Day 14 bone marrow examination in the management of acute myeloid leukemia

Abstract

The National Comprehensive Cancer Network (NCCN) recommends that a repeat bone marrow evaluation is carried out seven to ten days following completion of induction therapy so that if a patient's day 14 bone marrow shows residual blast cell counts of >10%, the patient would proceed early to a second cycle of induction therapy. Although blast cell counts of <5% on day 14 bone marrow is sensitive in predicting remission on day 28, various studies have found that day 14 bone marrow is highly nonspecific because a large proportion of patients with blast cell counts of >5% on day 14 bone marrow would still attain a complete remission of the disease without any further chemotherapy. Clinical decision based on day 14 bone marrow will result in some of these patients being given a second induction therapy unnecessarily. A second cycle of chemotherapy is associated with not only higher risk for treatment-related mortality but also increased use of hospital resources such as increased intravenous antimicrobials use, longer hospital stay, and higher demand for blood products. In this article, we examined the utility, discussed the shortfalls, and re-appraised the values of day 14 bone marrow in the management of patients with AML. On the basis of our review, we suggest that the practice of day 14 bone marrow examination should be re-evaluated and should probably only be carried out in the setting of clinical trials with clear questions to address its role in predicting outcome of the therapeutic intervention.

Observation Versus Immediate Reinduction for Acute Myeloid Leukemia Patients With Indeterminate Day 14 Bone Marrow Results

“…A blast count of < 5% on day 14 has a sensitivity of w90% to 95% for the prediction of CR at the end of treatment. 9 However, even with such high sensitivity, a 5% to 10% risk exists that a patient will have refractory disease despite hypoplastic bone marrow found on the day 14 biopsy. 16,17 In contrast, patients with a hypercellular bone marrow with > 20% blasts will usually undergo reinduction therapy.…”

“…Those with hypoplastic (< 20% cellularity and < 5% residual blasts) bone marrow will usually be monitored for count recovery. 9,10 The outcomes of patients with indeterminate day 14 bone marrow ( 20% cellularity and 5%-20% blasts) remain unclear. The decision to proceed with immediate reinduction or observation has been at the discretion of the treating physician with no defined guidance currently available.…”

Peripheral blood blast rate of clearance is an independent predictor of clinical response and outcomes in acute myeloid leukaemia

“…In the current management of AML, the standing recommendation remains the pursuit of a D14BM during cytotoxic chemotherapy in order to confirm chemoablation and disappearance of leukemic blasts. If the blast count in the D14BM is >5%, the National Comprehensive Cancer Network (NCCN) recommends consideration of re-induction therapy (O'Donnell et al, 2017), but several studies have shown that this additional exposure to chemotherapy, along with the associated morbidity, is not always necessary to achieve CR (Norkin et al, 2016;Terry et al, 2017). The presence of residual blasts on the D14BM has been shown to be a sensitive predictor of achievement of CR on D28 in several studies (Liso et al, 2000;Hussein et al, 2008), but is not always highly specific (Norkin et al, 2016;Terry et al, 2017), nor always associated with OS (Hussein et al, 2008).…”

“…If the blast count in the D14BM is >5%, the National Comprehensive Cancer Network (NCCN) recommends consideration of re-induction therapy (O'Donnell et al, 2017), but several studies have shown that this additional exposure to chemotherapy, along with the associated morbidity, is not always necessary to achieve CR (Norkin et al, 2016;Terry et al, 2017). The presence of residual blasts on the D14BM has been shown to be a sensitive predictor of achievement of CR on D28 in several studies (Liso et al, 2000;Hussein et al, 2008), but is not always highly specific (Norkin et al, 2016;Terry et al, 2017), nor always associated with OS (Hussein et al, 2008). Specifically, one study illustrated the limitations of the D14BM by showing that 36% of the AML patient cohort who had residual blasts on their D14BM achieved CR or CR with incomplete count recovery without additional chemotherapy (Norkin et al, 2016).…”

“…While the D14BM is regularly used to predict achievement of complete remission (CR) for patients undergoing cytotoxic induction therapy, its utility and sensitivity have been questioned (Luger, ; Ofran, ). Several studies have found that D14BM evaluation may not be reliable in predicting induction outcome, leading to a false positive result in some cases, with patients achieving a CR without exposure to additional chemotherapy despite having residual blasts on D14BM (Norkin et al , ; Terry et al , ). The invasive nature of the D14BM procedure also leads to significant patient discomfort, anxiety and risk of complications (e.g.…”