Risk Factors and Outcomes Related to Pediatric Intensive Care Unit Admission after Hematopoietic Stem Cell Transplantation: A Single-Center Experience

Abstract To describe incidence, causes, and outcomes related to pediatric intensive care unit (PICU) admission for patients undergoing hematopoietic stem cell transplantation (HSCT), we investigated the risk factors predisposing to PICU admission and prognostic factors in terms of patient survival. From October 1998 to April 2015, 496 children and young adults (0 to 23 years) underwent transplantation in the HSCT unit. Among them, 70 (14.1%) were admitted to PICU. The 3-year cumulative incidence of PICU admission was 14.3%. The main causes of PICU admission were respiratory failure (36%), multiple organ failure (16%), and septic shock (13%). The overall 90-day cumulative probability of survival after PICU admission was 34.3% (95% confidence interval, 24.8% to 47.4%). In multivariate analysis, risk factors predisposing to PICU admission were allogeneic HSCT (versus autologous HSCT, P  = .030) and second or third HSCT ( P  = .018). Characteristics significantly associated with mortality were mismatched HSCT ( P  = .011), relapse of underlying disease before PICU admission ( P P  = .012), hepatic failure at admission ( P  = .021), and need for invasive ventilation during PICU course (

Pediatric IgG4-related lymphadenopathy: A rare condition associated with autoimmunity and lymphoproliferative disorders

gG4-related disease (IgG4-RD) is a clinical-pathological entity defined by the presence of tissue-based tumor lesions, histologically featuring a dense lymphoplasmacytic infiltrate with numerous IgG4-positive plasma cells (IgG4/IgG ratio >40%). Serum IgG4 concentration is often elevate

Treosulfan-based conditioning regimen in sibling and alternative donor hematopoietic stem cell transplantation for children with sickle cell disease

none20nononeMarzollo, Antonio; Calore, Elisabetta; Tumino, Manuela; Pillon, Marta; Gazzola, Maria Vittoria; Destro, Roberta; Colombatti, Raffaella; Marson, Piero; Tison, Tiziana; Colpo, Anna; Mainardi, Chiara; Gabelli, Maria; Boaro, Maria Paola; Rossin, Sara; Strano, Aurora; Quaglia, Nadia; Menzato, Federica; Basso, Giuseppe; Sainati, Laura; Messina, ChiaraMarzollo, Antonio; Calore, Elisabetta; Tumino, Manuela; Pillon, Marta; Gazzola, Maria Vittoria; Destro, Roberta; Colombatti, Raffaella; Marson, Piero; Tison, Tiziana; Colpo, Anna; Mainardi, Chiara; Gabelli, Maria; Boaro, MARIA PAOLA; Rossin, Sara; Strano, Aurora; Quaglia, Nadia; Menzato, Federica; Basso, Giuseppe; Sainati, Laura; Messina, Chiar

CK2β Regulates Hematopoietic Stem Cell Biology and Erythropoiesis

The Ser-Thr kinase CK2 plays important roles in sustaining cell survival and resistance to stress and these functions are exploited by different types of blood tumors. Yet, the physiological involvement of CK2 in normal blood cell development is poorly known. Here, we discovered that the β regulatory subunit of CK2 is critical for normal hematopoiesis in the mouse. Fetal livers of conditional CK2β knockout embryos showed increased numbers of hematopoietic stem cells associated to a higher proliferation rate compared to control animals. Both hematopoietic stem and progenitor cells (HSPCs) displayed alterations in the expression of transcription factors involved in cell quiescence, self-renewal, and lineage commitment. HSPCs lacking CK2β were functionally impaired in supporting both in vitro and in vivo hematopoiesis as demonstrated by transplantation assays. Furthermore, KO mice developed anemia due to a reduced number of mature erythroid cells. This compartment was characterized by dysplasia, proliferative defects at early precursor stage, and apoptosis at late-stage erythroblasts. Erythroid cells exhibited a marked compromise of signaling cascades downstream of the cKit and erythropoietin receptor, with a defective activation of ERK/JNK, JAK/STAT5, and PI3K/AKT pathways and perturbations of several transcriptional programs as demonstrated by RNA-Seq analysis. Moreover, we unraveled an unforeseen molecular mechanism whereby CK2 sustains GATA1 stability and transcriptional proficiency. Thus, our work demonstrates new and crucial functions of CK2 in HSPC biology and in erythropoiesis