Deletions of the 1p region appear as a pejorative prognostic factor in multiple myeloma patients (especially 1p22 and 1p32 deletions) but there’s a lack of data on the real impact of 1p abnormalities on an important and homogeneous group of patients. To address this issue we studied by fluorescence in situ hybridization (FISH) the incidence and prognostic impact of 1p22 and 1p32 deletions in 1195 patients from the IFM (Institut Francophone du Myélome) cell collection. Chromosome 1p deletions were present in 23.3% of the patients (271): 15.1% (176) for 1p22 and 7.3% (85) for 1p32 regions. In univariate analyses, 1p22 and 1p32 appeared as negative prognostic factors for PFS: 1p22: 19.8 months vs 33.6 months (p<0.001) and 1p32: 14.4 months vs 33.6 months p(<0.001); and OS: 1p22: 44.2 months vs 96.8 months (p=0.002) and 1p32: 26.7 months vs 96.8 months (p<0.001). In multivariate analyses 1p22 and 1p32 deletions still appear as independent negative prognostic factors for PFS and OS. In conclusion our data show that 1p22 and 1p32 deletions are major negative prognostic factors for PFS and OS for patients with MM. We thus suggest that 1p32 deletion should be tested for all patients at diagnosis
The aim of this retrospective analysis was to assess the benefit of reduced-intensity conditioning allo SCT (RIC allo-SCT) in a cohort of 32 relapsed multiple myeloma (MM) patients. A total of 19 patients had an HLAidentical sibling donor ('donor' group), while 13 patients had no donor ('no-donor' group). There were no significant differences between these two groups as for prognosis risk factors. Eighteen patients from the 'donor' group could actually proceed to RIC allo-SCT. With a median followup of 36 (range, 21-60) months, six patients died from transplant-related toxicity (cumulative incidence, 33% (95% CI, 11-55%)). Only 4 patients from the 18 transplanted patients (22%; 95% CI, 7-48%) progressed after RIC allo-SCT, as compared to 12 (86%; 95% CI, 56-98%; P ¼ 0.0003) among the nontransplanted patients. In an 'intention-to-treat' analysis, the Kaplan-Meier estimate of PFS was significantly higher in the 'donor' group as compared to the 'no-donor' group (P ¼ 0.01; 46 versus 8% at 3 years). There was no difference in terms of overall survival. However, in multivariate analysis, actual performance of RIC allo-SCT was associated with better PFS (relative risk, 0.35; 95% CI, 0.15-0.82; P ¼ 0.01). These data suggest a potential benefit for RIC allo-SCT in the management of relapsed MM warranting further prospective investigations.
The use of high-dose corticosteroids for graft-versus-host disease (GVHD) treatment represents a major risk factor for long-term invasive fungal infections. The aim of this study was to investigate the safety and tolerance of weekly prophylactic administration of once-weekly highdose (7.5 mg/kg) of liposomal amphotericin B (L-AmB) therapy in 21 adult patients receiving high-dose prednisone (2 mg/kg/day) for acute GVHD therapy after reduced intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT). Patients received a median of 4 (range, 1-8) infusions of L-AmB. Seven patients (33%; 95% confidence intervals (CI), 13-53%) discontinued taking the study drug owing to study drug-related adverse events, including elevated serum creatinine (41.5 times from baseline values; n ¼ 5), hypotension and pain (n ¼ 1), and violent chest pain and arrhythmia (n ¼ 1). The overall frequency of infusion-related reactions was 29% (n ¼ 6; 95% CI, 10-48%), but these reactions were always transient and relieved by stopping the infusion. This safety data provide support for an efficacy study of this prophylaxis strategy, because this may help further improving the outcome of RIC or nonmyeloablative allo-SCT.
One hundred and ten patients with multiple myeloma were treated with bendamustine as part of a French compassionate use program. To receive bendamustine, patients had to present with relapsed or refractory disease after prior therapies that had to include alkylators, steroids, IMiDs and bortezomib. The median number of bendamustine cycles administered was 4 (1-13). The overall response rate (≥ partial response) was 30%, including 2% complete responses. The median progression-free and overall survival for the entire cohort were 9.3 and 12.4 months, respectively. In this series of patients with advanced disease, both the response rate and the duration of response are encouraging and indicate that bendamustine presents a feasible option, which should be considered for the treatment of relapsed/refractory patients.
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