Summary 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 × 109/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.
Previous studies have suggested that the level of residual disease at the end of therapy predicts outcome in chronic lymphocytic leukemia (CLL). However, available methods for detecting CLL cells are either insensitive or not routinely applicable. A flow cytometric assay was developed that can differentiate CLL cells from normal B cells on the basis of their CD19/ CD5/CD20/CD79b expression. The assay is rapid and can detect one CLL cell in 10 4 to 10 5 leukocytes in all patients. We have compared this assay to conventional assessment in 104 patients treated with CAMPATH-1H and/or autologous transplant. During CAMPATH-1H therapy, circulating CLL cells were rapidly depleted in responding patients, but remained detectable in nonresponders. Patients with more than 0.01 ؋ 10 9 /L circulating CLL cells always had significant (> 5%) marrow disease, and blood monitoring could be used to time marrow assessments. In 25 out of 104 patients achieving complete remission by National Cancer Institute (NCI) criteria, the detection of residual bone marrow disease at more than 0.05% of leukocytes in 6 out of 25 patients predicted significantly poorer event-free (P ؍ .0001) and overall survival (P ؍ . IntroductionThe goal of conventional therapy for chronic lymphocytic leukemia (CLL) is to control the disease and rarely results in the complete eradication of detectable tumor cells. 1,2 Even purine analogue therapy, which is the most effective conventional therapy for inducing complete remission, 3 results in a return of normal polyclonal B lymphocytes in only 40% of patients. 4 This is the principle reason why the assessment of minimal residual disease (MRD) in CLL has not been considered to be important and why the criteria for response to therapy have defined "complete" remissions when there is likely to be a significant level of disease detectable by modern techniques. 5 The application of novel therapies, such as allogeneic or autologous hematopoietic stem cell transplantation 6 and monoclonal antibodies, 7,8 have resulted in a significant proportion of patients attaining much more profound responses. There is evidence to suggest that such responses may be associated with improved outcomes. 9,10 The current development of newer agents, the potential of immunomodulatory therapies, and the possible combination of 2 or more of these therapies promises to make the goal of eradicating detectable disease by the most sensitive techniques a realistic one.CAMPATH-1H (alemtuzumab) is a humanized monoclonal antibody specific for the CD52 antigen. The antigen is expressed on all lymphocytes as well as monocytes, macrophages, and spermatozoa. 11,12 CAMPATH-1H is extremely effective at killing lymphocytes in vitro and in vivo. 11,12 The humanization of the antibody has abrogated potential human antimurine antibody (HAMA) responses [13][14][15] and resulted in an agent that is extremely effective at inducing remission in patients with CLL. 8,16 Similarly, treatment with autologous transplantation has been shown to induce complete remissi...
Low-dose filgrastim significantly reduces neutrophil engraftment time post-PBSCT and also reduces in-patient stay and costs, which makes it economically viable for patients who are undergoing high-dose chemotherapy.
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