A Retrospective Study of the Combination of Rituximab, Cyclophosphamide and Dexamethasone for the Treatment of Relapsed/Refractory Warm Antibody Autoimmune Hemolytic Anemia

2019 ◽  
Vol 143 (3) ◽  
pp. 244-249 ◽  
Author(s):  
Caroline I. Piatek ◽  
Hillel Bocian ◽  
Sandra Algaze ◽  
Ilene C. Weitz ◽  
Casey O'Connell ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Immune Modulation ◽  
Complete Response ◽  
Primary Objective ◽  
Additional Treatment ◽  
Lymphocytic Leukemia ◽  
Immunocompromised Patients ◽  
Treatment Changes

The combination of rituximab, cyclophosphamide, and dexamethasone (RCD) is highly effective in the treatment of warm autoimmune hemolytic anemia (WAIHA) associated with chronic lymphocytic leukemia (CLL). We treated a cohort of patients with relapsed/refractory WAIHA, without CLL, with RCD. The primary objective was to evaluate the overall response (OR) of RCD therapy. Complete response (CR) was defined as a hemoglobin (Hgb) ≥12 g/dL. Partial response (PR) was defined as Hgb 10–11.9 g/dL or ≥2 g/dL increase in Hgb. Sustained response was defined as Hgb ≥10 g/dL with no treatment changes. A total of 16 patients with relapsed/refractory WAIHA received RCD (7 primary WAIHA, 9 secondary WAIHA) for a median of 4 cycles (range: 2–6). The median pretreatment Hgb was 10.0 g/dL (range: 4.3–12.2). The median best Hgb achieved was 12.5 g/dL (range: 10.6–15.1) with a median of 2 cycles until best Hgb response. The OR was 94% (11 CR, 4 PR). Two immunocompromised patients were admitted for infections during RCD treatment. There were no deaths during the treatment or follow-up period. Following a response to RCD, 4 patients received noncorticosteroid immune modulation therapy and 4 patients continued on corticosteroid therapy. Seven patients received no additional treatment.

Rituximab in the Treatment of Adults with Chronic Idiopathic Thrombocytopenic Purpura (ITP) and Autoimmune Hemolytic Anemia (AIHA).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3930-3930 ◽  
Author(s):  
Ghassan Zalzaleh ◽  
Ahmad Jajeh ◽  
Diemante Tamoseviciene
Keyword(s):  
Partial Response ◽  
Hemolytic Anemia ◽  
Complete Response ◽  
Pure Red Cell Aplasia ◽  
Lymphocytic Leukemia ◽  
Overall Response ◽  
Medical Centers ◽  
History Of ◽  
Refractory Itp

Abstract Corticosteroids have been the first line of treatment of ITP since 1950, however some patients do not respond to this treatment (refractory) and some will relapse after its discontinuation. For such patients second line treatments were introduced. Some patients will continue to be refractory to this treatment and need other therapy modality. Rituximab is a chimeric monoclonal antibody directed against the CD20 antigen exposing B Lymphocytes, causing its depletion. This could alter the production of auto-antibodies in some Auto-Immune diseases and thus could be used in their treatment. Few medical centers had reported using Rituximab in the treatment of refractory (ITP) and (AIHA), yet its definite role could not be determined, and here we share our experience. Patients with documented diagnosis of ITP or AIHA who were refractory to at least two lines of therapy including steroids were offered to receive Rituximab (375mg/m2 weekly for 4 weeks). 15 patients were enrolled, 10 with ITP, 4 with AIHA, 1 with Coombs negative Hemolytic anemia, and 1 with pure red cell aplasia. One had both ITP and AIHA. 10 were females and 5 males. 5 were >60 years old and 10 were < 60 years old. 2 out of the 10 patients with ITP had also Chronic Lymphocytic Leukemia (CLL). Duration of follow up ranged from 2 months to 17 months (average 7 mos). Of the 10 patients with refractory ITP treated with Rituximab overall response was 60%. 4 were NR (no response), 2 were MR (minimal response: Platelets increased to <50000), 2 were PR (Partial response: Platelets increased to <100000) and 2 were complete response (Platelets became normal). 3 patients of 6 with Hemolytic anemia or PRC aplasia had NR, 1 had MR (Hct <30), and 2 had partial response (Hct 30–35). No complete response was observed in this group. In 3 patients with hemolytic anemia and CLL 1 had MR, 1 had PR and 1 had NR. 2 patients with hemolytic anemia who had NR died as a complication of their disease (one with septic shock and one with severe autoimmune flare up). Only one patient with refractory ITP had mild allergic side effects and did not complete 4 doses. No Rituximab related mortality was observed. CONCLUSION: Rituximab therapy had a variable but valuable effect in the treatment of patients with chronic refractory ITP and refractory/ relapsed AIHA. Overall response in our group reached 60%. No clinical or laboratory parameters were found to predict response, although there was a suggestion that males, younger age, and no history of splenectomy have a better chance of response. As we lack an effective alternative treatment in chronic refractory ITP and AIHA, Rituximab use could be a valid option in view of its mild toxicity. Further follow up of our patients and input from other institutions in this regard are needed.

scholarly journals Safe Start of Ibrutinib in Patients with Chronic Lymphocytic Leukemia and Uncontrolled Autoimmune Hemolytic Anemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5560-5560 ◽  
Author(s):  
Alejandro Garcia-Horton ◽  
Rosanne St. Bernard ◽  
Alejandro Lazo-Langner ◽  
Anargyros Xenocostas ◽  
Joy Mangel ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Conflicts Of Interest ◽  
Case Reports ◽  
Laboratory Data ◽  
Case Series ◽  
Lymphocytic Leukemia ◽  
Positive Direct

Abstract It is estimated that 4-10% of patients with chronic lymphocytic leukemia (CLL) will develop autoimmune hemolytic anemia (AIHA) over the course of their disease. Ibrutinib has proven to be effective in treatment of relapsed, refractory, 17p deleted, and treatment naïve CLL. The effect of ibrutinib on AIHA in the context of CLL has not been established since patients with active hemolysis were excluded from major trials. In this abstract, we present a case series of patients that were actively hemolyzing at the start of ibrutinib therapy and in which their AIHA achieved prolonged response. Patient characteristics and laboratory data are shown in Table. Five patients (3 women, 2 men), median age 61 years (range 57 to 78), with CLL and active, uncontrolled AIHA at the time of ibrutinib initiation were identified. Uncontrolled AIHA was defined as anemia with evidence of hemolysis (at least two of the following: increased reticulocyte count, elevated lactate dehydrogenase, elevated indirect bilirubin, and reduced haptoglobin and a positive direct antiglobulin test (DAT)). Patients had a median hemoglobin of 70 g/L (range 69-96) prior to start of ibrutinib and 3 of them required transfusion support for symptomatic anemia. All patients were receiving prednisone for management of AIHA at the time of ibrutinib initiation and had been on it for a median of 10 days (range 9 - 25) without AIHA resolution. 1 patient received intravenous immunoglobulin concurrently. All patients had received at least one line of therapy for CLL in the past and 3 had experienced previous AIHA responsive to steroids. AIHA in 2 patients was related to previous fludarabine exposure but had responded to a prednisone tapering schedule and were off steroids by the time of the new AIHA flare. Median hemoglobin of 130 g/L (range 113-149) was reached at time of AIHA response. All 5 patients tolerated 420mg oral daily of ibrutinib therapy and AIHA was controlled in a median of 6.5 weeks (range 6-10). Discontinuation of steroids was achieved in all patients at a median of 10 weeks (range 6-17) without evidence of further hemolysis. All patients except one are receiving ongoing follow up and have been followed up for a median of 130 weeks (range 15-150) since ibrutinib start. Patients have not shown evidence of AIHA relapse and continue off AIHA treatment (prednisone). One patient required discontinuation of ibrutinib 6 months after starting due to neutropenia but there was no evidence of AIHA relapse in follow up. The patient has passed away from unrelated GI bleed 2 years after the initial AIHA event. This is the largest case series to our knowledge on the safe start of ibrutinib in CLL complicated by active AIHA. Hemolysis in all patients responded to a short prednisone taper with ibrutinib concurrently and obtained a sustained response at follow up without any flare ups or further AIHA treatment use. These cases suggest that it is safe to start ibrutinib during uncontrolled, active hemolysis in contrast to 2 previous case reports that suggested causal relationship between ibrutinib and onset of severe CLL-associated AIHA (Rider et al, 2015; Hodskins et al, 2014). As previously reported, AIHA occurrence or relapse once ibrutinib has been started is rare (Rogers et al, 2016). Disclosures No relevant conflicts of interest to declare.

Favorable and Sustained Response of Primary Autoimmune Hemolytic Anemia to Rituximab

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5160-5160
Author(s):  
Abdul Kareem M Al-Momen ◽  
Aamer Aleem ◽  
Farjah Al Gahtani ◽  
Rana Hasanato ◽  
Farhan Ali Anjum ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Age Groups ◽  
Autoimmune Disorder ◽  
Significant Rise ◽  
Lymphocytic Leukemia ◽  
Variable Response ◽  
Immune Modulators ◽  
Adults And Children

Abstract Abstract 5160 Background: Primary autoimmune hemolytic anemia (PAIHA) is a rare autoimmune disorder that males and females of all age groups, but more frequent in young adults. Most patients respond initially to steroids and intravenous immunoglobulin's followed by Splenectomy for non-responders. Around one third of the patients do not respond to any standard treatment and another one third show only transient response and therefore labeled as refractory PAIHA. In this refractory group, various immune modulators and suppressants are used with variable response. These include azathioprine, vincristine, cyclophosphamide and mycophenolate. The Aim: The aim of our study is to explore the safety and efficacy of Rituximab in the treatment of refractory, PAIHA. Patients and methods: Thirteen patients (seven males and six females, aged 33. 7 +/− 15 years) with refractory PAIHA (Hb 73. 1 +/− 13. 9 g/l) were given Rituximab 375 mg/m2 intravenously weekly for four weeks, then monthly for four months. Results: All patients showed a rapid and favorable response with significant rise in Hb level to 128 +/− 10. 8 g/l within four months. Rituximab was tolerated very well and the response was sustained in all patients during the follow up to 25. 6 +/− 21. 8 months Conclusion: Rituximab is probably highly effective in the treatment of refractory PAIHA with sustainable response. This has been shown in refractory autoimmune hemolytic anemia in adults and children as well as in chronic lymphocytic leukemia associated autoimmune hemolytic anemia (1–3) Disclosures: Off Label Use: Rituximab was used in Primary Autoimmune Hemolytic Anemia compassionately.

Efficacy and Safety of Monoclonal Anti-CD20 Antibody Rituximab Combined Cyclophosphamide in Treatment of Refractory and Recurrent Autoimmune Hemolytic Anemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5161-5161
Author(s):  
Zonghong Shao ◽  
Hong Liu ◽  
Limin Xing ◽  
Yuhong Wu ◽  
Wen Qu ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Conflicts Of Interest ◽  
Additional Treatment ◽  
Efficacy And Safety ◽  
Indirect Bilirubin ◽  
Mean Response Time ◽  
Cd20 Antibody ◽  
Anti Cd20

Abstract Abstract 5161 Objectives: To better assess the efficacy and safety of monoclonal anti-CD20 antibody rituximab in the treatment of refractory and recurrent autoimmune hemolytic anemia. Patients and methods: 7 cases with autoimmune hemolytic anemia (including 1 case of Evans syndrome) were enrolled into this study, they were treated with rituximab (375 mg/m2, once per week, 2–6 times) and Cyclophosphamide(1g/10days, 2–6 times) combined with intravenous immunoglobulin (IVIG) (10g/week, given 1 day after rituximab treatment). Results: All 7 patients showed good responses. 6 achieved complete remission (CR) and 1 achieved partial remission (PR). Responses were seen at 1th to 10th month after the first dose of rituximab and the mean response time was approximately 2. 5 months. Average follow-up time for them isfor the patients was 27 months. All patients remained in remission at the 12-month follow-up. At the time of 24-month follow up, 3 patients showed elevated indirect bilirubin and increased reticulocyte counts. One of the 3 patients achieved CR after additional rituximab therapy, and the other 2 PR after additional cyclophosphamide therapy. At the time of 36-month follow up, 1 patient relapsed and was retreated with 3 cycles of rituximab and eventually reached PR. All patients tolerated the treatment well with only mild side effects. Conclusion: rituximab is highly effective and relatively safe in patients with refractory and recurrent autoimmune hemolytic anemia. Maybe Additional treatment can be given in patients with relapse after 1–2 years. Disclosures: No relevant conflicts of interest to declare.

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

1996 ◽  
Vol 38 (4) ◽  
pp. 359-360 ◽  
Author(s):  
G. Tertian ◽  
J. Cartron ◽  
C. Bayle ◽  
A. Rudent ◽  
T. Lambert ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Lymphocytic Leukemia

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 &gt;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.

Kaposi sarcoma following autoimmune hemolytic anemia in a patient with chronic lymphocytic leukemia

2018 ◽  
Vol 12 (1) ◽  
pp. 99-102 ◽  
Author(s):  
Utku Iltar ◽  
Vedat Aslan ◽  
Mesut Gocer ◽  
Fatma Aykac ◽  
İlknur Nizam ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Kaposi Sarcoma ◽  
Lymphocytic Leukemia

scholarly journals Autoimmune Hemolytic Anemia After Relapse of Chronic Myeloid Leukemia: A Case Report

2019 ◽  
Vol 12 ◽  
pp. 1179545X1989457
Author(s):  
Tahseen Hamamyh ◽  
Mohamed A Yassin
Keyword(s):  
Case Report ◽  
Chronic Myeloid Leukemia ◽  
Chronic Lymphocytic Leukemia ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Lymphocytic Leukemia ◽  
Sudden Drop ◽  
Leukemia Relapse

Autoimmune hemolytic anemia is one of the differential diagnoses for anemia in patients with lymphoproliferative neoplasia, such as chronic lymphocytic leukemia, who experience sudden drop in hemoglobin. The association between autoimmune hemolytic anemia and chronic myeloid leukemia on the contrary is unusual. Here we present a patient with a background of chronic myeloid leukemia treated previously with Tyrosine Kinase Inhibitors, then developed autoimmune hemolysis simultaneously with chronic myeloid leukemia relapse. Hemolysis was treated with steroids with good response.

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