Cesare Bergonzi

Incidence of bacterial and fungal infections in newly diagnosed acute myeloid leukaemia patients younger than 65 yr treated with induction regimens including fludarabine: retrospective analysis of 224 cases

Objectives:  Infections are the major cause of morbidity and mortality in patients with acute myeloid leukaemia (AML). They primarily occur during the first course of induction chemotherapy and may increase the risk of leukaemia relapse, due to a significant delay in consolidation therapy. The intensification of induction chemotherapy and the use of non‐conventional drugs such as fludarabine are considered responsible for the increased risk of infections.

Case-control study of multidrug resistance phenotype and response to induction treatment including or not fludarabine in newly diagnosed acute myeloid leukaemia patients

One hundred and six patients aged ≤60 years with newly diagnosed acute myeloid leukaemia (AML) treated with fludarabine‐based regimens (cases) were matched with 106 AML patients treated with conventional non‐fludarabine‐based regimens (controls). The cases and controls were matched by expression of the multidrug resistance P‐glycoprotein (MDR‐Pgp), measured by flow cytometry as mean fluorescence index (MFI), cytogenetics, and age. The complete remission (CR) rate of the cases was 61% among the MDR‐Pgp‐positive (posve) patients (MFI ≥ 6) vs. 75% among the MDR‐Pgp‐negative (negve) ones (MFI < 6) (P = 0·16). Conversely, in the controls, the CR rate was 44% among the MDR‐Pgp‐posve patients vs. 67% among the MDR‐Pgp‐negve ones (P = 0·02). The 4‐year disease‐free survival (DFS) and overall survival (OS) of MDR‐Pgp‐posve cases were significantly longer than those of MDR‐Pgp‐posve controls (DFS, 28·1% vs. 6·5%, P = 0·004; OS, 33·5% vs. 9·6%, P = 0·01). This difference was not found among the MDR‐Pgp‐negve patients. By univariate (P = 0·007) and multivariate (P = 0·007) analysis, the MDR‐Pgp‐posve phenotype was negatively correlated with CR and it emerged as the most important independent negative prognostic factor, after cytogenetics. Our study confirms the prognostic impact of the MDR phenotype in AML and strongly suggests fludarabine‐based induction treatments as a promising strategy for MDR‐Pgp‐posve AML patients. In this setting of patients, large prospective randomised studies should be planned.

Treatment of Chronic Myeloid Leukemia Elderly Patients in the Tyrosine Kinase Inhibitor Era

The prevalence of chronic myeloid leukemia (CML) is expected to double in the next 15 years. The introduction of imatinib significantly changed the prognosis of CML, challenging the concept of a fatal disease. Nowdays, imatinib, nilotinib and dasatinib are registered for first-line treatment of CML patients in chronic phase (CP). Considering elderly patients, the most extensively studied TKI is imatinib, that induces a rate of cytogenetic and molecular responses comparable between the younger and the elderly patients. Once a CCgR with imatinib is achieved, the probability to be alive and disease free at 8 years is more than 80%. These results confirm that imatinib has to be considered the first-line treatment for the elderly and that the CCgR is the guide parameter for treatment modulation and the most solid marker of long term outcome. Nevertheless, older patients tolerate imatinib worse in comparison to the younger, and this causes a higher rate of therapy discontinuation and less adherence to chronic treatment. Thus, the toxic profile of each TKI is one of the most important factors driving the choice of the best drug. Another important factor is the potency of the TKI. Since nilotinib and dasatinib are more potent than imatinib in inducing cytogenetic and molecular responses, they could be preferred for increasing the proportion of patients who can achieve deeper molecular responses, allowing treatment discontinuation. This approach is intriguing, but it is still experimental. Another therapeutic strategy could be the identification of the minimal effective dose of TKI in order to maintain the CCgR, but also this approach is under clinical investigation.