Risk factors and screening for neurocognitive impacts of therapy

Krull, Kevin R.

doi:10.1182/hematology.2022000409

Cited by 2 publications

(1 citation statement)

References 38 publications

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“… 6 , 16 The cohort of pediatric cancer survivors followed up at SJCRH constitutes a unique dataset. Survivors of treatment for childhood cancer are already known to have poorer neurocognitive performance than their unaffected peers, 18 and a recent study showed that experiencing bacteremic sepsis during leukemia treatment was associated with declining attention performance over time. 16 Here, we show that the increase in attention impairment and higher-grade neurocognitive dysfunction do not appear driven by higher proportions of neurological conditions such as cerebrovascular accidents or seizures among those with sepsis.…”

Section: Discussionmentioning

confidence: 99%

Severe Sepsis During Treatment for Childhood Leukemia and Sequelae Among Adult Survivors

Goggin,

Lu,

Lee

et al. 2024

JAMA Netw Open

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ImportanceChildren undergoing treatment for leukemia are at increased risk of severe sepsis, a dysregulated immune response to infection leading to acute organ dysfunction. As cancer survivors, they face a high burden of long-term adverse effects. The association between sepsis during anticancer therapy and long-term organ dysfunction in adult survivors of childhood cancer has not been examined.ObjectiveTo determine whether severe sepsis during therapy for leukemia in childhood is associated with subsequent chronic health conditions in adult survivors.Design, Setting, and ParticipantsThis cohort study included 644 adult survivors of childhood leukemia who were diagnosed between January 1, 1985, and July 19, 2010, and participated in the St Jude Lifetime Cohort Study. Participants were excluded if they received hematopoietic cell transplant or had relapsed leukemia. Data collection ended June 30, 2017. Data were analyzed from July 1, 2020, to January 5, 2024.ExposuresSevere sepsis episodes, defined according to consensus criteria as septic shock, acute respiratory distress syndrome, or multiorgan dysfunction associated with infection occurring during anticancer therapy, were abstracted by medical record review for all participants.Main Outcomes and MeasuresCommon Terminology Criteria for Adverse Events–defined chronic health condition outcomes were independently abstracted. Associations between sepsis and cumulative incidence of chronic health conditions (eg, cardiovascular, pulmonary, kidney, neurological, and neurocognitive outcomes) were compared by adjusted hazard ratios from Cox proportional hazards logistic regression. Inverse propensity score weighting was used to adjust for potential confounders, including age, year of diagnosis, and leukemia type.ResultsThe study sample consisted of 644 adult survivors of pediatric leukemia (329 women [51.1%] and 315 men [48.9%]; including 56 with a history of acute myeloid leukemia and 585 with a history of acute lymphoblastic leukemia) who were most recently evaluated at a median age of 24.7 (IQR, 21.2-28.3) years at a median time after leukemia diagnosis of 17.3 (IQR, 13.7-21.9) years. Severe sepsis during treatment of acute childhood leukemia occurred in 46 participants (7.1%). Participants who experienced severe sepsis during treatment were more likely to develop moderate to severe neurocognitive impairment (29 of 46 [63.0%] vs 310 of 598 [51.8%]; adjusted hazard ratio, 1.86 [95% CI, 1.61-2.16]; P &lt; .001) significantly affecting attention, executive function, memory and visuospatial domains. Sepsis was not associated with long-term risk of cardiovascular, pulmonary, kidney, or neurological chronic health conditions.Conclusions and RelevanceIn this cohort study of long-term outcomes in survivors of pediatric leukemia, severe sepsis during anticancer therapy for leukemia was associated with a selectively increased risk for development of serious neurocognitive sequelae. Efforts to reduce the effects of anticancer therapy on long-term function and quality of life in survivors might include prevention of severe sepsis during therapy and early detection or amelioration of neurocognitive deficits in survivors of sepsis.

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Section: Discussionmentioning

confidence: 99%

Severe Sepsis During Treatment for Childhood Leukemia and Sequelae Among Adult Survivors

Goggin,

Lu,

Lee

et al. 2024

JAMA Netw Open

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Long-term follow-up of CD19-CAR T-cell therapy in children and young adults with B-ALL

Epperly,

Shah

2023

Hematology

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The tremendous successes of CD19-directed CAR T cells in children and young adults with B-cell acute lymphoblastic leukemia (B-ALL) has led to the more widespread use of this important treatment modality. With an ability to induce remission and potentially lead to long-term survival in patients with multiply relapsed/chemotherapy refractory disease, more children are now receiving this therapy with the hope of inducing a long-term durable remission (with or without consolidative hematopoietic cell transplantation). While overcoming the acute toxicities was critical to its broad implementation, the emerging utilization requires close evaluation of subacute and delayed toxicities alongside a consideration of late effects and issues related to survivorship following CAR T cells. In this underexplored area of toxicity monitoring, this article reviews the current state of the art in relationship to delayed toxicities while highlighting areas of future research in the study of late effects in children and young adults receiving CAR T cells.

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Risk factors and screening for neurocognitive impacts of therapy

Cited by 2 publications

References 38 publications

Severe Sepsis During Treatment for Childhood Leukemia and Sequelae Among Adult Survivors

Severe Sepsis During Treatment for Childhood Leukemia and Sequelae Among Adult Survivors

Long-term follow-up of CD19-CAR T-cell therapy in children and young adults with B-ALL

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