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

Abdul Hamid Bazarbachi, Rama Al Hamed, Myriam Labopin, Boris Afanasyev, Rose Marie Hamladji, Dietrich Beelen, Matthias Eder, Christof Scheid, Depei Wu, Donald Bunjes, Polina Stepensky, Johanna Tischer, Nicolaus Kröger, Zina Peric, Mahmoud Aljurf, Sebastian Giebel, Arnon Nagler, Mohamad Mohty

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)595-602
Number of pages8
JournalBone marrow transplantation
Volume55
Issue number3
DOIs
StatePublished - Mar 1 2020

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ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Bazarbachi, A. H., Al Hamed, R., Labopin, M., Afanasyev, B., Hamladji, R. M., Beelen, D., Eder, M., Scheid, C., Wu, D., Bunjes, D., Stepensky, P., Tischer, J., Kröger, N., Peric, Z., Aljurf, M., Giebel, S., Nagler, A., & Mohty, M. (2020). 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. Bone marrow transplantation, 55(3), 595-602. https://doi.org/10.1038/s41409-019-0702-2