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Aplastic anaemia (AA) is infrequently observed in pregnancy. We describe 19 pregnancies in 9 women at a tertiary care centre over a period of 30 years. Spontaneous resolution of AA did not occur postpartum in the five pregnancies where AA was first diagnosed in pregnancy. In the remaining pregnancies, although haematological indices declined and transfusion support was needed in 35% of pregnancies, relapses were not observed. There were no deaths, but complications occurred in 79% of pregnancies. Preterm delivery and postpartum haemorrhage were observed in 21% and 26% of pregnancies, respectively.

Although the combination of tyrosine kinase inhibitors with chemotherapy is widely used for young adults with Philadelphia chromosome positive-acute lymphoblastic leukaemia (Ph+ ALL), the outcome and safety of this combination using intensive paediatric-based protocols has not been well described. The clinical course of 32 adults age 18-60 years with Ph+ ALL treated with a paediatric-based protocol plus imatinib was evaluated. The complete response rate was 94%. Grade 3-4 infections, neuropathy, myopathy and liver function abnormalities were common, resulting in major treatment delays and dose reductions, and declines in performance status (physical deconditioning), particularly in patients aged 41-60 years. Median and 3-year overall survival (OS) was 40·7 months and 53%, respectively, and median and 3-year even-free survival (EFS) was 30·1 months and 50%, respectively. OS and EFS were inferior in deconditioned patients. Of 16 patients who underwent haematopoietic stem cell transplantation (HSCT) in first complete remission, six died of non-relapse complications. There was no significant difference in OS and EFS between transplanted and non-transplanted patients, based on an intention-to-treat and time-to-donor identification analysis. The combination of imatinib with a paediatric-based regimen in adults produced high response rates, but was associated with considerable toxicity and high non-relapse mortality post-HSCT.

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 age35 years, high white blood cell count, MLL rearrangement, allogeneic stem cell transplantation in first complete remission and80% of the planned asparaginase dose delivered during intensification. Patients agedor = 35 years had a 3 year OS of 83%, as compared to 52% for patients aged35 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.

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.

All newly diagnosed patients aged 60-79 years with acute lymphoblastic leukaemia (ALL) receiving induction chemotherapy with a modified paediatric-based regimen over a 7-year period were retrospectively analysed (n = 51, median age 65 years). The treatment regimen consisted of induction, central nervous system prophylaxis, seven cycles of intensification and 24 cycles of maintenance. BCR-ABL1 negative patients received weekly asparaginase during intensification, while BCR-ABL1+ patients received daily imatinib. Post-remission therapy was given in an outpatient setting. The complete response rate was 75%, with an induction mortality of 20%; 6% of patients had resistant disease. 37% of patients who achieved a complete remission relapsed. The estimated 5-year overall survival was 40% for BCR-ABL1 negative and 47% for BCR-ABL1+ patients (P = not significant); the 5-year disease-free survival was 57% and 39%, respectively (P = NS). The post-induction phase was generally well tolerated, with 81% able to complete the intensification phase and proceed to maintenance. In conclusion, administration of this modified paediatric-based protocol is feasible and active for elderly patients with ALL. Survival is superior to most previously reported series in this age group, but remains worse compared to younger patients. Further improvement of the toxicity profile, particularly during induction, is required to improve outcomes.