ABSTRACT
The clinical phenotype of primary and post-polycythemia vera and post-essential thrombocythemia myelofibrosis (MF) is dominated by splenomegaly, symptomatology, a variety of blood cell alterations and a tendency to develop vascular complications and blast phase. Diagnosis requires to assess cell blood counts, bone marrow morphology, deep genetic evaluations and disease history. Driver molecular events consist of JAK2V617F mutation, CALR and MPL mutations, while about 8-10% of PMF are 'triple-negative'. Additional myeloid-gene variants are described in roughly 80% of patients. Currently available clinical-based and integrated clinical/molecular-based scoring systems predict survival of MF patients, and are applied for conventional treatment decision-making, indication to stem cell transplant (SCT) and allocation in clinical trials. Standard treatment consists of anemia-oriented therapies, hydroxyurea, and JAK inhibitors as ruxolitinib, fedratinib, pacritinib, momelotinib. Overall, spleen volume reduction of 35% or greater (SVR35) at week 24 can be achieved by 42% of ruxolitinib-, 47% of fedratinib-, 19% of pacritinib- and 27% of momelotinib-treated patients. Now, it is time to move from SVR35-oriented drugs to treatments with new paradigms as disease modification, that we intend as a robust and unequivocal effect on disease biology and/or on patient survival. The growing number of clinical trials potentially pave the way for new strategies in MF patients. Translational studies of some molecules showed an early effect on bone marrow fibrosis and on variant allele frequencies of myeloid genes. SCT is still the only curative option, however, associated with relevant challenges. This review focuses on diagnosis, prognostication, and treatments of MF.
ABSTRACT
Vaccines against SARS-CoV-2 have shown remarkable efficacy and thus constitute an important preventive option against coronavirus disease 2019 (COVID-19), especially in fragile patients. We aimed to systematically analyze the outcomes of patients with hematological malignancies who received vaccination and to identify specific groups with differences in outcomes. The primary end point was antibody response after full vaccination (2 doses of mRNA or one dose of vectorbased vaccines). We identified 49 studies comprising 11,086 individuals. Overall risk of bias was low. The pooled response for hematological malignancies was 64% (95% confidence interval [CI]: 59-69; I²=93%) versus 96% (95% CI: 92-97; I²=44%) for solid cancer and 98% (95% CI: 96-99; I²=55%) for healthy controls (P<0.001). Outcome was different across hematological malignancies (P<0.001). The pooled response was 50% (95% CI: 43-57; I²=84%) for chronic lymphocytic leukemia, 76% (95% CI: 67-83; I²=92%) for multiple myeloma, 83% (95% CI: 69-91; I²=85%) for myeloproliferative neoplasms, 91% (95% CI: 82-96; I²=12%) for Hodgkin lymphoma, and 58% (95% CI: 44-70; I²=84%) for aggressive and 61% (95% CI: 48-72; I²=85%) for indolent non-Hodgkin lymphoma. The pooled response for allogeneic and autologous hematopoietic cell transplantation was 82% and 83%, respectively. Being in remission and prior COVID-19 showed significantly higher responses. Low pooled response was identified for active treatment (35%), anti-CD20 therapy ≤1 year (15%), Bruton kinase inhibition (23%), venetoclax (26%), ruxolitinib (42%), and chimeric antigen receptor T-cell therapy (42%). Studies on timing, value of boosters, and long-term efficacy are needed. This study is registered with PROSPERO (clinicaltrials gov. Identifier: CRD42021279051).