Myeloablative allogeneic hematopoietic stem cell transplantation in elderly patients.
ABSTRACT This study aimed to evaluate the outcome following myeloablative allogeneic hematopoietic stem cell transplantation (SCT) among patients older than 50 yr of age. A total of 215 patients with a median age of 57 yr underwent allogeneic hematopoietic SCT for early (41%) or advanced (59%) hematologic malignancies. After a median follow-up of 36 months a 10-yr survival estimate of 56 +/- 6% could be assessed for patients in early disease stages while patients with advanced diseases showed a significantly decreased survival probability of 31 +/- 5% (p < 0.0002). Transplant related mortality (TRM) at day 100 and 365 post-transplant was 13% and 30% for early but increased to 21% and 49% for advanced disease stages. As major determinants of TRM advanced disease stage (p < 0.0001) and occurrence of grades II-IV graft-vs.-host disease (GVHD) (p < 0.0001) were identified. These results show that hematopoietic SCT following myeloablative conditioning is also applicable to elderly patients whereas disease stage and high-grade GVHD represent the essential prognostic factors for outcome.
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ABSTRACT: This study aimed to evaluate the efficacy of a nonmyeloablative conditioning consisting of fludarabine and TBI in patients aged > or =60 years.A total of 32 patients (median age 62 years; range 60-70) with hematological malignancies were treated with fludarabine (30 mg/m(2) x 3-5 days) and 200 cCy TBI followed by allogeneic hematopoietic stem cell transplantation (HSCT) from a matched-sibling donor. GVHD prophylaxis consisted of cyclosporine and mycophenolate. Neutrophil recovery occurred in all patients at a median time of 16 days (range 9-34). Six patients did not become granulocytopenic. On day +30, 10 patients had >95% donor chimerism and 19 patients had mixed chimerism. The cumulative probabilities of Grade II-IV acute GVHD and chronic GVHD were 48 and 83%, respectively. Transplant-related mortality at 100 days and 1 year was 6 and 10%, respectively. The probabilities of 2-year overall (OS) and progression-free survival (PFS) were 39 and 35%, respectively. The estimated 2-year probability of OS and PFS for patients in early disease stages were 77 and 64%, respectively, which were significantly higher than the survival and PFS estimates of 0% obtained in patients with advanced disease stages at the time of transplant. Our analysis would suggest that for patients older than 60, this regimen is well tolerated and associated with a low incidence of transplant-related mortality. The leukemic burden at time of transplant has proven to be the most important risk factor for the outcome.American Journal of Hematology 11/2007; 82(10):863-6. · 4.00 Impact Factor
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ABSTRACT: Allogeneic haematopoietic cell transplantation (HCT) is the most effective curative therapy in acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). Incidence of AML and MDS increases with age, peaking in the seventh decade. Despite improved Ara-C and anthracyclin-based chemotherapy regimens, the prognosis of AML in patients beyond 60 years of age is dismal. The introduction of peripheral blood-derived stem cell grafts into allogeneic HCT and the known anti-leukaemic effect of donor lymphocyte infusions paved the way for reduced-intensity conditioning (RIC) allogeneic stem-cell transplantation, which makes transplant in advanced age possible and significantly reduces transplant-related organ toxicity and mortality. The success of RIC HCT relies on the alloreactivity of the donor immune system and the graft-versus-leukaemia effect. We try to answer the following questions in this paper: who should receive RIC HCT? when and how should the transplant be performed? is there an upper age limit and what is the future of RIC HCT?Leukemia 08/2007; 21(7):1357-62. · 10.16 Impact Factor
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ABSTRACT: The aim of this article is to compare the differences in efficacy and toxicity between the various conditioning regimens for allogeneic stem cell transplantation. Several studies, all retrospective, that compare the impact of various different conditioning regimens amongst each other are presented. Reduced intensity conditioning apparently lowered transplant-related mortality in patients with minimal residual disease who were at high risk for treatment-related mortality. In contrast, patients with active disease could only be salvaged when a myeloablative conditioning regimen was used. By consequence, it was concluded that patients without contraindications for a myeloablative conditioning regimen should not receive reduced regimens outside a prospective randomized trial. Despite high expectations, non-myeloablative conditioning regimens and regimens that have been reduced in intensity did not prove to be superior in survival when the outcomes were compared with those obtained with conventional myeloablative conditioning. Randomized prospective studies are needed to explore the appropriate niche for the various different regimens.Current opinion in oncology 12/2006; 18(6):667-70. · 4.09 Impact Factor