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All trans-retinoic acid (ATRA) syndrome is a life-threatening complication of uncertain pathogenesis that can occur during the treatment of acute promyelocytic leukemia (APL) by ATRA. Since its initial description, however, no large series of ATRA syndrome has been reported in detail. We analyzed cases of ATRA syndrome observed in an ongoing European trial of treatment of newly diagnosed APL. In this trial, patients 65 years of age or less with an initial white blood cell count (WBC) less than 5,000/μL were initially randomized between ATRA followed by chemotherapy (CT) (ATRA→CT group) or ATRA with CT started on day 3; patients with WBC greater than 5,000/μL received ATRA and CT from day 1; patients aged 66 to 75 received ATRA→CT. In patients with initial WBC less than 5,000/μL and allocated to ATRA→CT, CT was rapidly added if WBC was greater than 6,000, 10,000, 15,000/μL by days 5, 10, and 15 of ATRA treatment. A total of 64 (15%) of the 413 patients included in this trial experienced ATRA syndrome during induction treatment. Clinical signs developed after a median of 7 days (range, 0 to 35 days). In two of them, they were in fact present before the onset of ATRA. In 11 patients, they occurred upon recovery from the phase of aplasia due to the addition of CT. Respiratory distress (89% of the patients), fever (81%), pulmonary infiltrates (81%), weight gain (50%), pleural effusion (47%), renal failure (39%), pericardial effusion (19%), cardiac failure (17%), and hypotension (12%) were the main clinical signs, and 63 of the 64 patients had at least three of them. Thirteen patients required mechanical ventilation and two dialysis. A total of 60 patients received CT in addition to ATRA as per protocol or based on increasing WBC; 58 also received high dose dexamethasone (DXM); ATRA was stopped when clinical signs developed in 30 patients. A total of 55 patients (86%) who experienced ATRA syndrome achieved complete remission (CR), as compared with 94% of patients who had no ATRA syndrome (P= .07) and nine (14%) died of ATRA syndrome (5 cases), sepsis (2 cases), leukemic resistance (1 patient), and central nervous system (CNS) bleeding (1 patient). None of the patients who achieved CR and received ATRA for maintenance had ATRA syndrome recurrence. No significant predictive factors of ATRA syndrome, including pretreatment WBC, could be found. Kaplan Meier estimates of relapse, event-free survival (EFS), and survival at 2 years were 32% ± 10%, 63% ± 8%, and 68% ± 7% in patients who had ATRA syndrome as compared with 15% ± 3%, 77% ± 2%, and 80% ± 2% in patients who had no ATRA syndrome (P= .05, P = .003, and P = .03), respectively. In a stepwise Cox model that also included pretreatment prognostic variables, ATRA syndrome remained predictive for EFS and survival. In conclusion, in this multicenter trial where CT was rapidly added to ATRA in case of high or increasing WBC counts and DXM generally also used at the earliest clinical sign, the incidence of ATRA syndrome was 15%, but ATRA syndrome was responsible for death in only 1.2% of the total number of patients treated. However, occurrence of ATRA syndrome was associated with lower EFS and survival. © 1998 by The American Society of Hematology.

Purpose and Methods ISOSFER is an epidemiological cross-sectional study with prospective recruitment whose objectives are to evaluate patient characteristics, quality of life (QoL), compliance and patient satisfaction with deferoxamine (DFO) therapy. Results Among 278 consecutive patients receiving regular transfusions for thalassemia major (TM), sickle cell disease (SCD) or myelodysplastic syndromes (MDS) who consulted between October 2005 and February 2006 in 24 French centers, 161 were on chelation therapy. 124 patients were treated with DFO alone for more than 1 year. Among them, 67 aged 14 years or more agreed to participate. QoL was studied using the Short Form-36 scale. Compliance was assessed with the Morisky scale and a specific questionnaire. DFO was administered via subcutaneous (sc) infusion for 70% of patients, mainly nightly and with a mean duration of 10 hours. Other ways of administering DFO included intravenous (iv) infusion (15%), sc bolus (9%) and combined sc and iv treatment (5%). Patient characteristics are summarized in the table below. In comparison with the French general population, all dimensions of QoL are impaired in all three diseases and in all dimensions (physical activities, emotional problems, social activities, bodily pain, and vitality). TM and SCD patients had a better physical activities score than MDS patients but experienced more bodily pain than MDS patients. The global physical score was significantly influenced by age, marital status and occurrence of a co-morbidity related to hemosiderosis. Good compliance scores (0 and 1 on the Morisky scale) were found in only 74%, 67% and 87% of TM, SCD, MDS patients, respectively. In addition, DFO infusion was missed at least once a week during the past month in 17%, 44% and 4% of TM, SCD, MDS patients, respectively. Compliance was influenced by age, duration and number of weekly DFO infusions. Iron chelation with DFO was generally found to be inconvenient and more than half of the patients were unsatisfied with its parenteral mode of administration. Nonetheless, patients, particularly those with TM, were convinced that DFO was an effective treatment for iron overload and a very important drug for their health. Conclusions These results suggest that QoL is severely compromised in patient on DFO and that compliance to DFO is poor. These results could help ascertain the improvement in QoL and compliance, which would result from the use of oral chelation in patients with transfusional iron overload. TM (n=24) SCD (n=17) MDS (n=26) *Cardiac, liver and endocrine diseases, lens opacities, osteoporosis Median age in years (range) 30 (15–70) 32 (14–57) 69 (45–85) Sex, M/F 11/13 6/11 14/12 Geographic origin: EU/subS; Africa/North; Africa/others 16/0/6/2 1/12/3/1 26/0/0/0 Employment/university (%) 45 27 8 Marital status + (patients >18 yrs old) 9/21 7/15 25/26 Organ dysfunction potentially related to hemosiderosis* (%) 75 47 54 Median ferritin level (μg/L) 1049 2653 2627 Nb of TF >100 (%) 100 82 42 Mean DFO frequency/week 3.7 4.5 4 Mean dose 40 17 43