Treatment of early chronic lymphocytic leukemia: Intermittent chlorambucil versus observation

Abstract

The effect of early therapy on the course of chronic lymphocytic leukemia (CLL) has not been established. Fifty-nine patients with indolent Rai stage I and II CLL were randomized to receive intermittent chlorambucil once a month or to receive no treatment. The two groups were comparable in entry characteristics. At 5 years from randomization there was no significant difference in survival between the two groups although the proportion of patients exhibiting active disease 5 years after randomization is 70 per cent in the untreated group and 55 per cent in the treated group. In this study, early treatment of CLL with intermittent chlorambucil did not result in a survival advantage for patients with indolent stage I and II CLL.

Alkylating agents and nucleoside analogues in the treatment of B cell chronic lymphocytic leukemia

“…Furthermore, there were six cases of acute leukemia in the group of 422 patients treated with chlorambucil as initial or secondary treatment, but no such cases among those patients who were never treated with this agent. 10 Similar conclusions were drawn from the studies performed by the IGCI CLL Cooperative Group, 15 and the Cancer and Leukemia group B, 16 which compared patients with B-CLL who received early treatment with chlorambucil to a group of B-CLL patients with deferred therapy in relation to the time of progression of the disease.…”

“…Several randomized trials indicate that initiation of chlorambucil-related therapy during the indolent phase of CLL does not prolong the survival time of CLL patients. 10,[15][16][17] Dighiero and Binet note that approximately one-third of CLL patients never require treatment and die from causes unrelated to this disease. 4 Only one-third have aggressive disease at diagnosis and should be immediately treated.…”

“…[7][8][9][10] More recently, renewed interest in CLL therapy has been created by the introduction of novel nucleoside analogues (NA), particularly fludarabine (FAMP) and cladribine (2-chlorodeoxyadenosine, 2-CdA), as well as combined chemotherapy. [11][12][13][14][15][16][17][18] The place of alkylating agents and NA in the management of CLL patients at the beginning of the new millennium, based on the results of randomized clinical trials, is the subject of this review.…”

Cyclophosphamide followed by fludarabine for untreated chronic lymphocytic leukemia: a phase II SWOG TRIAL 9706

“…Lymphocyte doubling time in the peripheral blood, histological pattern of lymphocytic infiltration in the bone marrow biopsy specimen, cytogenetics, and more recently CD38 expression are known to assist in predicting the clinical course and duration of survival. [6][7][8][9][10][11] Patients with CLL who are asymptomatic and do not have evidence of progression can be safely watched to assess their disease's clinical behavior. 12,13 Treatment is eventually required for most patients with CLL because of progressive disease (PD) or disease-related morbidity from infection, hemorrhage, constitutional symptoms, and/or problems resulting from lymphadenopathy and hepatosplenomegaly.…”

Indicações para início de tratamento na leucemia linfóide crônica

“…Dois estudos, um europeu, do grupo francês cooperativo em LLC, 19 e outro dos EUA, do grupo CALGB, 20 confirmaram que, em estágios iniciais, o tratamento imediato não prolonga a sobrevida global. Estes estudos foram, no entanto, realizados utilizando-se tratamento baseado em agentes alquilantes.…”