Acute lymphoblastic leukemia relapsing after first-line pediatric-inspired therapy: a retrospective GRAALL study.

The outcome of adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL) relapsing after pediatric-inspired front-line therapy is ill known. Here 229 relapsing Ph- ALL younger adults (18-63 years) treated within the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/-2005 trials were considered. Salvage regimens consisted of potentially curative therapies in 194 cases, low-intensity therapies in 21, allogeneic stem cell transplant (allo-SCT) in 6 and best supportive care in 8. Overall, 77 patients received allo-SCT after relapse. The median follow-up was 3.1 years. A second complete remission (CR2) was achieved in 121 patients (53%). In multivariate analysis, only younger age <45 years (P=0.008) and CR1 duration ⩾18 months (P=0.009) predicted CR2. Overall survival (OS) at 2 and 5 years was 19.3% (14-24%) and 13.3% (8-18%), respectively. In CR2 patients, disease-free survival (DFS) at 2 and 5 years was 29.0% (21-38%) and 25% (17-33%). In multivariate analysis, CR1 duration ⩾18 months and allo-SCT after relapse were associated with longer DFS (P<0.009 and P=0.004, respectively) and longer OS (P=0.004 and P<0.0001, respectively). In conclusion, although younger adults relapsing after pediatric-inspired ALL therapies retain a poor outcome, some of them may be cured if CR1 duration ⩾18 months and if allo-SCT can be performed in CR2. New therapies are definitely needed for these patients.

Equivalent outcomes using reduced intensity or conventional myeloablative conditioning transplantation for patients aged 35 years and over with AML.

Allogeneic hematopoietic stem cell transplantation provides the best chance of long-term survival for patients with AML, but is associated with an unpredictable risk of treatment-related mortality. From January 2000 to December 2010, we compared the outcomes for patients with AML aged 35 and over using reduced-intensity conditioning (RIC, N=60) or conventional myeloablative conditioning (MAC) regimen (N=72) transplantation. The median follow-up was 47 months (10-134). The 4-year cumulative incidence of non-relapse mortality was 21%. After adjusting for cytogenetic risk, gender donor/recipient mismatch and CD34+ cells, non-relapse mortality was significantly lower with the RIC regimen (P=0.027). The 4-year cumulative incidence of relapse was 38% and no difference was observed in the adjusted relapse rate between the two groups. The 4-year OS rate was 46%. Using both Cox regression and inverse probability-of-treatment weighted (IPTW) method, a similar OS rate was found with both regimens (adjusted hazard ratios for conventional vs reduced of 1.14 (95% CI 0.67-1.93, P=0.64) with Cox regression, and 1.14 (95% CI 0.55-2.34, P=0.73) with IPTW). Until prospective trials are completed, this study supports the use of a reduced-intensity regimen prior to transplantation for patients with AML aged 35 and over.

Prognostic significance of routine clinical and laboratory data in advanced head and neck cancers.

Predictive factors for toxicity and response to chemotherapy in patients with advanced head and neck cancer are seldom reported. Therefore, from a short series of patients with a histologically proven cancer, who were treated by a neo-adjuvant protocol with cisplatin and fluorouracil, routine clinical and laboratory data were investigated. ALT (alanine aminotransferase) and Hb (hemoglobin) appeared to be predictive for efficacy. By multivariate analysis (principal component analysis), these laboratory data were involved in two independent axes: one which was considered as "inflammatory" and the other as "hepatic". Initial obesity indices were associated with the former. The predictive variables for toxicity (i.e. age, serum creatinine level, weight loss and plasma cisplatin) were probably biased in this series. Nevertheless cisplatin concentration regularly increased in each cycle. Hence it was dependent on the rank of the course. According to this preliminary study, it would be of interest to conduct future investigations on acquired protein-energy malnutrition, as well as on selected soluble mediators of cellular and humoral immune response.

[Carcinomatous meningitis: rare complication of bladder cancer]. / La méningite carcinomateuse: une complication rare du cancer de la vessie.

The sites of metastases of transitional cell carcinoma of the bladder are nodes, liver, lung and bone, but the meningeal infiltration is rare. Therefore, one case of meningeal carcinomatosis is reported. After cystectomy for an undifferentiated carcinoma of the bladder, the patient received adjuvant chemotherapy. Three months after treatment completion, symptoms of cerebellar ataxia occurred and gradually confusion appeared. The initial cerebra spinal fluid showed clumps of malignant cells. The patient died 15 days after the neurological symptoms occurred. The clinical diagnosis of meningeal carcinomatosis is based on neurological manifestations at more than one level of the neuraxis. Symptoms may present simply as headache or confusion. Meningeal carcinomatosis from urothelial cancer seems to show some specific features: poorly differentiated tumour and high frequency of cerebellar symptoms. Intrathecal treatment essentially has a pain-effect. Mean survival time is as short as 20 weeks. The increasing incidence of this neurological complication in urothelial cancer does not only result from an increase in patient longevity but also from possible side-effects of chemotherapy, so as localized changes in blood-brain barrier permeability induced by antineoplastic drugs. Therefore, we may wonder whether meningeal carcinomatosis might not be regarded as an iatrogenic effect.

Matched unrelated or matched sibling donors result in comparable outcomes after non-myeloablative HSCT in patients with AML or MDS.

The impact of allelic HLA matching in patients with AML and myelodysplastic syndrome (MDS) who receive allogeneic PBSC after a reduced-intensity conditioning (RIC) regimen is unclear. From January 2000 to December 2010, 108 consecutive patients with AML (n=63) and MDS (n=45) received PBSC after RIC in our center, either from siblings (n=70) or from matched unrelated donors (MUD; 10/10 high resolution, n=38). Conditioning regimen was fludarabine based in 95% of patients and GvHD prophylaxis was mostly cyclosporine plus mycophenolate. Patient characteristics were similar between sibling and MUD for age (median 57 years), gender and disease distribution. Conditioning regimen (more anti-thymocyte globulin (ATG) in MUD), donor age (younger for MUD) and number of CD34+ cells infused (higher in MUD) were different. The median follow-up was 36 months (range 2-72). Engraftment, GvHD, TRM, relapse rate and OS at 3 years were comparable between sibling and MUD. After adjustment for age, cytogenetic risk, ATG and number of CD34+ cells infused, donor type still did not influence OS. In patients with AML or MDS, HSCT from MUD using PBSC after a RIC regimen led to similar outcomes than from Siblings.