Summary Fludarabine plus cytarabine (Ara‐C) and idarubicin (FLAI) is an effective and well‐tolerated induction regimen for the treatment of acute myeloid leukaemia (AML). This phase III trial compared the efficacy and toxicity of FLAI versus idarubicin plus Ara‐C and etoposide (ICE) in 112 newly diagnosed AML patients <60 years. Fifty‐seven patients received FLAI, as the first induction–remission course, and 55 patients received ICE. Post‐induction treatment consisted of high‐dose Ara‐C (HDAC). After HDAC, patients in complete remission (CR) received a second consolidation course (mitoxantrone, etoposide, Ara‐C) and autologous stem cell transplantation (auto‐SCT) or allogeneic (allo)‐SCT, according to the age, disease risk and donor availability. After a single induction course, CR rate was 74% in the FLAI arm and 51% in the ICE arm (P = 0·01), while death during induction was 2% and 9% respectively. Both haematological (P = 0·002) and non‐haematological (P = 0·0001) toxicities, especially gastrointestinal (i.e. nausea, vomiting, mucositis and diarrhoea), were significantly lower in FLAI arm. In both arms, relapses were more frequent in patients who were not submitted to allo‐SCT. After a median follow‐up of 17 months, 30% and 38% of the patients are in continuous CR in FLAI and ICE arm respectively. Our prospective randomised study confirmed the anti‐leukaemic effect and the low toxic profile of FLAI as induction treatment for newly diagnosed AML patients.

Progress in treatment of acute myeloid leukemia (AML) is slow and treatment intensification alone has limited effects, particularly in poor-risk cases. Poor-risk cases, that are identified mainly by prior history, leukemic cell mass and cytogenetic abnormalities, share multiple mechanisms of drug resistance that are responsible for treatment failure. Since Pgp-mediated resistance to anthracycline can be reduced with Idarubicin (IDA) and resistance to arabinosyl cytosine (AC) can be reduced with Fludarabine (FLUDA), we tested a combination of high dose AC (2000 mg/sqm, 5 doses), FLUDA (30 mg/sqm, 5 doses) and IDA (12 mg/sqm, 3 doses) for remission induction and consolidation in 45 consecutive cases of poor-risk AML. The complete remission (CR) rate was 71% after the first course and 82% overall, with a projected 2-year survival and relapse-free survival of 44% and 50% respectively. Non-hematologic toxicity was very mild, that is very important in elderly patients, but hemopoietic toxicity was substantial, with a time to hematologic recovery of 3 to 4 weeks and two cases of death in CR. Peripheral blood stem cells (PBSC) could be mobilized and collected successfully only in 11 cases. This three-drug combination is effective and has a limited non-hematologic toxicity, but FLUDA may increase the difficulty of obtaining PBSC early after remission induction.

Summary:An interim report evaluating the feasibility of myeloablative therapy followed by peripheral blood stem cell (PBSC) autotransplant in patients aged Ͼ60 years is presented. In the last 2 years 19 patients Ͼ60 years old with several oncological conditions, mostly hematological, underwent PBSC autotransplant either as salvage therapy following relapse or resistance to conventional treatment, or as consolidating therapy as a part of a well defined protocol. There were 13 males and six females; the mean age was 66.9 years (range 61-76 years); nine patients had resistant or relapsed lymphoma, six myeloma, two acute leukemia, one Waldenstrom's disease and one lung cancer. Myeloablative schemes included BEAM exclusively for lymphomas, busulfan and melphalan (Bu-MPH) mainly for myeloma, busulfan and cyclophosphamide (Bu-CTX) for lymphomas and leukemia and VP-16 and CTX for lung cancer. Mobilization of CD34 ϩ cells was achieved in all patients with the combination of high-dose CTX and G-CSF with collections between 2.83 to 19.04 × 10 6 /kg (mean 7.1). All patients engrafted with a median time for recovery of PMN (Ͼ0.5 × 10 3 / l) of 10 days (range 8-12 days) and for PLT (Ͼ20 × 10 3 / l) of 12 days (range 10-17 days). Major responses were obtained in 15 of 16 patients evaluable for response and eight patients entered CR; overall eight patients are in CR, five are alive with disease, five are dead from disease progression and one is dead because of congestive heart failure 7 months following PBSC autotransplant. No early deaths following the procedure occurred; major side-effects were grade I-II mucositis (58%), fever with documented sepsis (10%), pneumonia (5%), cardiac, renal and liver toxicity (5%). Cardiac function was evaluated before and after myeloablative therapy by VEF in all patients; no significant modifications were necessary. In conclusion, our experience demonstrates that myeloablative therapies in older selected patients can be feasible; the feasibility of introducing PBSC

Background: A novel coronavirus (SARS-CoV-2)-induced pneumonia (COVID-19) emerged in December 2019 in China, spreading worldwide. The aim of the present investigation was to evaluate the immunological response and the clinical subset of peripheral lymphocyte subset alteration in COVID-19 infection. Methods: the study was conducted on four different clinical groups (n = 4; total n = 138). Each individual was assigned to different groups based on specific criteria evaluated at the admission such as fever, dyspnea, arterial blood gas analysis (ABG), oral-nasopharyngeal swab/RT-PCR, and thoracic CT-scan. Treatment was performed only after blood samples were collected from each patient (PP and PP) at day 1. The blood samples were analyzed and tested the same day (CBC and Flowcytometry). The positive–positive group (PP n = 45; F = 18/ M = 27; median age = 62.33), comprised individuals affected by COVID-19 who showed fever, dyspnea (ABG = pO2 < 60), confirmed positive by oral-nasopharyngeal swab/RT-PCR and with CT-scan showing ground-glass opacities. The negative–positive (NP; n = 37; F = 11/M = 26; median age = 75.94) or “COVID-like” group comprised individuals with fever and dyspnea (ABG = pO2 < 60), who tested negative to nasopharyngeal swab/RT-PCR, with CT-scans showing ground-glass opacities in the lungs. The negative–affected group (NA; n = 40; F = 14/M = 26; median age = 58.5) included individuals negative to COVID-19 (RT-PCR) but affected by different chronic respiratory diseases (the CT-scans didn’t show ground-glass opacities). Finally, the negative–negative group (NN; n = 16; F = 14/M = 2) included healthy patients (NN; n = 16; median age = 42.62). Data and findings were collected and compared. Results: Lymphocytes (%) cells showed a decline in COVID-19 patients. The subsets showed a significant association with the inflammatory status in COVID-19, especially with regard to increased neutrophils, T-killer, T-active, T-suppressor, and T-CD8+CD38+ in individuals belong to the either COVID-19 and Covid-like NP group. Conclusions: Peripheral lymphocyte subset alteration was associated with the clinical characteristics and progression of COVID-19. The level of sub-set cells T-lymphocytes (either high or low) and B-lymphocytes could be used as an independent predictor for COVID-19 severity and treatment efficacy.

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