Association between prolonged neutropenia and reduced relapse risk in pediatric AML: A report from the children's oncology group

Abstract

Objective was to describe the relationship between the number of sterile site infections and duration of neutropenia during the first four cycles of chemotherapy and the risk of recurrence and overall survival. AAML0531 was a Children’s Oncology Group (COG) randomized phase 3 clinical trial that included 1022 children with de novo AML. For this analysis, we focused on non-Down syndrome favorable and standard risk patients who completed at least 4 cycles of chemotherapy without recurrence or withdrawal during protocol therapy. Those receiving hematopoietic stem cell transplantation in first remission were excluded. 569 patients were included; 274 (48.2%) were favorable risk. The median cumulative time with neutropenia between Induction II to completion of Intensification II was 96 (range 54–204) days. Number of sterile site infections did not influence the risk of relapse or overall survival. However, longer duration of neutropenia was associated with a lower risk of relapse (hazard ratio 0.81 per 20 days neutropenia, P=0.007). Longer duration of neutropenia was associated with a reduced risk of relapse for children with favorable and standard risk AML. Toxicity may be influenced by pharmacogenomics suggesting that individualized chemotherapy dosing may be an effective strategy.

Associations between neutrophil recovery time, infections and relapse in pediatric acute myeloid leukemia

“…A recent study of pediatric patients with AML found longer cumulative time in neutropenia to be associated with a reduced risk of relapse . In contrast, we found a trend for higher mean neutrophil recovery time to be associated with increased risk of relapse.…”

“…Infection in pediatric patients with AML is the most frequent cause of treatment‐related mortality . Even within the same AML protocol, the duration of neutropenia varies significantly between patients . Children have highly variable pharmacokinetics of the therapeutic drugs used for treating AML which may partly explain the variability in duration of neutropenia.…”

“…Previous studies in adults and children show that neutropenia before and during AML treatment is associated with increased risk of infection . A recent study showed that longer cumulative time in neutropenia is associated with a reduced risk of relapse in pediatric patients with AML . In pediatric AML, neutrophil recovery time after the first induction may therefore give an early indication of the risk of both toxicity and outcome.…”

“…[1][2][3] Even within the same AML protocol, the duration of neutropenia varies significantly between patients. 4,5 Children have highly variable pharmacokinetics of the therapeutic drugs used for treating AML [6][7][8][9] which may partly explain the variability in duration of neutropenia. Previous studies in adults and children show that neutropenia before and during AML treatment is associated with increased risk of infection.…”

Predisposition to prolonged neutropenia after chemotherapy for paediatric acute myeloid leukaemia is associated with better prognosis in the Japanese Paediatric Leukaemia/Lymphoma Study Group AML‐05 study

“…This would also mean that myelosuppression could be indicative of outcome and not directly responsible for it. However, there are discrepancies regarding the role of myelosuppression in the outcome in AML patients 7,8 and we therefore analysed the association between the duration of neutropenia (indicative of the degree of myelosuppression) and prognosis in our Japanese Paediatric Leukaemia/Lymphoma Study Group (JPLSG) AML-05 cohort.…”