ABSTRACT
Biological complexity of mechanisms of autoimmune hemolytic anemia (AHAI) in chronic lymphocytic leukemia B (CLL) and the relation cause / effect between these two diseases has been extensively researched, but currently is still far from being completely understood. It is known that the immune system has an important role in the pathogenesis of autoimmune diseases but also in the chronic lymphoproliferative malignancies. In this process of autoimmunity associated with immunodeficiency, the CLL neoplastic cells, the non-malignant B cells, T cells, and the cellular microenvironment cells are also involved. CLL pathological lymphocytes change peripheral immune tolerance acting as an antigen presenting cells and / or cells expressing inhibitory cytokines. The two subpopulations of T cells also have an important place: self-reactive T helper cells (TH) and regulatory T cells (Treg). The Fas / Fas ligand - cell death mechanism has a significant role both in maintaining cellular homeostasis, malignant hematopoietic cell expansion and the development of autoimmune disorders, including AIHA. The article reviews the etiopathogenesis of the autoimmune mechanism of AIHA in CLL, and its impact on the prognosis and long - term survival of patients with chronic lymphocytic leukemia B.
ABSTRACT
Chronic lymphocytic leukemia is still one of the most common hematologic malignancies. Finding a curative solution is the objective of numerous followed cases and clinical trials. Diagnosis is based on the interlocking of classic elements and newly identified prognostic factors but time to first treatment is still an open issue. CD38, ZAP 70, IgHV gene mutational status and cytogenetic changes are proven negatively influence the evolution of chronic lymphocytic leukemia. Whether through aggressive rapid evolution or by the difficulty of obtaining a complete remission or risk of early relapse, CLL is still important. Adapted to these prognostic factors, combined therapeutic regimens have proved to be effective in achieving a durable complete remission, new agents, with encouraging partial results, being studied. Requiring initial screening, for comparative purposes, a current and growing importance has minimal residual disease; its absence at the end of treatment represents a strong positive prognostic factor.
ABSTRACT
Acute myeloid leukemia (AML) is a heterogeneous disease in clinical presentation, outcome and therapeutic response. Cytogenetic and molecular characteristics are important prognostic indicators allowing the identification of distinct subtypes of AML, prognostic stratification and risk-adapted treatment. We present our experience during 5 years, in which we treated 245 patients with AML, of which we could genetically characterize 48 cases (26 females, 22 males) with a median age of 52 years. Cytogenetic analysis was performed by GTG banding on cultures of marrow cells treated with colcemid. Molecular analysis used RT-PCR performed on ABI 9700 platform in order to identify the following fusion genes: E2A-PBX1, TEL-AML1, AML1-ETO, PML-RARα, MLL-AF4, CBFC-MYH11, BCR-ABL, SIL-TAL, and MLL-AF9as well as mutations in Flt3, NPM1, WT1 genes. Fourteen patients were older than 60 years. In 12 we performed cytogenetic analysis showing 5 cases with complex karyotype, 2 normal karyotypes, 1 case of del(21), del (9), 11q- and t(3;15) respectively as well as 2 unevaluable karyotypes. These anomalies were associated with a high incidence of secondary AMLs (10/14) and with a low remission (CR) rate (5/14). Out of the 35 patients younger than 60 years, 25 were evaluated by cytogenetics showing a high incidence of favorable cytogenetic changes: 6 anomalies of chromosome 16 (5 inv (16) and 1 t (16; 16)), 3 t (15; 17), 3 cases of t (8; 21) of which 2 with additional abnormalities, 7 normal karyotypes and 1 case of 7q-, -y,-3 and respectively -8 associated with +18. In 25 cases molecular analysis was performed showing alterations in 21 patients: 6 cases with AML/ETO, 3 PML/RAR, 7 Flt3 mutations (2 associated with NPM1 mutation) as well as 1 case of isolated mutation of NPM1 and respectively WT1. CR rate was of 28/35. All cases with t (15; 17) and PML/RAR as well all cases with t (8; 21) and/or AML/ETO achieved CR. Out of the 7 cases with Flt3 mutations only 4 achieved CR including the 2 cases with associated NPM1 mutations. In our experience, genetic characteristics correlate with other prognostic markers such as age and secondary leukemia; "favorable" genetic anomalies were associated with a high CR rate; association of t (8; 21) with additional abnormalities did not influence CR rate.
