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1.
Pediatr Blood Cancer ; 70(11): e30634, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37592363

RESUMO

Chemotherapy-induced peripheral neuropathy (CIPN), a common condition in children with acute lymphoblastic leukemia, can be challenging to diagnose. Using data from Children's Oncology Group AALL0932 physical function study, we sought to determine if parent/guardian proxy-reported responses from the Pediatric Outcomes Data Collection Instrument could identify children with motor or sensory CIPN diagnosed by physical/occupational therapists (PT/OT). Four variables moderately discriminated between children with and without motor CIPN (c-index 0.76, 95% confidence interval [CI]: 0.64-0.84), but sensory and optimism-corrected models had weak discrimination (c-index sensory models 0.65, 95% CI: 0.54-0.74). New proxy-report measures are needed to identify children with PT/OT diagnosed CIPN.


Assuntos
Antineoplásicos , Doenças do Sistema Nervoso Periférico , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Criança , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Exame Físico , Qualidade de Vida , Antineoplásicos/uso terapêutico
2.
Pediatr Blood Cancer ; 66(11): e27948, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31347788

RESUMO

BACKGROUND: Despite the intensity of hematopoietic stem cell transplantation (HCT), relapse remains the most common cause of death in juvenile myelomonocytic leukemia (JMML). In contrast to other leukemias where therapy is used to reduce leukemic burden prior to transplant, many patients with JMML proceed directly to HCT with active disease. The objective of this study was to elucidate whether pre-HCT therapy has an effect on the molecular burden of disease and how this affects outcome post-HCT. PROCEDURE: Twenty-one patients with JMML who received pre-HCT therapy and were transplanted at UCSF were analyzed in this study. The mutant allele frequency of the driver mutation was assessed before and after pre-HCT therapy, using custom amplicon next-generation sequencing. RESULTS: Of the 21 patients, seven patients (33%) responded to therapy with a significant reduction in their mutant allele frequency and were classified as molecular responders. Six of these patients received moderate-intensity chemotherapy, one patient received only azacitidine. The 5-year progression-free survival after HCT of molecular responders was 100% versus 61% for nonresponders (P = .12). Survival of molecular nonresponders was not improved by use of high-intensity conditioning, but patients were salvaged if they experienced severe graft versus host disease. There were no baseline clinical characteristics that were associated with response to pre-HCT therapy. CONCLUSIONS: Despite the myelodysplastic nature of JMML, patients treated with pre-HCT therapy can achieve molecular remissions. These patients experienced a trend toward improved outcomes post-HCT. Importantly, molecular testing can be helpful to distinguish between responders and nonresponders and should become an integral part of clinical care.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Genes Neoplásicos , Transplante de Células-Tronco Hematopoéticas , Leucemia Mielomonocítica Juvenil/tratamento farmacológico , Terapia Neoadjuvante , Análise de Sequência de DNA , Carga Tumoral/efeitos dos fármacos , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , DNA de Neoplasias/sangue , Avaliação de Medicamentos , Monitoramento de Medicamentos , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/terapia , Humanos , Lactente , Leucemia Mielomonocítica Juvenil/sangue , Leucemia Mielomonocítica Juvenil/genética , Leucemia Mielomonocítica Juvenil/terapia , Masculino , Proteínas de Neoplasias/genética , Intervalo Livre de Progressão , Recidiva , Estudos Retrospectivos , Esplenectomia , Condicionamento Pré-Transplante
3.
Leukemia ; 32(6): 1370-1379, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29472723

RESUMO

Minimal residual disease (MRD) after initial therapy is integral to risk stratification in B-precursor and T-precursor acute lymphoblastic leukemia (B-ALL, T-ALL). Although MRD determines depth of remission, remission remains defined by morphology. We determined the outcomes of children with discordant assessments of remission by morphology vs. flow cytometry using patients age 1-30.99 years enrolled on Children's Oncology Group ALL trials who underwent bone marrow assessment at the end of induction (N = 9350). Morphologic response was assessed locally as M1 (<5% lymphoblasts; remission), M2 (5-25%), or M3 (>25%). MRD was centrally measured by flow cytometry. Overall, 19.8% of patients with M2/M3 morphology had MRD < 5%. M1 with MRD ≥ 5% was less common in B-ALL (0.9%) than T-ALL (6.9%; p < 0.0001). In B-ALL, M1/MRD ≥ 5% was associated with superior 5-year event-free survival (EFS) than M2/MRD ≥ 5% (59.1% ± 6.5% vs. 39.1% ± 7.9%; p = 0.009), but was inferior to M1/MRD < 5% (87.1% ± 0.4%; p < 0.0001). MRD levels were higher in M2/MRD ≥ 5% than M1/MRD ≥ 5% patients. In T-ALL, EFS was not significantly different between M1/MRD ≥ 5% and M2/MRD ≥ 5%. Patients with morphologic remission but MRD ≥ 5% have outcomes similar to those who fail to achieve morphological remission, and significantly inferior to those with M1 marrows and concordant MRD, suggesting that flow cytometry should augment the definition of remission in ALL.


Assuntos
Citometria de Fluxo/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Adulto Jovem
4.
J Clin Oncol ; 35(23): 2700-2707, 2017 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-28671857

RESUMO

Purpose Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for neurocognitive deficits that are associated with treatment, individual, and environmental factors. This study examined the impact of different methotrexate (MTX) and corticosteroid treatment strategies on neurocognitive functioning in children with high-risk B-lineage ALL. Methods Participants were randomly assigned to receive high-dose MTX with leucovorin rescue or escalating dose MTX with PEG asparaginase without leucovorin rescue. Patients were also randomly assigned to corticosteroid therapy that included either dexamethasone or prednisone. A neurocognitive evaluation of intellectual functioning (IQ), working memory, and processing speed (PS) was conducted 8 to 24 months after treatment completion (n = 192). Results The method of MTX delivery and corticosteroid assignment were unrelated to differences in neurocognitive outcomes after controlling for ethnicity, race, age, gender, insurance status, and time off treatment; however, survivors who were age < 10 years at diagnosis (n = 89) had significantly lower estimated IQ ( P < .001) and PS scores ( P = .02) compared with participants age ≥ 10 years. In addition, participants who were covered by US public health insurance had estimated IQs that were significantly lower ( P < .001) than those with US private or military insurance. Conclusion Children with high-risk B-lineage ALL who were age < 10 years at diagnosis are at risk for deficits in IQ and PS in the absence of cranial radiation, regardless of MTX delivery or corticosteroid type. These data may serve as a basis for developing screening protocols to identify children who are at high risk for deficits so that early intervention can be initiated to mitigate the impact of therapy on neurocognitive outcomes.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cognição/efeitos dos fármacos , Inteligência/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Tempo de Reação/efeitos dos fármacos , Corticosteroides/administração & dosagem , Adultos Sobreviventes de Eventos Adversos na Infância , Fatores Etários , Asparaginase/administração & dosagem , Criança , Dexametasona/administração & dosagem , Feminino , Humanos , Seguro Saúde , Leucovorina/administração & dosagem , Masculino , Medicaid , Metotrexato/administração & dosagem , Polietilenoglicóis/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras B/psicologia , Prednisona/administração & dosagem , Estados Unidos
5.
Int J Cancer ; 138(2): 332-9, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26235006

RESUMO

Standard risk acute lymphoblastic leukemia (SR-ALL) has high cure rates, but requires 2-3 years of therapy. We aimed to (i) prospectively evaluate health-related quality of life (HRQOL) during and after SR-ALL therapy, and (ii) identify associated predictors. Parents of 160 SR-ALL patients enrolled on Children's Oncology Group (COG) therapeutic trial AALL0331 at 31 sites completed the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales (physical, emotional and social functioning) and Family Assessment Device-General Functioning (FAD-GF) at 1, 6 and 12 months after diagnosis, and 3 months post-therapy. Mean PedsQL scores in physical, emotional and social functioning were impaired 1 month after diagnosis but steadily improved. Three months post-therapy, impaired physical and social functioning was observed in 27.8 and 25.8% of patients, respectively. In repeated-measures analysis, problematic family functioning predicted emotional (OR = 1.85, 95% CI 1.03-3.34) and social (OR = 1.99, 95% CI 1.21-3.27) impairment. Larger household size was associated with social impairment (OR = 1.21, 95% CI 1.02-1.45). Adverse neurological event(s) during therapy predicted post-therapy physical (OR = 5.17, 95% CI 1.61-16.63) and social (OR = 8.17, 95% CI 1.19-56.16) impairment. HRQOL 1 month after diagnosis was not predictive of HRQOL 3 months after therapy completion. In conclusion, children with SR-ALL experience considerable impairment in HRQOL at the end of induction, but rapidly improve. However, many still experience physical and social impairment 3 months post-therapy, suggesting a role for continued family and physical functioning support. Longer follow-up is needed to determine if post-therapy deficits change over time.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/psicologia , Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Estudos Longitudinais , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estudos Prospectivos , Inquéritos e Questionários
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