Relapse treatment FCR combination treatment is also effective in the relapse setting. The REACH study included patients at first relapse.41 However, the majority of patients in the study had previously received chlorambucil and were rituximab na?ve. After a median follow up time of 25 Apatinib YN968D1 months, rituximab significantly improved progression free survival in patients with previously treated CLL. Relapse data on patients previously treated with FCR is emerging. In a single centre study, 33 of 112 patients who relapsed after initial treatment with FCR were retreated with FCR. Patients who relapsed after 3 years had an ORR and CR of 86% and 23% compared to 54% and 0% for those relapsing within 3 years.42 On the basis of these data, FCR has therefore become the standard relapse treatment for GO GO patients.
However, there is still some debate around the definition of FCR refractoriness. Bearing in mind side effects from FCR and it,s cost, it is reasonable to assume that re treatment with FCR should only be attempted if the PFS after first line FCR is more than 2 years. Patients with del17p/TP53 mutation and purine analogue refractory patients Patients with deletions of chromosome 17p or TP53 mutation or purine analogue refractory disease have a poor prognosis and usually show only limited response to salvage chemotherapy. Alternative treatments are therefore urgently required. Subcutaneous administration of alemtuzumab20,43,44 is as effective and safe as intravenous administration with response rates ranging between 22% and 34% and median overall survival times between 10 and 19 months.
Despite the absence of randomised studies, it has become the standard of care for patients with TP53 deleted/mutated or purine analogue refractory disease. Alemtuzumab is not effective in patients with bulky lymphadenopathy. Combination treatment with high dose steroids, in particular high dose methylprednisolone or pulsed dexamethasone, is therefore being evaluated. An initial Phase 2 study showed improved ORR and CR rates of 85% and 36%, respectively, and a median PFS and OS of 11.8 months and 23.5 months.45 Further intensification has been achieved by combining alemtuzumab to FCR treatment. Using CFAR, patients with high risk CLL achieved ORR of 92% and CR rates of 70% in first line.46 However, combinations of alemtuzumab with fludarabine are not recommended outside clinical trials due to the increased rate of fatal infectious episodes.
47 An EBMT retrospective study of 44 transplants performed between 1995 and 2006 for del17p CLL showed that about one third of patients achieved longterm remission.50 A retrospective case control study suggested a survival advantage for patients with high risk CLL treated with reduced intensity conditioning BMT.51 Data from Seattle on 82 patients undergoing RIC allografting quotes 5 year incidences of non relapse mortality, progression/relapse, overall survival, and progression free survival of 23%, 38%, 50%, and 39%, respectively.52 In this study, a lymph node size of / 5cm, but not cytogenetic abnormalities, was associated with outcome.