Post-Induction Minimal Residual Disease Study by Flow Cytometry in Pediatric B ALL and Its Correlation with Initial Clinical and Laboratory Parameters
Main Article Content
Keywords
B-cell acute lymphoblastic leukemia, minimal residual disease, pediatric leukemia, flow cytometry
Abstract
Background: Acute lymphoblastic leukemia (ALL) is a cancer characterized by the rapid and uncontrolled growth of immature lymphoid cells. Among its subtypes, B-lineage ALL in children represents the most frequently diagnosed malignancy in the pediatric population. Despite high survival rates, relapsed or refractory cases remain challenging. Minimal Residual Disease (MRD), detected by flow cytometry, is a strong prognostic marker that guides the intensity of post-induction therapy. Aim: This study aims to evaluate the correlation between post-induction MRD, measured by multicolor flow cytometry, and the initial clinical and laboratory parameters in pediatric patients with B-ALL. Methods: A retrospective cross-sectional study was conducted at the Children’s Specialty Hospital in Basrah, including 51 pediatric B-ALL patients (aged 1–14 years) treated between April 2023 and August 2024. All patients successfully completed the induction phase of chemotherapy, and their MRD status was subsequently evaluated. Results: MRD was negative in 60.78% and positive in 39.22% of patients. The majority of patients in both MRD groups were under 10 years old, with no significant age-related difference (P = 0.732). Patients with positive MRD had significantly higher mean white blood cell (WBC) counts (58.62 ± 86.9 vs. 11.44 ± 13.04) and blast cell percentages (87.1% ± 7.6% vs. 76.6% ± 16%) compared to those with negative MRD (P = 0.004 and 0.008, respectively). No significant associations were found between MRD and hemoglobin levels, platelet counts, or National Cancer Institute (NCI) risk classification. Conclusions: Flow cytometric MRD detection is a valuable prognostic tool in pediatric B-ALL. Higher WBC counts and blast percentages at presentation are associated with positive MRD, while MRD was not significantly linked to age, hemoglobin, platelet count, or risk stratification
References
2. Islami F, Miller KD, Jemal A. Cancer burden in the United States—A review. Ann Cancer Epidemiol. 2018;2.
3. Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the Children's Oncology Group. J Clin Oncol. 2012;30(14):1663–9.
4. Inaba H, Pui CH. Advances in the diagnosis and treatment of pediatric acute lymphoblastic leukemia. J Clin Med. 2021;10(9):1926.
5. Hoffman LM, Gore L. Blinatumomab, a bi-specific anti-CD19/CD3 BiTE® antibody for the treatment of acute lymphoblastic leukemia: perspectives and current pediatric applications. Front Oncol. 2014;4:63.
6. Al-Hadad SA, Al-Dabbagh B, Al-Saad S, et al. Treatment of childhood acute lymphoblastic leukemia in Iraq: a 17-year experience from a single center. Leuk Lymphoma. 2021;62(14):3430–9.
7. Brüggemann M, Kotrova M. Minimal residual disease in adult ALL: technical aspects and implications for correct clinical interpretation. Hematology Am Soc Hematol Educ Program. 2017;2017(1):13–21.
8. Gaipa G, Basso G, Biondi A, Campana D. Detection of minimal residual disease in pediatric acute lymphoblastic leukemia. Cytometry B Clin Cytom. 2013;84(6):359–69.
9. Neale G, Coustan-Smith E, Stow P, et al. Comparative analysis of flow cytometry and polymerase chain reaction for the detection of minimal residual disease in childhood acute lymphoblastic leukemia. Leukemia. 2004;18(5):934–8.
10. Borowitz MJ, Devidas M, Hunger SP, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study. Blood. 2008;111(12):5477–85.
11. Pui CH. Central nervous system disease in acute lymphoblastic leukemia: prophylaxis and treatment. ASH Educ Program Book. 2006;2006(1):142–6.
12. Meraj F, Jabbar N, Nadeem K, Taimoor M, Mansoor N. Minimal residual disease in childhood B lymphoblastic leukemia and its correlation with other risk factors. Pak J Med Sci. 2020;36(1):S20–S26.
13. Katsibardi K, Moschovi MA, Braoudaki M, Papadhimitriou SI, Papathanasiou C, Tzortzatou-Stathopoulou F. Sequential monitoring of minimal residual disease in acute lymphoblastic leukemia: 7-year experience in a pediatric hematology/oncology unit. Leuk Lymphoma. 2010;51(5):846–52.
14. Borowitz M, Devidas M, Hunger SP, et al. Minimal residual disease detection in childhood precursor–B-cell acute lymphoblastic leukemia: relation to other risk factors. A Children's Oncology Group study. Leukemia. 2003;17(8):1566–72.
15. Tembhare PR, Sadalge PK, Mahapatra M, et al. Post-induction measurable residual disease using multicolor flow cytometry is strongly predictive of inferior clinical outcome in the real-life management of childhood T-cell acute lymphoblastic leukemia: a study of 256 patients. Front Oncol. 2020;10:577.
16. Yamaji K, Aoki K, Kobayashi R, et al. Minimal residual disease-based augmented therapy in childhood acute lymphoblastic leukemia: a report from the Japanese Childhood Cancer and Leukemia Study Group. Pediatr Blood Cancer. 2010;55(7):1287–95.
17. Zhou J, Coustan-Smith E, Sancho J, et al. Quantitative analysis of minimal residual disease predicts relapse in children with B-lineage acute lymphoblastic leukemia in DFCI ALL Consortium Protocol 95-01. Blood. 2007;110(5):1607–11.
18. Farweez BAT, Kassim NA, Abdelfataah MF, Hassan NM, Hassnien DEA, El-Sakhawy YN. Clinical impact of early minimal residual disease detection at day 15 in precursor B-childhood acute lymphoblastic leukemia: an Egyptian experience. Egypt J Med Hum Genet. 2020;21:1–11.
19. Borowitz MJ, Devidas M, Hunger SP, et al. Prognostic significance of minimal residual disease in high-risk B-ALL: a report from Children’s Oncology Group study AALL0232. Blood. 2015;126(8):964–71.
20. Vaitkevičienė G, Džiazko A, Kalėdienė R, et al. High white blood cell count at diagnosis of childhood acute lymphoblastic leukemia: biological background and prognostic impact. Results from the NOPHO ALL‐92 and ALL‐2000 studies. Eur J Haematol. 2011;86(1):38–46.
21. Petit A, Martinsson T, Porwit-MacDonald A, et al. Oncogenetic mutations combined with MRD improve outcome prediction in pediatric T-cell acute lymphoblastic leukemia. Blood. 2018;131(3):289–300.
