Thrombolysis beyond 3 hours for acute ischaemic stroke.

Intravenous thrombolysis is an accepted form of treatment for acute ischaemic stroke when administered within 3 h of symptom onset. However, evidence for its benefit when given beyond this time continues to strengthen. The case history of a young woman is presented with an ischaemic stroke who was successfully thrombolysed with recombinant tissue-type plasminogen activator more than 3 h after presentation. Perfusion CT scanning was used to stratify the likelihood of benefit. Thrombolysis was administered through a combination of intravenous and intra-arterial routes. This case illustrates the advances being made both in the imaging techniques used and the forms of drug administration which can be applied to maximise benefit in this extended therapeutic window. These recent advances are reviewed and their possible impact on current and future practice assessed. While the drive remains the introduction of thrombolysis at a local level for ischaemic stroke within 3 h of symptom onset, it is necessary to consider treatment of subjects presenting beyond 3 h in tertiary centres with the appropriate facilities and expertise.

Unrelated donor bone marrow transplantation for children with relapsed acute lymphoblastic leukaemia in second complete remission.

Allogeneic sibling bone marrow transplantation (BMT) is the recommended treatment for relapsed childhood acute lymphoblastic leukaemia (ALL), but appropriate donors are only available in 30% of cases. Unfortunately, BMT from unrelated donors (UD) has been associated with high rates of severe graft-versus-host disease (GvHD) and transplant-related mortality (TRM). In an attempt to improve outcome in UD-BMT we have assessed the impact of T-cell depletion using CAMPATH-1 (anti-CD52) monoclonal antibodies in 50 consecutively referred patients with relapsed ALL in second remission. All were previously treated according to MRC protocols UKALL X and XI, and then given chemotherapy on MRC R1 from relapse until UD-BMT, 19 patients had relapsed on and 31 off therapy. Patients and donors were fully matched at HLA-A, -B, -DR and -DQ loci in 29 cases and mismatched in 21 (four mismatched for more than one antigen). Pre-transplant conditioning comprised CAMPATH-1G, cyclophosphamide and total body irradiation. Bone marrow was T-cell depleted in vitro using CAMPATH-1 antibodies. Additional GvHD prophylaxis consisted of cyclosporin A (42 cases), cyclosporin plus methotrexate (four) or none (four). 47 patients engrafted. The incidence of acute GvHD was very low: two patients with grade II disease in the matched group, four with grade II-IV in the mismatched group. Only four patients have chronic GvHD. The actuarial event-free survival (EFS) at 2 years is 53%, with no significant difference between the matched and mismatched group. Further leukaemic relapse was the most important cause of failure. These results are similar to the most favourable published reports for HLA-matched sibling BMT in relapsed ALL.

Matched and mismatched unrelated donor bone marrow transplantation for juvenile chronic myeloid leukaemia.

Juvenile chronic myeloid leukaemia (JCML) is a rare haematological condition of childhood curable only by bone marrow transplantation (BMT). We report our experience using matched and mismatched unrelated donor BMT for JCML in five patients. Although the procedure is hazardous in terms of toxicity and relapse, two patients are alive and disease-free 28 and 49 months post BMT.