Introduction: the spectrum of autoimmune complications in patients with SARS-COV2 infection (also known as COVID-19) is broader and includes autoimmune thrombocytopenia and antiphospholipid syndrome among others. (Autoimmunity Reviews 19 (2020) 102597) The reports of autoimmune hemolytic anemia (AIHA) are increasing too, but mainly is an immune dysregulation setting. Cases: here we report two cases of AIHA in a non immune dysregulation setting. Two females, 35 and 58 years old, presented to emergency service due severe anemic syndrome, severe pallor, dyspnea and mild fever. Work up was started and warm IgG - C3d autoantibodies AIHA was diagnosed. Extension studies included chest X-rays that showed basal infiltrates in both patients; lung CT scan were performed and revealed interstitial pneumonia predominantly in both lung bases. The PCR fo SARS-COV2 was positive for both patients. Treatment with methylprednisolone 1 gr per day for three days and IgG IV 1 gr/kg days 1 and 3. Treatment for COVID-19 was started according to institutional protocols. The evolution in both patients were to partial remission and needs prednisone 20 mg/day and still in it at the time of these report. Images show lung infiltrates and increased 56% reticulocytes count from one of the patients. Conclusion: the exact etiology of autoimmune diseases still unknown, but there are various factors, including viral infections, that contributes to the trigger of these type of diseases. AIHA has been associated with COVID-19 and it is postulated that molecular mimicry between Ankyrin-1 in the erythrocyte surface and the viral protein spike as the precipitating event. (Br J Haematol 2020;190:e92-e93) There are scanty cases of AIHA in the setting of COVID-19, the majority in the previously immune dysregulated patients (lymphoid neoplasias and autoimmune diseases); only two previously cases of AIHA with no underlaying disorder. We suggest that the work up for every patient with AIHA would include a lung CT Scan and PCR for SARS-COV2. There are not guidelines for treatment, but the lowest dose and time of steroids with IgG IV could be an option as recommended in guidelines for primary immune thrombocytopenia in the setting of COVID-19 infection. (Br J Haematol 2020;189:1038-1043). Figure Disclosures No relevant conflicts of interest to declare.
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.
Hematological cancer has risk of venous thromboembolism of 28 fold compared to sex and age adjusted incidence in general population (JAMA 2005;293:715-722). This risk increases in patients with MM receiving dexamethasone and immunomodulatory drug. Thus, thromboprophylaxis with aspirin in low risk patients and LMWH or warfarin in high risk patients are recommended (Leukemia 2008;22:414-423). Direct oral anticoagulants are promising due to their convenience and costs-effectiveness in preventing VTE in other settings. They have not been extensively studied in myeloma therapy. From January of 2010 to December of 2017, 105 with MM received thalidomide and dexamethasone based triplet induction therapy, maintenance with thalidomide and creatinine clearance > 30 mL/min. From those, 23 (21.9%) had only an additional risk factor and were randomized 5:1 to receive 100 mg aspirin or 10 mg rivaroxaban until relapse and need another treatment. Doppler ultrasound was performed every six months or as medical indication in all patients and pulmonary CT scan if EP was suspected. Five patients received rivaroxaban, 3 males and 2 females, median age of 67.5 years; additional factors were obesity in 4 and DM in one. Aspirin was received by 18 patients, 10 males an 8 females, median age 66.8 years; additional factors were obesity in 10, DM in 5, erythropoietin in 3. No patient in the Rivaroxaban arm developed thrombosis; bleeding episodes were self-limited to the gums and easy bruising; no major bleeding was detected. One patient in the Aspirin arm, with body mass index of 31.22 kg/m2 as an additional risk factor, developed right iliofemoral DVT without PE; he was changed to rivaroxaban at therapeutic doses for six months with resolution of the DVT and then continue with 10 mg dose; bleeding episodes in all patients were similar to the rivaroxaban arm. In this small group of patients with a low risk factors with an additional one, that could be in an intermediate risk, the use of rivaroxaban showed a good efficiency and security profiles. Either, rivaroxaban or aspirin could be used in this situations and deserve further investigation. Disclosures No relevant conflicts of interest to declare.
Las neoplasias mieloproliferativas (NMP) son alteraciones crónicas de las células madre hematopoyéticas clonales caracterizadas por una mayor producción de granulocitos, glóbulos rojos o plaquetas. Una de las principales complicaciones de las NMP es la aparición de problemas trombóticos venosos y arteriales causados por un aumento en la agregación plaquetaria y la generación de trombina. Se evaluaron once casos de mielofibrosis primaria (MP), de los cuales dos debutaron con trombosis venosa esplácnica (TVE).Tras observar los resultados de este estudio y de la literatura mundial, se sugiere que al evaluar pacientes con TVE se incluyan métodos diagnósticos para MP, como la mutación JAK2V617F.
Introduction: The 5-year relative survival in patients aged 15-24 years old is around 57% (Blood 2019; 134: 407-410), with a median survival after relapse of 10 months. No uniform consensus about rescue treatment is available, but those who achieve a complete remission can undergo to an allogeneic transplant if feasible. The use of intense rescue chemotherapy is associated with systemic toxicities and risk of serious infections that can delay an allogeneic transplant. Objective: We describe the combination of two ALL targeted therapies, combining bispecific T-cell engager (BiTE) against CD 19 (Blinatumomab) and selective inhibitor of the B-cell lymphoma 2 (Bcl-2) regulator protein, an antiapoptotic protein (Venetoclax). This combination was developed based in their mechanism of action that offers synergetic effects against ALL cells and the reports of ongoing clinical trials using Venetoclax combinations for ALL, but no with Blinatumomab. Patients and methods: Patients with B cell precursors ALL in minimal residual disease relapse by flow cytometry. Rescue treatment with Blinatumomab and Venetoclax before allogeneic transplant. Results: Two patients treated with LAFAMI-LLA-2002 Protocol (Blood 2009; 114: 4104 and Hematologia 2016; 17: 5137), adapted to young adults with high dose methotrexate at 5 gr/m2 every four months in the maintenance phase, had MDR positivity by FC in the surveillance phase, with normal CBC. One male with 22 years old at the time of relapse, after 60 months of surveillance with 1.9 % of malignant lymphoblasts. One female with 21 years old at the time of relapse, after 25 months of surveillance with 0.2 % of malignant lymphoblasts. Both relapses were confirmed with an additional MRD one week after. Extension studies were performed, including PET-CT, to determinate other affected sites and were negative. Treatment administrated was Blinatumomab at 9 mcg/day continuous IV infusion on days 1-7 and 28 mcg/day on days 8-14 with Venetoclax in a ramp-up phase for 5 weeks. Both patients were in negative MRD after the complete Blinatumomab and continue with Venetoclax while a donor was available. No side effects were observed during and after the treatment. Both patients had a compatible sibling and underwent for allogeneic transplant. At the moment of this report the patients have 11 months and 18 months after transplant with EMR negative and complete donor cells from the bone marrow, with no secondary effects. Conclusion: This is a novel combination with no reports of its use before our communication. Targeted therapies in low leukemic burden is a feasible treatment with no side effects and rapid control of the relapse, allowing the patients to reach an allogeneic transplant as soon as possible avoiding substantial toxicity and risk of infections. No infusion related reaction or cytokine release syndrome were observed due low leukemic burden. More patients need to be included to this combination to demonstrate reproducibility, optimizing time and costs. OffLabel Disclosure: Blinatumomab and Venetoclax combination for acute lymphoblastic leukemia relapse
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