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, Dietrich; Trenschel, Rudolf; Stelljes, Matthias; Groth, Christoph; Masszi, Tamás; Reményi, Péter; Wagner-Drouet, Eva; Hauptrock, Beate; Dreger, Peter; Luft, Thomas; Bethge, Wolfgang; Vogel, W.; Ciceri, Fabio; Peccatori, Jacopo; Stölzel, Friedrich; Schetelig, Johannes; Junghanß, Christian; Große-Thie, Christina; Michallet, Mauricette; Labussière‐Wallet, Hélène; Schaefer‐Eckart, Kerstin; Dressler, Sabine; Grigoleit, Goetz Ulrich; Mielke, Stephan; Scheid, Christof; Holtick, Udo; Patriarca, Francesca; Medeot, Marta; Rambaldi, Alessandro; Micò, Maria Caterina; Niederwieser, Dietger; Franke, Georg-Nikolaus; Hilgendorf, Inken; Winkelmann, Nils; Russo, Domenico; Socié, Gèrard; Latour, Régis Peffault de; Holler, Ernst; Wolff, Daniel; Glaß, Bertram; Casper, Jochen; Wulf, Gerald; Menzel, Helge; Basara, Nadežda; Bieniaszewska, Maria; Stuhler, Gernot; Verbeek, Mareike; Grass, Sandra; Iori, Anna Paola; Finke, Juergen; Benedetti, Fabio; Pichlmeier, Uwe; Hemmelmann, Claudia; Tribanek, Michael; Klein, Anja; Mylius, Heidrun A.; Baumgart, Joachim; Dzierżak‐Mietła, Monika; Markiewicz, Mirosław

doi:10.1016/s2352-3026(19)30157-7

Cited by 115 publications

(142 citation statements)

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“…The report from Seattle of 1055 patients undergoing allo‐HSCT showed that the 2‐year TRM was 14%, 21%, and 41% for the patients with HCT‐CI scores 0, 1‐2, and 3 or more, respectively 31 . Beelen et al reported 476 older or comorbid AML/MDS patients with a median HCT‐CI of 3.0 undergoing allo‐HSCT showed that the 2‐year TRM was up to 28.2% 32 . In the present study, the 2‐year cumulative incidences of TRM were 17.2% in the HID and 17.4% MSD in the HID.…”

Section: Discussionmentioning

confidence: 99%

Haploidentical related donor vs matched sibling donor allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndrome aged over 50 years: A single‐center retrospective study

Huang

Zhang

et al. 2020

Cancer Medicine

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Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a potentially curative therapeutic option for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Increasing data suggest that haploidentical donor (HID) transplantation achieve comparable outcomes with HLA‐matched sibling donor (MSD) in adult AML/MDS. This retrospective study compared the outcomes of AML or MDS patients age ≥50 years underwent HID and MSD transplantation. One hundred and fifty‐six patients were enrolled in this study, including 75 HID and 81 MSD transplantation. The 100‐day cumulative incidence of II‐IV° acute graft‐versus‐host disease (GVHD) was 33.3 ± 5.4% vs 22.2 ± 4.6%, respectively, in HID and MSD groups (P = .066), and III‐IV° acute GVHD was not significantly different between two groups (5.3%±2.6% vs 6.2%±2.7%, respectively, P = .823). The 2‐year cumulative incidence of limited and extensive chronic GVHD was not statistically different in HID and MSD groups (20.9 ± 5.5% vs 18.9 ± 4.8% and 13.0 ± 4.7% vs 19.7 ± 5.0%, P = .889 and P = .269, respectively). The 2‐year cumulative incidences of relapse (27.0 ± 5.6% vs 22.7 ± 5.1%, P = .509), 2‐year overall survival (63.0 ± 5.8% vs 66.7 ± 5.4%, P = .454), 2‐year transplant‐related mortality (17.2 ± 4.6% vs 17.4 ± 4.4%, P = .847), 2‐year progression‐free survival (59.3 ± 5.8% vs 64.5 ± 5.4%, P = .437), 2‐year GVHD‐free relapse‐free survival (42.6 ± 5.9% vs 40.9 ± 5.6%, P = .964) were not significantly different in the two groups. The present data showed equivalent outcomes in AML or MDS patients age ≥50 years underwent HID and MSD transplantation.

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Section: Discussionmentioning

confidence: 99%

Haploidentical related donor vs matched sibling donor allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndrome aged over 50 years: A single‐center retrospective study

Huang

Zhang

et al. 2020

Cancer Medicine

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“…However, both regimens are associated with a considerable risk of acute and late serious adverse events (AEs) [1][2][3][4][5]. Clinical studies, including prospective phase III trials in adults with AML and MDS, have shown that treosulfan-based conditioning has myeloablative, immunosuppressive, and antineoplastic effects associated with a low non-relapse mortality (NRM) [6][7][8][9][10][11]. Furthermore, several reports have been published that show an indication for treosulfan-based conditioning in children undergoing alloHSCT for nonmalignant and malignant disorders [12][13][14][15][16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Treosulfan–fludarabine–thiotepa-based conditioning treatment before allogeneic hematopoietic stem cell transplantation for pediatric patients with hematological malignancies

Kałwak

Mielcarek

Patrick

et al. 2020

Bone Marrow Transplant

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Treosulfan-based conditioning prior to allogeneic transplantation has been shown to have myeloablative, immunosuppressive, and antineoplastic effects associated with reduced non-relapse mortality (NRM) in adults. Therefore, we prospectively evaluated the safety and efficacy of treosulfan-based conditioning in children with hematological malignancies in this phase II trial. Overall, 65 children with acute lymphoblastic leukemia (35.4%), acute myeloid leukemia (44.6%), myelodysplastic syndrome (15.4%), or juvenile myelomonocytic leukemia (4.6%) received treosulfan intravenously at a dose of 10 mg/m 2 / day (7.7%), 12 g/m 2 /day (35.4%), or 14 g/m 2 /day (56.9%) according to their individual body surface area in combination with fludarabine and thiotepa. The incidence of complete donor chimerism at day +28 was 98.4% with no primary and only one secondary graft failure. At 36 months, NRM was only 3.1%, while relapse incidence was 21.7%, and overall survival was 83.0%. The cumulative incidence of acute graft-vs.-host disease was 45.3% for grades I-IV and 26.6% for grades II-IV. At 36 months, 25.8% overall and 19.4% moderate/severe chronic graft-vs.-host disease were reported. These data confirm the safe and effective use of treosulfan-based conditioning in pediatric patients with hematological malignancies. Therefore, treosulfan/fludarabine/thiotepa can be recommended for myeloablative conditioning in children with hematological malignancies.

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“…It has been used increasingly in conventional donor HCT, frequently in combination with fludarabine (FLU), where it has been effective in establishing engraftment with low TRM. 11 In addition, it has several attractive characteristics as compared with BU, including predictable pharmacokinetics, allowing for outpatient administration and, importantly, a decreased risk of TRM 12 and potential for higher antileukemic activity that can induce sustained remissions in high-risk patients. 13 These characteristics make TREO particularly appealing as an agent in less-intensive HCT-conditioning regimens.…”

Section: Introductionmentioning

confidence: 99%

Treosulfan-based conditioning is feasible and effective for cord blood recipients: a phase 2 multicenter study

et al. 2020

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Although the use of treosulfan (TREO) in conventional donor hematopoietic cell transplantation (HCT) has been extensively evaluated, its use in cord blood transplantation (CBT) for hematologic malignancies has not been reported. Between March 2009 and October 2019, 130 CBT recipients were enrolled in this prospective multicenter phase 2 study. The conditioning regimen consisted of TREO, fludarabine, and a single fraction of 2 Gy total-body irradiation. Cyclosporine and mycophenolate mofetil were used for graft-versus-host disease prophylaxis. The primary end point was incidence of graft failure (GF), and based on risk of GF, patients were classified as low risk (arm 1, n = 66) and high risk (arm 2, n = 64). The median age was 45 years (range, 0.6-65 years). Disease status included acute leukemias in first complete remission (CR; n = 56), in ≥2 CRs (n = 46), and myelodysplastic (n = 25) and myeloproliferative syndromes (n = 3). Thirty-five patients (27%) had received a prior HCT. One hundred twenty-three patients (95%) engrafted, with neutrophil recovery occurring at a median of 19 days for patients on arm 1 and 20 days for patients on arm 2. The 3-year overall survival, relapse-free survival (RFS), transplant-related mortality, and relapse for the combined groups were 66%, 57%, 18%, and 24%, respectively. Among patients who had a prior HCT, RFS at 3 years was 48%. No significant differences in clinical outcomes were seen between the 2 arms. Our results demonstrate that TREO-based conditioning for CBT recipients is safe and effective in promoting CB engraftment with favorable clinical outcomes. This trial was registered at www.clinicaltrials.gov as #NCT00796068.

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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

Cited by 115 publications

References 29 publications

Haploidentical related donor vs matched sibling donor allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndrome aged over 50 years: A single‐center retrospective study

Haploidentical related donor vs matched sibling donor allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndrome aged over 50 years: A single‐center retrospective study

Treosulfan–fludarabine–thiotepa-based conditioning treatment before allogeneic hematopoietic stem cell transplantation for pediatric patients with hematological malignancies

Treosulfan-based conditioning is feasible and effective for cord blood recipients: a phase 2 multicenter study

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