Is the D14 bone marrow in acute myeloid leukemia still the gold standard?

Ofran, Yishai

doi:10.1097/moh.0000000000000214

Cited by 4 publications

(3 citation statements)

References 38 publications

(38 reference statements)

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“…Varying therapy regimens are used worldwide, that mostly differ in time and duration of chemotherapy administering [8]. The presented treatment model is also suitable for a planned comparison of different double induction concepts like TAD-HAM vs. S-HAM [7].…”

Section: Discussionmentioning

confidence: 99%

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In-silico comparison of two induction regimens (7 + 3 vs 7 + 3 plus additional bone marrow evaluation) in acute myeloid leukemia treatment

Banck

Görlich

2019

BMC Syst Biol

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BackgroundClinical integration of systems biology approaches is gaining in importance in the course of digital revolution in modern medicine. We present our results of the analysis of an extended mathematical model describing abnormal human hematopoiesis. The model is able to describe the course of an acute myeloid leukemia including its treatment. In first-line treatment of acute myeloid leukemia, the induction chemotherapy aims for a rapid leukemic cell reduction. We consider combinations of cytarabine and anthracycline-like chemotherapy. Both substances are widely used as standard treatment to achieve first remission. In particular, we compare two scenarios: a single-induction course with 7 days cytarabine and 3 day of anthracycline-like treatment (7 + 3) with a 7 + 3 course and a bone marrow evaluation that leads, in case of insufficient leukemic cell reduction, to the provision of a second chemotherapy course. Three scenarios, based on the leukemias growth kinetics (slow, intermediate, fast), were analyzed. We simulated different intensity combinations for both therapy schemata (7 + 3 and 7 + 3 + evaluation).ResultsOur model shows that within the 7 + 3 regimen a wider range of intensity combinations result in a complete remission (CR), compared to 7 + 3 + evaluation (fast: 64.3% vs 46.4%; intermediate: 63.7% vs 46.7%; slow: 0% vs 0%). Additionally, the number of simulations resulting in a prolonged CR was higher within the standard regimen (fast: 59.8% vs 40.1%; intermediate: 48.6% vs 31.0%; slow: 0% vs 0%). On the contrary, the 7 + 3 + evaluation regimen allows CR and prolonged CR by lower chemotherapy intensities compared to 7 + 3. Leukemic pace has a strong impact on treatment response and especially on specific effective doses. As a result, faster leukemias are characterized by superior treatment outcomes and can be treated effectively with lower treatment intensities.ConclusionsWe could show that 7 + 3 treatment has considerable more chemotherapy combinations leading to a first CR. However, the 7 + 3 + evaluation regimen leads to CR for lower therapy intensity and presumably less side effects. An additional evaluation can be considered beneficial to control therapy success, especially in low dose settings. The treatment success is dependent on leukemia growth dynamics. The determination of leukemic pace should be a relevant part of a personalized medicine.Electronic supplementary materialThe online version of this article (10.1186/s12918-019-0684-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

“…Different 7 + 3 regimens are preferred depending on respective region, e.g. an evaluation process with potential re-induction in the United States compared to a preferred double induction in Europe [8].…”

Section: Introductionmentioning

confidence: 99%

In-silico comparison of two induction regimens (7 + 3 vs 7 + 3 plus additional bone marrow evaluation) in acute myeloid leukemia treatment

Banck

Görlich

2019

BMC Syst Biol

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“…Despite the ability to predict chemosensitivity with current prognostic models incorporating karyotype and mutations, initial demonstration of chemosensitivity requires a day 14 bone marrow aspirate and biopsy (D14BM) during induction treatment with cytarabine and anthracycline‐based regimens. 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 , ).…”

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

et al. 2019

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Summary The day 14 bone marrow aspirate and biopsy (D14BM) is regularly used to predict achievement of complete remission (CR) with induction chemotherapy in acute myeloid leukemia (AML), however its utility has been questioned. Clearance of peripheral blood blasts (PBB) may serve as an early measure of chemosensitivity. PBB rate of clearance (PBB‐RC) was calculated for treatment‐naive AML patients (n = 164) undergoing induction with an anthracycline and cytarabine (7+3) and with detectable PBB at diagnosis. PBB‐RC was defined as the percentage of the absolute PBB count on the day of diagnosis that was cleared with each day of therapy, on average, until D14 or day of PBB clearance. Each 5% increase in PBB‐RC approximately doubled the likelihood of D14BM clearance (OR = 1·81; 95% CI: 1·24–2·64, P < 0·005). PBB‐RC was also associated with improved CR rates (OR per 5% = 1·97; 95% CI: 1·27–3·01, P < 0·005) and overall survival (OS) [hazard ratio (HR) per 5% = 0·67; 95% CI: 0·52–0·87]. African American patients had poorer OS adjusted for PBB‐RC (HR = 2·18; 95% CI: 1·13–4·23), while race was not associated with D14BM or CR rate. PBB‐RC during induction chemotherapy is predictive of D14BM clearance, CR, and OS, and can therefore serve as a prognostic marker for clinical outcomes in AML.

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Diagnosis and Treatment of Adult Acute Myeloid Leukemia Other than Acute Promyelocytic Leukemia

Wiernik¹

2017

Neoplastic Diseases of the Blood

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Is the D14 bone marrow in acute myeloid leukemia still the gold standard?

Abstract: Early bone marrow evaluation has a potential to personalize the induction regimen, but because of limitations of day 14 bone marrow results, earlier bone marrow evaluation or the use of flow cytometry to detect minor blast populations may improve remission prediction in AML.

Cited by 4 publications

References 38 publications

In-silico comparison of two induction regimens (7 + 3 vs 7 + 3 plus additional bone marrow evaluation) in acute myeloid leukemia treatment

In-silico comparison of two induction regimens (7 + 3 vs 7 + 3 plus additional bone marrow evaluation) in acute myeloid leukemia treatment

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

Diagnosis and Treatment of Adult Acute Myeloid Leukemia Other than Acute Promyelocytic Leukemia

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