Global characteristics and outcomes of autologous hematopoietic stem cell transplantation for newly diagnosed multiple myeloma: A study of the worldwide network for blood and marrow transplantation (WBMT).

Autologous hematopoietic cell transplantation (AHCT) is a commonly used treatment in multiple myeloma (MM). However, real-world global demographic and outcome data are scarce. We collected data on baseline characteristics and outcomes from 61 725 patients with newly diagnosed MM who underwent upfront AHCT between 2013 and 2017 from nine national/international registries. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), relapse incidence (RI) and non-relapse mortality (NRM). Median OS amounted to 90.2 months (95% CI 88.2-93.6) and median PFS 36.5 months (95% CI 36.1-37.0). At 24 months, cumulative RI was 33% (95% CI 32.5%-33.4%) and NRM was 2.5% (95% CI 2.3%-2.6%). In the multivariate analysis, superior outcomes were associated with younger age, IgG subtype, complete hematological response at auto-HCT, Karnofsky score of 100%, international staging scoring (ISS) stage 1, HCT-comorbidity index (CI) 0, standard cytogenetic risk, auto-HCT in recent years, and use of lenalidomide maintenance. There were differences in the baseline characteristics and outcomes between registries. While the NRM was 1%-3% at 12 months worldwide, the OS at 36 months was 69%-84%, RI at 12 months was 12%-24% and PFS at 36 months was 43%-63%. The variability in these outcomes is attributable to differences in patient and disease characteristics as well as the use of maintenance and macroeconomic factors. In conclusion, worldwide data indicate that AHCT in MM is a safe and effective therapy with an NRM of 1%-3% with considerable regional differences in OS, PFS, RI, and patient characteristics. Maintenance treatment post-AHCT had a beneficial effect on OS.

IL-12p40 and sRAGE in serum correlate with chemically induced cleft palate in mice.

Cleft palate (CP), a congenital defect in the oral and maxillofacial regions, is difficult to detect prenatally. This study investigated the correlation between differentially expressed proteins in serum and CP induced by all-trans retinoic acid (atRA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice. We studied 80 mice in the following groups: male mice (male; n = 6), nonpregnant female control mice (NP-CRL; n = 6), healthy pregnant controls (P-CRL; Con; n = 24), pregnant mice with CP induced by atRA (n = 24), or pregnant mice with CP induced by TCDD (TCDD; n = 20). Pregnant mice were given with atRA (100 mg/kg) or TCDD (40 µg/kg), or corn oil by oral gavage at E10.5. The serum samples were collected and eight proteins-including interleukin (IL)-12p40, IL-12p70, receptor for advanced glycation end products (RAGE), interferon (IFN)-γ, IFN-ß, IL-10, leukemia inhibitory factor (LIF), and epiregulin-were detected by enzyme-linked immunosorbent assay. Placental tissues were immunostained for IL-12p40 and RAGE from stages E13.5 to E16.5. In P-CRL mice, serum IL-12p40 was significantly increased at E13.5 and declined over E14.5-E16.5. P-CRL had lower IFN-γ levels at E13.5 compared with NP-CRL. The CP groups showed lower concentrations of IL-12p40 at E13.5-E14.5 and clearly higher concentrations of soluble RAGE (sRAGE) at E13.5 when compared with P-CRL. IL-12p40 immunostaining clearly decreased in placental tissue sections obtained from E13.5 to E14.5 in both CP groups. These findings suggest that reduced levels of IL-12p40 and increased levels of sRAGE in serum may be correlated with chemically induced CP in mice, but further studies would be required to establish this.

Invasive and prognostic significance of pRB in esophageal squamous cell carcinoma: a meta-analysis.

This paper investigates the association between protein retinoblastoma (pRB) loss and the T,N stage and prognosis in esophageal squamous cell carcinomas (ESCCs) using meta-analysis. We conducted a meta-analysis of 16 studies, comprising 1,117 patients to clarify this issue. All the studies searched by the electronic literature PubMed and http://www.KJEBM.com, which had been published during the period from January 1996 to January 2012 according to the inclusion criteria. Summary odds ratios (OR) were calculated using fixed or random-effects models. The summary odds ratios (ORs) for pRB inactive were 0.64 (95% confidence interval [CI]:0.45-0.91, P = 0.01) for T1/T2 versus T3/T4 tumors; summary OR = 0.69 (95% CI:0.51-0.94, P = 0.02) for N0 versus N1 tumors. The association between pRB loss and prognosis was examined in nine studies, and the summary hazard ratio was 1.39 (95% CI:1.11-1.74, P = 0.004). pRB inactive was significant associated with T3/T4 tumors and N1 stage as well as adverse prognosis for ESCCs. It appears warranted to prospectively validate that pRB loss may be used for subdividing the T,N stage evaluation of patients with ESCCs, and these patients may be the preponderant people for individualized treatment or target therapy.