Simultaneous presentation of acute monoblastic leukemia and mantle cell lymphoma: case report and review of the literature

This paper reports a 73-year old woman with simultaneous presentation of acute monoblastic leukemia (acute myeloid leukemia (AML), French-American-British (FAB) type M5a) and mantle cell lymphoma. The patient presented with wasting, generalized lymphadenopathy, an extensive infiltrative rash and pancytopenia. Bone marrow and lymph node histopatholology showed extensive infiltration by leukemic monoblasts. Marrow cytogenetics revealed a complex karyotype, including t(8;16)(p11;p13). Flow cytometric immunophenotyping of peripheral blood, lymph node and bone marrow demonstrated two populations, expressing CD5, CD19, CD20 and CD22 and CD45, HLA-DR, CD13, CD33, CD14 and CD38, respectively. A focus of abnormal lymphocytes in the lymph node biopsy demonstrated BCL1 expression and t(11;14)(p11;p13) by fluorescence in situ hybridization and immunoglobulin heavy chain gene rearrangement by the polymerase chain reaction. The patient received infusional cytarabine, daunorubicin and etoposide chemotherapy, with complete remission of both the AML and the mantle cell leukemia. To the authors' knowledge, this is the first report of simultaneous presentations of AML, FAB M5a and mantle cell lymphoma. The case is discussed and the literature is reviewed.     

Glucocorticoid-induced redistribution lymphocytosis in mantle cell lymphoma with hyaline vascular Castleman disease-like features

We report a case of mantle cell lymphoma mimicking Castleman disease. A 76-year-old man presented with generalized lymphadenopathy, splenomegaly, anemia, polyclonal gammopathy, and pulmonary infiltrations. Lymph node biopsy revealed histological features of hyaline vascular Castleman disease. Treatment with prednisolone induced lymphocytosis with immunophenotypic and genetic features of mantle cell lymphoma. A detailed immunohistochemical study of the lymph node demonstrated a mantle cell lymphoma-mantle zone growth pattern. Glucocorticoid-induced distribution lymphocytosis has not been reported in mantle cell lymphoma. Careful observation of circulating lymphocytes during steroid treatment may enable diagnosis of the underlying occult lymphoma in a subset of patients exhibiting clinical manifestations of Castleman disease.     

套细胞淋巴瘤的多层螺旋CT影像学表现及其在分期中的应用价值

目的探讨多层螺旋CT(multidetector computed tomography,MDCT)中套细胞淋巴瘤(mantle cell lymphoma,MCL)的影像学表现,以及在分期中的应用价值。方法回顾性分析23例MCL患者初诊及随诊MDCT图像,以病理和临床诊断作为金标准。结果 MCL患者23例,多表现为全身多区域淋巴结受侵(91.3%,21/23).各区域内肿大淋巴结可呈融合状,亦可呈孤立状,CT增强扫描呈中等、均匀强化。与金标准比较,MDCT检出区域淋巴结受侵的敏感性为82.1%,特异性为75.2%,MDCT对受侵淋巴结区域检出的一致性适中(Kappa值为0.410)。MDCT检出结外受侵10例(52.6%,10/19),包括肺受侵2例、脾受侵6例、扁桃体受侵3例、肠道受侵2例、乳腺受侵1例,其敏感性为75.4%,特异性为91.6%。与临床分期对照.23例患者中MDCT分期Ⅰ期1例(4.3%),Ⅱ期2例(8.7%),Ⅲ期13例(56.5%),Ⅳ期7例(30.5%).其分期准确率为73.9%(17/23)除4例因骨髓受侵将Ⅳ期低估为Ⅲ期外,将Ⅰ期高估为Ⅱ期1例,将Ⅲ期低估为Ⅱ期1例。结论 MDCT对MCL全身淋巴结受侵区域的检出具有较高的敏感性,分期准确率较高;除骨髓外,MDCT对结外受侵器官的检出敏感性亦较好。     

A severe combined immunodeficient-hu in vivo mouse model of human primary mantle cell lymphoma.

PURPOSE: To establish a severe combined immunodeficient (SCID)-hu in vivo mouse model of human primary mantle cell lymphoma (MCL) for the study of the biology and novel therapy of human MCL. EXPERIMENTAL DESIGN: Primary MCL cells were isolated from spleen, lymph node, bone marrow aspirates, or peripheral blood of six different patients and injected respectively into human bone chips, which had been s.c. implanted in SCID-hu. Circulating human beta(2)-microglobulin in mouse serum was used to monitor the engraftment and growth of patient's MCL cells. H&E staining and immunohistochemical staining with anti-human CD20 and cyclin D1 antibodies were used to confirm the tumor growth and migration. RESULTS: Increasing levels of circulating human beta(2)-microglobulin in mouse serum indicated that the patient's MCL cells were engrafted successfully into human bone chip of SCID-hu mice. The engraftment and growth of patient's MCL cells were dependent on human bone marrow microenvironment. Immunohistochemical staining with anti-human CD20 and cyclin D1 antibodies confirmed that patient's MCL cells were able to not only survive and propagate in the bone marrow microenvironment of the human fetal bone chips, but also similar to the human disease, migrate to lymph nodes, spleen, bone marrow, and gastrointestinal tract of host mice. Treatment of MCL-bearing SCID-hu mice with atiprimod, a novel antitumor compound against the protection of bone marrow stromal cells, induced tumor regression. CONCLUSION: This is the first human primary MCL animal model that should be useful for the biological and therapeutic research on MCL.     

套细胞淋巴瘤的临床特征和治疗学进展

 套细胞淋巴瘤（MCL）包括在WHO分类中具t(11;14)(q13;q23)易位的淋巴瘤,是以CyclinD1过度表达为特征的独立淋巴瘤亚型。临床表现常包括结外累及,尤其是骨髓和肠道。在B细胞淋巴瘤患者中预后最差,中位总生存期3～5年,常规化疗不能治愈,但常可获得60 %～90 %的缓解率,其缓解期比其他淋巴瘤为短（1～2年）。很强烈的治疗（包括自体和异基因干细胞移植）为改善转归所必需,但对于诊断时中位年龄≥60岁的患者其可行性有限。预后因子前瞻性调查有助于对患者的诊断、治疗。     

Trisomy 12-associated, t(11;14)-negative mature B-cell leukemia with gene expression profile resembling mantle cell lymphoma

Trisomy 12 can be seen in many different lymphoid neoplasms. However, many or most mature B-cell leukemias associated with isolated trisomy 12 are reported in the literature as chronic lymphocytic leukemia (CLL) or 'atypical CLL'. This study reports a case of a mature B-cell leukemia, morphologically and immunophenotypically similar to cases previously published as atypical CLL, in which cytogenetic evaluation revealed an isolated clonal trisomy 12 but no evidence of the mantle cell lymphoma-associated t(11;14)(q13;q32). Further analysis confirmed absence of cyclin-D1 expression. Subsequent lymph node biopsy revealed evidence of large cell transformation of the underlying chronic lymphoproliferative disorder. Gene expression profiling of the initial peripheral blood sample using a cDNA micro-array of ∼10,000 expressed genes revealed a close resemblance between the reported case and 2 cases of known mantle cell lymphoma. When further compared to 7 known 'typical' CLL cases, the reported case was classified as mantle cell lymphoma by hierarchical cluster analysis. The case reported here raises interesting questions regarding the nature of cases reported previously as trisomy 12-associated CLL and reinforces the fact that other leukemic lymphoproliferative disorders should be included in the differential diagnosis of such cases. Further study is indicated to elucidate the nature and diversity of disorders previously reported as trisomy 12-associated chronic lymphocytic leukemia.     

套细胞淋巴瘤的临床特征和治疗学进展

套细胞淋巴瘤(MCL)包括在WHO分类中具t(11;14)(q13;q23)易位的淋巴瘤,是以CyclinD1过度表达为特征的独立淋巴瘤亚型.临床表现常包括结外累及,尤其是骨髓和肠道.在B细胞淋巴瘤患者中预后最差,中位总生存期3～5年,常规化疗不能治愈,但常可获得60%～90%的缓解率,其缓解期比其他淋巴瘤为短(1～2年).很强烈的治疗(包括自体和异基因干细胞移植)为改善转归所必需,但对于诊断时中位年龄≥60岁的患者其可行性有限.预后因子前瞻性调查有助于对患者的诊断、治疗.     

套细胞淋巴瘤的临床特征和治疗学进展

套细胞淋巴瘤(MCL)包括在WHO分类中具t(11;14)(q13;q23)易位的淋巴瘤,是以CyclinD1过度表达为特征的独立淋巴瘤亚型.临床表现常包括结外累及,尤其是骨髓和肠道.在B细胞淋巴瘤患者中预后最差,中位总生存期3～5年,常规化疗不能治愈,但常可获得60%～90%的缓解率,其缓解期比其他淋巴瘤为短(1～2年).很强烈的治疗(包括自体和异基因干细胞移植)为改善转归所必需,但对于诊断时中位年龄≥60岁的患者其可行性有限.预后因子前瞻性调查有助于对患者的诊断、治疗.     

A patient with mantle cell lymphoma who successfully underwent auto-PBSCT in combination with in vivo purging of tumor cells using rituximab

The chimeric anti-CD20 monoclonal antibody rituximab was recently approved for the treatment of malignant B cell lymphoma. We report the case of a 49 year-old female with advanced mantle cell lymphoma (MCL), who successfully underwent auto-peripheral blood stem cell transplant (auto-PBSCT) in combination with in vivo purging of tumor cells using rituximab. Systemic swelling was detected in her lymph nodes, and she was histologically diagnosed with MCL. From bone marrow involvement and 28% of lymphoma cells in her peripheral blood, she was identified as stage IV of MCL. She achieved a partial response (PR) after three cycles of standard chemotherapy (ProMACE-CytaBOM) followed by 1 course of rituximab at 375 mg/m2 per week for four weeks. Prior to treatment with rituximab, IgH/bcl-1 translocation in her peripheral blood was found to be positive in 0.5% of 199 cells. After administration of rituximab, this fell to 0% in her peripheral blood and bone marrow. Stem cells were mobilized with cyclophosphamide at 2,000 mg/m2 for 2 days, followed by granulocyte colony-stimulating factor (G-CSF). On one day prior to harvest, rituximab was infused at 375 mg/m2 for in vivo purging of tumor cells. The IgH/bcl-1 translocation in the peripheral blood stem cell harvest (PBSCH) product was found to be 0%. Subsequently, a pretreatment regimen of CBDCA at 350 mg/m2 x 4, ETP at 500 mg/m2 x 3, MCNU at 200 mg/m2 x 1, and CPA at 2,000 mg/m2 x 2 was adopted to condition the transplant, followed by auto-PBSCT. After the transplant, the patient achieved an uncertain complete response (CRu). The present case suggests in vivo purging with rituximab is effective, and that this method may have a role as a first-line therapy in MCL patients who respond poorly to standard treatment.     

High incidence of MYC and BCL2 abnormalities in mantle cell lymphoma,although only MYC abnormality predicts poor survival

The incidence and prognostic role of MYC and BCL2 rearrangements in mature B-cell lymphomas have been extensively studied, except the infrequent mantle cell lymphoma (MCL). Here, we analyzed the MYC and BCL2 abnormalities and other cytogenetic aberrations by fluorescence in situ hybridization (FISH) in 50 MCL patients with bone marrow involvement. Eighteen patients (36.0%) had MYC gains and/or amplifications, and twelve patients (24.0%) had BCL2 gains and/or amplifications. Among the 18 patients with MYC abnormality, four had simultaneous MYC translocations, but no BCL2 translocation was detected among patients with BCL2 abnormality. Only two patients (4.0%) had both MYC and BCL2 abnormalities. The patients with a MYC abnormality had a significantly higher tumor burden, a higher percentage of medium/high risk MIPI group and genomic instability compared to those without this abnormality. However, no significant difference was observed between patients with or without a BCL2 abnormality in terms of clinical and cytogenetic factors. Patients with a MYC abnormality had poorer progress-free survival (PFS) (9.0 vs. 48.0 months, p = .000) and overall survival (OS) (12.0 vs. 94.5 months, p = .000), but the presence of a BCL2 abnormality did not significantly influence either PFS or OS. In multivariate analysis, the MYC abnormality was the independent adverse factor for both PFS and OS, and intensive chemotherapy did not improve the outcome of these patients. Thus, the presence of a MYC but not BCL2 abnormality predicted the poor survival of MCL patients, and a new treatment strategy should be developed for these patients.     

Subclonal evolution of a classical Hodgkin lymphoma from a germinal center B‐cell‐derived mantle cell lymphoma

Composite lymphomas (CL) represent the occurrence of two distinct lymphomas in the same patient. Often, CL share a common cellular origin, thus representing a unique model to investigate the multistep genetic path leading to lymphomagenesis in general and to the specific development of each distinct lymphoma component in particular. Here, we present the molecular analysis of a case consisting of an unusual Hodgkin lymphoma (HL) and a mantle cell lymphoma (MCL), intimately admixed within one another in lymph nodes and bone marrow yet phenotypically distinct, in a patient who first presented with splenic/leukemic MCL two years earlier. MCL and Hodgkin and Reed/Sternberg (HRS) cells harbored identical immunoglobulin (Ig) V_H gene rearrangements with shared somatic mutations, proving their common clonal origin from a (post‐)germinal center (GC) B cell. This also demonstrates the (post‐)GC origin of MCL with mutated IgV genes. Both lymphomas carried the same CCND1/IGH translocation and, unexpectedly for HL, expressed cyclin D1 and OCT2. Thus, HRS cells are able to preserve IGH locus activity (otherwise usually silenced in HL) to promote expression of an oncogene translocated into this locus. Both lymphoma populations further showed an identical TP53 function‐impairing mutation, and later acquired a TP53 heterozygous deletion independently from one another (convergent evolution). The surprisingly close genetic relationship of the lymphomas, together with their histological intermingling and the clinical history of the patient, suggests subclonal evolution of HL from MCL as a plausible pathway in alternative to that so far described in CL, i.e. separate development from a common precursor.     

Screening for adenoviruses in haematological neoplasia: High prevalence in mantle cell lymphoma

Human adenoviruses possess oncogenic capacity which is well documented in mammalian animal models, but their possible implication in human malignancy has remained enigmatic. Following primary infection, adenoviruses can persist in a latent state in lymphocytes where the virus is apparently able to evade immune surveillance. In the present study, we have employed a broad-spectrum adenovirus polymerase chain reaction (PCR) assay to systematically screen more than 200 diagnostic specimens of different lymphoid malignancies including acute lymphocytic leukaemia (n = 50), chronic lymphocytic leukaemia (n = 50), various types of malignant lymphoma (n = 100) and multiple myeloma (n = 11) for the presence of adenoviral sequences. While most entities analysed revealed negative findings in virtually all specimens tested, adenoviral DNA was detected in 15/36 (42%) mantle cell lymphomas investigated. The most prevalent adenoviral species detected was C, and less commonly B. Adenovirus-positive findings in patients with mantle cell lymphoma were made at different sites including bone marrow (n = 7), intestine (n = 5), lymph nodes (n = 2) and tonsillar tissue (n = 1). The presence of adenoviral sequences identified by PCR was confirmed in individual cells by fluorescence in-situ hybridisation (FISH). The frequent observation of adenoviruses in mantle cell lymphoma is intriguings, and raises questions about their possible involvement in the pathogenesis of this lymphoid malignancy.     

Minichromosome maintenance protein 6, a proliferation marker superior to Ki-67 and independent predictor of survival in patients with mantle cell lymphoma

Minichromosome maintenance protein 6 (MCM6) is one of six proteins of the MCM family which are involved in the initiation of DNA replication and thus represent a marker of proliferating cells. Since the level of cell proliferation is the most valuable predictor of survival in mantle cell lymphoma (MCL), we investigated lymph node biopsy specimens from 70 patients immunohistochemically with a monoclonal antibody against MCM6. The percentage of MCM6 expressing lymphoma cells ranged from 12.0 to 95.6%, with a mean of 61.0%, and was significantly higher than the percentage of Ki-67-positive cells (P<0.0001). Surprisingly, the ratio of MCM6-positive cells to Ki-67-positive cells was higher than in normal stimulated peripheral blood mononuclear cells, indicating a cell early G1-phase arrest in MCL. A high MCM6 expression level of more than 75% positive cells was associated with a significantly shorter overall survival time (16 months) compared to MCL with a low MCM6 expression level of less than 25% (no median reached, P<0.0001). Multivariate analysis revealed MCM6 to be an independent predictor of survival that is superior to the international prognostic factor and the Ki-67 index. Therefore, aside from gene expression profiling, immunohistochemical detection of MCM6 seems to be the most promising marker for predicting the outcome in MCL.     

32例套细胞淋巴瘤中BTK蛋白的表达及临床意义

  目的  检测套细胞淋巴瘤(mantle cell lymphoma,MCL)患者病理组织中Bruton酪氨酸激酶(Bruton tyrosin kinase,BTK)表达水平并分析其与患者临床特征及预后的相关性。  方法  选取天津医科大学肿瘤医院2011年1月至2015年12月期间经病理检测诊断为MCL且随访资料完整的32例患者和10例良性淋巴结增生患者的病理组织。采用免疫组织化学法对32例MCL组织和10例良性淋巴结组织染色,并采用SPSS 17.0统计学软件对所收集的患者临床数据资料进行分析。  结果  BTK蛋白在MCL组织和正常的淋巴组织中均呈阳性表达,但在MCL病理组织中多为强阳性表达;BTK阳性表达与Ki-67和MIPI评分相关;应用Kaplan-Meier法对预后进行分析,显示BTK强阳性表达患者的无进展生存期(progression free survival,PFS)显著低于BTK弱表达患者(P=0.030),但总生存期(overall survival,OS)无统计学意义(P=0.073);PFS的单因素分析结果显示,年龄≥65岁,ECOG评分≥2分,骨髓受累,BTK强阳性表达,Ki-67＞30%,根据套细胞淋巴瘤国际预后指数(mantle cell lymphoma international prognostic index,MIPI)评分≥6分,皆是MCL患者的不良预后因素,但在Cox多因素分析结果中仅MIPI评分≥6分可作为MCL患者的独立不良预后因素。  结论  BTK在MCL患者中多为强阳性表达,且与Ki-67和MIPI评分呈正相关;BTK强阳性表达患者的PFS显著低于BTK弱表达患者,但由于随访时间短暂和样本量限制,BTK的强阳性表达尚不能作为PFS的一项独立不良预后因素。      

Biological rational for sequential targeting of Bruton tyrosine kinase and Bcl-2 to overcome CD40-induced ABT-199 resistance in mantle cell lymphoma

The aggressive biological behavior of mantle cell lymphoma (MCL) and its short response to current treatment highlight a great need for better rational therapy. Herein, we investigate the ability of ABT-199, the Bcl-2-selective BH3 mimetic, to kill MCL cells. Among MCL cell lines tested (n = 8), only three were sensitive (LD₅₀ < 200 nM). In contrast, all primary MCL samples tested (n = 11) were highly sensitive to ABT-199 (LD₅₀ < 10 nM). Mcl-1 and Bcl-x_L both confer resistance to ABT-199-specific killing and BCL2/(BCLXL + MCL1) mRNA ratio is a strong predictor of sensitivity. By mimicking the microenvironment through CD40 stimulation, we show that ABT-199 sensitivity is impaired through activation of NF-kB pathway and Bcl-x_L up-regulation. We further demonstrate that resistance is rapidly lost when MCL cells detach from CD40L-expressing fibroblasts. It has been reported that ibrutinib induces lymphocytosis in vivo holding off malignant cells from their protective microenvironment. We show here for two patients undergoing ibrutinib therapy that mobilized MCL cells are highly sensitive to ABT-199. These results provide evidence that in situ ABT-199 resistance can be overcome when MCL cells escape from the lymph nodes. Altogether, our data support the clinical application of ABT-199 therapy both as a single agent and in sequential combination with BTK inhibitors.     

Detection of hematogenic and lymphogenic tumor cell dissemination in patients with medullary thyroid carcinoma by cytokeratin 20 and preprogastrin-releasing peptide RT-PCR

Despite an extensive surgical approach only 50% of the patients with medullary thyroid carcinoma (MTC) are biochemically cured. The failure to cure a larger number of patients is a result of the early dissemination of MTC. The present study evaluates two RT-PCR based assays for the detection of disseminated tumor cells in blood, bone marrow and lymph node samples of patients with MTC. Frozen tissue and blood samples of 19 patients with MTC and 61 cervical lymph nodes of these patients were obtained intraoperatively during thyroidectomy and lymphadenectomy. Preoperative bone marrow samples were obtained from 8 patients with MTC. An expression of CK20 and preproGRP was found in all MTC tissue samples. Using CK20-PCR, disseminated MTC cells were detected in 67% of the cervical lymph nodes of patients with MTC, compared to 72% involved lymph nodes, detected by preproGRP-PCR. In 16 of 61 nodes (26%) each PCR-system detected disseminated tumor cells in histologically tumor-free lymph nodes. Disseminated tumor cells were detected with CK20-PCR and preproGRP in 5 of 18 (28%) preoperative blood samples, each. The detection of a hematogenic tumor cell dissemination by preproGRP correlated significantly with the tumor stages (p = 0.019). Circulating MTC cells were found in 3 of 8 bone marrow samples with CK20-PCR, compared to 1 of 8 samples with preproGRP-PCR. Both PCR assays are highly sensitive to detect disseminated MTC cells in blood, bone marrow and lymph node samples. Our results of disseminated MTC cells in 26% of histologically tumor-free cervical lymph nodes and in 28% of the blood samples of patients with MTC might therefore explain the low biochemical cure rates.     

Inhibition of Lyn is a promising treatment for mantle cell lymphoma with bortezomib resistance

Although proteasome inhibition with bortezomib (BTZ) is a validated treatment for relapsed or refractory mantle cell lymphoma (MCL), many patients show resistance to BTZ. However, the molecular mechanism of BTZ resistance in MCL has not been elucidated. In the present study, we investigated BTZ-resistant MCL cells in vitro and in vivo. We demonstrate that BTZ-resistant MCL cells showed highly increased expression of the B-cell receptor (BCR) components CD79A and CD19. Activation of the BCR signaling pathway enhanced the activity of Src family kinases (SFKs), especially Lyn, and downstream kinases PI3K/AKT/mTOR in BTZ-resistant MCL cells. Depletion of CD79A and Lyn significantly reduced several kinase activities involved in PI3K signaling, leading to inhibition of proliferation. In addition, the SFKs inhibitor dasatinib inhibited the proliferation of BTZ-resistant cells, preventing the binding of CD19 with Lyn and PI3K p85. We also verified our findings with the mouse xenograft tumor model. Dasatinib treatment significantly decreased tumor size in the mouse bearing BTZ-resistant MCL cells, but not in the mouse bearing BTZ-sensitive MCL cells. Collectively, our data show that overexpression of the BCR and its activated signaling confers BTZ resistance in MCL cells. Thus, targeting BCR signaling with dasatinib could be a novel therapeutic approach for patients with MCL that has relapsed or is refractory to treatment with BTZ.     

miR-150在套细胞淋巴瘤中的表达及意义

  目的   探讨套细胞淋巴瘤（mantle cell lymphoma,MCL）中miR-150的表达情况及其临床意义。   方法   通过定量RT-PCR检测29例初治MCL患者及7例正常人外周血B细胞中miR-150和c-Myc的表达水平,探索miR-150和c-Myc表达之间的关系;利用RNAi阻断MCL细胞系Mino和HBL-2中c-Myc表达后,检测miR-150的变化,确定c-Myc是否参与miR-150的表达调控;抑制P493-6细胞表达c-Myc后,观察miR-150的变化,进一步明确miR-150是否受c-Myc调节;将pre-miR-150电转HBL-2细胞系,通过集落形成试验明确miR-150对细胞增殖的影响,Western blot检测c-Myb蛋白的变化。   结果   与正常人外周血B细胞相比,MCL患者低表达miR-150、过表达c-Myc,两者的表达呈负相关;阻断c-Myc后,Mino和HBL-2细胞的miR-150表达增加;抑制c-Myc表达后,P493-6细胞的miR-150表达增高;过表达miR-150后,HBL-2的c-Myb蛋白表达水平和集落形成能力下降。   结论   MCL患者低表达miR-150的原因可能与其c-Myc过表达有关。miR-150能够抑制MCL的增殖,在MCL的治疗中具有潜在价值。      

套细胞淋巴瘤治疗进展

套细胞淋巴瘤(MCL)是一种侵袭性的非霍奇金淋巴瘤(NHL),占成年人NHL的6%~8%,常表现为淋巴结、胃肠道、骨髓等受累,虽最初治疗有效,但易复发或耐药.第58届美国血液学会年会关于MCL的研究涵盖了基础研究、临床治疗、新药研究等多个方面,一些新动物模型的建立、信号通路靶点的研究为完善MCL发病机制及新药研究提供了基础;VcR-CVAD、VCR方案及对于年轻、 老年患者治疗新方案的尝试都取得了不错的效果;周期蛋白依赖性激酶(CDK)抑制剂、 磷脂酰肌醇3激酶(PI3K)抑制剂、bcl-2抑制剂等新型药物在初期临床试验中也显示出令人欣喜的结果,IACS-010759等小分子的出现为MCL治疗提供了新方向.     

High-dose chemotherapy with peripheral blood stem cell rescue in blastoid natural killer cell lymphoma

A 25-year-old man was referred because of skin rash, lymphadenopathy and anemia. Laboratory examinations revealed severe anemia (Hb, 4.8 g/dl) and elevated levels of GOT, GPT, LDH and soluble interleukin-2 receptor. Work-up studies disclosed the involvement of lymphoma cells in lymph nodes, skin, bilateral kidneys and bone marrow. Lymph node biopsy revealed diffuse proliferation of medium- to large-sized lymphoblastic cells. Bone marrow aspiration showed massive infiltration of large blastic cells with no cytoplasmic granules. The lymphoma cells in bone marrow and lymph node showed surface CD3-, cytoplasmic CD3epsilon+, CD4+, CD8-, CD56+, CD57-, CD16- and CD43 (MT-1)+ phenotype. Analyses of T cell receptor beta and gamma genes showed germ line configurations. EBER-1 was not detectable in the lymphoma cells. He was diagnosed as having blastoid natural killer (NK) cell lymphoma. In spite of several courses of combination chemotherapy, the lymphoma was progressive. He was then treated with high-dose chemotherapy and peripheral blood stem cell rescue, achieving remission which has now lasted for more than 12 months. We consider that blastoid NK cell lymphoma is an extremely aggressive subtype of CD56-positive lymphomas, and high-dose chemotherapy with peripheral blood stem cell rescue should be included for the choice of the treatment.