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Despite the success in treating the majority of children with newly diagnosed acute leukemia, children with relapsed or refractory disease are an exceptionally difficult group of patients to cure. We assessed the combination of fludarabine with cytarabine and granulocyte colony-stimulating factor (FLAG) and non-pegylated liposomal doxorubicin (Myocet) in children with either acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) refractory to first-line therapy or who had relapsed after risk-tailored chemotherapy. We treated 35 patients with FLAG-Myocet. The median age at treatment was 9 years and 7 months (range, 1 to 18 y). The 94% of ALL patients (16/17) and the 61% AML patients (11/18) achieved complete remission after FLAG-Myocet. A partial response was observed in the 17% of AML patients (3/18). Twenty-eight of 35 (80%) patients received hematopoetic stem cell transplantation in remission induced by FLAG-Myocet regimen. The ALL and AML overall survival at 3 years after FLAG-Myocet is 33% and 38%, respectively. The probability of ALL and AML event-free survival at 3 years after FLAG-Myocet is 33% and 40%, respectively. The probability of ALL and AML disease-free survival at 3 years after hematopoietic stem cell transplantation is 19% and 58%, respectively. Non-hematological toxicity was remarkably low, while almost all patients showed severe hematological toxicity. FLAG-Myocet is an efficient and a well-tolerated regimen that allows nearly all patients to undergo hematopoetic stem cell transplantation. FLAG-Myocet proved to be safe in terms of acute cardiac toxicity although particular care must be taken to reduce infectious complications due to severe myelosuppression. The promising results shown in our study need to be confirmed by larger and possibly randomized trials.

We report the long-term follow-up (median 39.5 months) of 49 paediatric patients (33 females and 16 males) with refractory symptomatic immune thrombocytopenic purpura (ITP) treated with rituximab. The overall response rate was 69% (34/49 patients). Twenty-one responders had a platelet count >50 x 10(9)/l at a median 20.2 months from treatment. Kaplan-Meier analysis showed a probability of relapse-free survival (RFS) of 60% at 36 months from the first rituximab infusion. The number of infusions and a previous splenectomy did not influence overall response rate. Patients who achieved complete response were significantly older at diagnosis and first rituximab infusion than partial responders (P = 0.027). Older children displayed a significantly greater probability of sustained response (RFS) at 36 months than younger children (88.9% vs. 56.7%, P = 0.037). Earlier responses (within 20 d from treatment) were significantly associated with both complete (P = 0.004) and sustained response (P = 0.002). Only mild and transient side-effects were observed in 9/49 children; no major infections nor delayed toxicities were recorded during the follow-up.

BACKGROUND In thalassemic major patients liver fibrosis may be influenced by independent factors as hepatitis, degree of iron loading and iron chelation, and the specific effect of drugs. Due to its invasive nature, the histological evaluation of liver fibrosis on biopsy samples is difficult to be done and repeated. We analysed the relationship of these factors with the degree of liver fibrosis assessed non-invasively by ultrasound elastometry expressed as liver stiffness. We also compared the liver stiffness in patients on long term therapy with different iron chelators. METHODS We applied the ultrasound elastometry (Fibroscan®, Fibrosens, Paris) to a consecutive series of patients with ß thalassemia major on regular transfusion and chelation. Liver Iron Concentration (LIC) has been assessed by SQUID magnetic susceptometry (Tristan Technologies, Inc., San Diego, USA). We considered, as control, a group of healthy persons. All the subjects signed a written informed consent. RESULTS We studied 115 patients (64 males, 51 females) with beta thalassemia major, with mean age of 27.7 ± 7.6 years (range: 6.7–48.3). Eighty-six (75%) patients were HCV-Ab positive, and 52 (45%) HCV-RNA positive. Mean stiffness was 9.0 ± 6.6 KPa (range 3.3–43.5), significantly higher than in controls (4.0 ± 1.0, CI 3.3–4.8). Seven (6%) patients had a stiffness value above the cirrhosis threshold, and 18 (16%) were above the severe fibrosis threshold. Mean serum ferritin was 2064 ± 2011 μg/L, and mean LIC was 1845 ± 1199 microg/g ww. Considering the chelator, 34 patients have been on deferoxamine (DFO) therapy for 19.2 ± 9 years, 53 patients on deferiprone (L1) for 5.7 ± 3.7 years, and 28 on deferasirox (ICL670) for 3.3 ± 1.1 years. Mean stiffness was 9.5 ± 7.4 kPa, 9.9 ± 7.3 and 6.6 ± 2.8, respectively. On multivariate analysis, HCV Ab, HCV RNA and LIC were independent factors determining the degree of stiffness, while the chelator used was not significant. CONCLUSIONS Thalassemia major patients on regular transfusion and chelation have significantly abnormal degree of liver fibrosis. HCV positivity and the amount of iron overload seem to be the main related factors. The type of chelator used does not seem important.