Desensitization to pegaspargase in children with acute lymphoblastic leukemia and lymphoblastic lymphoma

Hypersensitivity to pegaspargase is associated with inferior survival in pediatric patients with acute lymphoblastic leukemia and lymphoblastic lymphoma. In the past year, drug‐supply shortages have led to the lack of an available alternative to pegaspargase. Rather than omit asparaginase from the treatment of acute lymphoblastic leukemia or lymphoblastic lymphoma patients with hypersensitivity to pegaspargase, we continued pegaspargase treatments for nine pediatric patients, utilizing a rapid desensitization protocol. There were no adverse events related to the pegaspargase during desensitization, and all patients who were checked had asparaginase serum levels above the threshold of 0.1 IU/mL at 7 to 14 days after pegaspargase therapy.     

Development of acute lymphoblastic leukemia following treatment for acute myeloid leukemia in children with Down syndrome: A case report and retrospective review of Children's Oncology Group acute myeloid leukemia trials

Children with Down syndrome have a 150‐fold increased risk of developing acute myeloid leukemia (AML) and 20‐fold increased risk of developing acute lymphoblastic leukemia (ALL). Although the risk of developing AML and ALL is significantly increased in children with Down syndrome, the development of both malignancies in the same patient is very rare. We describe a patient with Down syndrome who developed ALL 6 years after being diagnosed with AML. We performed a literature review and Children's Oncology Group query and discovered eight published cases and five cases of ALL following AML in pediatric patients with Down syndrome, as well as six cases of ALL following AML in non‐Down syndrome patients. There was a similar cumulative incidence of ALL after treatment for AML in the Down syndrome and non‐Down syndrome populations. Overall survival in patients with Down syndrome who developed ALL after treatment for AML was comparable to overall survival for patients with Down syndrome with de novo ALL with an average follow‐up of 7 years after ALL diagnosis. Clinical data collected were used to discuss whether this phenomenon represents a secondary leukemia, second primary cancer, or mixed‐lineage leukemia.     

Acute lymphoblastic leukemia and Klinefelter syndrome in children: two cases and review of the literature

The occurrence of mediastinal germ cell tumor and breast cancer have been repeatedly reported in men with Klinefelter syndrome (KS) but this association is debated controversially for patients with hematologic malignancies. The authors describe 2 tall adolescents in whom diagnostic workup for acute lymphoblastic leukemia (ALL) revealed 47, XXY and 47, XXY/48, XXXY karyotype, respectively. Among 4195 registered male patients in the ALL-BFM study group since 1983, no further patients with ALL and KS were identified. Given the lack of epidemiological data, this retrospective analysis illustrates the association of previously described cases of hematologic malignancies with KS. In contrast to other chromosomal aberrations, the incidence of ALL does not seem to be increased in pediatric patients with KS.     

Transient hyperglycemia in Hispanic children with acute lymphoblastic leukemia

BACKGROUND: Transient hyperglycemia occurs commonly during the treatment for childhood acute lymphoblastic leukemia (ALL). The purpose of this study was to examine the incidence of and risk factors for transient hyperglycemia during induction chemotherapy in Hispanic pediatric patients diagnosed with B-Precursor ALL. PROCEDURE: The study cohort consisted of 155 Hispanic pediatric patients diagnosed with ALL and treated at one of two South Texas pediatric oncology centers between 1993 and 2002. Hyperglycemia was defined as > or = 2 glucose determinations of > or = 200 mg/dl during the first 28 days of induction chemotherapy. RESULTS: Overall, 11.0% of the study cohort developed transient hyperglycemia during induction chemotherapy. Age and body mass index (BMI) were both positively associated with the risk of hyperglycemia. Females exhibited a substantially higher risk of hyperglycemia than males, but this association did not reach statistical significance after adjusting for other covariates. Among patients who developed hyperglycemia, 100% of those who required insulin were in the 13-18-year age group and reported a family history of diabetes. Hyperglycemic patients classified as obese (BMI > or = 95 centile) were more than twice as likely to have required insulin therapy compared to overweight patients (BMI 85-<95 centile) and three times as likely to have required insulin compared to normal weight (BMI < 85 centile) patients. CONCLUSIONS: The incidence of chemotherapy-induced transient hyperglycemia in the present study cohort is comparable to that reported in previous pediatric ALL patients. This finding is interesting in view of the elevated prevalence of obesity and the underlying dietary behaviors in this Hispanic study cohort.     

Acute lymphoblastic leukemia in patients with Down syndrome with a previous history of acute myeloid leukemia

Patients with Down syndrome (DS) are predisposed to acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in early and later childhood, respectively, but rarely experience both. We herein discuss four patients with DS with ALL and a history of AML who were treated with various chemotherapies, one of whom later received a bone marrow transplantation. Three patients survived and remain in remission. One patient died of fulminant hepatitis during therapy. No common cytogenetic abnormalities in AML and ALL besides constitutional +21 were identified, indicating that the two leukemia types were independent events. However, the underlying pathomechanism of these conditions awaits clarification.     

小儿急性淋巴细胞白血病中枢神经系统白血病诊治现状

中枢神经系统白血病(CNSL)的防治是小儿急性淋巴细胞白血病(ALL)治疗的一部分。诊断时高白细胞计数、T细胞型及分子遗传学为t(4;11)和Ph 是CNS复发的危险因素,脑脊液不同检查结果的预后价值有待明确。头颅放疗已不用于标危ALL患儿,头颅放疗的预防剂量已减为12Gy,鞘内及全身化疗对CNSL的治疗有重要作用。部分小儿CNS复发经挽救治疗可以长期存活,早期CNS复发的患儿应在第2次CR期进行异基因骨髓移植。     

Nutritional status of children during treatment for acute lymphoblastic leukemia in Guatemala

Background

Most children with cancer live in developing countries where the prevalence of malnutrition may reach 50% and influence the course of the disease. This study examined the prevalence and severity of malnutrition at diagnosis, as well as after 3 and 6 months of chemotherapy, in children with acute lymphoblastic leukemia (ALL) in Guatemala.

Methods

Triceps skin fold thickness (TSFT) and mid upper arm circumference (MUAC) provided measures of nutritional status (NS) in three categories: adequately nourished (A): TSFT and MUAC > 10th percentile; severely depleted (SD): TSFT or MUAC < 5th percentile; and moderately depleted (MD): all the remaining patients.

Results

Of 331 new patients, 241 had NS assessed at diagnosis. A = 113 (46.9%); MD = 28 (11.6%); SD = 100 (41.5%). At 3 months A = 106 (52.2%); MD = 25 (12.3%); SD = 72 (35.5%). At 6 months A = 146 (76.0%); MD = 12 (6.3%); SD = 34 (17.7%). In multivariate analysis, SD children at 6 months of treatment had a hazard of death that was 2.4‐fold the hazard of those A or MD (95% CI: 1.3–4.7)

Conclusions

Malnutrition is prevalent in newly diagnosed children with ALL in Guatemala and severe nutritional depletion is apparently predictive of abandonment of therapy and relapse of disease, but if children survive and improve their NS in the first 6 months after diagnosis, their chances of survival may improve significantly to approximate those in children not presenting with nutritional depletion. Pediatr Blood Cancer 2013; 60: 911–915. © 2012 Wiley Periodicals, Inc.     

Testicular morphological changes in children with acute lymphoblastic leukemia following chemotherapy

Morphological changes in the testis induced by chemotherapy given according to the Tokyo Children's Cancer Study Group (TCCSG) regimens were studied in children with acute lymphoblastic leukemia (ALL). After informed consent, testicular biopsies were performed 14 times in 12 patients at the end of treatment. The testicular morphology in all cases had sustained a degree of damage. The tubular fertility index (TFI), calculated as the percentage of seminiferous tubules containing identifiable spermatogonia, was from 0 to 42.8% (mean 33.4%) below the normal value. Infiltration of leukemic cells was the most significant factor contributing to the decrease in TFI. There were no-differences in the TFI among the TCCSG protocols. Formation of sperm was recognized in six cases, whose ages were 7, 8, 9, 10, 15 and 19 years. In two children, testicular biopsy was performed twice. In the second biopsy, TFI was elevated and sperm formation with the maturation of Leydig cells was observed. A number of other pathological changes were observed: modification of spermatogonia, Sertoli cells and inclusion bodies in spermatogonia, abnormal maturation of Leydig cells, evidence of interstitial fibrosis and thickening of the basement membrane. These results suggest that recent strong chemotherapy for the treatment of ALL might cause severe but not fatal damage to children's testicular tissue. As chemotherapy escalates, more investigation of testicular function will be necessary.     

Vincristine disposition in children with acute lymphoblastic leukemia

Vincristine (VCR) has been widely used to treat childhood malignancies for over thirty years, but its plasma disposition has not yet been well-defined. Therefore, we conducted a pharmacokinetic study of VCR in 17 children with acute lymphoblastic leukemia (ALL) receiving the first dose of VCR. A new high-performance liquid chromatographic assay was used for the measurement of VCR in plasma. A two-compartment pharmacokinetic model was fit to the data by nonlinear least-squares regression. Estimated pharmacokinetic parameters were highly variable; mean (S.D.) volume of distribution at steady-state was 360 (176) L.m^?2; total body clearance was 431 (238) ml. min^?1.m^?2, and elimination half-life was 823 (390) min. These results were compared to data from eight adults with lung cancer. Mean volume of distribution in adults and children were similar, but VCR clearance was significantly larger in children (P = 0.01), resulting in a significantly longer elimination half-life in the adults (P < 0.01). We conclude that administration of a standard dosage of VCR to children with ALL results in a highly variable systemic drug exposure, which may have implications for the oncolytic effect and/or toxicity in individual patients. Comparison of data from children and adults suggests that VCR elimination rate is a function of age; this could account for more severe neurotoxicity in older patients. However, it cannot be excluded that differences between the children and adults may be due to other variables than age. Future studies should focus on the possible influence of multidrug resistance modulating agents on VCR pharmacokinetics and on pharmacokinetic-pharmacodynamic relationships in individual patients. © 1995 Wi1ey-Liss Inc.     

急性淋巴细胞白血病患儿中可逆性脑病临床总结

目的探讨急性淋巴细胞白血病患儿化疗后可逆性脑病的临床和影像学特点。方法回顾分析2015年9月1日至2018年9月1日住院时发生脑病的急性淋巴细胞白血病患儿的临床资料。结果研究期间共收治新发急性淋巴细胞白血病582例,9例患儿发生10次可逆性脑病(1例患儿发生2次),其中男6例、女3例,脑病发生中位年龄6.55岁(3.9~12.5岁)。最常见的神经系统临床表现是抽搐,其次是肌无力和感觉异常。7例患儿曾接受培门冬治疗;5例患儿在脑病发生前有急性高血压病史;6例患儿在脑病发生时有低钠血症,部分有低纤维蛋白原血症。头颅磁共振成像检查均提示T1和T2信号异常,累及部位多见于顶枕叶。结论联合化疗、化疗药物鞘内注射和急性高血压是可逆性脑病发生的高危因素;监测血压、血钠、纤维蛋白原,以及头颅磁共振成像检查有助于早期发现可逆性脑病。     

Management of brain abscesses in children treated for acute lymphoblastic leukemia

Brain abscesses in children with leukemia or other malignancies are rare and potentially fatal. We report on four children who developed brain abscesses during treatment for acute lymphoblastic leukemia (ALL). All patients received multimodal broad-spectrum antibiotic therapy and liposomal amphotericin-B in combination with hyperbaric oxygen. First-line antimicrobial treatment was modified when a causative organism was isolated. All four patients survived, with two patients showing complete resolution of neurological and MRI abnormalities and with two patients still having residual lesions. To date, all patients are in remission with three patients still receiving antileukemic therapy. Brain abscesses can be successfully managed by a multimodality approach even in severely immunocompromised cancer patients.     

Osteonecrosis in children treated for acute lymphoblastic leukemia

The purpose of the study was to find out the prevalence of osteonecrosis in children with acute lymphoblastic leukemia (ALL) in complete bone marrow remission at the end of the treatment. Twenty-eight children with ALL underwent MRI of the upper and/or lower extremities. Bone marrow signal intensity was analyzed on T1-weighted images, where cir-cumscribed lesions with a rim of low signal intensity were considered typical of osteonecrosis. Osteonecrosis was found in 9 of the 28 children (32%, 95% CI 16% to 52%). Five of them were asymptomatic. They had been treated with high risk and intermediate risk protocols, both of which include a delayed intensification phase with dexamethasone. None of the patients with standard risk ALL were found to have developed osteonecrosis. Osteonecroses occurred unexpectedly in symptomless patients and in patients with mild transient symptoms treated with high risk and intermediate risk protocols. Our study suggests that the intensification phase of the treatment protocols with intensive dexamethasone medication might be responsible for the development of osteonecrosis. Med. Pediatr. Oncol. 29:260–265, 1997. © 1997 Wiley-Liss, Inc.     

Osteonecrosis is unrelated to hip anatomy in children with acute lymphoblastic leukemia

Osteonecrosis is a debilitating toxicity associated with acute lymphoblastic leukemia (ALL) treatment. A recent report associated interindividual differences in hip anatomy with the development of idiopathic osteonecrosis in adults. To evaluate the impact of hip anatomy on the development of therapy‐related osteonecrosis, we retrospectively evaluated the femoral neck‐shaft angle, femoral neck offset, and lateral center‐edge angle using x‐rays of 18 osteonecrosis cases and 46 control children treated for newly diagnosed ALL on a single protocol. Despite adequate statistical power, we found no association between hip anatomy and osteonecrosis. Investigation of other factors contributing to ALL‐associated osteonecrosis is warranted.