Momcilo Jankovic

Association of 1800 cGy cranial irradiation with intellectual function in children with acute lymphoblastic leukaemia

Cranial radiation therapy in childhood acute lymphoblastic leukaemia has been associated with adverse neuropsychological effects, such as low intelligence. However, records show that these associations usually occur when the dose of radiation used is 2400 cGy. We investigated whether a lower dose of 1800 cGy had the same adverse effects on long-term survivors and whether high doses of methotrexate but no radiation therapy would have a more beneficial effect. We evaluated 203 children for six years in a multi-centre European study. The patients were divided into two groups: 129 children treated with 1800 cGy of cranial radiation therapy and 74 children who received high-dose methotrexate but no radiation therapy. We used full scale intelligence quotient, verbal, and performance IQ tests to assess the patients intelligence. We found a significant decline in full scale intelligence quotient in the irradiated group that increased with the length of time from diagnosis. Younger age at diagnosis was associated with lower full scale intelligence quotient in the radiated group. Our results indicate that a radiation dose of 1800 cGy can have negative effects on neurocognitive function and we continue to question the benefit of low-dose cranial radiation therapy.

Microgranular Variant of Acute Promyelocytic Leukemia in Children

PURPOSE The microgranular variant (M3v) of acute promyelocytic leukemia (APL) rarely has been reported in a pediatric series of acute nonlymphoblastic leukemia (AnLL). We reviewed the clinical and biologic features of childhood M3v cases in our AnLL series. PATIENTS AND METHODS From January 1970 to January 1991, 11 children with M3v were admitted and treated at our center. A diagnosis was made according to French-American-British (FAB) criteria. Morphologic examination, cytochemical analysis, and immunophenotyping were performed by a single pathologist. From January 1984, the diagnosis was confirmed by cytogenetic and, subsequently, by molecular analysis on frozen material. RESULTS In our series, the overall incidence of children with APL was unusually high, 31.2% of the AnLL and M3v constituted one case in every four cases of APL. Even restriction of the analysis to the time when either cytogenetic and DNA studies confirmed the diagnosis, the incidence did not change. The immunophenotype of M3v cases was identical to that described for the hypergranular type, but an unexpected association of CD2 with M3v was shown. The onset was characterized by marked hyperleukocytosis (median WBC count, 87 x 10(9)/L) unlike classic APL. Disseminated intravascular coagulation (DIC) was always present and severe. Hyperleukocytosis and DIC were responsible for the high incidence of deaths for hemorrhagic events in the first days after onset (eight of 11 patients). CONCLUSIONS In our experience, for unknown reasons, M3v may occur in childhood more than generally was considered. The clinical course and prognosis seem worse in M3v than in typical APL cases.

Guidelines for assistance to terminally ill children with cancer: A report of the SIOP working committee on psychosocial issues in pediatric oncology

This, the sixth official document of the SIOP Working Committee on psychosocial issues in pediatric oncology, develops another important and especially difficult topic: assistance for terminally ill children with cancer. This is provided for the pediatric oncology community as a useful set of guidelines. It should be always possible for a declining child to die without unnecessary physical pain, fear, or anxiety. It is essential that he or she receive adequate medical, spiritual, and psychological support, and that the child at no point feels abandoned. Palliative care, in the terminal phase of cancer, should be tailored to the different needs and desires of the child and the family, with the goal of providing the best possible quality of life for the days that remain.

Clinical and laboratory features of 103 patients from 42 Italian families with inherited thrombocytopenia derived from the monoallelic Ala156Val mutation of GPIbα (Bolzano mutation)

Background Bernard-Soulier syndrome is a very rare form of inherited thrombocytopenia that derives from mutations in GPIbα, GPIbβ, or GPIX and is typically inherited as a recessive disease. However, some years ago it was shown that the monoallelic c.515C>T transition in the GPIBA gene (Bolzano mutation) was responsible for macrothrombocytopenia in a few Italian patients. Design and Methods Over the past 10 years, we have searched for the Bolzano mutation in all subjects referred to our institutions because of an autosomal, dominant form of thrombocytopenia of unknown origin. Results We identified 42 new Italian families (103 cases) with a thrombocytopenia induced by monoallelic Bolzano mutation. Analyses of the geographic origin of affected pedigrees and haplotypes indicated that this mutation originated in southern Italy. Although the clinical expression was variable, patients with this mutation typically had a mild form of Bernard-Soulier syndrome with mild thrombocytopenia and bleeding tendency. The most indicative laboratory findings were enlarged platelets and reduced GPIb/IX/V platelet expression; in vitro platelet aggregation was normal in nearly all of the cases. Conclusions Our study indicates that monoallelic Bolzano mutation is the most frequent cause of inherited thrombocytopenia in Italy, affecting 20% of patients recruited at our institutions during the last 10 years. Because many people from southern Italy have emigrated during the last century, this mutation may have spread to other countries.

Encephalopathy syndrome in children with hemato-oncological disorders is not always posterior and reversible.

Posterior reversible leukoencephalopathy (PRES) is a clinical‐radiological event that can affect children undergoing chemotherapy regimen. Studies have shown that it is not always reversible, in spite of its original definition. We analyzed PRES cases which occurred during the last 10 years at our institute to focus on their clinical, radiological and EEG follow‐up.

Marriage and parenthood among childhood cancer survivors: a report from the Italian AIEOP Off-Therapy Registry

Background The aim of this study was to describe the patterns of marriage and parenthood in a cohort of childhood cancer survivors included in the Off-Therapy Registry maintained by the Italian Association of Pediatric Hematology and Oncology. Design and Methods We analyzed a cohort of 6,044 patients diagnosed with cancer between 1960 and 1998, while aged 0 to 14 years and who were 18 years old or older by December 2003. They were followed up through the regional vital statistics registers until death or the end of follow up (October 30, 2006), whichever occurred first, and their marital status and date of birth of their children were recorded. The cumulative probabilities of being married and having a first child were computed by gender and compared by tumor type within the cohort. Marriage and fertility rates (the latter defined as the number of live births per woman-year) were compared with those of the Italian population of the same age, gender, area of residence and calendar period by means of the observed to expected (O/E) ratios. Results During the follow-up period, 4,633 (77%) subjects had not married. The marriage O/E ratios were 0.56 (95% CI: 0.51–0.61) and 0.70 (95% CI: 0.65–0.76) among men and women, respectively. Overall, 263 men had 367 liveborn children, and 473 women had 697 liveborn children. The female fertility O/E ratio was 0.57 (95% CI: 0.53–0.62) overall, and 1.08 (95% CI: 0.99–1.17) when analyses were restricted to married/cohabiting women Conclusions Childhood cancer survivors are less likely to marry and to have children than the general population, confirming the life-long impact of their previous disease on their social behavior and choices. The inclusion of counseling in the strategies of management and long-term surveillance of childhood cancer patients could be beneficial to survivors as they approach adulthood.

Guidelines for a therapeutic alliance between families and staff: A report of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology

This, the fifth official document of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology, develops another important topic: the Therapeutic Alliance between families and staff. This is addressed to the Pediatric Oncology Community as Guidelines that could be followed. Every parent, medical staff member, and psychosocial professional involved in the care of the child should be responsible for cooperating in the childs best interest. Everyone must work together toward the common goal of curing the cancer and minimizing its medical and psychosocial side-effects.

Effect of eradication of Helicobacter pylori in children with chronic immune thrombocytopenia: A prospective, controlled, multicenter study†

The eradication of Helicobacter pylori has been associated with remission of immune thrombocytopenia (ITP) in approximately half of eradicated patients. Data on children are limited to small case series.

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.

Impact of influenza-like illness and effectiveness of influenza vaccination in oncohematological children who have completed cancer therapy

Abstract In order to evaluate the impact of influenza-like illness and the effectiveness of influenza vaccination in children with oncohematological disease who have completed cancer therapy, 182 children with a diagnosis of oncohematological disease were divided into two subgroups on the basis of the length of time off therapy (<6 months or 6–24 months) and randomised 1:1 to receive influenza vaccination or not. The controls were 91 otherwise healthy children unvaccinated against influenza. The results show that the clinical and socioeconomic impact of influenza-like illnesses and the effectiveness of influenza vaccination in oncohematological children who have completed cancer therapy are related to the length of the off therapy period, and seem to be significantly greater in those who have been off therapy for less than 6 months in comparison with healthy controls. This suggests that the administration of influenza vaccination should be strongly recommended only among oncohematological children who have been off therapy for less than 6 months.