Cytomegaloviremia in children with acute lymphocytic leukemia.

Leukocyte and urine cultures were done at monthly intervals in 36 children with acute lymphocytic leukemia known to be excreting cytomegalovirus in their or saliva in order to determine the relationship of viremia to clinical cytomegalic inclusion disease. Eleven of 36 (30.5%) patients had viremia. Viremia was related to clinical disease in only three patients; two with chorioretinitis and one with a CMV monomucleosis syndrom. However, the presence of viremia did not serve as a useful means to determine active CID. Viremic patients with CID all had elevated serum levels of IgM and multiple episodes of viremia. Viremia was not related to the duration, type or number of drugs used in immunosuppression, nor to the hematologic status of leukemia. Viremic patients received more blood transfusions than noviremic patients, but the administration of blood products could not be related to the acquisition of infection. Leukopenia, neutropenia, total lymphocyte count, fourfold rise or fall in complement-fixing titer, and viruria had no consistent relationship to viremia or clinical CID.     

Prognosis of black children with acute lymphocytic leukemia.

To assess the racial differences in survival of children with acute lymphocytic leukemia, we analyzed data for 1,675 white and 126 black children, diagnosed from 1955 to 1969. Blacks had a significantly shorter median survival and lower one-year and three-year survival rates than whites. There was substantial variation in racial differences by age. In addition, much of the variation between races seemed to be due to socioeconimic factors rather than strictly racial ones. Identification of the specific factors responsible for the poorer survival of children from lower social classes is sorely needed.     

Herpes zoster in children with acute lymphocytic leukemia

Herpes zoster (HZ) occurred in 25% (28/88) of a population of children with acute lymphocytic leukemia (ALL) who were seropositive for varicella zoster virus antibody before its onset; 16.5% (33/199) of the total group of children with ALL developed HZ. There were no deaths and only one significant complication, cutaneous disseminated disease, as a result of HZ. The small number of patients studied may have accounted for the failure to find a significant association between the occurrence of HZ and the type of ALL or chemotherapy protocol employed. Although HZ seemed to be more common in those patients who experience relapses of their leukemia, it did not portend a poor outcome for ALL.     

Pneumococcal vaccination in children with acute lymphocytic leukemia

Sixty-three children with ALL in CCR and treated according to a standard therapy protocol were immunized with the 14-valent pneumococcal vaccine. Forty-six children were vaccinated 1, 3, or 6 months following initial induction remission; 15 were vaccinated 4-6 weeks following successful completion of 30 months of antileukemia therapy; and two were vaccinated at the time of diagnosis. Response to the vaccine was suboptimal and by the 6-month follow-up there were only two serotypes for which more than half the patients tested had greater than or equal to 300 ng antibodies N/ml.     

Prognosis of black children with acute lymphocytic leukemia

To assess the racial differences in survival of children with acute lymphocytic leukemia, we analyzed data for 1,675 white and 126 black children, diagnosed from 1955 to 1969. Blacks had a significantly shorter median survival and lower one-year and three-year survival rates than whites. There was substantial variation in racial differences by age. In addition, much of the variation between races seemed to be due to socioeconomic factors rather than strictly racial ones. Identification of the specific factors responsible for the poorer survival of children from lower social classes is sorely needed.     

An outbreak of pneumocystis pneumonia in children with acute lymphocytic leukemia.

Between Jan 1 and Oct 31, 1975, a cluster of ten cases of pneumocystis pneumonia occurred in children with acute lymphocytic leukemia (ALL) at the James Whitcomb Riley Hospital for Children in Indianapolis. The risk of infection appeared to be related to the intensity of chemotherapy. Furthermore, illness developed in nine of the ten patients between 30 and 100 days after initiation of therapy, suggesting a period of heightened susceptibility to infection. An indirect immunofluorescent test was used to detect antipneumocystis antibodies in serum samples collected from patients with pneumocystis pneumonia and their contacts. Members of the Riley Hospital staff who had close contact with infected children had a higher prevalence of elevated antibody titers (7/12) than other staff members (2/22; P = .004) or parents of infected patients (0/8; P = .01). This suggests that transmission of pneumocystis may occur within the hospital environment.     

高效液相色谱法测定小儿急性淋巴细胞白血病红细胞中硫嘌呤甲基转移酶活性的研究

目的探讨急性淋巴细胞白血病患儿红细胞中的硫嘌呤甲基转移酶(TPMT)活性的高效液相色谱(HPLC)测定法。方法采用反相HPLC直接测定酶促反应的产物浓度,从而计算红细胞中TPMT的活性。以S-腺苷-L-甲硫氨酸(S-adenosyl-L-methionine,SAM)作为甲基供给体,6-硫鸟嘌呤(6-thioguanine,6-TG)作为酶反应底物,TPMT催化6-TG生成2-氨基-6-甲基巯基嘌呤(2-amino-6-methyl mercaptopurine,6-MTG),采用高氯酸溶液终止反应及沉淀蛋白,分离上清液进行色谱分析。色谱柱为AichromBond-1 C18柱(5μm,4.6mm×150mm);等梯度洗脱,流动相为乙腈:0.01mol/L磷酸钾缓冲溶液(用盐酸调pH=2.74)(6∶94,V/V),流速为1.0mL/min;柱温为35℃;进样量为50μL。荧光检测器检测,激发波长为310nm,发射波长为390nm。结果6-MTG在0~250μg/L范围内呈良好的线性关系,相关系数r=0.9999,最低检出限为0.093μg/L(S/N=3),回收率为81.4~106.3%。结论本方法操作简便、分析速度快、检出限低、重现性好、易于推广,能满足巯基嘌呤类药物代谢动力学研究和临床用药监测常规分析。     

Immune status in children with acute lymphocytic leukemia. Observations in 67 cases.

67 children affected with acute lympocytic leukemia were immunologically evaluated for lymphocytic markers, serum immunoglobulins and delayed hypersensitivity skin tests at the onset, in remission and after cessation of therapy. E, EA rosettes and surface Ig assayed significantly lower in leukemic children than in matched controls, except for three cases of T-cell leukemia in which E rosettes were very high. After cessation of therapy almost normal results were obtained. As for serum Ig, the only abnormal finding was that of low IgM during therapy. The skin tests with Varidase, Candidine, Mumps antigen and DNCB were not significantly different at onset and in remission. As for DNCB test, the negative responses at onset often became positive in remission, but only when the test was performed before any treatment (anamnestic-like response?). One of the three patients with T-cell leukemia relapsed after 8 months: strangely enough, no surface marker could be detected on that occasion. We could not find any relationship between various immunological tests, or between these tests and prognosis; chemotherapy proved active in suppressing cellular immunity, especially the primary cellular response.     

Neutropenia, fever, and infection in children with acute lymphocytic leukemia.

In an attempt to determine the relationship between neutropenia (absolute granulocyte count less than 1,000/cu mm), infection, and disease status, 20 patients with acute lymphoblastic leukemia were observed for a total of 34 patient-years. Febrile episodes occurred with much greater frequency in patients during the course of treatment induction (0.9/mo), or while in relapse (2.46/mo) than while in remission (0.19/mo). A cause for fever was identified much more frequently in patients in remission, both when neutropenic and nonneutropenic. When absolute granulocyte counts fell below 200/cu mm, a cause for fever was generally identified regardless of disease status. We propose that the majority of febrile episodes in patients at the time of induction of treatment or in relapse with neutrophil counts of more than 200/cu mm are caused by the disease process rather than secondary to a diagnosable infection.     

Evaluation of different induction regimens in children with acute lymphocytic leukemia

Four induction regimens-prednisolone and 6- mercaptopurine (group I), prednisolone and vincristine (group II), prednisolone, vincristine & asparaginase (group III) and prednisolone, vincristine and adriamycin followed by cyclophosphamide and 1-asparaginase (group IV)- have been evaluated. Successful induction remission was achieved in 16 (69.6%) in group I, 23 (92.0%) in group II, 36 (94.7%) in group III, 31 (96.8%) in group IV. Relapses were seen in 10 (62.5%), 10 (73.8%), 25 (69.4%) and 9 (29.0%) in the four groups respectively. Relapses seen in group IV were infrequent as compared to children of group I, II & III. Adverse risk factors were similar in all the four groups. Ninety four children (61.3%) had one or more poor prognostic factors at diagnosis. Three of 43(7%) children with no poor prognostic factors died during induction therapy as compared to 18 of 94 (19.1%) children associated, with poor prognostic factors at diagnosis. Higher mortality was seen under two years of age.     

Intermittent chemotherapy and BCG in continuation therapy of children with acute lymphocytic leukemia.

Continuation therapy using intermittent chemotherapy and BCG inoculation was commenced in 28 children with acute lymphocytic leukemia (ALL) immediately after remission induction and "CNS prophylaxis." At a median followup time of 17 months, 71% remain in total remission and 86% in bone marrow remission. Complications of the therapy were minimal. Major infections occurred on two occasions and there were no deaths in remission. Neutropenia, "minor" infections and postponement of chemotherapy occurred most often during the first three courses of treatment. There were no local or systemic BCG infections. Tuberculin sensitivity was tested in 25 patients. It was positive in 17 of 18 patients in total remission and all four patients with only CNS relapse, and was negative prior to relapse in three patients who developed bone marrow disease.     

Electrophoretic examination of cerebrospinal fluid proteins in children with acute lymphocytic leukemia

The cerebrospinal fluid of 28 children with acute lymphocytic leukemia were investigated by means of electrophoresis on cellulose-acetate membranes. The study included children with meningeal leukemia who were in the first or a further central nervous system remission; those who received prophylactic central nervous system therapy were also studied. In cases of acute leukemia, decreases of the prealbumin fraction and coincident increases of albumin as well as ₂ globulins were found to be clinically important signs of a disturbed blood-CSF barrier, reversible or not. Changes in protein composition, which led to a pattern similar to that of serum, indicated very severe disorder of the barrier function, as was observed during meningeal leukemia. Prolongation of this pathological pattern points to an infaust prognosis. 4 patients who maintained CSF patterns resembling that of serum died 2 to 7 months after the first abnormalities were evident. CSF electrophoresis is of much greater diagnostic value than determination of the cell count, total protein content, and individual proteins.

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Zusammenfassung Es wurden die Liquores von 28 Kindern mit akuter lymphatischer Leukämie nach Bestimmung von Zellzahl und Gesamteiweiß auf Cellulose-Acetat-Folien elektrophoretisch aufgetrennt. Die Untersuchung umfaßte Kinder mit einer Meningosis, solche im symptomenfreien Intervall zwischen Meningosisrezidiven und Patienten, die nach der ersten hämatologischen Remission einer Meningosisprophylaxe unterzogen wurden. Als verwertbare kriterien für eine Schädigung der Blut-Liquor-Schranke ergaben sich eine Verminderung der Präalbuminfraktion sowie die gleichzeitige Zunahme des Albuminanteils. Als schwerste Form der Schrankenstörung zeigte sich ein serumgleiches Elektropherogramm des Liquors. Dieses Mischelektropherogramm beobachteten wir vorübergehend während der Meningosis leucaemica. Bleibt es bestehen, so gilt es als Hinweis auf eine schlechte Prognose. 4 der 28 Kinder behielten ein serumähnliches Elektropherogramm. Sie starben 2 bis 7 Monate nach Auftreten der ersten Veränderungen. Der Aussagewert der Liquorelektrophorese reicht prognostisch weiter als die Bestimmung von Zellzahl, Gesamteiweiß und einzelnen Proteinen.

     

Treatment of children with refractory acute lymphocytic leukemia with vincristine and diltiazem

Six children with refractory acute lymphocytic leukemia were treated with vincristine combined with diltiazem. In four of five children who took the drug as scheduled, a cytolytic effect was observed. One child showed massive cell destruction which caused hyperuricemic nephropathy. The only adverse effect was atrioventricular block in two children, which was completely reversible. Increased neurotoxicity was not observed in any child.     

MR imaging of osteonecrosis of the knee in children with acute lymphocytic leukemia

This essay illustrates various patterns of progression of osteonecrosis of the knee and the relationship between early MR imaging findings and radiologic outcome in children with acute lymphocytic leukemia. It also includes a review of nonosteonecrosis signal abnormalities, which are common in the knee region and are often transient. Such abnormalities must be distinguished from osteonecrosis, which can lead to joint collapse and predispose to secondary arthritis.     

Liver function studies in children with acute lymphocytic leukemia after cessation of therapy

We investigated liver function in 27 children with acute lymphocytic leukemia (ALL) after cessation of therapy. Induction therapy consisted of prednisolone + vincristine (VP regimen) alone (16 patients) or with addition of daunorubicin (4 patients) or L-asparaginase (7 patients). Patients treated with VP regimen short courses of VP regimen every 12 weeks for the first year of maintenance. Twenty-five patients remained in first complete remission and had completed 3-year maintenance therapy with methotrexate (MTX) and 6-mercaptopurine (6-MP) 1–7 years prior to this study. Twenty-three patients had transfusions of packed red blood cells or fresh whole blood (1–11 units; median: 2 units) but none had evidence of either hepatitis B or hepatitis C. Alanine aminotransferase (ALT), which was measured every 3 months during maintenance therapy, had values more than three times the upper limit of the normal range in 25% of the measurements in more than half of the patients. However, by 3 months after the completion of maintenance therapy, ALT had normalized in all patients and remained normal in all but two patients until the time of this study. Serum bilirubin, serum albumin, and prothrombin time were all within normal limits. Fasting and 2-hour postprandial total serum bile acids were high in 5 of 13 patients and in 6 of 13 patients, respectively. The ratio of cholic acids + deoxycholic acids to chenodeoxycholic acids + lithocholic acids was below 1 in all but two patients, whereas this ratio was above 1 in all controls. Our bile acid profile results indicate the necessity of careful long-term follow-up of survivors of ALL treated with hepatotoxic chemotherapy during childhood. © 1994 Wiley-Liss, Inc.