Treatment‐related death in childhood acute lymphoblastic leukaemia in the Nordic countries: 1992–2001

Abstract

SummaryDespite continuously more successful treatment of childhood acute lymphoblastic leukaemia (ALL), 2-5% of children still die of other causes than relapse. The Nordic Society of Paediatric Haematology and Oncology-ALL92 protocol included 1652 patients £15 years of age with precursor Band T-cell ALL diagnosed between 1992 and 2001. Induction deaths and deaths in first complete remission (CR1) were included in the study. A total of 56 deaths (3%) were identified: 19 died during induction (1%) and 37 in CR1 (2%). Infection was the major cause of death in 38 cases. Five patients died of early death before initiation of cytotoxic therapy. Five patients died because of toxicity of inner organs and one of accidental procedure failures. Seven patients died of complications following allogenic haematopoietic stem cell transplantation (HSCT) in CR1. Girls were at higher risk of treatmentrelated death (TRD) [relative risk (RR) ¼ 2AE2; 95% confidence interval (CI 95% ): 1AE2-4AE0, P < 0AE01], mostly because of infections. Risk of TRD was also higher in children with Down syndrome (RR ¼ 4AE5; CI 95% : 2AE0-10AE2, P < 0AE00). In conclusion, 3% of children with ALL died of TRD, with bacterial infections as the most common cause of death. Girls and Down syndrome patients had a higher risk of TRD. Infections still remain a major challenge in childhood ALL.

Treatment‐related mortality in children with acute lymphoblastic leukemia in Central America

“…7,10,11 The Nordic and Dutch groups, for example, in their definition of induction death, do not include children who die after achieving remission. 8,9 Thus, comparing our results with the results reported by these groups is problematic. Indeed, standard international definitions of TRM in acute leukemia are needed.…”

“…In HICs, age, sex, high-risk status, higher initial WBC counts, T-cell lineage immunophenotype, and trisomy 21 have been associated with an increased risk of TRM. [7][8][9]11 In an Indian study, malnutrition, lymphadenopathy, and lower hemoglobin levels were associated with TRM. 13 In our previous study in El Salvador, we observed that socioeconomic variables predicted TRM, whereas biologic parameters did not.…”

“…5 TRM commonly causes treatment failure in LICs. Whereas ALL in HICs has been associated with TRM rates of 1% to 3%, [6][7][8][9][10][11] the few studies that have investigated LICs have identified rates from 11% to 21%. 4,[12][13][14][15] In El Salvador, 12.5% of children with ALL experienced TRM.…”

Personal practice: How we manage the risk of bleeding and thrombosis in children and young adults with acute lymphoblastic leukaemia

“…For example, the only two cases of intra-cranial haemorrhage during induction reported among over 2500 patients recruited to the current UK childhood ALL trial, UKALL 2003 (unpublished data) were associated with hyperleucocytosis in one and intra-cranial fungal infection in the other. This concords with the extremely low incidence of haemorrhagic deaths reported in older Nordic (Christensen et al, 2005), St Jude's (Ribeiro & Pui, 1986), UK (Wheeler et al, 1996) and German (Sutor et al, 1999) trials. In the German Berlin-Frankfürt-Münster (BFM) 90 trial (Sutor et al, 1999), there was no correlation between risk of serious haemorrhage and presence of coagulopathy or use of prophylactic plasma components and AT concentrates.…”

Analysis of Induction Phase Glucocorticoid Use on Adrenal Suppression in Pediatric Patients With Acute Lymphoblastic Leukemia

“…Reports from several studies showed mortality due to infection as a form of side effects of chemotherapy and high-dose steroids (Conter et al 2009, Prucker et al 2009, Silverman et al 2000, Pui et al 2000, Christensen et al 2005. One cause of mortality due to infection in patients with LLA caused by glucocorticoids suppress adrenal inadequacy causing the body's defense against infection (Shulman et al 2007).…”