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.

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.

Clinical Heterogeneity Of Autoimmune Hemolytic Anemia: A 35-Years Retrospective Study Of 157 Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3428-3428
Author(s):  
Wilma Barcellini ◽  
Bruno Fattizzo ◽  
Tommaso Radice ◽  
Anna Zaninoni ◽  
Nicoletta Revelli ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Conflicts Of Interest ◽  
Acute Infection ◽  
Thermal Characteristics ◽  
Response Rates ◽  
Cytotoxic Drugs ◽  
Clinical Heterogeneity ◽  
Life Threatening

Abstract The clinical presentation of autoimmune hemolytic anemia (AIHA) is greatly heterogeneous, from mild/compensated to life-threatening forms. The aim of this study was to correlate the clinical and serological characteristics of the disease, usually classified as warm (WAIHA), cold (CHD), and mixed, based on the thermal and isotype characteristics of the anti-RBC antibody (IgG, IgM or both, respectively). One-hundred fifty seven AIHA patients (61 M and 96 F, median age 57, range 5-95) referred to our institution from 1978 to September 2012 were investigated. They had been followed-up for a median of 26 months (range 12-271), and 50% were still in follow-up. As regards the thermal characteristics 40% of cases were WAIHA, 32% CHD, 19% mixed forms and 9% atypical (12 DAT negative and 1 DAT positive for IgA only). Considering the severity of anemia at onset 33% of cases had Hb levels<6 g/dl, 34% Hb 6-8 g/dL, 18% Hb 8-10 g/dL, and 15% Hb>10 g/dL. The most severe AIHA cases were mainly mixed (18/30, 60% p=0.001) and atypical (6/13, 46%) forms, whereas only a small fraction of CHD was characterized by a severe onset (8/51, 16% p=0.002). Reticulocytopenia (<100.000 mmc) was more frequently observed in cases with severe onset (14/52, 27%), possibly contributing to the clinical picture. Eleven patients experienced an acute event at the onset of hemolysis and the majority of them (7/11, 63% ) were WAIHA; we recorded 4 deep venous thrombosis (with 2 subsequent pulmonary embolisms), 1 disseminated intravascular coagulation, 3 cardiac ischemic events, 2 acute renal failure and 4 acute infection (3 pneumonias and 1 sepsis); 18 patients died because of AIHA during the follow up. As regard therapy, we considered steroids, splenectomy, cytotoxic drugs and rituximab: 45% of cases (mostly WAIHA) were treated with steroids only, 23% with 2 lines, 10% with 3, and 6% with 4 or more lines; splenectomy was performed in 20 cases, mostly mixed and severe forms (p=0.001); 23 patients were treated with various cytotoxic drugs, and 33 with rituximab (the latter was more frequently administered in clinically severe cases, and in mixed and atypical forms, p=0.009). On the whole, the most severe patients were those who underwent 3 or more lines of therapy, compared with the other cases (14/52 versus 11/105, p=0.015). Finally, 16% of cases have never been treated, mostly CHD with mild anemia. Transfusions were performed in 65 cases, plasma-exchange in 3 (all with Hb<6 g/dL), and erythropoietin administered in 6 cases. Of note, the presence of an Hb value lower than 6 g/dL at onset was a risk factor for the requirement of 3 or more lines of therapy (odds ratio 3.148, CI 95% 1.312-7.552). Response rates to steroid therapy were similar in warm, cold, mixed and atypical AIHAs (on average 70%). Responses to rituximab were similar in cold and other AIHA forms (70-80%). Splenectomy, was ineffective in the 2 CHD who underwent surgery, whereas response rates were 63% in WAIHA and 80% in mixed and atypical cases. In conclusion, AIHAs showed a marked clinical heterogeneity, 1/3 of cases with a severe onset and with life threatening complications. These cases are frequently mixed or atypical forms and refractory to different therapies. Disclosures: No relevant conflicts of interest to declare.

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.

A Rare Cause of Anemia in Inflammatory Bowel Diseases: A Case Report and Review of Literature

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5385-5385
Author(s):  
Waqas Ahmed ◽  
Kevin Monroe ◽  
James Essell ◽  
E. Randolph Broun
Keyword(s):  
Case Report ◽  
Hemolytic Anemia ◽  
Inflammatory Bowel Diseases ◽  
Autoimmune Hemolytic Anemia ◽  
Blood Smear ◽  
Rare Complication ◽  
Peripheral Blood Smear ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Introduction: Anemia is a common problem in patients with inflammatory bowel diseases (IBD), and its etiology is usually multifactorial. It can be produced by chronic blood loss, nutritional deficiencies, and drugs such as salazopyrine; however it can also due to auto immune hemolysis, which is a rare complication of IBD. We report a case of coombs positive autoimmune hemolytic anemia associated with ulcerative colitis both diagnosed at the same presentation. Case Report: A 32 year old man with no significant past medical history presented with complaint of dark colored urine, jaundiced skin and fatigue for 4 weeks. He also reported diarrhea mixed intermittently with blood for last few months. Physical exam was consistent with jaundice and anemia (pallor and icterus) with slightly palpable spleen. Initial lab work up showed Hb of 3.8 with normal platelet and WBC count, high reticulocytes count of 7% .LFT showed serum bilirubin of 3.6 (direct 0.4) with normal serum ALT and AST levels .Serum LDH was high (1032 U/l) while serum haptoglobin was low (0.11 mg/dl). Peripheral smear showed anisopoikilocytosis & spherocytosis. (See Figure 1) Further investigations revealed a positive direct Coombs test consistent with diagnosis of autoimmune hemolytic anemia. CT abdomen and pelvis showed mild splenomegaly & non-specific enlarged mesenteric lymph nodes. Colonoscopy revealed ulcerative pancolitis confirmed by histological findings of biopsies taken. Patient received PRBC transfusions and was started on steroids and mesalamine and was discharged on maintenance dose. His symptoms resolved in 4 weeks and Hb remained stable with no evidence of further hemolysis at 4 month follow up .Repeated CT abdomen & pelvis showed resolution of the lymphadenopathy. Figure 1: Peripheral Blood smear showing anisopoikilocytosis & spherocytosis. Figure 1:. Peripheral Blood smear showing anisopoikilocytosis & spherocytosis. Discussion: Autoimmune hemolytic anemia (AIHA) is a rare complication of IBD. The exact underlying pathogenesis of this association remains obscure; however it has been attributed to the production of cross reacting anti erythrocyte antibodies. In AIHA associated with IBD, corticosteroids are considered to be first line therapy and often cause remission of hemolysis along with treatment for IBD Immunomodulators and splenectomy has been used for patients with refractory AIHA. Colectomy done for fulminant colitis has also been reported to induce remission of AIHA. Further studies for long term follow up and pathogenesis of this association are warranted.

The First Reported Case of Prenatal Diagnosis for Pyruvate Kinase Deficiency in a Chinese Family

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5276-5276
Author(s):  
Jason CC So ◽  
Mary Tang ◽  
Rever Li ◽  
Shau Yin Ha ◽  
Serge Pissard ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Prenatal Diagnosis ◽  
Ethnic Groups ◽  
Pyruvate Kinase ◽  
Hemolytic Anemia ◽  
Pediatric Patients ◽  
Conflicts Of Interest ◽  
Chinese Family ◽  
First Case

Abstract Abstract 5276 Pyruvate kinase (PK) deficiency of red cells (EC: 2.7.1.40) is the commonest inherited enzyme deficiency in the glycolytic pathway, leading to chronic non-spherocytic hemolytic anemia (CNSHA). There are over 220 characterized mutations deposited in a public database (PKLR Mutation Database http://www.pklrmutationdatabase.com). Heterozygous carriers are asymptomatic but homozygotes or compound heterozygotes can have significant anemia leading to transfusion dependency, neonatal death and hydrops fetalis. All ethnic groups are affected but data on Chinese are very scanty. We describe the first case of prenatal diagnosis for PK deficiency in Chinese and emphasize that this disease is an important differential diagnosis in pediatric patients with hemolytic anemia. A Han Chinese presented with hepatosplenomegaly, severe anemia and unconjugated hyperbilirubinemia at birth, necessitating exchange transfusion on day 1 and prolonged phototherapy till day 10 of life. Glucose-6-phosphate dehydrogenase level was normal. His parents were unrelated and asymptomatic. Family history was unremarkable. He developed severe CNSHA on follow up, requiring monthly red cell transfusion to relieve symptoms and to maintain satisfactory growth. Iron chelation therapy was started at 2 years of age and splenectomy was performed at 4 years to reduce transfusion requirement. The baseline PK enzyme level was not known but both parents had a mildly reduced PK level. Genetic analysis of PKLR gene was performed. All 11 exons and promoter were screened using polymerase chain reaction (PCR)-denaturing high performance liquid chromatography followed by PCR-sequencing. The father was found to carry a mutation in exon 8: PKLR: c.1073 G>A (p.Gly358Glu) while the sequencing result was normal in the mother. Quantitative multiplex PCR of short fluorescent fragments detected a rare large deletion removing exon 4 to exon 10 of the PKLR gene in the mother. Gap-PCR mapping confirmed that it to be a deletion previously found in a Vietnamese family (Costa C et al Haematologica 2005) and an Australian family (Fermo E et al Br J Haematol 2005). Both mutations have not been previously reported in Chinese. The proband was found to carry the paternal point mutation and the maternal deletion. Because of the severe clinical course of their first child, the couple requested prenatal biopsy was performed at 12 week of gestation. The fetus was found to be simple heterozygous for the paternal mutation. Pregnancy was allowed to continue and a healthy baby was born. A PK assay performed at the age of 9 months was normal. Mutation studies in a peripheral blood sample at 10 months of age confirmed the PKLR genotype. There was no evidence of hemolytic anemia after 3 years of follow up. Because of its perceived rarity and benignity in many ethnic groups, PK deficiency does not enter early into the differential diagnosis of anemia in pediatric patients. Its potential to cause severe disease is often overlooked and delay in diagnosis is common (Pissard S et al J Pediatr 2007). Genetic characterization and genotype-phenotype correlation studies on PKLR in different populations are indicated to better characterize the disease spectrum and to define the role of prenatal diagnosis in PK deficiency. Disclosures: No relevant conflicts of interest to declare.

Low doses of humanized anti-CD20 antibody, IMMU-106 (hA20), in refractory or recurrent NHL: Phase I/II results

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8032-8032 ◽  
Author(s):  
F. Morschhauser ◽  
J. P. Leonard ◽  
L. Fayad ◽  
B. Coiffier ◽  
M. Petillon ◽  
...  
Keyword(s):  
Adverse Events ◽  
B Cell ◽  
Serum Levels ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Open Label ◽  
Clear Cut ◽  
Cd20 Antibody ◽  
Anti Cd20

8032 Background: An open-label, multicenter study has shown that the humanized anti-CD20 antibody, IMMU-106 (hA20), which has framework regions of epratuzumab, has a good safety and efficacy profile in NHL pts when administered once-weekly × 4 at different doses. The trial is now focused on confirming the efficacy of lower doses (80–120 mg/m2/wk × 4). Methods: A total of 68 pts (35 male, 33 female; age 34–84) received hA20 at 750 (N=3), 375 (N=27), 200 (N=11), 120 (N=21), or 80 mg/m2 (N=6). They had follicular (FL, N=47) or other (N=21) B-cell NHL, were predominantly stage III/IV (N=47) at study entry, and had received 1–8 prior treatments (median, 2), including 1 (N=40) or more (N=21) rituximab regimens (without progression within 6 months). Results: Sixty- six pts completed all 4 infusions; 1 pt progressed during treatment and withdrew, while another pt with hives and chills after prior rituximab discontinued treatment after a similar episode at 1st infusion. hA20 was generally well tolerated, with shorter infusion times (typically 2 h initially and 1 h subsequently) at lower doses. Drug-related adverse events were transient, Grade 1–2, most occurring only at 1st infusion, and there was no evidence of HAHA in 54 pts now evaluated. Mean antibody serum levels increased with dose and infusions; serum clearance at 375 mg/m2 appears similar to rituximab. Currently, 48 pts with at least 12 wks follow-up were evaluated by Cheson criteria: 32 FL pts had 15 (47%) OR's with 7 (22%) CR/CRu's, even after 2–4 prior rituximab-regimens, and 17 non-FL pts had 6 (38%) OR's, with 1 CRu in a marginal zone NHL pt. At a median follow-up of 11 mo., 9/21 pts with ORs are continuing responses, including 4 long-lived responses (15–20 mo). The evaluated pts include 17 pts at 120 mg/m2 who had 5 (29%) ORs with 3 (17%) CR/CRu's. Responses at 80 mg/m2 remain to be evaluated, but B-cell depletion occurs after the 1st infusion even at this low dose. Conclusions: hA20 appears well-tolerated, with no evidence of significant adverse events other than minor infusion reactions, even at short infusion times. B-cell depletion and responses have occurred at all doses evaluated, with no clear-cut evidence of a dose-response. As such, the study is continuing to confirm the efficacy of lower doses. No significant financial relationships to disclose.

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