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Fludarabine-treosulfan versus fludarabine-melphalan or busulfan-cyclophosphamide conditioning in older AML or MDS patients - A clinical trial to registry data comparison
Beelen, D. W., Iacobelli, S., Koster, L., Eikema, D. J., van Biezen, A., Stölzel, F., Ciceri, F., Bethge, W., Dreger, P., Wagner-Drouet, E. M., et al
Bone marrow transplantation. 2024
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Editor's Choice
Abstract
A randomized study (acronym: MC-FludT.14/L Trial II) demonstrated that fludarabine plus treosulfan (30 g/m²) was an effective and well tolerated conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT) in older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). To further evaluate this regimen, all 252 study patients aged 50 to 70 years were compared with similar patients, who underwent allo-HCT after fludarabine/melphalan (140 mg/m²) (FluMel) or busulfan (12.8 mg/kg)/cyclophosphamide (120 mg/kg) (BuCy) regimens and whose data was provided by the European Society for Blood and Marrow Transplantation registry. In 1:1 propensity-score matched-paired analysis (PSA) of AML patients, there was no difference in 2-year-relapse-incidence after FluTreo compared with either FluMel (n = 110, p = 0.28) or BuCy (n = 78, p = 0.98). However, 2-year-non-relapse-mortality (NRM) was lower compared with FluMel (p = 0.019) and BuCy (p < 0.001). Consequently, 2-year-overall-survival (OS) after FluTreo was higher compared with FluMel (p = 0.04) and BuCy (p < 0.001). For MDS patients, no endpoint differences between FluTreo and FluMel (n = 30) were evident, whereas 2-year-OS after FluTreo was higher compared with BuCy (n = 25, p = 0.01) due to lower 2-year-NRM. Multivariate sensitivity analysis confirmed all significant results of PSA. Consequently, FluTreo (30 g/m²) seems to retain efficacy compared with FluMel and BuCy, but is better tolerated by older patients.
PICO Summary
Population
Adults aged 50-70 years with primary or secondary AML in complete remission or MDS, receiving a peripheral blood allogeneic transplant (n=1220)
Intervention
Participants in the MC-FludT.14/L trial who received fludarabine-treosulfan conditioning (FluTreo, n=252)
Comparison
Propensity-score matched patients identified from the EBMT registry (n=968) who received fludarabine/melphalan (FluMel, n=338) or busulfan/cyclophosphamide (BuCy, n=630) regimens
Outcome
In 1:1 propensity-score matched-paired analysis (PSA) of AML patients, there was no difference in 2-year-relapse-incidence after FluTreo compared with either FluMel (n=110) or BuCy (n=78). However, 2-year-non-relapse-mortality (NRM) was lower compared with FluMel and BuCy. Consequently, 2-year-overall-survival (OS) after FluTreo was higher compared with FluMel and BuCy. For MDS patients, no endpoint differences between FluTreo and FluMel (n=30) were evident, whereas 2-year-OS after FluTreo was higher compared with BuCy (n=25) due to lower 2-year-NRM. Multivariate sensitivity analysis confirmed all significant results of PSA.
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Validation of the transplant conditioning intensity (TCI) index for allogeneic hematopoietic cell transplantation
Spyridonidis, A., Labopin, M., Gedde-Dahl, T., Ganser, A., Stelljes, M., Craddock, C., Wagner-Drouet, E. M., Versluis, J., Schroeder, T., Blau, I. W., et al
Bone marrow transplantation. 2023
Abstract
The intensity of the conditioning regimen given before allogeneic hematopoietic cell transplantation (allo-HCT) can vary substantially. To confirm the ability of the recently developed transplant conditioning intensity (TCI) score to stratify the preparative regimens of allo-HCT, we used an independent and contemporary patient cohort of 4060 transplant recipients with acute myeloid leukemia meeting inclusion criteria from the discovery study (allo-HCT in first complete remission, matched donor), but who were allografted in a more recent period (2018-2021) and were one decade older (55-75 years, median 63.4 years), we assigned them to a TCI category (low n = 1934, 48%; intermediate n = 1948, 48%, high n = 178, 4%) according to the calculated TCI score ([1-2], [2.5-3.5], [4-6], respectively), and examined the validity of the TCI category in predicting early non-relapse mortality (NRM), 2-year NRM and relapse (REL). In the unadjusted comparison, the TCI index provided a significant risk stratification for d100 and d180 NRM, NRM and REL risk. In the multivariate analysis adjusted for significant variables, there was an independent association of TCI with early NRM, NRM and REL. In summary, we confirm in contemporary treated patients that TCI reflects the conditioning regimen related morbidity and anti-leukemic efficacy satisfactorily and across other established prognostic factors.
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Impact of disease burden on clinical outcomes of AML patients receiving allogeneic hematopoietic cell transplantation: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
Abou Dalle, I., Labopin, M., Kröger, N., Schroeder, T., Finke, J., Stelljes, M., Neubauer, A., Blaise, D., Yakoub-Agha, I., Salmenniemi, U., et al
Bone marrow transplantation. 2023
Abstract
Pre-transplant detectable measurable residual disease (MRD) is still associated with high risk of relapse and poor outcomes in acute myeloid leukemia (AML). We aimed at evaluating the impact of disease burden on prediction of relapse and survival in patients receiving allogeneic hematopoietic cell transplantation (allo-HCT) in first remission (CR1). We identified a total of 3202 adult AML patients, of these 1776 patients were in CR1 and MRD positive and 1426 patients were primary refractory at time of transplant. After a median follow-up of 24.4 months, non-relapse mortality and relapse rate were significantly higher in the primary refractory group compared to the CR1 MRD positive group (Hazards Ratio (HR) = 1.82 (95% CI: 1.47-2.24) p < 0.001 and HR = 1.54 (95% CI: 1.34-1.77), p < 0.001), respectively. Leukemia-free survival (LFS) and overall survival (OS) were significantly worse in the primary refractory group (HR = 1.61 (95% CI: 1.44-1.81), p < 0.001 and HR = 1.71 (95% CI: 1.51-1.94), p < 0.001, respectively). Our real-life data suggest that patients in CR1 and MRD positive at time of transplant could still be salvaged by allo-HCT with a 2-year OS of 63%, if negative MRD cannot be obtained and their outcomes are significantly better than patients transplanted with active disease.
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Impact of conditioning regimen intensity on outcomes of second allogeneic hematopoietic cell transplantation for secondary acute myelogenous leukemia
Nagler, A., Peczynski, C., Dholaria, B., Labopin, M., Valerius, T., Dreger, P., Kröger, N., Reinhardt, H. C., Finke, J., Franke, G. N., et al
Bone marrow transplantation. 2022
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Editor's Choice
Abstract
Limited data is available on factors impacting the outcomes of second hematopoietic cell transplantation (HCT2) in patients with secondary acute myeloid leukemia (sAML). This study aimed to assess HCT2 outcome for sAML comparing reduced-intensity (RIC) to myeloablative (MAC) conditioning. Two hundred and fifteen patients were included: RIC (n = 134), MAC (n = 81). The median follow-up was 41.1 (95% CI: 26.7-69.3) and 28.5 (95% CI: 23.9-75.4) months, respectively. At two years, the relapse incidence (RI) was 58.3% versus 51.1% in RIC and MAC, respectively. The 2-year leukemia free survival (LFS) was 26.6% versus 26%, and the graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) was 16.4% versus 12.1%, while OS was 31.4% and 39.7%, for RIC and MAC respectively. MVA showed a significantly lower RI [hazard ratio (HR) = 0.46 (95% CI, 0.26-0.8, p = 0.006)] and improved LFS [HR = 0.62 (95% CI, 0.39-0.98, p = 0.042)] with MAC versus RIC. The choice of conditioning regimen did not impact non-relapse mortality [HR = 1.14 (95% CI, 0.52-2.5, p = 0.74)], overall survival (OS) [HR = 0.72 (95% CI, 0.44-1.17, p = 0.18)] or GRFS [HR = 0.89 (95% CI, 0.59-1.36, p = 0.6)]. In conclusion, MAC was associated with a lower RI and superior LFS. These results support the use of MAC for eligible patients with sAML who are being considered for HCT2.
PICO Summary
Population
Adult patients with relapsed secondary acute leukaemia (sAML) receiving a second hematopoietic cell transplant (HCT2) from mulitple centre registries across Europe (n=215)
Intervention
Reduced-intensity pre-HCT2 conditioning (RIC, n=134)
Comparison
Myeloablative pre-HCT2 conditioning (MAC, n=81)
Outcome
Median follow-up was 41.1 (RIC, 95% CI: 26.7-69.3) and 28.5 (MAC, 95% CI: 23.9-75.4) months. At two years, the relapse incidence (RI) was 58.3% versus 51.1% in RIC and MAC, respectively. The 2-year leukemia free survival (LFS) was 26.6% versus 26%, and the graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) was 16.4% versus 12.1%, while OS was 31.4% and 39.7%, for RIC and MAC respectively. Multivariate analysis showed a significantly lower RI [hazard ratio (HR) = 0.46 (95% CI, 0.26-0.8)] and improved LFS [HR = 0.62 (95% CI, 0.39-0.98)] with MAC versus RIC. The choice of conditioning regimen did not impact non-relapse mortality [HR = 1.14 (95% CI, 0.52-2.5)], overall survival (OS) [HR = 0.72 (95% CI, 0.44-1.17)] or GRFS [HR = 0.89 (95% CI, 0.59-1.36)].
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5.
Thiotepa-fludarabine-treosulfan conditioning for 2nd allogeneic HCT from an alternative unrelated donor for patients with AML: a prospective multicenter phase II trial
Finke, J., Schmoor, C., Stelljes, M., Burchert, A., Dreger, P., Hegenbart, U., Wagner-Drouet, E. M., Bornhäuser, M., Sohlbach, K., Schub, N., et al
Bone marrow transplantation. 2022
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Editor's Choice
Abstract
Therapeutic options for patients with AML relapsing after allogeneic HCT range from chemotherapy or hypomethylating agents with or without donor lymphocyte infusions to a 2nd allogeneic HCT. Available data are based on retrospective single center or registry studies. The aim of this multicenter trial was to investigate prospectively intensive conditioning with Thiotepa, Fludarabine and Treosulfan (TFT) for 2nd allogeneic HCT from an alternative unrelated donor in patients with AML relapse > 6 months after a 1st allogeneic HCT. Primary endpoint was disease-free survival (DFS) at one year after 2nd HCT. 50 patients median age 53.5 years, in CR/PR (34%) or active relapse (66%) were included. 33 of 38 patients (86.8%) with available data achieved CR 100 days post transplant. 23 patients were alive and free of relapse at primary endpoint one year after 2nd HCT (DFS rate 0.46, 95%-CI (0.32-0.61). Three-year rates of DFS, relapse, non-relapse mortality, and overall survival were 0.24, 95%-CI (0.13-0.36); 0.36 (0.25-0.52); 0.40 (0.29-0.57); and 0.24 (0.13-0.37). Second HCT with TFT conditioning is feasible and has high anti-leukemic efficacy in chemosensitive or refractory AML relapse after prior allogeneic HCT. Still, relapse rates and NRM after 2nd allogeneic HCT remain a challenge. The trial is registered in the German Clinical Trials Registry (number DRKS00005126).
PICO Summary
Population
Participants with acute myeloid leukaemia (AML) relapsing after allogeneic transplant, from fourteen centres in Germany (n=50)
Intervention
Second allogeneic transplant from an alternative donor >6 months after 1st allogeneic transplant
Comparison
None
Outcome
50 patients median age 53.5 years, in CR/PR (34%) or active relapse (66%) were included. 33 of 38 patients (86.8%) with available data achieved CR 100 days post transplant. 23 patients were alive and free of relapse at primary endpoint one year after 2nd HCT (DFS rate 0.46, 95%-CI (0.32-0.61). Three-year rates of DFS, relapse, non-relapse mortality, and overall survival were 0.24, 95%-CI (0.13-0.36); 0.36 (0.25-0.52); 0.40 (0.29-0.57); and 0.24 (0.13-0.37). Second HCT with TFT conditioning is feasible and has high anti-leukemic efficacy in chemosensitive or refractory AML relapse after prior allogeneic HCT.
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6.
Pre-Transplant Serum Leptin Levels and Relapse of Acute Myeloid Leukemia after Allogeneic Transplantation
Schwarzbich, M. A., Dai, H., Kordelas, L., Beelen, D. W., Radujkovic, A., Müller-Tidow, C., Dreger, P., Luft, T.
International journal of molecular sciences. 2022;23(4)
Abstract
Weight loss and metabolic activity influence outcome after allogeneic stem cell transplantation (alloSCT). This study evaluates pre-conditioning Leptin, a peptide hormone involved in metabolism and immune homeostasis, as a prognostic factor for survival, relapse and non-relapse mortality (NRM) following alloSCT. Leptin serum levels prior to conditioning were determined in a cohort of patients transplanted for various hematologic malignancies (n = 524) and correlated retrospectively with clinical outcome. Findings related to patients with acute leukemia (AL) from this sample were validated in an independent cohort. Low pre-conditioning serum Leptin was an independent prognostic marker for increased risk of relapse (but not of NRM and overall mortality) following alloSCT for AL of intermediate and advanced stage (beyond first complete remission). Multivariate analysis revealed a hazard ratio (HR) for relapse of 0.75 per log2 increase (0.59-0.96, p = 0.020). This effect was similar in an independent validation cohort. Pre-conditioning serum Leptin was validated as a prognostic marker for early relapse by fitting the multivariate Cox model to the validation data. Pre-conditioning serum Leptin levels may serve as an independent prognostic marker for relapse following alloSCT in intermediate and advanced stage AL patients. Prospective studies are required to prove whether serum Leptin could be used for guiding nutritional intervention in patients with AL undergoing alloSCT.
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Evaluation of six different types of sequential conditioning regimens for allogeneic stem cell transplantation in relapsed/refractory acute myelogenous leukemia - a study of the Acute Leukemia Working Party of the EBMT
Heinicke, T., Labopin, M., Polge, E., Stelljes, M., Ganser, A., Tischer, J., Brecht, A., Kröger, N., Beelen, D. W., Scheid, C., et al
Leukemia & lymphoma. 2020;:1-11
Abstract
The Acute Leukemia Working Party (ALWP) of the EBMT assessed the outcome of allogeneic stem cell transplantation (alloSCT) in patients with relapsed/refractory AML (r/rAML) evaluating six sequential conditioning regimens (SR) groups. A total of 2132 patients were included. LFS at 2 years was 28.9%, 33.6%, 35.3%, 20.6%, 24.4%, and 27% for the FLAMSA-TBI4, FLAMSA-Chemo, Mel-Flu-TBI8, Mel-Treo-Flu, Thio-ETO-Cy-Bu2-Flu, and Clo-ARAC-(Bu2/TBI4)-Cy groups, respectively. In patients <55 years of age Mel-Flu-TBI8 had the best LFS, which was statistically significant only in comparison to the Mel-Treo-Flu group, while in patients =55 years LFS was best with FLAMSA-Chemo without significant differences compared to FLAMSA-TBI4 and Mel-Flu-TBI8. Furthermore, best NRM rates were obtained with the two FLAMSA regimens groups. Our study suggests that in younger (<55 years) patients a more intense regimen might be used whereas in older (=55 years) patients the focus might be more on tolerability.
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Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial
Beelen, D. W., Trenschel, R., Stelljes, M., Groth, C., Masszi, T., Remenyi, P., Wagner-Drouet, E. M., Hauptrock, B., Dreger, P., Luft, T., et al
The Lancet. Haematology. 2019
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Editor's Choice
Abstract
BACKGROUND Further improvement of preparative regimens before allogeneic haemopoietic stem cell transplantation (HSCT) is an unmet medical need for the growing number of older or comorbid patients with acute myeloid leukaemia or myelodysplastic syndrome. We aimed to evaluate the efficacy and safety of conditioning with treosulfan plus fludarabine compared with reduced-intensity busulfan plus fludarabine in this population. METHODS We did an open-label, randomised, non-inferiority, phase 3 trial in 31 transplantation centres in France, Germany, Hungary, Italy, and Poland. Eligible patients were 18-70 years, had acute myeloid leukaemia in first or consecutive complete haematological remission (blast counts <5% in bone marrow) or myelodysplastic syndrome (blast counts <20% in bone marrow), Karnofsky index of 60% or higher, and were indicated for allogeneic HSCT but considered at an increased risk for standard myeloablative preparative regimens based on age (≥50 years), an HSCT-specific comorbidity index of more than 2, or both. Patients were randomly assigned (1:1) to receive either intravenous 10 g/m(2) treosulfan daily applied as a 2-h infusion for 3 days (days -4 to -2) or 0.8 mg/kg busulfan applied as a 2-h infusion at 6-h intervals on days -4 and -3. Both groups received 30 mg/m(2) intravenous fludarabine daily for 5 days (days -6 to -2). The primary outcome was event-free survival 2 years after HSCT. The non-inferiority margin was a hazard ratio (HR) of 1.3. Efficacy was assessed in all patients who received treatment and completed transplantation, and safety in all patients who received treatment. The study is registered with EudraCT (2008-002356-18) and ClinicalTrials.gov (NCT00822393). FINDINGS Between June 13, 2013, and May 3, 2016, 476 patients were enrolled (240 in the busulfan group received treatment and transplantation, and in the treosulfan group 221 received treatment and 220 transplanation). At the second preplanned interim analysis (Nov 9, 2016), the primary endpoint was met and trial was stopped. Here we present the final confirmatory analysis (data cutoff May 31, 2017). Median follow-up was 15.4 months (IQR 8.8-23.6) for patients treated with treosulfan and 17.4 months (6.3-23.4) for those treated with busulfan. 2-year event-free survival was 64.0% (95% CI 56.0-70.9) in the treosulfan group and 50.4% (42.8-57.5) in the busulfan group (HR 0.65 [95% CI 0.47-0.90]; p<0.0001 for non-inferiority, p=0.0051 for superiority). The most frequently reported grade 3 or higher adverse events were abnormal blood chemistry results (33 [15%] of 221 patients in the treosulfan group vs 35 [15%] of 240 patients in the busulfan group) and gastrointestinal disorders (24 [11%] patients vs 39 [16%] patients). Serious adverse events were reported for 18 (8%) patients in the treosulfan group and 17 (7%) patients in the busulfan group. Causes of deaths were generally transplantation-related. INTERPRETATION Treosulfan was non-inferior to busulfan when used in combination with fludarabine as a conditioning regimen for allogeneic HSCT for older or comorbid patients with acute myeloid leukaemia or myelodysplastic syndrome. The improved outcomes in patients treated with the treosulfan-fludarabine regimen suggest its potential to become a standard preparative regimen in this population. FUNDING medac GmbH.
PICO Summary
Population
Patients with acute myeloid leukaemia in first or consecutive complete haematological remission or myelodysplastic syndrome considered at an increased risk for standard myeloablative preparative regimens based on age (>/=50 years), an HSCT-specific comorbidity index of more than 2, or both. (n=460)
Intervention
Intravenous 10 g/m(2) treosulfan daily for 3 days followed by intravenous fludarabine daily for 5 days (n=221)
Comparison
0.8 mg/kg busulfan at 6-h intervals on days -4 and -3, followed by 30 mg/m(2) intravenous fludarabine daily for 5 days (n=240)
Outcome
Median follow-up was 15.4 months for patients treated with treosulfan and 17.4 months for those treated with busulfan. 2-year event-free survival was 64.0% in the treosulfan group and 50.4% in the busulfan group. The most frequently reported grade 3 or higher adverse events were abnormal blood chemistry results (15% patients in the treosulfan group vs 15% in the busulfan group) and gastrointestinal disorders (11% patients vs 16% patients). Serious adverse events were reported for 8% of patients in the treosulfan group and 7% of patients in the busulfan group. Causes of deaths were generally transplantation-related.
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9.
Long-term efficacy of reduced-intensity versus myeloablative conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: retrospective follow-up of an open-label, randomised phase 3 trial
Fasslrinner, F., Schetelig, J., Burchert, A., Kramer, M., Trenschel, R., Hegenbart, U., Stadler, M., Schafer-Eckart, K., Batzel, M., Eich, H., et al
The Lancet. Haematology. 2018
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Editor's Choice
Abstract
BACKGROUND The impact of the intensity of conditioning before allogeneic haemopoietic cell transplantation (HCT) has been studied in a randomised phase 3 trial comparing reduced-intensity conditioning with myeloablative conditioning in patients with acute myeloid leukaemia in first complete remission. Because of the short follow-up of the original trial, whether reduced-intensity conditioning increases the risk of late relapse compared with myeloablative conditioning remained unclear. To address this question, we present retrospective 10-year follow-up data of this trial and focus on late relapse. METHODS The original randomised phase 3 trial included patients aged 18-60 years, with intermediate-risk or high-risk acute myeloid leukaemia, an adequate organ function, and an available HLA-matched sibling donor or an unrelated donor with at least nine out of ten HLA alleles matched. Patients were randomly assigned (1:1) to 120 mg/m(2) fludarabine combined with four 2 Gy doses of total-body irradiation (reduced-intensity conditioning) or six 2 Gy doses of total-body irradiation and 120 mg/kg cyclophosphamide (myeloablative conditioning). The primary and secondary efficacy endpoints of this trial have been published previously. In this retrospective, long-term follow-up analysis, data were collected from medical reports from individual participating study centres, and from physician and patient interviews. Endpoints included in this analysis were cumulative relapse incidence, overall survival, disease-free survival, and non-relapse mortality in the original study population and in patients alive and relapse-free at 12 months after HCT (landmark analysis). 10-year time to event rates were calculated in the intention-to-treat population and were compared with the Gray test. The trial is registered with ClinicalTrials.gov, number NCT00150878. FINDINGS In the original trial, 195 patients were randomly assigned to receive reduced-intensity conditioning (n=99) or myeloablative conditioning (n=96). For this retrospective analysis, data were collected with a nearly complete follow-up (completeness index 99%). Median follow-up time for surviving patients was 9.9 years (IQR 8.5-11.4), during which the cumulative incidence of relapse in the complete study population was identical in both groups (30% [95% CI 20-39] in the reduced-intensity conditioning group vs 30% [21-40] in the myeloablative conditioning group; Gray test p=0.99). Relapse occurred at a median of 5.0 months (IQR 3.0-8.8) in the reduced-intensity conditioning group versus 9.5 months (4.5-20.5) in the myeloablative conditioning group. 10-year disease-free survival was 55% (95% CI 45-66) in the reduced-intensity conditioning group and 43% (34-55) in the myeloablative conditioning group (hazard ratio [HR] 0.76 [0.51-1.14]; p=0.19). 10-year non-relapse mortality was 16% (95% CI 8-24) in the reduced-intensity conditioning group and 26% (17-36) in the myeloablative conditioning group (subdistribution HR 0.60 [95% CI 0.32-1.11]; Gray test p=0.10). The incidence of long-term toxicities associated with total-body irradiation was comparable; secondary malignancies occurred in six (6%) of 94 patients in the reduced-intensity conditioning group and five (6%) of 90 in the myeloablative conditioning group (p=1.00). INTERPRETATION There is no evidence that reduced-intensity conditioning increases the risk of late relapse compared with myeloablative conditioning. Given that the reduced-intensity conditioning group in the original trial was associated with lower early morbidity and toxicity, reduced-intensity conditioning with moderately reduced total-body irradiation doses could be the preferred conditioning strategy for patients with acute myeloid leukaemia who are younger than 60 years and transplanted in first complete remission. FUNDING None.
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10.
Conditioning intensity in secondary AML with prior myelodysplastic syndrome/myeloproliferative disorders: an EBMT ALWP study
Sengsayadeth, S., Gatwood, K. S., Boumendil, A., Labopin, M., Finke, J., Ganser, A., Stelljes, M., Ehninger, G., Beelen, D., Niederwieser, D., et al
Blood advances. 2018;2(16):2127-2135
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Abstract
Patients with secondary AML (sAML) with antecedent myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPNs) tend to have high-risk disease based on the older age of patients, high-risk cytogenetics, and higher number of prior treatments. Allogeneic hematopoietic cell transplant (HCT) is the only potentially curative therapy available. Eight hundred and two adults with sAML and prior MDS/MPN who received a first HCT between 2000 and 2016 were included in the European Society for Blood and Marrow Transplant (EBMT) Acute Leukemia Working Party (ALWP) study. Median age of the cohort was 59.6 years (range, 18.6-78.6 years). Myeloablative conditioning (MAC) was given to 40% of patients, and 60% received reduced-intensity conditioning (RIC). Overall, the 2-year cumulative incidence of relapse (RI) was 37%, leukemia-free survival (LFS) was 40%, overall survival (OS) was 46%, nonrelapse mortality (NRM) was 23%, and chronic graft-versus-host disease (cGVHD) was 39%. In univariate analysis, a statistical difference between conditioning regimens 6 months after HCT in favor of the MAC group was noted with regard to RI (hazard ratio [HR], 1.47; P = .03), LFS (HR, 1.43; P = .01), and OS (HR, 1.55; P < .05). There was no difference in the cumulative incidence of NRM (HR, 1.38; P = .15). This effect was similarly seen in multivariate analysis (MVA): cumulative incidence of relapse (HR, 1.79; P < .05), LFS (HR, 1.43; P = .02), and OS (HR, 1.53; P = .005) with no difference in NRM (HR, 1; P = .98). This EBMT ALWP analysis suggests that long-term survival can be achieved in patients with sAML with antecedent MDS/MPN and that MAC is a suitable conditioning regimen in patients with sAML.