Allo-SCT for high-risk AML-CR1 in the molecular era: impact of FLT3/ITD outweighs the conventional markers.

Seventy-nine patients with AML in CR1 received allo-SCT between May 2006 and May 2011, and the prognostic impact of FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) mutation was evaluated in the context of other clinical prognostic factors. Patients with FLT3/ITD + AML had significantly inferior DFS (2-year DFS: 19% vs 64%, P = 0.0027), increased risk of relapse (1-year: 59% vs 19%, P = 0.01), and a trend towards decreased OS (P = 0.08) compared with patients without FLT3/ITD. Multivariate analysis confirmed FLT3/ITD + independently predicted a shorter DFS (HR, 3.0; 95% CI), 1.4-6.5; P = 0.01) and increased risk of relapse (HR, 4.9; 95% CI, 2.0-12.3, P = 0.01). Time to relapse in patients with FLT3/ITD + was short with 100-day cumulative risk of 45% (95% CI, 33-57). Our data suggest that the poor prognostic implication of FLT3/ITD positivity remains even after early allo-SCT in patients with FLT3/ITD + AML, and patients remain at high risk of early relapse. FLT3/ITD positivity also outweighs other conventional prognostic markers in predicting relapse.

Prevalence and risk factors associated with development of ocular GVHD defined by NIH consensus criteria.

We studied 172 patients for development of ocular graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT) from 2002 to 2009. Ocular GVHD was diagnosed in 60 patients (38%), with 27 (16%) being diagnosed at days 100 and 33 (23%) beyond day 100 for a 2-year cumulative incidence of 35% (95% confidence interval (CI), 28-43). The positive and negative predictive values of a Schirmer I test score (using 5 mm as a cutoff) in predicting ocular GVHD (day 100) were 41 and 82%, respectively. In patients with ocular GVHD beyond day 100, extraocular manifestations of GVHD preceded the development of ocular GVHD in most patients (27 of 33, 81%). Prior acute skin GVHD (odds ratio 2.57, 95% CI 1.17-5.64, P=0.019) and male recipients of female donors (odds ratio 2.57, 95% CI 1.09-6.06, P=0.03) were independent risk factors for ocular GVHD. We recommend comprehensive ocular evaluation rather than a screening Schirmer's test to establish the diagnosis of ocular GVHD. Early diagnosis and preventive strategies in high-risk populations need to be studied in clinical trials to prevent devastating impact on quality of life in patients with prolonged ocular GVHD.

Extracorporeal photopheresis in patients with refractory bronchiolitis obliterans developing after allo-SCT.

Extracorporeal photopheresis (ECP) has been shown to be a promising treatment for chronic graft-versus-host disease; however, only a few case reports are available that examine the effectiveness of ECP for bronchiolitis obliterans (BO) after allo-SCT. Because of the poor response to traditional therapies, ECP has been explored as a possible therapeutic option for severe BO after allo-SCT. Nine patients received ECP between July 2008 and August 2009 after a median follow-up of 23 months (range 9-93 months) post transplant. The primary indication for ECP was the development of BO in patients who had failed prior multidrug regimens. The median number of drugs used for BO management before ECP was 5 (range 2-7); this included immunosuppressive therapy. Six of nine (67%) patients responded to ECP after a median of 25 days (range 20-958 days). No ECP-related complications occurred. ECP seemed to stabilize rapidly declining pulmonary function tests in about two-thirds of patients with severe and heavily pretreated BO that developed after allo-SCT. This finding supports the need for a larger prospective study to confirm the impact of ECP on BO, and to consider earlier intervention with ECP to improve the outcome of BO after allo-SCT.