The prognostic significance of minimal residual disease in adult Egyptian patients with precursor acute lymphoblastic leukemia

Samra, Mohamed; Mahmoud, Hossam K.; Abdelhamid, Thoraya; Sharkawy, Nahla M. El; Elnahass, Yasser; Elgammal, Mossaad; Abdelfattah, Rafaat Ms; Eid, Salem; Ghaleb, Fayek M.; Kamel, Azza M.

doi:10.1016/j.jnci.2013.05.004

Cited by 9 publications

(7 citation statements)

References 22 publications

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“…The cumulative DFS at 2 years for our study group was 43% in comparison to 42% DFS at 2 years in NCI [11], and 64% & 53% reported by others [19] & [20], while the cumulative OS at 2 years for our study group was 46% in comparison to 49% in NCI [11] and 43% at 3-years follow up reported by Larson et al [21].…”

Section: Discussionsupporting

confidence: 45%

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Study of Minimal Residual Disease in Adults with B-Lineage Acute Lymphoblastic Leukemia by Flowcytometry

Ghonaim¹,

Elgohary²

2017

JCT

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Background: After achieving morphological remission, existence of few number of leukemic cells in the patient's blood represents the minimal residual disease (MRD) and its monitoring helps in evaluating early treatment response and future relapse. Patients and methods: Eighty seven newly diagnosed (B-ALL) cases were enrolled in the present study in the time period from October 2013 to October 2016. A panel of 4 monoclonal antibodies (CD10FITC, CD19PE, CD34PercP and CD45APC) were defined at diagnosis and after morphological remission for tracing of minimal residual disease (MRD). Results: Eighty seven newly diagnosed B-ALL cases were included in the present study of which 73 (84%) showed positive expression to CD45 in combination with (CD10, CD19 and CD34) at diagnosis, which allow us to use this combination for further assessment of MRD after morphological remission. In our study 65% of patients had negative MRD (<0.01), while 35% of patients had positive MRD (≥0.01). The DFS and OS for patients with MRD−ve were significantly higher than those with MRD + ve (P = 0.01 & P = 0.04) respectively. Conclusion: MRD detection by flow cytometry using the combination of CD45 with CD10, CD19 & CD34 is an easy and reliable method. Patients with positive MRD are at higher risk of relapse and have inferior overall survival rates compared to those with MRD−ve. Future studies focusing on treatment intensification for the group of patients with +ve MRD aiming to improve the treatment outcome are warranted.

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Section: Discussionsupporting

confidence: 45%

“…The CR rate in our study was 74% compared to 88% in a study done in NCI [11], however their study included patients with both B and T-ALL, while our patients were B-ALL as shown in Table 1.…”

Section: Discussionmentioning

confidence: 57%

Study of Minimal Residual Disease in Adults with B-Lineage Acute Lymphoblastic Leukemia by Flowcytometry

Ghonaim¹,

Elgohary²

2017

JCT

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“…Several groups showed the predictive value of MRD at the end of induction therapy with low MRD values correlating with better long-term outcome. [10,11] This study demonstrates the feasibility of administering 8 doses of L-asparaginase over two phases rather than over the 4-week period as per the original BFM protocols. This was associated with reduced toxicity and did not compromise the efficacy of the therapy.…”

Section: Discussionmentioning

confidence: 87%

Effect of Dose and Schedule of L-Asparaginase Administration on Early Minimal Residual Disease in Acute Lymphoblastic Leukemia

Gupta

Sehrawat²,

Dang³

et al. 2019

Indian Journal of Medical and Paediatric Oncology

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Background and Objectives: L-asparaginase has become the backbone of acute lymphoblastic leukemia induction. In Berlin–Frankfurt–Munster (BFM) 95/2000 protocols, L-asparaginase was given twice weekly for initial 4 weeks. While sufficient L-asparaginase levels are important, there is no apparent correlation between high L-asparaginase levels and minimal residual disease (MRD). In view of toxicities of L-asparaginase, we planned to study the effect of dose and schedule of Escherichia coli -derived L-asparaginase on early MRD by phasing the same total dose, once a week over 8 weeks. Methods: This prospective, observational study enrolled 45 children and young adults ≤40 years. Modified BFM 95 protocol was followed. Weekly 5000 IU/m 2 L-asparaginase was given intravenously, and MRD was analyzed at the end of 4 weeks (MRD1) and at 8 weeks (MRD2), using multicolor flow cytometry. MRD positive was defined as residual blasts ≥0.01%. Results: Thirty-one patients were eligible for final analysis. Nine could receive scheduled eight doses of L-asparaginase and 22 patients received less than eight doses. We analyzed age, gender, diagnosis, prednisone response, cytogenetics, central nervous system status, BFM risk group, MRD2, and relapse. L-asparaginase dose association was not statistically significant with respect to MRD2 ( P = 0.237). There were no cases of pancreatitis, hypersensitivity, bleeding, or thrombosis. Reasons for patients receiving less than the scheduled eight doses were low serum fibrinogen levels and liver dysfunction. This study revealed 8 MRD1-negative and 13 MRD2-negative patients. Conclusion: L-asparaginase dose intensity does not affect early MRD. Phasing L-asparaginase over 8 weeks could lead to the achievement of more MRD2-negative status and thereby improve long-term outcome. This strategy may also reduce the incidence of adverse drug events.

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“…All constitutes 30% of all pediatric malignancies and 70% of pediatric leukemia [6]. Minimal residual disease (MRD) studies in childhood acute lymphoblastic leukemia (ALL) give highly significant prognostic information superior to other standard criteria as age, gender and total leucocytic count (TLC) in distinguishing patients at high and low risk of relapse [7]. The approach used in this study was to determine whether panel of antibodies combination are more suitable for detection of MRD in childhood B lineage ALL.…”

Section: Discussionmentioning

confidence: 99%

Detection of Minimal Residual Disease in Childhood B-Acute Lymphoblastic Leukemia by 4-Color Flow Cytometry

Baraka¹,

Sherief²,

Kamal³

et al. 2017

J Hematol Thrombo Dis

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Monitoring of minimal residual disease (MRD) is today considered the most powerful predictor of outcome in acute leukemias, including acute lymphoblastic leukemia (ALL). The study aimed to determine whether panel of antibodies combination are more suitable than others for detection of MRD in Childhood B-lineage ALL. Eighty four (84) patients of ALL (B-lineage subtype) were enrolled in this study. Normal template for B. Cell precursors were been established in 15 control Patients by using 4 panels of monoclonal Abs (Mo Abs), {CD22, CD45, CD58 and CD97 in combination with CD10, CD19, CD34}. At diagnosis CD22 having the lowest incidence expression between the patients in 50% only, but CD45, CD58, and CD97 were expressed in 80.9%, 52.3% and 92.8% respectively. Analysis of MRD was performed for each Mo Abs combination at day 0 and day 14 post induction of chemotherapy by 4-color flow cytometer (FCM). The incidence of MRD were 61.9%, 70.6%, 60.0% and 55.5% for CD22,CD45,CD58 and CD97 respectively. Seventy-six from total 84 cases studied (90.0%) had at least one LAIP. Of these, 22 (29.0%) had only one LAIP and 54 cases (71.0%) had ≥ 2 LAIPS Conclusion: In the B-ALL patients (CD10/CD19/CD34/CD45)+ and (CD10/CD19/CD34/CD97)+, represented the highest incidence markers expression of leukemic cells with a significant correlation with blasts count, so it's the more specific for MRD detection.

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The prognostic significance of minimal residual disease in adult Egyptian patients with precursor acute lymphoblastic leukemia

Abstract: MRD by FCM is a strong independent predictor of outcome in terms of DFS and OS and is a powerful informative parameter in guiding individual treatment in ALL patients.

Cited by 9 publications

References 22 publications

Study of Minimal Residual Disease in Adults with B-Lineage Acute Lymphoblastic Leukemia by Flowcytometry

Study of Minimal Residual Disease in Adults with B-Lineage Acute Lymphoblastic Leukemia by Flowcytometry

Effect of Dose and Schedule of L-Asparaginase Administration on Early Minimal Residual Disease in Acute Lymphoblastic Leukemia

Detection of Minimal Residual Disease in Childhood B-Acute Lymphoblastic Leukemia by 4-Color Flow Cytometry

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