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

• Published in: Biology of blood and marrow transplantation 2018-05, Vol.24 (5), p.1013-1021
• Main Authors: Duléry, Rémy, Ménard, Anne-Lise, Chantepie, Sylvain, El-Cheikh, Jean, François, Sylvie, Delage, Jérémy, Giannotti, Federica, Ruggeri, Annalisa, Brissot, Eolia, Battipaglia, Giorgia, Malard, Florent, Belhocine, Ramdane, Sestili, Simona, Vekhoff, Anne, Delhommeau, François, Reman, Oumédaly, Legrand, Ollivier, Labopin, Myriam, Rubio, Marie-Thérèse, Mohty, Mohamad
• Format: Article
• Language: English
• Subjects: Antithymocyte globulin; Cancer; Conditioning; Haploidentical transplantation; Hematology; Human health and pathology; Life Sciences; Refractory hematologic malignancy
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2018.01.005

•Thiotepa-based sequential conditioning is safe in a haploidentical transplantation setting.•This sequential approach is efficient in patients with refractory hematologic malignancies.•Patients had better outcomes with haploidentical donors than with unrelated donors.•This study does not support the use of unrelated donors in refractory patients.•Related donors, either matched or haploidentical, should be preferred. 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