Use of granulocyte colony‐stimulating factor and risk of relapse in pediatric patients treated for acute myeloid leukemia according to NOPHO‐AML 2004 and DB AML‐01

Abstract

Background Supportive‐care use of granulocyte colony‐stimulating factor (G‐CSF) in pediatric acute myeloid leukemia (AML) remains controversial due to a theoretical increased risk of relapse and limited impact on neutropenic complications. We describe the use of G‐CSF in patients treated according to NOPHO‐AML 2004 and DB AML‐01 and investigated associations with relapse. Procedure Patients diagnosed with de novo AML completing the first week of therapy and not treated with hematopoietic stem cell transplantation in the first complete remission were included (n = 367). Information on G‐CSF treatment after each course (yes/no) was registered prospectively in the study database and detailed information was gathered retrospectively from each center. Descriptive statistics were used to describe G‐CSF use and Cox regression to assess the association between G‐CSF and risk of relapse. Results G‐CSF as supportive care was given to 128 (35%) patients after 268 (39%) courses, with a large variation between centers (0‐93%). The use decreased with time—the country‐adjusted odds ratio was 0.8/diagnostic year (95% confidence interval [CI] 0.7‐0.9). The median daily dose was 5 μg/kg (range 3‐12 μg/kg) and the median cumulative dose was 75 μg/kg (range 7‐1460 μg/kg). Filgrastim was used in 82% of G‐CSF administrations and infection was the indication in 44% of G‐CSF administrations. G‐CSF was associated with increased risk of relapse—the adjusted hazard ratio was 1.5 (95% CI 1.1‐2.2). Conclusions G‐CSF as supportive care was used in a third of patients, and use decreased with time. Our results indicate that the use of G‐CSF may be associated with an increased risk of relapse.

Upregulation ofAKR1C1in mesenchymal stromal cells promotes the survival of acute myeloid leukaemia cells

“…G‐CSF is essential for the survival and proliferation of the granulocyte haematopoietic stem (progenitor) cells, and has been used to decrease severe infections and treatment‐related mortality in AML due to the widespread expression of its receptor (G‐CSFR) on AML cells. However, although Saito et al () found that G‐CSF increased elimination of human primary AML stem cells in vivo , other studies have suggested that G‐CSF contributes to myeloid cell growth (Zhu et al , ) and even increases the risk of relapse (Lohmann et al , ). G‐CSF secretion increased significantly in MSC‐AML cell co‐cultures (Brenner et al , ), and van den Berk et al () observed a clear upregulation of G‐CSF along with leukaemic cell expansion in the presence of MSCs.…”

Treating acute myeloid leukemia among children with down syndrome

“…In our study, we used prophylactic G-CSF in all patients with no adverse outcomes even though some studies have documented higher risk of relapse with G-CSF. [21,22] Our policy of use of G-CSF in children with AML post induction chemotherapy is guided by various publications in literature where G-CSF has not been associated with increased risk of relapse. [23] In a Cochrane review where 19 studies with more than 5000 patients were analyzed, relapse rates did not increase due to use of CSFs.…”

Supportive care in pediatric acute myeloid leukemia:Expert-based recommendations of the NOPHO-DB-SHIP consortium

“…Later, the same group reported that children with the isoform IV of the G-CSF receptor might have an increased risk of relapse when prophylactically treated with G-CSF [61]. A retrospective study by NOPHO-AML2004 and DB-AML-01 showed that patients who had received G-CSF during treatment, mainly due to infection, had a higher risk of relapse than those who had not received G-CSF [62].…”