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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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. / Bazarbachi, Abdul Hamid; Al Hamed, Rama; Labopin, Myriam; Afanasyev, Boris; Hamladji, Rose-Marie; Beelen, Dietrich; Eder, Matthias; Scheid, Christof; Wu, Depei; Bunjes, Donald; Stepensky, Polina; Tischer, Johanna; Kröger, Nicolaus; Peric, Zina; Aljurf, Mahmoud; Giebel, Sebastian; Nagler, Arnon; Mohty, Mohamad.
In: BONE MARROW TRANSPL, Vol. 55, No. 3, 03.2020, p. 595-602.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - 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
AU - Bazarbachi, Abdul Hamid
AU - Al Hamed, Rama
AU - Labopin, Myriam
AU - Afanasyev, Boris
AU - Hamladji, Rose-Marie
AU - Beelen, Dietrich
AU - Eder, Matthias
AU - Scheid, Christof
AU - Wu, Depei
AU - Bunjes, Donald
AU - Stepensky, Polina
AU - Tischer, Johanna
AU - Kröger, Nicolaus
AU - Peric, Zina
AU - Aljurf, Mahmoud
AU - Giebel, Sebastian
AU - Nagler, Arnon
AU - Mohty, Mohamad
PY - 2020/3
Y1 - 2020/3
N2 - 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.
AB - 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.
U2 - 10.1038/s41409-019-0702-2
DO - 10.1038/s41409-019-0702-2
M3 - SCORING: Journal article
C2 - 31562398
VL - 55
SP - 595
EP - 602
JO - BONE MARROW TRANSPL
JF - BONE MARROW TRANSPL
SN - 0268-3369
IS - 3
ER -