Osteonecrosis in Children and Adolescents With Acute Lymphoblastic Leukemia: Early Diagnosis and New Treatment Strategies

Biddeci, Giada; Bosco, Gerardo; Varotto, Elena; Corradin, Marco; Geranio, Giulia; Tridello, Gloria; Pillon, Marta; Carraro, Elisa; Garetto, G; Assadi, Roya; Gigante, Cosimo; Putti, Maria Caterina

doi:10.21873/anticanres.13236

Cited by 13 publications

(20 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The most severe skeletal complication is symptomatic ON, caused by bone death resulting from poor blood supply. Biddeci et al (15) evaluated 495 children and young adolescents with a diagnosis of ALL between 2000 and 2017. A total of 23 4.6%)/495 patients presented ON.…”

Section: Discussionmentioning

confidence: 99%

Grade 3 and 4 Toxicity Profiles During Therapy of Childhood Acute Lymphoblastic Leukemia

Zawitkowska

Lejman

Zaucha‐Prażmo

et al. 2019

In Vivo

View full text Add to dashboard Cite

Background/Aim: The risk factors, clinical features and non-hematological toxicity profiles during chemotherapy in acute lymphoblastic leukemia (ALL) patients treated in pediatric hematology centres were analysed. Materials and Methods: A total of 902/1872 children were reported as having grade 3 or 4 toxicity. Results: Among the analysed toxicities, infection and gastrointestinal and liver toxicities were the most common. The median follow-up was 6.8 years. Overall survival and event-free survival rates for the analysed group were lower than those reported for the group without grade ≥3 toxicity. In univariate analysis, we identified the number of toxic episodes, the risk group and remission status that had a significant impact on the outcome. Multivariate analysis demonstrated the risk group and the number of toxic episodes ≥3 to be statistically significant for the results. Conclusion: The toxic profiles investigated in our report should be used in future efforts to decrease the burden of side effects during chemotherapy. Over the last years, there has been an improvement in the overall survival of childhood acute lymphoblastic leukemia (ALL), which is now around 80-90%. This is due to contemporary multidrug therapy regimens but, on the other hand, patients are burdened with severe complications of treatment (1, 2). Chemotherapy has a range of side-effects, such as infection, organ damage, hematological and other (malnutrition, hair loss). Most agents causing immunosuppression and myelosuppression increase the risk of bacterial, viral and fungal infections. The infection is still a major cause of death in ALL children (3, 4). Every organ may be adversely affected by anti-leukemic treatment, the most 1333 This article is freely accessible online.

show abstract

Section: Discussionmentioning

confidence: 99%

Grade 3 and 4 Toxicity Profiles During Therapy of Childhood Acute Lymphoblastic Leukemia

Zawitkowska

Lejman

Zaucha‐Prażmo

et al. 2019

In Vivo

View full text Add to dashboard Cite

show abstract

“…In general, total joint replacement is delayed as long as possible as children are expected to significantly outlive their prostheses [63,65]. Promising new approaches include core decompression with implantation of autologous mesenchymal stem cell therapy [66] and the use of hyperbaric oxygen therapy (HBOT) [67,68]. Controversial is the use of medical therapies targeting pathophysiologic mechanisms such as bone metabolism, lipid metabolism or microvascular health, and including calcium channel blockers, prostaglandins (iloprost), low molecular weight heparin, statins, and bisphosphonates [63,65].…”

Section: Osteonecrosis In Childhood Leukemia: Treatment Strategies Anmentioning

confidence: 99%

Pain Management in Childhood Leukemia: Diagnosis and Available Analgesic Treatments

Coluzzi

Rocco

Gladden

et al. 2020

Cancers

View full text Add to dashboard Cite

Pain is one of the most common symptoms in children suffering from leukemia, who are often misdiagnosed with other childhood painful diseases such as juvenile idiopathic arthritis. Corticosteroid-induced osteonecrosis (ON) and vincristine-induced peripheral neuropathy (VIPN) are the most common painful manifestations. Additionally, ongoing pain may continue to impact quality of life in survivorship. This narrative review focuses on the pathophysiological mechanisms of pain in childhood leukemia and current available indications for analgesic treatments. Pain management in children is often inadequate because of difficulties in pain assessment, different indications across countries, and the lack of specific pediatric trials. Analgesic drugs are often prescribed off-label to children by extrapolating information from adult guidelines, with possible increased risk of adverse events. Optimal pain management should involve a multidisciplinary team to ensure assessment and interventions tailored to the individual patient.

show abstract

“…Az osteonecrosis, más néven asepticus/avascularis csontnecrosis vagy csontelhalás az ALL kemoterápiájának egyik ismert és súlyos szövődménye, melynek kialakulásában a kortikoszteroidok alkalmazásának (prednizolon, illetve még inkább a dexametazon) van kulcsszerepe. Különböző súlyossági fokozatai vannak, a legenyhébb esetben tünetmentes is lehet; ekkor még csak mágnesesmagrezonancia-képalkotó vizsgálattal (MRI) lehet igazolni az elváltozást, súlyos esetben azonban az érintett ízület akár mozgásképtelenné válhat [13,14]. A szimptomatikus esetekben legjellemzőbb tünet a csont vagy az ízület fájdalma, funkcióvesztése [8].…”

Section: Eredeti Közleményunclassified

Az akut lymphoblastos leukaemiával kezelt gyermekek csontrendszerét érintő mellékhatások

Beniczky

Hosszú

Erdélyi

et al. 2020

View full text Add to dashboard Cite

Összefoglaló. Bevezetés: A gyermekkori akut lymphoblastos leukaemia kezelése napjainkban 80% feletti túlélést tesz lehetővé, de fontos cél a kezelés okozta mellékhatások kivédése és a gyermekek hosszú távú életminőségének javítása is. Célkitűzés: A kemoterápia csontrendszerre kifejtett mellékhatásainak vizsgálata és a prognosztikai tényezők feltárása, a rizikófaktorok összegyűjtése. Módszerek: Retrospektív vizsgálatunkba a Semmelweis Egyetem II. Gyermekgyógyászati Klinikáján 2007 és 2016 között kezelt 215, akut lymphoblastos leukaemiás gyermek közül a csontelváltozást észlelt betegeket vontuk be a következő, csontrendszert érintő megbetegedésekkel: 38 gyermeknél csökkent csontásványianyag-tartalom, 5 főnél osteonecrosis, 3 főnél osteomyelitis és 2 fő esetében patológiás fractura volt detektálható. Különböző követési időpontokban gyűjtöttünk oszteodenzitometriai adatokat, D-vitamin-, foszfát-, alkalikusfoszfatáz- és lipidszinteket is. Eredmények: Az oszteodenzitometriai értékek már a diagnóziskor csökkent értéket mutatnak, az intenzív vénás kemoterápia hatására pedig további csökkenés figyelhető meg (a lumbális gerinc Z-score-értéke a kezelés kezdetén: –1,5 ± 1,02, az intenzív vénás kezelés végén –1,8 ± 0,5). A Z-score-értékek a fenntartó terápia végére javuló tendenciát mutattak (–1,6 ± 0,5; p<0,05), majd az utánkövetés során ismételt javulás (–1,2 ± 0,4 [p<0,01] és –0,9 ± 0,4) figyelhető meg. A D-vitamin-szintek esetében az intenzív vénás kemoterápiát követően fokozatos javulást láthattunk (20 ± 3,1 ng/ml vs. többéves utánkövetéskor 31 ± 2,6 ng/ml; p<0,001). A foszfát- és alkalikusfoszfatáz-szintek nem változtak számottevő mértékben a vizsgált időtartam során. A koleszterinszintek a terápia során folyamatos növekedést mutattak (a kemoterápia kezdetén 3,28 ± 0,3 mM/l vs. a fenntartó kezelés végén 4,62 ± 0,2 mM/l; p<0,0001). A HDL-koleszterin esetében szintén hasonló tendenciát figyelhettünk meg (a diagnóziskor 0,53 ± 0,09 mM/l vs. a fenntartó kezelés végén 1,48 ± 0,14 mM/l). Következtetés: Kiemelendő, hogy a gyógyult gyermekek utánkövetése, az oszteodenzitometriai mérések és a laborparaméterek ellenőrzése rendkívül fontos, mivel csontelváltozásokkal a leukaemiás betegek esetén számolni kell. Orv Hetil. 2020; 161(49): 2086–2093. Summary. Introduction: Current treatment of pediatric acute lymphoblastic leukemia allows survival above 80%, but it is also very important to prevent treatment-related side effects and to improve long-term quality of life. Objective: Our aim was to assess the side effects of chemotherapy on the skeletal system and to identify prognostic and risk factors. Methods: Between 2007 and 2016, 215 children were treated with acute lymphoblastic leukemia at the 2nd Department of Paediatrics, Semmelweis University. In our retrospective study, we analyzed data of these children with skeletal-related side-effects (38 children with reduced bone mineral density, 5 with osteonecrosis, 3 with osteomyelitis and 2 with pathologic fracture). Results: Osteodensitometric data, vitamin D, phosphate, alkaline phosphatase and lipid levels were collected at different follow-up times. Osteodensitometric values were already reduced at the time of diagnosis (lumbar spine Z-score: –1.5 ± 1.02) and intensive venous chemotherapy caused further decrease (–1.8 ± 0.5). Z-score showed an improving tendency at the end of the maintenance therapy (–1.6 ± 0.5; p<0.05), followed by further improvement later (–1.2 ± 0.4 [p<0.01] and –0.9 ± 0.4). Vitamin D levels showed improvement after intensive venous chemotherapy (20 ± 3.1 ng/ml vs. 31 ± 2.6 ng/ml at multi-year follow-up; p<001). Phosphate and alkaline phosphatase levels did not change considerably during the period considered. Cholesterol levels increased continuously during treatment (at the time of diagnosis 3.28 ± 0.3 mM/l vs. at the end of the maintenance therapy 4.62 ± 0.2 mM/l; p<0.0001). A similar trend was observed with HDL cholesterol levels (0.53 ± 0.09 mM/l vs. 1.48 ± 0.14 mM/l). Conclusion: In summary, we can conclude that follow-up of these children, osteodensitometric measurements and monitoring of laboratory parameters are extremely important, as bone abnormalities can occur in leukemia patients. Orv Hetil. 2020; 161(49): 2086–2093.

show abstract

Osteonecrosis in Children and Adolescents With Acute Lymphoblastic Leukemia: Early Diagnosis and New Treatment Strategies

Cited by 13 publications

References 37 publications

Grade 3 and 4 Toxicity Profiles During Therapy of Childhood Acute Lymphoblastic Leukemia

Grade 3 and 4 Toxicity Profiles During Therapy of Childhood Acute Lymphoblastic Leukemia

Pain Management in Childhood Leukemia: Diagnosis and Available Analgesic Treatments

Az akut lymphoblastos leukaemiával kezelt gyermekek csontrendszerét érintő mellékhatások

Contact Info

Product

Resources

About