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Hairy cell leukaemia (HCL) was first described 50 years ago. Median survival was then 4 years. The purine analogues, introduced in the 1980s, transformed this prognosis. We reviewed data retrospectively from 233 patients, treated with pentostatin (n = 188) or cladribine (n = 45), to investigate the current long-term outlook. Median follow-up was 16 years. There were no significant differences in outcome between the two agents. Overall, the complete response (CR) rate was 80% and median relapse-free survival was 16 years. After relapse (n = 79) or non-response (n = 5), 26 patients received pentostatin and 58 cladribine; 69% achieved CR and median relapse-free survival was 11 years. After third-line therapy (n = 23), 50% achieved CR and median relapse-free survival was 6.5 years. However, CRs were equally durable, whether after first, second or third-line therapy. Complete responders and those with both haemoglobin >100 g/l and platelet count >100 x 10(9)/l before treatment had the longest relapse-free survival (P < 0.0001). Patients still in CR at 5 years had only a 25% risk of relapse by 15 years. Outcomes for patients with recurrent disease improved with the monoclonal antibody rituximab, combined with either purine analogue. Overall only eight patients died of HCL-related causes. Patients achieving a CR can expect a normal lifespan.

A phase II study was undertaken to evaluate the efficacy and toxicity of a new schedule of cladribine administration (10 mg/m2 orally daily for 3 d every 3 weeks) in 107 patients with B-cell chronic lymphocytic leukaemia (CLL). To minimize toxicity, treatment withdrawal criteria were defined. The results of the 63 previously untreated patients were retrospectively compared with 63 from an earlier study using a 5-d monthly schedule. The compiled data were analysed for prognostic factors for survival. No significant difference regarding response were seen in the two cohorts of the 126 previously untreated patients. The complete response (CR), nodular partial response (nPR) and partial response (PR) rates were 15%, 21% and 41%. Quality of response had no impact on survival. The 3- and 5-year overall survival for previously untreated patients was 73% and 58%, respectively, with a median follow-up of 54 months. Pretreatment haemoglobin <11.0 g/dl and elevated beta-2-microglobulin had a negative influence on survival. Major infections occurred in 21% of patients in the 3-d study compared with 35% in the 5-d study. The overall response (OR) and CR rates in the 40 previously treated patients were 34% and 5% respectively. Median overall survival was 24 months and median progression-free survival for responding patients was 14 months. Cladribine used as a single agent is an effective treatment with an acceptable safety profile for pretreated and untreated B-CLL. The achievement of complete remission was not a prerequisite for long-term survival.

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.

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.

The cytotoxic antimetabolite fludarabine is a widely used active agent in chronic lymphocytic leukaemia (CLL). However, cost and occasional adverse side-effects necessitate careful use. Identifying before treatment patients not likely to benefit from fludarabine could advance disease management both clinically and financially. We used the DiSC (differential staining cytotoxicity) assay, an ex vivo apoptotic drug response test, to identify the sensitivity or resistance to fludarabine of lymphocytes from B-cell CLL patients and compared the results with subsequent patient treatment, response and survival. Patients were grouped thus: those receiving fludarabine within 1 year of assay (+/- other cytotoxic drugs), and those receiving other chemotherapy (excluding fludarabine) within 1 year of assay. Fludarabine-test-resistance was found in 12/100 (12%) of untreated patients and 45/143 (31%) of previously treated patients (17/32 (53%) of patients previously treated with fludarabine). Treating fludarabine-test-resistant patients with fludarabine resulted in poor response compared with fludarabine-test-sensitive patients (7% v 69%) and short survival (median 7.9 v 41.7 months; relative risk (RR) = 14.8; P < 0.0001). 81% of fludarabine-test-resistant patients were test sensitive to other regimens. If treated with chemotherapy other than fludarabine, test-resistant patients responded better and survived substantially longer than those treated with fludarabine (RR = 2.9; P = 0.001). Not all CLL patients should receive fludarabine. Fludarabine-test-resistance by DiSC assay is a powerful independent prognostic factor. Pretreatment DiSC assay results could enable the toxic, clinical and financial costs of fludarabine treatment to be avoided in fludarabine-test-resistant patients. Disease management, response, survival and use of financial resources might be significantly improved if therapy choice in CLL patients was guided by DiSC assay.

We have undertaken a prospective randomized study in 90 patients with relapsed or resistant lymphomas to assess the value of G-CSF (lenograstim) in the acceleration of myeloid recovery after peripheral blood stem cell transplantation (PBSCT). A common regimen of cyclophosphamide 1.5 g/m2 on day 1 and lenograstim 263 microg s.c. on days 2-10 with two aphereses on days 10 and 11 was used for stem cell mobilization. 77% of patients achieved an adequate PBSC collection in two harvests (> 2 x 10(8) MNC/kg or > 2 x 10(6) CD34+ cells/kg). 65 patients went on to receive high-dose BEAM chemotherapy and engraftment data was available for 62. 34 patients had been randomized to receive lenograstim 263 microg/d s.c. and 28 to no growth factor. The median time to ANC > 0.5 x 10(9)/l was 9 d in the lenograstim arm versus 12.5 d in the no-lenograstim arm (P=0.0001). This was associated with a median duration of time in hospital post PBSCT of 13 d in the lenograstim arm versus 15.5 d in the no-lenograstim arm (P=0.0002). Median days to platelet independence, platelet transfusions, incidence of infection and red cell transfusion were the same in both arms. These data indicate that lenograstim significantly accelerated myeloid recovery after PBSCT and shortened the duration of hospital stay.

Peripheral blood values and bone marrow appearances were monitored in eight patients treated for chronic granulocytic leukaemia in transformation by cytotoxic drugs with or without total body irradiation followed by autografting with cryopreserved-thawed peripheral blood nucleated cells. One of the patients was 'autografted' on two occasions. Five patients had been splenectomized early in the first chronic phase and the other three patients had their spleens intact. Recovery of peripheral blood values was more rapid in the splenectomized than in the non-splenectomized patients. CFUc were present in the circulation immediately after autografting in each case but subsequently the pattern of CFUc changes differed between patients. The bone marrow was hypocellular at the time of autografting but the rate at which it returned to a typical chronic phase picture varied. Peripheral blood nucleated cells collected at the time of diagnosis include stem cells with the capacity to repopulate the marrow after 'ablative' therapy for transformation. Elective splenectomy in the chronic phase may promote more rapid recovery of peripheral blood values but its long-term importance is unknown.