Publication Only: Stem cell transplantation - Clinical
The role of autologous stem cell transplantation (ASCT) as consolidation therapy in acute myeloid leukemia (AML) remains unclear although most studies comparing ASCT with repeated cycles of intensive chemotherapy demonstrated a significantly lower rate of relapse following ASCT. Evaluation of minimal residual disease (MRD) can better identify patients who benefit from ASCT.
We report our single center experience to evaluate long term outcome in terms of overall survival (OS) and disease free survival (DFS) of AML patients who consecutively received ASCT and to retrospectively analyze the correlation between MRD status pre ASCT and OS in patients with molecularly detectable MRD.
From 1998 to 2018, 65 adult patients with de novo (61/65) or secondary (4/65) AML underwent ASCT at Seràgnoli Hematology Institute. Median age was 50 (range 16-68 years). Most patients had favorable (23/65) or intermediate (35/65) cytogenetic-molecular profile according to ELN2017 risk classification. 24 patients (MRD marker group) had any of the following detectable leukemia-specific molecular markers at diagnosis evaluated through qPCR: 9 NPM1, 5 RUNX1/RUNX1T1, 10 CBFB/MYH11. All the patients received intensive induction chemotherapy: 24 patients received a “3+7” like induction therapy, 23 were treated with fludarabine-based induction and 18 received a gemtuzumab ozogamicin-containing regimen.
Sixty-two out of 65 patients (95.4%) obtained complete remission (CR) after induction chemotherapy. In the MRD group, 13 obtained MRD negativity after induction, 2 after first and 8 after the second consolidation. The median number of consolidation cycles before ASCT was two. All patients received myeloablative busulphan based-conditioning regimen in association to melphalan (74%) or cyclophosphamide (26%). 35 patients received bone marrow stem cells and 30 peripheral blood stem cells. Before ASCT five patients were MRD+ (2 NPM1, 3 CBFs). With a median follow up of 10 years, median OS of the population was not reached and median DFS was 2470 days. OS estimates at 3, 5 and 10 years were respectively 68%, 61% and 54%. Better outcome was observed in patients receiving more than one consolidation cycle in terms of DFS (p = 0.006) and OS (p = 0.03). MRD marker group patients had estimated OS at 3 and 5 years of 90% and 85% respectively. Of 30 patients who relapsed after ASCT, 16 received a rescue therapy and were successfully candidate to allogeneic stem cell transplantation (alloSCT) in second CR with a long survival rate of 50%. In the MRD marker group, 2/2 NPM1 MRD+ relapsed and 3/3 CBFs MRD+ (all with CBFB/MHY11 fusion transcript) obtained molecular remission and are still alive in CR. Pre-ASCT MRD positivity do not impact prognosis in term of OS (10-yr OS 80% for MRD+, 88% for MRD-) or DFS (2-yr DFS 70% and 61% for MRD- and MRD+ respectively). Of note, NPM1 MRD- patients who underwent ASCT remained in CR for a long time after ASCT (median OS not reached and median DFS of 1156 in NPM1- and 249 NPM1+).
our study confirm that ASCT is a feasible and effective strategy for adult AML patients, mainly in those with low-intermediate ELN2017 risk and treated with at least 2 post-remissional cycles and it can concede long term survival mainly to NPM1 AML patients MRD- before ASCT. Relapse after ASCT can be successfully rescue by alloSCT. The application of prospective evaluation of MRD through more sensitive molecular methods (qPCR) on a wider population of adult AML patient may better select the patients who could benefit from ASCT.