Nilotinib is a highly selective Bcr-Abl inhibitor approved for imatinib-resistant chronic myeloid leukemia (CML). Nilotinib and dasatinib, a multi-targeted kinase inhibitor also approved for second-line therapy in CML, have different patterns of kinase selectivity, pharmacokinetics, and cell uptake and efflux properties, and thus patients may respond to one following failure of the other. An international phase II study of nilotinib was conducted in CML patients (39 chronic phase (CP), 21 accelerated phase (AP)) after failure of both imatinib and dasatinib. Median times from diagnosis of CP or AP to nilotinib therapy were 89 and 83 months, respectively. Complete hematological response and major cytogenetic response (MCyR) rates in CP were 79% and 43%, respectively. Of 17 evaluable patients with CML-AP, 5 (29%) had a confirmed hematological response and 2 (12%) a MCyR. The median time to progression has not yet been reached in CP patients. At 18 months 59% of patients were progression-free. Median overall survival for both populations has not been reached, and the estimated 18-month survival rate in CML-CP was 86% and that at 12 months for CML-AP was 80%. Nilotinib is an effective therapy in CML-CP and -AP following failure of both imatinib and dasatinib therapy.
Pattern 1 represents an indolent phase/grade of AITL, unassociated with the development of secondary B-lineage lymphoma and uninfluenced by treatment regimen.
The prevalence of JAK2 mutations in this population of Asian ET patients was 34%. Patients with the JAK2 mutation were significantly more likely to have high-risk disease. Further studies are required to assess the role of JAK2 mutations in risk stratification in ET and compare the phenotype of Asian patients with other populations.
The adult transplant programme at Singapore General Hospital (SGH) was established in 1985 and more than 820 transplants have been performed to date. An average of about 60 adult transplants (autologous and allogeneic) are performed each year. Transplants offered at SGH run the range from autologous to mismatched cord and unrelated transplants. Special interests of the transplant programme include non-myeloablative transplants in aplastic anaemia, cell therapy protocols including cytokine-induced killer cells, patterns of GVHD, cord blood transplantation for autoimmune diseases and graft engineering. A cGMP (good manufacturing practice) cell therapy laboratory was recently established to facilitate bench-to-bedside translational cell therapy trials. A BMT consortium has been formed among the various paediatric and adult transplant centres for harmonization of protocols and research activities.
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