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Bone Marrow Transplant. 2019 Sep 27. doi: 10.1038/s41409-019-0702-2. [Epub ahead of print]

Allogeneic stem-cell transplantation with sequential conditioning in adult patients with refractory or relapsed acute lymphoblastic leukemia: a report from the EBMT Acute Leukemia Working Party.

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EBMT Paris Office, CEREST-TC, Department of Hematology, Saint Antoine Hospital, Paris, France.
First State Pavlov Medical University of St. Petersburg, Raisa Gorbacheva Memorial Research Institute for Paediatric Oncology, Hematology, and Transplantation, St Petersburg, Russia.
Centre Pierre et Marie Curie, Service Hématologie Greffe de Moëlle, Alger, Algeria.
Department of Bone Marrow Transplantation, University Hospital, Essen, Germany.
Department of Haematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
University of Cologne, I. Department of Medicine, Cologne, Germany.
Department of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China.
Klinik fuer Innere Medzin III, Universitätsklinikum Ulm, Ulm, Germany.
Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
Department of Internal Medicine III, LMU, University Hospital of Munich, Munich, Germany.
Bone Marrow Transplantation Centre, University Hospital Eppendorf, Hamburg, Germany.
University Hospital Centre Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia.
Department of Oncology, King Faisal Specialist Hospital Center & Research, Riyadh, Saudi Arabia.
Department of Bone Marrow Transplantation and Oncohaematology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
Chaim Sheba Medical Center, Tel Aviv University, Tel-Hashomer, Israel.
EBMT Paris Office, CEREST-TC, Department of Hematology, Saint Antoine Hospital, Paris, France.


Treatment of relapsed/refractory acute lymphoblastic leukemia (RR-ALL) remains a clinical challenge with generally dismal prognosis. Allogeneic stem-cell transplantation using sequential conditioning ("FLAMSA"-like) has shown promising results in relapsed/refractory acute myeloid leukemia, but little is known about its efficacy in RR-ALL. We identified 115 patients (19-66 years) with relapsed (74%) or primary-refractory (26%) ALL allografted from matched related (31%), matched unrelated (58%), or haploidentical donor (11%). Median follow-up was 37 (13-111) months. At day 100, cumulative incidences of grade II-IV/III-IV acute graft-versus-host-disease (GVHD) were 30% and 17%, respectively. Two-year cumulative incidence of chronic GVHD was 25% with 11% extensive cases. Two-year relapse incidence (RI) was 45%, non-relapse mortality was 41%. Two-year leukemia free survival (LFS) was 14%, overall survival (OS) 17%, and GVHD relapse-free survival (GRFS) was 14%. In multivariable analysis, Karnofsky score <90 negatively affected RI, LFS, OS, and GRFS. Conditioning with chemotherapy alone, compared with total body irradiation (TBI) negatively affected RI (HR = 3.3; p = 0.008), LFS (HR = 1.94; p = 0.03), and OS (HR = 2.0; p = 0.03). These patients still face extremely poor outcomes, highlighting the importance of incorporating novel therapies (e.g., BITE antibodies, inotuzumab, CAR-T cells). Nevertheless, patients with RR-T-cell ALL remain with an unmet treatment need, for which TBI-based sequential conditioning could be one of few available options.


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