Acute lymphoblastic leukemia in children: immunologic, cytochemical, morphologic, and cytogenetic studies in relation to pretreatment risk factors.

Thirty children with previously untreated acute lymphoblastic leukemia were studied prior to therapy to determine whether sheep erythrocyte (E)-receptor status correlated with clinical factors, cytochemical staining characteristics, FAB morphologic classification, and karyotype. Five patients (17%) with more than 50% E+ blasts had intense focal acid phosphatase staining and distinct clinical characteristics, including high leukocyte counts, mediastinal masses, and involvement of the central nervous system at diagnosis. Focal acid phosphatase activity was present in blasts of patients with greater than 20% E+ blasts, but this group had fewer poor risk factors. Morphologic and karyotypic features were not related to erythrocyte-receptor status, but the L2 morphologic appearance occurred more frequently in older patients (P less than 0.05). Erythrocyte receptors have both qualitative and quantitative clinical correlations in childhood acute lymphoblastic leukemia; however, E+ and E- groups are heterogeneous and E+ groups must be analyzed for other risk factors and relapse rates determined before firm conclusions can be made about erythrocyte rosetting as an independent risk variable.     

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.     

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.     

Longitudinal growth and risk factors for growth deficiency in children treated for acute lymphoblastic leukemia

BACKGROUND: Growth deficit has been reported as a frequent complication of the treatment of acute lymphoblastic leukemia (ALL). PROCEDURE: Longitudinal analysis of the growth of 129 children, from a total of 351 cases diagnosed between 1987 and 1994 in Brazil, was determined. Height data were converted into standard deviation Z scores. Only girls younger than 10 and boys younger than 12 years old at diagnosis were included. Patients were treated according to a German BFM-83 based protocol. Fifty-eight children received 18 Gy cranial irradiation, four 12 Gy, and two 24 Gy. Patients were aggregated into five non-excluding groups according to availability of height data at diagnosis, during the treatment, at the end of it, and several years after; 35 children reached their final height. RESULTS: Height deficit at the end of the therapeutic treatment was evident (P < 0.0001). Catch-up occurred 1 year after stopping treatment (P = 0.016). At the last follow-up, over 5 years after the end of treatment (n = 83) or at final height (n = 35), impressive height deficits were recorded (P < 0.0001 for both end points). Multivariate analysis demonstrated that growth impairment was more severe in children younger than 4 years at diagnosis and in those who received cranial irradiation. No significant effect of gender was observed. Children who were treated solely with chemotherapy also had significant height loss. CONCLUSIONS: Treatment of ALL in children is associated with growth deficit during the treatment and several years after it, affecting the final height negatively, particularly in patients younger than 4 and in those who received cranial irradiation.     

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.     

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.     

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。     

Acute lymphoblastic leukemia and lymphoblastic lymphoma in adolescents and young adults

Compared to younger and older age groups, the incidence of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) has increased more in the adolescent and young adult (AYA) population, the cause of which is unknown. As of the last decade, only half of the AYA patients with these diseases were surviving 10 years. Strong evidence exists that favors “pediatric” treatment regimens for AYAs compared to “adult” treatment regimens in terms of survival rates, hospitalization time, toxicities, late effects, and quality of life both during and after treatment. Targeted agents are clinically accessible for certain subsets of patients with Philadelphia‐like ALL, the incidence of which peaks in AYAs. Treatment teams must appreciate the complex psychosocial underpinnings in these patients in order to maximize compliance with the prolonged and complex treatment plans during the AYA years. 1     

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.     

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.     

Childhood relapsed acute lymphoblastic leukemia: Biology and recent treatment progress

Acute lymphoblastic leukemia (ALL) is the most frequent cancer in children. Despite remarkable improvement in the prognosis of childhood ALL over the past few decades, the treatment of relapsed ALL is still challenging. The prognosis of first ALL relapse is associated with time of relapse after initial therapy, sites of relapse, and immunophenotype. More recently, response to treatment, which is evaluated by assessment of minimal residual disease (MRD), has been found to be clinically significant in relapsed ALL as well as in the initially diagnosed disease. Utilizing these factors, risk‐oriented treatment stratification for first ALL relapse has been established. In the standard‐risk group for first ALL relapse, intensification of conventional ALL‐type therapy can provide a cure in approximately 70% of patients. It is important to assess MRD after reinduction therapy to determine the indications for stem cell transplantation in the standard‐risk group. In contrast, no standardized therapy has been established for the high‐risk group, which accounts for more than half of relapsed ALL patients. Recent studies have shed light on the clonal origin of relapsed ALL, which usually exists as a minor subclone at the time of initial diagnosis. Clonal selection and evolution take place during chemotherapy, resulting in distinct genetic and epigenetic characteristics of relapsed ALL, some of which are linked to drug resistance, a common and problematic feature of ALL after relapse. To overcome resistance to standard ALL‐type therapy, and considering the heterogeneous biological background of high‐risk relapsed ALL, innovative therapies using new agents are necessary.     

Acute nonlymphoblastic leukemia in children treated for acute lymphoblastic leukemia with an intensive regimen including teniposide

Some cases of conversion from acute lymphoblastic leukemia (ALL) to acute nonlymphoblastic leukemia (ANLL) at relapse have been reported recently. We report three cases initially diagnosed as having ALL and showing morphological, cytochemical, and immunophenotypic features of ANLL at relapse (lineage switch). Conversion was observed among 14 patients who developed bone marrow relapse while undergoing intensive treatment with our ALL protocol, which includes teniposide, and that had been administered to 62 patients. The three cases converted at first relapse, with a mean time of 20 months (13–29 months). Clinical and immunologic characteristics of T-cell leukemia were present in one patient. Changes documented in cytogenetic studies are discussed. The underlying mechanisms for the lineage switch remain unclear as does its relation with mixed lineage leukemias, but we believe that drugs employed in our therapy protocol could have had an influence on this conversion.