Phase II prospective study of treosulfan-based reduced-intensity conditioning in allogeneic HSCT for hematological malignancies from 10/10 HLA-identical unrelated donor

Michallet, Mauricette; Sobh, Mohamad; Milpied, Noël; Bay, Jacques‐Olivier; Fürst, Sabine; Harousseau, Jean‐Luc; Mohty, Mohamad; Nicolini, Franck E.; Labussière, Hélène; Tedone, Nathalie; Morisset, Stéphane; Vigouroux, Stéphane; Baumgart, Joachim; Tabrizi, Reza; Blaise, Didier

doi:10.1007/s00277-012-1429-y

Cited by 19 publications

(12 citation statements)

References 40 publications

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“…However, it should be noted that 1 heavily pretreated patient with AML/MDS in the FluTreoATG group presented post-transplantation lymphoproliferative disorder. Similar cases have been previously reported after treosulfan conditioning in unrelated transplantations [27,28]. Therefore, cautious management of EBV reactivation in patients receiving ATG is advisable.…”

Section: Discussionsupporting

confidence: 81%

Survival Advantage and Comparable Toxicity in Reduced-Toxicity Treosulfan-Based versus Reduced-Intensity Busulfan-Based Conditioning Regimen in Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients after Allogeneic Hematopoietic Cell Transplantation

Sakellari

Mallouri

Gavriilaki

et al. 2017

Biology of Blood and Marrow Transplantation

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Treosulfan has been incorporated in conditioning regimens for sustained remission without substantial toxicity and treatment-related mortality (TRM). We aimed to analyze the safety and efficacy of a fludarabine 150 mg/m and treosulfan 42 g/m (FluTreo) conditioning regimen in medically infirm patients. Outcomes were compared with those of a similar historical group treated with fludarabine 150 mg/m to 180 mg/m, busulfan 6.4 mg/kg, and antithymocyte globulin (ATG) 5 mg/kg to 7.5 mg/kg (FluBuATG). Thirty-one consecutive patients with acute myeloid leukemia (AML; n = 21), myelodysplastic syndrome (MDS; n = 6), or treatment-related AML (n = 4) received FluTreo conditioning. The historical group consisted of 26 consecutive patients treated with FluBuATG. In the FluTreo group, engraftment was prompt in all patients and 74% achieved >99% donor chimerism by day +30. No grades III or IV organ toxicities were noted. One-year cumulative incidences (CI) of acute and chronic graft-versus-host disease (GVHD) were 19.4% and 58.4%. The groups were similar for age, disease risk, lines of treatment, hematopoietic cell transplantation-specific comorbidity index, and acute or chronic GVHD incidence, except that there were more matched unrelated donor recipients in the FluTreo group (P < .001). With 20 (range, 2 to 36) months follow-up for FluTreo and 14 (range, 2 to 136) for FluBuATG, the 1-year cumulative overall survival (OS) probability was 76% versus 57%, respectively (P = .026); 1-year disease-free survival (DFS) was 79% versus 38% (P < .001). In multivariate analysis, the only significantly favorable factor for OS and DFS was FluTreo (P = .010 and P = .012). The CI of relapse mortality was markedly decreased in FluTreo versus FluBuATG (7.4% versus 42.3%, P < .001). In conclusion, the treosulfan-based regimen resulted in favorable OS and DFS with acceptable toxicity and low relapse rates compared with busulfan-based conditioning.

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Section: Discussionsupporting

confidence: 81%

Survival Advantage and Comparable Toxicity in Reduced-Toxicity Treosulfan-Based versus Reduced-Intensity Busulfan-Based Conditioning Regimen in Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients after Allogeneic Hematopoietic Cell Transplantation

Sakellari

Mallouri

Gavriilaki

et al. 2017

Biology of Blood and Marrow Transplantation

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“…Nevertheless, while improvements in supportive care over the years may contribute to favorable outcome, several studies found improved OS with treosulfan-based conditioning in comparison to historical data 24,42–44 . Ruutu et al and Casper et al showed 2-year NRM of 17% and 11%, and OS of 71% and 61%, respectively, in patients with MDS or AML conditioned with treosulfan/fludarabine and transplanted from HLA-matched related or unrelated donors 24,38 .…”

Section: Discussionmentioning

confidence: 99%

Treosulfan, Fludarabine, and 2-Gy Total Body Irradiation Followed by Allogeneic Hematopoietic Cell Transplantation in Patients with Myelodysplastic Syndrome and Acute Myeloid Leukemia

Gyurkocza

Gutman

Nemecek

et al. 2014

Biology of Blood and Marrow Transplantation

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Allogeneic hematopoietic cell transplantation (HCT) offers curative therapy for many patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). However, post-HCT relapse remains a major problem, particularly in patients with high-risk cytogenetics. In this prospective phase II trial we assessed the efficacy and toxicity of treosulfan, fludarabine and 2 Gy total body irradiation (TBI) as conditioning for allogeneic HCT in patients with MDS or AML. Ninety-six patients with MDS (n=36; 15 RMCD; 10 RAEB-1; 10 RAEB-2; 1 CMML-1) or AML (n=60; 35 CR1; 18 CR2; 3 advanced CR; 4 refractory relapse) were enrolled; median age was 51 (range: 1–60) years. Twelve patients had undergone a prior HCT with high intensity conditioning. Patients received intravenous (IV) treosulfan, 14 g/m2/day on days −6 to −4, IV fludarabine, 30 mg/m2/day on days −6 to −2, and 2 Gy TBI on day 0, followed by infusion of hematopoietic cells from related (n=27) or unrelated (n=69) donors. Graft-vs.-host disease prophylaxis consisted of tacrolimus and methotrexate. With a median follow-up of 30 months, the 2-year overall survival (OS), relapse incidence and non-relapse mortality were 73%, 27% and 8%, respectively. The incidences of grades II–IV (III–IV) acute and chronic graft-versus-host disease were 59% (10%) and 47%, respectively. Two-year OS was not significantly different between MDS patients with poor risk and good/intermediate risk cytogenetics (69% and 85%, respectively), or between AML patients with unfavorable and favorable/intermediate risk cytogenetics (64% and 76%, respectively). In AML patients, minimal residual disease (MRD; n=10) at the time of HCT predicted higher relapse incidence (70% vs. 18%) and lower OS (41% vs. 79%) at 2 years, when compared to patients without MRD. In conclusion, treosulfan, fludarabine and low-dose TBI provided effective conditioning for allogeneic HCT in patients with MDS or AML, and resulted in low relapse incidence, regardless of cytogenetic risk. In patients with AML, MRD at the time of HCT remained a risk factor for post-HCT relapse.

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“…The cumulative incidence of relapse was 25% at 3 years and the NRM at 12 and 24 months was 20% and 23%, respectively. 30 The studies from groups in Germany and Israel has shown promising efficacy with TREO-based regimens. 31,32 Kroger et al 31 investigated a dose-reduced conditioning regimen consisting of TREO and FLU followed by allo-HSCT in 26 patients with secondary AML or MDS.…”

Section: Busulfan Cyclophosphamide (Bu-cy) Vs Cyclophosphamide Tbi mentioning

confidence: 99%

Conditioning regimens for allogeneic hematopoietic stem cell transplants in acute myeloid leukemia

Jethava

Sica

Savani

et al. 2017

Bone Marrow Transplant

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AML is currently the first indication for allogeneic hematopoietic stem cell transplantation (allo-HSCT), as shown by international transplant registries. The conditioning regimens are classified as myeloablative conditioning, non-myeloablative or reduced intensity conditioning. Targeted radioimmunotherapy such as anti-CD45 antibody have also been added to the conditioning regimen in an attempt to improve tumor cell kill. Refinement of standard regimens has led to a reduction of non-relapse mortality, also in the older age group over 60 or 70 years of age. Relapse post allo-HSCT remains an important issue, especially for patients who undergo transplant with residual or refractory disease. In these patients, pre- and post-transplant interventions need to be considered.

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Phase II prospective study of treosulfan-based reduced-intensity conditioning in allogeneic HSCT for hematological malignancies from 10/10 HLA-identical unrelated donor

Cited by 19 publications

References 40 publications

Survival Advantage and Comparable Toxicity in Reduced-Toxicity Treosulfan-Based versus Reduced-Intensity Busulfan-Based Conditioning Regimen in Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients after Allogeneic Hematopoietic Cell Transplantation

Survival Advantage and Comparable Toxicity in Reduced-Toxicity Treosulfan-Based versus Reduced-Intensity Busulfan-Based Conditioning Regimen in Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients after Allogeneic Hematopoietic Cell Transplantation

Treosulfan, Fludarabine, and 2-Gy Total Body Irradiation Followed by Allogeneic Hematopoietic Cell Transplantation in Patients with Myelodysplastic Syndrome and Acute Myeloid Leukemia

Conditioning regimens for allogeneic hematopoietic stem cell transplants in acute myeloid leukemia

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