Causes of death – other than progressive leukemia – in childhood acute lymphoblastic (ALL) and myeloid leukemia (AML): the Dutch Childhood Oncology Group experience

Abstract

We analyzed causes of death, other than resistant disease or relapse, in 875 children with acute lymphoblastic leukemia (ALL) and 229 with acute myeloid leukemia (AML), treated on three different Dutch Childhood Oncology Group (DCOG) ALL and three AML protocols. Overall, 23 (2.6%) ALL and 44 (19.2%) AML patients died. Early death (ED, before remission was reached) occurred in nine ALL (1%) and thirty AML (13.1.%) patients, including three and ten deaths before treatment was initiated. Chemotherapy-related mortality in remission (CRM) occurred in nine ALL (1.1%) and eight AML (4.4%) patients. For ALL, both ED and CRM declined over time, although this was not statistically significant. For AML a decrease in ED was observed (from 26% to approximately 10%), but counterbalanced by an increase in CRM (from 3 to 8%), maybe related to the scheduling of intensification blocks in AML-92/94. Including transplant-related mortality, death in CR rates in AML increased from 3 to 15% in the last study. The main cause of ED was hemorrhage, often associated with hyperleucocytosis, and infection for CRM. We conclude that mortality dropped favorably in ALL, but not in AML. Especially for AML, effective but less toxic therapy and better supportive care guidelines need to be developed.

Incidence and predictors of treatment-related mortality in paediatric acute leukaemia in El Salvador

“…Death in complete remission was defined as any death occurring 42 days or later after diagnosis in patients who achieved remission. These definitions are consistent with those used by others (Christensen et al, 2005;Slats et al, 2005) to facilitate future comparisons across studies.…”

“…However, our report is the first to compare the relative contribution of TRM with treatment failure for children with ALL and AML in an LIC. In HICs, TRM accounts for more treatment failure in children with AML than ALL (Christensen et al, 2005;Ravindranath et al, 2005;Slats et al, 2005;Creutzig et al, 2006;Pui and Evans, 2006). Our finding suggests that in LICs, efforts to reduce TRM are as important for children with ALL as for those with AML.…”

“…Among patients with ALL in HICs, studies have identified gender, age, high white blood cell count, high-risk ALL, T-ALL, and Down's syndrome as TRM risk factors, although these have not been consistent (Wheeler et al, 1996;Rubnitz et al, 2004;Christensen et al, 2005;Slats et al, 2005). Conversely, Advani et al (1999) found that in the LIC of India, low haemoglobin, lymphadenopathy, and malnutrition were all associated with increased risk of TRM in ALL.…”

“…Although several studies have examined predictors of TRM in HICs (Wheeler et al, 1996;Riley et al, 1999;Creutzig et al, 2004;Rubnitz et al, 2004;Christensen et al, 2005;Slats et al, 2005), very few have looked at similar risk factors in LICs (Advani et al, 1999). Among patients with ALL in HICs, studies have identified gender, age, high white blood cell count, high-risk ALL, T-ALL, and Down's syndrome as TRM risk factors, although these have not been consistent (Wheeler et al, 1996;Rubnitz et al, 2004;Christensen et al, 2005;Slats et al, 2005).…”

Cure trends in acute lymphoblastic leukemia: is it time for a revised concept of cure?

“…More recently, therapy optimization focusses on asparaginase, including asparaginase dose intensification, therapeutic drug monitoring, and the use of novel pegylated formulations, as reviewed by Pieters et al 8 The progress made with these changes are not yet visible in the results reported by Gatta et al as these developments are too recent. At least as important are the improvements in supportive care reducing the number of patients dying from treatment-related mortality, 9 including developments in blood-banking, antibiotics and antifungals, parenteral nutrition and tumor lysis prevention.…”