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

2012 ◽  
Vol 30 (22) ◽  
pp. 2760-2767 ◽  
Author(s):  
Nathalie Alos ◽  
Ronald M. Grant ◽  
Timothy Ramsay ◽  
Jacqueline Halton ◽  
Elizabeth A. Cummings ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Vertebral Fractures ◽  
Lymphoblastic Leukemia ◽  
Thoracolumbar Spine ◽  
Mineral Density ◽  
Fractures In Children ◽  
High Incidence ◽  
Z Scores ◽  
Initiation Of Therapy ◽  
Incident Vertebral Fractures

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. Patient 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 semiquantitative 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% CI, 11% to 23%) had a total of 61 incident vertebral fractures, of which 32 (52%) were moderate or severe. Thirteen (52%) of the 25 children with incident vertebral fractures 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 = .001). In addition, for every one standard deviation reduction in spine BMD Z-score at baseline, there was 1.8-fold increased odds of incident vertebral fracture at 12 months (95% CI, 1.2 to 2.7; P = .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.

CRHR1 Polymorphisms Predict Bone Density in Survivors of Acute Lymphoblastic Leukemia

2008 ◽  
Vol 26 (18) ◽  
pp. 3031-3037 ◽  
Author(s):  
Terreia S. Jones ◽  
Sue C. Kaste ◽  
Wei Liu ◽  
Cheng Cheng ◽  
Wenjian Yang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Bone Density ◽  
Bone Mineral ◽  
Lymphoblastic Leukemia ◽  
Quantitative Computed Tomography ◽  
Nucleotide Polymorphisms ◽  
Mineral Density ◽  
Specific Manner ◽  
Osteoporosis Risk Factors ◽  
Z Scores

Purpose Corticosteroids are a critical component of therapy for acute lymphoblastic leukemia (ALL) but are associated with late effects, such as osteoporosis. Risk factors remain poorly defined. Because CRHR1 polymorphisms have been associated with other corticosteroid effects, our goal was to define whether CRHR1 polymorphisms predict which patients with ALL are likely to develop bone mineral deficits. Patients and Methods The mean bone mineral density z scores of 309 long-term survivors of ALL were determined by quantitative computed tomography of the trabecular lumbar spine. We analyzed whether CRHR1 genotypes, adjusted for sex, ALL treatment regimen, and weight, could predict bone density. Results We found that three single nucleotide polymorphisms (SNPs), all in linkage disequilibrium, were associated with bone density in a sex-specific manner. Bone density was lower in males (P = .001), in nonblack patients (P < .08), in those who were not overweight (P < .001), and in those who received intensive antimetabolites and glucocorticoids (P < .001). After adjustment for these features, the G allele at the rs1876828 SNP was associated with lower z scores (P = .02) in males but tended to have the opposite association in females (P = .09). Conclusion CRHR1 polymorphisms may impact the risk of bone density deficits in patients treated with corticosteroids and antimetabolites in a sex-specific manner.

scholarly journals Longitudinal Assessment of Bone Density and Structure in Childhood Survivors of Acute Lymphoblastic Leukemia without Cranial Radiation

2012 ◽  
Vol 97 (10) ◽  
pp. 3584-3592 ◽  
Author(s):  
Sogol Mostoufi-Moab ◽  
Jill Brodsky ◽  
Elizabeth J. Isaacoff ◽  
Anne Tsampalieros ◽  
Jill P. Ginsberg ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Quantitative Computed Tomography ◽  
Peripheral Quantitative Computed Tomography ◽  
Longitudinal Assessment ◽  
Linear Regression Models ◽  
Mineral Density ◽  
Z Scores ◽  
Childhood Survivors

Abstract Purpose: Children with acute lymphoblastic leukemia (ALL) are at risk for impaired bone accrual. This peripheral quantitative computed tomography study assessed changes in bone mineral density (BMD) and structure after completion of ALL treatment. Methods: Fifty ALL participants, ages 5–22 yr, were enrolled within 2 yr (median 0.8 yr) after completing ALL therapy. Tibia peripheral quantitative computed tomography scans were performed at enrollment and 12 months later. Age-, sex-, and race-specific Z-scores for trabecular BMD (TrabBMD), cortical BMD (CortBMD), and cortical area (CortArea) were generated based on more than 650 reference participants. Multivariable linear regression models examined determinants of changes in Z-scores. Results: At enrollment, mean TrabBMD (−1.03 ± 1.34) and CortBMD (−0.84 ± 1.05) Z-scores were low (both P &lt; 0.001) compared with reference participants. TrabBMD and CortBMD Z-scores increased to −0.58 ± 1.41 and −0.51 ± 0.91 over 1 yr, respectively (both P &lt; 0.001). Changes in cortical outcomes varied according to the interval since completion of therapy. Among those enrolled less than 6 months after therapy, CortArea Z-scores increased and CortBMD Z-scores decreased (both P &lt; 0.01). Among those enrolled 6 months or more after therapy, CortArea Z-scores did not change and CortBMD Z-scores increased (P &lt; 0.01). Changes in CortArea and CortBMD Z-scores were inversely associated (r = −0.32, P &lt; 0.001). Cumulative glucocorticoid exposure, leukemia risk status, and antimetabolite chemotherapy were not associated with outcomes. Conclusion: TrabBMD was low after completion of ALL therapy and improved significantly. Early increases in cortical dimensions were associated with declines in CortBMD; however, participants further from ALL therapy demonstrated stable cortical dimensions and increases in CortBMD, potentially reflecting the time necessary to mineralize newly formed bone.

Chronic Progressive Cardiac Dysfunction Years After Doxorubicin Therapy for Childhood Acute Lymphoblastic Leukemia

2005 ◽  
Vol 23 (12) ◽  
pp. 2629-2636 ◽  
Author(s):  
Steven E. Lipshultz ◽  
Stuart R. Lipsitz ◽  
Stephen E. Sallan ◽  
Virginia M. Dalton ◽  
Suzanne M. Mone ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Left Ventricular ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Cardiac Abnormalities ◽  
Z Scores ◽  
Long Term Survivors ◽  
Fractional Shortening

Purpose Cross-sectional studies show that cardiac abnormalities are common in long-term survivors of doxorubicin-treated childhood malignancies. Longitudinal data, however, are rare. Methods Serial echocardiograms (N = 499) were obtained from 115 doxorubicin-treated long-term survivors of childhood acute lymphoblastic leukemia (median age at diagnosis, 4.8 years; median follow-up after completion of doxorubicin, 11.8 years). Results were expressed as z scores to indicate the number of standard deviations (SDs) above (+) or below (−) the normal predicted value. Median individual and cumulative doxorubicin doses were 30 mg/m2 per dose and 352 mg/m2, respectively. Results Left ventricular fractional shortening was significantly reduced after doxorubicin therapy, and the reduction was related to cumulative dose. z scores for fractional shortening transiently improved before falling to −2.76 more than 12 years after diagnosis. Reduced fractional shortening was related to impaired contractility and increasing afterload, consequences of a progressive reduction of ventricular mass, and wall thickness relative to body-surface area. Left ventricular contractility fell significantly over time and was depressed at last follow-up in patients receiving more than 300 mg/m2 of doxorubicin. Systolic and diastolic blood pressures were below normal more than 9 years after diagnosis. Even patients receiving lower cumulative doxorubicin doses experienced reduced mass and dimension. Fractional shortening and dimension at the end of therapy predicted these parameters 11.8 years later. Conclusion Cardiac abnormalities were persistent and progressive after doxorubicin therapy. Inadequate ventricular mass with chronic afterload excess was associated with progressive contractile deficit and possibly reduced cardiac output and restrictive cardiomyopathy. The deficits were worst after highest cumulative doses of doxorubicin, but appeared even after low doses.

Bone Mineral Density, Fracture Risk and Avascular Bone Necrosis in Childhood Acute Lymphoblastic Leukemia; an Up-Date of the Prospective DUTCH ALL9 Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1962-1962
Author(s):  
Marry M. Van den Heuvel-Eibrink ◽  
Inge M. Van der Sluis ◽  
Bert A. Leeuw ◽  
Gaby Kardos ◽  
Lizet M. te Winkel ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Acute Lymphoblastic Leukemia ◽  
Fracture Risk ◽  
Bone Mineral ◽  
Lymphoblastic Leukemia ◽  
Fracture Incidence ◽  
Rapid Decline ◽  
Mineral Density ◽  
Discontinuation Of Treatment ◽  
One Year

Abstract The high cumulative dose of dexamethasone, applied in the DCOG ALL9 protocol, prompted us to investigate the risk of osteoporosis, fractures and avascular necroses of bone (AVN) in children treated with acute lymphoblastic leukemia (ALL). Fracture risk and incidence of symptomatic AVN was assessed in 778 patients(482 boys, 297 girls), included in the ALL9 protocol since 1997. Total cumulative doses (TCD) of dexamethasone were 1370 mg/m2 and 1244 mg/m2 and of MTX 8.1g/m2 13.6g/m2 for NHR and HR patients respectively. No CNS-irradiation was applied. In children aged >3 years, lumbar spine bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXAscan), at diagnosis(T0), after 32 weeks(T1), at discontinuation of treatment at 109 weeks(T2), and one year after discontinuation of treatment(T3). Results were expressed as standard deviation scores (SDS). Symptomatic AVN was defined as on MRI confirmed AVN lesions in combination with non-vincristine related persistent pain in arms or legs. Fractures were reported in 82/778 (10.5%) patients. Most occurred after mild trauma. No difference was found in fracture incidence between boys and girls. BMD was measured in 387/427 (90.6%) eligible patients. Median BMD-SDS was significantly lower than zero at all times of evaluation, the lowest BMD values were found at T2 (−1.47 SDS). Fracture risk was 3.9 times higher as compared to healthy school children. Fracture incidence was correlated with BMD at T2 and T3(p=0.04 and p=0,04 respectively), but not at T0 and T1. A significant more rapid decline in BMD from T0 to T2 and to T3 was seen in patients with fractures as compared to patients without fractures. After discontinuation of therapy, BMD recovered faster in cases without fractures. Symptomatic AVN occurred in 33/778 (4.2%) of our patients (med age 14, range 6,5–18 years) showing irreversibility in 22 % of the cases. Differences found in the incidence between the centers may suggest underestimation of the risk of fractures and AVN in this prospective study. Children with ALL show a significantly increased fracture risk. Patients with a more severe reduction in BMD during treatment are more susceptible to fractures. The AVN incidence in this protocol did not exceed previous reports of prednisolone-based protocols.

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