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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.

Purpose A randomized clinical trial compared efficacy and toxicity of standard all-trans-retinoic acid (ATRA) plus chemotherapy versus ATRA plus arsenic trioxide in patients with newly diagnosed, low- or intermediate-risk acute promyelocytic leukemia (APL). Here, we report health-related quality-of-life (HRQOL) results. Patients and Methods HRQOL was a secondary end point of this trial. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 was used to assess HRQOL at end of induction and after consolidation therapy. All analyses were based on 156 patients who received at least one dose of treatment, with groups defined according to randomly assigned treatment. Primary analysis was performed, estimating mean HRQOL score over time and differences between treatment arms using a linear mixed model. Results Overall, 162 patients age 18 to 70 years were enrolled. Of these, 150 and 142 patients were evaluable for HRQOL after induction therapy and third consolidation course, respectively. Overall compliance with HRQOL forms was 80.1%. The largest difference, favoring patients treated with ATRA plus arsenic trioxide, was found for fatigue severity (mean score difference, −9.3; 95% CI, −17.8 to −0.7; P = .034) at end of induction therapy. This difference was also clinically relevant. HRQOL differences between treatment arms at end of consolidation showed that for several scales, differences between treatment arms were marginal. Conclusion Overall, current HRQOL findings further support the use of ATRA plus arsenic trioxide as preferred first-line treatment in patients with low- or intermediate-risk APL.

All-trans-retinoic acid (ATRA) combined with anthracyclines is currently the standard treatment for acute promyelocytic leukemia (APL). In elderly patients the presence of comorbidities, such as cardiomyopathy or different organ failures, often represents an absolute contraindication to standard chemotherapy. In this particular setting of patients, alternative front-line approaches are needed. Here we report the use of gemtuzumab ozogamicin as consolidation therapy in a 68-year-old patient not eligible for standard dose anthracycline due to severe cardiac failure and chronic anticoagulant therapy, affected by low-risk APL. Induction therapy was started with ATRA alone, at a dose of 45 mg/m2 for 80 days. The patient obtained a complete hematological and molecular remission. At day +170 the patient was treated with 6 mg/m2 gemtuzumab ozogamicin monthly for two months (2 total doses) as a consolidation therapy and then started a maintenance program with ATRA 45 mg/m2 for 15 days every three months, for a total time of two years. No adverse events were observed in every phase of treatment and the patient is still in complete continuous hematological and molecular remission 29 months from diagnosis. This approach represents an intriguing therapeutic option to be investigated in randomized studies in low- and intermediate-risk elderly patients (older than 65 years), aiming to minimize or to eliminate standard chemotherapy in advantage of new non-conventional agents, including ATO.

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

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.

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.

Background The combination of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy regimens is currently considered the standard of care for newly diagnosed acute promyelocytic leukemia (APL) patients. This combination has greatly contributed to convert APL from a frequently fatal disease to a highly curable one. However, there is lack of data on the impact of such therapies on patients’ health-related quality of life (HRQOL). Objective The main objective of this study was thus to investigate long-term HRQOL of APL patients previously treated with ATRA plus anthracycline-based chemotherapy. The physical and mental HRQOL profile of these patients was compared with that of matched control subjects from the general population to identify specific areas most in need of attention in long-term follow-up care. A secondary objective was to outline symptoms’ burden from the patients’ perspective. Patients and Methods Data were gathered through an ongoing multicenter survivorship study that recruits APL patients previously enrolled in two large GIMEMA trials (i.e., AIDA0493 and AIDA 2000). In both trials, APL patients were treated with ATRA plus Idrarubicin (AIDA). The main inclusion criterion was having survived the initial diagnosis for more than 5 years and being in complete remission (CR). Generic HRQOL was assessed with the SF-36 that consists of 36 items covering eight generic health status/QoL domains: physical functioning (PF), role limitations due to physical health (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF), role limitations due to emotional problems (RE) and mental health (MH). All scales ranged between 0 and 100, with the higher scores representing better outcomes. Clinical significance was evaluated and eight points were considered to be a minimally important difference for the eight SF-36 scales. Mean SF-36 scores were compared to available national general population reference values (i.e., 1997 subjects without cancer) and all analyses were adjusted for age and gender. Symptom burden was assessed according to the M.D. Anderson Symptom Inventory (MDASI). Symptom severity was assessed for the following symptoms: fatigue, pain, sleep disturbance, drowsiness, poor appetite, shortness of breath, nausea, vomiting, dry mouth, numbness, difficulty remembering, distress and sadness. All items were rated on a numeric rating scale from 0 to 10, with the higher scores indicating a higher level of symptoms. These were categorized as “mild” (ratings between 0 and 3) and “moderate to severe” (ratings between 4 to 10). Results Analysis is based on 136 adult APL patients who agreed to participate. At study participation, the mean age of patients was 52 years (55% males and 45% females) and the median time from diagnosis was 13 years (range: 4.5-20). Age and gender adjusted comparisons between APL patients and the general population norms revealed worse outcomes for the following scales: RP (P Conclusions Although ATRA plus anthracycline-based chemotherapy regimens have greatly increased cure rates in APL, the HRQOL of these patients is heavily affected by the consequences of the disease and treatment, that persists many years after diagnosis and treatment. Disclosures: No relevant conflicts of interest to declare.