胃肠套细胞淋巴瘤1例

报道1例因腹部不适诊断胃肠套细胞淋巴瘤结肠镜下表现,有助于内镜医师了解和认识镜下套细胞淋巴瘤的表现。     

Temsirolimus for the treatment of mantle cell lymphoma

Although recent progress has been made in the treatment of mantle cell lymphoma (MCL) the majority of patients experience relapse and ultimately die of their disease. The translocation t(11;14) is a prerequisite for the diagnosis of MCL and results in overexpression of cyclin D1. Its protein translation is controlled by mTOR, a key element of the PI3K/Akt pathway, and mTOR constitutes an attractive therapeutic target. Temsirolimus, a specific inhibitor of mTOR, has been evaluated in two Phase II trials in patients with relapsed MCL, and promising response rates up to 40% were found. Subsequently, a randomized Phase III trial was initiated, in which superiority in remission induction and progression-free survival could be demonstrated for a regimen of temsirolimus 175 mg for 3 weeks, followed by a 75-mg weekly application in comparison with established agents. This adds temsirolimus to the therapeutic armamentarium for the treatment of MCL. Further developments target combination therapy in MCL and other lymphoid neoplasms.     

套细胞淋巴瘤21例临床分析

目的探讨套细胞淋巴瘤（MCL）的临床特点,并对合并骨髓侵犯患者临床资料进行分析。方法回顾性分析我院21例套细胞淋巴瘤的临床特点,比较有骨髓侵犯者的发病年龄、乳酸脱氢酶（LDH）、β2-微球蛋白、白细胞数及生存时间与无骨髓侵犯者有无差异。结果21例患者中男15例,女6例,中位年龄55岁,Ⅲ～Ⅳ期者17例,其中有骨髓侵犯者10例。有骨髓侵犯者的发病年龄、LDH、β2-微球蛋白、白细胞数等指标与无骨髓侵犯者比较均无统计学差异（P均〉0．05）。总体生存时间,两者分别为（23．4±4．2）月和（72．6±15．4）月,差异有统计学意义（P=0．035）。结论MCL有骨髓侵犯患者生存期短。     

Clinical features and treatment outcomes of lymphoplasmacytic lymphoma: a single center experience in Korea

Lymphoplasmacytic lymphoma (LPL) constitutes less than 5% of all non-Hodgkin lymphomas, and little is known about clinical features and treatment outcomes for patients with LPL in East Asia. In this study, we summarize our experiences managing patients diagnosed with LPL in Korea. A retrospective analysis was performed using data for 22 patients with LPL diagnosed at Samsung Medical Center. LPL was more common among males (77.3%), with a median age of diagnosis of 63 years (range 26-86). The most common presenting symptom was fatigue related to anemia (59.1%), and the bone marrow was commonly involved at diagnosis (90.9%). IgM paraproteinemia was found in 15 patients, and only one patient had anti-hepatitis C virus. Although some patients could be observed without treatment, the majority of patients required systemic treatment. Chlorambucil alone and cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) or CHOP-like combination chemotherapy was frequently used as a first-line treatment, and a fludarabine-based regimen was commonly used as salvage therapy. However, responses to those treatments were not satisfactory. Even patients who could be monitored without therapy became refractory to salvage therapies once their disease progressed. Eight patients died due to disease progression, and the median overall survival was 70.8 months (95% CI: 31.4-109.2 months). This study describes the clinical features and treatment outcome of LPL in Korea. The treatment approach was too heterogeneous to draw firm conclusions, however, and treatment recommendations in the future should utilize a uniform treatment strategy.     

Endoscopic features and prognoses of mantle cell lymphoma with gastrointestinal involvement

AIM: To evaluate the endoscopic manifestations and prognoses of gastrointestinal (GI) mantle cell lymphoma (MCL). METHODS: A database search at the Department of Pathology of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences revealed 57 MCL patients with GI involvement. Clinical records were available for 35 of the 57 patients from 21 institutions, and those 35 patients were enrolled in this study. We summarized the gross types of endoscopic features, event-free survival...     

套细胞淋巴瘤治疗的现状

套细胞淋巴瘤(mantle cell lymphoma,MCL)来源于相对成熟的B淋巴细胞,1997年国际淋巴瘤研究组(ILSG)的非霍奇金淋巴瘤(non-Hodgin's lymphoma,NHL)分型报道提出,MCL发病率占NHL的6%,北美年发病率约为1/10万。中位发病年龄为63岁,男性为主,约占74%。19%患者的临床分期为Ⅰ～Ⅱ期,63%有骨髓累及,57%患者的国际预后指数(IPI)为0/1,19%IPI为4/5[1]。     

Phase II trial of rituximab plus CVP combination chemotherapy for advanced stage marginal zone lymphoma as a first-line therapy: Consortium for Improving Survival of Lymphoma (CISL) study

We conducted a multicenter, phase II trial to investigate the efficacy and safety of rituximab plus CVP (R-CVP) combination therapy for patients with previously untreated stage III or IV marginal zone lymphoma (MZL). The treatment consisted of rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2) and vincristine 1.4 mg/m(2) (maximum 2.0 mg) being given intravenously on day 1 and oral prednisolone 100 mg on days 1-5. The treatment was repeated every 3 weeks and this was continued for six or eight cycles. Forty-two patients were enrolled from 13 institutes in Korea. Among them, two patients were dropped after the first and second cycles of chemotherapy, respectively, without evaluation. The 40 patients received a total of 287 cycles of R-CVP chemotherapy. The overall response rate was 88% (95% CI, 77-98%) with 24 complete responses (60%). The median duration of response was 28.3 months. After a median follow-up of 38.2 months, the estimated 3-year progression-free survival and overall survival were 59% and 95%, respectively. There were 30/287 cycles (11%) and 5/287 cycles (2%) of grade 3 or 4 neutropenia and febrile neutropenia, respectively. The R-CVP regimen can be an effective and tolerable first-line immunochemotherapy regimen for advanced stage MZL.     

Properties of the mantle cell and mantle cell lymphoma.

The major lymphoid inhabitant of the follicular mantle is the mantle cell, an immunologically na?ve B cell. It is the putative cell of origin of mantle cell lymphoma (MCL), the cells of which have similar morphologic, immunophenotypic, and molecular characteristics to the normal B lymphocytes of the mantle zone. In the past year a number of advances have been made in the biology of the normal mantle cell, its interactions with the other constituents of the follicular and mantle zone microenvironments, and the development of neoplasia in this cell population. In addition, new developments in diagnostic molecular pathology have been used to more readily identify cases of MCL. The authors summarize these new advances in the understanding of the biology of the mantle cell and newer ancillary techniques in the diagnosis of lymphomas arising from this cell type.     

Response to thalidomide in chemotherapy-resistant mantle cell lymphoma: a case report

Mantle cell lymphoma is an aggressive B-cell lymphoma with a poor median survival despite conventional therapy. Here, we present the case of a patient with multiply relapsed mantle cell lymphoma, having failed treatment with chemotherapy, steroids and rituximab. He was treated with single-agent thalidomide at a dose of 800 mg daily and entered a good partial remission which was maintained for the next 6 months. There is clearly a need for further studies of thalidomide in mantle cell lymphoma to confirm this promising initial result.     

Successful treatment of refractory mantle cell lymphoma with irinotecan

A 59-year-old man presented in January 2003 with generalized lymphadenopathy. An inguinal lymph node biopsy showed mantle cell lymphoma (MCL). After four courses of Rituximab-CHOP therapy were administered, complete response (CR) was achieved. However, in August 2003, he presented with neck lymphadenopathy and was found to have relapsed. Several salvage therapies (ESHAP, Hyper-CVAD/MTX-ara-C) were administered, but CR was not achieved. After two courses of single-agent chemotherapy with CPT-11 (40 mg/m2) were administered on days 1, 2, 3, 8, 9, and 10, CR was achieved. Several studies reveal that the long-term prognosis for MCL with conventional therapy is poor. This report describes CPT-11 therapy for MCL and provides evidence that CPT-11 is another therapeutic option in refractory cases of MCL.     

Autologous stem cell transplantation in mantle cell lymphoma: a report from the SFGM-TC

Autologous stem cell transplantation (ASCT) is considered as an attractive treatment option for young mantle cell lymphoma (MCL) patients. This retrospective SFGM-TC study analyzed the outcome of 500 MCL patients treated with ASCT and investigated parameters that may modify the outcome of patients who proceeded to ASCT upfront (n?=?396). For all patients, median age at ASCT was 56 years (range, 26–71). Median follow-up was 34 months. Three-year progression free survival (PFS) and overall survival (OS) were 63.5 % [95 % CI, 58.7–68.6 %] and 79.5 % [95 % CI, 75.3–83.4 %], respectively. Median time from ASCT to relapse was 22 months (range, 0–136 m). For patients transplanted upfront and in multivariate analysis, age (HR?=?2 [1.2–3.4], p?=?.01, and HR?=?2.3 [1.2–4.5], p?=?.01), disease status at time of ASCT (HR?=?1.7 [1.1–2.6], p?=?.01 and HR?=?1.8 [1.1–3.1], p?=?.03), and use of rituximab (HR?=?0.5 [0.3–0.8], p?=?.002 and HR?=?0.5 [0.3–0.9], p?=?.01) were statistically predictive for both PFS and OS. Also, first line treatment including anthracycline and high-dose cytarabine followed by ASCT conditioned with TAM improved PFS. To conclude, this study suggests that ASCT in MCL can provide a high response rate but may not be sufficient to cure MCL even when ASCT is performed upfront, highlighting the need for innovative approaches before ASCT, aiming to increase complete response rate, and after ASCT, to maintain response.     

Current treatment strategy and new agents in mantle cell lymphoma

Mantle cell lymphoma (MCL) is a well-recognized lymphoma subtype that accounts for about 5% of all patients with non-Hodgkin lymphoma. The clinical course of MCL ranges from an indolent disease to a rapidly progressive malignancy, with a poor prognosis and a median overall survival (OS) of about 3–5 years reported in earlier data sets. Knowledge of its biology has increased in the last few years. Unfortunately, this progress has not yet brought any major improvements in therapeutic approaches, which still remain highly unsatisfactory. Recent improvement has been achieved by the successful introduction of monoclonal antibodies and dose-intensified approaches including autologous stem cell transplantation strategies. However, with the exception of allogeneic hematopoietic stem cell transplantation, current treatment approaches are non-curative, and the corresponding survival curves are characterized by a delayed but continuous decline and a median survival of 4–6 years. In recent years, new insights into the biology of MCL have been obtained which have provided the rationale for the development of novel therapeutic strategies. Emerging new drugs such as bendamustine, proteasome inhibitors, antibodies, mTOR inhibitors, and immunomodulatory drugs and others are based on the dysregulated control of cell cycle machinery and impaired apoptotic pathways. The efficacy of these agents as monotherapy was demonstrated to be comparable to conventional chemotherapy in relapsed MCL, and combination strategies are currently being investigated in clinical trials.     

Ibrutinib resistance in mantle cell lymphoma: clinical,molecular and treatment aspects

Mantle cell lymphoma (MCL) is a lymphoproliferative disorder comprising about 6–10% of all B cell lymphoma cases. Ibrutinib is an inhibitor of Bruton tyrosine kinase (BTK), a key component of early B‐cell receptor (BCR) signalling pathways. Although treatment with ibrutinib has significantly improved the outcome of MCL patients, approximately one‐third of the patients have primary drug resistance while others appear to develop acquired resistance. Understanding the molecular events leading to the primary and acquired resistance to ibrutinib is essential for achieving better outcomes in patients with MCL. In this review, we describe the biology of the BCR signalling pathway and summarize the landmark clinical trials that have led to the approval of ibrutinib. We review the molecular mechanisms underlying primary and acquired ibrutinib resistance as well as recent studies dealing with overcoming ibrutinib resistance.     

Blastoid variant of mantle cell lymphoma: late progression from classical mantle cell lymphoma and quantitation of minimal residual disease

OBJECTIVES: Classical mantle cell lymphoma (MCL) and its blastoid variant (MCL-BV) are characterized by an extremely poor prognosis. Long-time survivors are rare, only very few patients with an overall survival over 10 years have been reported. We present a case of a 41-year-old male with a 12 yr history of MCL stage I to show, that very late relapses in MCL are possible and may present as a transformation into an aggressive blastoid variant and to illustrate the value of quantitative minimal residual disease (MRD) monitoring for treatment guidance. METHODS: Diagnostic lymph node and bone marrow samples were investigated by immunohistochemistry. Clonality analysis was performed by immunoglobulin heavy chain gene (IGVH) and t(11;14) PCR. The MRD assessment was done by real-time quantitative PCR (RQ-PCR) on available follow-up samples. RESULTS: By histologic review and sequencing of the clonal IGVH and t(11;14) PCR products we demonstrated a common clonal origin of the leucemic MCL-BV and the classical MCL diagnosed 12 yr earlier. Quantitative MRD assessment revealed significant MRD levels after intensive conventional chemotherapy including Rituximab. Therefore, treatment was early intensified by myeloablative radio-chemotherapy and allogeneic peripheral stem cell transplantation from an unrelated HLA-identical donor. This did not translate into a sustained remission as reflected by persisting MRD levels after transplantation and the patient died from rapid progressive disease 3.5 months after transplant. CONCLUSION: This report presents a rare case of long-term survivor of MCL with a progression of the original MCL cell clone to MCL-BV and demonstrates the clinical value of quantitative MRD assessment for optimized therapeutic management.     

Allogeneic haematopoietic cell transplantation impacts on outcomes of mantle cell lymphoma with TP53 alterations

TP53 alterations portend extremely poor prognosis in patients with mantle cell lymphoma treated with standard treatment modalities. We reviewed outcomes of 42 patients with available TP53 status who had received a reduced-intensity or non-myeloablative allogeneic haematopoietic cell transplant at our institution. We demonstrated a 2-year overall survival and progression-free survival of 78% [95% confidence interval (CI) 60–88] and 61% (95% CI 43–75), respectively. The 2-year cumulative incidences of relapse and non-relapse mortality were 19% and 20%, respectively. Importantly, there is no significant difference among patients with and without TP53 alterations, suggesting for the first time a beneficial treatment modality for these high-risk patients.     

以淋巴增殖性疾病为表现的套细胞淋巴瘤的临床与诊断分析

目的：研究以慢性B淋巴细胞增殖性疾病（B-LPD）为表现的套细胞淋巴瘤（MCL）的临床特点与诊断。方法：对过去7年间以LPD为主要表现并可诊断为MCL的15例患者的临床特点和诊断进行回顾性分析。结果：①15例MCI。中,依靠病理及CyclinD1诊断6例,依靠典型的免疫表型特征诊断9例;②部分以LPD表现的MCL患者临床表现、瘤细胞形态与慢性淋巴细胞白血病（CLL）难以区别,而免疫表型分析不符合CLL特点;③淋巴结或脾脏病理检查结合免疫组织化学是诊断MCL的主要依据,典型的免疫表型对MCL的诊断价值值得探讨。结论：部分MCL患者以广泛侵犯骨髓的LPD发病,对不典型LPD应进行病理检查明确诊断,而不能按CLL处理,以免贻误治疗。     

Rituximab-based pre-emptive treatment of molecular relapse in follicular and mantle cell lymphoma

Pre-emptive rituximab (pRTX) might represent an effective approach for patients with follicular (FL) and mantle cell lymphoma (MCL) experiencing molecular relapse (M-rel). However, available experience is still limited. We retrospectively collected FL and MCL cases that underwent pRTX with four weekly rituximab infusions (375 mg/m²) due to molecular persistence or M-rel. M-rel was assessed using nested polymerase chain reaction (PCR) and real-time quantitative PCR using the Bcl-1/IGH, Bcl-2/IGH or the immunoglobulin heavy chain rearrangement. Twenty-three occurrences of M-rel or persistence were treated in 18 patients (nine MCL and nine FL). The pRTX reinduced molecular remission (MR) in 17/23 cases (7/9 FL and 10/14 MCL). The median time to MR reinduction was 4.5 months (range 3–12), and the median duration of the first MR reinduction was 34 months (range 12–72). In five MCL cases, pRTX was used to treat subsequent M-rels, with success in four cases. No clinical relapses were seen within 2 years of successful reinduction of MR. Progression-free survival after pRTX was 64 % at a median follow-up of 6 years. pRTX was feasible and safe and effectively reinduced MR in FL and MCL patients (74 %). Prospective trials are needed to verify the clinical benefit of similar approaches.