Project description:Data on the effect of ruxolitinib on antibody response to severe acute respiratory coronavirus 2 (SARS-CoV-2) vaccination in patients with myeloproliferative neoplasms (MPN) is lacking. We prospectively evaluated anti-spike-receptor binding domain antibody (anti-S Ab) levels after the second dose of the BNT162b2 (Pfizer-BioNTech) vaccine in MPN patients. A total of 74 patients with MPN and 81 healthy controls who were vaccinated were enrolled in the study. Of the MPN patients, 27% received ruxolitinib at the time of vaccination. Notably, MPN patients receiving ruxolitinib had a 30-fold lower median anti-S Ab level than those not receiving ruxolitinib (p < 0.001). Further, the anti-S Ab levels in MPN patients not receiving ruxolitinib were significantly lower than those in healthy controls (p < 0.001). Regarding a clinical protective titre that has been shown to correlate with preventing symptomatic infection, only 10% of the MPN patients receiving ruxolitinib had the protective value. Univariate analysis revealed that ruxolitinib, myelofibrosis, and longer time from diagnosis to vaccination had a significantly negative impact on achieving the protective value (p = 0.001, 0.021, and 0.019, respectively). In subgroup analysis, lower numbers of CD3+ and CD4+ lymphocytes were significantly correlated with a lower probability of obtaining the protective value (p = 0.011 and 0.001, respectively). In conclusion, our results highlight ruxolitinib-induced impaired vaccine response and the necessity of booster immunisation in MPN patients. Moreover, T-cell mediated immunity may have an important role in the SARS-CoV-2 vaccine response in patients with MPN, though further studies are warranted.

| S-EPMC8990027 | biostudies-literature

Antibody and T-cell responses to SARS-CoV-2 vaccination in myeloproliferative neoplasm patients.

Project description: Not available

| S-EPMC8873343 | biostudies-literature

Low titers of SARS-CoV-2 neutralizing antibodies after first vaccination dose in cancer patients receiving checkpoint inhibitors.

Project description:Vaccination for SARS-CoV-2 provides significant protection against the infection in the general population. However, only limited data exist for patients with cancer under systemic therapy. Based on this, our site has initiated a study evaluating safety and efficacy of SARS-CoV-2 vaccination in patients with solid and hematological malignancies under several systemic therapies. The initial results of the cohort of 59 patients receiving Immune Checkpoint Inhibitors are presented here. Despite no new safety issues have been noticed, the levels of SARS-CoV-2 neutralizing antibodies are significantly lower in comparison to matched healthy volunteers up to day 22 post the first dose. These results should be taken into consideration for the patients under treatment.

| S-EPMC8165511 | biostudies-literature

Humoral and cellular responses after third dose of SARS-CoV-2 vaccine in myeloproliferative neoplasms patients on ruxolitinib therapy.

Project description: Not available

| S-EPMC10226289 | biostudies-literature

Low-dose methotrexate in myeloproliferative neoplasm models.

Project description: Not available

| S-EPMC5685234 | biostudies-literature

Low-dose ruxolitinib plus steroid in severe SARS-CoV-2 pneumonia.

Project description: Not available

| S-EPMC7654848 | biostudies-literature

Large Scale Internet-based Survey of Patients With a Myeloproliferative Neoplasm: Opinions and Experiences Regarding SARS-CoV-2 (COVID-19) Vaccination Strategies in 2021.

Project description:Supplemental Digital Content is available in the text.

| S-EPMC8225363 | biostudies-literature

Concomitant ruxolitinib with cytarabine-based induction chemotherapy in secondary acute myeloid leukemia evolving from myeloproliferative neoplasm.

Project description: Not available

| S-EPMC10548284 | biostudies-literature

Distinct effects of ruxolitinib and interferon-alpha on murine JAK2V617F myeloproliferative neoplasm hematopoietic stem cell populations.

Project description:JAK2V617F is the most common mutation in patients with BCR-ABL negative myeloproliferative neoplasms (MPNs). The eradication of JAK2V617F hematopoietic stem cells (HSCs) is critical for achieving molecular remissions and cure. We investigate the distinct effects of two therapies, ruxolitinib (JAK1/2 inhibitor) and interferon-alpha (IFN-α), on the disease-initiating HSC population. Whereas ruxolitinib inhibits Stat5 activation in erythroid progenitor populations, it fails to inhibit this same pathway in HSCs. In contrast, IFN-α has direct effects on HSCs. Furthermore, STAT1 phosphorylation and pathway activation is greater after IFN-α stimulation in Jak2V617F murine HSCs with increased induction of reactive oxygen species, DNA damage and reduction in quiescence after chronic IFN-α treatment. Interestingly, ruxolitinib does not block IFN-α induced reactive oxygen species and DNA damage in Jak2V617F murine HSCs in vivo. This work provides a mechanistic rationale informing how pegylated IFN-α reduces JAK2V617F allelic burden in the clinical setting and may inform future clinical efforts to combine ruxolitinib with pegylated IFN-α in patients with MPN.

| S-EPMC9221569 | biostudies-literature

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