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Sequential Conditioning with Thiotepa in T Cell- Replete Hematopoietic Stem Cell Transplantation for the Treatment of Refractory Hematologic Malignancies: Comparison with Matched Related, Haplo-Mismatched, and Unrelated Donors.
Biol Blood Marrow Transplant. 2018 05; 24(5):1013-1021.BB

Abstract

The results of conventional allogeneic stem cell transplantation (SCT) in refractory hematologic malignancies are poor. Sequential strategies have shown promising results in refractory acute myelogenous leukemia (AML), but have not been validated in a haploidentical (Haplo) transplant setting. We have developed a new sequential approach combining chemotherapy with broad antitumor activity (thiotepa 10 mg/kg, etoposide 400 mg/m2, and cyclophosphamide 1600 mg/m2 from day -15 to day -10), followed after 3 days of rest by a reduced-intensity conditioning regimen (fludarabine 150 mg/m2, i.v. busulfan 6.4 mg/kg, and thymoglobulin 5 mg/kg from day -6 to day -2). High-dose post-transplantation cyclophosphamide was added in cases with Haplo donors. Seventy-two patients (median age, 54 years) with a refractory hematologic malignancy (44 with acute myelogenous leukemia, 7 with acute lymphoblastic leukemia, 15 with myelodysplastic syndrome/myeloproliferative neoplasms, and 6 with lymphomas) were included in this retrospective multicenter study. Donors were Haplo (n = 27), matched related (MRD; n = 16), and unrelated (UD; n = 29). With a median follow-up of 21 months, the 2-year overall survival (OS) and event-free survival (EFS) were 54.7% and 49.3%, respectively, in recipients of Haplo transplants, 49.2% and 43.8%, respectively, in recipients of MRD transplants, and 37.9% and 28%, respectively, in recipients of UD transplants. Compared with UD, the outcomes were improved in Haplo in terms of the incidences of acute grade II-IV graft-versus-host disease (GVHD) (11.1% versus 41.4%; P < .001) and GVHD-free, relapse-free survival (44.4 versus 10.3%; P = .022). These results support the safety and efficacy of a thiotepa-based sequential approach in allogeneic SCT with a Haplo donor with post-transplantation immune modulation. Thus, in patients with refractory hematologic malignancies, there seems to be no benefit in searching for a UD when a Haplo donor is readily available.

Authors+Show Affiliations

Department of Hematology and Cellular Therapy, Saint Antoine Hospital, AP-HP, Paris, France; UMRS 938, Inserm, Paris, France; Université Pierre et Marie Curie Paris VI, Sorbonne University, Paris, France.Department of Hematology, Henri Becquerel Center, Rouen, France.Department of Hematology, Caen University Hospital, Caen, France.Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut, Beirut, Lebanon.Department of Hematology, Angers University Hospital, Angers, France.Department of Hematology, University Hospital of Montpellier, Montpellier, France.Department of Hematology and Cellular Therapy, Saint Antoine Hospital, AP-HP, Paris, France; Université Pierre et Marie Curie Paris VI, Sorbonne University, Paris, France.Department of Hematology and Cellular Therapy, Saint Antoine Hospital, AP-HP, Paris, France.Department of Hematology and Cellular Therapy, Saint Antoine Hospital, AP-HP, Paris, France; UMRS 938, Inserm, Paris, France; Université Pierre et Marie Curie Paris VI, Sorbonne University, Paris, France.Department of Hematology and Cellular Therapy, Saint Antoine Hospital, AP-HP, Paris, France; Department of Hematology and Marrow Transplantation, Federico II University, Naples, Italy.Department of Hematology and Cellular Therapy, Saint Antoine Hospital, AP-HP, Paris, France; UMRS 938, Inserm, Paris, France; Université Pierre et Marie Curie Paris VI, Sorbonne University, Paris, France.Department of Hematology and Cellular Therapy, Saint Antoine Hospital, AP-HP, Paris, France.Department of Hematology and Cellular Therapy, Saint Antoine Hospital, AP-HP, Paris, France.Department of Hematology and Cellular Therapy, Saint Antoine Hospital, AP-HP, Paris, France.Department of Hematology and Cellular Therapy, Saint Antoine Hospital, AP-HP, Paris, France; UMRS 938, Inserm, Paris, France; Université Pierre et Marie Curie Paris VI, Sorbonne University, Paris, France; Department of Biological Hematology, Saint Antoine and Armand-Trousseau Hospitals, AP-HP, Paris, France.Department of Hematology, Caen University Hospital, Caen, France.Department of Hematology and Cellular Therapy, Saint Antoine Hospital, AP-HP, Paris, France; UMRS 938, Inserm, Paris, France; Université Pierre et Marie Curie Paris VI, Sorbonne University, Paris, France.Department of Hematology and Cellular Therapy, Saint Antoine Hospital, AP-HP, Paris, France; UMRS 938, Inserm, Paris, France; Université Pierre et Marie Curie Paris VI, Sorbonne University, Paris, France; Paris Study Office/CEREST-TC, European Group for Blood and Marrow Transplantation, Paris, France.Department of Hematology and Cellular Therapy, Saint Antoine Hospital, AP-HP, Paris, France.Department of Hematology and Cellular Therapy, Saint Antoine Hospital, AP-HP, Paris, France; UMRS 938, Inserm, Paris, France; Université Pierre et Marie Curie Paris VI, Sorbonne University, Paris, France. Electronic address: mohamad.mohty@inserm.fr.

Pub Type(s)

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

Language

eng

PubMed ID

29337223

Citation

Duléry, Rémy, et al. "Sequential Conditioning With Thiotepa in T Cell- Replete Hematopoietic Stem Cell Transplantation for the Treatment of Refractory Hematologic Malignancies: Comparison With Matched Related, Haplo-Mismatched, and Unrelated Donors." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 24, no. 5, 2018, pp. 1013-1021.
Duléry R, Ménard AL, Chantepie S, et al. Sequential Conditioning with Thiotepa in T Cell- Replete Hematopoietic Stem Cell Transplantation for the Treatment of Refractory Hematologic Malignancies: Comparison with Matched Related, Haplo-Mismatched, and Unrelated Donors. Biol Blood Marrow Transplant. 2018;24(5):1013-1021.
Duléry, R., Ménard, A. L., Chantepie, S., El-Cheikh, J., François, S., Delage, J., Giannotti, F., Ruggeri, A., Brissot, E., Battipaglia, G., Malard, F., Belhocine, R., Sestili, S., Vekhoff, A., Delhommeau, F., Reman, O., Legrand, O., Labopin, M., Rubio, M. T., & Mohty, M. (2018). Sequential Conditioning with Thiotepa in T Cell- Replete Hematopoietic Stem Cell Transplantation for the Treatment of Refractory Hematologic Malignancies: Comparison with Matched Related, Haplo-Mismatched, and Unrelated Donors. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 24(5), 1013-1021. https://doi.org/10.1016/j.bbmt.2018.01.005
Duléry R, et al. Sequential Conditioning With Thiotepa in T Cell- Replete Hematopoietic Stem Cell Transplantation for the Treatment of Refractory Hematologic Malignancies: Comparison With Matched Related, Haplo-Mismatched, and Unrelated Donors. Biol Blood Marrow Transplant. 2018;24(5):1013-1021. PubMed PMID: 29337223.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sequential Conditioning with Thiotepa in T Cell- Replete Hematopoietic Stem Cell Transplantation for the Treatment of Refractory Hematologic Malignancies: Comparison with Matched Related, Haplo-Mismatched, and Unrelated Donors. AU - Duléry,Rémy, AU - Ménard,Anne-Lise, AU - Chantepie,Sylvain, AU - El-Cheikh,Jean, AU - François,Sylvie, AU - Delage,Jérémy, AU - Giannotti,Federica, AU - Ruggeri,Annalisa, AU - Brissot,Eolia, AU - Battipaglia,Giorgia, AU - Malard,Florent, AU - Belhocine,Ramdane, AU - Sestili,Simona, AU - Vekhoff,Anne, AU - Delhommeau,François, AU - Reman,Oumédaly, AU - Legrand,Ollivier, AU - Labopin,Myriam, AU - Rubio,Marie-Thérèse, AU - Mohty,Mohamad, Y1 - 2018/01/11/ PY - 2017/10/04/received PY - 2018/01/02/accepted PY - 2018/1/18/pubmed PY - 2019/4/20/medline PY - 2018/1/17/entrez KW - Antithymocyte globulin KW - Conditioning KW - Haploidentical transplantation KW - Refractory hematologic malignancy SP - 1013 EP - 1021 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 24 IS - 5 N2 - The results of conventional allogeneic stem cell transplantation (SCT) in refractory hematologic malignancies are poor. Sequential strategies have shown promising results in refractory acute myelogenous leukemia (AML), but have not been validated in a haploidentical (Haplo) transplant setting. We have developed a new sequential approach combining chemotherapy with broad antitumor activity (thiotepa 10 mg/kg, etoposide 400 mg/m2, and cyclophosphamide 1600 mg/m2 from day -15 to day -10), followed after 3 days of rest by a reduced-intensity conditioning regimen (fludarabine 150 mg/m2, i.v. busulfan 6.4 mg/kg, and thymoglobulin 5 mg/kg from day -6 to day -2). High-dose post-transplantation cyclophosphamide was added in cases with Haplo donors. Seventy-two patients (median age, 54 years) with a refractory hematologic malignancy (44 with acute myelogenous leukemia, 7 with acute lymphoblastic leukemia, 15 with myelodysplastic syndrome/myeloproliferative neoplasms, and 6 with lymphomas) were included in this retrospective multicenter study. Donors were Haplo (n = 27), matched related (MRD; n = 16), and unrelated (UD; n = 29). With a median follow-up of 21 months, the 2-year overall survival (OS) and event-free survival (EFS) were 54.7% and 49.3%, respectively, in recipients of Haplo transplants, 49.2% and 43.8%, respectively, in recipients of MRD transplants, and 37.9% and 28%, respectively, in recipients of UD transplants. Compared with UD, the outcomes were improved in Haplo in terms of the incidences of acute grade II-IV graft-versus-host disease (GVHD) (11.1% versus 41.4%; P < .001) and GVHD-free, relapse-free survival (44.4 versus 10.3%; P = .022). These results support the safety and efficacy of a thiotepa-based sequential approach in allogeneic SCT with a Haplo donor with post-transplantation immune modulation. Thus, in patients with refractory hematologic malignancies, there seems to be no benefit in searching for a UD when a Haplo donor is readily available. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/29337223/Sequential_Conditioning_with_Thiotepa_in_T_Cell__Replete_Hematopoietic_Stem_Cell_Transplantation_for_the_Treatment_of_Refractory_Hematologic_Malignancies:_Comparison_with_Matched_Related_Haplo_Mismatched_and_Unrelated_Donors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(18)30020-X DB - PRIME DP - Unbound Medicine ER -