SummaryTo date, no prospective study on Plerixafor 'on-demand' in combination with chemotherapy and granulocyte colony-stimulating factor (G-CSF) has been reported. We present an interim analysis of the first prospective study in which Plerixafor was administered on-demand in patients affected by multiple myeloma and lymphoma who received high dose cyclophosphamide or DHAP (dexamethasone, cytarabine, cisplatin) plus G-CSF to mobilize peripheral blood stem cells (PBSC). One hundred and two patients were evaluable for response. A cohort of 240 patients receiving the same mobilizing chemotherapy was retrospectively studied. Failure to mobilize CD34 + cells in peripheral blood was reduced by 'on-demand' strategy compared to conventional mobilization; from 13Á0 to 3Á0% (P = 0Á004). Failure to harvest CD34 + cells 2 9 10 6 /kg decreased from 20Á9 to 4Á0% (P = 0Á0001). The on-demand Plerixafor strategy also resulted in a lower rate of mobilization failure (P = 0Á03) and harvest failure (P = 0Á0008) when compared to a 'bias-adjusted set of controls'. Evaluation of economic costs of the two strategies showed that the overall cost of the two treatments were comparable when salvage mobilizations were taken into account. When in combination with cyclophosphamide or DHAP plus G-CSF, the 'on-demand' use of Plerixafor showed, in comparison to conventionally treated patients, a significant improvement in mobilization of PBSC with no increase in overall cost.
The approval of second-generation tyrosine kinase inhibitors (TKIs) for the first-line treatment of chronic myeloid leukemia (CML) has generated an unmet need for baseline molecular parameters associated with inadequate imatinib responses. We correlated and transcripts at diagnosis with the outcome-defined by the 2013 European LeukemiaNet recommendations-of 272 patients newly diagnosed with CML receiving imatinib 400 mg/daily. Applying receiver-operating characteristic curves, we defined and levels associated with lower probabilities of optimal response, failure-free (FFS), event-free (EFS), transformation-free (TFS), and overall survival (OS). With a median follow-up of 60 months, 65.4% of patients achieved an optimal response (OR), 5.6% were classified as "warnings," 22.4% failed imatinib, and 6.6% switched to a different TKI because of drug intolerance. We recorded 19 deaths (6.9%), seven (2.5%) attributable to disease progression. We found that higher levels at diagnosis were associated with inferior rates of OR ( < 0.001), FFS ( < 0.001), and EFS ( < 0.001). Elevated levels were also associated with lower rates of TFS ( = 0.029) but not with OS ( = 0.132). Similarly, high levels at diagnosis were associated with inferior rates of OR ( = 0.03), FFS ( = 0.001), and EFS ( = 0.005), but not with TFS ( = 0.167) or OS ( = 0.052). However, in internal validation experiments, outperformed in samples collected at diagnosis as the latter produced 80% misclassification rates. Our data suggest that high transcripts at diagnosis measured using as a reference gene identify patients with CML unlikely to benefit from standard-dose imatinib. .
Patients with acute graft-versus-host disease (GvHD) grade I were randomized to an observation arm (n=85) or to a treatment arm (n=86) consisting of 6-methylprednisolone 1 mg/kg/day, after stratification for age and donor type. The primary end point was development of grade II–IV GvHD. The cumulative incidence of grade II–IV GvHD was 50% in the observation arm and 33% in the treatment arm (P=0.005). However, grade III–IV GvHD was comparable (13% vs. 10%, respectively; P=0.6), and this was true for sibling and alternative donor transplants. Moderate/severe chronic GvHD was also comparable (17% vs. 9%). In multivariate analysis, an early interval between transplant and randomization (
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