Key Points• The total number of somatic mutations was inversely correlated with survival and risk of leukemic transformation in MPN.• The great majority of somatic mutations were already present at MPN diagnosis, and very few new mutations were detected during follow-up.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.

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.

Our prenatal prediction model increases the efficacy of obtaining informed consent for UCB banking while still allowing relevant numbers of CBUs to be banked.

volume was 77 mL/kg, twice the laboratory's top normal range in women (28 mL/kg). Serum erythropoietin level was repeated and was found to have decreased below normal at 3.0 mU/mL. A diagnosis of PV was made, and a therapeutic phlebotomy was initiated.To date, the patient has undergone 38 therapeutic phlebotomies during a 6-year period, and the patient continues with elevated hemoglobin concentrations and platelet counts. Her symptoms are well controlled, although she continues to have splenomegaly according to both physical examination and radiographic imaging results. She has never had a thrombotic event, nor has she ever received a cytotoxic agent.Result of a repeated bone marrow biopsy, performed 12 years after the initial diagnosis of PMF and 6 years after the diagnosis of PV, was a markedly hypercellular presence, without reticulum or fibrosis. Genetic study results showed a normal karyotype, and fluorescence in situ hybridization testing results did not reveal abnormalities. A quantitative JAK2 assay result showed an allele burden of 54%. At this point in the course of the disease, there is no evidence of prior MF in this patient.The case of this patient demonstrates the evolution of transfusiondependent PMF into phlebotomy-dependent PV, a reversal of the usual progression. According to the DPSS-plus risk system, the patient had 3 adverse features on presentation, placing her in the Intermediate-2 group with a median survival time of 3.6 years. Despite these adverse features on presentation, she has now survived 13 years after the intial presentation and is behaving in an indolent fashion, typical of PV and not PMF.

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