Author:
Chen Huan,Liu Kai-yan,Xu Lan-ping,Liu Dai-hong,Chen Yu-hong,Zhao Xiang-yu,Han Wei,Zhang Xiao-hui,Wang Yu,Zhang Yuan-yuan,Qin Ya-zhen,Liu Yan-rong,Huang Xiao-jun
Abstract
Abstract
Background
Maintenance therapy with imatinib during the post-transplant period has been used for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL); however, its efficacy has not been demonstrated. A study was designed to investigate the safety of imatinib and its efficacy in preventing hematological relapse and improving disease-free survival (DFS) when administered after allogeneic hematopoietic stem cell transplantation (allo-HCT).
Methods
Patients with Ph + ALL that received allo-HCT were enrolled in the study. Real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to detect BCR-ABL transcript levels. Imatinib therapy was initiated if patient neutrophil counts were > 1.0 × 109/L and platelet counts were > 50.0 × 109/L, or if they displayed either elevated BCR-ABL transcript levels in two consecutive tests, or a BCR-ABL transcript level ≥ 10-2 after initial engraftment. Patients receiving imatinib after relapse were assigned to the non-imatinib group. The imatinib treatment was scheduled for 3–12 months, until BCR-ABL transcript levels were negative at least for three consecutive tests or complete molecular remission was sustained for at least 3 months.
Results
A total of 82 patients were enrolled. Sixty-two patients initiated imatinib therapy post-HCT. Imatinib therapy was initiated at a median time of 70 days post-HCT. Grade 3–4 adverse events (AEs) occurred in 17.7% of patients. Ten patients (16.1%) terminated imatinib therapy owing to AEs. Among the patients in imatinib and non-imatinib groups, the estimated 5-year relapse rate was 10.2% and 33.1% (p = 0.016), and the 5-year probability of DFS was 81.5% and 33.5% (p = 0.000) with the median follow-up of 31 months (range, 2.5-76 months) and 24.5 months (range, 4–72 months), respectively. Multivariate analysis identified imatinib maintenance therapy post-HCT as an independent prognostic factor for DFS (p = 0.000, hazard ratio [HR] =4.8) and OS (p = 0.000, HR = 6.2).
Conclusions
These results indicate that relapse rate can be reduced and DFS may be improved in Ph + ALL patients with imatinib maintenance therapy after HCT. BCR-ABL monitoring by qRT-PCR can guide maintenance therapy with imatinib including initiation time and treatment duration after allo-HCT.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Molecular Biology,Hematology
Reference31 articles.
1. Rdich JP: Philadelphia chromosome-positive acute lymphoblastic leukemia. Hematol Oncol Clin North Am. 2001, 15: 21-36. 10.1016/S0889-8588(05)70198-2.
2. Sierra J, Radich J, Hansen JA, Martin PJ, Petersdorf EW, Bjerke J: Marrow transplants from unrelated donors for treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 1997, 90: 1410-1414.
3. Laport GG, Alvarnas JC, Palmer JM, Snyder DS, Slovak ML: Long-term remission of Philadelphia chromosome-positive acute lymphoblastic leukemia after allogeneic hematopoietic cell transplantation from matched sibling donors:a 20 year experience with the fractionted total body irradiation-etoposide regimen. Blood. 2008, 112: 903-909. 10.1182/blood-2008-03-143115.
4. Xu LP, Huang XJ, Liu KY, Chen Huan, Liu DH, Zhang YC: Allogeneic hematopoietic stem cell transplantation for treatment of Philadelphia chromosome positive acute lymphoblastic leukemia. Beijing Da Xue Xue Bao. 2005, 37 (3): 231-235. Chinese
5. Wei G, Rafiyath S, Liu DL: First-line treatment for chronic myeloid leukemia: dasatinib, nilotinib, or imatinib. J Hematol Oncol. 2010, 3: 47-10.1186/1756-8722-3-47.