侵袭型非霍奇金淋巴瘤合并纯红细胞再生障碍性贫血

目的:研究侵袭性非霍奇金淋巴瘤并发纯红细胞再生障碍性贫血(PRCA)的临床特点和治疗结果。方法:报告两例分别并发于非特指型外周T细胞淋巴瘤(PTCL-NOS)和弥漫大B细胞淋巴瘤(DLBCL)的PRCA,并复习相关文献。结果:在联合化疗治疗后,DLBCL及其相关的PRCA均获完全缓解,而PTCL-NOS虽获缓解,但其相关的PRCA未好转,加用泼尼松治疗后PRCA缓解。结论:NHL相关的PRCA在联合化疗或免疫抑制治疗后可获完全缓解,且可不需维持治疗。     

侵袭型非霍奇金淋巴瘤合并纯红细胞再生障碍性贫血

目的：研究侵袭性非霍奇金淋巴瘤并发纯红细胞再生障碍性贫血（PRCA）的临床特点和治疗结果。方法：报告两例分别并发于非特指型外周T细胞淋巴瘤（PTCL-NOS）和弥漫大B细胞淋巴瘤（DLBCL）的PRCA,并复习相关文献。结果：在联合化疗治疗后,DLBCL及其相关的PRCA均获完全缓解,而PTCL-NOS虽获缓解,但其相关的PRCA未好转,加用泼尼松治疗后PRCA缓解。结论：NHL相关的PRCA在联合化疗或免疫抑制治疗后可获完全缓解,且可不需维持治疗。     

Autoimmune hemolytic anemias, Evans' syndromes, and pure red cell aplasia in non-Hodgkin lymphomas

We analyzed 108 cases of non-CLL non-Hodgkin lymphoma (NHL) associated with autoimmune hemolytic anemia (AIHA) (+/- pure red cell aplasia (PRCA)) or Evans' syndrome. The analysis was based on cases reported in the literature, which were retrieved by means of Pubmed and Medline searches and of an original series of 121 patients with NHL as well as reference lists of papers in the field. The number of cases in various NHL subtypes was small (n = 6 - 25). Nevertheless, interesting and sometimes unexpected differences in sex prevalence, temporal relationship between onset of lymphoma and AIHA, stage of lymphoma, relative frequency of warm antibody-AIHA (WA-AIHA) and cold antibody (CA-AIHA), association with PRCA and response of AIHA to treatments were noted for various lymphoma entities. WA-AIHA was more frequent in B-cell lymphomas, while CA-AIHA and PRCA predominantly occurred in T-cell lymphomas. Anti-lymphoma treatment seemed to be more effective against AIHA than conventional therapy with steroids or immunoglobulin. Although generated by a literature survey, this compilation of data indicates a complex relation of lymphoma and AIHA and warrants more attention and specific studies.     

近30年中国文献报道恶性淋巴瘤合并自身免疫性血细胞减少症的系统性分析

本文通过收集1989年1月至2019年12月国内学者发表在国内外期刊上的文献及参考文献,共纳入符合标准的140例恶性淋巴瘤(malignant lymphoma,ML)合并自身免疫性血细胞减少(autoimmune cytopenia,AIC)病例,包括溶血性贫血(autoimmune hemolytic anemia,AIHA)、免疫性血小板减少症(immune thrombocytopenia,ITP)、纯红细胞再生障碍性贫血(pure red cell aplasia,PRCA)及Evans综合征等。虽然各亚型淋巴瘤病例数均较少(n=1~28),但通过系统性分析仍得到部分有意义的发现。除免疫性中性粒细胞减少(autoimmune neutropenia,AIN)外,各类AIC均有报道,发生率依次为AIHA>ITP>冷凝集素综合征(cold agglutinin syndrome,CAS)>PRCA>Evans综合征。AIC见于各亚型淋巴瘤,但各类AIC在不同亚型发生率存在差异。CAS仅见于淋巴瘤B细胞非霍奇金淋巴瘤(B cell nonHodgkin′slymphoma,B-NHL)、AIHA、ITP,Evans综合征多见于B-NHL,PRCA则多见于T细胞非霍奇金淋巴瘤(T cell non Hodgkin′s lymphoma,T-NHL)。相较于糖皮质激素等常规治疗,合并ML的AIC抗肿瘤治疗对有效率更高。恶性淋巴瘤合并AIC临床情况复杂,需引起临床关注。     

Pure red cell aplasia in B-cell lymphoproliferative disorder treated with rituximab: report of two cases and review of the literature

Pure red cell aplasia (PRCA) is an unusual cause of anemia in patients with chronic lymphoproliferative disorders. Here, we present two cases of PRCA, one associated with chronic lymphocytic leukemia (CLL) and the other with splenic marginal zone lymphoma, in which the PRCA responded dramatically to treatment with rituximab. We then review the literature on PRCA in lymphoma and response to rituximab. PRCA associated with CLL or lymphoma may be another indication for rituximab therapy.     

Activity of rituximab monotherapy in refractory splenic marginal zone lymphoma complicated with autoimmune hemolytic anemia

We describe the case of a 61-year-old patient with refractory splenic marginal zone lymphoma and secondary autoimmune hemolytic anemia, both successfully treated with rituximab. This case demonstrates that rituximab monotherapy might also be a valid therapeutic approach in marginal zone lymphoma and autoimmune hemolytic anemia after failure of first-line treatment. Maintenance therapy, although expensive, could be useful to improve event-free survival in patients with unfavorable clinical behavior.     

血管免疫母细胞性T细胞淋巴瘤14例临床分析

目的探讨血管免疫母细胞性T细胞淋巴瘤(AITL)的临床病理特征及治疗。方法分析1997年2月至2004年7月收治的14例AITL。结果14例就诊的AITL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,3例并发自身免疫性溶血性贫血。病理组织学呈淋巴结结构破坏,免疫母细胞增生,树枝状血管增生的特点,免疫表型全部为T细胞性。14例均用ProMACE-CytaBOM方案化疗,CR3例,PR5例,总有效率57%。2年生存率为60%,全组中位生存25个月,3例缓解的患者已无瘤生存超过5年。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策略。     

Pure red cell aplasia associated with B cell lymphoma: demonstration of bone marrow colony inhibition by serum immunoglobulin.

A 58-year old male with follicular small cleaved B cell lymphoma developed pure red cell aplasia (PRCA) during chemotherapy. To understand the etiology of the PRCA, we studied the effects of patient sera on the progenitor cell colony formation of normal human bone marrow cells in vitro. We demonstrated a marked inhibition of normal bone marrow progenitor cell colony formation by patient sera, but not pooled normal human sera. Immunoglobulin was then precipitated from patient sera for similar studies. The majority of the precipitated immunoglobulin was of the IgG type. The immunoglobulin fraction markedly inhibited normal bone marrow progenitor cell colony formation, whereas the non-immunoglobulin fraction was not inhibitory. The presence of inhibitory serum immunoglobulin correlated with the hematologic status of the patient. We conclude that the development of PRCA in patients with B cell lymphoma may be due to a serum IgG inhibitor of bone marrow progenitor cell growth.     

704 Cold-Agglutinin Hemolytic Anemia: A Harbinger of Recurrent Lymphoma

Cold-agglutinin Hemolytic anemia (CAHA) is an uncommon cause of hemolysis that usually occurs in the setting of recent mycoplasma infection or lymphoma. We present the case of a patient who presented with CAHA and was subsequently found to have a recurrence of lymphoma, which had been previously miss-diagnosed as a lesser-grade disease.

Full Abstract: Introduction

Cold-agglutinin Hemolytic anemia is an uncommon cause of hemolysis that represents 13-15% of all autoimmune hemolytic anemias. Cold agglutinins are typically IgM auto-antibodies that bind to the surface of erythrocytes, causing complement activation and hemolytic anemia at an optimal temperature of 0-4oC. Clinical presentation is similar to other hemolytic anemias; with increasing dyspnea and fatigue-usually in the setting of recent mycoplasma infection or lymphoma.

Case

The patient is a 72 year-old Cuban-American man with a past medical history of diffuse B-cell lymphoma (DLBCL) diagnosed one year prior and amyloidosis who presented from clinic with increasing dizziness, dyspnea, night sweats, and fatigue over one month. The lymphoma had been treated with 6 cycles of chemotherapy and was found to be in remission with no sign of residual disease on imaging. Laboratory values demonstrated hemolytic anemia with a hemoglobin of 5.6 g/dL, and direct Coombs test was

Discussion

The patient in this report had a recurrence of lymphoma, which presented initially with cold agglutinin disease. This case is unique in several aspects. First, the patient had a positive direct Coombs test, indicating that at least some of the antibodies were of the IgG, and not the typical IgM type. Second, the patient was initially miss-diagnosed with DLBCL when he actually had a more aggressive immunoblastic lymphoma. This case illustrates the necessity to investigate the underlying cause of

     

外周T细胞淋巴瘤合并自身免疫性溶血性贫血的临床特点分析

背景与目的:与自身免疫性溶血性贫血(autoimmune hemolytic anemia,AIHA)相关的淋巴瘤病理学类型多见于惰性B细胞淋巴瘤,而很少见于弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)及外周T细胞淋巴瘤(peripheral T-cell lympho...     

Epstein-Barr virus associated diffuse large B-cell lymphoma complicated by autoimmune hemolytic anemia and pure red cell aplasia.

A 53-year old man with systemic lymphadenopathy and hepatosplenomegaly was diagnosed with diffuse large B cell-lymphoma after inguinal lymph node biopsy. Anemia was noted, direct and indirect Coombs tests were positive, and the haptoglobin level was low. However, the bone marrow aspirate revealed erythroid aplasia. Co-existing autoimmune haemolytic anemia (AIHA) and pure red cell aplasia (PRCA) were diagnosed. In situ hybridization with Epstein-Barr virus (EBV) encoded small RNA (EBER) showed positive findings in lymphoma cells. Southern blot hybridization revealed immunoglobulin heavy chain gene rearrangement and a clonal EBV terminal repeat, indicating monoclonal proliferation of EBV in infected B cells. The patient was treated with CHOP, resulting in a complete remission (CR). AIHA and PRCA subsided after 3 courses of chemotherapy. In conclusion, this case demonstrates not only the association of B-cell lymphoma with autoimmune disorders but also the involvement of EBV in these conditions.     

Autoimmune Hemolytic Anemia as a Risk Factor of Poor Outcome in Patients with Splenic Marginal Zone Lymphoma

Splenic marginal zone lymphoma is a rare disease, accounting for 1% of all lymphomas. We reviewed our single center experience of 13 patients with splenic marginal zone lymphoma (SMZL). Based on the prognostic model developed by Intergruppo Italiano Linfomi, 31% (4/13) of our patients had good, 38% (5/13) had intermediate and 31% (4/13) had a poor prognosis. The presence of two out of three prognostic factors (anemia, elevated LDH, low serum albumin) assignes the patient into the high risk category. In patients with anemia and an elevated LDH due to hemolysis, the outcome seems to be especially poor. Three out of 13 (23%) cases were complicated by autoimmune hemolytic anemia. All patients with autoimmune hemolytic anaemia (AIHA) died 7–28 months after the diagnosis. The mean follow-up time of those nine patients who are still alive is longer than 5 years (36–100 months). Patients with AIHA had significantly (p < 0.001) worse survival than those without AIHA. The main finding of our study is that the presence of AIHA is an adverse prognostic factor in SMZL.     

Hodgkin lymphoma presenting with various immunologic abnormalities, including autoimmune hepatitis, Hashimoto's thyroiditis, autoimmune hemolytic anemia, and immune thrombocytopenia

Immunologic abnormalities have been described in patients with Hodgkin lymphoma, including autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP). In this report, we describe a rare case of a 59-year-old woman who had autoimmune-mediated hepatitis and Hashimoto's thyroiditis at initial presentation of Hodgkin lymphoma. She was treated with ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine), which induced a complete remission. One year later, she developed a sudden Coombs-positive hemolytic anemia and immune thrombocytopenia. She was diagnosed with Evans syndrome and was treated with prednisolone and intravenous immunoglobulin. However, the response of the therapies was poor; she died of progressive thrombocytopenia. The autopsy revealed the relapse of Hodgkin lymphoma of cervical lymph nodes. Although autoimmune disorders are described in Hodgkin lymphoma, our case shows a rare instance of a patient who had various immunologic abnormalities, including autoimmune-mediated hepatitis, Hashimoto's thyroiditis, AIHA, and ITP.     

Thymoma with Autoimmune Hemolytic Anemia

A 38-year-old Japanese male was referred to our hospital with abnormal chest X-ray results and severe Coombs-positive hemolytic anemia. He was diagnosed with a stage IV, WHO type A thymoma and was treated with oral prednisolone (1 mg/kg/day) and subsequent chemotherapy. After chemotherapy, the patient underwent surgical resection of the thymoma. Hemolysis rapidly disappeared and did not return after the discontinuation of oral corticosteroids. Corticosteroid therapy may be preferable to chemotherapy or thymoma surgical resection in the management of autoimmune hemolytic anemia with thymoma.Key words: Thymoma, Autoimmune hemolytic anemia, Chemotherapy, Corticosteroid therapy     

Sickle cell anemia and hematological neoplasias

Sickle cell disease (SCD) is a congenital hemolytic anemia with various clinical findings. In some cases hematological neoplasias and some solid tumors may accompany this disease but these have rarely been reported. Here we report five cases with SCD and accompanying hematological neoplasias including lymphoblastic lymphoma, multiple myeloma and hairy cell leukemia in four cases with sickle cell trait and one case of Hodgkin' disease in sickle cell anemia. All of the cases except one had no previously diagnosed congenital hemolytic anemia and/or family history. Peripheral blood findings suggestive for an underlying hemolytic anemia were the first step and the most important initial lead in the detection of SCD. Severe musculoskeletal signs during the first presentation was seen in the lymphoma case, residual renal dysfunction after remission of multiple myeloma, and areas of infarction in the spleen in CT scans in the patient with sickle cell anemia were the most interesting findings in these cases. A standard therapeutic approach without any additional toxicity was relevant in all cases. Detailed clinical presentation and outcome of these five cases are documented here and the literature has been reviewed.     

脾边缘区淋巴瘤伴自身免疫性溶血性贫血1例并文献复习

目的：提高对脾边缘区淋巴瘤(splenic marginal zone lymphoma,SMZL)的认识。方法：详细报告1例典型患者临床及实验室特征,并复习相关文献。结果：SMZL是一少见的原发于脾脏的低度恶性B细胞淋巴瘤。临床以脾脏明显肿大、淋巴细胞增多为特征,易浸润骨髓,可合并自身免疫疾患。肿瘤细胞表达成熟B细胞免疫表型,CD5^-、CD10^-、CD23^-、CD103^-,不表达T细胞相关分化抗原。结论：SMZL起病潜隐,进展缓慢,生存期长,容易漏诊。糖皮质激素和环孢菌素A治疗SMZL合并自身免疫性溶血性贫血(AIHA)近期疗效好,对SMZL本身也有一定治疗作用。     

Autoimmune hemolytic anemia with myelodysplastic features followed by bilateral adrenal non-hodgkin lymphoma: a case report and review of the literature

Primary adrenal lymphoma is a rare entity characterized mainly by bilateral involvement, presenting predominantly diffuse large B-cell histology, adrenal insufficiency and poor prognosis. Approximately 85 cases have been described in the literature. We report here a case of a 77-year-old man who presented with autoimmune hemolytic anemia (AIHA), which preceded the diagnosis of lymphoma by more than 2 years. An ultrasound guided biopsy revealed diffuse, large B-cell, lymphoma; subsequent staging revealed no other disease site, and the patient was considered to have primary adrenal lymphoma. The patient had adrenal insufficiency at diagnosis. He received hormonal replacement and chemotherapy, but he succumbed to his disease because of sepsis and multi-organ failure a few days post diagnosis. To our knowledge, this is the first case in the literature in which AIHA preceded bilateral adrenal lymphoma. We also provide a summary of the current data for the clinical features, diagnosis and treatment of primary adrenal lymphoma.     

Monotherapy with rituximab induces rapid remission of recurrent cold agglutinin-mediated hemolytic anemia in a patient with indolent lympho-plasmacytic lymphoma

Cold agglutinin mediated immune hemolytic anemia secondary to lymphoproliferative disease (LPD), is primarily treated with measures directed to eliminate the malignant clone and as such, chemotherapy is usually given. The recent availability of monoclonal antibodies, has made it feasible to obtain both a clinical and molecular remission, as well as a remission on the functional level, such as elimination of secondary autoimmune phenomena. Recently we have administered a course of monotherapy with rituximab (4 weekly injections, x 375 mg/m2) to a patient with refractory and transfusion dependent cold agglutinin mediated hemolytic anemia secondary to indolent B-cell lymphoma. She achieved complete remission with a significant improvement in hemolysis and also became transfusion independent with a current follow-up of over one year. In individual cases, Rituximab has the potential of achieving not only a complete clinical remission (CR) but also a molecular CR, as well as a "functional" CR, by eliminating the clinical manifestations of autoimmunity; in this case, cold agglutinin mediated hemolytic anemia, secondary to NHL. Good results in autoimmunity secondary to lymphoma raises the possibility of future potential benefit of this agent in other primary autoimmune disorders.     

Pure red cell aplasia and myasthenia gravis with thymoma: a case report and review of the literature

A case of pure red cell aplasia (PRCA), myasthenia gravis (MG) and thymoma is reported. A 70-year-old woman presented with severe anemia. She had been diagnosed as having MG 8 years earlier and her symptoms were adequately controlled with ambenonium chloride. When she visited our hospital, her hematocrit was 13.7% with a hemoglobin concentration of 4.7 g/dl and her reticulocyte counts were persistently abnormal at 0.1%. Although both direct and indirect Coombs' tests were positive, there was no evidence of hemolysis. Routine screening tests for other etiologies of anemia were negative. Serological tests for anti-DNA and anti-acetylcholine receptor antibodies gave positive results. A bone marrow examination revealed severe erythroid hypoplasia. PRCA was diagnosed and the patient was treated with periodic transfusions. A lateral view chest roentgenogram and a computed tomography scan of the thorax showed the presence of an anterior mediastinal mass which was suspected to be thymoma. The patient underwent thymothymectomy and the tumor was diagnosed as a thymoma. Although the patient received no treatment for MG and PRCA after surgery, her hematological test results rapidly improved and she was discharged from the hospital on the 29th postoperative day. At that time, her hematocrit was 33.2%, her hemoglobin concentration was 10.0 g/dl, her peripheral reticulocyte level was 1.8% and her left partial ptosis had improved. She is doing well, 9 months after surgery. For a patient to remain in remission without treatment for PRCA and MG after thymothymectomy is extremely rare.