Search

Hemophilia A is a hereditary genetic disorder caused by acongenital deficiency of coagulation factor VIII (FVIII) and re-placement therapy with FVIII products is the mainstay care. Thehealth-related quality of life of patients has been much improvedwith a favorable orthopedic outcome after prophylactic regimensintroduced [1]. However, managing patients with hemophilia Awho have inhibitory antibodies against infused FVIII, which neu-tralize the infused FVIII and result in treatment failure, is still anobstacle in their treatment course [2]. The presence of FVIIIinhibitors occurs in 20–30% of patients with hemophilia A [2–4] and are generally categorized into low responders (LR) andhigh responders (HR) according to their inhibitor titers and/oranamnestic response to FVIII. Although several treatment strate-gies, such as bypass therapy, plasma exchange and extra-corporealimmunoabsorption, which aim to overcome the impact of FVIIIinhibitors, may control the bleeding event in short term, buteradicating the FVIII antibodies is the main goal of managementfor these patients.Immune tolerance induction (ITI) therapy is the only provenmodality for achieving antigen-specific tolerance to FVIII andeliminating FVIII antibodies in patients with hemophilia A [5].Since ITI was first described by Brackmann and Gormsen in1977, various regimens using different FVIII dosages and inter-vals with or without concurrent immune modulation therapy havebeen used [6–10]. Although there are several large study cohorts,including North America Immune Tolerance Registry (NAITR),International Immune Tolerance Registry (IITR) and the GermanImmune Tolerance Registry (GITR), conducted for determinationof optimal practices, the dosing regimens and FVIII purity of ITItreatment were still under debate [11–13]. The experiments pub-lished in literature from many study groups recruited patientsmainly from Europe and North America [14–19]. Therefore, theapplication and experience of ITI in Eastern Asian is still limited.In this report, we conducted ITI therapy with various dosingregimens for our patients with FVIII inhibitor attempted to iden-tify whether low-dose ITI can be an alternative strategy besideshigh-dose ITI or bypassing therapies.

Background Deferasirox is an oral iron-chelating agent taken once-daily by patients with transfusion-dependent iron overload. However, some patients are unresponsive or unable to tolerate once-daily deferasirox. The current study evaluated whether twice-daily deferasirox treatment showed increased efficacy or tolerability in unresponsive or intolerant patients. Procedure Patients from two Taiwanese hospitals with transfusion-dependent β-thalassemia, including those who showed increasing serum ferritin levels for six consecutive months, with at least one level >2,500 ng/dl, while treated with >30 mg/kg/day of once-daily deferasirox (unresponsive) or developed deferasirox-related adverse events (AEs) at the dosage required to maintain the iron burden balance (intolerant) and were treated twice-daily with the same total daily dose of deferasirox since 2008, were enrolled in the study and evaluated retrospectively by medical record review. Results Eighteen patients were included for analysis. A statistically significant median decrease in serum ferritin levels was detected in the 11 unresponsive patients after 6 months of continuous twice-daily deferasirox treatment. Five out of the seven intolerant patients experienced either no deferasirox-related AEs or less severe AEs. The 12 patients from both groups (11 unresponsive, 1 intolerant) who received continuous twice-daily deferasirox for 6 months showed a mild but significant median increase in serum creatinine levels. Conclusions Twice-daily deferasirox dosing is effective in iron chelation and improves tolerability in transfusion-dependent β-thalassemia patients who are unresponsive to or intolerant of once-daily deferasirox. Future studies with greater patient numbers will be required to confirm the results reported herein. Pediatr Blood Cancer 2011;56:420–424. © 2010 Wiley-Liss, Inc.

Background In childhood acute lymphoblastic leukemia (ALL), t(1;19)(q23;p13.3) with TCF3-PBX1 fusion is one of the most frequent translocations. Historically, it has been associated with poor prognosis. Intensive treatment, however, has improved its outcome. We determined the outcome of children with this genotype treated with contemporary intensive chemotherapy in Taiwan. Procedure In Taiwan Pediatric Oncology Group 2002 ALL studies, genotypes were determined by cytogenetic analysis and/or reverse transcriptase polymerase chain reaction assay. Based on presenting features, immunophenotype and genotype, patients were assigned to one of the three risk groups: standard risk (SR), high risk (HR), or very high risk (VHR). The patients with t(1;19)/TCF3-PBX1 were treated in the HR arm receiving more intensive chemotherapy. The outcomes of patients with t(1;19)/TCF3-PBX1 were compared to that of patients with other subtypes of B-precursor ALL (B-ALL). Results Of the 1,129 patients with B-ALL, 64 (5.7%) had t(1;19)/TCF3-PBX1; 51 of whom were treated in the HR arm, but 11 were treated in the VHR and 2 in the SR arm because of physician's preference. As a group, 64 patients with t(1;19)/TCF3-PBX1 had similar 5-year event-free survival (83.3 ± 4.8%) as those with TEL-AML1 (85.2 ± 3.4%, P = 0.984) or those with hyperdiploidy >50 (84.0 ± 3.1%, P = 0.748). The cumulative risk of any (isolated plus combined) central nervous system relapse among patients with t(1;19)/TCF3-PBX1 (8.7 ± 3.8%) tended to be higher than that of patients with TEL-AML1 (5.8 ± 2.3%, P = 0.749) or those with hyperdiploidy (4.1 ± 1.8%, P = 0.135), albeit the differences did not reach statistical significance. Conclusions With contemporary intensive chemotherapy, children with t(1;19)/TCF3-PBX1 fared as well as those with favorable genotypes (TEL-AML1 or hyperdiploidy).