Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial.
In patients with relapsed or refractory (r/r) acute myeloid leukemia (AML), long-term disease control can only be achieved by allogeneic hematopoietic stem cell transplantation (HSCT). We studied the safety and efficacy of clofarabine-based salvage therapy. The study was designed as phase II, multicenter, intent-to-transplant (ITT) study. A total of 84 patients with r/r AML were enrolled. All patients received at least one cycle of CLARA (clofarabine 30 mg/m(2) and cytarabine 1 g/m(2), days 1-5). Chemo-responsive patients with a donor received HSCT in aplasia after first CLARA. Generally, HSCT was performed as soon as possible. The conditioning regimen consisted of clofarabine (4 × 30 mg/m(2)) and melphalan (140 mg/m(2)). The median patient age was 61 years (range 40-75). On day 15 after start of CLARA, 26% of patients were in a morphologically leukemia-free state and 79% exposed a reduction in bone marrow blasts. Overall, 67% of the patients received HSCT within the trial. The primary end point, defined as complete remission after HSCT, was achieved by 60% of the patients. According to the ITT, overall survival at 2 years was 43% (95% confidence interval (CI), 32-54%). The 2-year disease-free survival for transplanted patients was 52% (95% CI, 40-69%). Clofarabine-based salvage therapy combined with allogeneic HSCT in aplasia shows promising results in patients with r/r AML.
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany.
J M
JM
Middeke
Medizinische Klinik III, Klinikum Chemnitz, Chemnitz, Germany.
R
R
Herbst
Rems-Murr-Klinikum Winnenden, Winnenden, Germany.
S
S
Parmentier
Medizinische Klinik II, Klinikum der Johann Wolfgang Goethe Universität Frankfurt am Main, Frankfurt, Germany.
G
G
Bug
Medizinische Klinik III, Klinikum Chemnitz, Chemnitz, Germany.
M
M
Hänel
Zentrum für Blutstammzell- und Knochenmarktransplantation, DKD Helios Klinik Wiesbaden, Wiesbaden, Germany.
G
G
Stuhler
5. Medizinische Klinik, Städtisches Klinikum Nord, Nürnberg, Germany.
K
K
Schäfer-Eckart
Medizinische Klinik 5, Universitätsklinikum Erlangen, Erlangen, Germany.
W
W
Rösler
III. Medizinische Klinik, Universitätsklinikum Mannheim, Mannheim, Germany.
S
S
Klein
Abteilung für Hämatologie, Onkologie, Immunologie, Rheumatologie und Pulmologie, Medizinische Universitätsklinik Tübingen, Tübingen, Germany.
W
W
Bethge
Klinik für Hämatologie, Onkologie und Palliativmedizin, HELIOS Klinikum Bad Saarow, Bad Saarow, Germany.
U
U
Bitz
Klinikapotheke, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany.
B
B
Büttner
Klinikapotheke, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany.
H
H
Knoth
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany.
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http://orcid.org/0000-0003-3669-5564
N
Alakel
Rems-Murr-Klinikum Winnenden, Winnenden, Germany.
M
M
Schaich
Medizinische Klinik III, Klinikum Chemnitz, Chemnitz, Germany.
A
A
Morgner
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany.
M
M
Kramer
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany.
K
K
Sockel
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
M
M
von Bonin
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany.
F
F
Stölzel
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany.
U
U
Platzbecker
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany.
C
C
Röllig
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany.
C
C
Thiede
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany.
G
G
Ehninger
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany.
M
M
Bornhäuser
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany.|DKMS, German Bone Marrow Donor Center, Tübingen, Germany.
J
J
Schetelig
D000227:Adenine Nucleotides / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000627:therapeutic use*; D000077866:Clofarabine; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D016879:Salvage Therapy; D014184:Transplantation, Homologous
D000227:Adenine Nucleotides; D000964:Antimetabolites, Antineoplastic; D001087:Arabinonucleosides; D000077866:Clofarabine