Philadelphia-like acute lymphoblastic leukemia is associated with minimal residual disease persistence and poor outcome. First report of the minimale residual disease-oriented GIMEMA LAL1913

Early recognition of Ph-like acute lymphoblastic leukemia cases could impact on the management and outcome of this subset of B-lineage ALL. To assess the prognostic value of the Ph-like status in a pediatric-inspired, minimal residual disease (MRD)-driven trial, we screened 88 B-lineage ALL cases negative for the major fusion genes (BCR-ABL1, ETV6-RUNX1, TCF3-PBX1 and KTM2Ar) enrolled in the GIMEMA LAL1913 front-line protocol for adult BCR/ABL1-negative ALL. The screening - performed using the “BCR/ABL1-like predictor” - identified 28 Ph-like cases (31.8%), characterized by CRLF2 overexpression (35.7%), JAK/STAT pathway mutations (33.3%), IKZF1 (63.6%), BTG1 (50%) and EBF1 (27.3%) deletions, and rearrangements targeting tyrosine kinases or CRLF2 (40%). The correlation with outcome highlighted that: i) the complete remission (CR) rate was significantly lower in Ph-like compared to non-Ph-like cases (74.1% vs 91.5%, p=0.044); ii) at time point 2 (TP2), decisional for transplant allocation, 52.9% of Ph-like cases vs 20% of non-Phlike were MRD-positive (p=0.025); iii) the Ph-like profile was the only parameter associated with a higher risk of being MRD-positive at TP2 (p=0.014); iv) at 24 months, Ph-like patients had a significantly inferior event-free and disease-free survival compared to non-Ph-like patients (33.5% vs 66.2%, p=0.005 and 45.5% vs 72.3%, p=0.062, respectively). This study documents that Ph-like patients have a lower CR rate, EFS and DFS, as well as a greater MRD persistence also in a pediatric-oriented and MRD-driven adult ALL protocol, thus reinforcing that the early recognition of Ph-like ALL patients at diagnosis is crucial to refine risk-stratification and to optimize therapeutic strategies

Relationship between T cell subsets and suppressor cell activity in chronic hepatitis B virus (HBV) infection

The relationship between T cell subset, as defined by monoclonal antibodies, and suppressor cell function, using a short lived suppressor cell assay, was studied in 38 chronic hepatitis B virus (HBV) carriers and in 32 patients with HBsAg negative chronic active hepatitis (CAH). Patients with HBV chronic infection showed an absolute reduction in the OKT4 positive subset and a significantly decreased OKT4/OKT8 ratio, as compared with healthy controls. Patients with anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) positive CAH with or without antibodies to HBV antigens, namely anti-HBs and anti-HBc, demonstrated a significant reduction in cytotoxic/suppressor T cells and an increase helper/suppressor ratio. A negative correlation between suppressor index (SI) and OKT4/OKT8 ratio (P<0.01), and a positive correlation between SI and OKT8 positive cells absolute number (P<0.01) were also observed

Relationship between T cell subsets and suppressor cell activity in chronic hepatitis B virus (HBV) infection.

The relationship between T cell subset, as defined by monoclonal antibodies, and suppressor cell function, using a short lived suppressor cell assay, was studied in 38 chronic hepatitis B virus (HBV) carriers and in 32 patients with HBsAg negative chronic active hepatitis (CAH). Patients with HBV chronic infection showed an absolute reduction in the OKT4 positive subset and a significantly decreased OKT4/OKT8 ratio, as compared with healthy controls. Patients with anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) positive CAH with or without antibodies to HBV antigens, namely anti-HBs and anti-HBc, demonstrated a significant reduction in cytotoxic/suppressor T cells and an increased helper/suppressor ratio. A negative correlation between suppressor index (SI) and OKT4/OKT8 ratio (P less than 0.01), and a positive correlation between SI and OKT8 positive cells absolute number (P less than 0.01) were also observed