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Background: Low bone mineral density is encountered in children with acute lymphoblastic leukemia (ALL) before, during, and after treatment. Prior experience with alendronate, an oral bisphosphonate, demonstrated high tolerability and evident clinical efficacy. However, concerns have been expressed about the long-term safety and utility of such agents in children., Procedure: Sixty-nine children with ALL received alendronate for a mean of 87 weeks after dual-energy radiograph absorptiometry. Dual-energy radiograph absorptiometry was repeated following the completion of alendronate, and 5 to 9 years later in a subgroup of 32 children. Lumbar spine areal bone mineral density (LS aBMD) Z scores were obtained., Results: The mean LS aBMD Z score rose from -1.78 to-0.47 ( P <0.0001). There was a modest median loss of LS aBMD subsequently in the 32 subjects on long-term follow-up. Almost 80% (N=172) of the children remain in continuous complete remission at a mean of 14.5 years from diagnosis. Of those who received alendronate, which was almost uniformly well tolerated, 7/69 (10.3%) relapsed compared with 19/89 (21.3%) who did not receive the drug., Discussion: Alendronate appears to be well tolerated and moderately effective in osteopenic children with ALL. Whether it offers protection against relapse of leukemia needs further study., Competing Interests: The authors have no conflicts of interest to declare, (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The normal interrelationship of body composition with bone health is less clear in the context of disease. Survivors of acute lymphoblastic leukemia (ALL) exhibit sarcopenic obesity and osteopenia. The impact of body composition on bone health in such survivors was examined., Subjects and Methods: Survivors of ALL (N=74), >10 years from diagnosis, underwent dual-energy radiograph absorptiometry and peripheral quantitative computed tomography., Results: Whole-body bone mineral content (WB BMC) Z scores were greater in males than females, but WB BMC indices (WB BMC/height 2 ) were comparable (0.74±0.125 and 0.72±0.069, respectively). WB BMC index (I) and fat-free mass index correlated significantly with trabecular bone mineral density, only in males. Fat mass index and appendicular lean mass index showed no such correlations. WB BMCI and fat-free mass index also correlated, again predominantly in males, with measures of strength in both trabecular and cortical bone. WB BMCI also correlated strongly with trabecular number, thickness, and hole size, also only in males., Conclusions: The results point to the need for enhancing muscle mass, measured by appendicular lean mass index, while reducing fat mass and maintaining good bone mineralization in long-term survivors of ALL to ensure the integrity of healthy bones., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive malignancy commonly involving the abdomen and/or pelvic peritoneum. Despite aggressive therapy, the prognosis remains poor. Central nervous system relapse is rare in abdominal/pelvic primary DSRCT., Observation: We report a case of a 10-year-old female with a large pelvic DSRCT and involvement of the rectosigmoid colon and liver. Following treatment with chemotherapy, and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy an initial response was noted. With progressive lower limb weakness, recurrence with perineural invasion in the lumbosacral nerve root involving the conus was noted 2.5 years from diagnosis. Cerebrospinal fluid showed tumor cells with a molecular confirmation., Conclusions: Perineural invasion and ascending paralysis secondary to primary abdominal DSRCT has not been previously reported to our knowledge. We recommend a high index of suspicion for early and accurate diagnosis of this rare presentation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Few studies have evaluated the impact of ABO blood group on the risk of venous thromboembolism (VTE) in pediatric populations. We performed a systematic review to determine whether children (0 to 18 y old) with non-O blood group have an increased risk of developing VTE compared with those with O blood group., Methods: We searched Ovid Medline, Embase, PubMed, Cochrane, Web of Science, and CINAHL online databases from inception to December 2018 to find studies involving blood grouping and VTE. Data was collected regarding patients' underlying diseases, sex, age, ABO blood group, and VTE frequency. A meta-analysis using the random effect model was performed, and heterogeneity was assessed with the I2 value., Results: Among 1280 unique articles identified, 7 studies (3 conference abstracts, 4 peer-reviewed journal articles) involving 609 VTE cases were included in the systematic review. Six studies were eligible for a meta-analysis; all involved patients with cancer. Blood group O was protective against VTE (odds ratio, 0.56; 95% confidence interval, 0.43-0.79). Findings were similar across sensitivity analyses., Conclusions: This systematic review has documented that O blood group is protective against new-onset VTE in children with cancer. Larger studies across different ethnic backgrounds and disease categories are needed to confirm these findings., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Children with leukemia commonly receive red blood cell (RBC) transfusions and transfusion-related iron overload (TRIO) is a major complication. However, few studies have evaluated TRIO in children with leukemia and no guidelines for screening exist. This retrospective, observational cohort study in children with acute leukemia evaluates the prevalence of TRIO and its impact on end-organ function., Results: The study included 139 patients; 60% standard-risk acute lymphoblastic leukemia (ALL), 32% high-risk (HR) ALL, and 9% acute myeloid leukemia (AML). The mean age at diagnosis was 6 years (range: 5 mo to 18 y). Patients with HR-ALL and AML were more likely to be transfused with ≥10 RBC units (59% and 92%, respectively) compared with those with standard-risk ALL (18%) (P<0.0001). Ferritin levels were measured in 68% patients and elevated (>1000 mcg/L) in 23%. Endocrinopathies were the most common end-organ abnormality. Hepatic dysfunction was significantly higher in patients with ≥10 RBC units transfused compared with those with <10 units (P=0.008)., Conclusions: Although the RBC transfusion burden is highest in patients with AML and HR-ALL, TRIO screening was not commonly performed. Patients who receive ≥10 RBC units are at risk for hepatic and endocrine dysfunction. We recommend routine screening for TRIO in children with leukemia, who are at risk for a higher transfusion burden.

Hand mirror cell (HMC) leukemia is a variant of acute lymphoblastic leukemia previously described in the adult population where lymphoblasts manifest distinctive hand mirror morphologic features. HMC has been previously identified in 23% of childhood acute lymphoblastic leukemia patients, but its prognostic significance in children is not well understood. Hypercalcemia is also uncommon in childhood leukemias. Hypercalcemia associated with HMC leukemia has not been previously reported. We report a 5-year-old boy with HMC B-lymphoblastic leukemia who presented with hypercalcemia.

Health-related quality of life (HRQL) improved progressively during therapy and beyond in children treated for acute lymphoblastic leukemia on the Dana-Farber Cancer Institute (DFCI) 95-01 protocol. This study aimed to validate that trajectory in a successor study (DFCI 00-01) and to compare the HRQL of patients in the 2 studies. Children aged above 5 years were assessed during each phase of treatment (N=4) and 2 years after completion of therapy. Health status and HRQL were measured using Health Utilities Index (HUI) instruments, HUI2 and HUI3. Quality-adjusted life years (QALYs) were calculated and compared with the general population, and patients treated on DFCI 95-01. Over 5 intervals and 758 HUI assessments, mean HRQL increased progressively from remission induction to the time after treatment (P<0.001). During intensification, high-risk patients had lower HRQL than standard-risk patients (P<0.001). During remission induction, patients on DFCI 95-01 had lower HRQL than patients on DFCI 00-01. Patients on DFCI 00-01 had ~0.2 and 0.3 fewer QALYs than controls, measured by HUI2 and HUI3, respectively. QALYs for DFCI 00-01 patients during treatment were similar to those for DFCI 95-01 patients. The trajectory of improvement in HRQL during the treatment of acute lymphoblastic leukemia in children was confirmed.

The aim of this study was to investigate the effects of high-dose corticosteroids on behavior and quality of life of children with acute lymphoblastic leukemia (ALL) in maintenance therapy. Forty-three families (patient and/or parent) completed the Child Behavior Checklist (CBCL), the Pediatric Quality of Life Inventory (PedsQL) Cancer module questionnaires, a checklist of common complaints, and a descriptive intervention data questionnaire, on and off steroids, each child serving as his/her own control. Children 5 years and younger had higher CBCL scores in the somatic complaints, affective problems, internalizing, externalizing, and total problem scales, when comparing "on-steroid" to "off-steroid" periods (P<0.01). Children 6 years and above had higher CBCL scores in the externalizing, aggressive, and oppositional defiant problem scales on steroids compared with off steroids (P<0.05). Older children had larger changes on dexamethasone, compared with prednisone (P<0.05). On the PedsQL questionnaire, parents reported more pain and hurt (P<0.001), nausea (P=0.042), and procedural anxiety (P=0.013) when children were on steroids compared with off steroids. Corticosteroid treatment during ALL maintenance therapy is associated with behavior and emotional disturbances and adversely affects quality of life. Dexamethasone is associated with more significant behavioral changes in older children.

Purpose: To compare the use of reverse transcriptase polymerase chain reaction (RT-PCR) with that of morphology-based methods for diagnosis, staging, and detection of metastatic disease in pediatric alveolar rhabdomyosarcoma (ARMS), Ewing sarcoma family of tumors (ESFT), and desmoplastic small round cell tumors (DSRCT)., Materials and Methods: RT-PCR assays for the EWS-FLII, EWS-ERG, PAX3-FKHR, PAX7-FKHR, and EWS-WTI fusion transcripts were performed on RNA extracted from the primary tumor tissue, bone marrow, and body fluids obtained at initial presentation and relapse. Molecular findings were compared with original histologic diagnoses and results of staging procedures., Results: Eighty-eight samples from 47 patients with ARMS (n = 13), ESFT (n = 31), or DSRCT (n = 3) were analyzed. The detection rate of metastatic disease was significantly higher with RT-PCR (95%) as compared with the morphologic methods (70%) for the three pediatric sarcomas studied. In primary tumors with characteristic fusion transcript, RT-PCR was positive in all cases with morphologic evidence of metastatic disease. Moreover, in six patients (3 with ARMS, 2 with DSRCT, and 1 with ESFT) with metastatic disease, micrometastases in bone marrow (4) and other sites (2) were detected by RT-PCR alone. Importantly, none of the patients with localized disease diagnosed had micrometastases detected by RT-PCR in bone marrow., Conclusions: The high sensitivity and specificity of RT-PCR for the characteristic fusion transcripts of pediatric sarcomas make it an ideal method to aid in the routine staging of these patients. In addition, the 100% sensitivity of RT-PCR in detection of micrometastasis makes it useful for follow-up and detection of minimal residual disease. However, the clinical significance of molecularly-detectable disease remains unknown. Further studies should aim to elucidate the therapeutic and prognostic implications of micrometastases detected by RT-PCR alone.