CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) PRESENTING WITH SEVERE OSTEOLYSIS: A Model to Study Leukemia-Bone Interactions and Potential Targeted Therapeutics

Jayanthan, Aarthi; Miettunen, Paivi; Incoronato, Andrea; Ortiz‐Neira, Clara L.; Lewis, Victor; Anderson, Ronald; D, Fröhlich; Narendran, Aru

doi:10.3109/08880011003663382

Cited by 17 publications

(8 citation statements)

References 22 publications

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“…At ALL diagnosis, bone fragility has been linked to excessive skeletal resorption through liberation of osteoclast-activating factors by the leukemic cells (including interleukins 6 and 8). 37 This observation is supported by our data showing excessive osteolysis on the second metacarpal endosteal surface among children with vertebral fractures and recently diagnosed ALL, resulting in reduced metacarpal cortical width. 11 Vassilopoulou-Sellin and Ramirez 38 reported a young ALL patient with back pain and subtle vertebral changes at diagnosis followed by severe vertebral fractures just two months later.…”

Section: Discussionsupporting

confidence: 80%

High Incidence of Vertebral Fractures in Children With Acute Lymphoblastic Leukemia 12 Months After the Initiation of Therapy

Alos

Grant²,

Ramsay³

et al. 2012

JCO

110

129

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Purpose-Vertebral fractures due to osteoporosis are a potential complication of childhood acute lymphoblastic leukemia (ALL). To date, the incidence of vertebral fractures during ALL treatment has not been reported. CIHR Author ManuscriptCIHR Author Manuscript CIHR Author ManuscriptPatient and Methods-We prospectively evaluated 155 children with ALL during the first 12 months of leukemia therapy. Lateral thoracolumbar spine radiographs were obtained at baseline and 12 months. Vertebral bodies were assessed for incident vertebral fractures using the Genant semi-quantitative method, and relevant clinical indices such as spine bone mineral density (BMD), back pain and the presence of vertebral fractures at baseline were analyzed for association with incident vertebral fractures.Results-Of the 155 children, 25 (16%, 95% Confidence Interval (CI) 11% to 23%) had a total of 61 incident vertebral fractures, of which 32 (52%) were moderate or severe. Thirteen of the 25 children with incident vertebral fractures (52%) also had fractures at baseline. Vertebral fractures at baseline increased the odds of an incident fracture at 12 months by an odds ratio of 7.3 (95% CI 2.3 to 23.1, p = 0.001). In addition, for every one standard deviation reduction in spine BMD Zscore at baseline, there was 1.8-fold increased odds of incident vertebral fracture at 12 months (95% CI 1.2 to 2.7, p = 0.006).Conclusion-Children with ALL have a high incidence of vertebral fractures after 12 months of chemotherapy, and the presence of vertebral fractures and reductions in spine BMD Z-scores at baseline are highly associated clinical features.

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Section: Discussionsupporting

confidence: 80%

High Incidence of Vertebral Fractures in Children With Acute Lymphoblastic Leukemia 12 Months After the Initiation of Therapy

Alos

Grant²,

Ramsay³

et al. 2012

JCO

110

129

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“…Beyond MM, although more rarely observed, the same kind of skeletal lesions may also occur in the course of several HM [13,[21][22][23][24]. As previously mentioned, patients with skeletal lesions suffer from a localized and sometimes irradiated nociceptive continuous pain at rest, possibly complicated by neuropathic symptoms (mixed pain), and by movement-related incidental pain.…”

Section: Nociceptive Painmentioning

confidence: 97%

Pain in malignant hematology

Niscola

Tendas

Scaramucci

et al. 2011

Expert Review of Hematology

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Pain is frequently experienced by patients with hematological malignancies, although it often receives little attention. Different underlying causes and mechanisms may sustain several pain syndromes in hematological malignant patients. Pain may be due to disease itself, to disease-related complications, to iatrogenic causes or may be associated with unrelated medical conditions. The management of pain in this setting requires a multidisciplinary approach, integrating analgesics and causal interventions. An accurate diagnostic assessment and the identification of the underlying causes and pathogenetic mechanisms may dictate the treatment approach. For most pain patients, the WHO's three-step analgesic scale for cancer pain relief can provide adequate relief with oral options, although difficult-to-treat pain syndromes, requiring a more complex treatment approach, may also be observed.

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“…However, reduction in lumbar spine BMD Z-score at diagnosis is clearly associated with increased odds for vertebral fracture (OR 1.8; 95 % CI 1.10–2.9; P < 0.001) [13]. Bone fragility at the time of ALL diagnosis has been linked to increased skeletal resorption due to cytokine-mediated enhanced osteoclast activity [16••, 17]. …”

Section: Skeletal Abnormalities At Leukemia Diagnosismentioning

confidence: 99%

Bone Morbidity in Childhood Leukemia: Epidemiology, Mechanisms, Diagnosis, and Treatment

Mostoufi‐Moab

Halton

2014

Curr Osteoporos Rep

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Skeletal abnormalities are commonly seen in children and adolescents with leukemia. The spectrum ranges from mild pain to debilitating osteonecrosis (ON) and fractures. In this review, we summarize the skeletal manifestations, provide an update on therapeutic strategies for prevention and treatment, and discuss the most recent advances in musculoskeletal research. Early recognition of skeletal abnormalities and strategies to optimize bone health are essential to prevent long-term skeletal sequelae and diminished quality of life observed in children and adolescents with leukemia.

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CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) PRESENTING WITH SEVERE OSTEOLYSIS: A Model to Study Leukemia-Bone Interactions and Potential Targeted Therapeutics

Cited by 17 publications

References 22 publications

High Incidence of Vertebral Fractures in Children With Acute Lymphoblastic Leukemia 12 Months After the Initiation of Therapy

High Incidence of Vertebral Fractures in Children With Acute Lymphoblastic Leukemia 12 Months After the Initiation of Therapy

Pain in malignant hematology

Bone Morbidity in Childhood Leukemia: Epidemiology, Mechanisms, Diagnosis, and Treatment

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