References of "Sandmaier, B. M"
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See detailTotal body irradiation dose escalation decreases risk of progression and graft rejection after hematopoietic cell transplantation for myelodysplastic syndromes or myeloproliferative neoplasms
Monaco, F.; Scott, B. L.; Chauncey, T. R. et al

in Haematologica (2019), 104(6), 1221-1229

Anon-myeloablative regimen of fludarabine and 200 cGy total body irradiation combined with post-grafting immunosuppression with mycophenolate mofetil and a calcineurin inhibitor facilitates allogeneic ... [more ▼]

Anon-myeloablative regimen of fludarabine and 200 cGy total body irradiation combined with post-grafting immunosuppression with mycophenolate mofetil and a calcineurin inhibitor facilitates allogeneic hematopoietic cell transplantation from HLA-matched related or unrelated donors in older patients and/or those with comorbidities. However, outcomes of prior studies have been disappointing in patients with myelodysplastic syndromes or myeloproliferative neoplasms due to high incidences of progression or graft failure (together termed hematopoietic cell transplantation-failure). We hypothesized that escalating the total body irradiation dose may improve the outcomes and subsequently performed a phase II total body irradiation dose-escalation trial. Patients with median age 66 years were enrolled in two arms to receive non-myeloablative conditioning followed by hematopoietic cell transplantation with total body irradiation dose escalation for excessive hematopoietic cell transplantation- failure: Arm A: Myeloproliferative neoplasm/myelodysplastic syndrome low risk (n=36); and Arm B: Myelodysplastic syndrome highrisk/chronic myelomonocytic leukemia (n=41). Total body irradiation dose levels were: Level-1 (300 cGy), Level-2 (400 cGy), or Level-3 (450 cGy). Patients received intravenous fludarabine 30 mg/m2 for three days. Total body irradiation was administered on day 0 followed by infusion of peripheral blood stem cells from HLA-matched related (n=30) or unrelated (n=47) donors. Post-grafting immunosuppression with mycophenolate mofetil and cyclosporine was administered. The primary end point was day 200 hematopoietic cell transplant failure, with the objective of reducing the incidence to <20%. The primary end point was reached on Arm A at dose Level-1 (300 cGy total body irradiation) with a cumulative incidence of day 200 hematopoietic cell transplant failure of 11%, and on Arm B at dose Level-3 (450 cGy) with a cumulative incidence of day 200 hematopoietic cell transplant failure of 9%. Increasing the total body irradiation dose leads to a higher success rate with non-myeloablative conditioning by reducing relapse and rejection. Further studies are necessary to decrease non-relapse mortality, especially among patients with high-risk disease. Trial registered under clinicaltrials.gov identifier: NCT00397813. © 2019 Ferrata Storti Foundation. [less ▲]

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See detailOutcomes of UCB transplantation are comparable in FLT3+ AML: Results of CIBMTR, eurocord and EBMT collaborative analysis.
Ustun, C.; Giannotti, F.; Zhang, M.-J. et al

in Leukemia (2017)

Allogeneic hematopoietic cell transplantation (HCT) from siblings or unrelated donors (URD) during complete remission (CR) may improve leukemia-free survival (LFS) in FLT3+ acute myeloid leukemia (AML ... [more ▼]

Allogeneic hematopoietic cell transplantation (HCT) from siblings or unrelated donors (URD) during complete remission (CR) may improve leukemia-free survival (LFS) in FLT3+ acute myeloid leukemia (AML) that has poor prognosis due to high relapse rates. Umbilical cord blood (UCB) HCT outcomes are largely unknown in this population. We found that compared with sibling HCT, relapse risks were similar after UCB (n=126), (HR 0.86, P=0.54) and URD (n=91) (HR 0.81, P=0.43). UCB HCT was associated with statistically higher non-relapse mortality compared with sibling HCT (HR 2.32, P=0.02), but not vs URD (HR 1.72, P=0.07). All three cohorts had statistically not significant 3-year LFS: 39% (95% CI 30-47) after UCB, 43% (95% CI 30-54) after sibling, and 50% (95% CI 40-60) after URD. Chronic GVHD rates were significantly lower after UCB compared with either sibling (HR 0.59, P=0.03) or URD (HR 0.49, P=0.001). Adverse factors for LFS included high leukocyte count at diagnosis and HCT during CR2. UCB is a suitable option for adults with FLT3+AML in the absence of an HLA-matched sibling and its immediate availability may be particularly important for FLT3+ AML where early relapse is common thus allowing HCT in CR1 when outcomes are best.Leukemia accepted article preview online, 25 January 2017. doi:10.1038/leu.2017.42. [less ▲]

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