A. G. Smith

A multicentre, open, non‐comparative phase II study of a combination of fludarabine phosphate, cytarabine and granulocyte colony‐stimulating factor in relapsed and refractory acute myeloid leukaemia and de novo refractory anaemia with excess of blasts in transformation

The primary objective of this study was to determine the complete remission (CR) rate achieved with the FLAG (fludarabine phosphate, cytarabine and granulocyte colony‐stimulating factor) regimen in patients with relapsed or refractory acute myeloid leukaemia (AML) or de novo refractory anaemia with excess of blasts in transformation (RAEB‐t). Secondary objectives were to evaluate survival and toxicity. Induction treatment consisted of between one and two courses of FLAG. Patients achieving CR received between one and two courses of consolidation treatment. Eighty‐three of the 89 patients entering the study were eligible for assessment. CR rates were: 17 out of 21 (81%) in late relapse AML (Group 1), 13 out of 44 (30%) in early relapse/refractory AML (Group 2), and 10 out of 18 (56%) in de novo RAEB‐t (Group 3). Thirty‐four of the 40 responders (85%) achieved CR after one induction course. Median survival times were 1·4 years, 3 months and 1·6 years in Groups 1, 2 and 3 respectively. Other than myelosuppression, the FLAG regimen was not generally associated with clinically significant toxicity and was well tolerated by most patients including the elderly. The FLAG regimen offers a very effective alternative treatment for CR induction in poor prognosis adult patients with either relapsed or refractory AML or de novo RAEB‐t. FLAG delivers high‐dose treatment without increasing overall toxicity, an approach which is of particular value in older patients, who constitute the majority in these diseases. It is therefore an important advance in developing new treatment options for these patients.

t(8;21) myelodysplasia, an early presentation of M2 AML

The reciprocal translocation of genetic material between chromosomes 8 and 21, t(8;21), is usually restricted to cases of acute myeloid leukaemia (AML). Cases of AML with t(8;21) exhibit characteristic dysplastic features in myeloid and erythroid lineages with reduction in megakaryoctes. We report details of three patients presenting with myelodysplastic features; two had a typical t(8;21), and the thir had a variant t(8;21) translocation. We discuss the signifcance of t(8;21) in the aetiology of myelodysplastic syndrome (MDS) and implications for the management of such patients.

Response to cladribine in previously treated patients with chronic lymphocytic leukaemia identified by ex vivo assessment of drug sensitivity by DiSC assay

The ability to identify non‐responders to cytotoxic chemotherapy has significant clinical and economic benefits. Differential staining cytotoxicity (DiSC) assays were performed in 34 previously treated patients with chronic lymphocytic leukaemia prior to treatment with cladribine. Of the 28 identified as ex vivo sensitive, 26 achieved a complete (CR) or partial response (PR) (median length of response 1.5 years, median survival 3.37 years) and two had a >70% fall in lymphocytes: six identified as ex vivo resistant failed to respond. The DiSC assay can accurately identify a subgroup of patients resistant to cladribine.

Del(15)(q11q15) associated with transformation of chronic myelomonocytic leukemia

Nonrandom cytogenetic abnormalities have been described in a variety of human malignancies including myelodysplastic syndromes (MDS). Acquisition of new chromosomal abnormalities may herald onset of a more aggressive disease. We report a patient with chronic myelomonocytic leukemia (CMMoL) who initially had a normal karyotype, but in whom the clonal interstitial deletion of chromosome 15 (q11-q15) was coincident with development of acute myeloid leukemia (AML) one year later. To date, this chromosomal change has not been reported in CMMoL, AML, or any other human malignancy.

Acute leukaemia in the elderly, remission induction versus palliative therapy.

Most patients with acute myeloid leukaemia (AML) are over 60 years old [1], remission rates are lower and survival poorer for this group in both AML [2] and for older patients with acute lymphocytic leukaemia (ALL) [3]. Current intensive therapy protocols have been proposed as the treatment of choice for these patients although published studies in AML advocating this approach contain a lower percentage of patients over 60 than would otherwise be expected [4, 5]. Such studies therefore do not appear to reflect the whole problem of acute leukaemia in the elderly.