Clinical Outcome of Autologous Hematopoietic Cell Transplantation in Adult Patients with Acute Myeloid Leukemia: Who May Benefit from Autologous Hematopoietic Cell Transplantation?

Abstract

The role of autologous hematopoietic cell transplantation (auto-HCT) for postremission therapy of acute myeloid leukemia is yet to be elucidated. We retrospectively analyzed 240 patients treated with auto-HCT in first remission. All patients were treated with standard induction chemotherapy, and CD34 stem cells were collected at each cycle of consolidation. Stem cells were infused after total body irradiation (1200 cGy), cytarabine (9 g/m), and melphalan (100 mg/m). Estimated 5-year overall survival, disease-free survival (DFS), cumulative incidence of relapse (CIR), and nonrelapse mortality were 58.4%, 55.3%, 38.8%, and 5.9%, respectively. We identified that poor-risk karyotype showed very poor outcome after auto-HCT, and then analyzed 85 patients with good to intermediate-risk molecular cytogenetics with available molecular study results and markers for minimal residual disease (MRD) such as WT1 and core-binding factor (CBF) associated MRD (ie, AML1/ETO and CBFβ/MYH11). Our data identified that old age, pre-HCT markers for MRD, and high post-HCT WT1, high dose of CD34 stem cell (≥4.5 × 10/kg) infusion, and c-kit or FLT3-ITD mutations were associated with higher relapse rate and poor DFS. Using pre-HCT parameters, except for post-HCT WT1, multivariate analysis revealed that patients with young age (<40 years old), no adverse mutations, and limited dose of CD34 stem cells might be good candidate for auto-HCT (3-year DFS and CIR were 83.4% and 16.6%, respectively). Young patients with good- to intermediate-risk molecular cytogenetics may benefit from auto-HCT if stem cell dose is limited.

Autologous Hematopoietic Stem Cell Transplantation in Acute Myelogenous Leukemia

“…Similarly, Qin et al [41] reported that a CBFB/MYH11 level of >.2% after 2 courses of consolidation was an independent prognostic factor for poor OS, DFS, and cumulative incidence of relapse in autografted patients. High expression of Wilms' tumor gene 1 (WT1) in leukapheresis of peripheral blood autografts pre-ASCT has been associated with a high risk of relapse (cutoff value for WT1: 80 copies/10 4 ABL; 87% versus 30%; P = .0001) [53], consistent with the results published by Yoon et al [21]. In addition, Mule et al [54] reported that individualized MRD parameters, combined with WT1 and other non-leukemia-specific genes, such as PRAME and MSLN, can predict prognosis after ASCT in patients with AML with high sensitivity.…”

“…Multivariate analysis identified risk stratification as an important prognostic factor for both OS and LFS after ASCT. Yoon et al [21] reported similar outcomes in 240 patients with AML in CR1 who underwent ASCT following a conditioning regimen including total body irradiation (TBI; 1200 cGy), cytarabine (9 g/m 2 ), and melphalan (100 mg/m 2 ); OS decreased as the cytogenetic risk increased at 5 years after ASCT, with the highest 5-year OS in 19 patients carrying t(8;21) with isolated Y chromosome loss. In a previous study, we identified cytogenetic risk as an independent prognostic factor for survival outcomes, with decreasing OS and DFS as risk increased [18].…”

“…AML with t(8;21) or inv (16) One study reported a 5-year OS of 88.8% following ASCT in patients with AML carrying t(8;21) with isolated Y chromosome loss [21], and comparable outcomes have been reported after ASCT and allo-SCT in patients with AML carrying t(8;21) [24,40,41]. Eom et al [24] reported an OS of 70.2% and a DFS of 68.4% at 5 years following ASCT in patients with AML with t (8;21) in CR1, and no significant differences in RR, OS, and DFS compared with patients who underwent allo-SCT with a reduced-intensity conditioning regimen.…”

“…Yoon et al [21] monitored AML1/ETO and CBFB/MYH11 through a more sensitive molecular method based on qPCR and found a higher 3-year RR in patients expressing higher levels of pre-ASCT MRD markers. Similarly, Qin et al [41] reported that a CBFB/MYH11 level of >.2% after 2 courses of consolidation was an independent prognostic factor for poor OS, DFS, and cumulative incidence of relapse in autografted patients.…”

Comparison of the effects of early intensified induction chemotherapy and standard 3+7 chemotherapy in adult patients with acute myeloid leukemia

“…For patients in CR, we searched for available donors for allogeneic-hematopoietic cell transplantation (HCT) during the consolidation period, giving initial preference to human leukocyte antigen (HLA)-matched sibling donors (MSDs), followed by HLA well-matched unrelated donors (URDs). When conventional donors were not available, we searched for haploidentical familial mismatched donors; if a patient refused allogeneic-HCT, we performed autologous-HCT or completed three cycles of consolidation chemotherapy alone according to the patient's and physician's joint decision [ 16 17 18 ]. If a patient was a candidate for autologous-HCT, CD34+ hematopoietic stem cells were collected for 3 days during consolidation chemotherapy after the neutrophil count had recovered.…”