No abstract

To evaluate caspofungin in high-risk invasive aspergillosis (IA) patient, a retrospective review of patient characteristics, antifungal therapies and clinical outcomes on hospitalised patients at sites in Russia, Canada, Germany, and Thailand was performed. Fifty-five patients were included, six with proven and 49 with probable aspergillosis; 76.4% had haematological diseases, 80% were on immunosuppressive drugs, 32.7% were neutropenic at caspofungin initiation. Median duration of prior antifungal therapy was 9 days (range 1-232). Reasons for initiating caspofungin included: disease refractory to first-line antifungal (49.1%) and toxicities with prior antifungals (18.2%). Median caspofungin therapy duration was 14 days (range 2-62), with a median of 13 days (range 1-62) as monotherapy. Favourable responses were observed in 45.5% of the patients, complete responses in 40% and partial responses in 5.5%; 74.5% survived 7 days after completion of caspofungin therapy with 69.1% having been successfully discharged from the hospital. Few patients (14.6%) on caspofungin switched because of suspected resistance, lack of response or adverse events. There were no increases in hospital stay as a result of adverse events or drug-drug interactions related to caspofungin; 7.3% of patients had a mean value of 13 (± 14.11) days of increased stay attributable to treatment failure. Caspofungin was well-tolerated. It exhibited effectiveness and high survival in treating severe IA patients.

T-cell acute lymphoblastic leukemia (T-ALL) is a rare disease usually treated with intensive, high-dose consolidation chemotherapy followed by an allotransplant in a substantial number of patients. The data of the RALL-2009 study on 125 adult T-ALL patients suggest that similar total chemotherapy doses given less intensively over a longer interval without interruptions and with an auto- rather than an allotransplant produce outcomes like current more intensive protocols and an allotransplant: 9-year cumulative incidence of relapse (CIR), leukemia-free survival (LFS), and survival were 24% (95% CI 16–33%), 70% (95% CI 59–79%) and 62% (95% CI 51–72%). In a landmark analysis, subjects achieving a complete remission and receiving an autotransplant had a lower 9-year CIR (9% [95% CI 2–22%] vs. 29% [95% CI 16–43%]; p = 0.0076) and better LFS (91% [95% CI 79–98%] vs. 58% [95% CI 41–74%]; p = 0.0009) and survival (92% [95% CI 77–99%] vs. 60% [95% CI 44–77%]; p = 0.001) compared with subjects not receiving an autotransplant. In a multivariate analysis, white blood cells ≥100 × 109/L at study entry were significantly associated with worse LFS (HR = 2.842 [95% CI 1.131–7.143]; p = 0.0263) and survival (HR = 6.085 [95% CI 1.918–19.3]; p = 0.0022) because of more early deaths (HR = 2.42 [95% CI 1.04–5.67]; p = 0.041). Receiving an autotransplant correlated with a lower CIR (HR = 0.23 [95% CI 0.07–0.73]; p = 0.0136) and better LFS (HR = 0.27 [95% CI 0.08–0.85]; p = 0.0256) and survival (HR = 0.158 [95% CI 0.045–0.550]; p = 0.0037).

A lower chemotherapeutic load and a small number of allogeneic BMTs did not affect total positive treatment results in adult patients with ALL, by complying with the principle achieving the continuity of cytostatic effects and by preserving the total cytostatic loading dose. The results of the Russian investigation casts some doubt on the necessity of using very intensive consolidation cycles and performing a large number of allogeneic BMTs in adult patients with ALL.

The ALL-2009 protocol allows both the federal and regional centers to obtain the long-term results comparable with those of current foreign studies: OS (54.2%), RFS (56.5%); and relapse risk (35.4%). Multivariate analysis has identified age (over 30 years), initial leukocytosis (30·109/l and more) and t(4;11) among the main clinical prognostic factors. Gene mutation detection evaluated in a small number of patients (8/36) is not a poor prognostic sign. There is a need for further investigations with centralized evaluation of the mutation status of leukemic cells and the clearance of minimal residual disease.