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Introduction: The combination of fludarabine, cyclophoshamide and rituximab (FCR) represents the current standard of treatment of fit patients with chronic lymphocytic leukemia (CLL). However, despite the success of the FCR regimen, a number of questions exist on its optimal administration as well as on its short and long term toxicity. As a consequence, in the daily practice (Knauf et al, Hematological Oncology, 2015) less intensive regimens such as bendamustine plus rituximab (BR) are often adopted also in fit patients. Most data on the FCR regimen derive from clinical trials, while data from real life are poor.

BACKGROUND. In recent years, new classes of drugs have been introduced for the treatment of Multiple myeloma (MM). Several randomized trials have investigated, in the setting of first line treatment of patients eligible for autologous transplant (ASCT), the efficacy of the combination of two to four new and old drugs given as induction. Among these, VTD combination (bortezomib plus thalidomide plus dexamethasone) provided impressive results, so that it is now considered at different Institutions the standard of care as pretransplant therapy. However, data of VTD derive from clinical trials and should be verified in the "real life" setting, in terms of either efficacy or toxicity.

The current study aimed to evaluate the efficacy and toxicity of a combination of intravenous (iv) busulfan (Bu) and continuous infusion Idarubicin (IDA) as a conditioning regimen to autologous haematopoietic stem cell transplantation (ASCT) in patients with acute myeloid leukaemia (AML). The protocol included IDA at 20 mg/sqm daily as 3 days continuous infusion (from day -13 to -11) and intravenous BU at 3.2 mg/kg daily from day -5 to -2. Patients aged over 60 years received a reduced schedule (2 days IDA and 3 days BU at the same dose). Twenty-live patients with a median age of 51 years (28-72) were enrolled. All patients received peripheral blood stem cells (PBSC). The median interval between diagnosis and ASCT was 4 months. The median number of CD34+ cells infused was 5.9 x 10E6/kg. The median number of days to PMN >500/cmm and platelets >20000/cmm was 10 and 13, respectively. In order to perform a comparison in terms of haematological and non haematological toxicity, a group of 30 patients, who were previously autografted after conditioning with IDA and oral Bu was considered. Selection of factors for a matched pair analysis included median age, percentage of subjects aged over 60 years, median CD34+ cell received, cytogenetic and molecular findings and per cent of secondary AML. As compared to previous series, the occurrence of severe mucositis was dramatically reduced (80 % vs. 12 %, p < 0.0001). In addition, need and duration of total parenteral nutrition (TPN), iv antibiotic therapy and hospitalization were also significantly reduced. We conclude that replacement of oral with intravenous BU results in a more favourable toxicity profile. A longer follow-up is required to assess a potential advantage in terms of disease free survival (DFS). Copyright (C) 2009 John Wiley & Sons, Ltd.

The clinical outcome of acute myelold leukemia (AML) is extremely variable, ranging from survival of a few days to cure [1-3]. In the recent years, different biological features at presentation have been reported as useful for the prediction of clinical outcome; in particular, nonrandom clonal chromosome aberrations, which are detectable in the leukemic cells of approximately 50% of adult AML patients, are not only diagnostic markers for specific AML subtypes but also provide prognostic Information for achievement of complete remission (CR), relapse risk, and survival [4-7]. Accordingly, pretreatment cytogenetics represent part of the routine diagnostics in patients with AML and the new World Health Organization classification of hematologic malignancies takes Into account specific chromosome aberrations and their molecular counterparts together with morphology, Immunophenotype, and clinical features [8]. Despite continuous Improvements In cytogenetic methodology, microscopically detectable chromosome abnormalities are not found in approximately 50% of AML patients and patients with normal karyotype are usually classified in the Intermediate-risk prognostic category [9,10]; In this AML patient subset, the clinical outcome Is very heterogeneous and 5-year survival rates vary between 25% and 45% in different studies. As a consequence, It is of utmost Importance to discriminate within this AML subgroup subjects with different prognostic characteristics at diagnosis [11-14].

Different studies have suggested the potential utility of autologous stem cell transplantation (ASCT) in acute myeloid leukaemia (AML) of the elderly with encouraging results in selected patients. However, while the introduction of peripheral blood stem cells (PBSC) has consistently reduced morbidity and mortality of the procedure, relapse still represents the major cause of ASCT failure. One possibility to ameliorate therapeutic results could rely on the adoption of conditioning regimens specifically designed for AML. We report therapeutic results from a series of 40 AML patients older than 60 years (median age 67 years) autografted in first complete remission (CR), after conditioning with continuous infusion (c.i.) high dose idarubicin and busulphan. Fourty patients (median age: 67 years) received 2 days c.i. idarubicin at 20 mg/m(2)/day, followed by 3 days oral or intravenous busulphan (4 mg/kg/day) as conditioning. No case of transplant-related mortality occurred. Cardiac toxicity was absent, while 31 patients (77%) had grade 3-4 mucositis. After a median follow-up of 25 months, median disease free and overall survival (OS) for the whole patient population were 13 and 22 months, respectively. Three patients died while in CR from causes unrelated to AML. Better results were achieved in patients with intermediate karyotype as opposed to those with adverse cytogenetics. Our data confirm the feasibility of a conditioning regimen based on high-dose idarubicin plus busulphan in older selected AML patients and suggest clinical improvement in patients with normal cytogenetics.

The upper age limit for autologous stem cell transplantation (ASCT) in acute myeloid leukemia (AML) is increasing and peripheral blood (PB) represents the standard source of stem cell (SC). However, no data are available on the impact of age on SC mobilization in AML. We analyzed a cohort of 150 consecutive AML patients in first complete remission in order to make a comparison between patients up to 60 years and above 60 years, by evaluating CD34(+) cells mobilization into PB and the number of leukapheresis needed to collect at least one single SC graft. The successful mobilization rate (> 2 x 10(6) CD34(+) cells/kg) was comparable between the two groups (87 % vs. 80 %, p = 0.29). In addition, no statistically significant difference was found in terms of either median number of CD34+ cells collected (p = 0.54) or CD34(+) cells peak in PB (p = 0.70). Both groups of patients needed a median of two apheresis and no difference was found in the median number of CD34+ cells collected per single apheresis (p = 0.67). Finally, no correlation was found between age and total number of CD34+ cells collected (r = 0.003, p = 0.58). We conclude that age has no impact on mobilization of PBSCs in AML. Copyright (c) 2007 John Wiley & Sons, Ltd.

High dose cyclophosphamide (HD-Cy) is commonly used to mobilize stem cells in multiple myeloma (MM). However, timing of collection is variable and incidence of side effects is substantial. We evaluated a combination of vinorelbine (VNB) (25 mg/m(2) day 1) plus Cy (1.5 g/m(2) day 2) and G-CSF as mobilizing regimen in 37 patients with MM. Results were compared to those achieved in 41 previously diagnosed patients mobilized with Cy at 4 g/m(2). Overall, 36/37 patients receiving VNB-Cy (97%) mobilized, as opposed to 40/41 (97%) in the controls (p:0.51). Median CD34+ cells peak was 94/mul for VNB-Cy patients and 96 for controls, p=0.36; median number of CD34+ cells collected was 9.2x10(6)/kg and 8.7x10(6)/kg, respectively (p=0.85). Median number of days to the highest CD34 count was shorter for VNB-Cy patients (nine vs 11, p=0.001). No VNB-Cy patient experienced grade 3-4 neutropenia and thrombocytopenia, as opposed to 63 and 19% in the controls (p=0.001 and 0.01, respectively). Hospitalization from toxicity was never required in VNB-Cy patients as compared to 19% in control group (p=0.01). We conclude that an outpatient combination of VNB plus intermediate dose Cy plus G-CSF is a safe, predictable, and highly effective mobilization regimen for patients with newly-diagnosed MM.

Forty patients with relapsed diffuse large B cell lymphoma (DLBCL) autografted in partial response (PR) (n = 23) or in refractory relapse (RR) (n = 17) achieved complete remission (CR) after autologous stem cell transplantation (ASCT). Salvage treatment consisted of ifosphamide, epirubicin and etoposide (IEV) in 33 patients and Cisplatinum, ARA-C and dexamethasone (DHAP) in 7 patients. All PR and 8 RR patients were conditioned with BEAM, while 9 RR cases received the BCV regimen. There were no significant differences between the two groups as age, serum LDH, duration of CR1 and IPI at relapse are concerned. Relapse rate after ASCT was 39% in PR group as opposed to 88% in RR group (p = 0.003). Median relapse free survival from ASCT was 6 months for RR patients as opposed to 34 months for PR patients (p = 0.003); median overall survival from ASCT was 10 months for RR subset as opposed to not reached for RR subgroup (p = 0.001). These data demonstrate that CR achieved after ASCT in DLBCL patients who are refractory to previous salvage therapy does not result in long-term disease control. Alternative preparative regimens, allogeneic SCT and/or monoclonal antibodies in the post-ASCT phase should be considered for RR patients despite CR achievement.

Most studies showing that autologous stem cell transplantation ( ASCT) is feasible in older patients with acute myeloid leukemia (AML) referred to highly selected patients considered as eligible after complete remission (CR) achievement and bone marrow or peripheral blood stem cell (PBSC) collection. This study evaluated the feasibility of ASCT from 155 consecutive AML patients aged over 60 years (median age 72 years, range 61-94) programmed to receive ASCT by using PBSCs after CR achievement. Overall, 90 out of 155 patients (58%) were judged as eligible for aggressive chemotherapy and 45 (50%) achieved CR. Among these, 36 (80%) received consolidation and 32 (89% of consolidated) were monitored for PBSC mobilization. A successful collection was registered in 25/32 patients (78% of monitored). Finally, 20 patients received ASCT. Reasons for not autografting five mobilizing patients included relapse pre-ASCT, toxicity, and refusal. Median survival was 4 months for the whole patient population and 19 months for patients actually autografted. Overall, 20 out of 90 patients accrued into intensive chemotherapy (22%) and 20 out of the entire patient population (13%) underwent ASCT. It is concluded that APBSCT can result in an improvement of therapeutic results in AML of the elderly, but it is feasible in a minority of selected patients.