastric MALT-lymphoma (EGML). Results: 66/170 patients (39%) had multiorgan-involvement upon presentation, while only 3 patients had bone marrow involvement. Patients with EGML (49/106, 46%) were at significantly higher risk for multiorgan-disease than patients with GML (17/64, 27%, p = 0.013). 58 patients had genetic aberrations, with t(11;18) being more common in GML (p = 0.002) and trisomy 3 (p = 0.03) and trisomy 18 (p = 0.02) in EGML. Among GML, translocation t(11;18) was significantly associated with multiorgan-disease, as was trisomy18 in EGML (p = 0.038). After a median follow-up time of 40 months, 139 patients (86%) are alive. 58 patients (39%) have relapsed, with the median to relapse being 60 months. Overall, multifocality and extragastric origin (p < 0.001) were significantly associcated with relapse, while patients with t(11;18) had a significantly longer time to relapse (131 vs 49 months). Survival and relapse were not affected by the form of therapy applied (i.e. local vs systemic). An underlying AD was found in 65 patients (38%), and was significantly associated with EGML (p = 0.007) and multifocality (p = 0.04), but did not influence relapse and survival. HP-positivity was significantly associated with GML (p = 0.001), and patients with EGML did not respond to HP-eradication. Conslusion: Our data suggest dissemination and (late) relapse to be relatively common in MALT-lymphoma. Based on our findings, however, an individualized staging approach and risk-assessment is possible. No significant financial relationships to disclose.
Clinical Lymphoma, Myeloma & Leukemia, Jun 1, 2015
ABSTRACT We have performed a retrospective analysis of all patients with extragastric mucosa-asso... more ABSTRACT We have performed a retrospective analysis of all patients with extragastric mucosa-associated lymphoid tissue (MALT) lymphoma treated at our institution to compare the efficacy of first-line therapeutic modalities including surgery, radiation, systemic therapy, and antibiotics. One hundred eighty-five patients with extragastric MALT lymphoma with a median age of 63 (interquartile range (IQR) 50-74) years and a median follow-up time of 49 (IQR 18-103) months were retrospectively analyzed. Time to progression and time to next therapy were used as surrogate endpoints for efficacy. Patients having either surgery (100 %), chemo/immunotherapy (85.5 %), or radiation (80 %) had significantly (p = 0.01) higher response rates than patients treated with antibiotics (33.3 %). Patients who were irradiated had significantly more progressive disease, but also the longest follow-up time. Stage, elevated LDH, anemia, elevated beta-2 microglobulin, plasmacytic differentiation, monoclonal gammopathy, or autoimmune disease did not influence the rate of disease progression nor did complete remission or partial remission from initial therapy influence time to and rate of progression. There was no significant difference in the median time to progression (p = 0.141), but the estimated time to progression (p = 0.023) as well as the estimated time to next therapy (p = 0.021) was significantly different among the various cohorts favoring surgery, chemo/immunotherapy, and radiation. Our results suggest extragastric MALT lymphoma as a potential systemic disease irrespective of initial stage. Radiation, surgery, and chemo/immunotherapy seem to be equally effective in achieving remissions and prolonged progression free survivals, but a curative potential is questionable. Localized MALT lymphomas affecting the thyroid gland or the lungs have excellent long-term progression-free survivals with surgical treatment only.
Mucosa associated lymphoid tissue lymphoma of the stomach is associated with Helicobacter pylori ... more Mucosa associated lymphoid tissue lymphoma of the stomach is associated with Helicobacter pylori (HP) infection in the large majority of patients [1]. Following initial pilot studies, large scale trials have consistently shown that HP eradication as sole treatment modality in patients with early stage HP-associated gastric MALT lymphoma can achieve sustained complete remission (CR) in *80% of selected patients [2,3]. Patients treated with antibiotic therapy have an exellent long-term outcome and a low rate of relapse, although a significant percentage remains monoclonal after HP eradication [4]. Recently, several prognostic factors contributing to the efficacy of HP eradication have been defined, including depth of invasion [5], presence of an underlying autoimmune disease [6], monoclonal gammopathy [7] and presence of t(11;18)(q21;21), which occurs exclusively in MALT lymphoma and defines the large majority of non-responders [8,9]. In 5 – 10% of patients with gastric MALT lymphoma, however, an infection with H. pylori cannot be detected with the currently available methods including breath test, histology, serology and stool antigen. With regards to such patients, there are only limited clinical data at the moment. A retrospective multi-center analysis [10] has shown a higher rate of t(11;18)(q21;q21) in H. pylori negative MALT lymphoma patients than in HP positive patients. In this analysis, a limited number of patients had not responded to HP eradication. These patients, however, had a high rate of t(11;18)(q21;q21) and/ or presented with advanced disease. As opposed to this, recent data from our institution [11] have demonstrated that antibiotic treatment might still constitute an effective form of treatment in selected patients with early stage gastric MALT lymphoma in the absence of parameters suggestive of HP infection. A total of six patients with localised gastric lymphoma were given antibiotic treatment, with four developing a sustained CR, one relapsing after 14 months and one having stable disease for 12 months before being referred to alternative treatment. One of the patients with CR tested positive for t(11;18)(q21;21), while the remaining five were negative. As opposed to HP positive gastric MALT lymphomas, which might respond to a second course of antibiotic treatment at relapse from initial remission, virtually nothing is known about the potential of antibiotic re-treatment in case of relapse from HP negative gastric MALT lymphoma. We present the case of a patient with HP negative gastric MALT lymphoma who developed a second CR when treated with an alternative antibiotic regimen following relapse 21 months after initial CR. A 59-year old man was referred to our department for treatment of gastric MALT-lymphoma diagnosed at another hospital. Unspecific epigastric complaints refractory to treatment with H2-blockers for 3 weeks had led to gastroscopy, disclosing multiple slight ulcerations. Histologic evaluation of the biopsies was
Memo – Magazine of European Medical Oncology, Oct 1, 2009
Mucosa-associated lymphoid tissue (MALT) lymphoma is amongst the most common lymphoma entities an... more Mucosa-associated lymphoid tissue (MALT) lymphoma is amongst the most common lymphoma entities and comprises about 7% of all newly diagnosed NHL. Roughly 50% of all MALT lymphomas are located in the stomach, where a pathophysiological link with Helicobacter pylori (HP) with consecutive response to HP eradication therapy has been established. In view of this, HP eradication has become the standard approach to patients with localised disease and signs of HP infection. Recent data, however, have suggested that also HP-negative patients might benefit from antibiotic treatment. On the other hand, an unexpectedly high rate of autoimmune diseases, e.g. Hashimoto’s thyroiditis or Sjogren’s syndrome has been found in gastric MALT lymphoma, and such patients do not respond to HP eradication in the large majority. In case of non-response to antibiotics the standard approach in such patients is currently not clear. Both radiation as well as chemotherapy has shown promising results, and currently there is only one randomised study, which nevertheless suggests superiority of chemotherapy in terms of event-free survival at 10 years. The optimal chemotherapeutic regimen, however, has not been established yet, although various agents and combinations have demonstrated high activity, albeit in small trials. In view of this, patients with gastric MALT lymphoma unresponsive to antibiotics should be included in clinical trials.
Background: The prognostic values of the International Prognostic Index (IPI) and the Follicular ... more Background: The prognostic values of the International Prognostic Index (IPI) and the Follicular Lymphoma International Prognostic Index (FLIPI) have widely been demonstrated in diffuse large B-cell lymphoma and follicular lymphoma. No attempts to assess their applicability in MALT lymphoma have been made so far. Patients and methods: A total of 143 patients with MALT-lymphoma were analysed. Parameters of both IPI and FLIPI were retrospectively assessed and correlated with relapse and time to relapse as markers of clinical course. Results: According to IPI, 96 patients (67%) were classified as low, 22 (15%) low-intermediate, 17 (12%) high-intermediate and 8 (6%) as high risk. FLIPI identified 99 patients (70%) at low risk, 35 (24%) at intermediate and 9 (6%) at high risk. After a median follow-up time of 39.5 months, 123 patients were alive and 46 patients had relapsed (median time to relapse 27 months). IPI significantly correlated with time to relapse, with the typical differentiation into low, low-intermediate and high risk groups. FLIPI divided patients into three groups, but the low and intermediate risk groups showed a similar clinical course. In terms of additional progonostic factors, univariate analysis suggested autoimmune disease and multifocal disease as correlated with relapse. Multiple regression analysis, however, identified only extragastric disease as predictive of relapse (p=0.001). Conclusion: Our data demonstrate that both IPI and FLIPI are able to discriminate prognostic subgroups in patients with MALT-lymphoma. However, the low and intermediate group of the FLIPI did not appear to prognostically differ.
Primary central nervous system lymphoma (PCNSL) is a rare and malignant tumour type. Established ... more Primary central nervous system lymphoma (PCNSL) is a rare and malignant tumour type. Established treatment approaches include high-dose methotrexate (HD-MTX) -based chemotherapy and whole-brain radiotherapy (WBRT). WBRT is associated with significant neurotoxicity and autologous haematopoietic stem cell transplantation (ASCT) has been proposed as an alternative treatment - either in the 1(st) line setting after HD-MTX based chemotherapy or as salvage treatment for relapsed/refractory PCNSL. We here report our single centre experience with five PCNSL patients, who had achieved an objective response after a high-dose methotrexate based induction therapy and consecutively received a high-dose chemotherapy, consisting of carmustine and thiotepa, followed by ASCT. We also provide a literature review on ASCL for PCNSL. Our data, with three out of five patients in continuous complete remission and four out of five patients alive after a median follow-up time of 8 months, as well as previously published results, show that ASCT is a safe treatment option that is able to induce tumour remissions in patients with PCNSL. However, controlled trials are needed to compare the long-term efficacy and tolerability of ASCT with other treatment approaches and also to establish the optimal sequence of treatment regimens in PCNSL patients. This article is protected by copyright. All rights reserved.
Enteropathy-associated T cell lymphoma (EATL) is a rare disease with a dismal prognosis. Due to t... more Enteropathy-associated T cell lymphoma (EATL) is a rare disease with a dismal prognosis. Due to the low efficacy of chemotherapy and the poor performance status of patients failing first line, no data on second line therapy exist. A retrospective analysis of 19 patients with EATL at our institution identified six patients (31%) undergoing second line chemotherapy after CHOP-like regimens. Three patients had progressive disease (PD) during first line therapy, while the other three patients showed relapse after an initial complete remission (CR). The time from the last cycle of first line chemotherapy to second line therapy was 1-62 months. Two patients received ifosfamide, carboplatin and etoposide (ICE), two were given fludarabine and cyclophosphamide (FC) and one each had dexamethasone, cisplatin and cytarabine (DHAP) and cladribine chemotherapy. One patient progressed after one course of cladribine, while two patients developed intestinal perforation and died after one course of ICE and DHAP, respectively. Three patients achieved a CR lasting 4, +7 and +64 months, with two being alive without evidence of disease. Our data again confirm the poor prognosis of patients with EATL. A small subset of patients, however, apparently benefits from initiation of second line chemotherapy.
Background: Mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) of the lung is a relativel... more Background: Mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) of the lung is a relatively rare disease. As little is known about the natural clinical course if left untreated, all patients undergoing a watch-and-wait policy at our institution were investigated. Patients and methods: A retrospective analysis identified a total of 11 patients with MALT lymphoma of the lung who did not undergo treatment following initial diagnosis. All patients had undergone extensive staging and were closely observed with restaging every three months. Histological assessment included immunhistochemistry for demonstration of the immunphenotype CD20+/CD5-/ CD10-/cyclinD1-/CD23-. Genetic aberrations were assessed, using RT-PCR for t(11;18) (q21;21) and fluorescence in situ hybridisation for the evaluation of t(14;18)(q32;q21), t(1;14) (p22;q32), trisomies 3 and 18. Results: Five patients had MALT lymphoma restricted to the lung, while the remaining six had additional extrapulmonary sites detected during staging. The median time of observation without therapy was 28.1 months (inter-quartile range: 5 to 60 months); within this time, all 11 patients showed at least stable disease. Six of these 11 patients, however, had spontaneous regressions and wax-and-wane phenomena of the pulmonary lesions, but not of extrapulmonary manifestations. Three of these patients had evidence of t(11;18)(q21;q21), while the remaining three had no evidence of genetic aberrations. One patient was referred for treatment after progression in the lung, while two patients experienced progression outside the lung. Currently, all patients are alive, with 8 patients still only being watched. Conclusion: Our findings suggest that MALT lymphoma of the lung is a very indolent disease with the potential for spontaneous regression. In view of this, patients diagnosed with pulmonary MALT lymphoma might not require immediate treatment in the absence of symptoms and a watch-and-wait policy could be adopted.
Mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively common lymphoma and comprises a... more Mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively common lymphoma and comprises approximately 7% of all newly diagnosed non-Hodgkin's lymphoma. It is mainly located in the stomach and has become a focus of interest due to its unique pathophysiological link with Helicobacter pylori (HP) and the consecutive response to HP eradication therapy. In view of this, HP eradication has become standard treatment for patients with localised disease, and recent data have suggested that HP-negative patients might benefit from antibiotic treatment. In case of non-response, however, the standard approach in such patients is unclear. Both radiation and chemotherapy have shown promising results, and at present there is only one randomised study, which nevertheless suggests chemotherapy as management of choice. The objective of this review is, therefore, to summarise and evaluate the data available for treatment of gastric MALT lymphoma and to highlight potential focus for further research.
In contrast to its gastric counterpart, mucosa-associated lymphoid tissue (MALT) lymphoma of the ... more In contrast to its gastric counterpart, mucosa-associated lymphoid tissue (MALT) lymphoma of the parotid gland has not been studied extensively. We analyzed the clinicopathological features and the clinical course of all patients with parotid gland MALT lymphoma diagnosed and treated at our institution. Patient characteristics including an underlying autoimmune disease, disease stage, genetic aberrations, treatment, and clinical course were assessed and evaluated. Twenty-eight patients (19 women, 9 men) were identified; median age at diagnosis was 49 years (interquartile range [IQR], 40-56), and 18 patients (64%) had an underlying autoimmune disease. Eleven had stage IE, 7 patients had stage IIE, and 10 had advanced disease (stage IV). Genetic aberrations were detected in 9 of 20 patients; 5 patients had trisomy 3, 2 patients had a t(11;18)(q21;21) translocation, 1 had trisomy 3 and 18, and 1 patient had a t(14;18)(q32;q21) translocation plus trisomy 18. After a median follow-up time of 62 months (IQR, 32-98 months), 24 patients (86%) are alive. Fifteen patients are free from lymphoma, whereas 13 patients (46%) have had a relapse. Our data suggest that MALT lymphoma of the parotid gland is often associated with autoimmune diseases and that trisomy 3 is the most common genetic feature of this disease. The high rate of relapse warrants further study on optimal therapy of such patients.
Radioimmunotherapy using (90)Y-ibritumomab tiuxetan has predominantly been used in patients with ... more Radioimmunotherapy using (90)Y-ibritumomab tiuxetan has predominantly been used in patients with follicular lymphoma, but little is known about its activity in patients with extranodal marginal zone lymphoma of the mucosa associated lymphoid tissue (MALT). A total of six patients progressing/relapsing following conventional therapy for MALT lymphoma were treated with (90)Y-ibritumomab tiuxetan at our institution. Two patients had gastric MALT lymphoma, one suffered from orbital MALT lymphoma, and two had cutaneous MALT lymphoma, while one patient had a widely disseminated lymphoma involving the stomach, lungs, lymph nodes, and salivary glands. All patients were at least in third relapse following various forms of therapy including Helicobacter pylori-eradication, radiation, chemotherapy, and application of rituximab. Following two doses of rituximab at 250 mg/m(2) at an interval of 1 week, (90)Y-ibritumomab tiuxetan was given immediately at a dose of 0.4 mCi/kg body weight. Treatment was well tolerated apart from one episode of pneumonia requiring hospitalization. Four patients developed a complete remission (ongoing now for 4, 16, 23, and 24 months), one patient had a partial response lasting for 5 months, and one patient had stable disease for 13 months. After a follow-up of 9-29 months, all patients are alive. Application of (90)Y-ibritumomab tiuxetan is active and safe in heavily pretreated patients with MALT lymphoma.
Background: Various chemotherapeutic agents as well as the anti-CD20 antibody rituximab (R) have ... more Background: Various chemotherapeutic agents as well as the anti-CD20 antibody rituximab (R) have been tested in patients with mucosa-associated lymphoid tissue (MALT) lymphoma, but no standard chemotherapeutic regimen has emerged so far. Judging from the data obtained in various types of lymphoma, the activity of R appears to be enhanced by combination with chemotherapy. As no data on this topic exist for MALT lymphoma, we have retrospectively analysed our experience with R plus cyclophosphamide, doxorubicin/mitoxantrone, vincristine and prednisone (R-CHOP/R-CNOP) in patients with relapsed MALT lymphoma. Patients and Methods: A total of 26 patients were identified, 15 were administered R-CHOP while 11 patients were given R-CNOP due to age >65 years or pre-existing cardiac conditions. Cycles were repeated every 21 days, and restaging was performed after 4 cycles of therapy. In case of complete remission, 2 further cycles were administered for consolidation while patients achieving partial remission or stable disease after restaging were given 4 further courses. Results: A total of 170 cycles were administered to our patients (median 6, range 2–8). Twenty of the 26 patients (77%) achieved a complete remission and 6 (23%) a partial remission. Toxicities were mainly haematological, with WHO grade III/IV leukocytopenia occurring in 5 patients. After a median follow-up of 19 months (range 10–45), all patients are alive: 22 are in ongoing remission, while 4 have relapsed between 12 and 19 months after treatment. Conclusions: Our data demonstrate a high activity of R-CHOP/R-CNOP in relapsing MALT lymphoma irrespective of prior therapy.
8099 Background: An evaluation of clinical characteristics and potential risk factors affecting o... more 8099 Background: An evaluation of clinical characteristics and potential risk factors affecting outcome in patients with MALT lymphoma was performed at our institution. Patients and Methods: As of 1997, a total of 170 consecutive patients with histologically verified MALT lymphoma (99 female/71 male) underwent uniform staging and assessment of clinical characteristics including assessment of genetic changes, presence of autoimmune disease (AD), Helicobacter pylori (HP)-status, monoclonal immunoglobulins (MG) and plasmacytic differentiation (PD). All patients with follow-up at our institution were analysed, and influence of various parameters on dissemination and outcome were evaluated. Sixty-four patients (38%) had gastric MALT-lymphoma (GML) and 106 (62%) extragastric MALT-lymphoma (EGML). Results: 66/170 patients (39%) had multiorgan-involvement upon presentation, while only 3 patients had bone marrow involvement. Patients with EGML (49/106, 46%) were at significantly higher risk for multiorgan-disease than patients with GML (17/64, 27%, p = 0.013). 58 patients had genetic aberrations, with t(11;18) being more common in GML (p = 0.002) and trisomy 3 (p = 0.03) and trisomy 18 (p = 0.02) in EGML. Among GML, translocation t(11;18) was significantly associated with multiorgan-disease, as was trisomy18 in EGML (p = 0.038). After a median follow-up time of 40 months, 139 patients (86%) are alive. 58 patients (39%) have relapsed, with the median to relapse being 60 months. Overall, multifocality and extragastric origin (p < 0.001) were significantly associcated with relapse, while patients with t(11;18) had a significantly longer time to relapse (131 vs 49 months). Survival and relapse were not affected by the form of therapy applied (i.e. local vs systemic). An underlying AD was found in 65 patients (38%), and was significantly associated with EGML (p = 0.007) and multifocality (p = 0.04), but did not influence relapse and survival. HP-positivity was significantly associated with GML (p = 0.001), and patients with EGML did not respond to HP-eradication. Conslusion: Our data suggest dissemination and (late) relapse to be relatively common in MALT-lymphoma. Based on our findings, however, an individualized staging approach and risk-assessment is possible. No significant financial relationships to disclose.
Clinical Lymphoma, Myeloma & Leukemia, Jun 1, 2015
ABSTRACT We have performed a retrospective analysis of all patients with extragastric mucosa-asso... more ABSTRACT We have performed a retrospective analysis of all patients with extragastric mucosa-associated lymphoid tissue (MALT) lymphoma treated at our institution to compare the efficacy of first-line therapeutic modalities including surgery, radiation, systemic therapy, and antibiotics. One hundred eighty-five patients with extragastric MALT lymphoma with a median age of 63 (interquartile range (IQR) 50-74) years and a median follow-up time of 49 (IQR 18-103) months were retrospectively analyzed. Time to progression and time to next therapy were used as surrogate endpoints for efficacy. Patients having either surgery (100 %), chemo/immunotherapy (85.5 %), or radiation (80 %) had significantly (p = 0.01) higher response rates than patients treated with antibiotics (33.3 %). Patients who were irradiated had significantly more progressive disease, but also the longest follow-up time. Stage, elevated LDH, anemia, elevated beta-2 microglobulin, plasmacytic differentiation, monoclonal gammopathy, or autoimmune disease did not influence the rate of disease progression nor did complete remission or partial remission from initial therapy influence time to and rate of progression. There was no significant difference in the median time to progression (p = 0.141), but the estimated time to progression (p = 0.023) as well as the estimated time to next therapy (p = 0.021) was significantly different among the various cohorts favoring surgery, chemo/immunotherapy, and radiation. Our results suggest extragastric MALT lymphoma as a potential systemic disease irrespective of initial stage. Radiation, surgery, and chemo/immunotherapy seem to be equally effective in achieving remissions and prolonged progression free survivals, but a curative potential is questionable. Localized MALT lymphomas affecting the thyroid gland or the lungs have excellent long-term progression-free survivals with surgical treatment only.
Mucosa associated lymphoid tissue lymphoma of the stomach is associated with Helicobacter pylori ... more Mucosa associated lymphoid tissue lymphoma of the stomach is associated with Helicobacter pylori (HP) infection in the large majority of patients [1]. Following initial pilot studies, large scale trials have consistently shown that HP eradication as sole treatment modality in patients with early stage HP-associated gastric MALT lymphoma can achieve sustained complete remission (CR) in *80% of selected patients [2,3]. Patients treated with antibiotic therapy have an exellent long-term outcome and a low rate of relapse, although a significant percentage remains monoclonal after HP eradication [4]. Recently, several prognostic factors contributing to the efficacy of HP eradication have been defined, including depth of invasion [5], presence of an underlying autoimmune disease [6], monoclonal gammopathy [7] and presence of t(11;18)(q21;21), which occurs exclusively in MALT lymphoma and defines the large majority of non-responders [8,9]. In 5 – 10% of patients with gastric MALT lymphoma, however, an infection with H. pylori cannot be detected with the currently available methods including breath test, histology, serology and stool antigen. With regards to such patients, there are only limited clinical data at the moment. A retrospective multi-center analysis [10] has shown a higher rate of t(11;18)(q21;q21) in H. pylori negative MALT lymphoma patients than in HP positive patients. In this analysis, a limited number of patients had not responded to HP eradication. These patients, however, had a high rate of t(11;18)(q21;q21) and/ or presented with advanced disease. As opposed to this, recent data from our institution [11] have demonstrated that antibiotic treatment might still constitute an effective form of treatment in selected patients with early stage gastric MALT lymphoma in the absence of parameters suggestive of HP infection. A total of six patients with localised gastric lymphoma were given antibiotic treatment, with four developing a sustained CR, one relapsing after 14 months and one having stable disease for 12 months before being referred to alternative treatment. One of the patients with CR tested positive for t(11;18)(q21;21), while the remaining five were negative. As opposed to HP positive gastric MALT lymphomas, which might respond to a second course of antibiotic treatment at relapse from initial remission, virtually nothing is known about the potential of antibiotic re-treatment in case of relapse from HP negative gastric MALT lymphoma. We present the case of a patient with HP negative gastric MALT lymphoma who developed a second CR when treated with an alternative antibiotic regimen following relapse 21 months after initial CR. A 59-year old man was referred to our department for treatment of gastric MALT-lymphoma diagnosed at another hospital. Unspecific epigastric complaints refractory to treatment with H2-blockers for 3 weeks had led to gastroscopy, disclosing multiple slight ulcerations. Histologic evaluation of the biopsies was
Memo – Magazine of European Medical Oncology, Oct 1, 2009
Mucosa-associated lymphoid tissue (MALT) lymphoma is amongst the most common lymphoma entities an... more Mucosa-associated lymphoid tissue (MALT) lymphoma is amongst the most common lymphoma entities and comprises about 7% of all newly diagnosed NHL. Roughly 50% of all MALT lymphomas are located in the stomach, where a pathophysiological link with Helicobacter pylori (HP) with consecutive response to HP eradication therapy has been established. In view of this, HP eradication has become the standard approach to patients with localised disease and signs of HP infection. Recent data, however, have suggested that also HP-negative patients might benefit from antibiotic treatment. On the other hand, an unexpectedly high rate of autoimmune diseases, e.g. Hashimoto’s thyroiditis or Sjogren’s syndrome has been found in gastric MALT lymphoma, and such patients do not respond to HP eradication in the large majority. In case of non-response to antibiotics the standard approach in such patients is currently not clear. Both radiation as well as chemotherapy has shown promising results, and currently there is only one randomised study, which nevertheless suggests superiority of chemotherapy in terms of event-free survival at 10 years. The optimal chemotherapeutic regimen, however, has not been established yet, although various agents and combinations have demonstrated high activity, albeit in small trials. In view of this, patients with gastric MALT lymphoma unresponsive to antibiotics should be included in clinical trials.
Background: The prognostic values of the International Prognostic Index (IPI) and the Follicular ... more Background: The prognostic values of the International Prognostic Index (IPI) and the Follicular Lymphoma International Prognostic Index (FLIPI) have widely been demonstrated in diffuse large B-cell lymphoma and follicular lymphoma. No attempts to assess their applicability in MALT lymphoma have been made so far. Patients and methods: A total of 143 patients with MALT-lymphoma were analysed. Parameters of both IPI and FLIPI were retrospectively assessed and correlated with relapse and time to relapse as markers of clinical course. Results: According to IPI, 96 patients (67%) were classified as low, 22 (15%) low-intermediate, 17 (12%) high-intermediate and 8 (6%) as high risk. FLIPI identified 99 patients (70%) at low risk, 35 (24%) at intermediate and 9 (6%) at high risk. After a median follow-up time of 39.5 months, 123 patients were alive and 46 patients had relapsed (median time to relapse 27 months). IPI significantly correlated with time to relapse, with the typical differentiation into low, low-intermediate and high risk groups. FLIPI divided patients into three groups, but the low and intermediate risk groups showed a similar clinical course. In terms of additional progonostic factors, univariate analysis suggested autoimmune disease and multifocal disease as correlated with relapse. Multiple regression analysis, however, identified only extragastric disease as predictive of relapse (p=0.001). Conclusion: Our data demonstrate that both IPI and FLIPI are able to discriminate prognostic subgroups in patients with MALT-lymphoma. However, the low and intermediate group of the FLIPI did not appear to prognostically differ.
Primary central nervous system lymphoma (PCNSL) is a rare and malignant tumour type. Established ... more Primary central nervous system lymphoma (PCNSL) is a rare and malignant tumour type. Established treatment approaches include high-dose methotrexate (HD-MTX) -based chemotherapy and whole-brain radiotherapy (WBRT). WBRT is associated with significant neurotoxicity and autologous haematopoietic stem cell transplantation (ASCT) has been proposed as an alternative treatment - either in the 1(st) line setting after HD-MTX based chemotherapy or as salvage treatment for relapsed/refractory PCNSL. We here report our single centre experience with five PCNSL patients, who had achieved an objective response after a high-dose methotrexate based induction therapy and consecutively received a high-dose chemotherapy, consisting of carmustine and thiotepa, followed by ASCT. We also provide a literature review on ASCL for PCNSL. Our data, with three out of five patients in continuous complete remission and four out of five patients alive after a median follow-up time of 8 months, as well as previously published results, show that ASCT is a safe treatment option that is able to induce tumour remissions in patients with PCNSL. However, controlled trials are needed to compare the long-term efficacy and tolerability of ASCT with other treatment approaches and also to establish the optimal sequence of treatment regimens in PCNSL patients. This article is protected by copyright. All rights reserved.
Enteropathy-associated T cell lymphoma (EATL) is a rare disease with a dismal prognosis. Due to t... more Enteropathy-associated T cell lymphoma (EATL) is a rare disease with a dismal prognosis. Due to the low efficacy of chemotherapy and the poor performance status of patients failing first line, no data on second line therapy exist. A retrospective analysis of 19 patients with EATL at our institution identified six patients (31%) undergoing second line chemotherapy after CHOP-like regimens. Three patients had progressive disease (PD) during first line therapy, while the other three patients showed relapse after an initial complete remission (CR). The time from the last cycle of first line chemotherapy to second line therapy was 1-62 months. Two patients received ifosfamide, carboplatin and etoposide (ICE), two were given fludarabine and cyclophosphamide (FC) and one each had dexamethasone, cisplatin and cytarabine (DHAP) and cladribine chemotherapy. One patient progressed after one course of cladribine, while two patients developed intestinal perforation and died after one course of ICE and DHAP, respectively. Three patients achieved a CR lasting 4, +7 and +64 months, with two being alive without evidence of disease. Our data again confirm the poor prognosis of patients with EATL. A small subset of patients, however, apparently benefits from initiation of second line chemotherapy.
Background: Mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) of the lung is a relativel... more Background: Mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) of the lung is a relatively rare disease. As little is known about the natural clinical course if left untreated, all patients undergoing a watch-and-wait policy at our institution were investigated. Patients and methods: A retrospective analysis identified a total of 11 patients with MALT lymphoma of the lung who did not undergo treatment following initial diagnosis. All patients had undergone extensive staging and were closely observed with restaging every three months. Histological assessment included immunhistochemistry for demonstration of the immunphenotype CD20+/CD5-/ CD10-/cyclinD1-/CD23-. Genetic aberrations were assessed, using RT-PCR for t(11;18) (q21;21) and fluorescence in situ hybridisation for the evaluation of t(14;18)(q32;q21), t(1;14) (p22;q32), trisomies 3 and 18. Results: Five patients had MALT lymphoma restricted to the lung, while the remaining six had additional extrapulmonary sites detected during staging. The median time of observation without therapy was 28.1 months (inter-quartile range: 5 to 60 months); within this time, all 11 patients showed at least stable disease. Six of these 11 patients, however, had spontaneous regressions and wax-and-wane phenomena of the pulmonary lesions, but not of extrapulmonary manifestations. Three of these patients had evidence of t(11;18)(q21;q21), while the remaining three had no evidence of genetic aberrations. One patient was referred for treatment after progression in the lung, while two patients experienced progression outside the lung. Currently, all patients are alive, with 8 patients still only being watched. Conclusion: Our findings suggest that MALT lymphoma of the lung is a very indolent disease with the potential for spontaneous regression. In view of this, patients diagnosed with pulmonary MALT lymphoma might not require immediate treatment in the absence of symptoms and a watch-and-wait policy could be adopted.
Mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively common lymphoma and comprises a... more Mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively common lymphoma and comprises approximately 7% of all newly diagnosed non-Hodgkin's lymphoma. It is mainly located in the stomach and has become a focus of interest due to its unique pathophysiological link with Helicobacter pylori (HP) and the consecutive response to HP eradication therapy. In view of this, HP eradication has become standard treatment for patients with localised disease, and recent data have suggested that HP-negative patients might benefit from antibiotic treatment. In case of non-response, however, the standard approach in such patients is unclear. Both radiation and chemotherapy have shown promising results, and at present there is only one randomised study, which nevertheless suggests chemotherapy as management of choice. The objective of this review is, therefore, to summarise and evaluate the data available for treatment of gastric MALT lymphoma and to highlight potential focus for further research.
In contrast to its gastric counterpart, mucosa-associated lymphoid tissue (MALT) lymphoma of the ... more In contrast to its gastric counterpart, mucosa-associated lymphoid tissue (MALT) lymphoma of the parotid gland has not been studied extensively. We analyzed the clinicopathological features and the clinical course of all patients with parotid gland MALT lymphoma diagnosed and treated at our institution. Patient characteristics including an underlying autoimmune disease, disease stage, genetic aberrations, treatment, and clinical course were assessed and evaluated. Twenty-eight patients (19 women, 9 men) were identified; median age at diagnosis was 49 years (interquartile range [IQR], 40-56), and 18 patients (64%) had an underlying autoimmune disease. Eleven had stage IE, 7 patients had stage IIE, and 10 had advanced disease (stage IV). Genetic aberrations were detected in 9 of 20 patients; 5 patients had trisomy 3, 2 patients had a t(11;18)(q21;21) translocation, 1 had trisomy 3 and 18, and 1 patient had a t(14;18)(q32;q21) translocation plus trisomy 18. After a median follow-up time of 62 months (IQR, 32-98 months), 24 patients (86%) are alive. Fifteen patients are free from lymphoma, whereas 13 patients (46%) have had a relapse. Our data suggest that MALT lymphoma of the parotid gland is often associated with autoimmune diseases and that trisomy 3 is the most common genetic feature of this disease. The high rate of relapse warrants further study on optimal therapy of such patients.
Radioimmunotherapy using (90)Y-ibritumomab tiuxetan has predominantly been used in patients with ... more Radioimmunotherapy using (90)Y-ibritumomab tiuxetan has predominantly been used in patients with follicular lymphoma, but little is known about its activity in patients with extranodal marginal zone lymphoma of the mucosa associated lymphoid tissue (MALT). A total of six patients progressing/relapsing following conventional therapy for MALT lymphoma were treated with (90)Y-ibritumomab tiuxetan at our institution. Two patients had gastric MALT lymphoma, one suffered from orbital MALT lymphoma, and two had cutaneous MALT lymphoma, while one patient had a widely disseminated lymphoma involving the stomach, lungs, lymph nodes, and salivary glands. All patients were at least in third relapse following various forms of therapy including Helicobacter pylori-eradication, radiation, chemotherapy, and application of rituximab. Following two doses of rituximab at 250 mg/m(2) at an interval of 1 week, (90)Y-ibritumomab tiuxetan was given immediately at a dose of 0.4 mCi/kg body weight. Treatment was well tolerated apart from one episode of pneumonia requiring hospitalization. Four patients developed a complete remission (ongoing now for 4, 16, 23, and 24 months), one patient had a partial response lasting for 5 months, and one patient had stable disease for 13 months. After a follow-up of 9-29 months, all patients are alive. Application of (90)Y-ibritumomab tiuxetan is active and safe in heavily pretreated patients with MALT lymphoma.
Background: Various chemotherapeutic agents as well as the anti-CD20 antibody rituximab (R) have ... more Background: Various chemotherapeutic agents as well as the anti-CD20 antibody rituximab (R) have been tested in patients with mucosa-associated lymphoid tissue (MALT) lymphoma, but no standard chemotherapeutic regimen has emerged so far. Judging from the data obtained in various types of lymphoma, the activity of R appears to be enhanced by combination with chemotherapy. As no data on this topic exist for MALT lymphoma, we have retrospectively analysed our experience with R plus cyclophosphamide, doxorubicin/mitoxantrone, vincristine and prednisone (R-CHOP/R-CNOP) in patients with relapsed MALT lymphoma. Patients and Methods: A total of 26 patients were identified, 15 were administered R-CHOP while 11 patients were given R-CNOP due to age >65 years or pre-existing cardiac conditions. Cycles were repeated every 21 days, and restaging was performed after 4 cycles of therapy. In case of complete remission, 2 further cycles were administered for consolidation while patients achieving partial remission or stable disease after restaging were given 4 further courses. Results: A total of 170 cycles were administered to our patients (median 6, range 2–8). Twenty of the 26 patients (77%) achieved a complete remission and 6 (23%) a partial remission. Toxicities were mainly haematological, with WHO grade III/IV leukocytopenia occurring in 5 patients. After a median follow-up of 19 months (range 10–45), all patients are alive: 22 are in ongoing remission, while 4 have relapsed between 12 and 19 months after treatment. Conclusions: Our data demonstrate a high activity of R-CHOP/R-CNOP in relapsing MALT lymphoma irrespective of prior therapy.
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