Conditioning with 8-Gy total body irradiation and fludarabine for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia

In this multicenter retrospective study, the long-term outcomes of 878 adults with AML and refractory anemia with excess blasts (RAEB) with BM blasts o10% who underwent transplantation with an HLA-identical sibling donor between 1998 and 2004 were analyzed according to four regimens of conditioning intensity: reduced-intensity conditioning (RIC) (either intermediate RIC (IntermRIC) or non-myeloablative (NMA) RIC), and myeloablative conditioning (MC) in 718 patients (either conventional MC or hyperintense MC. In multivariate cox analysis, patients undergoing NMA transplantation had lower non-relapse mortality risk in the first 100 days after transplantation (Po0.01), but a higher risk beyond day þ 100 (P ¼ 0.02), as well as higher relapse incidence in the first 12 months (Po0.01), but the risk was similar in all groups beyond 12 months. The probabilities of PFS and OS up to 7 years were significantly lower only in the NMA subgroup (Pp0.01 for both). The 7-year OS was 53%, 29%, 56% and 51%, respectively. Our data suggest that prospective studies comparing RIC regimens (especially IntermRIC) with MC are appropriate in patients with AML and RAEB who are in a non-advanced disease status.

Section: Discussionsupporting

confidence: 51%

“…32 The primary end point (NRM after 12 months) was lower in the IntermRIC (8%) than in the MC group (17%) (Po0.05), especially in patients 440 years of age (5 vs 20%, P ¼ 0.01). In addition, the incidence of relapse did not differ.…”

Section: Discussionmentioning

confidence: 99%

Comparison of conditioning regimens of various intensities for allogeneic hematopoietic SCT using HLA-identical sibling donors in AML and MDS with <10% BM blasts: a report from EBMT

Martino

Wreede

Fiocco

et al. 2012

“…Notably, severe side effects like veno-occlusive disease/sinusoidal obstructive syndrome or heart failure known for other even RIC regimens did not occur at all. 30 The resulting NRM of 11% at 2 years is very promising and lower than in our previous treosulfan dose-escalation study, where a NRM of 20% at 2 years was reported. 20 However, in this study, patients with compromised health status and a variety of hematological malignancies even not in CR at the time of transplantation were included.…”

Section: Discussionmentioning

confidence: 67%

Allogeneic hematopoietic SCT in patients with AML following treosulfan/fludarabine conditioning

Casper

Hołowiecki

Trenschel

et al. 2011

An alternative reduced-toxicity conditioning regimen for allogeneic transplantation, based on treosulfan and fludarabine, has recently been identified. The safety and efficacy of this new conditioning regimen has been investigated prospectively in patients with AML. A total number of 75 patients with AML in CR were treated with 3 Â 14 g/m 2 treosulfan and 5 Â 30 mg/m 2 fludarabine, followed by matched sibling or unrelated SCT. Patients were evaluated for engraftment, adverse events, GVHD, and for nonrelapse mortality, relapse incidence, overall and disease-free survival (DFS). All patients showed primary engraftment of neutrophils after a median of 20 days. Non-hematological adverse events grade III --IV in severity included mainly infections (59%) and gastrointestinal symptoms (7%). Acute GVHD grade II --IV occurred in 21% and extensive chronic GVHD occurred in 16% of the patients. After a median follow-up of 715 days, the 2-year overall and DFS estimates were 61% and 55%, respectively. The 2-year incidences of relapse and non-relapse mortality reached 34% and 11%, respectively. In summary, our data confirm promising safety and efficacy of the treosulfan-based conditioning therapy in AML patients, ClinicalTrials.gov Identifier: NCT01063660.

“…3 At least for patients with acute AML transplanted in first CR, some RIC regimens allow the reduction of NRM to 10% or less, without increasing the risk of relapse. 4 However, with relapse incidences exceeding up to 50%, for example, for patients with high-risk AML, relapse has become the leading cause of treatment failure after allo-SCT. 5 Once overt relapse has occurred, different treatment strategies are being evaluated, including the reduction of immunosuppressive therapy, DLI, chemotherapy with or without subsequent DLI or second allo-SCT.…”

Section: Introductionmentioning

confidence: 99%

CD34+ lineage specific donor cell chimerism for the diagnosis and treatment of impending relapse of AML or myelodysplastic syndrome after allo-SCT

Rosenow

Berkemeier

Krug

et al. 2013

After allo-SCT, analysis of CD34 þ lineage-specific donor cell chimerism (DCC) is a sensitive method for monitoring minimal residual disease in patients with AML or myelodysplastic syndrome (MDS) with CD34 expression. To substantiate evidence of whether immune interventions in patients with impending relapse, defined by incomplete lineage-specific DCC, may prevent hematological relapse, we performed a retrospective nested case control study. Unsorted and lineage-specific DCC were measured in 134 patients. Forty-three patients had an incomplete CD34 þ -DCC with no other evidence of relapse. After immediate tapering of immunosuppressive treatment (30 patients) and/or infusion of donor lymphocytes (10 patients), 21 patients remained in remission (conversion to complete lineage-specific DCC) and 22 relapsed. Relapse-free survival at 3 years of the 91 patients with stable DCC and of the 43 patients with incomplete DCC was 74% (95% confidence interval (CI), 64-83%) and 40% (95% CI, 24-58%), respectively. OS rates were 79% (95% CI, 70-88%) and 52% (95% CI, 35-69%), respectively. These results, with 49% of patients with impending relapse successfully treated with immune intervention, highly suggest that analysis of CD34 þ -DCC is an important tool for monitoring and the management of AML and MDS patients after allo-SCT.