Absolute Lymphocyte Count As a Novel Prognostic Predictor Compared to Minimal Residual Disease and Molecular Status in Patients with Acute Myeloid Leukemiatreated with Intensive Chemotherapy
Authors: Cristiano Gianluca , Nanni Jacopo , Zannoni Letizia , Zingarelli Federico , Ardizzoia Federica , Sartor Chiara , Parisi Sarah , Paolini Stefania , Papayannidis Cristina , Cavo Michele , Curti Antonio 
Published: December 2024

Background:
Absolute lymphocyte count (ALC)is known to be an independent prognostic factor for overall survival (OS) in patients with lymphomas as long as many solid cancers. In acute myeloid leukemia (AML) patients, enhanced ALC recovery after intensive chemotherapy (IC) has been associated with superior OS. However, there are still poor data correlating ALC recovery with novel therapy regimens, prognostic molecular European Leukemia Net (ELN) classification, allogeneic stem cell transplantation (HSCT) and minimal residual disease (MRD).
Aims:
Our study exploresALC recovery in newly diagnosed AML patients who were responsive to ICthrough its comparison to different factors including type of chemotherapy regimen,molecular status, HSCT and MRD.
Methods:
We evaluated 188AML patients from Bologna Seràgnoli Hematology Institute since 2007. All patients obtained complete remission (CR) and were assessed for MRD after two courses.MRD was evaluated by RT-PCR specific transcripts or WT1. We defined 4 ALC time-points (TPs): at 15, 21 and 28 days from IC start and before consolidation therapy (CC). ALC adopted cut-off was 500/mm3. Patients were also grouped in those who obtained ≥500/mm3ALC in all 4 TPs and those who had&lt;500/mm3ALC in at least one TP. Median follow-up was 51.4 months.
Results:
Considering the whole population, no meaningful differences were spotted between those who recovered ALC and all the others. No significant differences regarding age, ELN risk, cytogenetics, HSCT consolidation rate were identified. Nevertheless, among patients treated with “3+7-based” regimen (51,6%), at ALC-15 a relevant correlation with OS (p=0.10) of patients with ≥500/mm3ALC (31,9%) vs those under the cut-off (19,6%) was observed. This finding was further statistically significant in patients with ALC≥500/mm3 in all 4 TPs (25,5%) compared to those who had &lt;500/mm3ALC in at least one TP (26%)(p=0.02).
Conversely,in the “fludarabine-based” group (48,4%), ALC recovery showed a completely inverted correlation trend compared to “3+7”, even with a significant better outcomeof patientswho had &lt;500/mm3ALC.
As for mutational status, in the NPM1 mutated patients (35,1%) those who obtained ALC recovery in all 4 TPs (9.04%) were compared to those who missed recovery in at least one TP (26,06%) and it resulted not prognostically relevant; in FLT3-ITD positive patients (14,89%) a similar trend was shown.
Regarding the impact of ALC recovery in patients who received HSCT (66%) vs those who did not (34%), patients who had ALC &lt;500/mm3 in at least one TP and did not receive HSCT had the worst outcome. Interestingly, HSCT was capable to abolish the negative prognostic effect of reduced ALC recovery identifying a group of patients who may benefit from HSCT.
Finally, ALC recovery was correlated with MRD value. Among “3+7-based” patients who obtained MRD negativity (n = 52), those who had ≥500/mm3ALCin all ALC TPs (n=29)and in ALC-15 (n=35) resulted in a globally better OS as compared to patients with &lt;500/mm3 ALC at the two different evaluations (n=23 and n=17, respectively).
Summary/Conclusion:
Our study indicates ALC recovery after IC as a promising independent survival predictor in AML patients, who achieve CR. Its impact is different according to the used IC regimen type (3+7 versus fludarabine-based) whereas NPM1 and FLT3 mutational status maintains its prognostic significance regardless ALC recovery. ALC recovery seems to emphasize an OS difference among MRD negative patients and may represent a predictive biomarker to identify a group of responding patients who may benefit from HSCT. To dissect the predictive value of ALC recovery according to ELN 2022 and the use of novel drugs (such as FLT3 inhibitors), studies with larger cohorts of patients areneeded.