Evaluation of serological response to anti-SARS-CoV-2 mRNA vaccination in hematological patients.

Introduction: In immunocompromised patients, SARS-CoV-2 mRNA vaccine has been used in Italy from the beginning of the vaccination campaign, but several studies have shown that the serological response of onco-hematological patients was reduced compared to healthy subjects, due to the state of immunosuppression because of both underlying disease and administered therapy. Methods: We evaluated the association of anti-SARS-CoV-2 spike IgG titers in 215 hematological patients with clinical and demographic variables to verify if it was possible to identify predictive parameters of serological response, as well as using a control group, consisting of healthy health workers of San Carlo Hospital in Potenza. Anti-SARS-CoV2 IgG titers were evaluated after 30-45 days post second dose vaccine using chemiluminescent microparticle immunoassay technology. Results: Patients with hematological malignancies, compared with the control arm, had both a mean concentration of anti-SARS-CoV-2 IgG significantly lower and a seroconversion rate numerically lower. All chronic lymphatic leukemia patients showed levels of antibody titer below the mean concentration, also in only clinical surveillance patients. Comparing serological response in hematological malignancies, only acute leukemia patients who were off therapy had the highest seroconversion rate among the patients' cohorts and a mean antibody concentration greater than the control arm. Patients treated with steroids and rituximab showed a lower level of anti-SARS-CoV-2 spike IgG. Differences in anti-spike IgG levels among chronic myeloid leukemia patients stratified according to tyrosine kinase inhibitor therapy and molecular response were observed, and they could have interesting implications on the evaluation of the effects of these drugs on the immune system, but having not reached statistical significance at the moment. The cohort of patients who received a stem cell transplant was very heterogeneous because it included different hematological malignancies and different types of transplant; however, a mean concentration of anti-SARS-CoV2 IgG greater than the control arm was reported. Indeed, among patients who performed a transplant for over 6 months only one had a spike IgG concentration below the cutoff. Conclusions: Our data confirm reduced serological response in hematological patients after anti-SARS-CoV-2 vaccination. However, we found a great diversity of SARS-CoV-2 antibody response according to types of pathologies and therapies.

Thrombin Assessment on Nanostructured Label-Free Aptamer-Based Sensors: A Mapping Investigation via Surface-Enhanced Raman Spectroscopy.

Aptamers, synthetic single-stranded DNA or RNA molecules, can be regarded as a valuable improvement to develop novel ad hoc sensors to diagnose several clinical pathologies. Their intrinsic potential is related to the high specificity and sensitivity to the selected target biomarkers, being capable of detecting very low concentrations and thus allowing an early diagnosis of a possible disease. This kind of probe can be usefully integrated into a number of different devices in order to provide a reliable acquisition of the analyte and properly elaborate the related signal. The study presents the fabrication and characterization of a label-free aptamer sensor designed using a gold-coated silicon nanostructured substrate to map the target molecule by means of surface-enhanced Raman spectroscopy (SERS). As a proof, thrombin was used as a model at four different concentrations (i.e., 0.0873, 0.873, 8.73, and 87.3 nM). SERS mapping analysis was carried out considering each representative band of the aptamer-thrombin complex (centered at 822, 1140, and 1558 cm-1) and then combining them in order to acquire a comprehensive and unambiguous measure of the target. In both cases, a valuable correlation was evaluated, even if the first approach can suffer from some limitations in the third band related to lower definition of the characteristic peak compared to those in the other two bands.

Predicting failure of hematopoietic stem cell mobilization before it starts: the predicted poor mobilizer (pPM) score.

Predicting mobilization failure before it starts may enable patient-tailored strategies. Although consensus criteria for predicted PM (pPM) are available, their predictive performance has never been measured on real data. We retrospectively collected and analyzed 1318 mobilization procedures performed for MM and lymphoma patients in the plerixafor era. In our sample, 180/1318 (13.7%) were PM. The score resulting from published pPM criteria had sufficient performance for predicting PM, as measured by AUC (0.67, 95%CI: 0.63-0.72). We developed a new prediction model from multivariate analysis whose score (pPM-score) resulted in better AUC (0.80, 95%CI: 0.76-0.84, p < 0001). pPM-score included as risk factors: increasing age, diagnosis of NHL, positive bone marrow biopsy or cytopenias before mobilization, previous mobilization failure, priming strategy with G-CSF alone, or without upfront plerixafor. A simplified version of pPM-score was categorized using a cut-off to maximize positive likelihood ratio (15.7, 95%CI: 9.9-24.8); specificity was 98% (95%CI: 97-98.7%), sensitivity 31.7% (95%CI: 24.9-39%); positive predictive value in our sample was 71.3% (95%CI: 60-80.8%). Simplified pPM-score can "rule in" patients at very high risk for PM before starting mobilization, allowing changes in clinical management, such as choice of alternative priming strategies, to avoid highly likely mobilization failure.

Long-term outcome and prospective validation of NIH response criteria in 39 patients receiving imatinib for steroid-refractory chronic GVHD.

Forty adults aged 28 to 73 years were entered into a prospective trial of imatinib for the treatment of steroid-refractory chronic graft-versus-host disease (SR-cGVHD). After 6 months, intention-to-treat (ITT) analysis of 39 patients who received the drug, regardless of the duration of treatment, revealed 14 partial responses (PR), 4 minor responses (MR) with relevant steroid sparing (46%) according to Couriel criteria, and 20 ≥ PR (51.3%), as per the National Institutes of Health (NIH) criteria and NIH severity score changes. The best responses were seen in the lungs, gut, and skin (35%, 50%, and 32%, respectively). After a median follow-up of 40 months, 28 patients were alive, with a 3-year overall survival (OS) and event-free survival of 72% and 46%, respectively. The 3-year OS was 94% for patients responding at 6 months and 58% for nonresponders according to NIH response, suggesting that these criteria represent a reliable tool for predicting OS after second-line treatment. Monitoring of anti-platelet-derived growth factor receptor (PDGF-R) antibodies showed a significant decrease in PDGF-R stimulatory activity in 7 responders, whereas it remained high in 4 nonresponders. This study confirms the efficacy of imatinib against SR-cGVHD and suggests that the response at 6 months significantly predicts long-term survival.

Plerixafor added to chemotherapy plus G-CSF is safe and allows adequate PBSC collection in predicted poor mobilizer patients with multiple myeloma or lymphoma.

We evaluated the safety and efficacy of plerixafor, subsequent to disease-specific chemotherapy followed by granulocyte-colony stimulating factor (G-CSF), in 37 multiple myeloma (MM) or lymphoma patients, who were candidates for autologous stem cell transplantation (ASCT) predicted as poor mobilizers (PMs). Patients were identified as predicted PMs according to the history of a previously failed mobilization attempt or the presence of ≥1 factors predicting an unsuccessful harvest, such as advanced disease, prior extensive radiotherapy, or prolonged treatment, with stem cell poisons, advanced age, or extensive bone marrow involvement. Plerixafor (0.24 mg/kg) was administered subcutaneously for up to 3 consecutive days while continuing G-CSF for 9 to 11 hours before the planned apheresis. Plerixafor administration was safe and no significant adverse events were recorded. We observed a median 4-fold increase (range: 1.4-32) in the number of circulating CD34(+) cells following plerixafor compared with baseline CD34(+) cell concentration (from a median of 5 cells/µL, range: 1-32, to a median of 32 cells/µL, range: 6-201). Twenty-seven of the 37 patients (14 of 17 with MM and 13 of 20 with lymphoma) had ≥2×10(6) CD34(+) cells/kg collected in 1-3 apheretic procedures. Of the 27 patients rescued with plerixafor, 24 (13 MM, 11 lymphoma) have been transplanted with plerixafor-mobilized peripheral blood stem cells, showing a rapid and durable hematologic recovery. Our results suggest that the addition of plerixafor to G-CSF after disease-oriented chemotherapy is safe and allows for a satisfactory harvest in order to perform a safe ASCT, in a relevant proportion of lymphoma and MM patients considered to be PMs.