Condensed versus standard schedule of high-dose cytarabine consolidation therapy with pegfilgrastim in AML

Consolidation therapy with a condensed schedule of High-Dose cytarabine (HDAC) is more preferred than standard schedule according to a study published in Blood Cancer Journal on 26^th May 2017.

In this prospective study, Sonia Jaramillo, University of Ulm and colleagues compared a condensed schedule of High-Dose cytarabine (HDAC) on days 1, 2, and 3 (HDAC-123) with standard HDAC given on days 1, 3, and 5 (HDAC-135) in patients with Acute Myeloid Leukemia (AML). Furthermore, Jaramillo et al., evaluated the prophylactic use of pegfilgrastim, a pegylated formulation of Granulocyte-Colony Stimulating Factor (G-CSF) in consolidation therapy in AML patients.

In total, 568 AML patients were upfront randomized at 1:10 between the German Intergroup-arm and the AMLSF-07-04 study (NCT00511242) between 2004–2009. Patients in the AMLSF-07-04 study (n = 527) were then randomized to receive either HDAC-123 (n = 392) or HDAC (n = 135) with intended prophylactic pegfilgrastim at day 10 and 8, respectively. Patients in the German AML Intergroup protocol (n = 41) were treated with HDAC-135 without prophylactic use of pegfilgrastim.

The key results of the study were:

• Median recovery time for White Blood Cells (WBC) and neutrophil from start of chemotherapy was significantly shorter by an average of 4 days in the HDAC-123 schedule compared to HDAC-135 schedule; P < 0.0001
• Treatment with pegfilgrastim reduced the duration of leukopenia and neutropenia by a median of 2 days in both the HDAC-135 and HDAC-123 schedule; P < 0.0001
• Treatment with pegfilgrastim and HDAC-123 were significantly associated with shorter WBC recovery
• Treatment with pegfilgrastim (Odds Ratio [OR] = 0.68, P = 0.002) and HDAC-123 (OR = 0.58, P < 0.0001) were significantly associated with a reduction in infection rates
• There was a significant reduction of platelet transfusions in the HDAC-123 schedule compared to the HDAC-135; median units, 4 vs 8 units, P < 0.0001
• Patients on the HDAC-123 schedule had reduced days in the hospital compared to HDAC-135 schedule
• Overall Survival (OS), Relapse Free Survival (RFS), cumulative incidence of death and relapse were not different between both schedules

In summary, “condensed schedule of HDAC on days 1, 2 and 3 for consolidation therapy in younger adult patients with AML appears to be the preferred treatment schedule, resulting in faster hematologic recovery, lower infection rate as well as fewer platelet transfusions and days in hospital without affecting the RFS and OS rates”. Additionally, the “administration of pegfilgrastim may further reduce rate of infections and duration of hospitalization”.

Abstract

The aim of this cohort study was to compare a condensed schedule of consolidation therapy with high-dose cytarabine on days 1, 2 and 3 (HDAC-123) with the HDAC schedule given on days 1, 3 and 5 (HDAC-135) as well as to evaluate the prophylactic use of pegfilgrastim after chemotherapy in younger patients with acute myeloid leukemia in first complete remission. One hundred and seventy-six patients were treated with HDAC-135 and 392 patients with HDAC-123 with prophylactic pegfilgrastim at days 10 and 8, respectively, in the AMLSG 07-04 and the German AML Intergroup protocol. Time from start to chemotherapy until hematologic recovery with white blood cells >1.0 G/l and neutrophils >0.5 G/l was in median 4 days shorter in patients receiving HDAC-123 compared with HDAC-135 (P<0.0001, each), and further reduced by 2 days (P<0.0001) by pegfilgrastim. Rates of infections were reduced by HDAC-123 (P<0.0001) and pegfilgrastim (P=0.002). Days in hospital and platelet transfusions were significantly reduced by HDAC-123 compared with HDAC-135. Survival was neither affected by HDAC-123 versus HDAC-135 nor by pegfilgrastim. In conclusion, consolidation therapy with HDAC-123 leads to faster hematologic recovery and less infections, platelet transfusions as well as days in hospital without affecting survival.