Clinical and laboratory data of studied acute myeloid leukemia patients

Comparison between cytogenetic risk group AML patients as regard laboratory data showed that Hb, BM blasts, lactate dehydrogenase (LDH), total leukocyte count (TLC), PLT and BAALC were the statistical difference between different cytogenetic risk groups, as shown in [Table 2].

Comparison between cytogenetic risk and laboratory data, brain and acute leukemia, cytoplasmic among acute myeloid leukemia patients

ROC curve for BAALC as a prognostic factor for survival in AML patients is shown in [Figure 2] with sensitivity (86.1%), specificity (80%) with positive predictive value (88.6%) and negative predictive value (76.2%.) with P = 0.000 with cutoff value 2.11, where patients were classified into two groups based on BAALC value, also BAALC sensitivity and specificity as a prognostic factor for survival is shown in [Table 3].

Sensitivity and specificity of brain and acute leukemia, cytoplasmic as a prognostic factor for survival

BAALC high and low groups were compared using the Mann–Whitney U test regard age, laboratory and clinical data and response to therapy; our results showed HB, BM blast, LDH, TLC, PLT, gum hypertrophy, bleeding, purpura, cytogenetics, and response to induction therapy differ significantly between BAALC high and low groups, as shown in [Table 4].

Comparison between age, laboratory and clinical data, response to therapy in relation to brain and acute leukemia and cytoplasmic

Treatment

Different responses to induction therapy between both BAALC high or low is shown in [Table 4], 66 AML patients received induction chemotherapy “3 + 7” while 4 received 2 + 14 protocol. BMA was used to assess response at day 14, it was done for 65 patients (5 patients had induction death). At D28, the response was assessed using BMA, 63 patients were evaluated, 2 patients lost after D14 evaluation (induction death).

Association between survival and demographic, clinical and laboratory data among studied acute myeloid leukemia patients

When we evaluated mean overall survival time according to chemotherapy response, cytogenetics and BAALC among studied AML patients by Kaplan–Meier test, we found that mean survival time for patients who achieve complete remission (CR) (121.1 ± 4.9) was statistically significantly longer than those who not achieve CR (34.2 ± 2.8) (log-rank test = 62.62, P = 0.000). Mean survival time for cytogenetically normal AML patients (60.25 ± 7.13) was shorter than favorable group (114.00 ± 8.64) and (patients with abnormal cytogenetics in intermediate and poor-risk groups (107.16 ± 16.71) (log-rank test = 10.83, P = 0.004), also patients with low BAALC (123.1 ± 4.9) had longer mean survival time than patients with high BAALC (45.85 ± 5.1) (log-rank test = 31.20, P = 0.000) as shown in [Table 6] and [Figure 3].

Mean survival time according to chemotherapy response, cytogenetics and brain and acute leukemia, cytoplasmic among studied acute myeloid leukemia patients by Kaplan- Meier test

Forty-five patient died 45/70 (64.3%). 3 (4.3%) patients died initially before starting induction therapy related to disease (early death), 4 (5.7%) patients died throughout induction chemotherapy period (induction death), 7 (10%) died during consolidation due to chemotherapy toxicity, and 29 (41.4%) patients died as a result of salvage chemotherapy toxicity in nonresponding patients, cause of death was mainly toxicity of chemotherapy (septic shock, heart failure, acute respiratory distress syndrome, and cardiogenic shock), in our study causes of early deaths in our study were related to disease progression (i.e., septic shock, DIC, cerebral haemorrhage and multiorgan failure).

Concerning toxicity; nearly all patients developed variable degrees of haematological toxicities, there was no difference regard toxicity pattern between both BAALC high and low group, although sepsis was numerically more common during induction in BAALC high group. Toxicity was listed in [Table 7].

Toxicities during induction and consolidation therapy

Discussion

In this study, we analyzed BAALC gene expression in 58 adult de novo AML patients (18–60 years) and evaluated its prognostic significance.

Typically, BAALC mRNA isn't detected in normal individuals; there was a statistically significant difference in expression between patients group and control, similar to what was reported by other studies.[2],[9]

We found no correlation between age and BAALC gene expression, that agreed with what reported in other studies by Bienz et al.,[10] and Metzeler et al.[4] That differs from what was stated by Rashed et al.,[11] who detected a significant correlation between high BAALC gene expression and age. Patients older than 45 years had higher High BAALC expression. To confirm such an association, larger sample size may be needed.

BAALC gene expression no significant association different between sex, similar to what was declared in other studies.[7],[11],[12]

Patients in normal cytogenetic risk group had higher BAALC overexpression than the other two groups; this concurs with Zhou et al.[13]

We found that patients with CN-AML had higher (TLC, LDH level and blast cell count) and lower (PLT count and Hb level) that were statistically significant compared to the other groups. In patients with CN-AML median BAALC was 3.21, that was a statistically significant difference than the other two groups. This agreed with Zhou et al.,[13] where BAALC median was 3.74.

Our cut off value for BAALC gene expression was > 2.11 with sensitivity 86.1% and specificity 80%, near to what stated by Zhou et al., where the cut-off value was > 2.35 with sensitivity 55% and specificity 100.

No significant difference between both BAALC high expressed and low expressed patients regard age distribution, this agrees with Soliman et al.,[14] in contrary to Zhou et al.,[13] Rashed et al.,[11] who recorded that low BAALC expresser patients were significantly younger than high BAALC expresser patients.

Patients with low BAALC expression had significant lower BM blasts than in high BAALC expression group that work in with Qi et al.,[15] Zhou et al.,[13] Schwind et al. did not confirm these findings,[16] and Weber et al.,[7] who did not found the difference in BM blasts between low BAALC expressed and high BAALC expressed groups. We could be owed this to the differences in the distribution of AML subtype or ethnicity.

Regard correlation between BAALC expression and response rate was found that patient with low BAALC expression achieved higher CR rate (70%) in comparison to patients with high BAALC (40%), this agrees with El-Sharnouby et al.,[17] and Yahya et al.,[18] who found that frequency of CR was higher in low BAALC expresser patients than in high expressers 71.4% versus 50% and 73.9% versus 22.7% respectively. Also, patients with high BAALC expression had a significantly worse clinical outcome than low expressers.

Regard survival, we found low BAALC expression patients had significantly longer overall survival than high BAALC expression patients (123 vs. 45 weeks respectively), and this came in concordance with Zhou et al.,[13] and Yahya et al.,[18] who shows superior overall survival (15.02 vs. 7.02 months) in low BAALC expressers.

In concordance with what stated by Bienz et al.,[10] Baldus et al.,[2] Langer et al.,[3] Langer et al., 2009[19]; Schwind et al.,[16] and Eisfeld et al.,[20] we found that The likely hood of death was almost twice in high BAALC expression patients compared to low BAALC expression patients.

Limitation of our study

Risk stratification based on only cytogenetics. Were molecular markers such as FLT3, IDH1, NPM1. We used Doxorubicine as it is the available anthracycline in our institute.

Conclusion

AML patients had increased BAALC gene expression. High BAALC expression is associated with a higher risk of relapse and lower rates of CR. This molecular marker is specific significant associated with response to treatment, disease progression and survival. So its overexpression is a poor prognostic marker, it might be of a potential target for the evolution of new therapies.

Acknowledgements

We want to thank our patients for their participation and compliance.

Conflict of Interest

There are no conflicts of interest.

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Publication History

Received: 05 May 2020

Accepted: 02 October 2020

Article published online:
14 May 2021

© 2020. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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