Studies comparing survival of adolescent and young adult (AYA) patients to that of younger patients with newly diagnosed acute myeloid leukemia (AML) have yielded conflicting results. In order to ...more accurately characterize relative survival and other outcomes of AYA patients, a cross-study analysis was conducted using data from recent trials conducted by the Children's Cancer Group (CCG) and Children's Oncology Group (COG).
Data were combined from the CCG-2891, CCG-2941, CCG-2961, and AAML03P1 trials. The data set included 1840 patients, comprising 238 AYA and 1602 younger patients.
Overall survival was not significantly different in the 2 groups (AYA, 49% ± 7% versus younger, 54% ± 3% (± 2 standard errors), P = .058). Relapse was lower in AYA patients (30% ± 7% versus 41% ± 3%, P = .002), but treatment-related mortality (TRM) was higher (25% ± 6% versus 12% ± 2%, P < .001). After adjustment for other factors, older age remained strongly associated with TRM (hazard ratio = 2.30, 95% CI = 1.59-3.33, P < .001). Infection accounted for the excess TRM in AYA patients.
Survival in AYA and younger patients with newly diagnosed AML is similar; however, older patients are at higher risk for TRM. More effective strategies for preventing mortality from infection in AYA patients are needed.
Background: Treatment of anterior cruciate ligament rupture in adolescents with open physes is controversial.
Hypothesis: Delaying reconstruction until the physes bridge will affect the rate of ...additional knee injuries.
Study Design: Case control.
Methods: The physes group was 13 adolescents with open physes whose anterior cruciate ligament reconstructions were delayed until
their physes bridged. Specific types of activity were absolutely restricted during the delay. The physes groupsâ rates of
additional injuries, identified arthroscopically at reconstruction, were compared to rates among 116 skeletally mature adolescents.
The comparison adolescents were stratified into four groups by interval from injury to reconstruction (<1 week, 1 to 6 weeks,
6 to 26 weeks, >26 weeks).
Results: The additional injury rates in the physes and four comparison groups were 46%, 50%, 47%, 43%, and 69%, respectively. Severity
of additional injury, mechanism of injury, and rate of additional surgical procedures were similar among the groups.
Conclusions: There was no evidence that intentionally delayed anterior cruciate ligament reconstruction increased the rate of additional
knee injuries. Delayed reconstruction is a valid treatment option for adolescents with open physes at injury. Absolute activity
restriction is key to decreasing the risk of additional knee injuries.
Keywords:
skeletally immature
knee
risk
meniscus
activity
There is considerable variation in the use of HLA-matched related bone marrow transplantation (BMT) for the treatment of pediatric patients with newly diagnosed acute myeloid leukemia (AML). Some ...oncologists have argued that BMT should be offered to most patients in first complete remission (CR). Others have maintained that transplantation in first remission should be reserved for patients with high-risk disease. We performed this study to determine how disease risk influences the efficacy of BMT.
We combined data from four cooperative group clinical trials: Pediatric Oncology Group 8821, Children's Cancer Group (CCG) 2891, CCG 2961, and Medical Research Council 10. Using cytogenetics and the percentage of marrow blasts after the first course of chemotherapy, patients were stratified into favorable, intermediate, and poor-risk disease groups. Patients who could not be risk classified were analyzed separately. Outcomes for patients assigned to BMT and for patients assigned to chemotherapy alone were compared.
The data set included 1,373 pediatric patients with AML in first CR. In the intermediate-risk group, the estimated disease-free survival at 8 years for patients who did not undergo transplantation was 39% +/- 5% (2 SE), whereas it was 58% +/- 7% for BMT patients. The estimated overall survival for patients who did not undergo transplantation was 51% +/- 5%, whereas it was 62% +/- 7% for BMT patients. Both differences were significant (P < .01). There were no significant differences for survival in the other two risk groups or in the non-risk-stratified patients.
Our study indicates that HLA-matched related BMT is an effective treatment for pediatric patients with intermediate-risk AML in first CR.
Although the majority of children with acute lymphoblastic leukemia (ALL) are cured with current therapy, the event-free survival (EFS) of infants with ALL, particularly those with mixed lineage ...leukemia (MLL) gene rearrangements, is only 30% to 40%. Relapse has been the major source of treatment failure for these patients. The parallel Children's Cancer Group (CCG) 1953 and Pediatric Oncology Group (POG) 9407 studies were designed to test the hypothesis that more intensive therapy, including dose intensification of chemotherapy, and hematopoietic stem-cell transplantation (HSCT) would improve the outcome for this group of patients.
One hundred eighty-nine infants (CCG 1953, n = 115; POG 9407, n = 74) were enrolled between October 1996 and August 2000. For infants with the MLL gene rearrangement and an appropriate donor, HSCT was the preferred treatment on CCG 1953 and investigator option on POG 9407 after completion of the second phase of therapy. Fifty-three infants underwent HSCT.
The 5-year EFS rate was 48.8% (95% CI, 33.9% to 63.7%) in patients who received HSCT and 48.7% (95% CI, 33.8% to 63.6%) in patients treated with chemotherapy alone (P = .60). Transplantation outcomes were not affected by the preparatory regimen or donor source.
Our data suggest that routine use of HSCT for infants with MLL-rearranged ALL is not indicated. However, limited by small numbers, this study should not be considered the definitive answer to this question.
Background
Treatment‐related morbidity and mortality occur frequently in childhood acute myeloid leukemia (AML) induction. Yet the contributions of respiratory adverse events (AEs) within this ...population are poorly understood. Furthermore, the roles of fluid overload (FO) and infection in AML pulmonary complications have been inadequately examined.
Objectives
To describe the incidence, categories, and grades of respiratory AEs and to assess the associations of FO and infection on respiratory AE development in childhood AML induction.
Methods
We retrospectively examined the induction courses of a cohort of de novo pediatric AML patients for any NCI CTCAE grade 2 to 5 respiratory AE, FO, and systemic/pulmonary infection occurrence. Demographic, disease, and treatment‐related data were ed. Descriptive, univariate, survival, and multivariable analyses were conducted.
Results
Among 105 eligible subjects from 2009 to 2016, 49.5% (n = 52) experienced 63 discrete respiratory AEs. FO occurred in 28.6% of subjects (n = 30), with half occurring within 24 hours of hospitalization. Positive FO status < 10 days (aHR 5.5, 95% CI 2.3‐12.8), ≥ 10 days (aHR 13, 95% CI 4.1‐41.8), and positive infection status ≥ 10 days into treatment (aHR 14.9, 5.4‐41.6) were each independently associated with AE development.
Conclusions
We describe a higher incidence of respiratory AEs during childhood AML induction than previously illustrated. FO occurs frequently and early in this course. Late infections and FO at any time frame were strongly associated with AE development. Interventions focused on the prevention and management of FO and infectious respiratory complications could be instrumental in reducing preventable treatment‐related morbidity and mortality.
Summary
Acute myeloid leukaemia (AML) with t(6;9)(p23;q34) is a rare subtype associated with FLT3‐internal tandem duplication (ITD) and poor outcomes. The clinical outcomes of paediatric patients ...with t(6;9) with and without FLT3‐ITD treated on six consecutive cooperative trails were evaluated. In contrast to patients without t(6;9), those with t(6;9) had a significantly lower complete remission rate, higher relapse rate (RR), and poor overall survival (OS). Within t(6;9) patients, those with and without FLT3‐ITD had an OS of 40% and 27% respectively (P > 0·9), demonstrating that t(6;9) is a high‐risk cytogenetic feature in paediatric AML and its clinical impact is independent of the presence of FLT3‐ITD.
KIT receptor tyrosine kinase mutations are implicated as a prognostic factor in adults with core binding factor (CBF) acute myeloid leukemia (AML). However, their prevalence and prognostic ...significance in pediatric CBF AML is not well established. We performed KIT mutational analysis (exon 8 and exon 17) on diagnostic specimens from 203 pediatric patients with CBF AML enrolled on 4 pediatric AML protocols. KIT mutations were detected in 38 (19%) of 203 (95% CI, 14%-25%) patient samples of which 20 (52.5%) of 38 (95% CI, 36%-69%) involved exon 8, 17 (45%) of 38 (95% CI, 29%-62%) involved exon 17, and 1 (2.5%; 95% CI, 0%-14%) involved both locations. Patients with KIT mutations had a 5-year event-free survival of 55% (± 17%) compared with 59% (± 9%) for patients with wild-type KIT (P = .86). Rates of complete remission, overall survival, disease-free survival, or relapse were not significantly different for patients with or without KIT mutations. Location of the KIT mutation and analysis by cytogenetic subtype t(8;21) vs inv(16) also lacked prognostic significance. Our study shows that KIT mutations lack prognostic significance in a large series of pediatric patients with CBF AML. This finding, which differs from adult series and a previously published pediatric study, may reflect variations in therapeutic approaches and/or biologic heterogeneity within CBF AML. Two of 4 studies included in this analysis are registered at http://clinicaltrials.gov as NCT00002798 (CCG-2961) and NCT00070174 (COG AAML03P1).
Background
High‐risk pediatric acute myeloid leukemia confers a poor prognosis, and alternative strategies are needed to improve outcomes. We hypothesized that intensifying induction on the AAML1031 ...clinical trial would improve outcomes compared to the predecessor trial AAML0531.
Methods
Patients on AAML0531 received cytarabine (1600 mg/m2)/daunorubicin (150 mg/m2)/etoposide (ADE) for induction II and patients on AAML1031 received mitoxantrone (48 mg/m2)/cytarabine (8000 mg/m2) (MA). Stem cell transplant (SCT) conditioning included busulfan/cyclophosphamide on AAML0531, whereas AAML1031 used busulfan/fludarabine and liberalized donor eligibility. Patients were included in this analysis if they met high‐risk criteria common to the two trials by cytogenics or poor disease response after induction I ADE.
Results
MA provided no benefit over ADE at: induction II response (complete response CR: 64% vs. 62%, p = .87; measurable residual disease MRD+: 57% vs. 46%, p = .34); or intensification I response (CR: 79% vs. 94%, p = .27; MRD+: 27% vs. 20%, p = 1.0). When considered with altered SCT approach, MA did not improve 5‐year disease‐free survival (24% ± 9% vs. 18% ± 15%, p = .63) or 5‐year overall survival (35% ± 10% vs. 38% ± 18%, p = .66). MA was associated with slower neutrophil recovery (median 34 vs. 27 days, p = .007) and platelet recovery (median 29 vs. 24.5 days, p = .04) and longer hospital stay (32 vs. 28 days, p = .01) during induction II.
Conclusion
Intensification of induction II did not improve treatment response or survival, but did increase toxicity and resource utilization. Alternative strategies are urgently needed to improve outcomes for pediatric patients with high‐risk acute myeloid leukemia (trials registered at clinicaltrials.gov NCT01371981, NCT00372593).
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