title: Randomized comparison of prophylactic and minimal residual disease-triggered imatinib after allogeneic stem cell transplantation for BCR-ABL1-positive acute lymphoblastic leukemia.
abstract: Minimal residual disease (MRD) after allogeneic stem cell transplantation (SCT) for Ph+ acute lymphoblastic leukemia (ALL) is predictive of relapse. Imatinib administration subsequent to SCT may prevent relapse, but the role of scheduling and its impact on outcome are not known. In a prospective, randomized multicenter trial, we compared the tolerability and efficacy of post-transplant imatinib administered either prophylactically (arm A; n=26) or following detection of MRD (arm B; n=29). Prophylactic imatinib significantly reduced the incidence of molecular recurrence after SCT compared with MRD-triggered imatinib (40% vs 69%; P=0.046). Median duration of PCR negativity was 26.5 and 6.8 months, respectively (P=0.065). Five-year survival in both interventional groups was high (80 and 74.5%), despite premature discontinuation of imatinib in the majority of patients because of poor tolerability. Relapse probability was significantly higher in patients who became MRD positive (P=0.017). In conclusion, post-transplant imatinib results in a low relapse rate, durable remissions and excellent long-term outcome in patients with BCR-ABL1-positive ALL irrespective of whether it is given prophylactically or MRD-triggered. Reappearance of BCR-ABL1 transcripts early after SCT or at higher levels identifies a small subset of patients who do not benefit sufficiently from imatinib, and in whom alternative approaches should be explored.
authors.affiliation: Department of Hematology/Oncology of the University Hospitals, Frankfurt, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Pfeifer
authors.forename: B
authors.initials: B
authors.lastname: Wassmann
authors.forename: W
authors.initials: W
authors.lastname: Bethge
authors.forename: J
authors.initials: J
authors.lastname: Dengler
authors.forename: M
authors.initials: M
authors.lastname: Bornhäuser
authors.forename: M
authors.initials: M
authors.lastname: Stadler
authors.forename: D
authors.initials: D
authors.lastname: Beelen
authors.forename: V
authors.initials: V
authors.lastname: Vucinic
authors.forename: T
authors.initials: T
authors.lastname: Burmeister
authors.forename: M
authors.initials: M
authors.lastname: Stelljes
authors.forename: C
authors.initials: C
authors.lastname: Faul
authors.forename: P
authors.initials: P
authors.lastname: Dreger
authors.forename: A
authors.initials: A
authors.lastname: Kiani
authors.forename: K
authors.initials: K
authors.lastname: Schäfer-Eckart
authors.forename: R
authors.initials: R
authors.lastname: Schwerdtfeger
authors.forename: E
authors.initials: E
authors.lastname: Lange
authors.forename: B
authors.initials: B
authors.lastname: Kubuschok
authors.forename: H A
authors.initials: HA
authors.lastname: Horst
authors.forename: M
authors.initials: M
authors.lastname: Gramatzki
authors.forename: P
authors.initials: P
authors.lastname: Brück
authors.forename: H
authors.initials: H
authors.lastname: Serve
authors.forename: D
authors.initials: D
authors.lastname: Hoelzer
authors.forename: N
authors.initials: N
authors.lastname: Gökbuget
authors.forename: O G
authors.initials: OG
authors.lastname: Ottmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D010349:Patient Compliance; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000628:therapy*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate