Increasing Incidence of Late Second Malignancies After Conditioning With Cyclophosphamide and Total-Body Irradiation and Autologous Bone Marrow Transplantation for Non-Hodgkin’s Lymphoma
ABSTRACT Although the risk of myelodysplastic syndrome (MDS) has been well-described following autologous bone marrow transplantation (ABMT), the risk of solid tumors has been poorly characterized. We report the incidence and outcome of solid tumors at 10-year follow-up in a large cohort of uniformly treated patients who underwent ABMT for non-Hodgkin's lymphoma (NHL).
Between 1982 and 1997, 605 patients underwent ABMT for B-cell NHL, with uniform conditioning with cyclophosphamide and total-body irradiation followed by reinfusion of autologous bone marrow purged with anti-B-cell monoclonal antibodies. Current information on relapse of disease and second malignancies was obtained via an institutional review board-approved questionnaire sent to the referring oncologists.
Forty-two solid tumors, six non-MDS hematologic malignancies, 39 nonmelanoma skin cancers, and 68 cases of MDS/acute myelogenous leukemia (AML) were observed at a median follow-up of 9.5 years. A cumulative incidence model using death as a competing risk found that the 10-year incidence of second malignancy is 21%, with 10.0% non-MDS malignancies. The projected incidence of all malignancies at 15 years is 29%. The principal risk factor for second malignancy is increased age at ABMT (P = .0002). In the entire cohort, 9.6% of patients have died of second malignancy.
Lengthy follow-up demonstrates a significant incidence of second malignancies after ABMT for NHL. Although the incidence of MDS/AML starts to plateau, the incidence of solid tumors continues to rise. Second malignancies are responsible for a significant fraction of overall mortality following ABMT.
- SourceAvailable from: Shawnda Tench
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- "Patients who have undergone ASCT for relapsed or refractory DLBCL are at increased risk of mortality well beyond 5 years, which is the time point that has been widely accepted a surrogate for long-term survival (Pedersen-Bjergaard et al, 2000; Bhatia et al, 2005; Brown et al, 2005; Kalaycio et al, 2006a,b; Armenian et al, 2008). Whether deaths occurring after 5 years are due to disease relapse mortality (RM) or nonrelapse mortality (NRM) is poorly studied. "
ABSTRACT: High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the preferred treatment modality for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). To assess long-term outcomes of these patients, we retrospectively analysed data from 309 consecutive patients who underwent ASCT for DLBCL between 1994 and 2006. We found that non-relapse mortality (NRM) became the major cause of death beginning approximately 8 years after ASCT. The most common causes of NRM during the study period were respiratory failure (31%), infection (13%), cardiac toxicity (15%) and secondary malignancy (15%). The strongest predictor of relapse mortality (RM) was disease status at transplant: patients who were in second or greater complete or partial remission had a higher risk of RM than those in first complete or partial remission [hazard ratio (HR) 3·7, P<0·001], as did those who were relapsed or refractory (HR 4·9, P<0·001). We describe the longest reported follow-up of a large cohort of DLBCL patients uniformly-treated with ASCT. Although relapse was initially the more likely cause of death, NRM exceeded RM after 8 years. After ASCT, surviving patients have significantly increased risk mortality rates relative to the general population and this excess risk persists over time.British Journal of Haematology 03/2011; 152(5):561-9. DOI:10.1111/j.1365-2141.2010.08549.x · 4.96 Impact Factor
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ABSTRACT: Purpose High-dose chemotherapy with peripheral blood progenitor cell (PBPC) autograft is effective in high-risk lymphoma, particularly with the addition of rituximab; however, it is associated with risk of secondary malignancy. These issues have been addressed in a series of 1,347 patients with lymphoma treated with a high-dose sequential (HDS) program. Patients and Methods A total of 1,024 patients with B-cell lymphoma, 234 patients with Hodgkin's lymphoma, and 89 patients with T-cell lymphoma were treated with HDS between 1985 and 2005 at 11 Gruppo Italiano Terapie Innovative Linfomi centers. HDS was given as salvage treatment to 707 patients (52%); 655 patients (49%) received a modified HDS, with high-dose cytarabine and two consecutive PBPC harvests. Rituximab-supplemented HDS was given to 523 patients (39%).
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ABSTRACT: For decades, investigators have calculated antegrade and reflected pressure waves from measured aortic pressure and flow. Although the physics of reflection is well understood, there has been controversy concerning the effect of reflection on aortic pressure and stroke work. Two opposing views have arisen. In one view, reflection from the periphery is believed to increase systolic pressure and stroke work. In the other view, reflection, if it has an effect, decreases systolic pressure and stroke work. In an attempt to resolve this conflict, two popular arterial system models are applied. Both models reflect the same proportion of the antegrade pressure wave. The only difference between them is that one model includes an extra time delay between the antegrade and reflected waves. These two models yield opposite results. This exercise clearly illustrates that the direct effect of reflection depends on the timing of the reflected wave relative to the antegrade waveEngineering in Medicine and Biology Society, 1997. Proceedings of the 19th Annual International Conference of the IEEE; 01/1997