Autoimmune Cytopenias and Covid-19 Vaccination: Relapse and Suggested Treatment

Abstract Introduction: There are "de novo" and relapsed autoimmune diseases in patients with COVID-19 that includes autoimmune thrombocytopenia, Evans syndrome and autoimmune hemolytic anemia among others (Hematology 2021;26:225-239 and Curr Rheumatol Rev 2021;17:193-204). There is scanty material about relapse of autoimmune hematological diseases after vaccination for COVID-19 (Blood Adv 2021;13:2794-2798). Material and methods: Adult patients 18 years or older with autoimmune thrombocytopenia, Evans syndrome and autoimmune hemolytic anemia who completed SARS-Cov2 vaccination. Results: Between December 2020 and June 2021 there were identified 53 patients with autoimmune hematological disease that completed SARS-Cov2 vaccination. Thirty-six with autoimmune thrombocytopenia, all were preexisting. Twelve with autoimmune hemolytic anemia, 5 secondaries to previous COVID-19 and 7 preexisting. Five with Evans syndrome, all preexisting. Twenty-three patients with autoimmune thrombocytopenia did not develop any fall in the platelet count. Ten patients had a fall of 50 % from basal counts and recovered spontaneously. Three patients developed counts below 30,000 with purpuric symptoms and needed treatment that consisted in two courses of dexamethasone 40 mg daily for four days every three weeks; all patients reached complete remission without any further treatment. All patients with Evans syndrome developed hemolysis and low platelet counts. Two patients maintained Hb levels above 10 and platelet counts above 50,000; both patients had spontaneously recovery. Three patients developed Hb levels below 7 with anemic syndrome and platelets below 50,000 but without purpuric syndrome; they received the same treatment as patients with autoimmune thrombocytopenia and reached complete remission too. All five patients with autoimmune hemolytic anemia secondary to COVID-19 developed Hb levels below 7 with anemic symptoms and needed treatment as described. The remaining 7 patients with preexisting autoimmune anemia developed hemolysis; five with Hb levels above 7 and recovery without any treatment; two had Hb levels below 7 and received the same treatment with full recovery and complete remission. Conclusions: Autoimmune cytopenias can be trigger by vaccines and viral infections by involving molecular mimicry and circulating immune complexes, including SARS-Cov2. The viral protein spike from SARS-Cov2 has mimicry between the Ankyrin-1 in the erythrocyte surface, and has been linked as one of the pathogenesis pathways of autoimmune hemolytic anemia secondary to COVID-19 (Br J Haematol 2020;190:e92-e93 and Blood 2020;136:suppl8,138001). Relapse of autoimmune cytopenias after vaccination with SARS-Cov2 involves stimulation of autoantibodies production from preexisting B cells. Although relapses were observed in the three kinds of patients, all with hemolytic component developed a drop in the hemoglobin levels, most of them needed treatment. It is important to notice that patients with hemolytic autoimmune anemia secondary COVID-19 had severe relapse, event that support the mimicry mentioned lines above. It is important to follow up closely this kind of patients after SARS-CoV2 vaccination, we suggest weekly complete blood counts, and a short courses of high dose dexamethasone can induce curable responses if treatment is advised. Disclosures No relevant conflicts of interest to declare.

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Twice Daily Fludarabine and Cytarabine Combination (BID-FA) Is Effective in Pts with De Novo Acute Myeloid Leukemia (AML), Relapsed/Refractory (R/R) AML, High-Risk Myelodysplastic Syndromes (MDS), and Blast Phase Chronic Myeloid Leukemia (CML-BP)

Blood ◽

10.1182/blood.v120.21.4939.4939 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4939-4939

Author(s):

Hady Ghanem ◽

Hagop M. Kantarjian ◽

Farhad Ravandi ◽

Jorge E. Cortes ◽

Naveen Pemmaraju ◽

...

Keyword(s):

High Risk ◽

Complete Remission ◽

Myeloid Leukemia ◽

De Novo ◽

Chromosomal Abnormalities ◽

Conflicts Of Interest ◽

High Dose ◽

Platelet Recovery ◽

De Novo Aml ◽

To Receive

Abstract Abstract 4939 Background: High dose cytarabine containing regimens are still considered standard options for pts (pts) with AML relapsing after a first complete remission (CR1) lasting more than 12 months. No standard options exist for pts relapsing after shorter remission duration or with primary refractory disease. We conducted a phase II study assessing the efficacy and safety of twice daily fludarabine and cytarabine (BID FA) in pts with R/R AML, high-risk MDS and CML-BP. Pts and Methods: 147 pts with de Novo AML, R/R AML, intermediate-2 and high-risk MDS, and CML-BP, with a performance status of 3 or less, as well as normal organ functions were eligible. Pts were scheduled to receive fludarabine 15 mg/m2 intravenously (IV) q12 hrs on days 1 to 5 as well as cytarabine at the dose of 0. 5 g/m2IV over 2 hrs q12 hrs on days 1 to 5. GO was administered at the dose of 3 mg/m2 IV on day 1 for the first 70 pts enrolled. Courses were repeated every 4 to 6 weeks for a maximum of 7 courses. Pts with CML-BP were allowed to receive concomitant tyrosine kinase inhibitors. Four pts with AML who had FLT3 mutation were allowed to receive BID FA and sorafenib. Results: A total of 147 pts were treated. The median age was 63 years (range, 20 to 85 years). 131 (89%) had AML, 7 (5%) had high-risk MDS, and 9 (6%) had CML-BP. Of the 131 AML pts, 17 (12%) were de novo AML, 50 (38%) were in first salvage: first CR duration (CRD1) of less than 12 months in 39 pts (29%), and more than 12 months in 11 (9%) pts. Cytogenetic studies showed diploid karyotype in 52 pts (35%) and unfavorable chromosomal abnormalities involving chromosomes 5 and 7 in 30 pts (20%). 128 pts (87%) had a PS ≥1. Sixty-four pts (44%) had failed previous intensive chemotherapy, while 21 (14%) had failed targeted and hypomethylating agents. Forty-three (29%) pts had failed both. Overall, 34 pts (23%) achieved a complete remission (CR) and 8 (6%) achieved a CR without platelet recovery (CRp), for an overall response rate (ORR) of 29%. 6 pts received reinduction therapy, of which 3 achieved a CR. The CR rates for AML pts with frontline therapy, with relapsed AML with CRD1 ≥12 months, relapsed AML with CRD1< 12 months, and R/R AML beyond first salvage were 47%, 64%, 21%, and 14%, respectively. In CML-BP, 2 (22%) of 9 pts had objective responses (1 CR, 1 CRp). 1 of the 7 pts with MDS responded (Table 1). The treatment was well tolerated with only 7 of the pts experiencing grade 3 and 4 toxicities including mainly skin rash and increased liver enzymes. The overall 4-week mortality rate was 13%. With a median follow-up of 24 months (range, 10 to 33), 20 patients (14%) remained alive. The overall 6-month survival rate was 44%. The median overall survival (OS) and event free survival (EFS) were 5 months (range, 0. 1 to 33) and 1 month (range, 0. 1 to 33), respectively. The median CR/CRp duration was 12 months. Median OS for pts with de novo AML, a CRD1≥12 months, pts with CRD1<12 months and pts receiving second salvage and beyond were 8, 12, 5, and 4 months respectively. Median EFS for pts with de novo AML, a CRD1≥12 months, pts with CRD1<12 months and pts receiving second salvage and beyond were 3, 7, 1 and 1 month respectively. Conclusion: BID FA appears to be active with an ORR of 29% in a heavily pre-treated population. This combination is safe with a low rate of 4-week-mortality of 13%. Disclosures: No relevant conflicts of interest to declare.

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High-dose intravenous intact IgG infusion in refractory autoimmune hemolytic anemia (Evans syndrome)

The Journal of Pediatrics ◽

10.1016/s0022-3476(85)80405-4 ◽

1985 ◽

Vol 107 (5) ◽

pp. 744-746 ◽

Cited By ~ 47

Author(s):

Hideaki Oda ◽

Akihito Honda ◽

Katsuo Sugita ◽

Akira Nakamura ◽

Hironori Nakajima

Keyword(s):

Hemolytic Anemia ◽

Autoimmune Hemolytic Anemia ◽

High Dose ◽

Evans Syndrome

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High-dose cyclophosphamide for refractory autoimmune hemolytic anemia

Blood ◽

10.1182/blood-2002-01-0087 ◽

2002 ◽

Vol 100 (2) ◽

pp. 704-706 ◽

Cited By ~ 72

Author(s):

Victor M. Moyo ◽

Douglas Smith ◽

Isadore Brodsky ◽

Pamela Crilley ◽

Richard J. Jones ◽

...

Keyword(s):

Stem Cell ◽

Complete Remission ◽

Hemolytic Anemia ◽

Absolute Neutrophil Count ◽

Autoimmune Hemolytic Anemia ◽

High Dose ◽

Safety And Efficacy ◽

Stem Cell Rescue ◽

Age And Sex

Abstract High-dose cyclophosphamide, without stem cell rescue, has been used successfully to treat aplastic anemia and other autoimmune disorders. To determine the safety and efficacy of high-dose cyclophosphamide among patients with severe refractory autoimmune hemolytic anemia, we treated 9 patients with cyclophosphamide (50 mg · kg−1 · d−1 for 4 days) who had failed a median of 3 (range, 1-7) other treatments. The median hemoglobin before treatment was 6.7 g/dL (range, 5-10 g/dL). The median time to reach an absolute neutrophil count of 500/μL or greater was 16 days (range, 12-18 days). Six patients achieved complete remission (normal untransfused hemoglobin for age and sex), and none have relapsed after a median follow-up of 15 months (range, 4-29 months). Three patients achieved and continue in partial remission (hemoglobin at least 10 g/dL without transfusion support). High-dose cyclophosphamide was well tolerated and induced durable remissions in patients with severe refractory autoimmune hemolytic anemia.

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Most CD5+ B Lymphocytes Secrete IL-10 in Autoimmune Hemolytic Anemia/Evans Syndrome Patients

Blood ◽

10.1182/blood-2018-99-114395 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4887-4887

Author(s):

Limin Xing ◽

Manjun Zhao ◽

Hongli Zhu ◽

Zonghong Shao

Keyword(s):

B Cells ◽

Serum Level ◽

B Lymphocytes ◽

Hemolytic Anemia ◽

Autoimmune Hemolytic Anemia ◽

Cell Activation ◽

Conflicts Of Interest ◽

Enzyme Linked Immunosorbent Assay ◽

Newly Diagnosed ◽

Evans Syndrome

Abstract Objective: Autoimmune hemolytic anemia (AIHA)/Evans syndrome is a form of immune-related cytopenia characterized by autoantibodies directed against red blood cells. A subset of B lymphocytes expressing CD5 is found in patients with AIHA/Evans syndrome. Previous studies have shown that the number of CD5+ B lymphocytes is correlated with the severity of AIHA/Evans syndrome. IL-10 can be induced in various types of human B cells, including naive, memory, and CD5+B cells, following B-cell activation by Th-cell-dependent and TLR-dependent signals. This study is to investigate the secretion function of CD5+ B lymphocytes in AIHA/Evans syndrome (ES) patients. Methods: 25 untreated AIHA/ES patients, 28 remission AIHA/ES patients and 25 healthy controls (HCs) were enrolled in this study. The quantity of CD5+B lymphocytes which produce interleukin-10 (IL-10) (CD5+IL-10+) were detected by flow cytometry. CD5+ B lymphocytes were sorted from Peripheral blood (PB) by CytoFLEX Flow Cytometer. The expression of IL-10 mRNA in CD5+ B cells were measured by real-time PCR (RT-PCR). The concentrations of IL-10 in serum were detected by Enzyme-linked Immunosorbent assay (ELISA). Results: The percentage of CD5+IL-10+B cells in CD5+ B lymphocytes in newly diagnosed patients was 82.18±14.78%, which being significantly higher than that of remission AIHA/ES patients (56.68±24.39%) and HC (51.90±22.95%)(p<0.05). The percentage of CD5+IL-10+ B cells in CD5+ B lymphocytes in newly diagnosed patients was negatively correlated with their serum level of hemoglobin, C3 (P<0.05) and positively correlated with their serum level of LDH, TBIL and IBIL (P<0.05). The expression level of CD5+ B lymphocytes IL-10 mRNA in newly diagnosed patients (49.34±22.84) was higher than that of remission patients (3.97±3.83) and HC (1.78±1.66) (P<0.05). The concentration of IL-10 in serum in newly diagnosed patients (4.01±1.54 pg/ml) was lower than that of remission patients (5.08±1.72pg/ml) and HC (5.70±1.60pg/ml) (P<0.05). Conclusions: Most CD5+ B lymphocytes secrete IL-10 in AIHA/Evans patients and are positively correlated with the severity of the disease. The increased quantity of CD5+IL-10+ B cells and the decreased cytokines-secreted level maybe involved in the occurrence of AIHA/Evans syndrome. Disclosures No relevant conflicts of interest to declare.

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Expression of Activated Molecules on CD5+ b Cells in Autoimmune Hemolytic Anemia

Blood ◽

10.1182/blood.v126.23.4765.4765 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4765-4765

Author(s):

Hongli Zhu ◽

Limin Xing ◽

Hong Liu ◽

Huaquan Wang ◽

Rong Fu ◽

...

Keyword(s):

B Cells ◽

B Lymphocytes ◽

Hemolytic Anemia ◽

Autoimmune Hemolytic Anemia ◽

Conflicts Of Interest ◽

Newly Diagnosed ◽

Evans Syndrome ◽

Hla Dr ◽

Significant Difference ◽

Normal Controls

Abstract Objective To detect the percentage of CD5+ B cells in peripheral blood (PB) of patients with autoimmune hemolytic anemia (AIHA) /Evans syndrome and the expression of active molecules on CD5+ B cells. Methods The expressions of CD80, CD86, CD69 and HLA-DR on CD5+ B cells in PB of 25 cases with AIHA/Evans syndrome, (11 newly diagnosed, 14 remission) and 14 normal controls were detected by flow cytometry. Results (1) The percentage and the quantity of CD19+ B cells in newly diagnosed patients were [(22.78±19.77)%, (34.47±22.88)×107/L] respectively, which were obviously higher than those of remission patients [(6.80±5.47)%,(10.09±7.69)×107/L] and normal controls [(7.76±2.6)%,(10.03±3.31)×107/L](p<0.05), but there was no significant difference between the latter two groups. (2)The percentage of CD5+ B cells in B cells of untreated patients was [(27.44±18.43) %], which was higher than that of normal controls [(13.49±6.95) %, P=0.008]. The percentage of CD5- B cells of untreated patients and normal controls were [(72.56±18.43) %], [(83.92±11.46) %] and there was no significant difference. (3)CD80 on CD5+ B cells of untreated patients was [(46.04±26.93)%], which was obviously higher than that of remission patients [(8.82±8.78)%,P=0.003] and normal controls [(6.27±4.87)%,P=0.002], the latter two groups had no significant difference. There was no significant difference of CD80 on CD5- B cells among the three groups. CD86 on CD5+ B cells of untreated patients was [(37.37±24.18)%], which was significantly higher than that of remission patients [(16.53±10.31)%,P=0.004] and normal controls [(14.90±9.62)%,P=0.029], the latter two groups had no significant difference. But CD86 on CD5- B cells are similar in the three groups and there was no difference. CD69 on CD5+ B cells of newly diagnosed patients was (median: 5.77%), which was higher than that of remission patients (3.34%) and normal controls(4.01%), but without any significant difference within three groups. CD69 on CD5- B cells showed no significant difference among three groups. HLA-DR on CD5+ B cells and CD5- B cells showed no significantly difference within three groups. (4)The expression of CD80[(46.04±26.93)%] and CD86[(37.37±24.18)%] on CD5+ B cells were higher than those on CD5- B cells [(22.57±10.54)%,P=0.016], [(17.92±16.27)%,P=0.006]. The expression of CD69 (median: 5.77%) on CD5+ B cells was higher than that of on CD5- B cells (median: 1.20%), but without significant difference. The expression of HLA-DR on CD5+ B cells and CD5- B cells had no significant difference. (5)The expression of CD80 on CD5+ B cells [(8.82±8.78) %] was lower than that of on CD5- B cells [(28.68±18.59) %, P=0.001]. The expression of CD86, CD69 and HLA-DR on CD5+ B cells and CD5- B cells showed no significant difference. (6)The expression of CD80 on CD5+ B cells [(6.27±4.87)%] was lower than that of on CD5- B cells [(27.54±9.42)%,P<0.05]. The expression of CD86ACD69 and HLA-DR on CD5+ B cells and CD5- B cells had no significant difference. Conclusions The percentage and quantity of B lymphocytes in PB of AIHA/Evans syndromes patients increased. CD5+ B lymphocytes are mainly cells and CD80 and CD86 on CD5+ B cells went up. The activated molecules on cell surface may be the basis of the different function of CD5+ and CD5- B lymphocytes. Disclosures No relevant conflicts of interest to declare.

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Alemtuzumab Plus Cyclosporine Treatment of the Autoimmune Hemolytic Anemia in an Adult Bowel Transplant

Case Reports in Transplantation ◽

10.1155/2014/262953 ◽

2014 ◽

Vol 2014 ◽

pp. 1-4

Author(s):

A. Lauro ◽

M. Stanzani ◽

C. Finelli ◽

C. Zanfi ◽

M. C. Morelli ◽

...

Keyword(s):

Bone Marrow ◽

Hemolytic Anemia ◽

Bone Marrow Biopsy ◽

Autoimmune Hemolytic Anemia ◽

Leukocyte Count ◽

Pure Red Cell Aplasia ◽

Febrile Episode ◽

High Dose ◽

Laboratory Findings ◽

Transfusion Requirements

An adult male underwent a bowel transplant for tufting enteropathy, receiving alemtuzumab, tacrolimus, and steroids as immunosuppressants. Five years later, he developed an autoimmune hemolytic anemia (AIHA), anti-IgG positive, with reduced reticulocyte count, leukopenia, and thrombocytopenia with antiplatelet antibodies. After an unsuccessful initial treatment with high dose steroids, reduction in tacrolimus dose, and intravenous immunoglobulin (IVIG), a bone marrow biopsy revealed absence of erythroid maturation with precursor hyperplasia. The patient was switched to sirolimus and received four doses of rituximab plus two courses of plasmapheresis, which decreased his transfusion requirements. After a febrile episode one month later, the AIHA relapsed with corresponding decreases in platelet and leukocyte count: cyclosporine A (CsA) was started with a second course of rituximab and IVIG without response, even though repeat bone marrow biopsy did not reveal morphology correlated to an acquired pure red cell aplasia (APRCA). Considering the similarity in his clinical and laboratory findings to APRCA, alemtuzumab was added (three doses over a week) with CsA followed by steroids. The patient was eventually discharged transfusion-independent, with increasing hemoglobin (Hb) levels and normal platelet and leukocyte count. One year later he is still disease-free with functioning graft.

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