Mixed warm and cold antibody-type autoimmune hemolytic anemia in a healthy pregnant woman with primary cytomegalovirus infection

A 25-year-old previously healthy pregnant woman was admitted to our hospital because of severe anemia (Hb 6.7 g/dl), and diagnosed as having mixed-type autoimmune hemolytic anemia (AIHA) due to de novo cytomegalovirus (CMV) infection. After daily administration of prednisolone, the anemia gradually resolved and the patient delivered a healthy baby. This is the first report of a healthy person suffering from mixed-type AIHA due to de novo CMV infection.     

Autoimmune hemolytic anemia in patients with liver transplants for primary biliary cirrhosis: Three case reports and a review of the literature

BACKGROUND: Hemolytic anemia is rare after liver transplant and is usually associated with ABO mistmatch, post-transplant lymphoproliferative disorders, or medications. CASE REPORTS: We report three patients who had undergone successful liver transplants for primary biliary cirrhosis (PBC) and developed direct antibody test positive autoimmune hemolytic anemia (AIHA) several years into uncomplicated post-transplant management. For two of the patients, the hemolysis responded to steroids and rituximab. One patient required a surgical splenectomy. DISCUSSION: AIHA is an immune-mediated hemolysis that has been reported in patients with PBC. There are no reports of AIHA in patients following liver transplantation for this disease. AIHA should be considered in stable PBC patients who develop anemia years after liver transplant.     

De novo CD5-positive diffuse large B-cell lymphoma associated with autoimmune hemolytic anemia presenting as erythroid hypoplasia

A 54-year-old woman was admitted due to high-grade fever, cervical lymphadenopathy and general malaise in May 2003. On examination, severe anemia was noted, direct Coombs and cold hemagglutinin tests were positive and the haptoglobin level was low in the peripheral blood. However, a bone marrow examination revealed marked erythroid hypoplasia. A diagnosis was made of co-existing combined type autoimmune hemolytic anemia (AIHA) and erythroid hypoplasia. A pathologic diagnosis of de novo CD5-positive diffuse large B-cell lymphoma (de novo CD5+ DLBCL) was made based on a cervical lymph node biopsy. The patient was treated with CHOP accompanied by rituximab (R-CHOP), resulting in complete remission after 3 courses of chemotherapy. The AIHA and erythroid hypoplasia subsided after 2 courses of R-CHOP. The sera obtained during erythroid hypoplasia significantly inhibited the growth of erythroid progenitor cells (erythroid colony-forming units, CFU-E) from her bone marrow collected after recovery. We report here a patient with de novo CD5+ DLBCL associated with both AIHA and erythroid hypoplasia, suggesting that the lymphoma triggered an abnormal immunity which generated some humoral inhibitors against erythropoiesis.     

Hypersplenism induced by splenic vein ligation

Warm autoimmune hemolytic anemia (AIHA) is a rare clinical entity. It is usually caused by an IgG autoantibody directed against the red blood cell membrane that causes extravascular hemolysis predominantly in the spleen. As a result, disease states or procedures that result in hypersplenism would be expected to increase red cell destruction in patients with an underlying warm AIHA. We present the case of a patient with a previously undiagnosed warm AIHA, who developed worsening hemolysis after undergoing splenic vein ligation during a pancreaticoduodenectomy to remove a neuroendocrine tumor.     

Direct antiglobulin test reactive with complement only in warm type autoimmune hemolytic anemia

Direct antiglobulin test (DAT) with only complement detected on red blood cells is a rare laboratory finding, and its significance in the setting of warm autoimmune hemolytic anemia (AIHA) is controversial. During 2 years (2003-2004) 277 patients with positive DAT were recorded in the blood bank registries, 17 of them had DAT reactive with C3 alone with no cold agglutinin or other nonimmune causes for hemolysis diagnosed. Red cell eluate disclosed small amounts of IgG in two patients. In nine patients no signs of clinical hemolysis were found, however, all these patients had underlying conditions that are known to be associated with red cells autoantibodies (autoimmune disorder or malignancy). Eight patients developed AIHA, seven of them with severe hemolysis. Three patients had idiopathic AIHA, and the others have been diagnosed with infectious, lymphoproliferative and autoimmune disorders. In two patients with acute infection the hemolytic process spontaneously resolved, three responded to corticosteroid therapy, while three patients were refractory to two lines of drug therapy and underwent splenectomy. Reticulocytopenia was found in four patients. Our results emphasize that AIHA with DAT reactive with complement alone is a rare disorder and might be accompanied by severe, refractory to conventional treatment and life-threatening hemolysis.     

自身免疫性溶血性贫血红细胞相关抗体检测及临床分析

目的：分析自身免疫性溶血性贫血（AIHA）患者血液中红细胞相关抗体（EAIg）免疫分型的临床意义。方法;采用流式细胞仪和抗人单克隆抗体检测24例AIHA患者的EAIg,并分析其亚型及其与临床的关系。结果：24例AIHA患者直接抗人球蛋白试验（Coombs）仅8例阳性,阴性16例,而FCM检测出其中13例EAIg阳性,类型分布以IgG＋C3型多见,且贫血、溶血程度重,余依次为C3型、IgG型。结论：AIHA免疫分型可判定疾病的严重程度以及为临床治疗提供依据。     

Characterization of direct antiglobulin test‐negative autoimmune hemolytic anemia: A study of 154 cases

Direct antiglobulin test (DAT)‐negative (DAT‐)autoimmune hemolytic anemia (AIHA) is empirically thought to show the same clinical conditions as DAT‐positive (DAT+)AIHA, with the exception of an adequate amount of red blood cell (RBC)‐bound immunoglobulin (Ig)G. We investigated the clinical characteristics of DAT?AIHA in comparison with DAT+AIHA. Of the 582 patients referred to our laboratory with undiagnosed hemolytic anemia, AIHA was clinically diagnosed in 216 patients (DAT?AIHA, n = 154; DAT+AIHA, n = 62). The percentage of reticulocytes, mean corpuscular volume, RBC‐IgG levels, white blood cell count, and total protein (TP) levels were significantly higher in patients with DAT+AIHA than patients with DAT?AIHA. The hemoglobin level was significantly lower in patients with DAT+AIHA. No significant differences between patients with DAT?AIHA and DAT+AIHA existed with respect to age, gender, idiopathic/secondary nature, complications such as Evans syndrome, effectiveness of steroid treatment, or survival rate at 1 year following diagnosis. Patients with DAT?AIHA required significantly lower doses of steroids for maintenance therapy. Based on multivariate analysis of idiopathic DAT?AIHA (n = 110), TP and Evans syndrome were associated with the effectiveness of steroids (adjusted odds ratio [aOR], 1.36/[0.1 g/dl]; 95% confidence interval [CI], 1.01–1.84) and survival at the 1‐year follow‐up (aOR, 0.1; 95% CI, 0.01–0.88). Our results indicate that patients with DAT?AIHA generally suffer milder anemia and hemolysis than patients with DAT+AIHA, respond equally well to steroids, and have comparable survival at 1‐year. Am. J. Hematol. 88:93–96, 2013. © 2012 Wiley Periodicals, Inc.     

Refractory autoimmune hemolytic anemia in a patient with DiGeorge syndrome treated successfully with plasma exchange: a case report and review of the literature

Warm antibody autoimmune hemolytic anemia (AIHA) results from targeted antibodies towards the red blood cells (RBCs) and can be either idiopathic or secondary to certain diseases, such as autoimmune disorders or malignancy, drugs, or infection. Patients with DiGeorge syndrome are particularly vulnerable to autoimmune conditions secondary to thymic hypoplasia and dysfunction of the immune system. First-line therapy for AIHA consists of corticosteroids, with most patients showing signs of response. Relapses are not uncommon and are treated with splenectomy or rituximab. There is a paucity of reports in the literature regarding treatment options beyond this stage. Herein, we describe an unusual case of a 20-year-old female affected by DiGeorge syndrome with a history of immune thrombocytopenia (ITP), who presented with life-threatening AIHA. Standard first- and second-line therapeutic modalities were ineffective in controlling her disease and she ultimately underwent plasma exchange therapy with successful resolution of hemolysis. At her last follow-up, one year after her initial presentation, she remains clinically well without signs of hemolysis. We conclude that in refractory cases of warm AIHA, plasma exchange therapy can be a valuable tool in the therapeutic armamentarium.     

Pathogenesis, prevalence, and prognostic significance of cytopenias in chronic lymphocytic leukemia (CLL): a retrospective comparative study of 213 patients from a national CLL database of 1,518 cases

Utilizing the database of the Israeli CLL Study Group, we investigated the prevalence and prognostic significance of anemia and thrombocytopenia in patients with chronic lymphocytic leukemia (CLL). Of 1,477 patients, 113 had anemia and thrombocytopenia associated with “infiltrative” marrow failure, median survival of 41 and 86 months, respectively. Autoimmune cytopenias were diagnosed in 100 patients, autoimmune hemolytic anemia (AIHA) in 80, and immune thrombocytopenia (ITP) in 31, while 11 had both co-existent. Median survival of patients with AIHA and ITP, from CLL diagnosis, was 96 and 137 months, respectively, but 29 and 75 months from onset of cytopenia. Patients with AIHA from the time of CLL diagnosis had a significantly shorter survival than those without anemia (p?<?.0001). Survival was similar for patients with AIHA or anemia due to “infiltrative” bone marrow failure (p?=?.44). The presence of positive antiglobulin test even without hemolysis was associated with worse outcome. Overall survival of patients with ITP and those without cytopenias (p?=?0.94) were similar. In conclusion, laboratory or clinical evidence of AIHA has a significant negative impact on the survival of patients with CLL. Outcome for cases with ITP and patients without cytopenias was similar.     

Cut‐off value of red‐blood‐cell‐bound IgG for the diagnosis of Coombs‐negative autoimmune hemolytic anemia

Direct antiglobulin test (DAT)‐negative autoimmune hemolytic anemia (Coombs‐negative AIHA) is characterized by laboratory evidence of in vivo hemolysis, together with a negative DAT performed by conventional tube technique (CTT) in clinically suspected AIHA patients. The immunoradiometric assay (IRMA) for red‐blood‐cell‐bound immunoglobulin G (RBC‐IgG) can be used to diagnose patients in whom CTT does not detect low levels of red cell autoantibodies. We investigated the diagnostic cutoff value of the IRMA for RBC‐IgG in Coombs‐negative AIHA and calculated its sensitivity and specificity. Of the 140 patients with negative DAT by CTT referred to our laboratory with undiagnosed hemolytic anemia, AIHA was clinically diagnosed in 64 patients (Coombs‐negative AIHA). The numbers of Coombs‐negative AIHA and non‐AIHA patients changed with age and gender. The cutoff values were determined from receiver operating characteristic (ROC) curve according to age and gender. The IRMA for RBC‐IgG proved to be sensitive (71.4%) and specific (87.8%) when using these cutoffs. Using these cutoffs for 41 patients with negative DAT referred to our laboratory in 2006, all the pseudonegative cases were treated with steroids before the test. The 31 untreated cases could be grouped using one cutoff value of 78.5 and showed 100% sensitivity and 94% specificity, independent of gender and age. Results indicate that RBC‐IgG could become a standard approach for the diagnosis of Coombs‐negative AIHA, when measured before treatment. Am. J. Hematol., 2009. © 2008 Wiley‐Liss, Inc.     

Clinical and serological characterization of autoimmune hemolytic anemia in a tertiary care hospital in North India

Clinical and serological characterization of autoimmune hemolytic anemia (AIHA) helps in the diagnosis, management, and monitoring course of disease. In the present study, we serologically characterized the red-cell-bound autoantibodies in diagnosed AIHA patients with regards to antibody class, subclass, direct antiglobulin test (DAT) strength, and their correlation with in vivo hemolysis. A total of 157 samples were evaluated for DAT. Clinically and serologically, 43 of them were diagnosed as AIHA. Detailed serological characterization of autoantibodies was performed in these 43 patients using the gel technology. Hematological and biochemical parameters were obtained from the Hospital Information System. Polyspecific (immunoglobulin G (IgG) + C3) DAT-positive samples were tested for monospecific DAT (IgG, IgM, IgA, C3c, and C3d) and IgG subclass (IgG1 and IgG3). Thermal amplitude of autoantibodies was determined on eluates. Median age of the patients was 31 years (range, 12–70 years) with male to female ratio of 1:3.3. In 55.8% of patients, AIHA was secondary to an underlying disorder. Patients with strong reactive DAT had increased likelihood of hemolysis (p = 0.000). IgG was the solitary autoantibody coating the red cells in 72.1% of patients. Red cells coated with multiple immunoglobulins/complements and IgG subclass IgG1 and/or IgG3 were more susceptible to undergo hemolysis. Gel technology helps the immunohematologist to diagnose and serologically characterize AIHA patient with regard to red-cell-bound autoantibodies’ class, subclass, and titer as these correlate with in vivo hemolysis.     

Sacroiliitis as an Initial Manifestation of Acute Myelogenous Leukemia

Sacroiliitis is the most pathognomonic and earliest manifestation of ankylosing spondylitis. We herein report a 28-year-old female patient who presented with sacroiliitis as an initial manifestation of acute myelogenous leukemia (AML). She had a 3-month history of anemia and walking difficulty. Bone marrow findings revealed an increase of blasts with trilineage dysplasia. Although she was initially diagnosed with myelodysplastic syndrome (MDS), blasts rapidly increased and AML developed 1 month after the diagnosis of MDS with Sacroiliitis. Induction chemotherapy failed to induce a complete remission of AML, but it did effectively treat the sacroiliitis. However, the sacroiliitis relapsed when the leukemia cells progressed thereafter. Oral corticosteroids helped ameliorate the sacroiliitis. She underwent bone marrow transplantation (BMT) from an HLA-identical sister during a nonremission period; however, the leukemic cells began to rapidly increase from day 30 after BMT. The close relationship between the occurrence of sacroiliitis and AML suggested that autoimmune sacroiliitis was a paraneoplastic phenomenon of AML in this patient. Although autoimmune disorders develop in a substantial number of MDS patients, they are rarely observed in de novo AML. No previous report has described sacroiliitis as the initial manifestation of de novo AML.     

Is secondary leukemia an independent poor prognostic factor in acute myeloid leukemia?

Secondary leukemia is a poorly defined term that often refers to the development of acute myeloid leukemia (AML) following the history of a previous disease, such as a myelodysplastic syndrome or a chronic myeloproliferative disorder. Secondary leukemia can also be a consequence of treatment with chemotherapy, including alkylating agents and topoisomerase II inhibitors, and/or radiotherapy, or due to exposure to environmental carcinogens. Outcomes for this large and variable group of patients with secondary AML have been poor compared to people who develop AML de novo. The question arises whether a diagnosis of secondary leukemia per se indicates a poor prognosis or whether their bad outcomes result from an association with certain morphologic and biologic characteristics. Morphologic dysplasia in de novo AML is related to unfavorable cytogenetics, but has no independent prognostic relevance under the conditions of intensive chemotherapy. While there is no significant correlation between cytogenetic risk groups and dysplasia, cytogenetic features do have an impact on outcome among both de novo and secondary AML patients. In various subgroups of secondary AML, the spectrum of cytogenetic abnormalities is similar to de novo AML, but the frequency of abnormalities associated with unfavorable and intermediate risk cytogenetics, such as a complex karyotype, trisomy 8, monosomy 7, and others, is higher in secondary AML. The survival of patients with therapy-related myeloid leukemia (t-AML) is generally shorter than for those with de novo AML within the same cytogenetic risk group. Across the population of t-AML, however, survival varies according to cytogenetic risk group, with longer survival in patients with favorable-risk karyotypes. The term secondary AML is too broad and imprecise to be of importance and should not be used. These AML patients should be enrolled on front-line chemotherapy trials and should be stratified by pretreatment disease status and exposure history, if necessary. Most importantly, the molecular and genetic differences that appear to determine the phenotype and the outcome of these patients need to be investigated further.     

Apoptosis, bcl-2 expression and p53 accumulation in myelodysplastic syndrome, myelodysplastic-syndrome-derived acute myelogenous leukemia and de novo acute myelogenous leukemia

Apoptosis and its dysregulation have been implicated in dysplastic and ineffective hematopoiesis and the neoplastic transformation of bone marrow in myelodysplastic syndrome (MDS). To explore the role of apoptosis in hematological disorders, we examined the frequency of apoptotic cells by the in situ end labeling method in bone marrow specimens from 37 patients with MDS [refractory anemia (RA) 10 cases, RA with excess of blasts (RAEB) 27 cases including 12 cases with leukemic transformation], 12 patients with MDS-derived acute myelogenous leukemia (AML) and 13 patients with de novo AML. In addition, we investigated the relationship of apoptosis to the immunohistochemical expression of bcl-2 and p53 in these cases, and the association of apoptosis, bcl-2, and p53 with the leukemic evolution of MDS by examining sequential bone marrow samples of the same patient from the time of initial diagnosis to the time of overt leukemia. The percentage frequency of apoptotic cells was significantly greater in MDS (RA: 9.46 +/- 2.99%, m +/- SD; RAEB: 5. 60 +/- 3.09) as compared with those in MDS-derived AML (0.62 +/- 0. 37), de novo AML (0.28 +/- 0.11) and controls (1.00 +/- 0.59). On the other hand, the cases of RAEB with leukemic transformation exhibited a lower frequency of apoptotic cells and a higher frequency of bcl-2- and p53-positive cells than those without transformation. When the RAEB cases transformed to AML, the frequency of apoptotic cells was significantly reduced (2.96 +/- 1. 54 --> 0.62 +/- 0.37), while the frequencies of bcl-2-positive cells and p53-positive cells were greater (10.88 +/- 3.66 --> 30.54 +/- 7. 14, and 20.21 +/- 6.21 --> 32.34 +/- 14.71, respectively). In contrast to MDS-derived AML, over a half of de novo AML cases showed few p53-positive cells. These findings corroborate the earlier notion that apoptosis may play a substantial role in dysplastic and ineffective hematopoiesis in MDS. It is also suggested that the suppression of apoptosis associated with enhanced bcl-2 expression and p53 accumulation increases the probability of developing leukemia in MDS, and that oncogenetic development might be different between MDS-derived AML and de novo AML.     

Fatal intravascular autoimmune hemolytic anemia after fludarabine treatment for chronic lymphocytic leukemia

We report the case of a patient with chronic lymphocytic leukemia (CLL) who developed fatal intravascular autoimmune hemolytic anemia (AIHA) after fludarabine treatment. He had previously received several treatments including two courses of fludarabine. The direct antiglobulin test (DAT) was negative at diagnosis but was found to be positive with anti-IgG after the first fludarabine treatment. When the patient was treated again with fludarabine nine months later, the DAT became positive with anti-IgG and anti-C3d antiglobulins after the second course of treatment. Abrupt, fatal intravascular hemolysis occurred after the third course. The occurrence of severe AIHA in CLL patients treated with fludarabine has been reported by several authors. Physicians should be aware of the risk of severe AIHA in CLL patients with a history of AIHA or positivation of the DAT during previous fludarabine administration, or in case of secondary fixation of complement to the red cell membrane occurring during fludarabine treatment.     

Fatal intravascular autoimmune hemolytic anemia after fludarabine treatment for chronic lymphocytic leukemia

We report the case of a patient with chronic lymphocytic leukemia (CLL) who developed fatal intravascular autoimmune hemolytic anemia (AIHA) after fludarabine treatment. He had previously received several treatments including two courses of fludarabine. The direct antiglobulin test (DAT) was negative at diagnosis but was found to be positive with anti-IgG after the first fludarabine treatment. When the patient was treated again with fludarabine nine months later, the DAT became positive with anti-IgG and anti-C3d antiglobulins after the second course of treatment. Abrupt, fatal intravascular hemolysis occurred after the third course. The occurrence of severe AIHA in CLL patients treated with fludarabine has been reported by several authors. Physicians should be aware of the risk of severe AIHA in CLL patients with a history of AIHA or positivation of the DAT during previous fludarabine administration, or in case of secondary fixation of complement to the red cell membrane occurring during fludarabine treatment.     

Application of flow cytometry in detection of red-cell-bound IgG in Coombs-negative AIHA

Coombs negative autoimmune hemolytic anemia (AIHA) is characterized by laboratory evidence of in vivo hemolysis along with a negative direct antiglobulin test (DAT) performed by conventional tube technique (CTT) in clinically suspected AIHA patients. The sensitive gel test (GT) and flow cytometry (FC) can effectively diagnose such patients where CTT does not detect low level of red cell autoantibodies. We investigated the use of FC in the serological evaluation of CTT DAT negative AIHA and its comparison with GT DAT. Of the 50 patients with suspected AIHA, CTT DAT was negative in 5 patients (Coombs negative AIHA). GT DAT could detect red cell autoantibodies in 4 of these 5 patients. Monospecific GT DAT showed IgG and/or C3d as the responsible autoantibody. FC was considered as reactive when MFI was >3.6 (mean of 20 healthy negative volunteers +2SD). FC was reactive in all five Coombs negative AIHA patients. The mean MFI in five known CTT DAT positive samples taken for comparison was significantly higher compared to 5 DAT negative AIHA (18.3 +/- 7.78 vs. 7.88 +/- 1.35, p < 0.05). There was poor correlation between strength of GT DAT and MFI by FC. We conclude that FC is more sensitive test than the CTT and helps in the serological diagnosis of Coombs negative AIHA. However, in resource poor settings, GT DAT can be a good alternative to FC.     

Comparison of traditional methods and mitogen-stimulated direct antiglobulin test for detection of anti-red blood cell autoimmunity

The diagnosis of autoimmune hemolytic anemia (AIHA) is based on a positive direct antiglobulin test (DAT), which is performed using various methods with different sensitivities. Recently, mitogen-stimulated (MS)-DAT was suggested to be able to identify latent anti-erythrocyte autoimmunity. Traditional methods (tube, microcolumn, and solid phase) and MS-DAT were compared in 54 consecutive cases of suspected AIHA, 28 idiopathic AIHA in clinical remission, and 12 difficult-to-diagnose cases of DAT-negative AIHA, and the results (all cases) were correlated with hematologic and hemolytic parameters. DAT tube was confirmed as the gold standard to diagnose AIHA since almost all positive cases showed hemolytic anemia and positive eluates; 10 out of 26 tube-negative cases were positive on microcolumn and solid phase antiglobulin tests, and 22 out of 26 using MS-DAT, although only half of them showed clear signs of hemolysis. Mitogen stimulation increased the amount of IgG bound to red blood cells in all groups; moreover, MS-DAT was the only positive test in 10 cases of AIHA, and mitogen stimulation facilitated the identification of autoantibody specificity in culture supernatants. We conclude that a battery of tests rather than a single test is useful for the diagnosis of AIHA, including MS-DAT as an additional test for selected cases, although the results have to be cautiously interpreted based on the overall clinical context.     

An antecedent diagnosis of refractory anemia with excess blasts has no influence on mobilization of peripheral blood stem cells and hematopoietic recovery after autologous stem cell transplantation in acute myeloid leukemia

Several studies have reported data on factors influencing mobilization of peripheral blood stem cells (PBSC) in non-myeloid malignancies. On the contrary, data from patients with acute myeloid leukemia (AML) are very limited, in particular, as the impact of an antecedent diagnosis of refractory anemia with excess blasts (RAEB) on mobilization of PBSCs as well as hematopoietic recovery after autologous stem cell transplantation (ASCT) is concerned. We retrospectively analyzed a cohort of 150 consecutive AML patients in first complete remission in order to make a comparison between patients with de novo AML and secondary AML (s-AML) in terms of CD34 positive (CD34+) cells mobilization and number of leukapheresis needed to collect at least one single stem cell graft. Data concerning hematopoietic recovery after ASCT were also compared. The successful mobilization rate (>2 x 10(6) CD34+ cells/kg) was comparable between de novo AML patients (87%) and those with s-AML (76%), P:0.21. No statistically significant difference was found in terms of either median number of CD34+ cells collected (P:0.44) or CD34+ cells peak in peripheral blood (P:0.28). Both groups of patients needed a median of two apheresis (P:0.45) and no difference was found on the median number of CD34+ cells collected per single apheresis (P:0.59). Finally, neutrophil and platelet recovery after ASCT were comparable between the two groups. An antecedent diagnosis of RAEB has no impact on mobilization and collection of PBSCs in AML as well as on hematopoietic recovery after ASCT.     

The successful treatment of refractory autoimmune hemolytic anemia with rituximab in a patient with chronic lymphocytic leukemia

The most frequent autoimmune complication in chronic lymphocytic leukemia (CLL) is autoimmune hemolytic anemia (AIHA). There are various treatment modalities; however, there is not much experience with the use of the chimeric anti-CD20 monoclonal antibody rituximab in the autoimmune complications of CLL. Here, we present our patient with CLL and AIHA whose AIHA was unresponsive to various treatment modalities. The administration of 375 mg/m(2)/day rituximab weekly for four cycles halted hemolysis and resulted in resolution of the patient's anemia. One year after therapy, the patient is well with a normal blood count. Rituximab might be preferred over other treatment modalities in the autoimmune complications of CLL because it is effective and has fewer side effects than other therapies.