The effect of first-line imatinib interim therapy on the outcome of allogeneic stem cell transplantation in adults with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia

Abstract

Previously, we suggested that imatinib incorporation into conventional chemotherapy as an alternative (imatinib interim therapy) might be a useful strategy for bridging the time to allogeneic stem cell transplantation (

Impact of minimal residual disease kinetics during imatinib-based treatment on transplantation outcome in Philadelphia chromosome-positive acute lymphoblastic leukemia

“…Previously, we conducted a prospective, phase 2 trial of allogeneic SCT following first-line imatinib-based chemotherapy in adults with Ph-positive ALL, and in the trial, BCR-ABL1 transcript levels in the bone marrow (BM) were routinely monitored using real-time quantitative PCR (RQ-PCR). [12][13][14] Our interim analyzing data showed the positive impact of imatinib-based chemotherapy on the short-term SCT outcome 13 and the potential of a 3-log MRD reduction (individual log reduction) at the end of the first four weeks of imatinib administration as a risk factor of outcome. 14 However, in our previous reports, MRD kinetics, that is, the quality as well as the persistence of molecular response, by the end of whole pre-transplant imatinib-based chemotherapy courses were not included in the risk-factor analysis.…”

“…During the period between September 2000 and December 2009, 95 adults (median age 34 years (range 15-59 years)) with newly diagnosed Ph-positive ALL who received a uniform treatment protocol of allogeneic SCT following two courses of imatinib-based chemotherapy, as described previously in detail, 13,14 were included in this analysis. The treatment schedule is summarized in Table 1.…”

“…As previously described, 13,14,[17][18][19] all of the patients were transplanted from a fully matched sibling or a suitably matched (p2 allele-mismatched) unrelated donor after the completion of two courses of imatinib-based chemotherapy. In brief, donor selection was based on high-resolution human leukocyte antigen genotyping using PCR-sequence-specific primer for both class I and II antigens.…”

Comparable long‐term outcomes after reduced‐intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high‐risk acute lymphoblastic leukemia in complete remission

“…Induction therapy was started with hyper-fractionated cyclophosphamide (300 mg/m 2 , every 12 hr, days 1-3), vincristine (1.4 mg/m 2 , maximum dose 2 mg, days 4 and 11), idarubicin (12 mg/m 2 , days 4 and 11), and dexamethasone (40 mg, days 1-4 and days [11][12][13][14] [18,[21][22][23][24][25]. Subsequently, patients in CR received consolidation courses consisting of high-dose cytarabine (2 g/m 2 , every 12 hr, days 1-5) and mitoxantrone (12 mg/m 2 , days 1-2) therapy (at each odd cycle of consolidation) alternating with the above induction regimens (at each even cycle of consolidation), which were dependent on donor availability and the time of transplantation.…”

“…Central nervous system prophylaxis was performed by intrathecal administration of triple agents (methotrexate, cytarabine, and methylprednisolone; 6 times in total). Patients with Philadelphia chromosome (Ph)-positive ALL received imatinib-based chemotherapy before transplantation, as previously described [18,[21][22][23][24][25]. No prophylactic imatinib therapy was planned after transplantation.…”