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Key Points Patients with APL treated with ATRA-ATO reported better long-term quality of life outcomes than patients treated with chemotherapy.Late comorbidity and health problem prevalence was similar between patients with APL previously treated with ATRA-ATO or chemotherapy., Visual Abstract, The main objective of this study was to compare the long-term health-related quality of life of patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) vs ATRA plus standard chemotherapy. Patients previously enrolled in the randomized controlled trial APL0406 were considered eligible for this follow-up study. The following patient-reported outcome measures were used: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30), the EORTC Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20), and the Short Form Health Survey 36 (SF-36). The prevalence of late comorbidities and health problems was also assessed. The clinical significance of differences was evaluated based on predefined thresholds. A total of 161 of 232 potentially eligible patients were analyzed, of whom 83 were treated with ATRA-ATO and 78 were treated with ATRA chemotherapy. The median time since diagnosis of the study sample was 8 years. The 2 largest clinically meaningful differences in the EORTC QLQ-C30 were observed for role functioning (Δ = 8.4; 95% confidence interval [CI], 0.5 to 16.3) and dyspnea (Δ = −8.5; 95% CI, −16.4 to −0.7), favoring patients treated with ATRA-ATO. With regard to the SF-36 results, a clinically relevant better physical component score (Δ = 4.6; 95% CI, 1.3 to 7.8) was observed in patients treated with ATRA-ATO, but this was not the case for the mental component score. The 2 groups showed similar profiles in the scores of the EORTC QLQ-CIPN20 scales and in the prevalence of late comorbidities. Overall, our findings suggest that the greater and more sustained antileukemic efficacy of ATRA-ATO is also associated with better long-term patient-reported outcomes than ATRA chemotherapy. This study was registered at www.clinicaltrials.gov as #NCT03096496.

New drugs and high dose therapy with auto-transplantation (auto-SCT) has improved prognosis of multiple myeloma (MM). New drugs are promising in upfront therapy while the role of maintenance is still debated. Thalidomide (thal) is an active drug in the treatment of myeloma, and is been investigated as first line therapy, the limit of this drug is the toxicity dependent dose and this determines a poor compliance. It could be useful in the control of minimal residual disease. We used low dose of thal as maintenance after autologous transplantation in patient with MM from January 2002 and here we bring our experience after six years of observation. From January 2002 to August 2008 17 patients (8 males and 9 females) with MM have been treated in our institution. Median age was 59,5 years (range 48–72). 10 were IgG, 3 IgA, 3 light chains and 1 plasma-cell leukaemia. Treatment was 4 cycles of VAD regimen followed by auto-SCT. 4/17 performed double auto-SCT. Three months after SCT these patients has begun the maintenance with thal 50 mg/die, to start thal maintenance 9 patients were in CR, 5 in PR and 3 in resistant disease and the median somministration of thal has been of 12 months (range 3–24 months). Median follow up from the beginning of maintenance therapy was 40 months (range 4–76) with 11/17 (64%) patients in CR or stable disease, with progression free survival (PFS) and overall survival (OS) projected at 75 months respectively of 53% and 51% from to start thal. In our experience we have observed a neurological toxicity (grade I–III) in the 65% of the patients but only 4 have had to suspend the treatment; a haematological toxicity of grade I in the 55% of the patients that have not behaved interruption of the treatment and finally in any case we have documented thrombotic episodes. Finally we have compared this group of patients with another group (18 patients) with the same clinical characteristics that we have observed in the same period but that have not effected maintenance with thal. In this last group 13/18 patients (72%) relapsed with median follow-up of 36 months (range 14–75) and median PFS and OS of 16 and 30 months respectively. The difference between the 2 groups is statistically significant for PFS (p: 0.003) and OS (p: 0.04). The median overall survival observed after progression, in the two groups, has been of 13 months in thal group and 17 months in the group of patients that have not effected the maintenance, this difference is not statistically different (p:0.06). In conclusion in 6 years of observation our experience has shown, even if the number of the patients is small, that maintenance with low doses of thal, after auto-transplantation, it not only has a good compliance but it improves the PFS and OS in this cohort and it doesn’t worsen the OS from the relapse.

Autologous stem cell transplantation is an efficacy therapy for limphoproliferative disease. However a concern with the procedure is the potential of malignant cells to reinfuse with stem-cell graft. In the past five year, investigators have used rituximab to purge malignant cells in vivo without any manipulation in vitro. From April 2003 to June 2008 we have treated with Autologous stem cell transplantation, purged in vivo with monoclonal antibodies, 24 patients (8 F; 16 M median age: 55 years) with limphoproliferative diseases to poor prognosis (2 Burkitt lymphoma; 3 Burkitt like lymphoma; 4 mantle cells; 3 CLL; 3 NHL-T cells (1 peripheral and 2 lymphoblastic); 2 follicular and 7 large cells) and we have evaluated the results and the feasibility. In all patients, the purged in vivo, has been effected administering a dose of monoclonal antibodies (anti CD20 in B-NHL and anti CD52 in CLL and T-NHL) before the harvest and after the infusion of the stem-cells. To the transplantation 10 patients were in CR (2 Burkitt lymphoma; 3 Burkitt like lymphoma; 2 large cells; 2 NHL-T lymphoblastic and 1 mantle cells) 9 in PR (1 CLL; 3 mantle cells; 2 follicular and 4 large cells lymphoma) and 5 in resistant disease (2 CLL; 2 large cells and 1 NHL peripheral T cells). All patients have harvest (median CD34:4 ×106/Kg) and median minimal residual disease in the harvest has been < to 2%. All the patients have been conditioned with BEAM and the graft are documented in 22/24 patients (2 patients are dead to the day +4 and +10 for gastric haemorrhage and septic shock respectively) with neutrophils> 1000 in media to day + 11 (range 10–19 days). After transplantation 20/22 patients were in CR, a day +60 the MMR in bone marrow was

Association between fludarabine (Fluda) and cytosine arabinoside (ARA-C) have shown in a variety of single arm studies an effective antileukemic effect with acceptable toxicity in high risk myelodisplasias and acute myeloid leukemias in elderly patients. In order to increase the synergistic effect of fluda and ARA-C further association (i.e. anthracyclines) or different schedules of administration (i.e. continous infusion) have been performed but not compared. In order to asses if there is an advantage of an association or schedule compared to another we retrospectively analyzed results from two different fludarabine-based regimens administered as front-line therapy in patients with acute myeloid leukemias aged up to 60 years. A total of 42 patients were treated with fluda 25 mg/m2, ARA-C 1 gr/m2 and idarubicin 5 mg/m2 as single day administration for three days (FLAI) or fluda 20 mg/m2 and ARA-C 1,4 mg/m2 as continuous infusion for three days fluda and 4 days ARA-C (c.i.FLA). Total dosage of fluda was 75 mg/m2 in FLAI and 70 mg/m2 in c.i.FLA, while ARA-C total dose was 3 gr/m2 in FLAI and 6,15 gr/m2 in c.i.FLA. Dose administered of idarubicin in FLAI was 15 mg/m2. Patients who obtained complete remission (CR) defined as less of 5% of bone marrow blasts received a second course of the same chemotherapy as consolidation, reduced at 3 days in c.i.FLA. 19 patients were treated with FLAI regimen, 9 males and 10 females, mean age 69,3 years (range 61–75) and 23 received c.i.FLA regimen, 12 male and 11 female, mean age 69,4 years (range 61–84). 4 patients in each group showed unfavourable kariotype. Results were as follows: 8/19 (42%) patients obtained CR after induction with FLAI while 11/23 (48%) were in CR after first course c.i.FLA. Difference is not statistically significative. Median disease free survival (DFS) was 9,53 months for FLAI and 7,67 months for c.i.FLA (p=NS) and median overall survival (OS) in the group in CR was 10.8 in the FLAI group and 10 months in c.i.FLA group (p=NS). Induction deads were 1/19 in FLAI group (5%) and 3/23 in c.i.FLA group (13%). The global median OS, including resistant patients was 6,57 months for FLAI and 6 months for c.i.FLA (p=NS). Two patients in each group underwent autologous bone marrow transplantation in complete remission. Results of the comparison of this two different regimens suggest that there is no substantial difference between single daily administration added of idarubicin and continuous infusion of fluda and ARA-C. Both cycles seem to have the same antileukemic activity with overlapping toxicity. Median time to neutrophil recovery (> 1000/mmc) was 16 in c.i.FLA and 14,5 in FLAI while platelets recovery (> 20000/mmc) was 18 in c.i.FLA and 13 in FLAI. Both schedules can be, in our opinion, safely used as front-line therapy in elderly patients affected by acute myeloid leukemias. What is to underline in this setting of patients is the short duration of the CR. Probably some kind of maintenance or association without increasing toxicity is needed, and experience with monoclonal antibodies are an interesting way to follow.

Ca 15-3 is a glycoprotein present in the cells of the mammary carcinoma and in some epithelial cells. Is a marker used for the monitoring of the breast and gastrointestinal carcinoma. The megaloblastic anaemia is an anaemia characterized by deficit of absorption of Vitamin B12 and is associated with gastritis atrophic and the target cell is the parietal gastric cell. In our institution, from June 2003 to December 2004, the level of Ca15-3 and of others tumour markers (CEA; Ca125; Ca19.9; alfa-FETO) they have been tested in the serum of 16 patients (9 male and 7 female with median age of 64,5 and range of 37–80 years) with de novo megaloblastic anaemia, 2 patients were gastrectomized. In all patients has been effected: esophagogastroduodenoscopy and control anti-parietal gastric cells antibody (APCA). Increase level in the serum of CA 15-3 with normal level of other tumour markers have been found in 14/16 patient with median value of 61 U/ml (range 35–100 U/ml) in two patients (gastrectomized) the value of CA 15-3 was normal. Besides in 12/14 patients have shown positivity for the APCA, only in two patients has been diagnosed a gastritis atrophic, in the other patients has been observed a normal gastric mucous. After a median observation of 24 months any patient has developed a mammary or gastro-intestinal carcinoma These results indicate what the increased level of CA 15-3 antigen in patient with megaloblastic anaemia is positively correlated with APCA and with the presence of a normal gastric mucous. These clinical conditions make to suppose the destruction from the APCA of the parietal gastric cells with the liberation of this glycoprotein and this is shown in two patients gastrectomized with presence of APCA and not increased level of the CA 15-3. In conclusion the CA15-3 antigen is probably an specific marker for the diagnosis of megaloblastic anaemia and is probably associated with the destruction of parietal gastric cells.