⚡ Bone Marrow Risk Assessment

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Bone Marrow Risk Assessment

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Dr. Naglaa Salem, MD, FCAP- Interpretation of BM Biopsies

The results indicated the clastogenic action of etoposide in mouse bone marrow after a single treatment with such low doses. However, the drug did not interfere with cell cycle progression. Although it is a DNA-non-intercalating agent, etoposide is known for its interference in the activity of DNA topoisomerase IIalpha enzyme, particularly in the proliferative cells where the concentration and activity of the enzyme are greater.

This might be the reason for the induction of leukaemia in post-etoposide-treated cancer survivors. Therefore, it has become absolutely necessary to make etoposide target-specific, i. Abstract Increased clinical applications of the anticancer drug etoposide a non-intercalative epipodophyllotoxin derivative and the frequent induction of a second malignancy, particularly leukaemia, in post-etoposide-treated cancer survivors warrant detailed genotoxicity testing of etoposide. The same results were obtained among 55 patients in CR who received two or more cycles of intensification Fig.

In this study we found substantial agreement between observers using two different methods: a quantitative assessment, with the determination of the percentage of bone marrow blasts, and a qualitative, based on the perception of marrow infiltration. Moreover, we observed a higher OS in patients who obtained higher grades of cytoreduction by day 14 marrow evaluation. While risk assessment in AML relies mainly on age and cytogenetic profile [ 5 ], the assessment of in vivo chemosensitivity by determining early response to induction therapy is an additional predictive marker.

Indeed, this parameter has been used to guide clinicians in deciding for an early second cycle of chemotherapy [ 13 , 28 , 29 ]. In our study we observed that the qualitative and the quantitative methods were equally predictive of BMB results, with a substantial inter-observer agreement. Bone marrow evaluation by more than one observer has been previously reported [ 16 , 17 ], but to our best knowledge, our study was the first that reported the assessment of inter-observer agreement. Another point of controversy is the cutoff values of blast cell percentage in the quantitative assessment of BMA.

All analyzes of response assessment by D14 BMA by both methods qualitative and quantitative and both observers resulted in higher specificity than sensitivity. Therefore, there is no debate that a large amount of leukemic blast on day 14 constitutes unequivocal evidence of residual leukemia. However, the presence of a few blasts in a paucicellular or hemodilute marrow sample cannot be considered as definite evidence of residual disease. Few previous studies have shown an association between D14 marrow findings and long-term outcome [ 8 , 9 , 10 , 17 , 30 ].

In the present study, multivariate analysis showed that the evaluation of the bone marrow infiltration by Likert scale but not the percentage assessment was significantly associated with poor outcome. Our study shares the limitations of all retrospective studies. In addition, survival analysis was performed without the inclusion of well-known prognostic factors such as chromosomal and molecular abnormalities. Finally, we did not analyze the potential effect of the different induction regimens given throughout the study period and the number of entry-patients over the study period.

Despite these limitations, we were able to show that BMA may be considered the procedure of choice to assess treatment response on D14 because it provides results immediately, and exhibited good agreement between observers and good correlation with BMB and OS. We conclude that the assessment of BMA on day 14th of remission induction chemotherapy in patients with AML is a reproducible test with a substantial agreement between observers, both quantitatively and qualitatively, has good correlation with BMB and with OS. Estey E, Dohner H. Acute myeloid leukaemia. PubMed Article Google Scholar. Guidelines on the management of acute myeloid leukaemia in adults. Br J Haematol. Drug therapy for acute myeloid leukemia.

N Engl J Med. Double induction strategy for acute myeloid leukemia: the effect of high-dose cytarabine with mitoxantrone instead of standard-dose cytarabine with daunorubicin and 6-thioguanine: a randomized trial by the German AML Cooperative Group. J Clin Oncol. Acute Myeloid Leukemia Version 2. J Natl Compr Canc Netw. The prognostic significance of leukemic cells clearance kinetics evaluation during the initial course of induction therapy with HAD homoharringtonine, cytosine arabinoside, daunorubicin in patients with de novo acute myeloid leukemia. Am J Hematol. Day 14 bone marrow biopsy in predicting complete remission and survival in acute myeloid leukemia. Kinetics of bone marrow blasts during induction and achievement of complete remission in acute myeloid leukemia.

Bone marrow cellularity determination: comparison of the biopsy, aspirate, and buffy coat. Ann Intern Med. Characterization and analysis of the outcome of adults with acute myeloid leukemia treated in a Brazilian University hospital over three decades. Braz J Med Biol Res. Likert R. A Technique for the Measurement of Attitudes. Archives of Psychology. Google Scholar. The measurement of observer agreement for categorical data. Ludbrook J. Statistical techniques for comparing measurers and methods of measurement: a critical review. Clin Exp Pharmacol Physiol.

Statistical methods for assessing agreement between two methods of clinical measurement. Int J Nurs Stud. Article Google Scholar. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Anthracycline dose intensification in acute myeloid leukemia. Day 15 bone marrow driven double induction in young adult patients with acute myeloid leukemia: feasibility, toxicity, and therapeutic results.

Ann Hematol. Pullarkat V, Aldoss I. Prognostic and therapeutic implications of early treatment response assessment in acute myeloid leukemia. Crit Rev Oncol Hematol. Download references. You can also search for this author in PubMed Google Scholar. JTSF: data analysis and drafting of article; MML: design, critical revision of article and approval of article; WP: critical revision of article and approval of article; JCM: critical revision of article and approval of article; MN: design, critical revision of article and approval of article; RDP: design, data analysis, critical revision of article and approval of article.

All authors read and approved the final manuscript. Reprints and Permissions. Souto Filho, J. Evaluation of bone marrow aspirates in patients with acute myeloid leukemia at day 14 of induction therapy. Diagn Pathol 10, Download citation. Received : 08 June Accepted : 15 July Published : 25 July Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Abstract Background Early assessment of response to chemotherapy in acute myeloid leukemia may be performed by examining bone marrow aspirate BMA or biopsy BMB ; a hypocellular bone marrow sample indicates adequate anti-leukemic activity.

Methods A total of patients who received standard induction chemotherapy and had bone marrow samples were included. Conclusions Evaluation of D14 BMA using both methods had a significant agreement with BMB and between observers, identifying a population of patients with poor outcome. Background The outcome of patients with acute myeloid leukemia AML has improved substantially over the past decades, thanks to the development of more aggressive therapies and better supportive care.

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