PF180 THE SIGNIFICANCE OF MONOSOMAL KARYOTYPE IN PHILADELPHIA CHROMOSOME NEGATIVE ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: Li Z. , Jiang Q. , Lai Y. , Zhang X. , Xu L. , Liu K. , Wang Y. , Jiang H. , Huang X. 
Published: June 2019

Background:

Monosomal karyotype (MK) is a prognostic factor significantly associated with poor survival in acute myeloid leukemia and myelodysplastic syndrome. However, its significance in acute lymphoblastic leukemia (ALL) remains controversial.

Aims:

To explore the characteristics and outcomes of Philadelphia chromosome (Ph)‐negative ALL patients with MK.

Methods:

Data of consecutive patients with newly diagnosed Ph‐negative ALL were retrospectively analyzed. CODPL regimen and revised Hyper‐CVAD regimen were used as the induction and consolidation chemotherapy, respectively. Maintenance therapy consisted of monthly vindesine, prednisone, mercaptopurine and methotrexate for 2 years. Allogeneic hematopoietic stem‐cell transplantation (allo‐HSCT) was performed after at least 2 cycles of consolidation based on patients’ intention. Patients’ characteristics, treatment response and outcomes were compared between those with MK or not. COX regression model was used to identify factors associated with disease‐free survival (DFS) and overall survival (OS).

Results:

From January 1st 2008 to June 30th 2018, 313 patients with Ph‐negative ALL were included in this study. 184 (56%) were male. Median age was 30 years (range, 15–65 years). Compared with those without MK, patients with MK had lower platelet count (p = 0.021), higher blast percentage in peripheral blood (p = 0.010), and more complex karyotype (p < 0.001) at diagnosis. There was no difference on the probabilities of complete remission (CR, 82% vs 87%, p = 0.356) and minimal residual disease (MRD) negativity after induction chemotherapy (51% vs 52%, p = 0.911) and the first cycle of consolidation (60% vs 70%, p = 0.253) between those with MK or not. In the 270 CR patients, 99 (37%) received continuous chemotherapy; 171 (63%), allo‐HSCT in CR1. With a median follow‐up of 33 months (range, 1.5–125.3 months) for living patients, probabilities of DFS and OS at 5 years were 54.6% (95%CI, 47.5%>61.2%) and 57.8% (95%CI, 50.5%>65.1%), respectively. Variables including patients’ characteristics at diagnosis and early responses associated with outcomes were assessed in univariate analysis. In multivariate analysis, MK was not a factor associated the outcomes, however, age >45 year, plate count < 88x109/L, not achieving CR within 4 weeks, and receiving chemotherapy rather than allo‐HSCT were adverse factors associated with DFS and/or OS. In further analyses by post‐remission therapy, MK was identified as an independent factor associated with lower probabilities of DFS (HR 2.1, 95%CI 1.0–4.4, p = 0.050) and OS (HR 5.3, 95%CI 2.5–11.2, p < 0.001) in the chemotherapy group; in addition, age >45 year and MRD positivity after cycle 1 of consolidation were associated with shorter DFS. However, no variable was found to affect the outcomes in the allo‐HSCT group.

Summary/Conclusion:

Ph‐negative ALL patients with MK had lower platelet count, higher blast percentage in peripheral blood, and more complex karyotype at diagnosis. MK was an independent poor predictor of outcome in the patients with Ph‐negative ALL receiving continuous chemotherapy, but it had no significance in those receiving allo‐HSCT. Our study suggested that Ph‐negative ALL patients with MK might benefit from allo‐HSCT.