Contributions
Abstract: EP354
Type: E-Poster Presentation
Session title: Acute lymphoblastic leukemia - Clinical
Background
Unlike paediatric patients, adult ALL/LL patients face lower cure rates of about 40-50%.1 Certain cytogenetic abnormalities and advanced age are well accepted prognostic factors, as well as the presence of minimal residual disease.2 However, little is known about ALL/LL microenvironment and its impact on response to treatment and incidence of relapse. Monocytes are cells of the innate immune system that play an important role in cancer development. Different subsets of monocytes have been linked both to pro and anti-tumoral immunity.3 Recent work showed that a high monocyte count at diagnosis was associated with higher mortality and relapse rate on B ALL patients, suggesting a protective role on tumour cell survival.4 On the other hand, a normal monocyte count at first relapse have showed a benefit on overall survival (OS).5There is still uncertainty about the significance of monocytes on other time points of the disease course and what role they play on tumour cell survival at each moment.
Aims
To evaluate the prognostic significance of post induction monocyte count in ALL/LL adult patients.
Methods
Single centre, retrospective study of ALL/LL patients diagnosed between 2011-2020. Blood monocyte count at the time of response to induction assessment was correlated with OS and event free survival (EFS). Kaplan-Meier curves and log-rank test were used for comparison of OS and EFS. Univariate and multivariate Cox proportional hazard models were used for investigating factors associated with OS.
Results
Sixty-eight patients were included, 61.8% were male, median age of 46 years (IQR 24-64). Most patients (58) were diagnosed with ALL, 79.3% of B lineage and CD20+ in 26.9%. LL was diagnosed in 10 patients, 8 of T lineage. 21 patients had t(9;22), hyperdiploid karyotype was present in 6 patients, 2 patients had t(1;19) and 1 had complex karyotype. 7% of patients had CNS disease at diagnosis.
Most patients (70.6%) were treated with high intensity protocols, either HyperCVAD or DFCI-11001. The remaining patients were unfit for this approach and were treated with age-adjusted protocols. Response to induction was assessed in 52 patients, 85.5% of which were in complete response after induction.
OS and EFS were analysed according to monocyte count >1000cel/µL after induction. No significant differences on patient and disease characteristics were found between the two groups. At median follow up (FU) (10.5 months), OS and EFS were significantly higher in patients with >1000 monocytes/µL after induction: OS of 100% vs 68.5%, p=0.01; EFS of 85.7% vs 67%, p=0.03. In univariate analysis, blood monocyte count as a continuous variable had impact on OS (HR 0.99, 95% CI 0.997-1.00, p=0.018). This impact persisted in multivariate analysis against covariates hyperleukocytosis at diagnosis and age (HR 0.998, 95% CI 0.997-0.999, p=0.014). Of note, none of the patients with >1000 monocytes/µL after induction died so far and only one relapsed, with a median FU of 63 months in this subgroup.
Conclusion
Higher monocyte counts after induction were associated with higher OS and EFS. Interestingly, of all patients who had monocytosis after induction, only one relapsed, and all remain alive. These findings may represent a shift to an anti-tumoral monocyte phenotype and may be surrogate markers for bone marrow recovery and better disease control. To address these specific questions, prospective and translational studies are needed. Nevertheless, to the best of our knowledge, this is the first study on the impact of monocyte recovery after induction therapy concerning patients with B an T phenotype ALL/LL.
Keyword(s): Acute lymphoblastic leukemia, Innate Immunity, Monocyte, Survival
Abstract: EP354
Type: E-Poster Presentation
Session title: Acute lymphoblastic leukemia - Clinical
Background
Unlike paediatric patients, adult ALL/LL patients face lower cure rates of about 40-50%.1 Certain cytogenetic abnormalities and advanced age are well accepted prognostic factors, as well as the presence of minimal residual disease.2 However, little is known about ALL/LL microenvironment and its impact on response to treatment and incidence of relapse. Monocytes are cells of the innate immune system that play an important role in cancer development. Different subsets of monocytes have been linked both to pro and anti-tumoral immunity.3 Recent work showed that a high monocyte count at diagnosis was associated with higher mortality and relapse rate on B ALL patients, suggesting a protective role on tumour cell survival.4 On the other hand, a normal monocyte count at first relapse have showed a benefit on overall survival (OS).5There is still uncertainty about the significance of monocytes on other time points of the disease course and what role they play on tumour cell survival at each moment.
Aims
To evaluate the prognostic significance of post induction monocyte count in ALL/LL adult patients.
Methods
Single centre, retrospective study of ALL/LL patients diagnosed between 2011-2020. Blood monocyte count at the time of response to induction assessment was correlated with OS and event free survival (EFS). Kaplan-Meier curves and log-rank test were used for comparison of OS and EFS. Univariate and multivariate Cox proportional hazard models were used for investigating factors associated with OS.
Results
Sixty-eight patients were included, 61.8% were male, median age of 46 years (IQR 24-64). Most patients (58) were diagnosed with ALL, 79.3% of B lineage and CD20+ in 26.9%. LL was diagnosed in 10 patients, 8 of T lineage. 21 patients had t(9;22), hyperdiploid karyotype was present in 6 patients, 2 patients had t(1;19) and 1 had complex karyotype. 7% of patients had CNS disease at diagnosis.
Most patients (70.6%) were treated with high intensity protocols, either HyperCVAD or DFCI-11001. The remaining patients were unfit for this approach and were treated with age-adjusted protocols. Response to induction was assessed in 52 patients, 85.5% of which were in complete response after induction.
OS and EFS were analysed according to monocyte count >1000cel/µL after induction. No significant differences on patient and disease characteristics were found between the two groups. At median follow up (FU) (10.5 months), OS and EFS were significantly higher in patients with >1000 monocytes/µL after induction: OS of 100% vs 68.5%, p=0.01; EFS of 85.7% vs 67%, p=0.03. In univariate analysis, blood monocyte count as a continuous variable had impact on OS (HR 0.99, 95% CI 0.997-1.00, p=0.018). This impact persisted in multivariate analysis against covariates hyperleukocytosis at diagnosis and age (HR 0.998, 95% CI 0.997-0.999, p=0.014). Of note, none of the patients with >1000 monocytes/µL after induction died so far and only one relapsed, with a median FU of 63 months in this subgroup.
Conclusion
Higher monocyte counts after induction were associated with higher OS and EFS. Interestingly, of all patients who had monocytosis after induction, only one relapsed, and all remain alive. These findings may represent a shift to an anti-tumoral monocyte phenotype and may be surrogate markers for bone marrow recovery and better disease control. To address these specific questions, prospective and translational studies are needed. Nevertheless, to the best of our knowledge, this is the first study on the impact of monocyte recovery after induction therapy concerning patients with B an T phenotype ALL/LL.
Keyword(s): Acute lymphoblastic leukemia, Innate Immunity, Monocyte, Survival