[Show abstract][Hide abstract] ABSTRACT: Between 2000 and 2006, 85 adult BCR-ABL negative acute lymphoblastic leukaemia (ALL) patients between 18 and 60 years of age were treated using a modified paediatric regimen, which included high doses of asparaginase delivered weekly for 30 weeks during intensification. The complete response rate with induction therapy was 89%, and decreased with increasing age, mainly due to higher induction mortality. All post-induction treatments were delivered on an outpatient basis. The most common complications during intensification were infections (47%), osteonecrosis (32%), venous thromboembolism (23%) and neuropathy (22%). At a median follow-up of 4 years, the 5-year overall survival (OS) and relapse-free survival (RFS) were 63% and 71%, respectively. Significant adverse predictors for OS were age >35 years, high white blood cell count, MLL rearrangement, allogeneic stem cell transplantation in first complete remission and <80% of the planned asparaginase dose delivered during intensification. Patients aged < or = 35 years had a 3 year OS of 83%, as compared to 52% for patients aged >35 years. We conclude that the administration of this paediatric regimen is feasible and has considerable activity in adult ALL, particularly in younger patients. Effective delivery of asparaginase dosing appears to be important in achieving an optimal antileukaemic effect.
British Journal of Haematology 05/2009; 146(1):76-85. DOI:10.1111/j.1365-2141.2009.07712.x · 4.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a single center experience in treating 24 consecutive patients > or = 60 years old for aplastic anaemia (AA) with immunosuppressive therapy (IST). The main outcomes of interest were the tolerability and toxicity of IST, response rate and survival. Median age was 70 years (range 61-78). Seven patients received standard IST consisting of standard dose antithymocyteglobulin (ATG) with or without ciclosporin (CsA), and 17 patients received attenuated IST consisting of at least a 50% dose reduction of ATG with CsA or CsA alone. Six patients (25%) had early deaths, mostly due to infection. Early mortality appeared higher in the standard IST group although this was not statistically significant (43% vs. 18%, P = 0.4). The 2-year cumulative incidence of response was 42% [95% confidence interval (CI) 26-69%]. Responders had significantly better survival than non-responders (P = 0.0002). The 3-year probability of overall survival was 49% (95% CI 27-68%). Moderate or severe co-morbidities (P = 0.03) as determined by Charlson Co-morbidity Index and very severe AA (P = 0.007) were associated with significantly inferior overall survival while age was not. Nine out of 14 evaluable patients in the attenuated IST group had durable responses to treatment, suggesting that patients not suitable for standard IST can still benefit from attenuated IST.
British Journal of Haematology 01/2009; 143(5):738-43. DOI:10.1111/j.1365-2141.2008.07389.x · 4.71 Impact Factor