High mortality rate in COVID-19 patients with myeloproliferative neoplasms after abrupt withdrawal of ruxolitinib.

We report the clinical presentation and risk factors for survival in 175 patients with myeloproliferative neoplasms (MPN) and COVID-19, diagnosed between February and June 2020. After a median follow-up of 50 days, mortality was higher than in the general population and reached 48% in myelofibrosis (MF). Univariate analysis, showed a significant relationship between death and age, male gender, decreased lymphocyte counts, need for respiratory support, comorbidities and diagnosis of MF, while no association with essential thrombocythemia (ET), polycythemia vera (PV), and prefibrotic-PMF (pre-PMF) was found. Regarding MPN-directed therapy ongoing at the time of COVID-19 diagnosis, Ruxolitinib (Ruxo) was significantly more frequent in patients who died in comparison with survivors (p = 0.006). Conversely, multivariable analysis found no effect of Ruxo alone on mortality, but highlighted an increased risk of death in the 11 out of 45 patients who discontinued treatment. These findings were also confirmed in a propensity score matching analysis. In conclusion, we found a high risk of mortality during COVID-19 infection among MPN patients, especially in MF patients and/or discontinuing Ruxo at COVID-19 diagnosis. These findings call for deeper investigation on the role of Ruxo treatment and its interruption, in affecting mortality in MPN patients with COVID-19.

Impaired virus-specific T cell responses in patients with myeloproliferative neoplasms treated with ruxolitinib.

Ruxolitinib is effective in myeloproliferative neoplasms (MPN) but can cause reactivation of silent infections. We aimed at evaluating viral load and T-cell responses to human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in a cohort of 25 MPN patients treated with ruxolitinib. EBV-DNA and HCMV-DNA were quantified monthly using real-time polimerase chain reaction (PCR) on peripheral blood samples, and T-cell subsets were analyzed by flowcytometry. HCMV and EBV-directed T-cell responses were evaluated using the IFN-γ ELISPOT assay. Most patients had CD4+ and/or CD8+ T-cells below the normal range; these reductions were related to the duration of ruxolitinib treatment. In fact, reduced T-lymphocytes' subsets were found in 93% of patients treated for ≥5 years and in 45% of those treated for <5 years (P = .021). The former also had lower median numbers of CD4+ and CD8+ cells. Subclinical reactivation of EBV and HCMV occurred in 76% and 8% of patients. We observed a trend to an inverse relationship between EBV and CMV-specific CD4+ and CD8+ T-cell responses and viral load, and a trend to an inverse correlation with ruxolitinib dose. Therefore, our data suggest that the ruxolitinib treatment may interfere with immunosurveillance against EBV and HCMV.

Special considerations in the management of adult patients with acute leukaemias and myeloid neoplasms in the COVID-19 era: recommendations from a panel of international experts.

The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 is a global public health crisis. Multiple observations indicate poorer post-infection outcomes for patients with cancer than for the general population. Herein, we highlight the challenges in caring for patients with acute leukaemias and myeloid neoplasms amid the COVID-19 pandemic. We summarise key changes related to service allocation, clinical and supportive care, clinical trial participation, and ethical considerations regarding the use of lifesaving measures for these patients. We recognise that these recommendations might be more applicable to high-income countries and might not be generalisable because of regional differences in health-care infrastructure, individual circumstances, and a complex and highly fluid health-care environment. Despite these limitations, we aim to provide a general framework for the care of patients with acute leukaemias and myeloid neoplasms during the COVID-19 pandemic on the basis of recommendations from international experts.

Prevalence of hepatitis C virus infection in lymphoproliferative diseases other than B-cell non-Hodgkin's lymphoma, and in myeloproliferative diseases: an Italian Multi-Center case-control study.

BACKGROUND AND OBJECTIVES: Infection with hepatitis C virus (HCV) is associated with type II mixed cryoglobulinemia (MC), a lymphoproliferative disorder which, in some patients, evolves into overt B-cell non-Hodgkin's lymphoma (B-NHL). Recently, also the association between HCV infection and B-NHL, which had long been controversial, was confirmed in a large case-control study. Little knowledge is, however, available on possible associations between HCV infection and other lymphoid or myeloid malignancies. The present study was set up in order to investigate this aspect. DESIGN AND METHODS: The study was conducted in hematology departments of ten hospitals in different Italian cities. The cases consisted of consecutive patients with a new diagnosis of T-NHL, Hodgkin's disease (HD), chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), multiple myeloma (MM), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). The controls were patients in other departments of the same hospitals. HCV infection was investigated by testing for HCV antibodies and HCV-RNA in serum samples. RESULTS: The prevalence of HCV infection was not higher in patients with HD (3.2%, 5 out of 157 cases) or MM (4.7%, 5 out of 107) than in controls. On the other hand, it was consistently higher in T-NHL (13.8%, 4 out of 30), CLL (9.0%, 9 out of 100), ALL (7.6%, 5 out of 54), AML (7.9%, 11 out of 140), and CML (12.2%, 6 out of 49) patients. These patient groups were not, however, large enough to render statistically significant results. INTERPRETATION AND CONCLUSIONS: Our data suggest that HCV infection may be associated not only with B-NHL but also with some other lymphoid and myeloid malignancies.

Rapid presumptive diagnosis of hantavirus cardiopulmonary syndrome by peripheral blood smear review.

Hantavirus cardiopulmonary syndrome (HCPS) is a rare but frequently lethal acute zoonotic viral infection in rural North America. The rapidity of progression from febrile prodrome to cardiogenic shock and noncardiogenic pulmonary edema requiring intensive care creates high diagnostic urgency and a need for a rapid screening tool. In this retrospective cohort study, 2 pathologists scored blinded peripheral blood smears from 52 patients with HCPS and 128 seronegative patients referred for diagnosis of suspected hantavirus infection. During the prodromal phase, thrombocytopenia was the only consistent abnormality and could be used to indicate hantavirus serologic testing. After the onset of pulmonary edema detected radiographically, the presence of 4 of 5 findings (thrombocytopenia, myelocytosis, hemoconcentration, lack of significant toxic granulation in neutrophils, and more than 10% of lymphocytes with immunoblastic morphologic features) has a sensitivity for HCPS of 96% and a specificity of 99% and missed no patients with HCPS who required intensive care. While each abnormality is commonly seen, the combination of at least 4 of these CBC count data and peripheral blood smear findings can guide early treatment and patient transport decisions until rapid, specific, serologic testing becomes widely available.

Myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML) and chronic myeloproliferative disorder (CMPD) in cats.

Histological, enzyme histochemical and ultrastructural findings in three cases of feline bone marrow neoplasia are described. The following changes were observed: in myelodysplastic syndrome (MDS), a low medullary blast count, strongly atypical (micromegakaryocytic) proliferative megakaryocytopoiesis, hypoplastic erythrocytopoiesis with impairment of differentiation, multifocal extravasation and lymphoid aggregates; in acute myeloid leukaemia (AML), medullary proliferation of undifferentiated cell types; in chronic myeloIproliferative disorder (CMPD), trilinear medullary proliferation with complete cellular maturation, osteomyelosclerosis and extramedullary haemopoiesis. In two cases (MDS, AML), ultrastructural demonstration of C-type virus particles (feline leukaemia virus) suggested a viral aetiology.

Association of GB virus C (GBV-C)/hepatitis G virus (HGV) with haematological diseases of different malignant potential.

Among risk groups for GB virus C (GBV-C)/HGV infection, patients with haematological diseases are particularly exposed due to the combination of transfusional support and immunodeficiency status. To examine any association between GBV-C/HGV positivity and different malignancy potential of hematological diseases, we investigated two groups of patients, one with clonal stem cell disease with long latency period (myelodysplasia, myeloproliferative disease) and one with malignant haematological diseases (Hodgkin's lymphoma, non-Hodgkin's lymphoma, acute leukemia, multiple myeloma). Virus positivity was compared with the data from cytogenetic analysis at first diagnosis. The frequency of GBV-C/HGV infection in these patients was studied using reverse transcription-polymerase chain reaction (RT-PCR) and E2 antibody assay. Serum GBV-C RNA was found in 29/47 (62%) patients. The prevalence of GBV-C RNA in the group of oncological cases (72%) was significantly higher (P= .02) than in the patients with clonal stem cell diseases (28%). Among the GBV-C negative cases, only 25% had malignant haematological diseases. The data from GBV-C/ HGV tested cases for which cytogenetic analysis was carried out indicated an association of GBV-C/HGV positivity with genomic destabilization in general. Of the cases with numerical and structural aberrations, 64% were GBV-C positive. A correlation could not be confirmed between GBV-C/HGV and liver enzyme levels, blood transfusions, chemotherapy treatment, or viral coinfection. These findings suggest a high risk of GBV-C/HGV infection in patients with haematological disorders especially in the group of malignant diseases. These observations may indicate that the persistence of GBV-C/HGV in these patients could be associated with susceptibility to genomic destabilisation.

[A prevalence study on HBV and HCV infection status in patients with hemopathy].

A prevalence study on Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection in 144 patients with hemopathy was carried out, using an enzyme linked immunosorbent assay (ELISA). The HBsAg, HBcAb and anti-HCV positive rates in sera of these patients were 9.72%, 36.81% and 24.31% respectively, comparing with data from healthy control subjects, 12.03%, 46.30% and 0.93% respectively. No correlation between HCV infection and patient's age or sex was noticed. Nevertheless the incidence of HCV infection was closely related to the history and the frequency of blood transfusion. The ALT level in sera of patients with HCV infection was higher than that of patients without HCV infection. The ALT level in sera was the highest in patients superinfected with HBV and HCV. Our results suggested that blood transfusion and receiving blood products were important routes of HCV transmission in patients with hemopathy.

Demonstration of active and latent Epstein-Barr virus and human herpevirus-6 infections in bone marrow cells of patients with myelodysplasia and chronic myeloproliferative diseases.

After previous serological screening for Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6) and human cytomegalovirus (HCMV) showed elevated antibody titers against EBV and HHV-6 in more than 50% of patients with myelodysplasia and chronic myeloproliferative diseases, the present study was carried out in order to investigate viral antigen expression and distribution in bone marrow cells of these patients. Trephine biopsies were studied from 60 patients with myelodysplasia (MDS), 36 patients with chronic myelogenous leukemia (CML) and 18 patients with osteomyelofibrosis (PMF). Elevated anti-EBV EA titers were found in 62% of the MDS cases, in 33% of the CMLs and in 62% of the OMF patients. HHV-6 titers were elevated in 18% of the MDS cases, but in only one case each of CML and OMF. Antigen expression in bone marrow cells was even more frequent: EBV-EA was 76% in MDS cases, 77% in CML and 40% in OMF. HHV-6 p41 was observed in 47% of the MDS cases, in 54% of the CML cases and in 20% of the OMFs. In comparing these data with those from the literature and with our own studies in Hodgkin's disease, it is hypothesized that the reactivated herpesviruses may contribute to the pathogenesis of these hematopoietic disorders by interfering with the cytokine regulation of cell proliferation and differentiation.