Long-term follow-up of recovered mpn patients with covid-19

ABSTRACT

To our knowledge, there is no information on long-term follow-up of recovered patients with chronic myeloproliferative neoplasms (MPN) with COVID-19. It can be hypothesized that cytokine storm of the acute phase and the post-COVID persistence of a residual inflammatory state may contribute to elicit hematopoietic stem cell insults and continuous vascular endothelial damage, leading to MPN disease progression and persistent high risk of thrombosis. Aims: To describe sequelae of COVID-19 in surviving patients with MPN following COVID-19. Methods: MPN-COVID study involved 38 European blood centers, and accrued 180 patients with MPN diagnosed with COVID-19 from Feb to Jun 2020, assessing mortality and incidence of thrombosis and bleeding during the acute phase of the pandemic [Barbui T et al. Leukemia. 2021;35(2)485-493. Barbui T et al. Blood Cancer J. 2021;11(2)21]. One-hundred-twenty-five (69%) of these patients survived and were followed up for at least 6 months. Centers were asked to update symptoms, treatments, hematological changes, major outcomes (i.e., thrombosis, disease evolution and death). Results: Among the 125 surviving patients, all eligible for the follow-up update, with a median age 70 years (IQR 58-79), the following phenotypes were registered PV (n=38, 30%), ET (n=37, 30%), early PMF (n=14, 11%) and MF (n=36, 29%). During the acute phase of infection, 38 (30%) were managed at home, 80 (64%) in a regular ward and 7 (6%) in ICU. Symptoms (i)The 3 prevalent symptoms during the acute phase of the disease were fever (79%), cough (56%) and dyspnea (53%), while gastrointestinal, neurological, musculoskeletal symptoms, as well as fatigue and anosmia/ dysgeusia, were present in a minor proportion, ranging from 1.6% to 17%. (ii) In the post-acute COVID-19 phase, 36 of 125 patients (32%) declared the persistence of some of these symptoms, fatigue being the most frequent (19%), while none presented persistence of fever and only 10% of dyspnea. Major outcomes (i) Major thrombosis was documented in 5 patients and involved 3 patients with MF (one fatal intestinal ischemia, two non-fatal events splenic infarction and peripheral artery thrombosis), one case in PV (acute myocardial infarction) and one with ET (DVT of the legs with pulmonary embolism). Age varied from 61 to 80 years. The first event occurred five months after COVID-19 recovery and the Kaplan Meier thrombosis-free survival probability after 9 months was 82%. (ii) Acute myelogenous leukemia (AML) was ascertained in 3 patients (1 in MF, 1 in early-PMF, 1 in ET);one was fatal and occurred in a 49-yearold patient, the other 2 in 78- and 82-year-old patients, respectively. One non-Hodgkin′s lymphoma (in ET) and one progression of a previous parotid carcinoma (in MF) were seen in two patients aged 60 and 77 years, respectively. (iii) Deaths were reported in 8 patients (6.4%), due to AML (n=1), thrombosis (n=1), progression to prior carcinoma (n=2, 1 suspected), multi organ failure (n=1) and heart failure (n=2);the cause was unknown in a single patient. Five deaths (63%) occurred in MF patients. (iv) Overall, the event-free survival pooling together thrombosis, disease evolution and death reached 66% after 9 months from COVID- 19 recovery, indicating that, during this time of observation, 1 out of 3 patients died or have experienced at least one of the other two severe events. Summary/Conclusion: These results indicate that MPN patients who have survived SARS-CoV-2 infection continue to experience severe events suggesting an increased vigilance in the post-COVID period.