Myeloproliferative neoplasms (MPN) are uncommon in children/young adults. Here we present data on unselected patients diagnosed before 25 years of age included from 38 centres in 15 countries. Sequential patients were included. We identified 444 patients, with median follow up 9.7 years (0-47.8). Forty-nine (11.1%) had a history of thrombosis at diagnosis, 49 new thrombotic events were recorded (1.16 % pt/year), peri-hepatic vein thromboses were most frequent (47.6% venous events) and logistic regression identified JAK2V617F mutation (p=0.016) and hyperviscosity symptoms (visual disturbances, dizziness, vertigo, headache) as risk factors (p=0.040). New hemorrhagic events occurred in 44 patients (9.9%, 1.04 % pt/y). Disease transformation occurred in 48 patients (10.9%, 1.13 % pt/year), usually to myelofibrosis (7.5%) with splenomegaly as a novel risk factor for transformation in ET (p= 0.000) in logistical regression. Eight deaths (1.8%) were recorded, three after allogeneic stem cell transplantation. Concerning conventional risk scores: IPSET-T and IPSET-NT differentiated ET patients in terms of thrombotic risk. Both scores identified high-risk patients with the same median thrombosis-free survival of 28.5y. No contemporary scores were able to predict survival for young ET or PV patients. Our data represents the largest real-world study of MPN patients age <25 years at diagnosis). Rates of thrombotic events and transformation were higher than expected compared with the previous literature. Our study provides new and reliable information as a basis for prospective studies, trials, and development of harmonized international guidelines for the specific management of young patients with MPN.

Our previous studies established cardio-protective effects of furnidipine and its active metabolites called M-2 and M-3. The aim of current research was to compare the effects of single oral pretreatment with 20 mg kg−1 of M-2 and M-3 on mortality, different forms of arrhythmias, blood pressures parameters and ST-segment changes during occlusion (for 90 min) and reperfusion in the model of myocardial infarction in rats evoked by left anterior descending coronary artery occlusion. Additionally, the development of programmed cell death and biochemical parameters in blood serum were studied at 4th day after infarction. Furnidipines’ metabolites effectively reduced mortality index while did not markedly influence on blood pressures parameters, arrhythmias, ST-segment changes as well as biochemical parameters. Intriguingly, programmed cell death study (TUNEL) showed distinct increase in the amount of apoptotic nuclei in post-infarcted myocardium, granulation tissue and what is more in arteriolar walls after M-2 and M-3 application. Moreover, M-2 turned out to be more powerful in stimulation of apoptosis in granulation tissue surrounding infarcted area whereas M-3 presented balanced profile in this matter. Taking into account that programmed cell death plays positive role in post-infarcted heart healing, M-2 presents itself as more attractive agent for oral pretreatment in early stages of ischemia by non-stable individuals due to its more specific action in stimulation repairing processes in granulation tissue as well as in arteriolar walls. While M-2 and M-3 are common metabolites present in degradation pathways of many widely used dihydropyridines in clinic, this key fact put the new outlook on understanding additional mechanism and effects of not only furnidipines’ metabolites but also other dihydropyridines.

Autologous hematopoietic stem cell transplantation (AHSCT) is thought to be effective therapeutic approach in patients with poor prognosis systemic sclerosis; however, the toxicity remains a challenge. Between years 2003 and 2016, we enrolled 18 patients with systemic sclerosis at median age at transplant of 52 years (range 24–68). The median duration of disease before AHSCT was 14 months (range 2–85). Peripheral blood stem cells were mobilized with cyclophosphamide (CY) and granulocyte colony-stimulating factor. Conditioning regimen included CY (200 mg/kg) and alemtuzumab (median dose, 60 mg) [n = 11], melphalan (MEL; 140 mg/m2) and alemtuzumab [n = 2], CY and rabbit anti-thymocyte globulin (rATG; 7.5 mg/kg) [n = 4], and CY alone (n = 1). Four deaths occurred early after transplant. There were three males and one female at median age at death of 51 years (range 24–68). The AHSCT-related deaths have been observed on days + 1, + 4, + 9, and + 15 after procedure. The causes of death included bilateral pneumonia followed by multi-organ failure in three patients and myocardial infarction in one. Three patients expired late during post-transplant follow-up, after 5, 21, and 42 months. The causes of death were disease progression in two patients and sudden heart attack in one. Eleven patients are alive after median follow-up after AHSCT of 42.0 months (range 0–95). Before proceeding to AHSCT in systemic sclerosis, there is a strong need to optimize patient selection to reduce toxicity. The administration of alemtuzumab should be avoided due to high risk of life-threatening infectious complications.

In the pathway inhibitor era, the number of allogeneic stem cell transplantation (ASCT) for chronic lymphocytic leukemia (CLL) continues to decrease and this approach should be offered only after careful risk-benefit assessment. Nevertheless, ASCT still remains only curative therapeutic modality for CLL, especially in countries with limited access to novel agents. Thirty patients with CLL at median age of 42 years at diagnosis (range 29–64) underwent ASCT between years 2002 and 2018. Thirteen patients were transplanted in complete remission (CR), ten patients achieved partial response (PR), and seven had stable disease. The median time from diagnosis to transplant was 4 years (range 0.5–12). Twenty-three patients received HLA-matched related donor stem cell grafts, and seven patients received either matched unrelated donor or HLA-mismatched grafts. Reduced intensity conditioning (RIC) and myeloablative regimen (MAC) were used in 24 and 6 patients, respectively. Mortality to day + 100 after transplant was 16% (8% for RIC only). Acute and chronic graft versus host disease (GVHD) developed in 40% and 63% of patients, respectively. Fifteen patients relapsed or progressed after transplant. Thirteen patients (43%) are alive at last follow-up and 10 (77%) remain in clinical CR. Median follow-up for survivors was 6.8 years (range 0.4–15.2). Three-year progression-free and overall survivals were 56% and 60%, respectively. These outcomes were better for patients who received RIC conditioning: 64% and 72%, respectively. CR at transplant was found to have favorable impact on post-allograft survival. RIC should be preferred over MAC. ASCT may remain a valuable option for some CLL patients.

During the last 25 years angiotensin-converting enzyme inhibitors spectacularly conquered the field of cardiovascular diseases therapy. Nevertheless, lack of new studies concerning side effects associated with their chronic administration seems to be rather confusing. In our previous research, we proved that the main furnidipines’ metabolite (M-2) possess multiple cardioprotective actions. Currently, we compared effects of post-infarction long-term oral treatment with M-2 and captopril on hemodynamic parameters and “ischemic cardiomyopathy” development in rats. Myocardial infarction was evoked by permanent left anterior descending coronary artery occlusion for 35 days. Surviving rats were treated with captopril (2 × 25 mg/kg) or M-2 (4 mg/kg) from 6th– 35th day. At 35th day rats’ hearts were tested on working heart setup, where following parameters were measured: heart rate, preload pressure, aortic systolic and diastolic pressures, aortic maximum rise and fall, aortic and coronary flow, myocardial oxygen consumption and oximetry in perfusate. Subsequently, heart tissue specimens were assessed during morphological estimation. Captopril caused significant heart rate increase and markedly diminished preload pressure in comparison to M-2. Both drugs evoked essential aortic pressure increase. Aortic flow was significantly decreased after M-2, whereas captopril increased this parameter in comparison to M-2. Both agents caused marked coronary flow increase. Morphologic examination in captopril revealed cardiomyopathic process in 70% of hearts, whereas in M-2 this value reached 30%. Neovascularization of post-infarcted myocardium was visible only after M-2 therapy. Concluding, M-2 presented itself as more attractive agent in long-term post-infarction treatment by preventing cardiomyopathy development, angiogenesis stimulation and preserving cardiac performance.