Donor-specific differences in long-term outcomes of myeloablative transplantation in adults with Philadelphia-negative acute lymphoblastic leukemia

Abstract

We analyzed long-term outcomes of myeloablative stem cell transplantation (SCT) in 292 adults with Philadelphia (Ph)-negative acute lymphoblastic leukemia (ALL). Donors were related (RD; n ¼ 132), unrelated (URD; n ¼ 68; 30 well-matched (WM), 19 partially matched (PM), 19 mismatched (MM)) and autologous (AUTO; n ¼ 92). After a median follow-up of 85 months, the risk of relapse was higher for AUTO-SCT than for RD-SCT (Po0.001). MM-URD-SCT yielded higher risk of nonrelapse mortality than RD-SCT (P ¼ 0.010). As a result, diseasefree survival (DFS) at 5 years was inferior using AUTO (46.1%; P ¼ 0.010) or MM-URD (26.3%; P ¼ 0.036), whereas DFS from other donor sources was approximately equivalent (53.5% for RD, 63.3% for WM-URD and 57.0% for PM-URD). Other factors associated with poorer DFS included SCT beyond first complete remission (CR), older age and adverse cytogenetics. In a pairwise comparison of outcomes between RD-SCT and AUTO-SCT for patients in first CR, the inferiority of AUTO-SCT was observed, particularly in high-risk patients. Conversely, in standard-risk patients, AUTO-SCT yielded comparable outcomes to RD-SCT. SCT using RD, WM-URD or PM-URD may be considered the best donor sources for adult high-risk Ph-negative ALL.

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.…”

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.…”

“…The MAC regimen consisted of total body irradiation (13.2 Gy) and cyclophosphamide (120 mg/kg) [21][22][23][24][25]. As previously described [18,[21][22][23][24][25], GVHD prophylaxis was attempted by administering calcineurin inhibitors (cyclosporine for RD transplants, tacrolimus for URD transplants) plus methotrexate. If residual leukemia was detected in the absence of GVHD at 3 months after transplantation, calcineurin inhibitors were rapidly discontinued.…”

PBSC vs BM grafts with myeloablative conditioning for unrelated donor transplantation in adults with high-risk ALL

“…[30][31][32][33][34] Donor-recipient pairs were considered matched when the pair was identical at HLA-A, -B, -C and -DRB1 loci with high-resolution HLA genotyping. If a MSD was available, MSD-SCT was offered to any patient after the completion of the first consolidation course.…”