Intensive consolidation with G‐CSF support: Tolerability, safety, reduced hospitalization, and efficacy in acute myeloid leukemia patients ≥60 years

Abstract

The aim of this study was to evaluate the efficacy and feasibility of intensified consolidation therapy employing fludarabine and ARA-C in cycle 1 and intermediate-dose ARA-C (IDAC) in cycles 2 through 4, in elderly acute myeloid leukemia (AML) patients and to analyze the effects of pegfilgrastim on the duration of neutropenia, overall toxicity, and hospitalization-time during consolidation in these patients. Thirty nine elderly patients with de novo AML (median age 69.9 years) who achieved complete remission (CR) after induction-chemotherapy were analyzed. To examine the effect of pegfilgrastim on neutropenia and hospitalization, we compared cycles 2 and 4 where pegfilgrastim was given routinely from day 6 (IDAC-P) with cycle 3 where pegfilgrastim was only administered in case of severe infections and/or prolonged neutropenia. All four planned cycles were administered in 23/39 patients (59.0%); 5/39 patients (12.8%) received 3 cycles, 3/39 (7.7%) 2 cycles, and 8/39 (20.5%) one consolidation-cycle. The median duration of severe neutropenia was 7 days in cycle 2 (IDAC-P), 11.5 days in cycle 3 (IDAC), and 7.5 days in cycle 4 (IDAC-P) (P < .05). Median overall survival was 1.1 years and differed significantly between patients aged <75 and ≥75 years (P < .05). The probability to be alive after 5 years was 32%. Together, intensified consolidation can be administered in AML patients ≥60, and those who are <75 may benefit from this therapy. Routine administration of pegfilgrastim during consolidation shortens the time of neutropenia and hospitalization in these patients.

Methylation‐independent ITGA2 overexpression is associated with poor prognosis in de novo acute myeloid leukemia

“…We also observed that ITGA2 overexpression was an independent risk factor for prognosis in both overall AML cohort and non‐APL AML patients according to the multivariate analysis. According to the study reported by Sperr et al (), the results suggested that if patients who achieved CR were planned to receive an intensive consolidation therapy, then patients aged ≥60 years could achieve long‐term survival with conventional chemotherapy. Therefore, we think that in our ITGA2 high and ITGA2 low group, a less intensive chemotherapy program may not be the main factor affecting the poor prognosis of patients.…”

“…We also observed that ITGA2 overexpression was an independent risk factor for prognosis in both overall AML cohort and non-APL AML patients according to the multivariate analysis. According to the study reported by Sperr et al (2017), the results suggested that if patients who achieved CR were planned to receive an intensive consolidation therapy, then patients aged ≥60 years could achieve long-term survival with conventional chemotherapy. Therefore, we think that in our ITGA2 high and ITGA2 low group, a less intensive chemotherapy program may not be the main factor affecting the poor prognosis of patients.…”

Advances in treatment formulations for acute myeloid leukemia

“…The principal adverse effect generally observed in AML treatment is myelosuppression with neutropenia, which can lead to severe infections, anemias requiring red blood cell transfusions, and thrombocytopenia involving hemorrhagic events. Supportive care with anti-infectious treatments, such as antifungals, antibiotics, and antivirals [3,4] and growth factors [5] has led to improved overall survival rates for patients with AML over recent decades [6,7].…”

Ludwig Boltzmann Cluster Oncology (LBC ONC): first 10 years and future perspectives

“…A straightforward approach would be to intensify the overall chemotherapy in these patients; however, due to the risk of severe infections and other side effects this strategy is questionable. Therefore, members of the LBC ONC and the Medical University of Vienna conducted a clinical trial exploring the clinical tolerability and efficacy of a special form of intensified consolidation after remission induction in older patients with AML [ 92 ]. The consolidation regimen was developed on the basis of a previous study showing that intermediate ARA‑C (cytosine arabinoside) is not only a highly effective but also a less toxic and extremely well-tolerated type of consolidation chemotherapy [ 93 , 94 ].…”

“…This regimen was not only found to be feasible but also to be less toxic and highly effective with superior response and survival data compared to (all known) previous trials conducted in older AML patients so far. The median duration of severe neutropenia was 7 days in cycle 2 (IDAC-P), 11.5 days in cycle 3 (IDAC), and 7.5 days in cycle 4 (IDAC-P; p < 0.05) [ 92 ]. The probability of survival after 5 years was 32%.…”