Anti-CD20 Monoclonal Antibody in the Treatment of Refractory Autoimmune Cytopenias in Adults.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2717-2717
Author(s):  
Santhosh Narat ◽  
Jagdish Gandla ◽  
Atul B. Mehta
Keyword(s):  
Monoclonal Antibody ◽  
Median Time ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Complete Response ◽  
Maximum Response ◽  
Maximal Response ◽  
Effective Treatment Option ◽  
Number Of Patients ◽  
Anti Cd20

Abstract Anti-CD20 monoclonal antibody (rituximab) has been used in autoimmune cytopenia with variable success.We report 13 patients with chronic refractory autoimmune hemolytic anemia (AIHA) and idiopathic thrombocytopenic purpura (ITP) who each received 4 cycles of rituximab 375mg/m2 weekly. All 8 AIHA patients (6 idiopathic,2 secondary to a lymphoproliferative disorder, 5 splenectomised) had warm antibody type. Response was seen in 4(50%) of 8 patients (3 CR,1PR) and 3 patients remain in CR at 5,7,14 months post-therapy. Median time to maximum response (TMR) in responders was 9 weeks(range 6 – 18 weeks). In 5 ITP patients (4 splenectomised), 4(80%) responded (3CR) and one continues in CR 50 weeks after completion of rituximab treatment Median time to maximum response was 4 weeks (range 4 – 12 weeks). No pre-treatment clinical or laboratory parameters that predict response could be identifird in the AIHA or ITP groups.Our data indicate that rituximab is a relatively safe and effective treatment option in patients with refractory autoimmune hemolytic anemia and thrombocytopenia. Table 1 Number of patients Mean age (Years) Sex Overall response Complete response No response Time to maximal response AIHA 8 47.75 (26– 73) 3M:4F 4 (50%) 3 (37.5%) 4 (50%) 9 weeks ITP 5 58.6 (28–89) 4M:1F 5 (80%) 3 (60%) 2 (40%) 4 weeks

Rituximab Treatment for Autoinmune Hemolitic Diseases,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3168-3168
Author(s):  
Natalia Schutz ◽  
Jorge Arbelbide ◽  
Walter Skordo ◽  
Susana Viñuales ◽  
Elsa Nucifora ◽  
...  
Keyword(s):  
Partial Response ◽  
Median Time ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Response Rate ◽  
Complete Response ◽  
Infectious Complications ◽  
Hemoglobin Level ◽  
Published Data ◽  
Steroid Dependence

Abstract Abstract 3168 INTRODUCTION: Steroids are the first line treatment for Autoimmune Hemolytic Anemia (AHA) and Immune Thrombocytopenic Purpura (ITP). Second line treatments for patients with partial reponses or steroid dependence are controversial and have changed during the last decades. Several authors have proposed the use of Rituximab in these patients although published data are still sparse. OBJECTIVES: We reviewed the medical records of all the patients treated in our hospital with Rituximab in order to evaluate the response rate and security of this treatment. MATHERIALS AND METHODS: We included in the study all the patients older than 18 years with diagnoses of Immune Thrombocytopenia or Autoimmune Hemolytic Anemia treated with Rituximab. Patients with oncologic diseases that required specific chemotherapy apart from AHA or ITP were excluded. Rituximab was administered at a dose of 375mg/m3 weekly for 4 weeks. In patients with AHA we assessed the response according to the following criteria: complete response a hemoglobin level higher than 12 g/dl without hemolysis (normal bilirubin, LDH and haptoglobin) and partial response at least 2g/dl increase from the basal hemoglobin level with improvement in the hemolysis parameters. In patients with ITP we defined complete response as >100.000 platelets/mm3 and partial response >50.000 platelets/mm3. In both cases patients should be tapering steroids (less than 10mg/day of prednisone) and without transfusions. RESULTS: We performed 55 treatments with Rituximab in 37 pts., 19 AHA (12 cold hemolytic anemia) and 18 ITP. The median age was 60 years (26 – 86) and 31 pts. were female. Five patients had other autoimmune diseases (lupus, sjogren, autoimmune hepatitis), and six patients had an underlying onco-hematologyc disease (CLL, indolent lymphoma). All patients had been treated with steroids before and most of them had also received azathioprine, cyclophosphamide or gamaglobuline. The median of previous treatments was 3. Eight patients had undergone also splenectomy. The reason for the treatment was steroid dependence in 16 patients, partial response 6 patients and no response to previous treatment in 15 patients. The overall response rate was 79% for AHA and 94% for ITP, with 8pts (42%) and 13pts (72%) achieving a complete response and 7pts (37%) and 4pts (22%) achieving a partial response respectively. The median time to the complete response was 14 days for ITP and 28 days for AHA. The treatment was well tolerated with only one infusion related serious adverse event and one pulmonary thromboembolism during the period of treatment. Fourteen patients relapsed (8 AHA and 6 PTI). The response rate to Rituximab at relapsed for those patients that received a second or even third course of treatment were similar to the observed before. The median time of follow up was 50 months with and event free survival at 1 year of 34% (median 11,9 months) for AHA vs. 60% for PTI (median 38 months) (p 0,23). The overall survival at 5 years was 39% (median 53 months) vs. 86% (median not reached) (p 0,18) respectively. Seven patients with AHA and 2pts with ITP died, mostly of infectious complications. CONCLUSIONS: Rituximab is an effective treatment for ITP and AHA patients with no response to previous treatments or corticoid dependence. There were few serious adverse effects related to the treatment with Rituximab itself. The mortality rate was higher in patients with AHA although it wasn`t statistically significant. The main cause of death was related to infectious complications but most of the patients had a long history of immunosuppression treatment. Patients who relapsed and were treated again with rituximab had very good response rate. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Immunotherapy Treatments of Warm Autoimmune Hemolytic Anemia

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Bainan Liu ◽  
Wangang Gu
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Body Temperature ◽  
Hemolytic Anemia ◽  
Immune Suppression ◽  
Autoimmune Hemolytic Anemia ◽  
Clinical Studies ◽  
Treatment Strategies ◽  
Underlying Condition ◽  
Anti Cd20

Warm autoimmune hemolytic anemia (WAIHA) is one of four clinical types of autoimmune hemolytic anemia (AIHA), with the characteristics of autoantibodies maximally active at body temperature. It produces a variable anemia—sometimes mild and sometimes severe. With respect to the absence or presence of an underlying condition, WAIHA is either idiopathic (primary) or secondary, which determines the treatment strategies in practice. Conventional treatments include immune suppression with corticosteroids and, in some cases, splenectomy. In recent years, the number of clinical studies with monoclonal antibodies and immunosuppressants in the treatment of WAIHA increased as the knowledge of autoimmunity mechanisms extended. This thread of developing new tools of treating WAIHA is well exemplified with the success in using anti-CD20 monoclonal antibody, Rituximab. Following this success, other treatment methods based on the immune mechanisms of WAIHA have emerged. We reviewed these newly developed immunotherapy treatments here in order to provide the clinicians with more options in selecting the best therapy for patients with WAIHA, hoping to stimulate researchers to find more novel immunotherapy strategies.

scholarly journals Use of Rituximab in Autoimmune Hemolytic Anemia Associated with Non-Hodgkin Lymphomas

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Claudio Fozza ◽  
Maurizio Longinotti
Keyword(s):  
Monoclonal Antibody ◽  
Chronic Lymphocytic Leukemia ◽  
Hemolytic Anemia ◽  
Antibody Production ◽  
Autoimmune Hemolytic Anemia ◽  
Therapeutic Approach ◽  
Lymphoproliferative Disorders ◽  
Lymphocytic Leukemia ◽  
Pathogenetic Mechanism ◽  
Anti Cd20

The association between non-Hodgkin lymphomas and autoimmune disorders is a well-known event. Also autoimmune hemolytic anemia (AHA), although much more frequent in patients with chronic lymphocytic leukemia (CLL), has been described in this group of patients. In recent years, among the more traditional therapeutic options, rituximab, an anti-CD20 monoclonal antibody, has shown interesting results in the treatment of primary AHA. Although this drug has been frequently used for AHA in patients with CLL, much less data are available on its use in NHL patients. However, considering that the main pathogenetic mechanism of AHA in course of lymphoproliferative disorders seems to be an antibody production directly or indirectly mediated by the neoplastic clone, this monoclonal antibody represents an ideal therapeutic approach. In this paper we will briefly describe some biological and clinical features of NHL-patients with AHA. We will then analyze some studies focusing on rituximab in primary AHA, finally reviewing the available literature on the use of this drug in NHL related AHA.

scholarly journals Murine autoimmune hemolytic anemia resulting from Fc gamma receptor- mediated erythrophagocytosis: protection by erythropoietin but not by interleukin-3, and aggravation by granulocyte-macrophage colony- stimulating factor

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2960-2964 ◽  
Author(s):  
T Berney ◽  
T Shibata ◽  
R Merino ◽  
Y Chicheportiche ◽  
V Kindler ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Colony Stimulating Factor ◽  
Fc Gamma Receptor ◽  
Interleukin 3 ◽  
Gamma Receptor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract We have evaluated the therapeutic activity of recombinant erythropoietin (rEpo), in comparison with recombinant interleukin-3 (rIL-3) and granulocyte-macrophage colony-stimulating factor (rGM-CSF), on a lethal form of acute anemia resulting from Fc gamma receptor- mediated erythrophagocytosis after a single injection (500 micrograms) of a monoclonal anti-mouse red blood cell (MRBC) autoantibody. Continuous perfusion of rEpo before the administration of anti-MRBC monoclonal antibody completely protected animals from death due to anemia with a rapid recovery, while no protection was obtained by rIL-3 perfusion. In contrast, rGM-CSF perfusion markedly accelerated the progression of anemia and the mortality rate. This was found to result from an enhancement of erythrophagocytosis by Kupffer cells and by polymorphonuclear leukocytes that massively infiltrated the livers. Even after the injection of a sublethal dose (100 micrograms) of anti- MRBC monoclonal antibody, rGM-CSF-perfused mice died of a severe form of acute anemia. Furthermore, we have shown that rEpo was able to treat efficiently a spontaneous form of autoimmune hemolytic anemia in a majority of anemic NZB mice, whereas rGM-CSF markedly aggravated anemia. This may be of clinical importance, because GM-CSF administration could exhibit an adverse effect in some autoimmune diseases that involve autoimmune anemia.

scholarly journals Low Dose Rituximab Plus High Dose Dexamethasone As First-Line Treatment for Autoimmune Hemolytic Anemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-14
Author(s):  
Carlos Saúl Rodríguez-Roque ◽  
Andres Gomez-De Leon ◽  
Michelle Morcos-Sandino ◽  
Nelson Josafat López-Flores ◽  
David David Galindo-Calvillo ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Low Dose ◽  
Complete Response ◽  
Event Free Survival ◽  
First Line ◽  
Advisory Committees ◽  
Free Survival ◽  
Loss Of Response

Introduction Corticosteroids are the first line therapy for autoimmune hemolytic anemia (AIHA), but are associated with significant adverse events, dependency and frequent relapses. Rituximab is reserved for severe or steroid-resistant disease. Low-dose rituximab is also effective, but its efficacy in the first line has been poorly described. We report our results with this combination. Methods Adults older than 16 years newly diagnosed with warm antibody AIHA either primary or secondary were included. Patients systematically received dexamethasone 40 mg for 4 days followed by a 1 mg/kg rapid prednisone taper plus rituximab 100 mg weekly for 4 doses. Our primary outcome was response at day 28 based on the First International Consensus Meeting (complete response: normalization of Hb, no evidence of hemolysis and absence of transfusions; response: increase of Hb by >2g/dl, or normalization of biochemical resolution of hemolysis or absence of transfusion in 7 days), secondary outcome was event-free survival with an event defined as a laboratory or clinical relapse or loss of response. Results Sixteen patients were treated with low-dose rituximab during the study period, ten women (62.5%), six men (37.5%). The median age was 34 years (range, 17-78). Three (18.75%) were secondary to lupus erythematosus. The median follow-up was 20 months (range, 0.4-66). Most received 4 doses of rituximab (87.5%). All patients responded at day 28, (100%) 31.2% achieved a complete response (CR). Subsequently, 81.3% achieved CR. Ten (62.5%) were considered steroid-dependent, however, most discontinued treatment without loss of response (75%). The event-free survival was 63.8% to 5 years. Conclusion Low-dose rituximab therapy as a first-line in AIHA showed encouraging results as most patients were able to discontinue treatment without relapse. Disclosures Gomez-Almaguer: Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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