Association of Host Factors With Antibody Response to Seasonal Influenza Vaccination in Allogeneic Hematopoietic Stem Cell Transplant Patients.

BACKGROUND: Influenza vaccination efficacy is reduced after hematopoietic stem cell transplantation (HSCT) and patient factors determining vaccination outcomes are still poorly understood. METHODS: We investigated the antibody response to seasonal influenza vaccination in 135 HSCT patients and 69 healthy volunteers (HVs) in a prospective observational multicenter cohort study. We identified patient factors associated with hemagglutination inhibition titers against A/California/2009/H1N1, A/Texas/2012/H3N2, and B/Massachusetts/2012 by multivariable regression on the observed titer levels and on seroconversion/seroprotection categories for comparison. RESULTS: Both regression approaches yielded consistent results but regression on titers estimated associations with higher precision. HSCT patients required 2 vaccine doses to achieve average responses comparable to a single dose in HVs. Prevaccination titers were positively associated with time after transplantation, confirming that HSCT patients can elicit potent antibody responses. However, an unrelated donor, absolute lymphocyte counts below the normal range, and treatment with calcineurin inhibitors lowered the odds of responding. CONCLUSIONS: HSCT patients show a highly heterogeneous vaccine response but, overall, patients benefited from the booster shot and can acquire seroprotective antibodies over the years after transplantation. Several common patient factors lower the odds of responding, urging identification of additional preventive strategies in the poorly responding groups. CLINICAL TRIALS REGISTRATION: NCT03467074.

Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) are a group of clonal disorders characterized by aberrant hematopoietic proliferation and an increased tendency toward leukemic transformation. We used targeted next-generation sequencing (NGS) of 104 genes to detect somatic mutations in a cohort of 197 MPN patients and followed clonal evolution and the impact on clinical outcome. Mutations in calreticulin (CALR) were detected using a sensitive allele-specific polymerase chain reaction. We observed somatic mutations in 90% of patients, and 37% carried somatic mutations other than JAK2 V617F and CALR. The presence of 2 or more somatic mutations significantly reduced overall survival and increased the risk of transformation into acute myeloid leukemia. In particular, somatic mutations with loss of heterozygosity in TP53 were strongly associated with leukemic transformation. We used NGS to follow and quantitate somatic mutations in serial samples from MPN patients. Surprisingly, the number of mutations between early and late patient samples did not significantly change, and during a total follow-up of 133 patient years, only 2 new mutations appeared, suggesting that the mutation rate in MPN is rather low. Our data show that comprehensive mutational screening at diagnosis and during follow-up has considerable potential to identify patients at high risk of disease progression.

A prenatal prediction model for total nucleated cell count increases the efficacy of umbilical cord blood banking.

BACKGROUND: The most important factor for the selection of an umbilical cord blood unit (CBU) for hematopoietic stem cell transplantation is the total nucleated cell (TNC) count as a surrogate marker for stem cell content in the CBU. At present, about one in five donors can provide a CBU with a sufficient TNC count for umbilical cord blood (UCB) banking. It is labor-intensive to obtain consent of all eligible donors and optimization of the selection is needed. The purpose of this study was to investigate prenatal clinical predictors for TNC count that would help to identify successful UCB donors already on admission to the delivery unit. STUDY DESIGN AND METHODS: This study was a retrospective analysis of 758 cryopreserved CBUs, collected from 2002 to 2006. Maternal and fetal factors analyzed were maternal age, gravidity, parity, weight, height, diabetes, premature rupture of membranes, gestational age, fetal sex, and birthweight. The impact on a high TNC count (<150 × 10(7) vs. ≥ 150 × 10(7)) of the CBU was modeled in a multivariate analysis model. RESULTS: Fetal birthweight was the strongest predictor (p < 0.001) of TNC count of at least 150 × 10(7). With a composite score of parity, gestational week, maternal weight and height, fetal sex, and birthweight, a nomogram was developed that increased banking rates from 22.7% to 31.9% while decreasing the number of banked CBUs from 149 to 79. CONCLUSIONS: Our prenatal prediction model increases the efficacy of obtaining informed consent for UCB banking while still allowing relevant numbers of CBUs to be banked.

Lung histology predicts outcome of bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation.

Bronchiolitis obliterans (BO) is a severe complication after allogeneic hematopoietic stem cell transplantation with an unfavorable prognosis. Lung biopsy remains the gold standard for diagnosis. In this retrospective single-center study, we describe 33 patients who underwent biopsy for suspected BO. Ten patients had constrictive BO (CBO); 9 had lymphocytic bronchiolitis (LB), characterized by lymphocytic infiltration of the bronchioles. Six additional patients (4, CBO; 2, LB) had concomitant infection; 8 had other pathological diagnoses. Seven patients with CBO and 3 with LB met the National Institutes of Health consensus BO syndrome definition criteria. An additional 7 patients with histologically confirmed CBO did not meet the consensus definition, 4 of them because of concomitant airway infection. At diagnosis, there were no significant differences between the CBO and LB groups in clinical presentation; pulmonary function tests (median forced expiratory volume in one second [FEV1] at baseline, 90.4% and 99% predicted, at time of video-assisted thoracoscopic surgery, 55.1% and 60.8% for CBO and LB groups, respectively); and chest scans. Treatment was similar in both groups but outcome was different depending on histological findings. FEV1 significantly improved in LB patients compared with CBO patients. Survivals at 1 and 3 years were 77% ± 12% and 60% ± 14% for patients with CBO and 91% ± 9% for patients with LB (P = .028). Lung biopsy in patients with suspected BO enables better characterization of the pattern of BO syndrome. In contrast to CBO, LB is associated with a good long-term prognosis.

[Anticoagulation in Venous Thromboembolism: How Long and Which Dose?] / Antikoagulation bei venöser Thromboembolie: wie lange und welche Dosierung?

Anticoagulation in Venous Thromboembolism: How Long and Which Dose? Abstract. Venous thromboembolism is quite common in daily practice. As soon as the diagnosis is confirmed, anticoagulation should be started immediately. Nowadays DOACs are the first choice for treatment of VTE. An important issue is the duration of anticoagulation in an individual patient. Generally, the anticoagulation should be continued for at least three months in any patient. While anticoagulation can be safely stopped after three months in patients with isolated distal DVT it should be continued for an unlimited period in persons with unprovoked proximal DVT and PE. In the vast majority of cases making that decision is not straightforward. Decision making involves assessing risks and benefits on an individual basis. Another important issue is dose reduction of the DOACs during treatment. The goal of this article is to show the factors that must be considered for decision making.

Dkk3 levels in patients with myeloproliferative neoplasms.

INTRODUCTION: Dickkopf-3 (Dkk3) has been proposed as tumor suppressor gene and a marker for tumor blood vessels and has pro-angiogenic properties. Dkk3 is expressed in platelets and megakaryocytes from healthy controls and patients with BCR-ABL1-negative myeloproliferative neoplasms (MPN). The aim of this study is, to find out whether patients with MPN have higher Dkk3 serum levels than normal controls. MATERIAL & METHODS: We analyzed Dkk3 serum levels with ELISA in patients with newly diagnosed and untreated MPN, including 10 essential thrombocythemia (ET), 10 polycythemia vera (PV), 10 primary meylofibrosis (PMF) and 10 healthy blood donors and correlated these findings with biological and clinical key data and the JAK2-V617F status. Dkk3 levels were corrected to platelet count, Dkk3c, as patients with MPN have higher platelet counts than controls. RESULTS: As expected, patients with MPN have higher platelet counts than normal controls. Dkk3 serum levels of patients with MPN (5.4 ± 6.1 ng/ml) showed no significant difference compared to normal controls (4.4 ± 3.8 ng/ml). Regarding Dkk3c, a significant difference to controls was found in PV (8.5 ± 8.7 ng/ml; p=0.04), but not in ET and PMF (5.7 ± 3.8 ng/ml; p=0.07 and 2.7 ± 3.6 ng/ml; p=0.9; respectively. Dkk3c correlated with the JAK2-V617F mutational burden (p=0.014, Rho=0.445). CONCLUSION: Dkk3 levels corrected to platelet count showed higher levels in PV than normal controls. Elevated Dkk3c level could possibly correlate to platelet activation in PV patients and increased Dkk3 release. Whether this remains a surrogate marker of platelet release or it contributes to the thrombophilic state through its pro-angiogenic properties remains to be shown.