Reduced-intensity conditioning allogeneic stem cell transplantation is a potential therapeutic approach for adults with high-risk acute lymphoblastic leukemia in remission: results of a prospective phase 2 study

Abstract

The aim of this prospective study was to investigate the feasibility of reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT) in 37 adults with high-risk acute lymphoblastic leukemia (ALL) in first (n ¼ 30) or second (n ¼ 7) complete remission (CR). All patients were treated with fludarabine (150 mg/m 2 ) and melphalan (140 mg/m 2 ) followed by transplantation from matched sibling (n ¼ 27) or unrelated (n ¼ 10) donors. The indications for reduced-intensity conditioning allogeneic SCT (RIC-SCT) were as follows: (1) X50 years, 16 (43.2%) and (2) decreased organ function or active infections, 21 (56.8%). Graft-versus-host disease (GVHD) prophylaxis consisted of calcineurin inhibitor (cyclosporine for sibling and tacrolimus for unrelated transplants) and methotrexate. The cumulative incidence of acute (grades II-IV) and chronic GVHD was 43.2 and 65.6%, respectively. After a median follow-up of 36 months for surviving transplants, the 3-year relapse, non-relapse mortality, disease-free survival and overall survival rates were 19.7, 17.7, 62.6 and 64.1%, respectively. Transplants in first CR showed better transplantation outcomes than those in second CR. The potential of antileukemic activity of chronic GVHD was also found. This study suggests that RIC-SCT is a potential therapeutic approach for adults with high-risk ALL in remission who are ineligible for myeloablative transplantation.

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

“…Previously, we conducted a prospective, phase II trial of RIC-SCT in adults with high-risk ALL in CR who were ineligible for MAC-SCT [18]. Our interim analysis data showed the potential role of RIC-SCT, especially in patients in CR1.…”

“…During the period between July 2000 and February 2010, 60 consecutive patients (median age, 46 years [range, 15-63 years]) with newly diagnosed high-risk ALL who received a uniform treatment protocol of RIC-SCT in CR1 or CR2, as described previously in detail [18], were included in this analysis. The indications for RIC-SCT were advanced age ( 50 years; n 5 26; 43.3%) and the presence of organ dysfunction or active infections (n 5 34; 56.7%) ( Table I).…”

“…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.…”

“…To be eligible for MAC-SCT, patients had to be <50 years of age without any signs of organ dysfunction or active infections. RIC-SCT is being offered to high-risk patients who have a donor, but are not eligible for MAC-SCT [18].…”

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

“…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.…”