Outcome after cessation of therapy in childhood acute lymphoblastic leukaemia. The Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP).

A total of 2192 children with acute lymphoblastic leukaemia who had reached cessation of therapy in complete remission were followed for a median time of 52 months after treatment suspension. Of the 485 relapses observed, 62.3% occurred in the first year off therapy and 68.9% involved the bone marrow. Eight relapses were reported more than 5 years (62-143 months) after treatment withdrawal. Males fared worse than females consistently, experiencing 1.5 times more relapses (P < 0.0001). Thirteen patients died in continuous complete remission, 5 because of non-neoplastic central nervous system complications. There were 11 second solid malignancies, 8 of them in the central nervous system; 9 subjects presented an haematopoietic malignancy after ALL. The projected event-free survival at 8 years is 73%. Twenty-two of the 171 young adults (age > 20 years) were married and 16 have had 21 healthy children. Twenty-four per cent of patients experienced an unfavourable event. Relapses accounted for 93% of failures. Central nervous system late effects and second malignancies were the major causes of non-leukaemic morbidity and mortality.

Long-term effects of bone marrow transplantation on dental status in children with leukaemia.

Minimal data about oral and dental health in long-term survivors after BMT are available. We studied the dental status of 27 children (19 males, eight females) with leukaemia, followed up with a routine oral examination, panoramic tomogram and, when necessary, an endoral radiograph at a median of 2 years (range 1-10) after BMT. Community periodontal index treatment necessity (CPITN), dental caries, missing or filled permanent teeth (DMFT) and dento-facial alterations according to WHO criteria were registered and evaluated. Median age of the patients at BMT was 9 years (range 1.1-17.9). The mean DMFT score ranged from 1.6 to 12.4 according to age at examination and was slightly higher than that which we previously reported in children who received chemotherapy alone. CPITN showed the presence of soft deposits in 77.7%, serious gingivitis in 59.2% and parodontal involvement in 3.7% of cases. Dento-facial abnormalities were found in 55.5% of patients, while 62.9% of the patients had tooth abnormalities or agenesis. Nine out of 27 patients (33%) had root hypoplasia. A negative impact on DMFT index due to multiple post-BMT factors was found. Age is the crucial factor in determining a developmental defect of enamel and root. The follow-up of long-term survivors after BMT should include regular dental examination.

Evidence against the role of hepatitis C virus in severe liver damage occurring early in the course of acute leukemia in children.

Severe liver damage revealed by a sharp transaminase elevation may be seen in patients with leukemia. This may be due to several possible causes, including viral hepatitis, chemotherapy-induced hepatotoxicity and leukemic infiltration. HCV infection may be suspected to play a relevant role as these patients are often heavily transfused after the onset of their hematologic disorder. We have therefore examined the role of HCV in 15 children with leukemia who developed severe liver damage shortly after the diagnosis of leukemia. All patients were tested for HCV-RNA by the polymerase chain reaction at the time of peak SGPT elevation and for anti-HCV on serial serum samples taken thereafter. Only one patient (6.6%) showed hepatitis C viremia and none developed confirmed anti-HCV positivity during follow-up, suggesting that HCV had not played a major role in causing these severe episodes of liver necrosis. This is in agreement with observations made in non-immunocompromised patients in whom fulminant hepatitis is only exceptionally due to HCV.

[The use of urokinase and ammonium chloride in unblocking a central venous catheter in a child with acute lymphoblastic leukemia]. / Uso dell'urokinasi e del cloruro d'ammonio nella disostruzione di un catetere venoso centrale in un bambino con leucemia linfoblastica acuta.

Central venous catheter (C.V.C.) mechanical obstruction in immunocompromised patients can yield several complications sometime life-threatening and can be promptly solved by thrombolytic treatment. The authors describe a case of a child affected by acute lymphoblastic leukemia and experiencing an obstruction of his C.V.C. very difficult to treat with conventional urokinase treatment. Thinking the lack of success to be attributed to a calcium thrombus, the Authors before pulling out the C.V.C., made use of ammonium chloride solution in order to obtain the disappearance of the little bag covering the tip of C.V.C. The treatment was successful as confirmed by the contrast medium examination and the use of C.V.C. lasted for several months without other mechanical obstruction. In our best knowledge this is one of the first attempts with such ammonium chloride solution which have been used successful and rather safely. The only drug induced symptoms were constituted by mild and transient vomiting. Owing to this positive experience the authors believe useful to confirm this treatment in other cases. In this contest an experienced hematoncology team must take care of C.V.C. related complications.

Successful use of high-dose cyclophosphamide in a child with severe autoimmune hemolytic anemia.

We report the case of a five-month-old boy with a life-threatening autoimmune hemolytic anemia that was unresponsive to conventional therapy with steroids, high-dose immunoglobulin, azathioprine and splenectomy. Despite these therapies, the patient's condition worsened, requiring 2-3 blood transfusions/day, since the hemoglobin level was constantly below 4 g/dl. We eventually increased immunosuppression by giving high-dose cyclophosphamide and the child showed a striking, sudden improvement, followed by complete recovery. No major long-term complications were observed.

[DMFT index values in patients treated for leukemia during growth]. / Valori dell'indice DMFT in soggetti trattati per leucemia nell'eta evolutiva.

Patients affected by acute leukemia under radiotherapy and chemotherapy, less than 12 years old were investigated about DMFT index. Patients were in total remission. All erupted permanent teeth, with attention to an eventual oligodontia of non erupted teeth also, excluding third molars, were investigated by clinical and X-Ray examination. Authors concluded that there is no difference between these patients and normal subjects for this index.

Overdose of vinblastine in a child with Langerhans' cell histiocytosis: toxicity and salvage therapy.

The therapeutic index of antineoplastic agents is generally low, therefore, errors in administration can cause severe, life-threatening toxicity. The publication of cases of overdoses may provide useful information on the causes of the mistakes, on drug-induced toxic effects, and on salvage therapy. We report a case of vinblastine overdose in a child affected by Langerhans' cell histiocytosis, Hand-Schüller-Christian syndrome according with the previous classification of histiocytosis X. To our knowledge this is the highest dose of vinblastine ever administered. The child was given salvage therapy with steroids and citrovorum factor. Major side effects were neurologic toxicity (seizures, coma) and marrow aplasia, which improved and gradually resolved beginning day 12.

High-dose methotrexate administration and acute liver damage in children treated for acute lymphoblastic leukemia. A prospective study.

BACKGROUND: Methotrexate-induced hepatotoxicity following chronic low-dose administration has been extensively reported. Current protocols now include high-dose methotrexate (HDMTX), but there are few studies providing data on its acute hepatotoxicity in childhood leukemia. METHODS: To evaluate the prevalence of HDMTX-induced acute hepatotoxicity, sixty-eight consecutive children with ALL were prospectively studied from diagnosis to the end of HDMTX courses with biochemical and clinical evaluation performed at regular intervals. RESULTS: Prevalence of HDMTX-induced acute hepatotoxicity was 1.47% (1/68 patients). ALT values did not change in 22% (15/68) and decreased in 76.4% (52/68) after HDMTX infusion. Mean ALT levels calculated in all the patients decreased significantly during HDMTX administration when compared to the values reached during induction (p less than 0.0001). Direct hyperbilirubinemia was present only in the child with HDMTX-related hepatotoxicity. CONCLUSIONS: The use of HDMTX in the treatment of childhood ALL is not associated with major evidence of direct acute hepatotoxic effects, while it may modify the pattern of preexisting liver diseases.

Prevalence and natural history of hepatitis C infection in patients cured of childhood leukemia.

The aim of this study was to ascertain prevalence and natural history of hepatitis C virus (HCV) infection in a large cohort of patients cured of childhood leukemia who had been followed prospectively for liver disease for at least 10 years since chemotherapy withdrawal: 114 consecutive patients entered the study. Liver function tests and ultrasonography were used to assess presence of liver disease. Patients were tested for antibody to HCV and for serum HCV-RNA at the end of chemotherapy and at the end of follow-up. At chemotherapy withdrawal, 56 patients (49%) were HCV-RNA positive, often without detectable anti-HCV, and in these cases, transaminase levels were more elevated during (P = .08) and after (P = .04) chemotherapy compared with HCV-RNA negative cases. Patients were then followed-up 13 to 27 years (mean, 17) after chemotherapy withdrawal. During this period, 38 initially anti-HCV negative patients seroconverted to anti-HCV and 17 initially anti-HCV positive cases lost reactivity. Forty patients were persistently HCV-RNA positive in serum, while 16 initially viremic patients became HCV-RNA negative during follow-up. At the end of the observation period, a persistent transaminase elevation was detected only in four HCV-RNA positive and anti-HCV positive cases, while no patient developed signs or symptoms of decompensated liver disease. Thus, hepatitis C was a frequent finding in long-term survivors after chemotherapy. It was associated with an atypical serologic profile and did not cause severe liver impairment over a period of 13 to 27 years.

Self-image of adolescent survivors of long-term childhood leukemia.

The purpose of our research was to evaluate the attitude to face the life cycle and the impact that the experience of childhood leukemia may have had in a group of adolescents who had the disease cured. A questionnaire was administered at the Pediatric Hematology Center, San Gerardo Hospital, Monza, Italy, to all former patients age 12 to 20 years and off therapy from leukemia for at least 2 years (total of 116 adolescents) during 1997; 70 patients responded to the mailing and a comparison group of 70 secondary-school students was investigated. The two groups were matched as closely as possible on key characteristics (age, gender, socio-economic level of families, education and occupation of the parents, and geographic area of residence). The Offer Self-Image Questionnaire was the instrument used in this study. Overall, the teenagers in whom leukemia was cured showed a more positive and mature self-image (psychologic, social, attitude toward family, and coping) compared with the student group (statistical evidence, P < 0.05). An effective psychosocial support for patients and their families during their treatment, in addition to medical therapy, is strongly recommended. The majority of survivors of childhood cancer grow successfully without serious psychologic sequelae.

School functioning for the child with leukemia in continuous first remission: screening high-risk children.

It is well known in the literature that cancer creates educationally related barriers for all children, which may or may not contribute to clinically relevant school problems. The goal of this study was to obtain a base rate for the characteristic pattern of school functioning for children with leukemia, so that the children with the most serious difficulties might be discovered and given the different and flexible help needed. From 1988 through 1994, a questionnaire was administered annually to teachers of all leukemic children in our center. The 291 questionnaire were used to compare the school functioning of children with leukemia with that of matched controls chosen by each teacher as representative of the class as a whole, excluding special education and developmentally disabled students. This approach to matching was chosen as a control for socioeconomic factors as well. The study was conducted with all patients with leukemia entering the center residing in the region of Lombardy, attending school, and either in therapy or out of therapy. After initial treatment, the children with leukemia in our center as a group attended school regularly and willingly. Analyses of variance (ANOVAs) were conducted on the total scores and on scores for each of the subareas of learning, socialization, and emotionality. T-tests, were given to contrast individual item scores of patients with those of their matched controls. On most individual items, children with leukemia did not differ from their classmates. However, significant discrepancies between children with leukemia and their classmates appeared consistently year after year on overall total scores and on each of the three major subcomponents of the test (learning, socialization, and emotionality). The groups most affected were children who were cranially irradiated and children who were under 6 years of age at diagnosis. Children who have been irradiated and children diagnosed under 6 years of age have the greatest risk for difficulties in school functioning and are candidates for greater attention and preventive efforts.

[Evaluation of family satisfaction in pediatric oncology]. / La valutazione della soddisfazione delle famiglie in oncologia pediatrica.

The satisfaction for the care receveid following the diagnosis of acute linfoblastic leukemia in the Pediatric Division of the San Gerardo Hospital of Monza was explored with a questionnaire to the families of patients diagnosed from January 1984. 217 questionnaires were returned (59.2%); 67% were completed by both parents. Parents expressed overall a very high satisfaction for several areas of care: 93.8% for the information about diagnosis; 83% approved the use of the word "leukemia". Judgements on technical competence and communication skills of the health care professionals were analyzed separately for hospitalized and day-hospital patients, and for survivors and dead: results were highly positive for both groups. The expected higher of missing data for the questions related to satisfaction for communication on relapses, highlights the difficulty and the emotional load of the question. Data were discussed by the health care team as well as parents in order to obtain a feedback and practical suggestions for further improvement of care.

Number and distribution of melanocytic nevi in individuals with a history of childhood leukemia.

BACKGROUND: An increased number of melanocytic nevi at the termination of chemotherapy has been documented in children with hematologic malignancies. The persistence of the increased number of nevi over time and the relationship with personal (e.g. phenotype) and disease related variables remain to be explored. METHODS: One hundred Italian patients diagnosed as having acute lymphatic or myeloid leukemia, after 1975, were recruited and compared with a group of 100 control individuals drawn from friend of the enrolled patients. Information regarding lifetime sun exposure, phenotypic characteristics, and number of nevi was collected by experienced dermatologists. Counts of nevi were expressed both as totals and as counts per unit of body surface area ("density"). Multiple linear regression analysis was employed to control for potentially confounding factors when comparing patients and controls. RESULTS: The patients and controls were fairly comparable in terms of constitutional characteristics, but the patients had a significantly higher number and density of nevi > or = 2 mm or larger in diameter. In addition, patients had a greater number of large nevi ( > or = 6 mm in greatest dimension), and of nevi in unusual areas, such as the palms and soles. Differences in nevus density between patients and controls were notably maintained in the older age group ( > 12 years). None of the disease-related factors analyzed (e.g. treatment protocol and radiotherapy), appeared to be significantly correlated with nevus density. CONCLUSIONS: Patients with a history of childhood leukemia have a sustained increase in their nevus density. A fairly convincing body of evidence indicates that a large number of melanocytic nevi is the strongest risk factor for melanoma. Therefore, the utility of periodic skin examination of these should be considered.