The present study assessed the criteria for initiating cytoreduction and response to conventional therapies in 1446 patients with essential thrombocythemia (ET), 267 (17%) of which were CALR‐mutated. In low risk patients, time from diagnosis to cytoreduction was shorter in CALR‐positive than in the other genotypes (2·8, 3·2, 7·4 and 12·5 years for CALR, MPL, JAK2V617F and TN, respectively, P < 0·0001). A total of 1104 (76%) patients received cytoreductive treatment with hydroxycarbamide (HC) (n = 977), anagrelide (n = 113), or others (n = 14). The estimated cumulative rates of complete haematological response (CR) at 12 months were 40 % and 67% in CALR and JAK2V617F genotypes, respectively. Median time to CR was 192 days for JAK2V617F, 343 for TN, 433 for MPL, and 705 for CALR genotypes (P < 0·0001). Duration of CR was shorter in CALR‐mutated ET than in the remaining patients (P = 0·003). In CALR‐positive patients, HC and anagrelide had similar efficacy in terms of response rates and duration. CALR‐mutated patients developed resistance/intolerance to HC more frequently (5%, 23%, 27% and 15% for JAK2V617F, CALR, MPL and TN, respectively; P < 0·0001). In conclusion, conventional cytoreductive agents are less effective in CALR‐mutated ET, highlighting the need for new treatment modalities and redefinition of haematologic targets for patients with this genotype.

Background: Warm autoimmune hemolytic anemia (WAIHA) is a disorder with a usually good response to corticosteroid treatment, whereas in some cases first-line treatment's response is poor and other therapies such as intravenous immunoglobulins (IVIGs), rituximab, or splenectomy must be applied. Study Design and Methods: Herein, we describe two patients with severe WAIHA treated at our center, who obtained a response after therapeutic plasma exchanges (TPEs) combined with low doses of IVIG. Results: The first patient was an 18-year-old man with no relevant past medical history who was diagnosed with WAIHA. The patient presented a progressive clinical worsening despite treatment with prednisone, IVIG, and rituximab. After starting TPEs, signs of hemolysis rapidly improved and hemoglobin started to recover. The second patient was a 38-year-old man with a past history of immune thrombocytopenia and WAIHA. The patient presented a new flare of WAIHA, with no response after 2 weeks of treatment with corticosteroids, IVIG, and rituximab. After initiation of TPEs, the patient had an improvement in hemolysis biomarkers and recovery of hemoglobin concentration. Conclusion: Combination of TPEs with rituximab and IVIG might be considered as a therapeutic option in patients with severe WAIHA without response to corticosteroid and IVIG treatment.

BACKGROUND Left ventricular noncompaction (LVNC) has a wide phenotypic expression. Prognosis of patients with preserved ejection fraction (pEF) remains uncertain. PURPOSE To describe the characteristics and natural history of this subgroup of patients. METHODS LVNC patients were included in a multicentric registry. Those with pEF (LVEF &gt; 50%) were considered for the analysis. RESULTS 491 LVNC pts from 10 Spanish centres were recruited from 2000 to 2018. 239 (49%) had baseline pEF. Compared to those with reduced EF (rEF), they were younger, with no differences in gender and had less comorbilities (Table 1). Mean LVEF was 62% (SD 8). 18 pts (9% of the available CMR) had fibrosis even though LV volumes and LVEF were normal. Family screening was completed in 199 pts, being positive in 113 (57%). Genetic testing was performed in 146 index cases, being positive in 80 (55%): ACTC1 (40), MYH7 (17), TTN (8), HCN4 (6) and other individual variants. During a median follow-up of 4.9 years (IQR 2.1-7.3), there was a significant decrease in LVEF: last LVEF was 30- 40% in 5 pts (2%) and 40-50% in 21 (9%) (p = 0.01 compared to baseline LVEF). 6 pts (2.5%) died during follow-up, only 1 of cardiovascular cause. 9 patients (4%) presented heart failure (HF) and 25 (10.5%) ventricular tachycardia or fibrillation (VT/VF). All cardiovascular outcomes were less frequent compared to rEF (Image 1, all p &lt; 0.05). In multivariate analysis (including demographic, imaging, genetic and family aggregation parameters) the only predictor for HF was change in LVEF (OR 0.89, mean LVEF at the event 47%, p = 0.01 compared to no HF). Fibrosis was not associated with VT/VF. CONCLUSIONS Patients with LVNC and pEF have an overall excellent prognosis, which is markedly better than those with rEF. However, there is progressive decrease in LVEF, associated with heart failure, and moderate risk of life threatening arrhythmias. Therefore, periodic follow-up should be promoted. Table 1 LVNC pEF (n = 239) LVNC rEF (n = 252) p Men, n (%) 131 (55) 146 (58) 0.65 Median age at diagnosis (IQR) - yr 38 (23-54) 58 (42-72) 0.01 Median follow up (IQR) - yr 4.9 (2.1-7.3) 3.9 (1.4-7.9) 0.04 QRS (SD) - ms 93 (18) 117 (32) 0.01 LGE, n (%) 18 (9) 52 (30) 0.01 Abstract P1442 Figure. Image 1