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Allogeneic Hematopoietic Cell Transplantation (allogeneic + hematopoietic_cell_transplantation)
Selected AbstractsSerum bilirubin levels and mortality after myeloablative allogeneic hematopoietic cell transplantation,HEPATOLOGY, Issue 2 2005Ted A. Gooley Many patients who undergo hematopoietic cell transplantation experience liver injury. We examined the association of serum bilirubin levels with nonrelapse mortality by day +200, testing the hypothesis that the duration of jaundice up to a given point in time provides more prognostic information than either the maximum bilirubin value or the value at that point in time. We studied 1,419 consecutive patients transplanted from allogeneic donors. Total serum bilirubin values up to day +100, death, or relapse were retrieved,along with nonrelapse mortality by day +200 as an outcome measure,using Cox regression models with each bilirubin measure modeled as a time-dependent covariate. The bilirubin value at a particular point in time provided the best fit to the model for mortality. With bilirubin at a point in time modeled as an 8th-degree polynomial, an increase in bilirubin from 1 to 3 mg/dL is associated with a mortality hazard ratio of 6.42. An increase from 4 to 6 mg/dL yields a hazard ratio of 2.05, and an increase from 10 to 12 mg/dL yields a hazard ratio of 1.17. Among patients who were deeply jaundiced, survival was related to the absence of multiorgan failure and to higher platelet counts. In conclusion, the value of total serum bilirubin at a particular point in time after transplant carries more informative prognostic information than does the maximum or average value up to that point in time. The increase in mortality for a given increase in bilirubin value is larger when the starting value is lower. (HEPATOLOGY 2005,41:345,352.) [source] Outcome of 93 patients with relapse or progression following allogeneic hematopoietic cell transplantation,AMERICAN JOURNAL OF HEMATOLOGY, Issue 12 2009Saiko Kurosawa Relapse/progression after allogeneic hematopoietic cell transplantation (allo-HCT) remains the major cause of treatment failure. In this study, the subsequent clinical outcome was overviewed in 292 patients with leukemia/myelodysplastic syndrome who received allo-HCT. Among them, 93 (32%) showed relapse/progression. Cohort 1 was chosen to receive no interventions with curative intent (n = 25). Cohort 2 received reinduction chemotherapy and/or donor lymphocyte infusion (n = 48), and Cohort 3 underwent a second allo-HCT (n = 20). Sixty-three patients received reinduction chemotherapy, and 27 (43%) achieved subsequent complete remission (CR). The incidence of nonrelapse mortality (NRM) was similar among the three cohorts (4, 15, and 5%). The 1-year overall survival (OS) after relapse was significantly better in patients with a second HCT (58%) than in others (14%, Cohorts 1 and 2; P <.001). However, the 2-year OS did not differ between the two groups, which suggests that it is difficult to maintain CR after the second HCT. Multivariate analysis showed that reinduction chemotherapy, CR after intervention, second HCT, and longer time to post-transplant relapse were associated with improved survival. In conclusion, for patients with relapse after allo-HCT, successful reinduction chemotherapy and a second HCT may be effective for prolonging survival without excessive NRM. However, effective measures to prevent disease progression after a second HCT clearly need to be developed. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] Reduced-intensity allogeneic hematopoietic cell transplantation: Graft versus tumor effects with decreased toxicityPEDIATRIC TRANSPLANTATION, Issue 3 2003Jennifer E. Schwartz Abstract: The potentially curative role of allogeneic hematopoietic cell transplantation (HCT) in neoplastic and non-neoplastic diseases is offset by the substantial risks of morbidity and mortality from complications of the intensive myeloablative and immunosuppressive preparative regimen. These regimen-related toxicities have restricted allogeneic HCT to young, otherwise healthy individuals without comorbid diseases. Pediatric patients undergoing conventional allogeneic HCT have lower procedure-related mortality but are at risk for non-fatal late effects of the high-dose pretransplant chemoradiotherapy, such as growth retardation, sterility and other endocrine dysfunction. Evaluation of reduced-intensity preparative regimens is the major focus of current clinical research in allogeneic HCT. Reduced-intensity HCT (RI-HCT) relies on the use of immunosuppressive but non-myeloablative agents that allow engraftment of donor cells, which provide adoptive allogeneic cellular immunotherapy and graft versus tumor (GVT) effects, with decreased regimen-related toxicities. Although the experience with RI-HCT in pediatric patients is very limited at this time, results in adults indicate that attenuated-dose preparative regimens allow older patients and those with organ dysfunction to undergo successful allogeneic HCT with acceptable morbidity and mortality. In adults, the potency of the allogeneic GVT effect varies among neoplastic diseases, with better results observed in patients with indolent hematological malignancies or renal cell carcinoma. The effectiveness of RI-HCT as treatment for children with hemoglobinopathies, chronic granulomatous disease and cellular immunodeficiencies is encouraging, and the role of reduced-intensity preparative regimens for allogeneic HCT in pediatric malignancies is under investigation. [source] Chronic Kidney Disease Following Non-Myeloablative Hematopoietic Cell TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2006A. S. Weiss Chronic kidney disease (CKD) following myeloablative allogeneic hematopoietic cell transplantation (HCT) occurs in 20% of survivors at 1 year and is believed to be due to radiation nephritis. Non-myeloablative allogeneic HCT is a recent procedure that employs significantly lower doses of chemoradiotherapy, however, incidence and risk factors for CKD following non-myleoablative HCT have not been defined. We performed a retrospective cohort study of 122 patients from three institutions who were available for analysis at 6 months following non-myeloablative HCT. Patients received two Gy of radiation; 62% received fludarabine as preconditioning. CKD was defined as at least a 25% reduction in glomerular filtration rate (GFR) from baseline using the abbreviated modified diet in renal disease (MDRD) equation. Eighty-one of 122 patients (66%) showed evidence of CKD at follow-up. Multivariate analysis revealed that acute renal failure (ARF) during the first 100 days post-transplant was associated with development of CKD (Adjusted OR 32.8 with 95% CI 4.3,250) after controlling for other variables. Previous autologous HCT, long-term calcineurin inhibitor use and extensive chronic GVHD were independently associated with CKD. CKD following non-myeloablative HCT appears to be a distinct clinical entity and likely not related to radiation nephritis. Future research should focus on possible mechanisms for alleviating chronic injury and decreasing use of calcineurin inhibitors. [source] Minor histocompatibility antigens as targets for immunotherapy using allogeneic immune reactionsCANCER SCIENCE, Issue 8 2007Yoshiki Akatsuka Minor histocompatibility antigens (mHag) were originally identified as antigens causing graft rejection or graft-versus-host disease in human leukocyte antigen (HLA)-matched allogeneic transplantation. Molecular identification has revealed most to be major histocompatibility complex (MHC)-bound short peptide fragments encoded by genes which are polymorphic due to single nucleotide polymorphisms (SNP). Genotypic disparity of SNP between transplantation donors and recipients gives rise to mHag as non-self antigens for both the donor and the recipient. Subsequently, mHag have been explored as immunotherapeutic antigens for use against recurring hematological malignancies after allogeneic hematopoietic cell transplantation (HCT), because mHag expressed only on hematopoietic cells are considered to augment graft-versus-leukemia/lymphoma (GVL) effects without increasing the risk of life-threatening graft-versus-host disease (GVHD). Accumulating evidence suggests that T-cell responses to mHag aberrantly expressed on solid tumor cells are also involved in the eradication of sensitive tumors such as renal cell carcinomas following HCT. Over the past decade, the number of putative GVL-directed mHag has increased to a level that covers more than 30% of the Japanese patient population, so that clinical trials may now be executed in the setting of either vaccination or adoptive immunotherapy. As it is expected that immune responses to alloantigens are more powerful than to tumor antigens mostly derived from overexpressed self-proteins, mHag-based immunotherapy may lead to a new treatment modality for high-risk malignancies following allogeneic HCT. (Cancer Sci 2007; 98: 1139,1146) [source] Capillary electrophoresis for chimerism monitoring by PCR amplification of microsatellite markers after allogeneic hematopoietic cell transplantationCLINICAL TRANSPLANTATION, Issue 3 2005Alexandros Spyridonidis Abstract:, Background:, Hematopoietic chimerism has been demonstrated to be relevant for donor cell engraftment and detection of minimal residual disease after allogeneic hematopoietic cell transplantation (aHCT). In the light of increasing numbers of non-myeloablative aHCT as a treatment modality sensitive, rapid, and accurate chimerism monitoring techniques acquire novel relevance. Methods:, We evaluated the informativeness of five microsatellite markers in 376 donor/recipient pairs and evaluated the ability of capillary electrophoresis to detect mixed chimerism after aHCT. The sensitivity for capillary electrophoresis with respect to different markers was determined by limiting dilution assays with mixed chimerism samples containing defined amounts of cells or DNA. Furthermore, capillary electrophoresis was applied in 17 retrospectively selected patients with a mixed chimerism detected previously by gel electrophoresis, having undergone aHCT for different hematologic diseases and initially achieving a complete donor chimerism. Results:, In 163 of 165 (98%) of all related and 210 of 211 (99%) unrelated transplants the microsatellites identified informative alleles. The sensitivity and accuracy was higher with capillary electrophoresis when compared with gel electrophoresis with three of five microsatellites. Potential pitfalls with the application of capillary electrophoresis was preferential amplification and the occurrence of stutter peaks in the representative area. Investigation of the selected patient samples demonstrated that detection of a mixed chimerism was earlier with capillary electrophoresis when compared with gel electrophoresis. The detected recipient genotype by capillary electrophoresis examination, despite a negative gel electrophoresis result, ranged from 0.7 to 7.1%. Conclusions:, We conclude that chimerism assessment with our five microsatellites identified informative alleles in 99% of all donor/recipient pairs and may therefore be of use when establishing an institutional chimerism testing procedure. Capillary electrophoresis displayed a high sensitivity and accuracy for detecting a mixed chimerism in vitro and in vivo. [source] | ||||||||||