therapies resulting in longer survival.
Immune dysfunction effecting both the adaptive and innate immune responses occurs early in the course of CLL and high-count monoclonal B-cell lymphocytosis (MBL) [ 6 , 7 , 8 ]. The mechanism by which CLL induces immune dysfunction is poorly understood. Tcell dysfunction in CLL is characterized by abnormal CD4:CD8 effector ratios, skewed helper Tcell profiles (e.g., increased Th2:Th1), impaired immune synapse formation, and reduced proliferative and cytotoxic activities characteristic of Tcell exhaustion [ 8 , 9 , 10 , 11
Mateusz Nowicki, Piotr Stelmach and Anna Szmigielska-Kapłon
decreased expression of major histocompatibility complex (MHC) II antigens, which in turn impairs the function of T-lymphocytes [ 20 ]. This process is associated with decreased activity of NK-κB signaling pathway [ 8 ].
VEGF significantly regulates proliferation and migration of EC. By recruiting HSC and endothelial progenitor cells VEGF regulates microvessels development in the bone marrow niche and fundamentally affects hematopoiesis [ 15 , 21 ].
ANGPT1 and ANGPT2
Apart from VEGF, angiopoietin 1 (ANGPT1) and angiopoietin 2 (ANGPT2), both binding to receptor
Samia Abd El-Moneim Ebied, Nadia Aly Sadek, Nadia El-Sayed Zaki, Samir Ali Abd El- Kaream and Heba Khafagui Ahmed El Kashif
accumulation of blast cells in the bone marrow and peripheral blood [ 12 ]. Acute lymphoblastic leukemia (ALL) is a malignant disease characterized by the accumulation of lymphoblasts and it may be B or T lineages and the first attempt at classifying ALL was the French-American-British (FAB) morphological criteria that divided ALL into 3 subtypes (L1, L2 and L3) based on cell size, cytoplasm, nucleoli, vacuolation and basophilia. In 1997, the World Health Organization proposed a composite classification in an attempt to account for morphology and cytogenetic profile of the
European Congress, 02/11/2016, Vienna.
Schmitter S Brock E Holzerny P Günzel CA Ruckdäschel S Regulatory Agencies’ Perspective on “Progression-Free Survival” (PFS), Poster-No. PCN289, ISPOR 19th Annual European Congress, 02/11/2016 Vienna
 Ishikawa T, Akazawa K, Hasegawa Y, et al. Survival outcomes of neoadjuvant chemotherapy with zoledronic acid for HER2-negative breast cancer. J Surg Res 2017;220:46–51. 10.1016/j.jss.2017.05.066
Ishikawa T Akazawa K Hasegawa Y Survival outcomes of neoadjuvant chemotherapy with zoledronic acid