Background.

Pre-apoptotic exposure of calreticulin (CRT) – protein belonging to DAMPs family – on the surface of malignant blasts in response to anthracycline-based chemotherapy is an important activation signal for phagocytosis initiating mechanism of immunogenic cell death. This process is counterbalanced by the negative regulator of phagocytosis – an interaction of CD47-SIRPα. Regulatory T cells (Treg) are supposed to actively counteract antitumor immunity, contributing to the accelerated growth kinetics and cancer promotion.

Aims.

To investigate correlation of membrane expression of CRT, CD47 on blasts, percentage of CD4+CD25+ Treg cells in the peripheral blood before and 6-12 hours after first administration of anthracyclines with response to first-line induction chemotherapy and median survival time in patients with acute leukemias.

Methods.

The study was conducted in 29 patients (M/F=15/14) aged 20 to 68 years (median 55), including 25 with a diagnosis of AML, 4 – ALL. All patients received anthracycline-based induction chemotherapy according to protocols with daunorubicin - 20, epirubicin - 8, and idarubicin – 1. CRT, CD47 exposure, Treg percentages were determined by flow cytometry.

Results.

Of all the patients - 19 achieved complete remission (CR) after the first cycle of first-line induction chemotherapy, 5 - did not achieve any remission (NR), 5 – were not assessed due to death during the treatment. In the group of patients who achieved CR the median CRT expression was 41.5% prior to and 65.7% 6-12 hours after the first dose of anthracycline. The median expression of CD47 presented levels – 5.9% and 29.6%. The median percentage of Treg was characterized by a decreasing tendency – 6.1% and 5.4%, respectively. The median overall survival (OS) in these patients was 5.9 months in median follow-up of 7.2 months. In the group of patients, who did not achieve remission after administration of first-line induction chemotherapy (NR), we observed the lower levels of CRT and CD47 expression in both assays in comparison to the group with CR. The median CRT expression was 9.2% prior to administration and 40.5% 6-12 h after first dose of the chemotherapeutic agent. The median expression of CD47 – 0,5% and 6,3%, respectively. The percentage of T regulatory cells tended to increase following administration of anthracyclines and was higher than in patients with CR – the median - 9.3% and 14.1%. The median OS in that group was 1.3 months in median follow-up of 8.2 months. Furthermore, we showed that a higher percentage of CRT expression before and 6-12 hours after implementing chemotherapy was negatively correlated with OS of the patients (p =0,014, r=-0,46 and p<0,0001, r=-0,50). A similar correlation regarding CD47 expression and Treg percentage was not confirmed in our study.

Conclusion/Summary.

Labelling of CRT, CD47 exposure, Treg cells percentage might be useful in the assessment and prognosis of response to induction chemotherapy in acute leukemias, but it requires further investigations in a larger group of patients.

Figure 1
Figure 1.
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Figure 2
Figure 2.
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Disclosures

No relevant conflicts of interest to declare.

Topics:
anthracycline antibiotics, calr gene, cd47 antigen, chemotherapy, neoadjuvant, leukemia, acute, regulatory t-lymphocytes, chemotherapy regimen, disease remission, follow-up, antineoplastic agents

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2014 by The American Society of Hematology
2014
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