Eradication of Minimal Residual Disease in B-Cell Chronic Lymphocytic Leukemia After Alemtuzumab Therapy Is Associated With Prolonged Survival

Abstract

MRD-negative remission in CLL is achievable with alemtuzumab, leading to an improved overall and treatment-free survival.

Management of infections in patients with chronic lymphocytic leukemia treated with alemtuzumab

“…Importantly, several studies have shown that infectious events typically occur around the time of T-cell and neutrophil nadirs (Fig. 1) [13,30,38,40,49].…”

“…Similarly, in the pivotal study of 93 relapsed/refractory CLL patients, 25 patients (27%) experienced grade 3/4 infectious events (27%), which occurred more frequently in non-responders than in responders (36% versus 9.7%) [30]. In a recent study, 91 patients with relapsed/refractory CLL were treated with alemtuzumab until maximum response, which included achievement of minimal residual disease (MRD)-negative remission [38]. There were four infectious episodes in 18 MRD-negative patients, compared with 27 episodes in 73 patients who did not achieve MRD negativity.…”

“…CMV reactivation typically occurs between weeks 3 and 8 of alemtuzumab treatment, around the time of or shortly after T-cell nadir [30,38,40]. Routine CMV-specific prophylaxis is not recommended due to lack of data from large randomized studies.…”

Vaccination of B-CLL patients with autologous dendritic cells can change the frequency of leukemia antigen-specific CD8+ T cells as well as CD4+CD25+FoxP3+ regulatory T cells toward an antileukemia response

“…Treatment regimens with purine nucleoside analogues and monoclonal antibodies (mAb) have increased the rate of molecular complete remissions and may result in a longer time to progression. [1][2][3] However, these options bear significant risks for infectious complications, which must be carefully weighted against the risks by the underlying disease. 4,5 Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy for B-CLL, 6,7 but due to the high treatment-related mortality and advanced age of most patients, the procedure is not applicable for the majority of B-CLL patients.…”

The effect of immunoglobulin VH gene mutation status and other prognostic factors on the incidence of major infections in patients with chronic lymphocytic leukemia

“…It was demonstrated that fludarabine and alemtuzumab improved response rates compared with traditional alkylating agents but also caused significant immunosuppression. 11,12 Autologous and allogeneic hematopoietic cell transplantation (HCT) also are associated with prolonged neutropenia and immunosuppression, which results in fungal, viral, and other opportunistic infections. 13,14 The objective of the current study was to assess the relations between new prognostic markers and therapies on the type of infections encountered, the time taken to develop these infections, and the infection-related mortality (IRM) rate.…”