The Reduction of Leukemic Blasts In Bone Marrow Aspirate on Day 6 of Remission Induction Treatment Is Predictive for Complete Remission Rate and Survival in Adult Acute Myeloid Leukemia: The Results of Multicenter, Prospective Polish Adult Leukemia Group Study.

The goal of this study was to pr ove the significance of an early evaluation of leukemic blast reduction based on cytological examination of bone marrow aspirates obtained on day 6 of remission induction treatment.

Patients: 152 adult AML patients aged 18–60 (median 47) registered to the PALG prospective trial evaluating the efficacy of 3 remission induction protocols:

• DAF: daunorubicine (DNR) 60 mg/m2/d iv, d 1–3; cytarabine (AraC) 200 mg/m2/d ci, d 1–7, and fludarabine 25 mg/m2 2h inf. iv d 1–5)

• DAC (like DAF but cladribin is used at 5 mg/m2 instead of fludarabine) and

• the standard DA 3+7 regimen.

Patients achieving CR received two courses of subsequent intensive consolidation:

1. HAM (HD AraC, mitoxantrone)

2. HD AraC. In case of partial remission (PR) after the first induction course the same regimen was repeated.

Patients with no remission (NR) or with PR after 2 induction courses were withdrawn from the study. Bone marrow aspirates were performed before the treatment and on the 6-th day of the first remission induction course, and the MGG stained marrow smears were evaluated at each centre by two experienced hematologists.

Results: Based on the proportion of blasts in bone marrow specimen on day 6 patients were arranged into 2 groups:

1. “responders” with <5 % of blasts (n=59) and

2. “non responders” with >5% of blastic cells in bone marrow (n=31).

The complete remission rate (CR) in the “responders” group equaling 86% (82/95) was significantly higher in comparison to that found in the “non responders” group 33%(19/57), p=<0,00001. The probability of overall survival (OS) was also higher in the group of “responders” if compared to “non responders” one; 63% versus 33% respectively, p=0,0009. In multivariate analysis including bone marrow examination, cytogenetic risk group, age, leukocyte count at diagnosis and the induction arm, only the persistence of leukemic blasts >5% in bone marrow specimens on 6-th day of induction was associated with higher risk of not achieving CR (HR = 51,1; p=0,00002), and with shorter OS (HR=2,9; p=0,004).

Conclusion: This prospective, multicenter study demonstrates that a simple and commonly accessible evaluation of the leukemic blasts reduction in bone marrow smear on the 6-th day of remission induction treatment is a reliable and independent predictor for achieving CR and for overall survival. This offers a decision point for an early modification of the treatment strategy.