Comparison of Long-Term Neurocognitive Outcomes in Young Children With Acute Lymphatic Leukemia Treated With Cranial Radiation or High-Dose or Very High-Dose Intravenous Methotrexate

Purpose Cranial radiation therapy (CRT) is associated with neurocognitive morbidity in survivors of childhood acute lymphoblastic leukemia (ALL). For most patients, CRT has been replaced with intensified systemic and intrathecal chemotherapy, often including methotrexate (MTX). The impact of chemotherapy-only protocols on neurocognitive outcomes is unclear, and the importance of systemic MTX dose has not been established. Patients and Methods Seventy nine of 120 eligible children diagnosed with high-risk ALL between the ages of 1.0 and 4.9 years participated in this retrospective cohort study. All patients were treated on a uniform chemotherapy protocol with one of three modalities of CNS prophylaxis, depending on their treatment era. In addition to intrathecal therapy, CNS-directed therapy consisted of CRT (18 Gy in 10 fractions) in 25 patients, high-dose intravenous (IV) MTX (8 g/m2 × 3 doses) in 32 patients and very high-dose IV MTX (33.6 g/m2 x 3 doses) in 22 patients. Participants completed tests of intelligence, academic achievement, attention, and memory. Results Neurocognitive assessment was conducted at least 5 years after diagnosis (mean, 10.5 years, standard deviation, 2.7 years). No difference was detected on any neurocognitive measure between children treated with high-dose or very high-dose IV MTX. The combined MTX groups scored near the population mean on 17/18 measures. Children treated with CRT performed more poorly than the MTX group on most measures. Conclusion Treatment strategies for young children with ALL that avoid CRT are associated with good long-term neurocognitive outcomes. In this cohort, the dose of IV MTX did not influence these outcomes.

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Long-term neuropsychological follow-up of young children with medulloblastoma treated with sequential high-dose chemotherapy and irradiation sparing approach

Journal of Neuro-Oncology ◽

10.1007/s11060-017-2409-9 ◽

2017 ◽

Vol 133 (1) ◽

pp. 119-128 ◽

Cited By ~ 15

Author(s):

Taryn B. Fay-McClymont ◽

Danielle M. Ploetz ◽

Don Mabbott ◽

Karin Walsh ◽

Amy Smith ◽

...

Keyword(s):

Young Children ◽

High Dose Chemotherapy ◽

High Dose

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Evaluation of Soil S Pools under 23 Years of Maize Monoculture

Agronomy ◽

10.3390/agronomy11122376 ◽

2021 ◽

Vol 11 (12) ◽

pp. 2376

Author(s):

Pavel Suran ◽

Martin Kulhánek ◽

Jiří Balík ◽

Jindřich Černý ◽

Ondřej Sedlář

Keyword(s):

High Dose ◽

The Czech Republic ◽

S Uptake ◽

Biomass Yields ◽

Entire Experiment ◽

Initial Content ◽

Phosphorus And Potassium ◽

Very High ◽

Sulfur Nutrition

Sulfur nutrition is a critical part of proper crop growth and development. In our study, biomass yields (BY) and S uptake were investigated on long-term maize monoculture on haplic luvisol soil during the 23 years of this trial, as well as changes in water extractable (Sw), adsorbed (Sads), mineral (Sav), and pseudo-total S (St) fractions. Treatments used in this study are: (1) Control (Cont); (2) ammonium sulfate (AS); (3) urea and ammonium nitrate (UAN); (4) UAN + phosphorus and potassium (UAN + PK); (5) UAN + phosphorus, magnesium, sulfur (UAN + PMgS); and (6) Fallow. Recently, the Mehlich 3 method started to be used in the Czech Republic to determine content of plant available S. Using this method, it was found that the content of S extracted by Mehlich 3 (SM3) closely correlates to Sav in both topsoil and subsoil (r = 0.958 in 1997 and 0.990 in 2019, both at p < 0.001). We also found that, on average, during the entire experiment, all treatments had increased yields over Cont (135–147%) and increased S uptake (291, 192, 180, and 246% of Cont for AS, UAN, UAN + PK, and UAN + PMgS, respectively). Examining the changes from 1997 to 2019 in topsoil (0–30 cm depth), we discovered a decrease of S content in Sw, Sads, Sav, and St fractions on all treatments to an average of 34.6%, 65.8%, 42.2%, and 78.6% of their initial values. The exception was AS treatment, which doubled its initial content in mineral fractions and maintained the same levels of St, and which we attribute to the very high dose of S on this treatment (142 kg ha−1 year−1). Using the simple balance method, AS and UAN + PMgS treatments lost 142.2 and 95.3 kg S ha−1 year−1 to other sinks, except plant uptake, from the entire soil profile (0–60 cm) during 23 years of experiment. Other treatments also show significant losses with the exception of Fallow. Given these results, it is clear that content of sulfur in soil is generally decreasing and attention should be paid mainly towards minimizing of its losses.

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Can very high-dose anti-tumor necrosis factor blockade at onset of rheumatoid arthritis produce long-term remission?

Arthritis & Rheumatism ◽

10.1002/art.10274 ◽

2002 ◽

Vol 46 (7) ◽

pp. 1971-1972 ◽

Cited By ~ 17

Author(s):

Philip G. Conaghan ◽

Mark A. Quinn ◽

Philip O'Connor ◽

Richard J. Wakefield ◽

Zunaid Karim ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

High Dose ◽

Very High ◽

Necrosis Factor

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Cohen. High-dose compared with intermediate-dose methotrexate in children with a first relapse of acute lymphatic leukemia. Blood. 2008;112(3):910.

Blood ◽

10.1182/blood-2009-11-252387 ◽

2010 ◽

Vol 115 (1) ◽

pp. 154-154

Keyword(s):

High Dose ◽

Acute Lymphatic Leukemia ◽

Lymphatic Leukemia ◽

Dose Methotrexate ◽

First Relapse ◽

Intermediate Dose

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Long-term effects of cranial irradiation for childhood malignancy on sleep in adulthood

Acta Endocrinologica ◽

10.1530/eje.0.1500503 ◽

2004 ◽

pp. 503-510 ◽

Cited By ~ 32

Author(s):

EJ Van Someren ◽

J Swart-Heikens ◽

E Endert ◽

PH Bisschop ◽

DF Swaab ◽

...

Keyword(s):

Radiation Therapy ◽

Brain Tumours ◽

Cranial Irradiation ◽

High Dose ◽

Serum Concentrations ◽

Healthy Individuals ◽

Long Term Effects ◽

Cranial Radiation ◽

Serum Gh

BACKGROUND: Cranial radiation therapy (CRT) is required for successful treatment of a variety of brain tumours in childhood. OBJECTIVE: To investigate whether childhood CRT leads to altered sleep-wakefulness organization in adulthood, and to identify the determinants of such alterations. SUBJECTS AND METHODS: Subjective (questionnaires) and objective (actigraphy) measures of circadian rhythmicity and sleep were assessed in 25 individuals, 8-29 years after CRT for medulloblastoma (n=17) or other intracranial tumours (n=8), and in a group of 34 age-matched healthy individuals. Serum GH peak during insulin-induced hypoglycaemia and serum concentrations of prolactin and leptin (expressed per fat mass) were determined in the CRT group. RESULTS: The CRT group showed a markedly increased sleep duration (8.66 h, compared with 7.66 h in controls). In addition, the sleep-wake rhythm showed greater amplitude and less fragmentation, and less tolerance for alterations in the timing of sleep. Regression analysis showed both radiation dosage and neuroendocrine status to be determinants of sleep changes, suggesting that some of the alterations may be normalized with hormone supplementation. CONCLUSION: The present study shows that high-dose cranial radiation therapy in childhood is associated with objective and subjective changes in the sleep-wake rhythm in adulthood.

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High-dose-rate brachytherapy and hypofractionated external beam radiotherapy combined with long-term hormonal therapy for high-risk and very high-risk prostate cancer: outcomes after 5-year follow-up

Journal of Radiation Research ◽

10.1093/jrr/rrt128 ◽

2013 ◽

Vol 55 (3) ◽

pp. 509-517 ◽

Cited By ~ 12

Author(s):

H. Ishiyama ◽

T. Satoh ◽

M. Kitano ◽

K.-i. Tabata ◽

S. Komori ◽

...

Keyword(s):

High Risk ◽

External Beam Radiotherapy ◽

High Dose Rate ◽

High Dose ◽

External Beam ◽

High Risk Prostate Cancer ◽

Risk Prostate Cancer ◽

Very High

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Immunosuppressive therapy of aplastic anemia: results of a prospective, randomized trial of antithymocyte globulin (ATG), methylprednisolone, and oxymetholone to ATG, very high-dose methylprednisolone, and oxymetholone

Blood ◽

10.1182/blood.v79.10.2566.2566 ◽

1992 ◽

Vol 79 (10) ◽

pp. 2566-2571 ◽

Cited By ~ 46

Author(s):

K Doney ◽

M Pepe ◽

R Storb ◽

E Bryant ◽

C Anasetti ◽

...

Keyword(s):

Acute Leukemia ◽

Aplastic Anemia ◽

Causes Of Death ◽

Response To Therapy ◽

High Dose ◽

Actuarial Survival ◽

High Dose Methylprednisolone ◽

Significant Difference ◽

Very High

Abstract Sixty-eight patients with moderate (n = 15) or severe (n = 53) aplastic anemia were entered into a prospective, randomized, two-arm treatment study comparing antihuman thymocyte globulin (ATG), lower-dose methylprednisolone (LDM) and oxymetholone to ATG, higher-dose methylprednisolone (HDM), and oxymetholone. There were no differences between the two groups when comparing age, sex, etiology of aplasia, disease duration, severity of aplasia, or pretherapy granulocyte counts. Side effects of LDM and HDM were similar. Of the 64 patients evaluable for response to therapy, 12 of 33 (36%) who received LDM had complete, partial, or minimal responses compared with 15 of 31 patients (48%) who received HDM (P = .33). Actuarial survival at 4 years is 43% for patients in the LDM group and 47% for patients in the HDM group (P = .99). Causes of death included hemorrhage, infection, evolution to acute leukemia, and complications of subsequent bone marrow transplantation. Long-term complications included paroxysmal nocturnal hemoglobinuria (n = 3), evolution to myelodysplasia or acute leukemia (n = 6), and recurrent aplasia (n = 6). We were unable to show a significant difference in toxicity, response rate, or survival for patients treated with ATG, oxymetholone, and LDM compared with patients who received ATG, oxymetholone, and HDM.

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