Can Less Intensive Chemotherapy and an Autotransplant Cure Adult T-Cell Acute Lymphoblastic Leukemia?

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).

Retrospective evaluation of caspofungin therapy in invasive aspergillosis (RECAM-IA).

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.

Spread of vancomycin-resistant Enterococcus faecium in two haematological centres in Russia.

This paper describes the clonal diversity of vancomycin-resistant Enterococcus faecium isolated from patients with haematological malignancies in Russia. Pulsed-field gel electrophoresis (PFGE) typing of 129 vanA-positive E. faecium strains revealed 23 independent restriction profiles with two predominant clonal types. Multilocus sequence typing (MLST) of 16 strains selected from two predominant PFGE types showed that they belong to the epidemic clonal complex (CC) 17. Tn1546-like elements of isolates were compared with the prototype element from E. faecium BM4147 by polymerase chain reaction (PCR). Four different Tn1546 types were distinguished according to structural alternations. Polymorphism in the orf1 and vanSH genes was detected. However, a significant prevalence of the prototype Tn1546 was revealed. Tn1546-like elements with the same structures were observed in strains of different PFGE types. The virulence genes esp, gelE and hyl were detected by PCR in 118 isolates (91%), 87 isolates (67%) and 35 isolates (27%), respectively. In contrast, agg and cylA genes were not found. The detection frequency of esp was higher in epidemic strains than in sporadic ones (100% vs. 56%; P<0.05). This study describes a genetically variable population of vancomycin-resistant E. faecium in two Russian haematological centres. The spread of vancomycin resistance was mostly due to the distribution of the two subclones of E. faecium CC17, enriched with the virulence marker esp. At the same time, dissemination of an altered Tn1546 also occurred.