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Clofarabine (CLO) and cyclophosphamide (CY) combinations were tested in late stage refractory/relapsed (R/R) acute lymphoblastic leukemia (ALL) with disappointing results and high-grade toxicity. We designed a sequential 5-day combination of CLO 40 mg/m 2 /d plus CY 400 mg/m 2 /d as first salvage for Philadelphia-negative ALL patients refractory or relapsed until 24 months from complete remission (CR). Primary endpoint was an overall response rate (ORR) ≥ 40%. Among 26 study patients (median age 40.5 years) ORR was 57.6% (CR with complete [ n  = 8] or incomplete [ n  = 7] hematologic recovery). Despite severe myelotoxicity, no dose-limiting toxicity suggested de-intensification of CLO schedule. With a median follow-up of 17.0 months, median and 1-year overall and disease-free survival were 6.5 months and 28.6%, and 3.7 months and 28.1%, respectively. This association was tolerable and more effective in patients younger than 40 years with B-precursor ALL, longer first CR, not previously transplanted and achieving CR with full hematological recovery.

Genomic DNA extraction is a primary component of genomic research and diagnostic routine analysis. Recently, the importance of this process has been highlighted by the necessity to standardize the diagnostic procedure. In this regard, the Minimal Residual Disease (MRD) Network of the Fondazione Italiana Linfomi (FIL MRD Network) has performed a comparative study of four different commercially available kits for DNA extraction, applying them on a panel of cellular pellets, with the aim of defining possible technical recommendations in order to harmonize and standardize diagnostic procedures in the clinical setting. Overall, all four kits usually allowed the recovery of a significant quantity of high-quality DNA (in most conditions), although specific indications could be addressed for cellular pellets of different sizes.

The capacity to generate effective dendritic cells (DC) from adult acute lymphoblastic leukemia (ALL) patients in complete remission (CR) and off-therapy was investigated. Monocyte-derived DC cultured in the presence of granulocyte-macrophage colony-stimulating factor, interleukin (IL)-4 and tumor necrosis factor (TNF)-alpha expressed maturation markers, produced IL-12 and loaded apoptotic bodies to a similar extent to normal DC. Patients' circulating T and NK lymphocytes were normally represented and, after stimulation, were capable of producing TNF-alpha and interferon-gamma to a similar extent to control lymphocytes. DC loaded with leukemia-derived apoptotic bodies increased their ability to stimulate both allogeneic and autologous lymphocytes, and to generate specific anti-leukemic CD3 + cells. These findings offer a rationale for the design of DC-based vaccine programs for adult ALL patients in CR with the aim of controlling/eradicating the disease.