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Advanced age is a relative contraindication to myeloablative allogeneic transplantation due to the increased incidence of treatment related complications seen in older patients. Therefore, non-myeloablative stem cell transplantation (NST) is increasingly utilized in this population. The impact of the shift from myeloablative to NST upon relapse, tr...
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Context 1
... causes of non-relapse mortality for patients receiving non-myeloablative transplantation were graft versus host disease and infection. Pulmonary complications, in addition to GVHD and infection, were the major causes of treatment failure after myeloablative transplantation (Figure 2). There was a significantly higher incidence of fatal pulmonary complications after myeloablative transplantation, 28%, compared with 0% after non-myeloablative transplantation. ...
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Objective
To determine the incidence of infections in a population of systemic lupus erythematosus individuals and the characteristics of infections regarding original site, as well as to study the possible associations between infections and treatment.
Methods
An analytical retrospective study using data from medical charts of systemic lupus eryt...
Citations
... The advantages of lowly ablative transplantation in older age groups were shown for hematooncologic human patients older than 50 years: the 95% survival line decreased 5 months after a myeloablative transplantation, while 95% of nonmyeloablative patients were alive for at least 13 months; both 1 and 2 year survival rates were 50% higher in the nonmyeloablative than in myeloablative cohorts over 50 years of age ( Alyea et al., 2005). Nonablative or lowly ablative transplantation of SCs has already proved its usefulness in clinical practice for some human pathologies: multiple sclerosis, blood oncology, hereditary diseases ( Mielcarek et al., 2003;Alyea et al., 2006). ...
The goal of this work was to determine the effect of nonablative syngeneic transplantation of young bone marrow (BM) to laboratory animals (mice) of advanced age upon maximum duration of their lifespan. To do this, transplantation of 100 million nucleated cells from BM of young syngeneic donors to an old nonablated animal was performed at the time when half of the population had already died. As a result, the maximum lifespan (MLS) increased by 28 ± 5%, and the survival time from the beginning of the experiment increased 2.8 ± 0.3-fold. The chimerism of the BM 6 months after the transplantation was 28%.
... Various groups have reported on the feasibility of RIC transplants for older patients with myeloid malignancies. However, within this sub-group there remains a significant 1-year TRM of 21–55% (Wong et al, 2003; Ho et al, 2004; Alyea et al, 2005). Due to the heterogeneity of both conditioning regimens and composition of the study cohorts in most reports, the risk factors and outcome of RIC regimens using unrelated donors for patients with MDS remains unclear. ...
This prospective study evaluated the outcomes of 75 successive patients receiving a FBC (fludarabine, busulphan, alemtuzumab) reduced-intensity conditioning (RIC) regimen for myelodysplastic syndromes (MDS) using volunteer unrelated donors(VUD). The prognostic significance of a variety of clinical variables including the recently described haematopoietic cell transplantation co-morbidity index (HCT-CI) was assessed. The median age of the cohort was 52.0 years (range: 19-68 years) with a median follow-up of 1038.5 d. Forty-nine patients (65%) had an International Prognostic Scoring System stage of > or = Intermediate-2, 35 (46%) had intermediate or poor risk cytogenetics, and 23 patients(31%) were human leucocyte antigen-mismatched. The actuarial 3-year overall survival (OS) and disease-free survival (DFS) was 43% [95% confidence interval (CI): 37-49] and 41% (95%CI: 35-47) respectively, and the cumulative incidence of extensive chronic graft-versus-host disease was 22%. On multivariate analysis, presence of either one class II mismatch or a two-antigen mismatch adversely influenced transplant-related mortality, DFS and OS. In addition, disease status at transplantation and the haematopoietic cell transplantation-specific comorbidity index were independent variables for overall survival. In contrast, both advanced age and pre-transplant cytogenetic status did not significantly affect overall outcomes. RIC regimens using VUD was associated with durable long-term survival even in older patients with MDS, and the use of a pre-transplant comorbidity index may help to improve patient selection for transplantation.
... Although allogeneic stem cell transplantation (SCT) is the only curative treatment for some hematologic malignancies, success is limited by transplant-related mortality (TRM). Although reduced-intensity transplant conditioning regimens result in improved regimen-related toxicity, they are less effective at disease control [1]. Intensive conditioning regimens using total body irradiation (TBI) remain the most effective way to prevent relapse of disease after transplantation. ...
... Intensive conditioning regimens using total body irradiation (TBI) remain the most effective way to prevent relapse of disease after transplantation. However, approximately 20% of patients given such myeloablative conditioning regimens die of transplant-related causes [1,2]. Although multiple factors such as infection, graftversus-host disease (GVHD) and its treatment, and regimen-related toxicity contribute to TRM, the most fre-quent proximal causes of death are ventilatory failure, hepatic failure, and major injury to the central nervous system. ...
Between July 1997 and August 2004, 146 consecutive patients with hematologic malignancies received a T cell-depleted peripheral blood stem cell transplant from an HLA-identical sibling by using total body irradiation (TBI) and cyclophosphamide conditioning regimens. Eighty-five patients received 13.6 Gy of TBI with no lung shielding, and 61 received lung shielding (total lung dose, 6-12 Gy). Ninety-four patients (65.5%) had standard-risk disease; the remainder had more advanced disease or unfavorable diagnoses. Of the 21 transplant-related deaths, 14 were from pulmonary causes (10 idiopathic pulmonary syndromes and 4 from infection) that occurred at a median of 90 days (range, 23-238 days) after transplantation. Independent risk factors for pulmonary transplant-related mortality (PTRM) were pretransplantation diffusion capacity for carbon monoxide (relative risk, 5.7 for diffusion capacity for carbon monoxide <85%), smoking (relative risk, 5.0), and CD34 cell dose (relative risk, 9.4 for a CD34 dose of <5 x 10(6) cells per kilogram). Patients receiving lung shielding had significantly lower PTRM (3.3% versus 14.1%; P = .02) and better overall survival (70% +/- 6% versus 52% +/- 5%; P = .04), but lung shielding was not a significant independent factor for determining PTRM. These results suggest that pulmonary mortality after TBI-based preparative regimens is predictable and that higher CD34 cell doses can reduce the risk.
Hemopoietic cell transplantation (HCT) is presently the only therapy with curative potential for myelodysplastic syndromes (MDS) and myeloproliferative disorders (MPD). Among patients with less advanced MDS, 3-year survival figures of 65-80% are achieved with human leukocyte antigen (HLA)-identical related and unrelated donors. The probability of relapse is less than 5%. Among patients with advanced MDS (> or = 5% marrow blasts), about 35-50% of patients transplanted from related donors, and 25-40% transplanted from unrelated donors are surviving in remission beyond 3 years. The incidence of post-transplant relapse is 10-35%. Criteria of the International Prognostic Scoring System (IPSS) predict relapse and survival following HCT. In patients with myelofibrosis, allogeneic transplantation is successful in 50-80%, if performed during the fibrosis stage. The success rate declines to 25-40%, if the transplant is performed after leukemic transformation has occurred. About 40% of patients with chronic myelomonocytic leukemia survive in remission after transplantation. Results obtained with low/reduced-intensity conditioning regimens are encouraging because of a low incidence of early mortality. However, retrospective analyses comparing low intensity and conventional conditioning regimens have yielded inconclusive results regarding long-term outcome. Co-morbid conditions present at the time of transplantation have a major negative effect on transplant outcome. Controlled prospective trials are needed.
