Skeletal morbidity in childhood acute lymphoblastic leukaemia

Davies, Justin H; Evans, Bronwen Alice James; Jenney, Meriel; Gregory, John W.

doi:10.1111/j.1365-2265.2005.02263.x

Cited by 64 publications

(57 citation statements)

References 92 publications

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“…Pathological changes in bone with subsequent skeletal morbidity are caused by the leukemic cells as well as by the chemotherapeutic agents and glucocorticoids used in leukemia treatment [2,8,12,13].…”

Section: Introductionmentioning

confidence: 99%

Acute lymphoblastic leukemia in children: Correlation of musculoskeletal manifestations and immunophenotypes

Maman

Steinberg

Stark

et al. 2007

Journal of Children's Orthopaedics

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Purpose Studies on musculoskeletal manifestations (MSM) of childhood acute lymphoblastic leukemia (ALL) have yielded variable findings with regard to their clinical impact. We investigated the significance for differential diagnosis, treatment and outcome of musculoskeletal complaints as presenting symptoms of ALL, and their correlation with leukemia immunophenotypes, for which data is lacking. Methods Data on 783 children in the national study for childhood ALL between 1984 and 2003 were reviewed retrospectively. Statistical analysis examined possible relationships between MSM at the time of diagnosis and demographic and clinical data, biological features of leukemia (peripheral blood counts, immunophenotype and main cytogenetic aberration), response to initial prednisone treatment, and outcome.Results Of 765 children with data on orthopaedic complaints, 240 presented with MSM (31.4%). Among these children, B cell precursor (BCP) was much more common (209/576, 36.3%) than T cell ALL (25/176, 14.2%). Patients with MSM had lower white blood cell counts (WBC) (median of 9 vs. 20 · 10 9 /L, P < 0.001) and percentage of blast cells in the peripheral blood at diagnosis compared to those without (median of 27 vs. 53%, P < 0.001). Hepatomegaly and splenomegaly were less common in MSM group (67 vs. 53% <3 cm, P < 0.001, and 63 vs. 50% <3 cm, P < 0.001, respectively). Poor response to initial treatment with prednisone was recorded in 7.1% of patients with MSM versus 11.5% of those without (P = 0.086). The analysis revealed no independent effect of MSM on event-free survival (EFS), after correcting for differences in EFS related to immunophenotype or initial WBC. Conclusions MSM occur mostly in children with BCP ALL who present with less involvement of extramedullary organs, low peripheral blood blasts and white blood cells counts. These findings highlight the importance of including ALL in the differential diagnosis of MSM even in the presence of an apparently normal peripheral blood count. Our study also suggests that MSM are caused by leukemic cells with enhanced biological propensity to remain relatively confined within the intramedullary bone-marrow space.

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Section: Introductionmentioning

confidence: 99%

Acute lymphoblastic leukemia in children: Correlation of musculoskeletal manifestations and immunophenotypes

Maman

Steinberg

Stark

et al. 2007

Journal of Children's Orthopaedics

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“…Survivors of childhood acute lymphoblastic leukemia (ALL) account for 25% of all long-term survivors of childhood cancer, the result of achievements in combination chemotherapy and radiation therapy that have dramatically improved cure rates for ALL from 61% in the period from 1975 to 1984 to 83.6% in 1995 to 2001 (2,3). Secondary to their treatment exposures, survivors of childhood ALL are at increased risk of cardiovascular disease (4-6), obesity (7,8), osteoporosis (9,10), and cardiovascular and all-cause mortality (11).…”

Section: Introductionmentioning

confidence: 99%

Physical Inactivity in Adult Survivors of Childhood Acute Lymphoblastic Leukemia: A Report from the Childhood Cancer Survivor Study

Florin

Fryer

Miyoshi

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

192

160

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“…All chemotherapeutic agents that are used in the treatment of ALL were found to reduce the number of osteoblast-like cells in vitro (5), and combinations of different agents had more toxic effects compared with individual agents (30). GCs were found to exhibit the strongest risk of ON in the clinical setting during ALL therapy (2), although MTX and alkylating agents were also indicated to be associated with ON risk in certain studies (2,3,6). Therefore, we reviewed all used protocols to detect differences in administration schedule and doses of GC and MTX.…”

Section: Discussionmentioning

confidence: 99%

Risk factors for symptomatic osteonecrosis in childhood ALL: A retrospective study of a Slovenian pediatric ALL population between 1970 and 2004

Karas-Kuzelicki¹,

Mencej-Bedrač²,

Jazbec³

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Treatment induced non-traumatic osteonecrosis (ON) has been reported increasingly in children treated for acute lymphoblastic leukemia (ALL). Several risk factors for ON have been identified in childhood cancer patients; however, their diagnostic and prognostic power is limited and the etiology of the disease remains unclear. Therefore, a continuous effort is focused on the identification of additional ON risk factors. We performed a retrospective study of 313 childhood ALL patients to test the association between the ON occurrence in children receiving ALL therapy and common polymorphisms in potential target genes: Thiopurine S-methyltransferase (TPMT; 460G>A, 719A>G), 5,10-methylenetetrahydrofolate reductase (MTHFR; 677C>T, 1298A>C), estrogen receptor alpha 1 (ESR1; XbaI) and collagen type I, α1 (COL1A1; Sp1). In the present cohort, higher age and more recently developed treatment protocols were independent risk factors for ON. In children >14.5 years old, TPMT genotype modulated the risk of ON. Additionally, in children <12.9 years old ESR1 genotypes were also implicated in the pathogenesis of ON. Besides greater age and more recent treatment protocols, genetic factors (polymorphisms in ESR1 and TPMT genes) were suggested to be implicated in the pathogenesis of ON and could be potentially used as genetic prognostic markers for ON.

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Skeletal morbidity in childhood acute lymphoblastic leukaemia

Cited by 64 publications

References 92 publications

Acute lymphoblastic leukemia in children: Correlation of musculoskeletal manifestations and immunophenotypes

Acute lymphoblastic leukemia in children: Correlation of musculoskeletal manifestations and immunophenotypes

Physical Inactivity in Adult Survivors of Childhood Acute Lymphoblastic Leukemia: A Report from the Childhood Cancer Survivor Study

Risk factors for symptomatic osteonecrosis in childhood ALL: A retrospective study of a Slovenian pediatric ALL population between 1970 and 2004

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