Outstanding outcomes in infants with &lt;i&gt;KMT2A&lt;/i&gt;-germline acute lymphoblastic leukemia treated with chemotherapy alone: results of the Children’s Oncology Group AALL0631 trial

Guest, Erin; Kairalla, John A.; Hilden, Joanne M.; Dreyer, ZoAnn E.; Carroll, Andrew J.; Heerema, Nyla A.; Wang, Cindy Y.; Devidas, Meenakshi; Gore, Lia; Salzer, Wanda L.; Winick, Naomi J.; Carroll, William L.; Raetz, Elizabeth A.; Borowitz, Michael J.; Loh, Mignon L.; Hunger, Stephen P.; Brown, Patrick

doi:10.3324/haematol.2021.280146

Cited by 12 publications

(19 citation statements)

References 15 publications

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“…Consistent with evaluation of a prediction model developed to assess the risk of BSI in febrile children with cancer when not severely neutropenic, 11 clinical signs of sepsis such as hypotension, chills/rigors, and higher T max were independent predictors of BSI. Additionally, treatment on infant protocols was associated with BSI which is consistent with prior literature demonstrating high rates of infectious complications for this subpopulation 26,27 . Patients with these features likely benefit from empiric antibiotics as are indicated in patients with severe neutropenia 28 .…”

Section: Discussionsupporting

confidence: 84%

“…Additionally, treatment on infant protocols was associated with BSI which is consistent with prior literature demonstrating high rates of infectious complications for this subpopulation. 26,27 Patients with these features likely benefit from empiric antibiotics as are indicated in patients with severe neutropenia. 28 For the majority of the other patients, this study's low BSI rate adds further evidence toward efforts to withhold empiric antibiotics for well-appearing children with malignancy and fever in the absence of severe neutropenia.…”

Section: Discussionmentioning

confidence: 99%

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Infectious events in pediatric patients with acute lymphoblastic leukemia/lymphoma undergoing evaluation for fever without severe neutropenia

Patel

DeGroote

Jackson

et al. 2022

Cancer

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Background: Infections cause significant treatment-related morbidity during pediatric acute lymphoblastic leukemia/lymphoma (ALL/LLy) therapy. Fevers during periods without severe neutropenia are common, but etiologies are not welldescribed. This study sought to describe the bloodstream infection (BSI) and non-BSI risk in children undergoing therapy for ALL/LLy. Methods: Demographic and clinical data were abstracted for febrile episodes without severe neutropenia at two children's hospitals. Treatment courses were stratified by intensity. Multivariate logistic regression evaluated characteristics associated with infection. Results: There were 1591 febrile episodes experienced by 524 patients. Of these, 536 (34%) episodes had ≥1 infection; BSI occurred in 30 (1.9%) episodes. No BSIs occurred in episodes with a recent procedural sedation or cytarabine exposure.Presence of hypotension, chills/rigors, higher temperature, and infant phenotype were independently associated with BSI (p < .05). Of the 572 non-BSIs, the most common was upper respiratory infection (URI) (n = 381, 67%). Compared to episodes without infection, URI symptoms, higher temperature, absolute neutrophil count 500−999/μl, and evaluation during a low-intensity treatment course were more likely to be associated with a non-BSI (p < .05) and inpatient status was less likely to be associated with a non-BSI (p < .05). Conclusions:The BSI rate in pediatric patients with ALL/LLy and fever without severe neutropenia is low, but one-third of the time, patients have a non-BSI. Future research should test if the need for empiric antibiotics can be tailored based on the associations identified in this study.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Infectious events in pediatric patients with acute lymphoblastic leukemia/lymphoma undergoing evaluation for fever without severe neutropenia

Patel

DeGroote

Jackson

et al. 2022

Cancer

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“…47 In our study, quantitative assessment of MFC-MRD at EOI demonstrated a significant ability to predict relapse, although only a small number of patients were tested. Similar to other trials, 33,34,47 in MLL-Baby, none of the initial parameters, including genetics, were able to distinguish patients with different outcomes. However, there were few cases with NUTM1 and PAX5 fusions among our patients.…”

Section: Discussionsupporting

confidence: 67%

“…Adverse events were relapses only (eight of 64, 12.5%), and no patient died from treatmentrelated toxicity. Similar to the Interfant and COG studies, 4,34 all recorded relapses in the MLL-Baby study occurred early during treatment.…”

Section: Discussionsupporting

confidence: 65%

“…Patient numbers in the Japanese studies were small and, notably, there were no patients with initial CNS involvement and only three patients had a WBC more than 100 × 10 9 L. Comparably good results with a 5-year EFS rate of 0.87 (SE 0.05) were obtained in the AALL0631 study of the Children's Oncology Group. 34 However, here too the therapy was much more intensive and contained-as in the Japanese studyrelatively high doses of etoposide, cyclophosphamide, (high-dose) cytarabine, and also high-dose methotrexate (MTX). The proportion of CNS-positive patients (CNS 2 and 3) was 43%.…”

Section: Discussionmentioning

confidence: 99%

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Genetic characteristics and treatment outcome in infants with KMT2A germline B‐cell precursor acute lymphoblastic leukemia: Results of MLL‐Baby protocol

Popov¹,

Tsaur

Permikin

et al. 2023

Pediatric Blood & Cancer

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The aim of this study was to present the diagnostic and outcome characteristics of infants with germline status of KMT2A gene (KMT2A‐g) B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL) treated consistently according to the MLL‐Baby protocol, a moderate‐intensity protocol. Of the 139 patients enrolled in the MLL‐Baby study, 100 (71.9%) carried different types of rearranged KMT2A (KMT2A‐r), while the remaining 39 infants (28.1%) had KMT2A‐g. KMT2A‐g patients were generally older (77% older than 6 months), less likely to have a very high white blood cell count (greater than 100 × 109/L), less likely to be central nervous system (CNS)‐positive, and more likely to be CD10‐positive. The 6‐year event‐free survival and overall survival rates for all 39 patients were 0.74 (standard error [SE] 0.07) and 0.80 (SE 0.07), respectively. Relapse was the most common adverse event (n = 5), with a cumulative incidence of relapse (CIR) of 0.13 (SE 0.06), while the incidence of a second malignancy (n = 1) and death in remission (n = 3) was 0.03 (SE 0.04) and 0.08 (SE 0.04), respectively. None of the initial parameters, including genetics and the presence of recently described fusions of NUTM1 and PAX5 genes, was able to distinguish patients with different outcomes. Only rapidity of response, measured as minimal residual disease (MRD) by flow cytometry, showed a statistically significant impact. Moderate‐intensity therapy, as used in the MLL‐Baby protocol in infants with KMT2A‐g BCP‐ALL, yields results comparable to other infant studies. Patients with a slow multicolor flow cytometry (MFC)‐MRD response should be subjected to advanced therapies, such as targeted or immunotherapies.

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Minimal residual disease predicts outcomes in KMT2A‐rearranged but not KMT2A‐germline infant acute lymphoblastic leukemia: Report from Children's Oncology Group study AALL0631

Faulk

Kairalla

Dreyer

et al. 2023

Pediatric Blood & Cancer

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We measured minimal residual disease (MRD) by multiparameter flow cytometry at three time points (TP) in 117 infants with KMT2A (lysine [K]-specific methyltransferase 2A)-rearranged and 58 with KMT2A-germline acute lymphoblastic leukemia (ALL) on Children's Oncology Group AALL0631 study. For KMT2A-rearranged patients, 3-year event-free survival (EFS) by MRD-positive (≥0.01%) versus MRD-negative (<0.

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Outstanding outcomes in infants with <i>KMT2A</i>-germline acute lymphoblastic leukemia treated with chemotherapy alone: results of the Children’s Oncology Group AALL0631 trial

Abstract: Not available.

Cited by 12 publications

References 15 publications

Infectious events in pediatric patients with acute lymphoblastic leukemia/lymphoma undergoing evaluation for fever without severe neutropenia

Infectious events in pediatric patients with acute lymphoblastic leukemia/lymphoma undergoing evaluation for fever without severe neutropenia

Genetic characteristics and treatment outcome in infants with KMT2A germline B‐cell precursor acute lymphoblastic leukemia: Results of MLL‐Baby protocol

Minimal residual disease predicts outcomes in KMT2A‐rearranged but not KMT2A‐germline infant acute lymphoblastic leukemia: Report from Children's Oncology Group study AALL0631

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