الفهرس 
CHRONIC LYMPHOCYTIC LEUKAEMIAOnly 14 pages are availabe for public view
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Abstract
CLL follows an extremely variable clinical course with overall survival times ranging from months to decades. Some patients have no or minimal signs and symptoms during their entire disease course and have a survival time similar to age-matched controls. Other patients experience rapidly deteriorating blood counts and organomegaly and suffer from symptoms at diagnosis or soon thereafter necessitating therapy.
The standard clinical procedures to estimate prognosis are the clinical staging systems developed by Rai and Binet. However, there is heterogeneity in the course of the disease among individual patients within a single stage group. Most importantly, the clinical staging systems do not allow one to predict if and at what rate there will be disease progression in an individual patient diagnosed with early stage disease. Therefore, there is a need to identify markers that may help to refine outcome prediction for these individuals. Recently CD38 expression has demonstrated a highly predictive prognostic value. Other recent research has moved toward a molecular genetic marker that may not only provide insight into the biology and transforming events but may also define mechanisms directly responsible for the clinical behavior of the disease with regard to disease progression, response to treatment and overall survival.
One of the most important molecular genetic parameters defining pathogenic and prognostic subgroups of CLL is the mutation status of the IgVH genes. CLL separation was made into two different groups: one with unmutated IgVH genes, assumed to originate from pregerminal center cells, and another with mutated IgVH genes, thought to originate from postgerminal center cells. While CLL with unmutated IgVH gene shows an unfavorable course with rapid progression, CLL with mutated IgVH gene often shows slow progression and longer survival.
The present study aimed to assess the clinical usefulness of CD38 percent expression and IgVH gene mutational status in B-CLL patients in predicting disease course and outcome, to gain insight into the degree of association between them and to correlate these values with known clinical and haematological prognostic factors.
We studied CD38 % expression and IgVH gene mutational status in 20 B-CLL patients. Their age ranged from 42 years old to 83 years old with a mean of 59 years. They were 15 males and 5 females with a ratio of 3:1. DNA sequencing was successful in only 10 out of the 20 patients. We divided the patients into groups according to their CD38 % expression on B cells and IgVH gene mutational status into CD38 negative (<20% expression), CD38 positive (≥20% expression) groups and mutated (<98% homology), unmutated (≥98% homology) groups. We studied the correlation between the different groups with various patient characteristics including age, sex, Rai and Binet stages, haemoglobin level, TLC, platelet count, bone marrow % lymphocyte, hepatomegaly, splenomegaly, lymph node involvement and B cell immunophenotype. Then we assessed the correlation between CD38 % expression groups and the IgVH mutational status groups.
Our data confirmed that B cell CLL patients with positive CD38 expression and unmutated IgVH gene have aggressive clinical presentation with worse prognosis than patients with negative CD38 expression and mutated IgVH gene who have a less aggressive disease with better prognosis. We also found statistically significant correlation between positive CD38 expression with unmutated IgVH gene and between negative CD38 expressions with mutated IgVH gene, proving that CD38 % expression can be used as a surrogate marker to IgVH gene mutational status in CLL.