• Abdulrahman A. Muhsin Paediatric Haematology, Health Sciences, University of Duhok, Department of Medical laboratories , Kurdistan Region, Iraq.
  • Akrem M. Atrushi College of Medicine, University of Duhok, Department of Paediatric.
  • Adnan A. Al-Doski Department of Pathology, College of Medicine, University of Duhok.



Leukemia, minimal residual, flowcytometry, remission


In Acute lymphoblastic Leukemia (ALL) assessment of molecular response to treatment, assessing minimal residual disease (MRD) is a major independent predictor of treatment outcome. Consequently, MRD is implemented in all ALL-treatment protocols to fill up or to redefine stratification of multifactorial risk with optional intensity of customized treatment.

Aim: to specify the significance of MRD in the assessment of remission in children with ALL with results discordant between morphology and flow cytometry at the end of induction phase of therapy.

Materials and Methods: A descriptive cross-sectional study was conducted at Jin Oncology Center from March 2019 through November 2023. Data were taken out of the records of 58 patients who had ALL less than 16 years old. All patients were less than 16 years old and treated by ukall. They were diagnosed using peripheral blood morphology, bone marrow study and/or flow cytometry when lymphoblasts in peripheral blood or bone marrow aspirate are ≥20% and was confirmed by flow cytometry. On 29th day of induction therapy, bone marrow was examined for morphology and flow cytometry. The presence or absence of MRD was determined, and CD19, CD10 and tdt were tested. By morphologic assessment they were divided patients into: Category 1, C1 (<5% blasts), Category 2, C2 (5-20% blasts), and Category 3, C3 (>20% blasts). Statistical analysis was made using SPSS version 25. P value of less than 0.05 was considered significant.

Results: The study involved 58 patients who had ALL. with a median age of 6.5 years, male to females ratio of 1.76:1, mean platelet count of 96.6 x 10⁹/L ,mean hemoglobin of 8.6 g/dL, mean leucocyte count of 74.3 x 10⁹/L), 48 cases (82.7%) of B-cell lineage and 10 cases (17.3%) of T-cell lineage, 94.6% of the B-cell cases were of the common B-ALL and the rest Pro-BALL type, 54.6% of the T-cell ALL was cortical T-ALL  and 44.4% Early T-cell ALL.  They were tested for MRD by morphology and flow cytometry on day 29. By morphology, 46 patients had remission but by flow only 24 cases. Seventeen cases had residual blasts >5%. In 19 cases there was a discrepancy between the results of morphology and flow. Twenty-five cases (52.08% of B-cell cases) were positive for MRD by flow results. Eight of the ten cases of T-ALL (80%), were positive for MRD by flow cytometry. Among 48 cases of B-ALL, 36 were in C1 category (morphologically in remission), 11 cases were in C2 category and one case in the C3 category. Of cases in C1 category, 17 were MRD +ve and 19 were MRD –ve by flow cytometry. In the C2 category, only 2 out of the 11 cases (18.18%) had discordant results between morphology and flow results. The correlation between morphology and flow results was 100% in the C3 category.

Conclusion: MRD should not be the surrogate of morphology but to be used in conjunction in order to give us a more accurate representation of status of remission.


Howlader N., Noone A.M., Krapcho M., Miller D., Brest A., Yu M., Ruhl J., Tatalovich Z., Mariotto A., Lewis D.R., et al. SEER Cancer Statistics Review, 1975–2017. National Cancer Institute; Bethesda, MD, USA: 2020. [Google Scholar]

Lavi O., Gottesman M.M., Levy D. The dynamics of drug resistance: A mathematical perspective. Drug Resist. Updates. 2012;15:90–97. doi: 10.1016/j.drup.2012.01.003. [PMCfree article] [PubMed] [CrossRef] [Google Scholar]

Pui C.H., Yang J.J., Hunger S.P., Pieters R., Schrappe M., Biondi A., Vora A., Baruchel A., Silverman L.B., Schmiegelow K., et al. Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration. J. Clin. Oncol. 2015;33:2938–2948. doi: 10.1200/JCO.2014.59.1636. [PMCfree article] [PubMed] [CrossRef] [Google Scholar]

Della Starza I, De Novi LA, Santoro A, et al. Digital droplet PCR and next-generation sequencing refine minimal residual disease monitoring in acute lymphoblastic leukemia. LeukLymphoma. 2019;60(11):2838–2840. . [PubMed]

Wood B, Wu D, Crossley B, et al. Measurable residual disease detection by high-throughput sequencing improves risk stratification for pediatric ALL. Blood. 2018;131(12):1350–1359. . [PMC free article] [PubMed]

Medina A, Puig N, Flores-Montero J, et al. Comparison of Next-Generation Sequencing (NGS) and next-Generation Flow (NGF) for Minimal Residual Disease (MRD) Assessment in Multiple Myeloma. Blood Cancer J. 2020;10(10):108. . [PMC free article] [PubMed]

Drandi D, Kubiczkova-Besse L, Ferrero S, et al. Minimal Residual Disease Detection by Droplet Digital PCR in Multiple Myeloma, Mantle Cell Lymphoma, and Follicular Lymphoma: A Comparison with Real-Time PCR. J Mol Diagn. 2015;17(6):652–660. . [PubMed]

Aitken MJL, Ravandi F, Patel KP, Short NJ. Prognostic and therapeutic implications of measurable residual disease in acute myeloid leukemia. J Hematol Oncol. 2021;14(1):137. . [PMC free article] [PubMed]

Berry DA, Zhou S, Higley H, et al. Association of Minimal Residual Disease With Clinical Outcome in Pediatric and Adult Acute Lymphoblastic Leukemia: A Meta-analysis. JAMA Oncol. 2017;3(7):e170580. . [PMC free article] [PubMed]

Short NJ, Zhou S, Fu C, et al. Association of measurable residual disease with survival outcomes in patients with acute myeloid leukemia: a systematic review and meta-analysis. JAMA Oncol. 2020;6(12):1890–1899. . [PMC free article] [PubMed]

Avet-Loiseau H, Ludwig H, Landgren O, et al. Minimal Residual Disease Status as a Surrogate Endpoint for Progression-free Survival in Newly Diagnosed Multiple Myeloma Studies: A Meta-analysis. Clin Lymphoma Myeloma Leuk. 2020;20(1):e30–e37. . [PMC free article] [PubMed]

Galimberti S, Devidas M, Lucenti A, et al. Validation of Minimal Residual Disease as Surrogate Endpoint for Event-Free Survival in Childhood Acute Lymphoblastic Leukemia. JNCI Cancer Spectr. 2018;2(4):pky069. . [PMC free article] [PubMed]

Gökbuget N, Kneba M, Raff T, et al. Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies. Blood. 2012;120:1868–76. [PubMed] [CrossRef]

Bassan R, Spinelli O. Minimal residual disease monitoring in adult ALL to determine therapy. Curr Hematol Malig Rep. 2015;10:86–95. [PubMed] [CrossRef]

van Dongen J, van der Velden V, Brüggemann M, Orfao A. Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies. Blood. 2015;125:3996–4009. [PMC free article] [PubMed] [CrossRef]

McKenna RW, LaBaron WT, Aquino DB, Picker LJ, Kroft SH. Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone marrow specimens by 4-color flow cytometry. Blood. 2001. ;98(8):2498-507.

Coustan-Smith E, Mullighan CG, Onciu M, Behm F, Raimondi S, Pei D et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol. 2009. 10(2):147-56

Cazzaniga G, Valsecchi M, Gaipa G, Conter V, Biondi A. Defining the correct role of minimal residual disease tests in the management of acute lymphoblastic leukaemia. Br J Hematology. 2011

Campana D, Pui CH. Minimal residual disease-guided therapy in childhood acute lymphoblastic leukemia. Blood. 2017; 129(14): 1913–8.

van Dongen JJ, van der Velden VH, Brüggemann M, Orfao A. Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies. Blood. 2015. 125(26):3996-4009.

Roshal M, Fromm JR, Winter SS, Dunsmore KP, Wood BL. Immaturity associated antigens are lost during induction for T cell lymphoblastic leukemia: implications for minimal residual disease detection. Cytometry B Clin Cytom. 2010;78(3):139-46

Jalal SD, Al-Allawi NA, Al Doski AA. Immunophenotypic aberrancies in acute lymphoblastic leukemia from 282 iraqi Patients. Int J Lab Hematol. 2017;39(6):625-32.

Coustan-Smith E, Mullighan CG, Onciu M, Behm F, Raimondi S, Pei D et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol. 2009. 10(2):147-56

Rhein P, Scheid S, Ratei R, Hagemeier C, Seeger K, Kirschner-SchwabeGene R et al. expression shift towards normal B cells, decreased proliferative capacity and distinct surface receptors characterize leukemic blasts persisting during induction therapy in childhood acute lymphoblastic leukemia. Leukemia, 2021; 21: 897–905.

Dworzak MN, Fritsch G, Fleischer C, Printz D, Fröschl G, Buchingeret Pal. Multiparameter phenotype mapping of normal and post-chemotherapy B lymphopoiesis in pediatric bone marrow. Leukemia. 1997; 11(8):1266-73.

Dworzak MN, Gaipa G, Schumich A, Maglia O, Ratei R, Veltroni M et al. Modulation of antigen expression in B-cell precursor acute lymphoblastic leukemia during induction therapy is partly transient: evidence for a drug-induced regulatory phenomenon. Results of the AIEOP-BFM-ALL-FLOW-MRD-Study Group. Cytometry B Clin Cytom. 2010;78(3):147-53

Farahat N, Morilla A, Catovsky D, Ricardo Morilla Pinkerton C et al. Detection of minimal residual disease in B-lineage acute lymphoblastic leukaemia by quantitative flow cytometry Br J Haematol. 1998;101(1):158-64.

Yokota S., Hansen-Hagge TE, Ludwig WD, ReiterA, RaghavacharmA, Kleihauer E, et al. Use of polymerase chain reactions to monitor minimal residual disease in acute lymphoblastic leukemia patients. Blood. 1991; 77(2):331-9.

Rathe M, Preiss B, Marquart HV, Schmiegelow K, Wehner PS. Minimal residual disease monitoring cannot fully replace bone marrow morphology in assessing disease status in pediatric acute lymphoblastic APMIS. 2020; 128(5):414-




How to Cite

Muhsin, A. A., Atrushi , A. M., & Al-Doski, A. A. (2024). THE SIGNIFICANCE OF MINIMAL RESIDUAL DISEASE IN ACUTE LYMPHOBLASTIC LEUKAEMIA: A SINGLE CENTRE STUDY. Science Journal of University of Zakho, 12(2), 144–148.



Science Journal of University of Zakho