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HTLV-1-associated acute adult T-cell leukaemia-lymphoma (ATL) is a highly aggressive malignant disorder with a median survival of 6 months or less. We describe an Afro-Caribbean female with very poor prognosis ATL who underwent chemotherapy with a 4 d infusion schedule of cyclophosphamide, doxorubicin and etoposide, followed by successful allogeneic bone marrow transplantation (BMT) from her HTLV-1-negative histocompatible sister. The patient remains in complete remission 23 months after BMT and has 100% donor haemopoiesis with no evidence of HTLV-1 infection on PCR testing. We suggest that allo-BMT can prolong disease free survival or may even be curative in HTLV patients.

The pericentric inversion of chromosome 16 [inv(16)(p13q22)] and t(16;16)(p13;q22) are chromosomal rearrangements frequently associated with AML FAB type M4Eo resulting in the production of a fusion gene CBFB/MYH11. We studied 17 patients with a chromosome 16 abnormality (eight M4Eo, two M1, one M2, three M4 without abnormal eosinophils, three MDS) for the presence of CBFB/MYH11 transcripts using an RT-PCR technique. 10 AML patients with inv(16) tested RT-PCR positive (eight at presentation, one in remission, one in remission and relapse). Three of these patients were originally reported by cytogenetic analysis to have del(16q22) but the positive RT-PCR results prompted a cytogenetic re-examination, resulting in the correction of the reports to inv(16). We show that although inv(16) is closely associated with AML M4Eo, it can also be detected in cases of AML M4 without abnormal eosinophils. Three cases of MDS with inv(16) were also RT-PCR positive. Four patients with other chromosome 16 abnormalities were RT-PCR negative. Four AML patients with inv(16) were studied in remission. All were RT-PCR positive, including one patient in remission for 108 months and one 22 months post allogeneic bone marrow transplant. In the latter two remission patients, RT-PCR evaluation was positive in bone marrow (BM) but not in peripheral blood, suggesting that BM may be the more informative. We conclude that this technique is valuable in the accurate molecular classification of AML, particularly as treatment options may be influenced by such information. Though RT-PCR is highly sensitive in detecting CBFB/MYH11 fusion transcripts during remission, monitoring of minimal residual disease in patients with inv(16) remains to be established.

Intensive chemotherapy is the treatment of choice for selected elderly patients with acute myeloid leukaemia (AML). We recently developed a model to predict survival, thereby providing objective information upon which to select appropriate therapy for such patients. Such models, however, must be validated on a cohort of patients not used during the development of the model. We have tested the model using a series of 61 elderly patients consecutively treated with intensive chemotherapy. Using several statistical techniques, we have shown that the model is of value in predicting prognosis, though two patients did markedly better than the model prediction. This model may be useful for predicting survival in elderly patients with AML and warrants more extensive validation.

With an increasing number of elderly patients presenting with acute myeloid leukaemia and with recent reports of worthwhile remission rates and survival times following treatment with intensive chemotherapy, there is a pressing need to identify criteria to assist in the selection of appropriate therapy for elderly patients. We have performed multivariate Cox proportional hazard regression analysis of data prospectively collected during the treatment of 104 patients aged 60 and over treated in a multi-centre study with a standardized regimen of mitozantrone and cytosine arabinoside for induction and consolidation. Four readily available parameters, namely urea, performance status, peripheral blood blast count and presence of hepatomegaly, were identified from which a prognostic model to predict survival has been developed. The model was found to be accurate in predicting survival in the cohort of patients from which it was developed, but needs to be validated in a further test population studied prospectively. Its simplicity suggests that it may be particularly useful in the selection of elderly patients with AML most likely to benefit from intensive chemotherapy.

We have prospectively evaluated a regimen of mitozantrone and cytosine arabinoside (Ara-C) as first-line therapy in elderly patients with acute myeloid leukaemia (AML). One hundred and four patients with a median age of 68 (range 60-81) were studied, in whom 86 had de-novo AML, and 18 had preceding myelodysplasia or secondary AML. Complete remission was achieved in 64% of de-novo cases, in 28% of MDS/secondary cases, and in 58% overall. The incidence of early death within 28 d of chemotherapy was 11%. The median disease-free survival (DFS) was 11 months with an actuarial DFS of 15% at 43 months. The median overall survival was 9 months with an actuarial survival of 10% at 44 months. The incidence of non-haematological toxicity was acceptably low, and usually of mild to moderate severity. Quality of life was improved, or unchanged, in 90% of responders. We conclude that mitozantrone and ara-C is an effective and well-tolerated regimen which produces high remission rates in elderly patients with AML.