Randomized comparison of prophylactic and minimal residual disease-triggered imatinib after allogeneic stem cell transplantation for BCR–ABL1-positive acute lymphoblastic leukemia

• Published in: Leukemia Vol. 27; no. 6; pp. 1254 - 1262
• Main Authors: Pfeifer, H, Wassmann, B, Bethge, W, Dengler, J, Bornhäuser, M, Stadler, M, Beelen, D, Vucinic, V, Burmeister, T, Stelljes, M, Faul, C, Dreger, P, Kiani, A, Schäfer-Eckart, K, Schwerdtfeger, R, Lange, E, Kubuschok, B, Horst, H A, Gramatzki, M, Brück, P, Serve, H, Hoelzer, D, Gökbuget, N, Ottmann, O G
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2013; Nature Publishing Group
• Subjects: 692/308/409; 692/699/67/1990/283/2125; 692/700/565/251/1574; 692/700/565/545/576/1955; Acute lymphoblastic leukemia; Acute lymphocytic leukemia; Adolescent; Adult; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; BCR protein; Benzamides - adverse effects; Benzamides - therapeutic use; Bone marrow; Cancer Research; Combined Modality Therapy; Critical Care Medicine; Drug therapy; Female; Hematology; Humans; Imatinib; Imatinib Mesylate; Intensive; Internal Medicine; Kinases; Leukemia; Lymphatic leukemia; Male; Medical prognosis; Medicine; Medicine & Public Health; Middle Aged; Minimal residual disease; Neoplasm, Residual; Oncology; original-article; Patient Compliance; Patient outcomes; Piperazines - adverse effects; Piperazines - therapeutic use; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Stem Cell Transplantation; Stem cells; Survival Analysis; Transplantation; Young Adult; Germany; minimal residual disease; tyrosine kinase inhibitor; Philadelphia chromosome
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2012.352

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.