engleski

Chlorambucil maintenance significantly improves survival in B cell chronic lymphocytic leukemia : meta-analysis of IGCI CLL trials

In CLL therapy, treatment duration and, in particular, the role of maintenance is not established. Two consecutive randomized trials from the CLL co-operative IGCI group compared High Dose continuous chlorambucil (HD-CLB) (15 mg fixed dose daily up to response or a maximum of 6 months) to Standard Dose chlorambucil (IGCI-01) and CHOP (IGCI-02). After identical Induction with HD-CLB in both trials, low dose CLB maintenance (5-15 mg twice a week adjusted to tolerance) for at least 18 months was administered to CR patients in IGCI-01 study and to CR and PR cases in IGCI-02 trial. In June 1997 the results were updated and a meta-analysis was performed in order to evaluate the role of maintenance. Focusing on patients with the same entry criteria on HD-CLB, in IGCI-01 trial out of 78 patients 49 obtained CR, 18 PR and 11 NR, and in IGCI-02 trial out of 114 patients 69 obtained CR, 33 PR and 12 NR. Overall survival was comparable in the two trials for patients in CR (median 68 vs. 65 months, NS) and NR (24 vs. 27 months, NS), while a significant difference was found in PR patients with the median survival of 29 months in unmaintained IGCI-01 cases vs. 52 months in maintained IGCI-02 ones (p = 0.0168). The difference in survival remained significant in subset of PR patients who presented before treatment with bone marrow failure (Rai stages 3 and 4, Binet stage C), p = 0.0172. PR cases from the two studies were fully comparable in pre-treatment TTM-size, Rai and Binet stage distribution, while there was a significant preponderance of male sex and a marginally significant older mean age in IGCI-01 trial. In Cox multivariate analysis only IGCI-trial variate was significantly associated with survival out of entered variates (age, sex, TTM-size, TTM-distribution, Rai stages, Binet stages, bone marrow failure and IGCI-trial (p = 0.050). This meta-analysis suggests an important role of prolonged low-dose CLB maintenance with significant impact on survival in B-CLL patients. Prospective studies of this aspect of CLL therapy are needed and warranted.

chronic lymphocytic leukaemia; therapy; maintenance

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