scholarly journals Mantle Cell Lymphoma, Rare Lymphoma Entity: A Result of Lymphoma Registry in Thailand

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3326-3326
Author(s):  
Nonglak Kanitsap ◽  
Naree Wannissorn ◽  
Arnuparp Lekhakula ◽  
Jakrawadee Julamanee ◽  
Archrob Khuhapinant ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
High Intensity ◽  
Clinical Characteristics ◽  
Cell Lymphoma ◽  
Stage Iii ◽  
Newly Diagnosed ◽  
Treatment Groups ◽  
Western Countries ◽  
Kaplan Meier ◽  
Mantle Cell

Abstract Introduction: Mantle cell lymphoma (MCL) is a relatively rare and aggressive mature B-cell non-Hodgkin lymphoma (NHL) entity, encounting for 3-10% of newly diagnosed patients. The purpose of the study is to analyse the incidence, clinical features and outcomes of Thai patients with MCL and compare data with those of Western countries. Patients and methods: From the nationwide multicenter registry of 4,056 newly diagnosed NHL patients in Thailand between 2007-2014, patients with MCL were identified according to the criteria of diagnosis by WHO classification of lymphoid disorders, 2008. The incidence, baseline clinical characteristics and outcomes were then analysed. Results: Ninety-nine patients (2.4%) were found to have MCL. The median age was 59.8 years (range 33-86). Seventy-nine percent of patients were men. The primary sites of disease were lymph nodes (60%), bone marrow (19%), GI tract (9%), Waldeyer's ring (4%), sinonasal area (2%) and miscellaneous (6%). (Figure 1). Eighty-three percent of the patients had stage III/IV. Eighty-one patients (82%) received chemotherapy (60.5% with CHOP or CHOP-like chemotherapy, 30.9% with HyperCVAD, and 26% with rituximab-based). Other received palliative chemotherapy or did not receive any. At a median follow-up time of 42 months, the median survival was 30 months (range, 1-94 months). By using Cox analysis, only Ann Arbor stage had impact on overall survival. Conclusion: MCL is less frequent in Thailand compare to the Western countries. The long-term survival is also much inferior reflecting the limited access to rituximab as well as the high intensity therapy in treating MCL in Thailand. Table 1. Comparison of MCL patients according to treatment modalities Clinical characteristics (Total 81 cases) CHOP-like (n=49 ) High intensity CMT (n = 25 ) CVP or palliative CMT (n = 7 ) p-value No R 33 19 4 - Age > 60 19 (67%) 6 (24%) 5 (71%) - Stage III-IV 42 (85.7%) 21 (84%) 7 (100%) - Response Overall response Complete response 26 (53.1%) 19 (38.8%) 17 (68%) 11 (44%) 6 (85.7%) 3 (42.8%) - Survival Mean OS (months) (Min-Max) 3yr-OS 5yr-OS 26.8 (0.1-83) 52.2% 52.2% 38.8 (0.8-93.9) 51% 38.1% 34.3 (10.7-70.5) 51% 30.2% 0.44 0.44 Figure 1. Biopsy sites Figure 1. Biopsy sites Figure 2. The Kaplan-Meier plots of OS according to treatment groups Figure 2. The Kaplan-Meier plots of OS according to treatment groups Figure 3. The Kaplan-Meier plots of OS according to tretment with rituximab Figure 3. The Kaplan-Meier plots of OS according to tretment with rituximab Disclosures Khuhapinant: Roche: Honoraria.

scholarly journals Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

2014 ◽  
Vol 25 ◽  
pp. iii83-iii92 ◽  
Author(s):  
M. Dreyling ◽  
C. Geisler ◽  
O. Hermine ◽  
H.C. Kluin-Nelemans ◽  
S. Le Gouill ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Mantle Cell Lymphoma ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Cell Lymphoma ◽  
Newly Diagnosed ◽  
Mantle Cell

scholarly journals PF306 A PHASE 2 STUDY OF OFATUMUMAB IN COMBINATION WITH HYPER-CVAD/MA IN PATIENTS WITH NEWLY DIAGNOSED MANTLE CELL LYMPHOMA

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 105-106
Author(s):  
P. Torka ◽  
N. Reddy ◽  
A. Kader ◽  
A. Groman ◽  
A. Hutson ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Phase 2 Study ◽  
Mantle Cell

MCL-049: Clinical Characteristics and Outcomes of Primary Versus Secondary Gastrointestinal (GI) Mantle Cell Lymphoma (MCL)

2020 ◽  
Vol 20 ◽  
pp. S257-S258
Author(s):  
Yucai Wang ◽  
Aung Tun ◽  
Alessia Castellino ◽  
David Inwards ◽  
Thomas Witzig ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Clinical Characteristics ◽  
Cell Lymphoma ◽  
Mantle Cell

scholarly journals Concurrent TP53 and CDKN2A Gene Aberrations in Newly Diagnosed Mantle Cell Lymphoma Correlate with Chemoresistance and Call for Innovative Upfront Therapy

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2120 ◽  
Author(s):  
Diana Malarikova ◽  
Adela Berkova ◽  
Ales Obr ◽  
Petra Blahovcova ◽  
Michael Svaton ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Kinase Inhibitor ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Mantle Cell ◽  
Reliable Marker

Mantle cell lymphoma (MCL) is a subtype of B-cell lymphoma with a large number of recurrent cytogenetic/molecular aberrations. Approximately 5–10% of patients do not respond to frontline immunochemotherapy. Despite many useful prognostic indexes, a reliable marker of chemoresistance is not available. We evaluated the prognostic impact of seven recurrent gene aberrations including tumor suppressor protein P53 (TP53) and cyclin dependent kinase inhibitor 2A (CDKN2A) in the cohort of 126 newly diagnosed consecutive MCL patients with bone marrow involvement ≥5% using fluorescent in-situ hybridization (FISH) and next-generation sequencing (NGS). In contrast to TP53, no pathologic mutations of CDKN2A were detected by NGS. CDKN2A deletions were found exclusively in the context of other gene aberrations suggesting it represents a later event (after translocation t(11;14) and aberrations of TP53, or ataxia telangiectasia mutated (ATM)). Concurrent deletion of CDKN2A and aberration of TP53 (deletion and/or mutation) represented the most significant predictor of short EFS (median 3 months) and OS (median 10 months). Concurrent aberration of TP53 and CDKN2A is a new, simple, and relevant index of chemoresistance in MCL. Patients with concurrent aberration of TP53 and CDKN2A should be offered innovative anti-lymphoma therapy and upfront consolidation with allogeneic stem cell transplantation.

Rituximab Plus Hypercvad Alternating with High Dose Methotrexate and Cytarabine for Patients with Newly Diagnosed Mantle Cell Lymphoma. A Multicenter Trial from GISL

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3050-3050 ◽  
Author(s):  
Francesco Merli ◽  
Stefano Luminari ◽  
Fiorella Ilariucci ◽  
Caterina Stelitano ◽  
Mario Petrini ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Hematological Toxicity ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Dose Methotrexate ◽  
Mantle Cell

Abstract BACKGROUND. Rituximab plus HyperCVAD alternating with High Dose Methotrexate and Cytarabine (R-HCVAD) has been tested in patients with newly diagnosed Mantle Cell Lymphoma (MCL) with promising results (Romaguera et al. JCO 2005). In 2005 the Gruppo Italiano Studio Linfomi (GISL) started a phase II multicenter study investigating clinical activity and toxicity of R-HCVAD in a similar group of patients. PATIENTS AND METHODS. To be included in the trial patients must have histologically confirmed diagnosis of MCL, be younger than 70 years, have adequate organ function. Chemotherapy consisted of rituximab plus fractionated cyclophosphamide, vincristine, doxorubicine, and dexamethasone(considered one cycle) alternating every 21 days with rituximab plus high dose methotrexate-cytarabine (considered one cycle) for a total of eight cycles per the MD Anderson protocol. Patients with baseline PCR positivity for t(11;14) on bone marrow (BM) had to perform PCR assessment of BM at evaluation of response and during follow-up. Only patients achieving partial response (PR) were to be addressed to HDC followed by ASCT. RESULTS. Thirty-two patients were enrolled. There were 23 males and 9 females; median age was 54 yrs (29 to 66), 80% were in stage IV, 50% and 71% had Gastrointestinal (GI) and BM involvement, respectively; PCR for t(11;14) was positive on BM in 51% of cases. Seven patients did not complete treatment due to toxicity; of these, two patients died (one with septic shock at cycle 1, one with pulmonary aspergillosis at cycle 4), one patient had thrombosis of central line extended to right atrium at cycle 1, one had grade IV skin reaction at cycle 3, one had a severe pneumonia at cycle 1, two had persistent grade IV hematological toxicity after cycle 1 and 5, respectively. All patients had grade III–IV hematological toxicity. Response was assessed in 17 patients with 16 CR and 1 PR. PCR for t(11;14) negativity on BM was achieved in 4/9 patients after cycle 4 and in 8/9 after cycle 8. After a median follow-up of 24 months 1 patient progressed at 6 months and 1 patient relapsed after 26 months of follow-up. Two-year Failure Free Survival (FFS) was 75% (IC95% 53 to 87) and 2 year Disease Free Survival was 93%(IC95% 59–99). CONCLUSIONS. Though longer follow-up is needed R-HCVAD regimen used in our multicenter setting confirmed high efficacy in terms of response (both clinical and molecular) and FFS. However the regimen was associated to a severe toxicity profile that caused treatment discontinuation in several patients and that may limit its use in the clinical setting.

High Remission Rates and Prolonged Progression Free Survival in Newly Diagnosed Patients with Mantle Cell Lymphoma Treated with R-MACLOIVAM-T

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3597-3597 ◽  
Author(s):  
Peter J Hosein ◽  
Daniel Morgensztern ◽  
Francine Coleman ◽  
Gail Walker ◽  
Maricer Escalon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mantle Cell Lymphoma ◽  
Relapse Rate ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Mantle Cell ◽  
Grade 3

Abstract Background: Mantle cell lymphoma (MCL) is an unfavorable subtype of B-cell non-Hodgkin lymphoma characterized by median progression-free survival (PFS) and median overall survival (OS) of only 1.5 and 3–4 years respectively. Although high-dose therapy and an autotransplant may prolong OS, it does not result in a long-term disease free survival. Therefore, there is a need for novel therapeutic approaches for this entity. Methods: We conducted a single-arm phase II study in subjects with newly-diagnosed MCL to assess efficacy and safety of a novel intensive regimen R-MACLO-IVAM-T, a modification of a protocol designed by Magrath et al (JCO1996;14:925). The study size of 22 patients was based on precision of a two-sided 95% confidence interval for the 18-month progression free survival rate. Eligible subjects had a confirmed diagnosis of MCL using WHO criteria, age 18–75 years, ECOG PS ≤ 2, adequate organ function and no history of HIV or prior cancer. Lymphoma extent at presentation was assessed by standard staging procedures as well as esophagogastroduodenoscopy and colonoscopy. Prior to initiating thalidomide maintenance, subjects were enrolled in the STEPS® program. Cycle 1 consisted of R-MACLO: rituximab 375 mg/m2 IV on day 1, doxorubicin 45 mg/m2 IV on day 1, cyclophosphamide 800 mg/m2 IV on day 1 and 200 mg/m2/day on days 2–5, vincristine 1.5 mg/m2 on days 1 and 8 capped to 2mg, methotrexate 1.2 g/m2 IV on day 10 over 1 hour followed by 5.52 g/m2 IV over 23 hours followed by leucovorin 36 hours later. G-CSF was begun on day 13. When the ANC was >1.5×109/L, cycle 2 with R-IVAM was begun: rituximab 375 mg/m2 IV day 1, cytarabine 2 g/m2 IV every 12 hours on days 1 and 2, etoposide, 60 mg/m2 on days 1–5 and ifosfamide 1.5 g/m2 on days 1–5 with mesna. Fourteen days after ANC recovery from cycle 2, cycles 3 and 4 were given in identical fashion to 1 and 2. Four weeks after ANC recovery from cycle 4, subjects were re-staged and responses were assessed by standard criteria. Subjects achieving CR at the end of therapy received thalidomide 200 mg/day until MCL relapse or intolerable toxicity. Results: Accrual started in 4/2004 and ended in 3/2008 when the planned 22 subjects were enrolled. All subjects were evaluable for toxicity and 21 were evaluable for response. Median age was 56.5 years (range 39–73). All subjects had at least stage 3 disease with bone marrow involvement in 19 and gastrointestinal involvement in 10. Distribution according to IPI: 0–1 factor, 3; 2 factors, 8; 3 factors, 8; and 4 factors, 3. Twenty subjects had diffuse variant and 2 had blastic variant. Nineteen subjects completed all 4 cycles of therapy; treatment was stopped in 2 subjects after 2 and 3 cycles respectively, and one subject died during the first cycle. Of the 21 subjects completing 2 cycles of therapy, 20 achieved CR and one PR. Two subjects relapsed at 9 and 33 months respectively, while 19 remain relapse free after median follow-up of 25 months (range 5–51). With a total follow-up of 545 months, the estimated relapse rate is 4.4 per 100 patients per year. There were two deaths: 1 from sepsis on cycle 1 day 8 and the other in CR at 38 months from non-small cell lung cancer diagnosed 19 months after MCL. Common severe toxicities were grade 3–4 neutropenia, thrombocytopenia and anemia in 33%, 19% and 17% of R-MACLO cycles and in 50%, 88% and 68% of R-IVAM cycles respectively. There were 14 bacteremias in 82 cycles, 12 of which were after R-IVAM therapy. Six episodes of reversible grade 1–2 renal toxicity occurred after methotrexate. The thalidomide maintenance dose was reduced in 6 subjects due to grade 3–4 neutropenia and reduced or stopped in 8 subjects because of grade 3–4 peripheral neuropathy. Patients remain under follow-up for relapse and survival. Conclusions: R-MACLO-IVAM-T results in a high overall response rate of 100% (95% CR and 5% PR) and a low relapse rate. At a median follow-up of 25 months, median PFS and OS were not reached. The 2-year actuarial PFS of 94% compares favorably with previously reported 2-year actuarial PFS of 40% and 67% for CHOP-like regimens without and with upfront bone marrow transplantation (Blood2005;105: 2677). The contribution of thalidomide maintenance to this outcome requires additional study. A multicenter clinical trial is suggested.

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