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


Journal

Bone marrow transplantation
ISSN: 1476-5365
Titre abrégé: Bone Marrow Transplant
Pays: England
ID NLM: 8702459

Informations de publication

Date de publication:
10 2020
Historique:
received: 23 07 2019
accepted: 10 03 2020
revised: 04 03 2020
pubmed: 24 3 2020
medline: 25 5 2021
entrez: 24 3 2020
Statut: ppublish

Résumé

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

Identifiants

pubmed: 32203268
doi: 10.1038/s41409-020-0869-6
pii: 10.1038/s41409-020-0869-6
pmc: PMC7515850
doi:

Substances chimiques

Thiotepa 905Z5W3GKH
treosulfan CO61ER3EPI
Vidarabine FA2DM6879K
Busulfan G1LN9045DK
fludarabine P2K93U8740

Banques de données

EudraCT
['2013–003604–39']
ClinicalTrials.gov
['NCT02333058']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1996-2007

Références

Niemeyer CM, Kratz CP. Paediatric myelodysplastic syndromes and juvenile myelomonocytic leukaemia: molecular classification and treatment options. Br J Haematol. 2008;140:610–24. https://doi.org/10.1111/j.1365-2141.2007.06958.x.
doi: 10.1111/j.1365-2141.2007.06958.x. pubmed: 18302710
Peters C, Schrappe M, Stackelberg A, von Schrauder A, Bader P, Ebell W, et al. Stem-cell transplantation in children with acute lymphoblastic leukemia: a prospective international multicenter trial comparing sibling donors with matched unrelated donors-The ALL-SCT-BFM-2003 trial. J Clin Oncol. 2015;33:1265–74. https://doi.org/10.1200/JCO.2014.58.9747.
doi: 10.1200/JCO.2014.58.9747.
Beier R, Albert MH, Bader P, Borkhardt A, Creutzig U, Eyrich M, et al. Allo-SCT using BU, CY and melphalan for children with AML in second CR. Bone Marrow Transplant. 2013;48:651–6. https://doi.org/10.1038/bmt.2012.204.
doi: 10.1038/bmt.2012.204. pubmed: 23103678
Balduzzi A, Valsecchi MG, Silvestri D, Locatelli F, Manfredini L, Busca A, et al. Transplant-related toxicity and mortality: an AIEOP prospective study in 636 pediatric patients transplanted for acute leukemia. Bone Marrow Transplant. 2002;29:93–100. https://doi.org/10.1038/sj.bmt.1703337.
doi: 10.1038/sj.bmt.1703337. pubmed: 11850701
Bresters D, van Gils ICM, Kollen WJW, Ball LM, Oostdijk W, van der Bom JG, et al. High burden of late effects after haematopoietic stem cell transplantation in childhood: a single-centre study. Bone Marrow Transplant. 2010;45:79–85. https://doi.org/10.1038/bmt.2009.92.
doi: 10.1038/bmt.2009.92.
Shimoni A, Labopin M, Savani B, Hamladji R-M, Beelen D, Mufti G, et al. Intravenous busulfan compared with treosulfan-based conditioning for allogeneic stem cell transplantation in acute myeloid leukemia: a study on behalf of the acute leukemia working party of european society for blood and marrow transplantation. Biol Blood Marrow Transplant. 2018;24:751–7. https://doi.org/10.1016/j.bbmt.2017.12.776.
doi: 10.1016/j.bbmt.2017.12.776. pubmed: 29247780
Nagler A, Labopin M, Beelen D, Ciceri F, Volin L, Shimoni A, et al. Long-term outcome after a treosulfan-based conditioning regimen for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Cancer. 2017;123:2671–9. https://doi.org/10.1002/cncr.30646.
doi: 10.1002/cncr.30646. pubmed: 28329410
Ruutu T, Volin L, Beelen DW, Trenschel R, Finke J, Schnitzler M, et al. 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. Haematologica. 2011;96:1344–50. https://doi.org/10.3324/haematol.2011.043810.
doi: 10.3324/haematol.2011.043810. pubmed: 21659356 pmcid: 3166105
Kröger N, Bornhäuser M, Stelljes M, Pichlmeier U, Trenschel R, Schmid C, et al. Allogeneic stem cell transplantation after conditioning with treosulfan, etoposide and cyclophosphamide for patients with ALL: a phase II-study on behalf of the German Cooperative Transplant Study Group and ALL Study Group (GMALL). Bone Marrow Transplant. 2015;50:1503–7. https://doi.org/10.1038/bmt.2015.202.
doi: 10.1038/bmt.2015.202. pubmed: 26367236
Casper J, Knauf W, Kiefer T, Wolff D, Steiner B, Hammer U, et al. Treosulfan and fludarabine: a new toxicity-reduced conditioning regimen for allogeneic hematopoietic stem cell transplantation. Blood. 2004;103:725–31. https://doi.org/10.1182/blood-2002-11-3615.
doi: 10.1182/blood-2002-11-3615. pubmed: 12947008
Beelen DW, Trenschel R, Stelljes M, Groth C, Masszi T, Reményi P, et al. 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. Lancet Haematol. 2019:e28–39. https://doi.org/10.1016/S2352-3026(19)30157-7 .
Slatter MA, Rao K, Abd Hamid IJ, Nademi Z, Chiesa R, Elfeky R, et al. Treosulfan and fludarabine conditioning for hematopoietic stem cell transplantation in children with primary immunodeficiency: UK experience. Biol Blood Marrow Transplant. 2018;24:529–36. https://doi.org/10.1016/j.bbmt.2017.11.009.
doi: 10.1016/j.bbmt.2017.11.009. pubmed: 29155317
Burroughs LM, Shimamura A, Talano J-A, Domm JA, Baker KK, Delaney C, et al. Allogeneic hematopoietic cell transplantation using treosulfan-based conditioning for treatment of marrow failure disorders. Biol Blood Marrow Transplant. 2017;23:1669–77. https://doi.org/10.1016/j.bbmt.2017.06.002.
doi: 10.1016/j.bbmt.2017.06.002. pubmed: 28602958 pmcid: 5605451
Marzollo A, Calore E, Tumino M, Pillon M, Gazzola MV, Destro R, et al. Treosulfan-based conditioning regimen in sibling and alternative donor hematopoietic stem cell transplantation for children with sickle cell disease. Mediterr J Hematol Infect Dis. 2017;9:e2017014. https://doi.org/10.4084/MJHID.2017.014.
doi: 10.4084/MJHID.2017.014. pubmed: 28293402 pmcid: 5333731
Morillo-Gutierrez B, Beier R, Rao K, Burroughs L, Schulz A, Ewins A-M, et al. Treosulfan-based conditioning for allogeneic HSCT in children with chronic granulomatous disease: a multicenter experience. Blood. 2016;128:440–8. https://doi.org/10.1182/blood-2016-03-704015.
doi: 10.1182/blood-2016-03-704015. pubmed: 27216217 pmcid: 4957165
Slatter MA, Boztug H, Pötschger U, Sykora K-W, Lankester A, Yaniv I, et al. Treosulfan-based conditioning regimens for allogeneic haematopoietic stem cell transplantation in children with non-malignant diseases. Bone Marrow Transplant. 2015;50:1536–41. https://doi.org/10.1038/bmt.2015.171.
doi: 10.1038/bmt.2015.171. pubmed: 26259076
Strocchio L, Zecca M, Comoli P, Mina T, Giorgiani G, Giraldi E, et al. Treosulfan-based conditioning regimen for allogeneic haematopoietic stem cell transplantation in children with sickle cell disease. Br J Haematol. 2015;169:726–36. https://doi.org/10.1111/bjh.13352.
doi: 10.1111/bjh.13352. pubmed: 25818248
Dinur-Schejter Y, Krauss AC, Erlich O, Gorelik N, Yahel A, Porat I, et al. Bone marrow transplantation for non-malignant diseases using treosulfan-based conditioning. Pediatr Blood Cancer. 2015;62:299–304. https://doi.org/10.1002/pbc.25267.
doi: 10.1002/pbc.25267. pubmed: 25284797
Maschan M, Shelikhova L, Ilushina M, Kurnikova E, Boyakova E, Balashov D, et al. TCR-alpha/beta and CD19 depletion and treosulfan-based conditioning regimen in unrelated and haploidentical transplantation in children with acute myeloid leukemia. Bone Marrow Transplant. 2016;51:668–74. https://doi.org/10.1038/bmt.2015.343.
doi: 10.1038/bmt.2015.343. pubmed: 26808573
Boztug H, Sykora K-W, Slatter M, Zecca M, Veys P, Lankester A, et al. European Society for blood and marrow transplantation analysis of treosulfan conditioning before hematopoietic stem cell transplantation in children and adolescents with hematological malignancies. Pediatr Blood Cancer. 2016;63:139–48. https://doi.org/10.1002/pbc.25764.
doi: 10.1002/pbc.25764. pubmed: 26398915
Bernardo ME, Piras E, Vacca A, Giorgiani G, Zecca M, Bertaina A, et al. Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan. Blood. 2012;120:473–6. https://doi.org/10.1182/blood-2012-04-423822.
doi: 10.1182/blood-2012-04-423822. pubmed: 22645178
van der Stoep MYEC, Bertaina A, Brink MHten, Bredius RG, Smiers FJ, Wanders DCM, et al. High interpatient variability of treosulfan exposure is associated with early toxicity in paediatric HSCT: a prospective multicentre study. Br J Haematol. 2017;179:772–80. https://doi.org/10.1111/bjh.14960.
doi: 10.1111/bjh.14960. pubmed: 29048102
Romański M, Wachowiak J, Główka FK. 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. Clin Pharmacokinet. 2018;57:1255–65. https://doi.org/10.1007/s40262-018-0647-4.
doi: 10.1007/s40262-018-0647-4. pubmed: 29557088 pmcid: 6132445
Chiesa R, Standing JF, Winter R, Nademi Z, Chu J, Pinner D, et al. Proposed therapeutic range of treosulfan in reduced toxicity pediatric allogeneic hematopoietic stem cell transplant conditioning: results from a prospective trial. Clin Pharmacol Ther. 2019. https://doi.org/10.1002/cpt.1715 .
van der Stoep MYEC, Zwaveling J, Bertaina A, Locatelli F, Guchelaar HJ, Lankester AC, et al. Population pharmacokinetics of treosulfan in paediatric patients undergoing hematopoietic stem cell transplantation. Br J Clin Pharm. 2019;85:2033–44. https://doi.org/10.1111/bcp.13995.
doi: 10.1111/bcp.13995.
Reijmers T, Hemmelmann C, Sykora K-W, Vora A, Kehne J, Möller A-K, et al. Population PK-modelling of treosulfan in paediatric allogeneic transplant patients. Twenty-seventh Annual Meeting of the Population Approach Group in Europe (page), Montreux; 2018.
McCurdy SR, Kasamon YL, Kanakry CG, Bolaños-Meade J, Tsai H-L, Showel MM, et al. Comparable composite endpoints after HLA-matched and HLA-haploidentical transplantation with post-transplantation cyclophosphamide. Haematologica. 2017;102:391–400. https://doi.org/10.3324/haematol.2016.144139.
doi: 10.3324/haematol.2016.144139. pubmed: 5286947 pmcid: 5286947
Jones RJ, Lee KS, Beschorner WE, Vogel VG, Grochow LB, Braine HG, et al. Venoocclusive disease of the liver following bone marrow transplantation. Transplantation. 1987;44:778–83.
doi: 10.1097/00007890-198712000-00011
Bearman SI, Appelbaum FR, Buckner CD, Petersen FB, Fisher LD, Clift RA, et al. Regimen-related toxicity in patients undergoing bone marrow transplantation. J Clin Oncol. 1988;6:1562–8. https://doi.org/10.1200/JCO.1988.6.10.1562.
doi: 10.1200/JCO.1988.6.10.1562.
Maiolica A, Meunier L, Bialleck S, Guhde I, Wood S, Struwe P. Bioanalytical determination of treosulfan and its active metabolites. EBF 7th Open Meeting, Barcilona; 2014.
Nemecek ER, Hilger RA, Adams A, Shaw BE, Kiefer D, Le-Rademacher J, et al. Treosulfan, fludarabine, and low-dose total body irradiation for children and young adults with acute myeloid leukemia or myelodysplastic syndrome undergoing allogeneic hematopoietic cell transplantation: prospective phase II trial of the pediatric blood and marrow transplant consortium. Biol Blood Marrow Transplant. 2018;24:1651–6. https://doi.org/10.1016/j.bbmt.2018.04.025.
doi: 10.1016/j.bbmt.2018.04.025. pubmed: 29753157 pmcid: 6108922
Locatelli F, Nöllke P, Zecca M, Korthof E, Lanino E, Peters C, et al. Hematopoietic stem cell transplantation (HSCT) in children with juvenile myelomonocytic leukemia (JMML): results of the EWOG-MDS/EBMT trial. Blood. 2005;105:410–9. https://doi.org/10.1182/blood-2004-05-1944.
doi: 10.1182/blood-2004-05-1944. pubmed: 15353481
Lucchini G, Labopin M, Beohou E, Dalissier A, Dalle JH, Cornish J, et al. Impact of conditioning regimen on outcomes for children with acute myeloid leukemia undergoing transplantation in first complete remission. An analysis on behalf of the pediatric disease working party of the European Group for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2017;23:467–74. https://doi.org/10.1016/j.bbmt.2016.11.022.
doi: 10.1016/j.bbmt.2016.11.022. pubmed: 27916512
Strahm B, Nöllke P, Zecca M, Korthof ET, Bierings M, Furlan I, et al. Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome in children: results of the EWOG-MDS 98 study. Leukemia. 2011;25:455–62. https://doi.org/10.1038/leu.2010.297.
doi: 10.1038/leu.2010.297. pubmed: 21212791
Bartelink IH, van Reij EML, Gerhardt CE, van Maarseveen EM, Wildt A, de, Versluys B, et al. Fludarabine and exposure-targeted busulfan compares favorably with busulfan/cyclophosphamide-based regimens in pediatric hematopoietic cell transplantation: maintaining efficacy with less toxicity. Biol Blood Marrow Transplant. 2014;20:345–53. https://doi.org/10.1016/j.bbmt.2013.11.027.
doi: 10.1016/j.bbmt.2013.11.027. pubmed: 24315842
European Medicines Agency. Union register of medicinal products: marketing authorisation. Decision number (2019)4858 of 20 Jun 2019. 2019. https://ec.europa.eu/health/documents/community-register/html/h1351.htm .

Auteurs

Krzysztof Kalwak (K)

Department of Pediatric Hematology, Oncology and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland. krzysztof.kalwak@gmail.com.

Monika Mielcarek (M)

Department of Pediatric Hematology, Oncology and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland.

Katharine Patrick (K)

Sheffield Children's Hospital, Sheffield, UK.

Jan Styczynski (J)

Department of Pediatric Hematology and Oncology, Collegium Medicum UMK Torun, Bydgoszcz, Poland.

Peter Bader (P)

Department for Children and Adolescents, Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, Goethe University, Frankfurt, Germany.

Selim Corbacioglu (S)

University Hospital of Regensburg, Regensburg, Germany.

Birgit Burkhardt (B)

Department of Pediatric Hematology, Oncology and BMT, University Hospital Muenster, Muenster, Germany.

Karl Walter Sykora (KW)

Department of Pediatrics, Hannover Medical School, Hannover, Germany.

Katarzyna Drabko (K)

Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, Lublin, Poland.

Jolanta Gozdzik (J)

Medical College, University Children's Hospital in Cracow Jagiellonian University, Cracow, Poland.

Franca Fagioli (F)

Children's Hospital Regina Margherita, University of Turin, Turin, Italy.

Johann Greil (J)

University Children's Hospital Heidelberg, Heidelberg, Germany.

Bernd Gruhn (B)

Department of Pediatrics, Jena University Hospital, Jena, Germany.

Rita Beier (R)

Depertment of Pediatrics III, University Hospital of Essen, Essen, Germany.

Franco Locatelli (F)

IRCCS Bambino Gesú Children's Hospital, Sapienza University of Rome, Rome, Italy.

Ingo Müller (I)

University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Paul Gerhardt Schlegel (PG)

University Children's Hospital of Wuerzburg, Wuerzburg, Germany.

Petr Sedlacek (P)

Department of Pediatric Hematology and Oncology, University Hospital Motol, Prague, Czech Republic.

Klaus Daniel Stachel (KD)

Children's Hospital, University of Erlangen, Erlangen, Germany.

Claudia Hemmelmann (C)

medac GmbH, Wedel, Germany.

Ann-Kristin Möller (AK)

medac GmbH, Wedel, Germany.

Joachim Baumgart (J)

medac GmbH, Wedel, Germany.

Ajay Vora (A)

Great Ormond Street Hospital, London, UK.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH