To assess the efficacy of an original DAC-7 regimen: daunorubicine (DNR) 60 mg/m 2 /day, days 1-3; cytarabine (AraC) 200 mg/m 2 /day, days 1-7; cladribine (2-CdA) 5 mg/m 2 /day, days 1-5, 400 untreated adult acute myeloid leukemia patients (including 63 with preceding myelodysplastic syndrome), aged 45 (16-60) years were randomized to either DAC-7 (n ¼ 200) or DA-7 (without 2-CdA, n ¼ 200). The overall CR rate equaled 72% for DAC-7 and 69% for DA-7 arm (P ¼ NS). After a single course of DAC-7 induction, the CR rate equaled 64% and was significantly higher compared to 47% in the DA-7 arm (P ¼ 0.0009). Median hospitalization time during the induction was 7 days shorter for DAC-7 compared to the DA-7 group (33 vs 40 days, P ¼ 0.002). Toxicity was comparable in both groups. The probability of 3-year leukemia-free survival (LFS) for DAC-7 and DA-7 group equaled 43 and 34%, respectively (P ¼ NS). There was a trend toward higher LFS rate for patients aged 440 years receiving DAC-7 compared with DA-7 regimen (44 vs 28%, P ¼ 0.05). This study proves that addition of 2-CdA increases antileukemic potency of DNR þ AraC regimen, thus resulting in a higher CR rate after one induction cycle when compared to DA-7, without additional toxicity. It shortens hospitalization time and may improve long-term survival in patients aged 440 years.

SummaryThe treatment of adults with Philadelphia-negative acute lymphoblastic leukaemia (ALL) depends on the presence of risk factors including age, white blood cell count, immunophenotype and time to complete remission. In recent years, status of minimal residual disease (MRD) has been postulated as an additional risk criterion. This study prospectively evaluated the significance of MRD. Patients were treated with a uniform Polish Adult Leukemia Group (PALG) 4-2002 protocol. MRD status was assessed after induction and consolidation by multiparametric flow cytometry. Out of 132 patients included (age, 17-60 years), 116 patients were suitable for analysis. MRD level ‡0AE1% of bone marrow cells after induction was found to be a strong and independent predictor for relapse in the whole study population (P < 0AE0001), as well as in the standard risk (SR, P = 0AE0003) and high-risk (P = 0AE008) groups. The impact of MRD after consolidation on outcome was not significant. The combination of MRD status with conventional risk stratification system identified a subgroup of patients allocated to the SR group with MRD <0AE1% after induction who had a very low risk of relapse of 9% at 3 years as opposed to 71% in the remaining subjects (P = 0AE001). We conclude that MRD evaluation after induction should be considered with conventional risk criteria for treatment decisions in adult ALL.

Despite several recommendations for standardization of multiparameter flow cytometry (MFC) the number, specificity and combinations of reagents used by diagnostic laboratories for the diagnosis and classification of acute leukemias (AL) are still very diverse. Furthermore, the current diagnostic interpretation of flow cytometry readouts is influenced arbitrarily by individual experience and knowledge. We determined the potential value of a minimal four-color combination panel of 13 monoclonal antibodies (mAbs) with a CD45/sideward light scattergating strategy for a standardized MFC immunophenotyping of the clinically most relevant subgroups of AL. Bone marrow samples from 155 patients with acute myeloid leukemia (AML, n ¼ 79), B-cell precursor acute lymphoblastic leukemia (BCP-ALL, n ¼ 29), T-cell precursor acute lymphoblastic leukemia (T-ALL, n ¼ 12) and normal bone marrow donors (NBMD, n ¼ 35) were analyzed. A knowledge-based learning algorithm was generated by comparing the results of the minimal panel with the actual diagnosis, using discriminative function analysis. Correct classification of the test sample according to lineage, that is, BCP-ALL, T-ALL, AML and differentiation of NBMD was achieved in 97.2% of all cases with only six of the originally applied 13 mAbs of the panel. This provides evidence that discriminant function analysis can be utilized as a decision support system for interpretation of flow cytometry readouts.

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Sixty-four untreated adult acute lymphoblastic leukemia (ALL) patients were randomized to receive chemotherapy alone, n = 31 or chemotherapy and granulocyte colony stimulating factor (G-CSF), n = 33. During induction patients received G-CSF for 5 days between four weekly Epirubicin+Vcr administrations, starting 36 h after each application and finishing 48 h before the next one with the intention to possibly generate a cell cycle dependent protection of normal hematopoietic progenitors and to stimulate granulopoiesis. The complete remission (CR) rate equaled 94% in the G-CSF group and 87% in controls. Patients who received G-CSF, if compared to the controls, had shorter granulocytopenia during induction and consolidation, displayed a lower infection rate, completed the induction-consolidation quicker and stayed shorter in hospital during induction, p < 0.001-0.04. Follow-up at 2 years revealed a rather higher probability of survival (59 vs. 27%, p = 0.04) and a lower relapse rate (32 vs. 60%) in G-CSF arm than in controls. The beneficial influence of G-CSF administered in time-sequenced fashion on survival needs further confirmation.