Evaluating the impact of age and disease on survival of chronic lymphocytic leukaemia patients by a new method

Background: The impact of chronic lymphocytic leukaemia (CLL) on survival may be different in younger patients, but this remains controversial. Objectives: The aim of the study was to examine the effect of age on survival in CLL using an original method. Methods: Clinical, laboratory and survival data of 87 CLL patients treated in our institute were analysed. The survival of patients in different age groups was determined and compared, as related to the expected survival of age‐ and gender‐matched general population obtained from national statistical data. Results: The mean age in the younger (≤ 65 years, n = 37) and older (> 65 years) age groups was 56 and 74 years (p < 0.001). The younger group had more unfavourable presentation, with advanced stage (Rai 2–4) in 46% vs. 16% (p = 0.002), and diffuse involvement of bone marrow in 60% vs. 18% (p = 0.03), compared with the older group, and were more likely to require treatment (p = 0.02). The Kaplan–Meyer curve showed a more favourable survival for the younger group. However, the loss of expected survival exposed a reversed pattern: while the older patients lost only 13%, the survival loss in the younger patients was 44% (p < 0.001). Conclusions: Chronic lymphocytic leukaemia had a more unfavourable presentation and a more severe clinical course in the younger patients. Our method of evaluating the negative impact of disease on expected survival reveals that their survival also is significantly more affected than that of older patients. We suggest calculating the loss of expected survival as a new criterion for assessing disease impact.     

Toll-like receptors and their ligands control mesenchymal stem cell functions.

Mesenchymal stem cells (MSCs) are widespread in adult organisms and may be involved in tissue maintenance and repair as well as in the regulation of hematopoiesis and immunologic responses. Thus, it is important to discover the factors controlling MSC renewal and differentiation. Here we report that adult MSCs express functional Toll-like receptors (TLRs), confirmed by the responses of MSCs to TLR ligands. Pam3Cys, a prototypic TLR-2 ligand, augmented interleukin-6 secretion by MSC, induced nuclear factor kappa B (NF-kappaB) translocation, reduced MSC basal motility, and increased MSC proliferation. The hallmark of MSC function is the capacity to differentiate into several mesodermal lineages. We show herein that Pam3Cys inhibited MSC differentiation into osteogenic, adipogenic, and chondrogenic cells while sparing their immunosuppressive effect. Our study therefore shows that a TLR ligand can antagonize MSC differentiation triggered by exogenous mediators and consequently maintains the cells in an undifferentiated and proliferating state in vitro. Moreover, MSCs derived from myeloid factor 88 (MyD88)-deficient mice lacked the capacity to differentiate effectively into osteogenic and chondrogenic cells. It appears that TLRs and their ligands can serve as regulators of MSC proliferation and differentiation and might affect the maintenance of MSC multipotency.     

Expression of the chemokine receptor CCR2 on immature B cells negatively regulates their cytoskeletal rearrangement and migration

Immature B cells are targeted to specific areas in the spleen, where a fraction of these cells receive signals that induce them to mature and participate in the immune response. In this study, we show that the C-C chemokine receptor 2 (CCR2) is transcribed in immature B cells, while its message is dramatically down-regulated at the mature stage. CCR2-deficient cells exhibit up-regulation of chemokine-induced actin polymerization, migration, and homing to the lymph nodes of immature B cells. In addition, we demonstrate that control of homing by CCR2 is mediated by its ligand, CCL2/JE, which is secreted by B cells and down-regulates the stromal derived factor-1 (SDF-1) signaling cascade. Thus, this study describes an additional, previously uncharacterized, role for CCR2 and its ligand as negative regulators of the homing of immature B cells.     

Maternal medical compromise during pregnancy and pregnancy outcomes

Objective: To examine the outcomes of pregnancy and newborn following an event of maternal medical compromise during pregnancy.

Methods: A retrospective study was performed on all patients hospitalized following an event of medical compromise during pregnancy. Medical compromise was divided to acute or chronic bleeding, major or complicated operations, and admission to intensive care unit (ICU). Data collected included maternal, fetal, neonatal and child’s follow-up.

Results: The study included 51 pregnant patients and 58 fetuses. The study group had increased risk of preterm deliveries (35.0 versus 6.5%, p?p?p?=?0.002). Patients with acute bleeding had higher rates of cesarean sections, preterm deliveries, admissions to neonatal ICU and neonatal mortality. Two cases of fetal abnormalities included brain abnormalities and pericardial effusion. Three terminations of pregnancies were performed: two in patients in ICU due to severe maternal medical condition and one in the fetus with brain abnormalities.

Conclusions: Maternal medical compromise during pregnancy increases the risk for preterm deliveries, cesarean delivery and low Apgar scores. Acute bleeding was the main cause of medical compromised and with the higher rates of adverse outcomes.