Treosulfan compared with <scp>reduced‐intensity</scp> busulfan improves allogeneic hematopoietic cell transplantation outcomes of older acute myeloid leukemia and myelodysplastic syndrome patients: Final analysis of a prospective randomized trial

Beelen, Dietrich; Stelljes, Matthias; Reményi, Péter; Wagner‐Drouet, Eva‐Maria; Dreger, Peter; Bethge, Wolfgang; Ciceri, Fabio; Stölzel, Friedrich; Junghanß, Christian; Labussière‐Wallet, Hélène; Schaefer‐Eckart, Kerstin; Grigoleit, Goetz Ulrich; Scheid, Christof; Niederwieser, Dietger; Hilgendorf, Inken; Russo, Domenico; Socié, Gèrard; Holler, Ernst; Glaß, Bertram; Casper, Jochen; Wulf, Gerald; Basara, Nadežda; Bieniaszewska, Maria; Stuhler, Gernot; Verbeek, Mareike; Rocca, Ursula La; Finke, Juergen; Benedetti, Fabio; Pichlmeier, Uwe; Klein, Anja; Baumgart, Joachim; Markiewicz, Mirosław

doi:10.1002/ajh.26620

Cited by 29 publications

(25 citation statements)

References 29 publications

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“…Recently, a phase III randomized study was published, which compared RIC Tre/Flu and Flu/Bu2 RIC regimen for AML/MDS patients, 50–70 years or younger patients with significant comorbidities (HCT‐CI >2). The results revealed that 3‐year EFS and OS were superior in the Tre/Flu group (59.5% and 49.7%; p = .0006, OS 66.8% and 56.3%; p = .0037 respectively) 46 . However, it remains unclear if treosulfan‐based conditioning can outperform other commonly used melphalan‐based containing regimens.…”

Section: Conditioning Regimens For Transplantationmentioning

confidence: 98%

“…The results revealed that 3-year EFS and OS were superior in the Tre/Flu group (59.5% and 49.7%; p = .0006, OS 66.8% and 56.3%; p = .0037 respectively). 46 However, it remains unclear if treosulfanbased conditioning can outperform other commonly used melphalanbased containing regimens. A summary of conditioning regimens used for transplantation of MDS patients is presented in Table 6.…”

Section: Conditioning Regimens For Transplantationmentioning

confidence: 99%

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Allogeneic stem cell transplantation for patients with myelodysplastic syndromes

2022

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Myelodysplastic syndromes (MDS) are a heterogenous group of clonal hematopoietic stem cell neoplasms primarily affecting older persons, associated with dysplastic changes of bone marrow cells, peripheral cytopenias, and various risk of leukemic transformation. Although treatment with several drugs has shown improved disease control, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative treatment for MDS. The number of patients receiving a transplant, as well as survival, have increased past years because of the use of reduce-intensity conditioning regimens (RIC) as well as the use of haploidentical donors for transplantation. With treatment-related mortality as main limitation, pre-transplant evaluation is essential to assess risks for this older group of patients. In a recent randomized study, allo-HSCT with RIC for patients >50 years old with higher-risk MDS demonstrated superiority in survival compared with hypomethylating agents. Genetic mutations have been shown to significantly impact treatment outcomes including after transplant. Recently, a transplant-specific risk score (which includes age, donor type, performance status, cytogenetic category, recipient's cytomegalovirus status, percentage of blasts, and platelet count) has shown superiority in transplantation outcome prediction, compared with previous scoring systems. Survival remains low for most patients with TP53 mutations and novel treatment strategies are needed, such as administration of natural killer cells post-transplant, as there is no clear evidence that maintenance therapy after transplantation can improve outcomes.

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Section: Conditioning Regimens For Transplantationmentioning

confidence: 98%

Section: Conditioning Regimens For Transplantationmentioning

confidence: 99%

Allogeneic stem cell transplantation for patients with myelodysplastic syndromes

2022

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“…While comparative data of RIC regimens is lacking in CLL, a CIBMTR analysis of 1,823 patients undergoing RIC allogeneic HCT for non-Hodgkin lymphoma (NHL) found that Flu-Bu2 and fludarabine-cyclophosphamide (Flu-Cy) were associated with lower NRM and favorable OS compared to Flu-Mel140mg/m 2 ( 87 ). There is also growing interest in the use of treosulfan as a low-toxicity alternative to busulfan in RIC regimens, and a randomized trial in AML/MDS found that fludarabine-treosulfan (Flu-Treo) was associated with improved NRM and OS compared to Flu-Bu2 ( 88 , 89 ). Preliminary data suggest that Flu-Treo may also be a viable conditioning regimen in NHL ( 90 , 91 ), but confirmation in larger studies is required.…”

Section: Conditioning Regimensmentioning

confidence: 99%

The role of allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: A review

2023

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Although the use of allogeneic hematopoietic cell transplantation (HCT) for chronic lymphocytic leukemia (CLL) has declined with the development of novel targeted agents, it continues to play an important role for eligible patients with high-risk or heavily pretreated CLL who lack other treatment options. CLL is susceptible to a potent graft-versus-leukemia (GVL) effect which produces long-lasting remissions in 30-50% of transplanted patients. While allogeneic HCT is associated with significant risks of graft-versus-host disease (GVHD), infection, and non-relapse mortality (NRM), improvements in patient and donor selection, reduced intensity conditioning (RIC), GVHD prophylaxis, and supportive care have rendered this an increasingly safe and effective procedure in the current era. In this review, we discuss recent advances in allogeneic HCT for CLL, with a focus on the optimal evidence-based strategies to maximize benefit and minimize toxicity of this potentially curative cellular therapy.

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“…ATG was administered in addition to PTCy as GVHD prophylaxis in 13% of TBF and 11% of Treo patients, respectively. Median follow-up was 15 (range, 12-24) and 18 (range, [14][15][16][17][18][19][20][21][22] months in TBF and Treo, respectively.…”

Section: Patient Disease and Transplant Characteristicsmentioning

confidence: 99%

Thiotepa-busulfan-fludarabine Compared to Treosulfan-based Conditioning for Haploidentical Transplant With Posttransplant Cyclophosphamide in Patients With Acute Myeloid Leukemia in Remission: A Study From the Acute Leukemia Working Party of the EBMT

Saraceni,

Labopin,

Raiola

et al. 2023

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We conducted a registry analysis including adult acute myeloid leukemia (AML) patients in remission who had received thiotepa, busulfan, and fludarabine (TBF) or treosulfan-based (Treo) conditioning for haplo-hematopoietic stem cell transplant (HSCT) with posttransplant cyclophosphamide (PTCy) between 2010 and 2020. A total of 1123 patients met the inclusion criteria (968 received TBF and 155 received Treo). A 1:1 matched-pair analysis was performed on 142 TBF and 142 Treo patients. In the Treo group, 68% of patients received treosulfan at a dose ≥36 g/m2 and 54% of patients received a second alkylator (thiotepa or melphalan). We observed a trend toward increased incidence of grade II–IV acute (a) graft-versus-host disease (GVHD) at 180 days in the TBF group compared with Treo (29% versus 20%; P = 0.08), while incidence of grade III–IV aGVHD was not statistically different. Similarly, the incidence of chronic (c) GVHD was not statistically different in the 2 groups. Incidence of nonrelapse mortality at 2 years was 19% in TBF and 14% in Treo (P = 0.4). Relapse incidence at 2 years was not statistically different in the 2 groups (16% and 18% in TBF and Treo, respectively; P = 0.9). Leukemia-free survival, overall survival, and GVHD-free, relapse-free survival was 65% versus 68% (P = 0.6), 73% versus 76% (P = 0.5), and 54% versus 53% (P = 0.8) in TBF versus Treo, respectively. In conclusion, we did not find a significant difference between the 2 conditioning in the present study; Treo and TBF represent 2 valid alternative regimens for haplo-HSCT with PTCy for AML in remission.

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Treosulfan compared with reduced‐intensity busulfan improves allogeneic hematopoietic cell transplantation outcomes of older acute myeloid leukemia and myelodysplastic syndrome patients: Final analysis of a prospective randomized trial

Cited by 29 publications

References 29 publications

Allogeneic stem cell transplantation for patients with myelodysplastic syndromes

Allogeneic stem cell transplantation for patients with myelodysplastic syndromes

The role of allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: A review

Thiotepa-busulfan-fludarabine Compared to Treosulfan-based Conditioning for Haploidentical Transplant With Posttransplant Cyclophosphamide in Patients With Acute Myeloid Leukemia in Remission: A Study From the Acute Leukemia Working Party of the EBMT

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