中枢神经系统预防性治疗对急性淋巴细胞白血病儿童智力的影响

为研究中枢神经系统白血病（ＣＮＳＬ）不同预防性治疗对急性淋巴细胞白血病（ＡＬＬ）儿童智力的影响。按ＣＮＳＬ预防性治疗方案将１４７例患儿分为两组：Ａ组７５例，￣（６０）Ｃｏ颅脑放疗量为２４Ｇｙ，鞘注次数为１９±６次；Ｂ组７２例，颅脑放疗量为１８～２０Ｇｙ，鞘注次数为１０±４次；应用韦氏量表测定患儿总智商（ＩＱ）、语言ＩＱ、操作ＩＱ。结果表明，Ａ组ＩＱ显著低于正常对照组（Ｐ＜０．０１）；Ｂ组ＩＱ也明显低于对照组（Ｐ＜０．０５）；Ｂ组较Ａ组减低程度轻，两组相比有显著性差异（Ｐ＜０．０５）。提示颅脑放疗量越大，氨甲喋呤鞘注次数越多，影响智力的副作用越明显。     

SELECTIVE SURGICAL INDICATION IN THE MANAGEMENT OF NEUTROPENIC CHILDREN PRESENTING WITH ACUTE ABDOMEN

As the treatment of pediatric malignancies improves and survival increases, the diagnosis of acute abdomen in these patients also becomes more common. Nevertheless, the management of this a condition is still controversial. The authors report their experience in treating 12 neutropenic children with acute abdomen. The charts of 12 neutropenic patients with a diagnosis of acute abdomen treated at Boldrini Children's Cancer Center in Campinas, Brazil, between 1991 and 1996, were reviewed. Therapeutic strategy included an initial period of bowel rest, general supportive measures, and broadspectrum antibiotics while waiting for the neutrophil count to rise. Three patients recovered completely without surgery, 8 under went late surgery without complications, and 1 died due to uncontrolled sepsis before surgery. The treatment of acute abdomen in neutropenic children remains controversial. As shown in the present series, an initial nonoperative approach with selective surgical indication appears to be safe and to yield good results. Supportive treatment, until the neutrophil count rises, followed by surgery, if necessary, appears to be a sound therapeutic approach for neutropenic children with acute abdomen.     

ANTITHROMBIN III SUPPLEMENTATION IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA TREATED WITH L-ASPARAGINASE

The change of plasma antithrombin III (AT) levels after supplementation of AT concentrates was examined in ALL children with acquired AT deficiency following L-asparaginase (ASP) administration. The patients received AT concentrates of 34.5 &#45 7.6 U/kg. The increase of plasma AT activity and antigen was 2.07 &#45 0.62% and 0.70 &#45 0.16 mg/dL per unit AT infused per kilogram of body weight, respectively. The activity decreased to 62.0 &#45 7.7% of the peak values by 48 hours after supplementation. The administration of AT concentrates constantly increased the plasma AT activity in ALL children treated with ASP, which may minimize the acquired prothrombotic state.     

DOUBLE INVASIVE FUNGAL INFECTION AND TYPHLITIS IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA

Invasive fungal infection is one of the major causes of morbidity and mortality in immunocompromised patients. The occurrence of two invasive fungal infections in one patient at the same time is quite rare. Here the authors report on two adolescent patients with acute lymphoblastic leukemia who developed combined invasive pulmonary aspergillosis and hepatosplenic candidiasis during chemotherapy. They were treated with liposomal amphotericin B, but one of them died due to massive pulmonary hemorrhage during recovery from neutropenia.     

OVERALL AND EVENT-FREE SURVIVALS FOR ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN AT A SINGLE INSTITUTION IN TAIWAN

The results of treatment for childhood acute lymphoblastic leukemia (ALL) have improved dramatically over the past three decades. The authors present the long-term outcome of patients ( n = 151) with ALL enrolled in 4 consecutive clinical trials conducted from 1982 to 1993 at Mackay Memorial Hospital. During this period, the backbone of the treatment remained relatively unchanged, including a 3- to 4-drug remission induction, central nervous system(CNS)-directed therapy, and cyclic pulses of vincristine and dexamethasone during maintenance therapy. More intensive therapy, consisting of reintensification and addition of more drugs during maintenance, was reserved for high-risk and very-high-risk paitents. The overall survival and event-free survival ( ±1 SE) were 70 ±4.1% and 64 ±4.3%, respectively, with follow-up ranging from 7.6 to 18.7 years (median 12.2 year). The isolated CNS relapse rate was 4.3%. The dropout rate significantaly decreased from 35% in 1982-1984 to 0% in 1991-1993. Although the patient population is small, the overall results for childhood ALL at the authors' hospital are encouraging as compared to earlier reports in Taiwan.     

OVERALL AND EVENT-FREE SURVIVALS FOR ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN AT A SINGLE INSTITUTION IN TAIWAN

The results of treatment for childhood acute lymphoblastic leukemia (ALL) have improved dramatically over the past three decades. The authors present the long-term outcome of patients ( n = 151) with ALL enrolled in 4 consecutive clinical trials conducted from 1982 to 1993 at Mackay Memorial Hospital. During this period, the backbone of the treatment remained relatively unchanged, including a 3- to 4-drug remission induction, central nervous system(CNS)-directed therapy, and cyclic pulses of vincristine and dexamethasone during maintenance therapy. More intensive therapy, consisting of reintensification and addition of more drugs during maintenance, was reserved for high-risk and very-high-risk paitents. The overall survival and event-free survival ( &#45 1 SE) were 70 &#45 4.1% and 64 &#45 4.3%, respectively, with follow-up ranging from 7.6 to 18.7 years (median 12.2 year). The isolated CNS relapse rate was 4.3%. The dropout rate significantaly decreased from 35% in 1982-1984 to 0% in 1991-1993. Although the patient population is small, the overall results for childhood ALL at the authors' hospital are encouraging as compared to earlier reports in Taiwan.     

PSYCHIATRIC MORBIDITY IN CHILDREN SUFFERING FROM ACUTE LYMPHOBLASTIC LEUKEMIA

The study aimed at assessing the frequency of psychiatric disorders in children with acute lymphoblastic leukemia. Thirty consecutive subjects in the age range of 6-12 years were interviewed with the help of a symptom checklist soon after they had achieved their first remission. The children were also administered the Children's Depression Rating Scale and the State Trait Anxiety Inventory for Children. One-third (n = 10) of the subjects received a diagnosis according to the International Classification of Diseases , 9th ed. Ninety percent (n = 9) had emotional disorders. All the disorders were mild to moderate in intensity and were perceived to be easily treatable.     

SUCCESSFUL TREATMENT OF ASPERGILLUS BRAIN ABSCESS IN A CHILD WITH ACUTE LYMPHOBLASTIC LEUKEMIA

Cerebral aspergillosis carries a high mortality in immunocompromised patients. However, favorable outcome can be achieved by the prolonged use of antifungal agents and the maintenance of adequate drug levels. The authors report a 2-year-old girl who developed an aspergillus brain abscess during treatment for acute lymphoblastic leukemia. Predisposing factors for thefungal infection and details of the antifungal therapy are described. Prolonged treatment with AmBisome and 5-flucytosine successfully eradicated the lesion, but the girl's antileukemic therapy was compromised due to the infection. She developed a central nervous system and bone marrow relapse 9 and 15 months, respectively, after the initial presentation. The report emphasizes the need for further consideration of effective, long-term anti fungal prophylaxis and a careful balance between aggressive treatment for severe infection and antileukemic therapy.     

ACUTE LYMPHOBLASTIC LEUKEMIA IN SWEDISH CHILDREN 1973–1978

ABSTRACT. Gustafsson, G., Kreuger, A. and Dohlwitz, A. (Departments of Paediatrics, University Hospital, Uppsala, and County Hospital, Nykoping, Sweden). Acute lymphoblastic leukemia in Swedish children 1973–1978. Acta Paediatr Scand, 70:609,.–Three hundred and sixty-seven children with acute lymphoblastic leukemia have been diagnosed in Sweden 1973–1978, 345 of whom were treated according to the national uniform regimens of the Swedish Child Leukemia Group (SCLG). The patients were classified into an SR (standard risk) and an IR (increased risk) group. Remission was obtained in 354 patients (96%). With 12–84 months observation time the total survival was 54% and the diseasefree survival 44 %. A more intensive cytostatic regimen in the induction period increased considerably the diseasefree survival for the SR and to some extent also for the IR patients. Relapses were significantly more common in the IR group in spite of a more intensive cytostatic regimen. The most decisive IR criteria were B-LPK and age at diagnosis. Prognosis was significantly worse for boys in all groups. After 3 years in CCR treatment was discontinued in 95 out of 246 children (38%) of whom 19 later relapsed (20%)     

PROGNOSTIC VALUE OF DAY 14 BLAST PERCENTAGE AND THE ABSOLUTE BLAST INDEX IN BONE MARROW OF CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA

This study included all 690 children in Norway diagnosed as having acute lymphocytic leukemia (ALL) from July 1975 till the end of 1997. Relapses and deaths were monitored until the end of 2000. Neuroleukemia prophylaxis was intravenous methotrexate (MTX) infusions as intermediate-dose methotrexate (IDM) or high-dose methotrexate (HDM) combined with intrathecal MTX. From 1992, systemic therapy was considerably intensified, and, in addition, patients in a subgroup of the high-risk and very high-risk groups were given prophylactic cranial irradiation. The overall findings showed that MTX significantly reduced central nervous system (CNS)-related relapses, and, in general, reinforced systemic therapy reduced significantly non-CNS relapses and deaths. The overall crude survival was 75%. During the study period, the crude survival improved for patients on standard protocols from initially 65 to 90%. Forty patients (6%) developed isolated CNS relapse, 27 (4%) had combined CNS relapse, whereas 180 (26%) had non-CNS relapse. When IDM and HDM were compared, the cumulative risk for isolated CNS relapse was significantly lower with HDM, 12 and 5%, respectively. For any relapses that involved the CNS, the risk remained significantly lower for HDM, 8 versus 18%. Of the 40 patients with isolated CNS relapse, 23 survived (58%).     

THROMBIN GENERATION IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA: Effect of Leukemia Immunophenotypic Subgroups

In this study, it is hypothesized that a planned increase in the dose of recombinant human erythropoietin (rh-EPO) can prevent transfusion in very low birth weight infants. Two different regimens of rh-EPO were administrated, one consisting in increasing dosage up to 5000 U/kg/wk, according to the individual reticulocytes response, and the second in a standard therapy of 1250 U/kg/wk. Fifty-one infants participated. Despite a significant higher reticulocytosis, the study was prematurely terminated due to the results of an interim analysis showing that transfusion was not avoided by increasing the rh-EPO. No significant differences were found between the two regimens concerning transfusion rate, volume transfused, gain in weight, and adverse effects. Progressive titration of rh-EPO to improve the biological response does not leave premature infants free of transfusion.     

LATE CARDIAC DAMAGE OF ANTHRACYCLINE THERAPY FOR ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDHOOD

Long-termleukemia survivors (46) underwent cardiac evaluation, including physical examination, ECG, exercise testing, and echocardiography. They were 2-17 years old at diagnosis and 5-23 years old aftertreatment. Thirty-four survivors received anthracyclines (AC) (mean 203 mg/m2), 12 of them had also alkylating agents (AA) and 12 had no AC. Exercise tolerance was bellow predicted valuesin 21 (48%) survivors and 21 survivors had ECG abnormalities, which were more frequent in those treated with AC. Concomitant AC with AA was correlated with prolonged isovolumic relaxation time (IVRT) and influenced significantly the volume of left atrium (p = .02). Sixteen (52%) survivors had IVRT 90 ms. There were no significant differences in other parameters of diastolic orsystolic function. Despite the lack of clinical symptoms in the survivors treated with lower doses of AC, subtile abnormalities in myocardial function were found, mainly manifest as abnormal diastolic function. Prolonged IVRT may be a sensitive indicator for early detection of AC cardiotoxicity.     

ACALCULOUS CHOLECYSTITIS CAUSED BY SALMONELLA PARATYPHI B INFECTION IN A CHILD WITH ACUTE PRE-B-CELL LYMPHOBLASTIC LEUKEMIA

Acute acalculous cholecystitis (AC) rarely occurs in children with acute leukemia. The principal treatment modality of AC is emergency surgery. Medical treatment of AC is not a good therapeutic approach. The mortality rate of AC is approximately 100% for medical treatment and 10-15% for emergency surgery. A 9-year-old boy with acute pre-B-cell lymphoblastic leukemia and AC caused by Salmonella paratyphi B infection is presented. He was successfully treated with cefepime, amikacin, and granulocyte-colony stimulating factor (G-CSF). These treatment combinations led to uneventful recovery after 21 days. It appears that AC in children with acute leukemia may be treated with appropriate intravenous antibiotics. This may be the first case of AC caused by Salmonella paratyphi B infection reported in a child with acute pre-B-cell lymphoblastic leukemia.     

CARDIAC INVOLVEMENT IN AN ADOLESCENT WITH ACUTE LYMPHOBLASTIC LEUKEMIA

Cardiac complications of the pediatric patients with acute leukemia are common. Most of the cardiac complications may be due to chemotherapeutics such as antracyclins, besides anemia, infections, or direct leukemic infiltrations of the heart. It is reported that leukemic infiltration is frequent in the postmortem examination of the myocardium and pericardium. However, at the antemortem examination, pericardial involvement is rare and there is no myocardial involvement reported at the time of diagnosis in patients with acute leukemia in the English literature. Here, the authors report an adolescent with acute lymphoblastic leukemia who had myocardial infiltration at the time of diagnosis.     

NEPHROTOXICITY DUE TO INTERMEDIATE-DOSE METHOTREXATE WITHOUT RESCUE IN AN OBESE ADOLESCENT WITH ACUTE LYMPHOBLASTIC LEUKEMIA

Toxicity from intermediate-dose methotrexate (MTX)is unusual. A severely obese adolescent with acute lymphoblastic leukemia experienced significant, delayed nephrotoxicity from intermediate-dose MTX. Altered MTX disposition may occur as a consequence of other ingestions or conditions such as obesity. The use of radioisotope renography established the diagnosis and followed the resolution of the patient's MTX-induced nephrotoxicity.     

ACUTE VISION LOSS IN ACUTE LYMPHOBLASTIC LEUKEMIA

A retrospective study of 28 patients with biopsy proven Histiocytosis X confirmed a histologic and clinical classification into a benign and “malignant” entity. The selection of the tissue sampled for histologic examination is essential for a distinction to be made between unfavourable (type I) and favourable (type II) histology at diagnosis. Histologic examination of the lymph nodes was found to be the most adequate for this purpose. The incidence of unfavourable histology was low (3/28 patients). The clinical data of the 28 patients showed a high incidence of chronic otitis media, skull lesions, lymphadenopathy, diabetes insipidus and chronic disabilities in comparison with the literature. The incidence of solitary and multiple bone lesions without extraskeletal involvement in this study was low and the incidence of systemic Histiocytosis X was high. Nevertheless, we found a very low mortality rate of 14%. There is a fairly close relationship between the histologic classification, a clinical score and prognosis, which can be used as a guide to therapy. The occurrence of diabetes insipidus as a late complication of the disease during non-vigorous treatment is stressed. Our data suggest that adequate combination chemotherapy in patients with multiple bone lesions and in patients with benign disseminated disease decreases partial responses, mortality, chronic disabilities and relapses, especially diabetes insipidus.     

NEUROPSYCHOLOGIC SEQUELAE IN THE LONG-TERM SURVIVORS OF CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA

The neurotoxicity of either systemic chemotherapy or central nervous system prophylaxis was studied in 19 children treated for acute lymphoblastic leukemia (ALL). They had completed ALL therapy at least a year before and survived more than 5 years after diagnosis. The duration between age at diagnosis and age at investigation was 8.6 2.7 years (5-15 years). Neuropsychologic tests, cranial magnetic resonance imaging (MRI), and evoked potentials (EP) were studied. Seventeen healthy siblings were taken as a control group. Emotional evaluation was done using the childhood depression inventory and Beck depression inventory. Cognitive functions were evaluated using Wechsler's Intelligence Scale for Children-Revised (WISC-R) or the Wechsler's Adult Intelligence Scale-Revised (WAIS-R) tests, which were adapted to Turkish children. Performance and total IQ scores (94.0 16.8 and 92.2 16.5) were significantly low as compared to the control group (112.1 18.9 and 105.4 14.2) (p=.007 and p=.02). Abnormal MRI findings were found in 33.3% (6/18). Three out of 18 patients (16.6%) had abnormal auditory while 5 out of 17 patients (29.5%) displayed abnormal visual EPs. Abnormal findings in MRI, cognitive examination, and electrophysiologic testing were not associated with age at diagnosis, radiotherapy doses, intermediate/high-dose systemic methotrexate administration or central nervous system involvement. But more patients must be studied to demonstrate discrete outcomes of neurotoxicity in long-term survivors of childhood leukemia.     

KETAMINE ANESTHESIA WITH OR WITHOUT DIAZEPAM PREMEDICATION FOR BONE MARROW PUNCTURES IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA

Ketamine is a drug widely used for analgesia and sedation of children for diagnostic and therapeutic procedures. The authors investigated in a randomized controlled clinical trial if diazepam premedication would have a beneficial effect on side effects related to ketamine anesthesia for bone marrow punctures (BMPs) in children with acute lymphoblastic leukemia (ALL). Sixteen children 4 years or older at the time of BMP were eligible. The first 2 BMPs after complete remission was obtained were studied. BMPs were performed under ketamine anesthesia (1.0-1.5 mg/kg iv), as usual. Patients were randomized to receive 1 h before the first BMP blinded, either diazepam or placebo orally and before the second BMP the other way round. Blood pressure, heart rate, and oxygen saturation were monitored, and patients were observed for signs of anxiety, pain, and other side effects. The patients were interviewed after each BMP and asked for their preference 1 week after the second BMP. Ketamine anesthesia appeared as safe and effective after diazepam premedication as after placebo premedication. From the interviews and questionnaires, it was clear that half of the children preferred diazepam premedication because of less awful dreaming and more gradual falling asleep and waking up. Diazepam premedication may be useful for selected children with ALL receiving ketamine anesthesia for BMPs.