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Outcome of haematopoietic stem cell transplantation in dyskeratosis congenita
Fioredda, F., Iacobelli, S., Korthof, E. T., Knol, C., van Biezen, A., Bresters, D., Veys, P., Yoshimi, A., Fagioli, F., Mats, B., et al
British journal of haematology. 2018
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Abstract
Dyskeratosis congenita (DC) is a genetic multisystem disorder with frequent involvement of the bone marrow. Haematopoietic stem cell transplantation (HSCT) is the only definitive cure to restore haematopoiesis, even though it cannot correct other organ dysfunctions. We collected data on the outcome of HSCT in the largest cohort of DC (n = 94) patients ever studied. Overall survival (OS) and event-free survival (EFS) at 3 years after HSCT were 66% and 62%, respectively. Multivariate analysis showed better outcomes in patients aged less than 20 years and in patients transplanted from a matched, rather than a mismatched, donor. OS and EFS curves tended to decline over time. Early lethal events were infections, whereas organ damage and secondary malignancies appeared afterwards, even a decade after HSCT. A non-myeloablative conditioning regimen appeared to be most advisable. Organ impairment present before HSCT seemed to favour the development of chronic graft-versus-host disease and T-B immune deficiency appeared to enhance pulmonary fibrosis. According to the present data, HSCT in DC is indicated in cases of progressive marrow failure, whereas in patients with pre-existing organ damage, this should be carefully evaluated. Further efforts to investigate treatment alternatives to HSCT should be encouraged.
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Fludarabine-based reduced toxicity yet myeloablative conditioning is effective and safe particularly in patients with high-risk thalassemia undergoing allogeneic transplantation
Sheth, V., Grisariu, S., Avni, B., Stepensky, P., Ashkenazi, M., Shapira, M. Y., Or, R.
Pediatric blood & cancer. 2018;:e27312
Abstract
INTRODUCTION Thalassemia major (TM) is an inherited disorder caused by ineffective erythropoiesis. At the present time, allogeneic stem cell transplantation (allo-SCT) is a curative option. Conventional busulfan and cyclophosphamide based myeloablative conditioning regimens are limited by increased toxicity, especially in high-risk patients. Replacement of cyclophosphamide with fludarabine has reduced toxicity and nonrelapse mortality (NRM), thus improving outcomes. We analyzed long-term data of our fludarabine-based myeloablative, reduced toxicity protocol, specifically in high-risk patients. METHODS We retrospectively analyzed a cohort of 47 consecutive patients with TM undergoing allo-SCT from matched donors, using the fludarabine-based regimen (reduced toxicity regimen). The median age of the cohort was 10 years. Thirty-eight patients (80%) were in the high-risk and nine patients (20%) were in the low-risk category. The primary aim of this analysis was thalassemia-free survival (TFS). RESULTS The rejection rate was 11% within high-risk patients with NRM of 2%. With a median follow-up period of 7 years (1-15 years), the 10-year TFS in the entire cohort was 87%, and the overall survival (OS) was 97%. The 10-year TFS and OS among the low-risk and high-risk groups were 90% versus 84%, respectively (P = 0.45) and 100% versus 96%, respectively (P = 0.5), and both subsets of patients did equally well. CONCLUSION In conclusion, replacement of high-dose cyclophosphamide with fludarabine is well tolerated with minimal regimen-related toxicity and acceptable rejection rates, especially in high-risk patients.
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Long-term follow-up of a retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic transplantation from matched related donors in myelodysplastic syndromes
Martino, R., Henseler, A., van Lint, M., Schaap, N., Finke, J., Beelen, D., Vigouroux, S., Alessandrino, E. P., Mufti, G. J., Veelken, J. H., et al
Bone Marrow Transplantation. 2017;52(8):1107-1112
Abstract
This study shows the long-term updated outcomes of a multicenter retrospective study which analyzed 843 patients with myelodysplastic syndrome (MDS) who underwent transplantation with an HLA-identical sibling donor with either reduced-intensity conditioning (RIC) in 213 patients, or standard myeloablative conditioning (MAC) in 630 patients. In multivariate analysis, the 13-year relapse rate was significantly increased after RIC (31% after MAC vs 48% in RIC; HR, 1.5; 95% CI, 1.1-1.9; P=0.04), but with no differences in overall survival (OS) (30% after MAC vs 27% in RIC; P=0.4) and PFS (29 vs 21%, respectively, P=0.3). Non-relapse mortality was higher in MAC (40 vs 31%; P=0.1), especially in patients older than 50 years (50 vs 33%, P<0.01). In addition, long-term follow-up confirms the importance of other variables on 13-year OS, mainly MDS risk category, disease phase, cytogenetics and receiving a high donor cell dose, irrespective of the conditioning regimen used.
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Improved Outcomes of Hematopoietic Stem Cell Transplantation in Patients With Infantile Malignant Osteopetrosis Using Fludarabine-Based Conditioning
Natsheh, J., Drozdinsky, G., Simanovsky, N., Lamdan, R., Erlich, O., Gorelik, N., Or, R., Weintraub, M., Stepensky, P.
Pediatric Blood & Cancer. 2016;63(3):535-40
Abstract
BACKGROUND Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for infantile malignant osteopetrosis (IMO), but is associated with a high incidence of adverse outcomes. In this study, we present our experience with HSCT for IMO patients comparing different types of conditioning regimens. METHODS Thirty-eight patients with IMO (aged from 1 month to 6 years, median 0.66 years) who underwent allogeneic HSCT from 1983 in our hospital were included in this retrospective study. Fludarabine-based conditioning regimens were used in 26 patients and 12 patients were transplanted using other conditioning regimens. RESULTS The overall survival after conditioning with fludarabine was 96% (25/26) versus 58% (7/12) for the alternative regimens (P = 0.004), with significantly fewer adverse effects including hypercalcemia and veno-occlusive disease of liver. All patients who survive are clinically well. CONCLUSIONS We conclude that fludarabine-based conditioning regimens are safe and effective in patients with IMO, improving morbidity and mortality related to HSCT. Copyright © 2015 Wiley Periodicals, Inc.