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Flow-cytometric monitoring of disease-associated expression of 9-O-acetylated sialoglycoproteins in combination with known CD antigens, as an index for MRD in children with acute lymphoblastic leukaemia: a two-year longitudinal follow-up study.

Chowdhury S, Bandyopadhyay S, Mandal C, Chandra S, Mandal C - BMC Cancer (2008)

Bottom Line: A range of MRD values can be predicted for the patients in CR, irrespective of their lineage, being 0.03 +/- 0.01% (PB) and 0.05 +/- 0.015% (BM).Hence, MRD study beyond two-years follow-up is necessary to investigate further reduction in MRD, thereby ensuring their disease-free survival.Therefore, we suggest use of these templates for MRD detection, during and post-chemotherapy for proper patient management strategies, thereby helping in personalizing the treatment.

View Article: PubMed Central - HTML - PubMed

Affiliation: Immunobiology Division, Indian Institute of Chemical Biology, 4, Raja S, C, Mullick Road, Kolkata 700032, Kothari Medical Centre 8/3, Alipore Road, Kolkata 700027, India. suchandra_chowdhury@rediffmail.com

ABSTRACT

Background: Over expression of 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-GPs, abbreviated as OAcSGP) has been demonstrated as a disease-associated antigen on the lymphoblasts of childhood acute lymphoblastic leukaemia (ALL). Achatinin-H, a lectin, has selective affinity towards terminal 9-O-acetylated sialic acids-alpha2-6-Nacetylated galactosamine. Exploring this affinity, enhanced expression of OAcSGP was observed, at the onset of disease, followed by its decrease with chemotherapy and reappearance with relapse. In spite of treatment, patients retain the diseased cells referred to as minimal residual disease (MRD) responsible for relapse. Our aim was to select a suitable template by using the differential expression of OAcSGP along with other known CD antigens to monitor MRD in peripheral blood (PB) and bone marrow (BM) of Indian patients with B- or T-ALL during treatment and correlate it with the disease status.

Methods: A two-year longitudinal follow-up study was done with 109 patients from the onset of the disease till the end of chemotherapy, treated under MCP841protocol. Paired samples of PB (n = 1667) and BM (n = 999) were monitored by flow cytometry. Three templates selected for this investigation were OAcSGP+CD10+CD19+ or OAcSGP+CD34+CD19+ for B-ALL and OAcSGP+CD7+CD3+ for T-ALL.

Results: Using each template the level of MRD detection reached 0.01% for a patient in clinical remission (CR). 81.65% of the patients were in CR during these two years while the remaining relapsed. Failure in early clearance of lymphoblasts, as indicated by higher MRD, implied an elevated risk of relapse. Soaring MRD during the chemotherapeutic regimen predicted clinical relapse, at least a month before medical manifestation. Irrespective of B- or T-lineage ALL, the MRD in PB and BM correlated well.

Conclusion: A range of MRD values can be predicted for the patients in CR, irrespective of their lineage, being 0.03 +/- 0.01% (PB) and 0.05 +/- 0.015% (BM). These patients may not be stated as normal with respect to the presence of MRD. Hence, MRD study beyond two-years follow-up is necessary to investigate further reduction in MRD, thereby ensuring their disease-free survival. Therefore, we suggest use of these templates for MRD detection, during and post-chemotherapy for proper patient management strategies, thereby helping in personalizing the treatment.

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Details of the study population in childhren with ALL, beginning with diagnosis and ending with the completion of MCP841 protocol. n = Number of patients; percentage of patients among the total population is indicated in parentheses.
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Figure 8: Details of the study population in childhren with ALL, beginning with diagnosis and ending with the completion of MCP841 protocol. n = Number of patients; percentage of patients among the total population is indicated in parentheses.

Mentions: The templates used in this investigation enable MRD detection in both PB and BM of every B-and T-ALL patient. Patients in CR have MRD between 0.02–0.04% in PB and 0.04–0.06% in BM irrespective of B/T-ALL. Although the difference between the MRD in PB and BM is significant (p value < 0.0001, Table 1), the clinical status of the patients can be revealed even from PB. In the study population comprising 130 children with ALL at diagnosis, 21 patients could not be monitored after diagnosis, as they were not available. Among the remaining 109 children, 81.65% attained and remained in CR throughout the two-year chemotherapeutic regimen while 18.34% showed abnormal pattern in MRD. 8.26% of these patients had high MRD during induction 1 with subsequent relapse in 5.5% patients during maintenance. Among the relapsed patients, 1.83% died while the remaining attained CR.10.09% of the patients showed elevated MRD few weeks before relapse. While one of them escaped relapse, 7.34% experienced so, accomplishing CR and 1.83% dying post relapse (Figure 8).


Flow-cytometric monitoring of disease-associated expression of 9-O-acetylated sialoglycoproteins in combination with known CD antigens, as an index for MRD in children with acute lymphoblastic leukaemia: a two-year longitudinal follow-up study.

Chowdhury S, Bandyopadhyay S, Mandal C, Chandra S, Mandal C - BMC Cancer (2008)

Details of the study population in childhren with ALL, beginning with diagnosis and ending with the completion of MCP841 protocol. n = Number of patients; percentage of patients among the total population is indicated in parentheses.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2268943&req=5

Figure 8: Details of the study population in childhren with ALL, beginning with diagnosis and ending with the completion of MCP841 protocol. n = Number of patients; percentage of patients among the total population is indicated in parentheses.
Mentions: The templates used in this investigation enable MRD detection in both PB and BM of every B-and T-ALL patient. Patients in CR have MRD between 0.02–0.04% in PB and 0.04–0.06% in BM irrespective of B/T-ALL. Although the difference between the MRD in PB and BM is significant (p value < 0.0001, Table 1), the clinical status of the patients can be revealed even from PB. In the study population comprising 130 children with ALL at diagnosis, 21 patients could not be monitored after diagnosis, as they were not available. Among the remaining 109 children, 81.65% attained and remained in CR throughout the two-year chemotherapeutic regimen while 18.34% showed abnormal pattern in MRD. 8.26% of these patients had high MRD during induction 1 with subsequent relapse in 5.5% patients during maintenance. Among the relapsed patients, 1.83% died while the remaining attained CR.10.09% of the patients showed elevated MRD few weeks before relapse. While one of them escaped relapse, 7.34% experienced so, accomplishing CR and 1.83% dying post relapse (Figure 8).

Bottom Line: A range of MRD values can be predicted for the patients in CR, irrespective of their lineage, being 0.03 +/- 0.01% (PB) and 0.05 +/- 0.015% (BM).Hence, MRD study beyond two-years follow-up is necessary to investigate further reduction in MRD, thereby ensuring their disease-free survival.Therefore, we suggest use of these templates for MRD detection, during and post-chemotherapy for proper patient management strategies, thereby helping in personalizing the treatment.

View Article: PubMed Central - HTML - PubMed

Affiliation: Immunobiology Division, Indian Institute of Chemical Biology, 4, Raja S, C, Mullick Road, Kolkata 700032, Kothari Medical Centre 8/3, Alipore Road, Kolkata 700027, India. suchandra_chowdhury@rediffmail.com

ABSTRACT

Background: Over expression of 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-GPs, abbreviated as OAcSGP) has been demonstrated as a disease-associated antigen on the lymphoblasts of childhood acute lymphoblastic leukaemia (ALL). Achatinin-H, a lectin, has selective affinity towards terminal 9-O-acetylated sialic acids-alpha2-6-Nacetylated galactosamine. Exploring this affinity, enhanced expression of OAcSGP was observed, at the onset of disease, followed by its decrease with chemotherapy and reappearance with relapse. In spite of treatment, patients retain the diseased cells referred to as minimal residual disease (MRD) responsible for relapse. Our aim was to select a suitable template by using the differential expression of OAcSGP along with other known CD antigens to monitor MRD in peripheral blood (PB) and bone marrow (BM) of Indian patients with B- or T-ALL during treatment and correlate it with the disease status.

Methods: A two-year longitudinal follow-up study was done with 109 patients from the onset of the disease till the end of chemotherapy, treated under MCP841protocol. Paired samples of PB (n = 1667) and BM (n = 999) were monitored by flow cytometry. Three templates selected for this investigation were OAcSGP+CD10+CD19+ or OAcSGP+CD34+CD19+ for B-ALL and OAcSGP+CD7+CD3+ for T-ALL.

Results: Using each template the level of MRD detection reached 0.01% for a patient in clinical remission (CR). 81.65% of the patients were in CR during these two years while the remaining relapsed. Failure in early clearance of lymphoblasts, as indicated by higher MRD, implied an elevated risk of relapse. Soaring MRD during the chemotherapeutic regimen predicted clinical relapse, at least a month before medical manifestation. Irrespective of B- or T-lineage ALL, the MRD in PB and BM correlated well.

Conclusion: A range of MRD values can be predicted for the patients in CR, irrespective of their lineage, being 0.03 +/- 0.01% (PB) and 0.05 +/- 0.015% (BM). These patients may not be stated as normal with respect to the presence of MRD. Hence, MRD study beyond two-years follow-up is necessary to investigate further reduction in MRD, thereby ensuring their disease-free survival. Therefore, we suggest use of these templates for MRD detection, during and post-chemotherapy for proper patient management strategies, thereby helping in personalizing the treatment.

Show MeSH
Related in: MedlinePlus