Page last updated: 2024-12-05

treosulfan

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth

Description

treosulfan: immunosuppressant; RN given refers to (S-(R*,R*))-isomer [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID9882105
CHEMBL ID455186
CHEBI ID82557
SCHEMBL ID5399430
MeSH IDM0069890

Synonyms (62)

Synonym
l-threitol 1,4-dimethanesulfonate
treosulfan
299-75-2
nsc-39069
ovastat (tn)
D07253
treosulfan (inn)
treosulfanum [inn-latin]
l-threitol, 1,4-bismethanesulfonate
1,2,3,4-butanetetrol, 1,4-dimethanesulfonate, (s-(r*,r*))-
treosulfano [inn-spanish]
nsc 39069
threitol, 1,4-dimethanesulfonate, (2s,3s)-
ccris 2781
treosulphan
hsdb 6963
einecs 206-081-0
(s-(r*,r*))-1,2,3,4-butanetetrol, 1,4-dimethanesulfonate
l-threitol, 1,4-bis(methanesulfonate)
(2s,3s)-threitol 1,4-bismethanesulfonate
threitol, 1,4-dimethanesulfonate, l-(+)-
ovastat
chebi:82557 ,
threosulphan
CHEMBL455186
C19557
unii-co61er3epi
co61er3epi ,
who 3103
treosulfanum
treosulfano
treosulfan [usan:inn:ban]
treosulfan [iarc]
treosulfan [who-dd]
treosulfan [hsdb]
treosulfan [inn]
kepcondi
treosulfan [mart.]
treograft
grafapex
treosulfan [usan]
l-threitol 1,4-dimethanesulphonate
graftrevo
trecondyv
S6958
CS-3889
l-threitol-1,4-bis-methanesulfonate
SCHEMBL5399430
HY-16503
AKOS030231132
DB11678
l-threitol 1,4-bis(methanesulfonate)
YCPOZVAOBBQLRI-WDSKDSINSA-N
(2s,3s)-2,3-dihydroxybutane-1,4-diyl dimethanesulfonate
PS-12126
[(2s,3s)-2,3-dihydroxy-4-methylsulfonyloxybutyl] methanesulfonate
(s)-3-boc-amino-1-diazo-3-(4-benzyloxy)phenyl-2-butanone
A912763
treosulphannsc 39069
(2s,3s)-2,3-dihydroxy-4-(methanesulfonyloxy)butyl methanesulfonate
EN300-1703341
rel-(2s,3s)-2,3-dihydroxybutane-1,4-diyl dimethanesulfonate

Research Excerpts

Toxicity

The combination of treosulfan and fludarabine is a safe and efficient conditioning regimen. The study looked at patients with primary HLH transplanted 2009-2016.

ExcerptReferenceRelevance
" The major toxic effects were leukopenia and thrombocytopenia, which, however, were manageable and rapidly reversible."( Maintenance chemotherapy with oral treosulfan following first-line treatment in patients with advanced ovarian cancer: feasibility and toxicity.
Kuhn, W; Meden, H; Wittkop, Y,
)
0.13
" In summary, the combination of treosulfan and fludarabine is a safe and efficient conditioning regimen."( Treosulfan and fludarabine: a new toxicity-reduced conditioning regimen for allogeneic hematopoietic stem cell transplantation.
Casper, J; Dölken, G; Freund, M; Hammer, U; Hartung, G; Kiefer, T; Kleine, HD; Knauf, W; Knopp, A; Steiner, B; Wegener, R; Wilhelm, S; Wolff, D, 2004
)
0.32
" Patients were evaluated for engraftment, adverse events, graft-versus-host disease, non-relapse mortality, relapse incidence, overall survival and disease-free survival."( Reduced-toxicity conditioning with treosulfan and fludarabine in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndromes: final results of an international prospective phase II trial.
Baumgart, J; Beelen, DW; Blau, IW; Casper, J; Einsele, H; Finke, J; Freund, M; Giebel, S; Gramatzki, M; Holowiecki, J; Kienast, J; Larsson, K; Markiewicz, M; Mylius, HA; Pichlmeier, U; Repp, R; Ruutu, T; Schnitzler, M; Stelljes, M; Stuhler, G; Trenschel, R; Uharek, L; Volin, L; Zander, AR, 2011
)
0.37
" Non-hematologic adverse events of grade III-IV in severity included mainly infections and gastrointestinal symptoms (80% and 22% of the patients, respectively)."( Reduced-toxicity conditioning with treosulfan and fludarabine in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndromes: final results of an international prospective phase II trial.
Baumgart, J; Beelen, DW; Blau, IW; Casper, J; Einsele, H; Finke, J; Freund, M; Giebel, S; Gramatzki, M; Holowiecki, J; Kienast, J; Larsson, K; Markiewicz, M; Mylius, HA; Pichlmeier, U; Repp, R; Ruutu, T; Schnitzler, M; Stelljes, M; Stuhler, G; Trenschel, R; Uharek, L; Volin, L; Zander, AR, 2011
)
0.37
" Multivariate analysis (MVA) identified comorbidity score (HCT-CI) >2 and advanced disease as adverse factors with no independent impact of regimen."( Allo-SCT for AML and MDS with treosulfan compared with BU-based regimens: reduced toxicity vs reduced intensity.
Danylesko, I; Nagler, A; Shem-Tov, N; Shimoni, A; Volchek, Y; Yerushalmi, R, 2012
)
0.38
" This treosulfan-based preparation proved to be safe and effective for thalassemia patients given allogeneic HSCT."( Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan.
Bernardo, ME; Bertaina, A; Caocci, G; Contoli, B; Giorgiani, G; La Nasa, G; Locatelli, F; Mastronuzzi, A; Pagliara, D; Pinto, RM; Piras, E; Vacca, A; Zecca, M, 2012
)
0.38
" TBC combined with thiotepa is highly toxic to the skin with various cutaneous manifestations."( Skin toxicity following treosulfan-thiotepa-fludarabine-based conditioning regimen in non-malignant pediatric patients undergoing hematopoietic stem cell transplantation.
Altman Kohl, S; Even-Or, E; Molho-Pessach, V; Stepensky, P; Zaidman, I, 2020
)
0.56
"Patients with primary HLH transplanted 2009-2016 after treosulfan- or melphalan-based conditioning regimens were analyzed in a retrospective multicenter study for survival, engraftment, chimerism, and adverse events."( Risk factors for mixed chimerism in children with hemophagocytic lymphohistiocytosis after reduced toxicity conditioning.
Albert, MH; Bader, P; Beier, R; Burkhardt, B; Chada, M; Ehl, S; Greil, J; Gruhn, B; Janka, G; Kühl, JS; Lang, P; Lehmberg, K; Meisel, R; Müller, I; Ozga, AK; Schlegel, PG; Schulz, A; Seidel, M; Speckmann, C; Sykora, KW; Wawer, A; Wössmann, W; Wustrau, K, 2020
)
0.56

Pharmacokinetics

A Phase I dose escalation and pharmacokinetic study of the alkylating cytotoxic agent treosulfan was conducted to evaluate the maximum tolerated dose and the dose-limiting toxicities in patients with advanced malignancies rescued by autologous peripheral blood stem cell transplant.

ExcerptReferenceRelevance
"A Phase I dose escalation and pharmacokinetic study of the alkylating cytotoxic agent treosulfan was conducted to evaluate the maximum tolerated dose and the dose-limiting toxicities in patients with advanced malignancies rescued by autologous peripheral blood stem cell transplantation."( Clinical phase I dose escalation and pharmacokinetic study of high-dose chemotherapy with treosulfan and autologous peripheral blood stem cell transplantation in patients with advanced malignancies.
Baumgart, J; Berdel, WE; Bojko, P; Bornhäuser, M; Casper, J; Ehninger, G; Freund, M; Harstrick, A; Hilger, RA; Josten, KM; Oberhoff, C; Scheulen, ME; Schindler, AE; Seeber, S; Wolf, HH, 2000
)
0.31
" Intra- and inter-day precision and accuracy of the measurement fulfilled analytical criteria accepted in pharmacokinetic studies."( Determination of treosulfan in plasma and urine by HPLC with refractometric detection; pharmacokinetic studies in children undergoing myeloablative treatment prior to haematopoietic stem cell transplantation.
Grund, G; Główka, FK; Wachowiak, J; Łada, MK, 2007
)
0.34
" Pharmacokinetic parameters were evaluated following first dose using a two-compartment disposition model."( Pharmacokinetics of high-dose i.v. treosulfan in children undergoing treosulfan-based preparative regimen for allogeneic haematopoietic SCT.
Grund, G; Główka, FK; Karaźniewicz-Łada, M; Wachowiak, J; Wróbel, T, 2008
)
0.35
" Pharmacokinetic data to optimize treosulfan dosing are scarce in this patient population."( Pharmacokinetics of treosulfan in pediatric patients undergoing hematopoietic stem cell transplantation.
Ackaert, O; Bredius, RG; den Hartigh, J; Guchelaar, HJ; Lankester, AC; Smiers, FJ; Ten Brink, MH; Zwaveling, J, 2014
)
0.4
" Pharmacokinetic parameters were determined in six children who received intravenous treosulfan (dose range 12-24 g/m(2)) in combination with fludarabine prior to blood or marrow transplantation."( Development and Validation of a High Pressure Liquid Chromatography-UV Method for the Determination of Treosulfan and Its Epoxy Metabolites in Human Plasma and Its Application in Pharmacokinetic Studies.
Byrne, JA; Earl, JW; Fraser, CJ; Koyyalamudi, SR; Kuzhiumparambil, U; Nath, CE; O'Brien, TA; Shaw, PJ, 2016
)
0.43
" Then EBDM and DEB have the same elimination half-life as TREO, but the levels of EBDM and DEB in the body, including plasma, are much lower than TREO on account of their inherently high clearance."( Formation Rate-Limited Pharmacokinetics of Biologically Active Epoxy Transformers of Prodrug Treosulfan.
Główka, FK; Karbownik, A; Kasprzyk, A; Romański, M; Szałek, E, 2016
)
0.43
" For that purpose, pharmacokinetic analyses are ongoing within clinical phase II and III trials."( Clinical bioanalysis of treosulfan and its epoxides: The importance of collected blood processing for valid pharmacokinetic results.
Główka, F; Romański, M, 2018
)
0.48
" The significance of the elimination half-life of treosulfan and its epoxides for successful conditioning prior to HSCT is also raised."( Treosulfan Pharmacokinetics and its Variability in Pediatric and Adult Patients Undergoing Conditioning Prior to Hematopoietic Stem Cell Transplantation: Current State of the Art, In-Depth Analysis, and Perspectives.
Główka, FK; Romański, M; Wachowiak, J, 2018
)
0.48
" The aim of this study was to develop a population pharmacokinetic (PK) model of treosulfan in paediatric haematopoietic stem cell transplantation recipients and to explore the effect of potential covariates on treosulfan PK."( Population pharmacokinetics of treosulfan in paediatric patients undergoing hematopoietic stem cell transplantation.
Bertaina, A; Guchelaar, HJ; Lankester, AC; Locatelli, F; Moes, DJAR; van der Stoep, MYEC; Zwaveling, J, 2019
)
0.51
" The population pharmacokinetic model was established in NONMEM software with a first-order estimation method with interaction."( Population pharmacokinetic approach for evaluation of treosulfan and its active monoepoxide disposition in plasma and brain on the basis of a rat model.
Danielak, D; Główka, F; Kasprzyk, A; Romański, M; Teżyk, A, 2020
)
0.56
"One-compartment pharmacokinetic model best described changes in the concentrations of treosulfan in plasma, and EBDM concentrations in plasma and in the brain."( Population pharmacokinetic approach for evaluation of treosulfan and its active monoepoxide disposition in plasma and brain on the basis of a rat model.
Danielak, D; Główka, F; Kasprzyk, A; Romański, M; Teżyk, A, 2020
)
0.56
"The developed population pharmacokinetic model is the first that allows the prediction of treosulfan and EBDM concentrations in rat plasma and brain."( Population pharmacokinetic approach for evaluation of treosulfan and its active monoepoxide disposition in plasma and brain on the basis of a rat model.
Danielak, D; Główka, F; Kasprzyk, A; Romański, M; Teżyk, A, 2020
)
0.56
"The aim of this work is the development of a mechanistic physiologically-based pharmacokinetic (PBPK) model using in vitro to in vivo extrapolation to conduct a drug-drug interaction (DDI) assessment of treosulfan against two cytochrome p450 (CYP) isoenzymes and P-glycoprotein (P-gp) substrates."( Evaluation of the drug-drug interaction potential of treosulfan using a physiologically-based pharmacokinetic modelling approach.
Balazki, P; Baumgart, J; Beelen, DW; Böhm, S; Hemmelmann, C; Hilger, RA; Martins, FS; Ring, A; Schaller, S, 2022
)
0.72
" However, considering the comprehensive treosulfan-based conditioning treatment schedule and the respective pharmacokinetic properties of the concomitantly used drugs (eg, half-life), the potential for interaction on all evaluated mechanisms would be low (AUCR < 1."( Evaluation of the drug-drug interaction potential of treosulfan using a physiologically-based pharmacokinetic modelling approach.
Balazki, P; Baumgart, J; Beelen, DW; Böhm, S; Hemmelmann, C; Hilger, RA; Martins, FS; Ring, A; Schaller, S, 2022
)
0.72

Compound-Compound Interactions

The safety and efficacy of oral metronomic low-dose treosulfan chemotherapy in combination with the cyclooxygenase-2 (COX-2) inhibitor rofecoxib were assessed in pretreated advanced melanoma patients. The aim of this work is the development of a mechanistic physiologically-based pharmacokinetic (PBPK) model using in vitro to in vivo extrapolation.

ExcerptReferenceRelevance
"The safety and efficacy of oral metronomic low-dose treosulfan chemotherapy in combination with the cyclooxygenase-2 (COX-2) inhibitor rofecoxib as a compound with antiangiogenic potential, a therapeutic regimen optimally targeting endothelial cells instead of tumor cells, were assessed in pretreated advanced melanoma patients."( Metronomic oral low-dose treosulfan chemotherapy combined with cyclooxygenase-2 inhibitor in pretreated advanced melanoma: a pilot study.
Gille, J; Kaufmann, R; Spieth, K, 2003
)
0.32
"In this study we have used a standardised ATP-based tumour chemosensitivity assay (ATP-TCA) to measure the activity of gefitinib alone or in combination with different cytotoxic drugs (cisplatin, gemcitabine, oxaliplatin and treosulfan) against a variety of solid tumours (n = 86), including breast, colorectal, oesophageal and ovarian cancer, carcinoma of unknown primary site, cutaneous and uveal melanoma, non-small cell lung cancer (NSCLC) and sarcoma."( The in vitro effect of gefitinib ('Iressa') alone and in combination with cytotoxic chemotherapy on human solid tumours.
Cree, IA; Di Nicolantonio, F; Glaysher, S; Johnson, P; Knight, LA; Mercer, S; Sharma, S; Whitehouse, P, 2004
)
0.32
" Interestingly, gefitinib had both positive and negative effects when used in combination with different cytotoxics."( The in vitro effect of gefitinib ('Iressa') alone and in combination with cytotoxic chemotherapy on human solid tumours.
Cree, IA; Di Nicolantonio, F; Glaysher, S; Johnson, P; Knight, LA; Mercer, S; Sharma, S; Whitehouse, P, 2004
)
0.32
" Dose-escalated treosulphan (3 x 12 or 3 x 14 g/m2) combined with cyclophosphamide (Cy) was chosen for a new preparative regimen before allogeneic haematopoietic stem cell transplantation in 18 patients (median age 44, range 19-64 years) with haematological malignancies, considered ineligible for other myeloablative preparative regimens."( Dose-escalated treosulphan in combination with cyclophosphamide as a new preparative regimen for allogeneic haematopoietic stem cell transplantation in patients with an increased risk for regimen-related complications.
Basara, N; Baumgart, J; Beelen, DW; Casper, J; Fauser, AA; Freund, M; Hahn, JR; Hertenstein, B; Hilger, RA; Holler, E; Mylius, HA; Pichlmeier, U; Scheulen, ME; Trenschel, R, 2005
)
0.33
" Gastrointestinal toxicity was the dose-limiting factor of Treo in combination with TBI."( Preclinical analysis of treosulfan in combination with total body irradiation as conditioning regimen prior to bone marrow transplantation in rats.
Baumgart, J; Casper, J; Freund, M; Hofmeister-Mielke, N; Pichlmeier, U; Sender, V; Sievert, K; Teifke, JP; Vogel, H; Wolff, D, 2009
)
0.35
" This study evaluates the toxicity of escalating doses of topotecan alone or in combination with thiotepa or treosulfan."( Escalating topotecan in combination with treosulfan has acceptable toxicity in advanced pediatric sarcomas.
Bauer, F; Burdach, S; Filipiak-Pittroff, B; von Luettichau, I; Wawer, A, 2013
)
0.39
" We therefore investigated the antiproliferative effects of nilotinib in combination with drugs that are usually used for conditioning: the alkylating agents mafosfamide, treosulfan, and busulfan."( In vitro testing of drug combinations employing nilotinib and alkylating agents with regard to pretransplant conditioning treatment of advanced-phase chronic myeloid leukemia.
Dreger, P; Fruehauf, S; Ho, AD; Jens Zeller, W; Luft, T; Radujkovic, A; Topaly, J, 2014
)
0.4
"Treatment of imatinib-sensitive, BCR-ABL-positive K562 and LAMA84 cells with nilotinib in combination with mafosfamide, treosulfan, or busulfan resulted in synergistic (CI < 1), additive (CI ~ 1), and predominantly antagonistic (CI > 1) effects, respectively."( In vitro testing of drug combinations employing nilotinib and alkylating agents with regard to pretransplant conditioning treatment of advanced-phase chronic myeloid leukemia.
Dreger, P; Fruehauf, S; Ho, AD; Jens Zeller, W; Luft, T; Radujkovic, A; Topaly, J, 2014
)
0.4
" Additional drugs reported in combination with the Treo-Flu backbone are thiotepa and melphalan."( Treosulfan in combination with fludarabine as part of conditioning treatment prior to allogeneic hematopoietic stem cell transplantation.
Ussowicz, M, 2020
)
0.56
"The aim of this work is the development of a mechanistic physiologically-based pharmacokinetic (PBPK) model using in vitro to in vivo extrapolation to conduct a drug-drug interaction (DDI) assessment of treosulfan against two cytochrome p450 (CYP) isoenzymes and P-glycoprotein (P-gp) substrates."( Evaluation of the drug-drug interaction potential of treosulfan using a physiologically-based pharmacokinetic modelling approach.
Balazki, P; Baumgart, J; Beelen, DW; Böhm, S; Hemmelmann, C; Hilger, RA; Martins, FS; Ring, A; Schaller, S, 2022
)
0.72

Bioavailability

The high and relatively constant bioavailability of treosulfan indicates that capsules provide a satisfactory noninvasive treatment alternative.

ExcerptReferenceRelevance
" In a pharmacologic study of the bioavailability of treosulfan in a capsule formulation, patients with relapsed ovarian carcinoma were treated with alternating doses of oral and intravenous (i."( Investigation of bioavailability and pharmacokinetics of treosulfan capsules in patients with relapsed ovarian cancer.
Baumgart, J; Hilger, RA; Jacek, G; Kredtke, S; Oberhoff, C; Scheulen, ME; Seeber, S, 2000
)
0.31
"The high and relatively constant bioavailability of treosulfan indicates that capsules provide a satisfactory noninvasive treatment alternative."( Investigation of bioavailability and pharmacokinetics of treosulfan capsules in patients with relapsed ovarian cancer.
Baumgart, J; Hilger, RA; Jacek, G; Kredtke, S; Oberhoff, C; Scheulen, ME; Seeber, S, 2000
)
0.31

Dosage Studied

The main objectives were: (i) to establish a mechanistic pharmacokinetic-pharmacodynamic (PKPD) model for the treatment and engraftment effects on neutrophil counts comparing busulfan and treosulfan-based conditioning, and (ii) to explore current dosing schedules with respect to time to HSCT.

ExcerptRelevanceReference
" The probability of developing acute leukemia in this study was not significantly correlated to the total cumulative dosage of Treosulfan."( Acute non-lymphocytic leukemia in patients with ovarian carcinoma following long-term treatment with Treosulfan (= dihydroxybusulfan).
Ernst, P; Ersbøl, J; Hou-Jensen, K; Knudtzon, S; Larsen, MS; Nissen, NI; Pedersen-Bjergaard, J; Rose, C; Sørensen, HM, 1980
)
0.26
" To our knowledge, this is one of the few cases of ROC in which partial remissions using conventionally dosed chemotherapy were achieved repeatedly despite a unfavorable relapse-free interval after high-dose chemotherapy for primary disease."( Individualized long-term chemotherapy for recurrent ovarian cancer after failing high-dose treatment.
Breidenbach, M; Kurbacher, CM; Mallmann, P; Rein, DT, 2002
)
0.31
" Recent data revealed immunosuppressive characteristics and substantial haematopoietic stem cell toxicity after repeated dosing of mice."( Antileukaemic activity of treosulfan in xenografted human acute lymphoblastic leukaemias (ALL).
Baumgart, J; Becker, M; Fichtner, I, 2003
)
0.32
"Lower dosage of total body irradiation (TBI) and chemotherapy in reduced-intensity conditioning (RIC) regimens prior to allogeneic stem cell transplantation have reduced the toxicity of the conditioning and non-relapse mortality."( Intermediate intensity conditioning regimen containing FLAMSA, treosulfan, cyclophosphamide, and ATG for allogeneic stem cell transplantation in elderly patients with relapsed or high-risk acute myeloid leukemia.
Brossart, P; Chemnitz, JM; Hallek, M; Holtick, U; Krause, A; Scheid, C; Shimabukuro-Vornhagen, A; Theurich, S; von Lilienfeld-Toal, M, 2012
)
0.38
" Pharmacokinetic data to optimize treosulfan dosing are scarce in this patient population."( Pharmacokinetics of treosulfan in pediatric patients undergoing hematopoietic stem cell transplantation.
Ackaert, O; Bredius, RG; den Hartigh, J; Guchelaar, HJ; Lankester, AC; Smiers, FJ; Ten Brink, MH; Zwaveling, J, 2014
)
0.4
" Even though dosing and timing might have been the reasons for this failure, it might also be that TREO does not reach the brain in sufficient amount."( Transport of treosulfan and temozolomide across an in-vitro blood-brain barrier model.
Hupert, M; Linz, U; Santiago-Schübel, B; Stab, J; Wagner, S; Wien, S, 2015
)
0.42
"Currently, there is an urgent need to establish the optimal dosing of TREO in conditioning prior to hematopoietic stem cell transplantation, especially in children."( Clinical bioanalysis of treosulfan and its epoxides: The importance of collected blood processing for valid pharmacokinetic results.
Główka, F; Romański, M, 2018
)
0.48
" Of note, the optimal dosing of the prodrug is still unresolved, especially in infants."( Treosulfan Pharmacokinetics and its Variability in Pediatric and Adult Patients Undergoing Conditioning Prior to Hematopoietic Stem Cell Transplantation: Current State of the Art, In-Depth Analysis, and Perspectives.
Główka, FK; Romański, M; Wachowiak, J, 2018
)
0.48
" Conditioning with treosulfan alone at nonmyeloablative dosing (3."( Bone Marrow Transplantation after Nonmyeloablative Treosulfan Conditioning Is Curative in a Murine Model of Sickle Cell Disease.
Devadasan, D; Goldman, FD; Pawlik, KM; Sun, CW; Townes, TM; Westin, ER; Wu, LC, 2018
)
0.48
" A model-based dosing table is presented to target an exposure of 1650 mg*h/L (population median) for different weight and age groups."( Population pharmacokinetics of treosulfan in paediatric patients undergoing hematopoietic stem cell transplantation.
Bertaina, A; Guchelaar, HJ; Lankester, AC; Locatelli, F; Moes, DJAR; van der Stoep, MYEC; Zwaveling, J, 2019
)
0.51
" The main objectives were: (i) to establish a mechanistic pharmacokinetic-pharmacodynamic (PKPD) model for the treatment and engraftment effects on neutrophil counts comparing busulfan and treosulfan-based conditioning, and (ii) to explore current dosing schedules with respect to time to HSCT."( Modelling of neutrophil dynamics in children receiving busulfan or treosulfan for haematopoietic stem cell transplant conditioning.
Chiesa, R; Doncheva, B; Prunty, H; Solans, BP; Standing, JF; Trocóniz, IF; Veys, P, 2020
)
0.56
"25), if concomitantly administered drugs are dosed either 2 hours before or 8 hours after the 2-hour intravenous infusion of treosulfan."( Evaluation of the drug-drug interaction potential of treosulfan using a physiologically-based pharmacokinetic modelling approach.
Balazki, P; Baumgart, J; Beelen, DW; Böhm, S; Hemmelmann, C; Hilger, RA; Martins, FS; Ring, A; Schaller, S, 2022
)
0.72
" Model-informed dosing is recommended for patients under 2 years."( Evaluation of treosulfan cumulative exposure in paediatric patients through population pharmacokinetics and dosing simulations.
Chung, J; Fraser, C; Keogh, SJ; Kohli, S; Lee, S; McLachlan, AJ; Nath, CE; O'Brien, T; Rosser, SPA; Shaw, PJ, 2023
)
0.91
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
methanesulfonate esterAn organosulfonic ester resulting from the formal condensation of methanesulfonic acid with the hydroxy group of an alcohol, phenol, heteroarenol, or enol.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Bioassays (2)

Assay IDTitleYearJournalArticle
AID409958Inhibition of bovine brain MAOA2008Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
AID409960Inhibition of bovine brain MAOB2008Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (269)

TimeframeStudies, This Drug (%)All Drugs %
pre-199017 (6.32)18.7374
1990's19 (7.06)18.2507
2000's77 (28.62)29.6817
2010's101 (37.55)24.3611
2020's55 (20.45)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials67 (23.93%)5.53%
Reviews16 (5.71%)6.00%
Case Studies21 (7.50%)4.05%
Observational5 (1.79%)0.25%
Other171 (61.07%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (37)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Allogeneic Hematopoietic Cell Transplantation for Patients With Non-Malignant Disorders Using Treosulfan, Fludarabine, and Thiotepa [NCT03980769]Phase 240 participants (Anticipated)Interventional2021-05-05Recruiting
Evaluation of Treosulfan Pharmacokinetics (PK) in Children Undergoing Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) [NCT02048800]61 participants (Actual)Observational2014-03-31Completed
Treosulfan and Total-marrow Irradiation (TMI) Based Conditioning With Rapamycin Based Graft vs. Host Disease (GvHD) Prophylaxis for Allogenic Stem Cell Transplantation (Allo-HSCT) in Patients With High-risk Hematological Malignancies [NCT03963024]Phase 19 participants (Actual)Interventional2014-02-12Terminated(stopped due to low rate of enrolment)
A Randomized Phase II Trial Comparing Treosulfan and Melphalan With Melphalan Alone as Conditioning Regimen for Autologous Stem Cell Transplantation (ASCT) in Myeloma Patients (TreoMel Trial) [NCT05636787]Phase 2120 participants (Anticipated)Interventional2023-06-06Recruiting
Hematopoietic Cell Transplantation Using Treosulfan-Based Conditioning for the Treatment of Bone Marrow Failure Diseases [NCT04965597]Phase 240 participants (Anticipated)Interventional2022-04-19Recruiting
Phase II Trial of Fludarabine Combined With Intravenous Treosulfan and Allogeneic Hematopoietic Stem-cell Transplantation in Patients With Lymphatic Malignancies [NCT01079013]Phase 240 participants (Anticipated)Interventional2010-03-31Active, not recruiting
A Phase II Trial of Allogeneic Peripheral Blood Stem Cell Transplantation From Family Haploidentical Donors in Patients With Myelodysplastic Syndrome and Acute Leukemia Under Primary Antifungal Prophylaxis With Posaconazole. [NCT03434704]Phase 210 participants (Actual)Interventional2018-06-18Completed
Phase 3, Open Label, Multi-centre, Randomised Controlled International Study in Ewing Sarcoma [NCT00987636]Phase 3907 participants (Actual)Interventional2009-10-01Completed
Transplantation of Umbilical Cord Blood in Patients With Hematological Malignancies Using a Treosulfan Based Preparative Regimen [NCT00796068]Phase 2130 participants (Actual)Interventional2009-02-24Completed
Clinical Phase II Trial to Evaluate the Safety and Efficacy of Treosulfan Based Conditioning Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Patients With Acute Myeloid Leukaemia [NCT01063660]Phase 275 participants (Actual)Interventional2004-03-31Completed
Clinical Phase II Trial to Evaluate the Safety and Efficacy of Treosulfan Based Conditioning Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Patients With Myelodysplastic Syndrome (MDS) [NCT01062490]Phase 245 participants (Actual)Interventional2004-11-30Completed
A Multi-Center Study of Conditioning With Treosulfan, Fludarabine and Escalating Doses of TBI for Allogeneic Hematopoietic Cell Transplantation in Patients With Acute Myeloid Leukemia (AML) Myelodysplastic Syndrome (MDS), and Acute Lymphoblastic Leukemia [NCT00860574]Phase 296 participants (Actual)Interventional2009-02-28Completed
Clinical Phase III Trial to Compare Treosulfan-based Conditioning Therapy With Busulfan-based Reduced-intensity Conditioning (RIC) Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Patients With AML or MDS Considered Ineligible to Standard C [NCT00822393]Phase 3570 participants (Actual)Interventional2008-11-24Completed
Prospectively Randomized Phase III Study of an Individualized Sensitivity-Directed Combination Chemotherapy Versus DTIC as First-Line Treatment in Stage IV Metastatic Melanoma [NCT00779714]Phase 3360 participants (Anticipated)Interventional2008-10-31Recruiting
Clinical Phase II Trial to Evaluate the Safety and Efficacy of Treosulfan Based Conditioning Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Patients With Haematological Malignancies [NCT00598624]Phase 2175 participants (Anticipated)Interventional2005-09-30Recruiting
An Open-label, Non-randomized, Prospective Trial to Evaluate the Effect of Renal Function Impairment and Race/Ethnicity on Treosulfan Pharmacokinetics in Patients With AML or MDS Undergoing Allogeneic Hematopoietic Stem Cell Transplantation [NCT05534620]Phase 136 participants (Anticipated)Interventional2023-11-30Not yet recruiting
Randomized Phase II Study to Compare a Combination Therapy With Gemcitabine and Treosulfan Versus a Monotherapy as First-Line Chemotherapy for Patients With Metastatic Ocular Melanoma [NCT00168870]Phase 248 participants (Anticipated)Interventional2003-02-28Recruiting
Third-line Therapy of Multiple Myeloma With Lenalidomide in Combination With Pioglitazone, Dexamethasone and Metronomic Low-dose Chemotherapy With Treosulfan [NCT01010243]Phase 1/Phase 254 participants (Anticipated)Interventional2009-10-31Recruiting
Allogeneic Stem Cell Transplantation for Children and Adolescents With Acute Lymphoblastic Leukaemia [NCT01949129]Phase 2/Phase 31,000 participants (Anticipated)Interventional2013-04-30Recruiting
A Phase II Study of Treosulfan/Fludarabine/Low Dose Total Body Irradiation as a Preparative Regimen for Children With AML/MDS Undergoing Allogeneic Hematopoietic Cell Transplantation [NCT01772953]Phase 240 participants (Actual)Interventional2013-09-30Completed
Clinical Phase II Trial to Compare Treosulfan-based Conditioning Therapy With Busulfan-based Conditioning Prior to Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) in Paediatric Patients With Non-malignant Diseases [NCT02349906]Phase 2106 participants (Actual)Interventional2015-04-30Completed
A Prospective Phase II, Randomized Multi-center Trial of a Combined Modularized Treatment With Metronomic Low-dose Treosulfan, Pioglitazone and Clarithromycin Versus Nivolumab in Patients With Squamous Cell Lung Cancer and Non- Squamous Cell Lung Cancer, [NCT02852083]Phase 286 participants (Anticipated)Interventional2016-01-31Recruiting
Hematopoietic Stem Cell Transplantation From Haploidentical Donors in Patients With Hematological Malignancies Using a Treosulfan-Based Preparative Regimen [NCT04195633]Phase 260 participants (Anticipated)Interventional2021-01-25Recruiting
Allogeneic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia [NCT01423500]Phase 3405 participants (Anticipated)Interventional2007-01-31Active, not recruiting
Allogeneic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia [NCT01423747]Phase 3400 participants (Anticipated)Interventional2003-07-31Active, not recruiting
Präferenz-Studie Bei älteren Patientinnen Mit Ovarialkarzinomrezidiv: Treosulfan Oral vs. intravenös [NCT00170690]Phase 3123 participants (Actual)Interventional2004-08-31Completed
Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Advanced Hematological Malignancies After Treosulfan-based Conditioning Therapy - A Clinical Phase II Study [NCT01063647]Phase 1/Phase 256 participants (Actual)Interventional2001-11-30Completed
Phase II Trial of Fludarabine Combined With Intravenous Treosulfan and Allogeneic Hematopoietic Stem-cell Transplantation in Patients With Chemo-refractory or Previously Untreated Acute Myeloid Leukemia and Myelodysplastic Syndrome. [NCT00491634]Phase 224 participants (Anticipated)Interventional2007-06-30Completed
Allogeneic Hematopoietic Cell Transplantation for Patients With Nonmalignant Inherited Disorders Using a Treosulfan Based Preparative Regimen [NCT00919503]Phase 298 participants (Actual)Interventional2009-07-31Completed
A Study of a Reduced-Intensity Conditioning Regimen With Treosulfan and Fludarabine for Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Leukemia [NCT00253513]Phase 1/Phase 260 participants (Actual)Interventional2005-06-30Completed
Unrelated Reduced Intensity Conditioning With Treosulfan® for Allogeneic Stem Cell Transplantation in Patients With Hematological Malignancies [NCT00129155]Phase 230 participants (Anticipated)Interventional2005-02-28Recruiting
A Phase II Randomized Study to Assess Outcomes With Treosulfan-Based Versus Clofarabine-Based Conditioning in Patients With Myelodysplastic Syndromes With Excess Blasts (MDS-EB), or Acute Myeloid Leukemia (AML) Undergoing Allogeneic Hematopoietic Cell Tra [NCT04994808]Phase 280 participants (Anticipated)Interventional2023-08-11Recruiting
Evaluation of Safety and Efficacy of Treosulfan-cytarabine-fludarabine (FLAT) Combination Prior to Autologous Stem Cell Transplant (HSCT) in Elderly Patients With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) [NCT03961919]Phase 215 participants (Actual)Interventional2009-02-10Completed
A Phase II Multicentre, Randomized, Controlled Open-label Study on the Use of Anti-thymocyte Globulin and Rituximab for Immunomodulation of Graft-versus-host Disease in Allogeneic Matched Transplants for Non Malignancies [NCT01810926]Phase 2130 participants (Anticipated)Interventional2011-09-30Recruiting
Clinical Open-label Phase 2 Study of Low Dose Treosulfan Based Conditioning Regimen Efficacy in Hematopoietic Stem Cell Transplantation for Children With Nijmegen Breakage Syndrome [NCT04400045]Phase 210 participants (Anticipated)Interventional2020-05-22Recruiting
Clinical Phase II Trial to Describe the Safety and Efficacy of Treosulfan-based Conditioning Therapy Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Paediatric Patients With Haematological Malignancies [NCT02333058]Phase 270 participants (Actual)Interventional2014-11-21Completed
A Randomized Phase II Study of Treosulfan, Fludarabine and Low-Dose TBI as Conditioning for Allogeneic Hematopoietic Cell Transplantation in Patients With Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) [NCT01894477]Phase 2102 participants (Actual)Interventional2013-11-30Active, not recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00253513 (4) [back to overview]Incidence (Percent of Participants) With Nonrelapse Mortality (NRM) by Day 200 (Secondary Phase Only)
NCT00253513 (4) [back to overview]Number of Subjects Who Are Without Disease at One Year as Indicator of Disease Free Survival.
NCT00253513 (4) [back to overview]Number of Patients Experiencing Graft Failure
NCT00253513 (4) [back to overview]Number of Patients Experiencing Regimen-related Toxicity Events in Study Population
NCT00796068 (12) [back to overview]Duration (Days) Until Participants Obtained Platelet Engraftment
NCT00796068 (12) [back to overview]Incidence of Acute or Chronic Graft-versus-host Disease (GVHD)
NCT00796068 (12) [back to overview]Incidence of Clinically Significant Infections
NCT00796068 (12) [back to overview]Incidence of Relapse or Disease Progression
NCT00796068 (12) [back to overview]Non-relapse Mortality
NCT00796068 (12) [back to overview]Number of Participants Surviving by 1 Year
NCT00796068 (12) [back to overview]Number of Participants Surviving up to 2 Years Without Disease Progression
NCT00796068 (12) [back to overview]Number of Participants With Acute Graft-versus-host Disease (GVHD) Grade II-IV by Day 100
NCT00796068 (12) [back to overview]Number of Participants With Graft Failure/Rejection
NCT00796068 (12) [back to overview]Number of Participants With Secondary Graft Failure
NCT00796068 (12) [back to overview]Number of Patients With Non-relapse Mortality (NRM)
NCT00796068 (12) [back to overview]The Number of Participants Alive at Two-years Follow up.
NCT00860574 (8) [back to overview]Non Relapse Mortality Incidence
NCT00860574 (8) [back to overview]Overall Survival (OS)
NCT00860574 (8) [back to overview]Relapse Incidence
NCT00860574 (8) [back to overview]Relapse-free Survival
NCT00860574 (8) [back to overview]Incidence of Chronic GVHD
NCT00860574 (8) [back to overview]Incidence of Grades II-IV Acute GVHD
NCT00860574 (8) [back to overview]Median Donor CD3 + T Lymphocyte Chimerism in Peripheral Blood
NCT00860574 (8) [back to overview]Non Relapse Mortality (NRM) Incidence
NCT00919503 (10) [back to overview]Number of Patients With Grade II-IV Acute Graft-versus-host Disease
NCT00919503 (10) [back to overview]Number of Patients With of Chronic Graft-versus-host Disease
NCT00919503 (10) [back to overview]Overall Survival
NCT00919503 (10) [back to overview]Preliminary Efficacy
NCT00919503 (10) [back to overview]Donor Chimerism CD3 at 100 Days Post Transplant
NCT00919503 (10) [back to overview]Donor Chimerism CD33 at Day 100 Post Transplant
NCT00919503 (10) [back to overview]Disease Response at One Year Following Hematopoietic Cell Transplantation
NCT00919503 (10) [back to overview]Immune Reconstitution Following Hematopoietic Cell Transplantation
NCT00919503 (10) [back to overview]Non-relapse Mortality
NCT00919503 (10) [back to overview]Number of Participants With Infections
NCT01894477 (2) [back to overview]Number of Participants That Did Not Progress Within 6 Months
NCT01894477 (2) [back to overview]Number of Participants With Acute GVHD, Graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

Incidence (Percent of Participants) With Nonrelapse Mortality (NRM) by Day 200 (Secondary Phase Only)

NRM (Non relapse mortality) - death not attributed to the primary cancer. (NCT00253513)
Timeframe: 200 days

Interventionpercent of participants (Number)
Treosulfan and Fludarabine Conditioning5

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Number of Subjects Who Are Without Disease at One Year as Indicator of Disease Free Survival.

(NCT00253513)
Timeframe: One year

Interventionparticipants (Number)
Treosulfan and Fludarabine Conditioning58

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Number of Patients Experiencing Graft Failure

Graft versus Host Disease (GVHD) is a frequent complication of allogeneic bone marrow transplant in which the engrafted donor cells attacks the patient's organs and tissue. Acute GVHD (aGVHD) usually occurs during the first three months following an allogeneic BMT. Chronic GVHD (cGVHD) usually develops after the third month post-transplant. Patients may experience one, both or neither. (NCT00253513)
Timeframe: 42 days

Interventionparticipants (Number)
acute graft vs. host disease (aGVHD)chronic graft vs. host disease (cGVHD)
Treosulfan and Fludarabine Conditioning3631

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Duration (Days) Until Participants Obtained Platelet Engraftment

Summarized using a range and median of measure in days until participants reached platelet engraftment. Platelet engraftment was defined as the first of 7 consecutive days when the platelet count exceeded 20 x 109/L (untransfused). (NCT00796068)
Timeframe: At 6 months

Interventiondays (Median)
Arm I (Low Risk for Graft Failure)31
Arm II (High Risk for Graft Failure)31

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Incidence of Acute or Chronic Graft-versus-host Disease (GVHD)

Overall GVHD is determined based on the organ stage, response to treatment and whether GVHD was a major cause of death. Chronic GVHD will be defined according to the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease. Described as mild, moderate, or severe as graded according to the attached Organ Scoring Sheet. Symptoms consistent with both chronic and acute GVHD occurring after day 100 will be considered overlap chronic GVHD syndrome. (NCT00796068)
Timeframe: At 1 year

InterventionParticipants (Count of Participants)
Arm I (Low Risk for Graft Failure)7
Arm II (High Risk for Graft Failure)6

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Incidence of Clinically Significant Infections

Collected and graded according to the modified National Cancer Institute Common Toxicity Criteria. (NCT00796068)
Timeframe: At 6 months

InterventionParticipants (Count of Participants)
Arm I (Low Risk for Graft Failure)53
Arm II (High Risk for Graft Failure)61

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Incidence of Relapse or Disease Progression

Cumulative incidence estimates using non-relapse mortality as competitive event. (NCT00796068)
Timeframe: Up to 2 years

InterventionParticipants (Count of Participants)
Arm I (Low Risk for Graft Failure)17
Arm II (High Risk for Graft Failure)11

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Non-relapse Mortality

Death of any cause other than relapse or disease progression was considered. (NCT00796068)
Timeframe: Up to 2 years

InterventionParticipants (Count of Participants)
Arm I (Low Risk for Graft Failure)8
Arm II (High Risk for Graft Failure)10

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Number of Participants Surviving by 1 Year

Overall survival was measured from the first day of CBT infusion until death from any cause. (NCT00796068)
Timeframe: At 1 year

InterventionParticipants (Count of Participants)
Arm I (Low Risk for Graft Failure)51
Arm II (High Risk for Graft Failure)47

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Number of Participants Surviving up to 2 Years Without Disease Progression

Progression-free survival is the time interval from start of treatment to documented evidence of disease progression. Disease progression was defined by European LeukemiaNet 2017 criteria and International Working Group (IWG) within 3 years of transplant. (NCT00796068)
Timeframe: Up to 2 years

InterventionParticipants (Count of Participants)
Arm I (Low Risk for Graft Failure)37
Arm II (High Risk for Graft Failure)41

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Number of Participants With Acute Graft-versus-host Disease (GVHD) Grade II-IV by Day 100

Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening. Diagnosing and grading acute GVHD is based on clinical findings (the organ stage, response to treatment and whether GVHD was a major cause of death) and frequently varies between transplant centers and independent reviewers. (NCT00796068)
Timeframe: Day 100

InterventionParticipants (Count of Participants)
Arm I (Low Risk for Graft Failure)36
Arm II (High Risk for Graft Failure)37

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Number of Participants With Graft Failure/Rejection

"Patients will be considered primary graft failure provided they meet any criteria listed below, in the absence of documented disease persistence/recurrence or active bone marrow infection (ex. Cytomegalovirus (CMV)):~i. Absence of 3 consecutive days with neutrophils >500/u1 combined with host CD3+ peripheral blood chimerism ≥50% at day 42 ii. Absence of 3 consecutive days with neutrophils >500/u1 under any circumstances at day 55 iii. Death after day 28 with neutrophil count <100/u1 without any evidence of engraftment (< 5% donor CD3+) iv. Primary autologous count recovery with < 5% donor CD3+ peripheral blood chimerism at count recovery and without relapse" (NCT00796068)
Timeframe: Up to 100 days

InterventionParticipants (Count of Participants)
Arm I (Low Risk for Graft Failure)2
Arm II (High Risk for Graft Failure)5

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Number of Participants With Secondary Graft Failure

Secondary graft failure is defined as decline of neutrophil count to <500/ul with loss of donor chimerism after day 55 (NCT00796068)
Timeframe: Up to 2 years

InterventionParticipants (Count of Participants)
Arm I (Low Risk for Graft Failure)0
Arm II (High Risk for Graft Failure)0

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Number of Patients With Non-relapse Mortality (NRM)

Defined as death from any cause without sign of disease progression or relapse. Loss to follow up are censored, whereas disease relapse or progression are considered competing risks. (NCT00796068)
Timeframe: At day -200

InterventionParticipants (Count of Participants)
Arm I (Low Risk for Graft Failure)7
Arm II (High Risk for Graft Failure)6

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The Number of Participants Alive at Two-years Follow up.

Overall survival of participants after two-years of follow up. (NCT00796068)
Timeframe: Up to 2 years

InterventionParticipants (Count of Participants)
Arm I (Low Risk for Graft Failure)50
Arm II (High Risk for Graft Failure)44

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Non Relapse Mortality Incidence

(NCT00860574)
Timeframe: 1 year after HCT

InterventionParticipants (Count of Participants)
Treatment (Allogeneic Transplantation)6

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Overall Survival (OS)

(NCT00860574)
Timeframe: at 2 years

InterventionParticipants (Count of Participants)
Treatment (Allogeneic Transplantation)71

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Relapse Incidence

(NCT00860574)
Timeframe: At 6 months

InterventionParticipants (Count of Participants)
Treatment (Allogeneic Transplantation)18

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Relapse-free Survival

(NCT00860574)
Timeframe: at 2 years

InterventionParticipants (Count of Participants)
Treatment (Allogeneic Transplantation)62

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Incidence of Chronic GVHD

(NCT00860574)
Timeframe: at 6 months

InterventionParticipants (Count of Participants)
Treatment (Allogeneic Transplantation)20

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Incidence of Grades II-IV Acute GVHD

(NCT00860574)
Timeframe: at 6 months

InterventionParticipants (Count of Participants)
Treatment (Allogeneic Transplantation)57

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Median Donor CD3 + T Lymphocyte Chimerism in Peripheral Blood

Donor chimerism was evaluated in peripheral blood T cells (NCT00860574)
Timeframe: Day 28 after HCT

Interventionpercentage of T cells (Median)
Treatment (Allogeneic Transplantation)100

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Non Relapse Mortality (NRM) Incidence

Cumulative incidence of NRM at 6 months. NRM includes all deaths without relapse or disease progression. (NCT00860574)
Timeframe: At 6 months

InterventionParticipants (Count of Participants)
Treatment (Allogeneic Transplantation)6

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Number of Patients With Grade II-IV Acute Graft-versus-host Disease

Number of patients diagnosed with overall grade II-IV acute GVHD by Day 100 post transplant (NCT00919503)
Timeframe: Day 100 post transplant

InterventionParticipants (Count of Participants)
Regimen A (PBSCT and BMT)44
Regimen B (UBCT)8

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Number of Patients With of Chronic Graft-versus-host Disease

Number of patients diagnosed with chronic GVHD and requiring systemic immunosuppression within 1 year following transplant (NCT00919503)
Timeframe: 1 year following transplant

InterventionParticipants (Count of Participants)
Regimen A (PBSCT and BMT)29
Regimen B (UBCT)5

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Overall Survival

Number of patients alive at 1 year following transplant (NCT00919503)
Timeframe: 1 year following transplant

InterventionParticipants (Count of Participants)
Regimen A (PBSCT and BMT)80
Regimen B (UBCT)9

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Preliminary Efficacy

Number of patients engrafted (>5% donor CD3+ peripheral blood chimerisms) at 1 year following transplant (NCT00919503)
Timeframe: 1 year following transplant

InterventionParticipants (Count of Participants)
Regimen A (PBSCT and BMT)83
Regimen B (UBCT)10

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Donor Chimerism CD3 at 100 Days Post Transplant

Number of patients with peripheral blood donor chimerism for CD3 less than 5%, 5-49%, 50-94% and greater than or equal to 95% at 100 days post transplant. (NCT00919503)
Timeframe: Day 100 post transplant

,
InterventionParticipants (Count of Participants)
Greater than equal to 95%50 - 94%5-49%Less than 5%
Regimen A (PBSCT and BMT)492960
Regimen B (UBCT)7211

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Donor Chimerism CD33 at Day 100 Post Transplant

Number of patients with peripheral blood donor chimerism for CD33 less than 5%, 5-49%, 50-94% and greater than or equal to 95% at 100 days post transplant. (NCT00919503)
Timeframe: 100 days post transplant

,
InterventionParticipants (Count of Participants)
Greater than equal to 95%50-94%5-49%Less than 5%
Regimen A (PBSCT and BMT)72840
Regimen B (UBCT)7221

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Disease Response at One Year Following Hematopoietic Cell Transplantation

Number of patients with no evidence of disease at one year following transplant (NCT00919503)
Timeframe: 1 year following transplant

InterventionParticipants (Count of Participants)
Regimen A (PBSCT and BMT)78
Regimen B (UBCT)8

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Immune Reconstitution Following Hematopoietic Cell Transplantation

Number of patients with immune reconstitution (defined by a normal range CD3) at 1 year post transplant (NCT00919503)
Timeframe: 1 year following transplant

InterventionParticipants (Count of Participants)
Regimen A (PBSCT and BMT)39
Regimen B (UBCT)4

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Non-relapse Mortality

Number of patients who experienced non-relapse mortality by 1 year following transplant (NCT00919503)
Timeframe: 1 year following transplant

InterventionParticipants (Count of Participants)
Regimen A (PBSCT and BMT)2
Regimen B (UBCT)5

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Number of Participants With Infections

Number of participants with clinically significant infections (bacterial, fungal, viral) requiring treatment within 100 days following transplant (NCT00919503)
Timeframe: 100 days post transplant

InterventionParticipants (Count of Participants)
Regimen A (PBSCT and BMT)57
Regimen B (UBCT)9

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Number of Participants That Did Not Progress Within 6 Months

Progression is defined as relapse (NCT01894477)
Timeframe: At 6 months post-transplant

InterventionParticipants (Count of Participants)
Arm A (Treosulfan, Fludarabine Phosphate)20
Arm B (Treosulfan, Fludarabine Phosphate, TBI)48

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Number of Participants With Acute GVHD, Graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

(NCT01894477)
Timeframe: Up to 84 days

InterventionParticipants (Count of Participants)
Arm A (Treosulfan, Fludarabine Phosphate)29
Arm B (Treosulfan, Fludarabine Phosphate, TBI)50

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