美罗华联合自体造血干细胞移植治疗伴有自身免疫性溶血性贫血的CD5阳性弥漫大B细胞淋巴瘤

目的:分析总结CD5阳性弥漫大B细胞淋巴瘤合并自身免疫性溶血性贫血患者的临床特点和治疗经验。方法:对1例49岁女性患者进行了血常规检查、骨髓检测、Coombs试验、血清学检测、胸部CT、腹部MR和免疫组织化学测定,观察了含有美罗华的化疗方案联合自体造血干细胞移植治疗效果等。结果:患者颈部、腋窝多组淋巴结肿大,淋巴结活检表明为CD5+弥漫大B细胞淋巴瘤;患者重度贫血,网织红细胞升高,Coombs试验阳性,骨髓红系增生明显,提示并发自身免疫性溶血性贫血(AIHA)。经过血浆置换、甲基强的松龙免疫抑制、输血及"R-CHOP-E"方案治疗后,AIHA症状消失,继续"R-CHOP-E"方案治疗3个疗程后行中期评估出现骨髓浸润,评估为"进展",改为"R-ESHAP"方案4个疗程后评估为"完全缓解",行自体造血干细胞移植治疗,随访半年,仍处于"完全缓解"。结论:合并自身免疫性溶血性贫血的CD5+弥漫大B细胞淋巴瘤病情重,预后较差,联合含有美罗华的化疗方案加自体造血干细胞移植治疗效果良好。     

23例血管免疫母细胞性T细胞淋巴瘤回顾性分析

本研究旨在探讨血管免疫母细胞性T细胞淋巴瘤（angioimmunoblastic T cell lymphoma,AITL）的治疗和预后因素。收集23例AITL患者的临床资料,回顾性分析患者临床特征、实验室指标、患者的生存和预后因素。结果表明,23例AITL患者的中位年龄62岁,国际预后指数（IPI）评分为中高危/高危21例（91.3%）,14例患者（60.9%）存在结外侵犯,5例（21.7%）患者合并自身免疫性疾病。治疗总体反应率为68.2%,3年及5年生存率分别为38.3%和28.7%。化疗联合造血干细胞移植能够改善年轻患者预后,免疫抑制剂对于复发难治患者是可供选择的治疗方案。年龄大于65岁、IPI评分、血清乳酸脱氢酶（LDH）水平、淋巴结受累数目、近期疗效、纤维蛋白原水平、β2微球蛋白水平、骨髓是否受累为预后相关因子。多因素分析显示,LDH水平、β2微球蛋白水平及骨髓受累是影响患者生存的独立危险因素。IPI、T细胞淋巴瘤预后指数、修改的T细胞淋巴瘤预后指数的危险分层均可作为判断预后的指标。结论：AITL好发于老年患者,具有高度侵袭性,合并自身免疫功能异常,易感染,预后差,年轻、一般情况较好患者初始强化治疗有可能获益,大剂量化疗联合自体造血干细胞移植对年轻患者是可供选择的治疗方法,免疫抑制剂可作为复发难治患者治疗选择。     

首发症状Coombs试验阴性自身免疫性溶血性贫血的非何杰金淋巴瘤(英文)

非何杰金淋巴瘤(NHL)伴发自身免疫性溶血性贫血(AIHA)或AIHA发生在NHL诊断之前或治疗过程中已有不少报道,但以Coombs试验阴性AIHA为首发症状的NHL鲜有报道。在此,本文报道1例1.5年反复溶血发作的Coombs试验阴性AIHA后合并NHL的患者。患者女性,69岁,根据病史和实验室检查诊断为Coombs试验阴性AIHA,给予强的松治疗后血红蛋白恢复正常,停药后溶血反复复发2次,强的松治疗仍有效。第3次复发时强的松治疗无效,并出现颈部淋巴结肿大,病理检查确诊为NHL。给予6个疗程的CHOP方案化疗,NHL治愈,但溶血仍不能控制,给予小剂量利妥昔单克隆抗体(rituximab,RTX)治疗后,溶血很快停止,此后给予3次小剂量RTX进行维持治疗,NHL和AIHA呈持续缓解状态。结论:本文报告了一例十分罕见的非何杰金淋巴瘤,其发病时的主要临床症状为Coombs阴性自身免疫性溶血性贫血。     

血管免疫母细胞性T细胞淋巴瘤12例临床分析

为了探讨血管免疫母细胞性T细胞淋巴瘤(AITL)的临床、病理特征及预后情况,回顾性分析了经病理检查证实的12例AITL患者的临床特点、病理形态及免疫表型、治疗和生存情况。结果表明:12例患者主要症状为全身淋巴结肿大,9例伴有发热等全身症状。确诊依据淋巴结活检,病理组织学呈现淋巴结结构破坏,免疫母细胞增生,树枝状血管增生的特点,免疫表型全部为成熟外周T细胞性。12例患者均用CVP为主的化疗方案,总有效率58%。3年生存率为25%,全组中位生存25个月。结论:AITL临床过程呈侵袭性,进展快,中位生存期短,预后差,应探索更为有效的治疗方案。     

不一致性淋巴瘤临床病理观察

目的探讨不一致性淋巴瘤的临床病理学特征。方法结合临床、影像学、HE形态、免疫组化和分子病理学对1例不一致性腋窝弥漫性大B细胞淋巴瘤(DLBCL)和鼻咽、左颈部血管免疫母细胞性T细胞淋巴瘤(AITL)进行临床病理分析,并复习相关文献。结果患者以全身浅表淋巴结肿大为首发症状,腋窝淋巴结活检诊断为DLBCL,未作任何治疗。4年后发现鼻咽部新生物,活检提示T细胞性淋巴瘤,化疗2个疗程;5个月后出现全身浅表淋巴结肿大伴腹腔淋巴结肿大,活检左颈部淋巴结诊断为AITL;结合免疫组化、基因重排和EBER检测确诊为不一致性腋窝弥漫性大B细胞性淋巴瘤和鼻咽、左颈部血管免疫母细胞性T细胞性淋巴瘤。结论不一致性淋巴瘤罕见,早期很难明确诊断,易误诊而影响临床治疗导致预后不佳。     

13例血管免疫母细胞性T细胞淋巴瘤特征分析

目的分析血管免疫母细胞性T细胞淋巴瘤(AITL)骨髓涂片(BMA)及流式细胞术(FCM)的检测结果,探讨其骨髓侵犯的诊断依据。方法回顾性分析13例AITL BMA及FCM检测结果,并与临床特征作比较分析。结果经BMA检测13例AITL患者中5例为不确定,骨髓中瘤细胞异形度低、比例低;FCM检测1例阳性、2例为不确定,免疫表型特征不突出。与阴性病例比较,阳性及不确定病例在临床特征、实验室特征以及骨髓继发性改变的例数均高于阴性组,包括发热及肝、脾淋巴结肿大;贫血、血小板减低以及白细胞计数的异常;骨髓增生程度的异常、浆细胞及嗜酸性细胞比例的增高。结论 BMA、FCM检测AITL骨髓侵犯的敏感性不高,涂片中异形细胞与临床表现、实验检测结果及骨髓继发改变相关,明确诊断需进行骨髓活检并结合临床与实验室其他指标综合判断。     

胸腺瘤并纯红细胞再生障碍性贫血及自身免疫性溶血性贫血

目的探讨胸腺瘤合并纯红细胞再生障碍性贫血（pure red cell aplasia,PRCA）及自身免疫性溶血性贫血（autoimmune hemolytic anemia,AIHA）的发生机制,提高其诊断水平。方法对我科最近诊断的1例胸腺瘤并PRCA及AIHA的临床资料进行回顾性分析。结果患者因乏力伴心慌、气短就诊,经各项检查确诊为胸腺瘤伴PRCA及AIHA,行纵隔胸腺瘤切除术,病理证实为混合细胞型胸腺瘤,给予放疗及药物治疗,病情稳定。结论胸腺瘤并PRCA及AIHA极为少见,提示它们在发病机制上可能存在一定关联性。     

血管免疫母细胞性T细胞淋巴瘤误诊病例分析

目的探讨血管免疫母细胞性T细胞淋巴瘤(angioimmunoblastic T cell lymphoma,AITL)的诊治要点,以减少误诊误治。方法对AITL 1例误诊病例的临床资料进行回顾性分析并复习相关文献。结果本例为50岁男性,因淋巴结增大伴发热入院。根据临床表现、狼疮相关自身抗体异常及浅表淋巴结穿刺活检,初始考虑为系统性红斑狼疮、淋巴结炎,予相应治疗无效。后经多部位淋巴结穿刺活检、术后淋巴结组织学、免疫组织化学染色(免疫组化)和分子病理检测,确诊为AITL。予化疗及免疫抑制治疗,但患者继发肺部及颅内真菌感染,终因颅内出血死亡,发病至死亡历时8个月。结论对以淋巴结增大并伴有发热、免疫紊乱等表现就诊者,应考虑AITL的可能,注意鉴别诊断。淋巴结穿刺活检及免疫组化检查是确诊的主要手段。     

自身免疫性溶血性贫血的实验诊断及治疗

自身免疫性溶血性贫血（AIHA）是一组由B淋巴细胞功能异常亢进,产生抗自身红细胞抗体,使红细胞破坏增加而引起的贫血。有时红细胞的破坏能被骨髓红细胞生成所代偿,临床上不发生贫血,即仅有自身免疫性溶血（AIH）,     

慢性B细胞淋巴增殖性疾病合并自身免疫性溶血性贫血

本研究探讨慢性B细胞淋巴增殖性疾病（B-CLPD）并发自身免疫溶血性贫血（AIHA）的临床特征,提高对该疾病的认识。回顾性分析2000年至2012年治疗的B-CLPD合并AIHA患者14例,分析其临床特征、实验室检查结果、治疗及转归。结果表明,14例AIHA患者中慢性淋巴细胞白血病（CLL）9例、淋巴瘤5例;溶血发作时血红蛋白中位数61（33-84）g/L,网织红计数比例中位数12.0（3.1-35.0）%,Coombs试验阳性率100%;1例患者单用糖皮质激素治疗,5例采用化疗联合糖皮质激素治疗,8例采用利妥昔单抗免疫化疗联合糖皮质激素治疗,有效率达100%,其中完全缓解率78.6%（11/14）,部分缓解率21.4%（3/14）;随访至今,35.7%（5/14）出现溶血再发,经用既往治疗方案仍有效,应用过利妥昔单抗治疗的病例仅1例复发;14例中已有6例死亡,1例失访,其余7例存活。结论：AIHA是B-CLPD的常见并发症,可在疾病不同阶段出现。糖皮质激素免疫抑制剂疗效较好,但长期缓解率低,停药或减量后易复发,单克隆抗体具有较好的应用前景。     

Exacerbation of autoimmune hemolytic anemia associated with pure red cell aplasia after COVID-19: A case report

Autoimmune hemolytic anemia (AIHA) and pure red cell aplasia (PRCA) are rare complications of coronavirus disease 2019 (COVID-19). Herein, we report the case of a 28-year-old Japanese man who showed severe AIHA exacerbation associated with PRCA after COVID-19. AIHA was diagnosed and maintained for 5 years. Approximately 4 weeks after COVID-19, the patient developed severe anemia (hemoglobin level, 3.4 g/dL). Laboratory test results confirmed hemolytic exacerbation of IgG-mediated warm-type AIHA. Despite the hemolysis phase, the bone marrow revealed extreme hypoplasia of erythroblasts with a decreased reticulocyte count, similar to that observed in patients with PRCA. During oral prednisolone treatment, the patient recovered from anemia and showed increased reticulocyte count and reduced hypoplasia of marrow erythroblasts. Exacerbation of AIHA and PRCA was triggered by COVID-19 because other causes were ruled out. Although this case report highlights that COVID-19 could lead to hematological complications such as AIHA and PRCA, the exact mechanisms remain unclear.     

Pure red cell aplasia and myelofibrosis in B-cell neoplasm

We describe an unusual case of B-cell neoplasm accompanied by pure red cell aplasia (PRCA) and myelofibrosis in a 67-year-old male presenting with severe anaemia. A few unclassified, myeloperoxidase-negative blastoid cells were seen on bone marrow aspiration, and erythroid cell hypoplasia and myelofibrosis on bone marrow biopsy. An autoimmune PRCA was suspected, as serum CH50, C3 and C4 levels were consistently low. Ciclosporin was effective in treating the anaemia, but anaemia returned when the drug was discontinued. Thirteen months later, the patient was admitted with pleural effusion and ascites that contained monoclonal CD19+ CD20+ immature blast cells with a complex karyotype, thought to be neoplastic B-cells. The unclassified blastoid cells seen earlier may therefore have been from the same origin. The patient deteriorated rapidly and died. Only one case of non-Hodgkin's lymphoma with PRCA and myelofibrosis has been reported previously. We discuss the possibility that dysregulated T-cells induced by neoplastic B-cells may have given rise to concomitant PRCA and myelofibrosis.     

Pure red cell aplasia accompanied by COVID-19 successfully treated using cyclosporine

A 67-year-old Japanese man was admitted to our hospital with severe coronavirus disease 2019 (COVID-19) in March 2020. Mechanical ventilation was initiated 8 days after admission, due to severe respiratory failure. Multiple severe complications such as liver dysfunction, arrhythmia, brain infarction, and venous thromboembolism were also observed. We initially diagnosed Coombs test-positive warm autoimmune hemolytic anemia. Corticosteroids proved ineffective and anemia worsened with severe erythroid hypoplasia (0.5% erythroblasts in bone marrow), so we diagnosed pure red cell aplasia (PRCA). We also identified massive infiltration of cytotoxic T-lymphocytes expressing CD8, granzyme B, and perforin in bone marrow. Systemic cyclosporine was started, with full resolution of anemia and no need for blood transfusions after 4 weeks. We believe that this represents the first report of COVID-19-associated PRCA successfully treated using cyclosporine.     

Angio-immunoblastic T-cell lymphoma in evolution: A case report

Angio-immunoblastic T-cell lymphoma (AITL), a rare disease that constitutes 1% to 2% of non-Hodgkin's lymphomas, presents in middle-aged and elderly individuals. This report describes a patient with high-grade fever and lymphadenopathy. An extensive in-hospital work-up that included lymph node biopsy yielded negative results. The patient became asymptomatic for 4 wk, but then symptoms recurred with more pronounced lymphadenopathy. A computed tomography scan documented recurrent diffuse lymphadenopathy. Another lymph node biopsy revealed florid changes that strongly suggested AITL. Flow cytometry confirmed this diagnosis. The patient was treated with hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) and achieved complete remission after the first cycle. The patient developed sepsis during the second cycle and expired within 4 mo of diagnosis. The prognosis and natural course of AITL are poor when the classic chemotherapy protocol is administered. When infection has been ruled out, physicians should be wary of aggressive lymphomas that present with diffuse lymphadenopathy and fever.     

Pure red cell aplasia caused by parvovirus B19 in two patients without chronic hemolysis

Infection with human parvovirus B19 (PVB19) induces acquired pure red cell aplasia (PRCA). Chronic hemolytic anemia is well known as an underlying condition. However, additional factors have been recognized to accompany parvoviral PRCA; however, there are only limited reports on iron-deficiency anemia (IDA) and rituximab-induced B-cell dysfunction. We report two patients with PVB19-associated PRCA confirmed by positivity of viral DNA. Although they had no chronic hemolysis, patient 1 had IDA, and patient 2 had remitted small-lymphocytic lymphoma treated with rituximab-containing chemotherapy. Absence of reticulocytes in peripheral blood and marked depletion of erythroid precursors in bone marrow were observed both. Whereas patient 1 received only symptomatic therapy because anemia was not severe, patient 2 was treated with steroids, as PRCA etiology was at first uncertain, and immunological PRCA was not excluded. Both showed rapid increase of reticulocyte counts and recovery from anemia. Although immunoglobulin is considered effective for parvoviral PRCA, notable adverse reactions have been reported. When anemic symptom is not severe, reticulocyte observation only is recommended. The effects of steroids should also be re-evaluated. Optimal treatment according to disease severity remains to be established.     

口服环磷酰胺治疗难治性T细胞大颗粒淋巴细胞白血病合并纯红细胞再生障碍性贫血的疗效

目的:探讨小剂量环磷酰胺口服治疗难治性T-大颗粒淋巴细胞白血病(T-LGLL)伴纯红细胞再生障碍性贫血(PRCA)的疗效。方法:报告1例T-LGLL合并PRCA患者的临床表现、实验室检查特征,及应用环孢素A联合强的松无效后给予口服小剂量环磷酰胺的治疗经过,并结合文献进行讨论。结果:患者为老年女性,临床进展缓慢,以贫血为主要表现,骨髓红系细胞增生显著低下,血涂片以大颗粒淋巴细胞为主,免疫分型及基因重排符合T-LGLL,应用环孢素A联合强的松治疗5个月无效,需要依赖反复输血。二线改用环磷酰胺100 mg/d口服,血红蛋白恢复至正常水平,停药1年仍维持疗效。结论:T-LGLL合并PRCA少见,小剂量环磷酰胺可作为有效的治疗方案。     

1024例恶性淋巴瘤外周血及骨髓的检测分析

目的了解恶性淋巴瘤外周血表现和骨髓侵犯的概率,为淋巴瘤的早期诊断提供证据。方法对1 024例恶性淋巴瘤初诊患者外周血及骨髓涂片结果进行回顾性分析。结果经病理确诊的1 024例恶性淋巴瘤病例中血常规正常者744例,单纯红细胞减低者133例,红细胞合并白细胞减低者68例,红细胞、白细胞、血小板三系减低者49例,淋巴细胞增高者30例。骨髓涂片显示正常者788例,骨髓受侵犯者203例,合并白血病者33例。在236例受侵犯和合并白血病的病例中,非霍奇金氏淋巴瘤(NHL)占200例,而B细胞淋巴瘤占133例,T细胞占67例,霍奇金淋巴瘤(HL)仅占36例;淋巴瘤分期在1、2期的占788例,3、4期的占236例。结论淋巴瘤早期外周血往往表现正常,骨髓的受侵犯时外周血也可正常,而当淋巴瘤进入晚期时可合并白血病,早期的侵犯骨髓活检比涂片更具有诊断价值。     

骨髓单个核细胞Coomb's试验在淋巴瘤合并贫血患者诊断中的意义

目的探讨ML(淋巴瘤)合并贫血(外周血红细胞悬液Coomb,s试验阴性)患者对骨髓的单个核细胞进行Coomb,s试验的临床价值。方法抽取我院自2008年11月至2011年11月以来,于我科治疗的血液病患者临床资料进行回顾性分析,其中A组AIHA(自身免疫性的溶血性贫血)患者10例(阳性对照组),均系外周血红细胞悬液Coomb's试验呈阳性者;B组4名正常人与46例各类型(再障,PNH,IDA等)贫血患者共50例(阴性对照组),均已明确诊断;C组ML合并贫血患者100例(实验组)均系外周血红细胞悬液Coomb,s试验呈阴性者;对3组患者骨髓的单个核细胞进行Coomb,s试验,并予以对比分析。结果对A组骨髓的单个核细胞进行Coomb,s试验,10例均提示为阳性,而B组中50例均提示为阴性,C组23例结果呈阳性,而67例结果呈阴性,A组患者骨髓单个核细胞Coomb,s试验阳性率为100.0%(10/10),C组患者阳性率为23.0%(23/100),两组差异呈显著性(P<0.05)。结论 ML合并贫血(外周血红细胞悬液Coomb,s试验阴性)患者对骨髓的单个核细胞进行Coomb,s试验检查,能够对其诊断以及鉴别诊断均提供有效的实验依据,从而避免误诊情况的发生,同时也能够对患者进行有效并且及时的治疗,应予推广。