Subclinical cardiac dysfunction and exercise performance in childhood cancer survivors.

BACKGROUND: Although anthracycline cardiotoxicity is clearly related to the cumulative dose administered, subclinical cardiac dysfunction has been reported across a wide range of treatment regimens, and its clinical significance is still unclear. Purpose of this study is to investigate by exercise echocardiography for subclinical cardiac dysfunction in survivors of pediatric cancer treated with low-moderate anthracycline doses, and to evaluate whether it may alter the response of the cardiovascular system to dynamic exercise. PROCEDURE: Post-exercise left ventricular end-systolic wall stress (ESS), left ventricular posterior wall dimension and percent thickening at end systole, and cardiopulmonary exercise test-derived indexes of cardiac function were examined in 55 apparently healthy patients (mean age 13.5 ± 2.9 years, median anthracycline cumulative dose 240 mg/m(2)) and in 63 controls. RESULTS: Subclinical cardiac dysfunction was identified in 17 patients (30%) presenting reduced left ventricular posterior wall dimension or percent thickening, or increased values of left ventricular ESS as compared to controls (group A), while the remaining patients formed group B. Reduced oxygen consumption at peak exercise in both groups of patients was the only cardiopulmonary exercise test variable resulting significantly different between patients and controls: no differences were found among the groups of patients. CONCLUSIONS: Our results confirm that even patients treated with a median anthracycline dose of 240 mg/m(2) (range 100-490) are at considerable risk of exhibiting subclinical cardiac dysfunction that, however, does not seem to alter the physiologic response of the cardiovascular system to dynamic exercise.

Magnetic resonance imaging in childhood leukemia survivors treated with cranial radiotherapy: a cross sectional, single center study.

BACKGROUND: Children treated with cranial radiotherapy (CRT) for leukemia are at risk of developing central nervous system injuries. Magnetic resonance imaging (MRI) represents the examination method of choice for evaluating radiation-induced brain complications. The purpose of this report is to describe the spectrum of MRI abnormalities detected in a group of survivors of leukemia treated with cranial irradiation. PROCEDURES: In this cross-sectional, single center study, 56 patients (median age at follow-up 19 years) receiving CRT as cranial prophylaxis (CP) included in the leukemia protocol (total dose 1,800-2,400 cGy) and/or in the total body irradiation regimen (990-1,200 cGy) before hematopoietic stem cell transplant, were evaluated by MRI after a median interval of 11 years (range 2-27) following CRT. RESULTS: Fifty-nine MRI abnormalities (32 cavernomas, nine focal areas of gliosis, seven dystrophic mineralizations, five cerebral atrophies, four pituitary atrophies, one diffuse radiation leukoencephalopathy, and one meningioma) were found in 43 patients. The longest interval between CRT and MRI and oldest age at follow-up represented the two risk factors that were statistically associated with MRI lesions (P = 0.032 and 0.033, respectively). Cerebral cavernomas (CC) were the most frequent MRI abnormalities (57%). All patients with CC were asymptomatic at diagnosis and during follow-up, except one who had aspecific neurological manifestations and micro hemorrhages. CONCLUSIONS: These results confirm that total doses and modalities of fractionation dose of CRT were not significantly associated with MRI abnormalities. Moreover, in our experience none of the patients developed neurological symptoms related to MRI abnormalities, and furthermore, the CC remained substantially stable during follow-up.

Helicobacter pylori as cause of gastrointestinal disease in children with hemato-oncologic diseases.

After documentation of a case of life threatening Helicobacter pylori (H. pylori) gastric ulcer in an adolescent girl on treatment for acute lymphoblastic leukaemia, we started to systematically look for gastro-intestinal symptoms due to H. pylori infection in our cancer patients at G. Gaslini Children's Hospital. During a period of 46 months, we observed 13 further cases of severe dyspepsia syndrome or gastro intestinal bleeding associated with presence of H. pylori faecal antigen. All patients recovered with appropriate therapy. H. pylori may represent a cause of severe gastrointestinal complications in children with cancer or following bone marrow transplant.

Survival after relapse in children with solid tumors: a follow-up study from the Italian off-therapy registry.

BACKGROUND: Despite the increased survival of children with solid tumors, a significant proportion of cases still relapse following treatment discontinuation, and knowledge about the long-term outcome of this selected group of patients remains incomplete. OBJECTIVE: To describe the long-term outcome of children treated for a solid tumor who relapsed after the elective end of therapy, and to explore factors associated with survival. METHODS: All patients with the selected diagnoses-Hodgkin disease (HD), neuroblastoma (NB), tumor of the central nervous system (CNS), Wilms tumor (WT), or soft tissue sarcoma (STS)-enrolled in the Italian Pediatric Off-Therapy Registry in the period 1980-1998 were evaluated. Out of 3,927 patients, 694 had relapsed after treatment suspension; 639 were available for analysis. Survival and event-free survival were estimated by the Kaplan-Meier method. The log-rank test was used to assess differences in survival among the various types of cancer considered. Multivariate Cox proportional hazards analysis was adopted to explore possible prognostic factors. RESULTS: There were 335 deaths: most of them (93%) were related to the primary cancer. The overall survival rate after relapse was 38% (95% CI 33-42) at 5 years, and 32% (95% CI 27-36%) at 15 years, while event free survival was 31% (95% CI 26-35) and 26% (95% CI 22-30%), respectively. There were significant differences according to the original diagnosis, with patients with HD doing better, and those with NB, CNS, and STS worse. No improvement of prognosis was evident over time. Post-relapse stem cell transplantation was associated with decreased risk of death only in the first year, not thereafter. CONCLUSIONS: Overall, patients with solid tumors who relapse after treatment discontinuation have a poor outcome, but significant differences exist according to the tumor types.

Role of active follow-up for early diagnosis of relapse after elective end of therapies.

OBJECTIVE: To evaluate the role of active follow-up for the detection of relapses occurring after completion of therapy in children with cancer. METHODS: The clinical records of all children who had a cancer relapse more than 3 months after the end of therapies in the period 1985-2000 were reviewed. Relapses were defined "diagnosed at a scheduled visit" or "at an unscheduled visit" based upon how the visit that lead to the suspected diagnosis was scheduled. Information was collected on how the first suspicion of relapse was made. Survival after relapse was calculated, by type of visit and tumor type. RESULTS: Among 739 children who completed therapy for a malignant tumor in first complete remission (CR), 101 relapses [74 after solid tumors (ST), 27 after leukemia/lymphoma (L)] occurred after a median time of 12 months (range 3-87). Fifty-one (50.5%) first relapses were diagnosed during a visit scheduled because of symptoms (36 ST, 15 L), and 50 relapses (49.5%) at a regularly scheduled visit (38 ST, 12 L). Overall, 75% of relapses were first suspected on clinical basis, 16% via imaging, and only 9% via lab tests. Survival more than 10 years from first relapse was 25.7% (SE: 0.05%), with no significant differences between relapses diagnosed at a scheduled visit (20.5%), or at an unscheduled visit (32.1%; P = 0.826). Children with L had a better overall survival (OS, 70.6%) as compared to those with ST (9.2%, P < 0.001), probably because of a more extensive use of stem cell transplantation (SCT) as part of the salvage regimens. CONCLUSIONS: Scheduled follow-up programs failed to detect relapses in 50% of cases presented here. Survival after relapse is not affected by whether relapse was detected at a scheduled or an unscheduled visit.

Re-immunisation schedule in leukaemic children after intensive chemotherapy: a possible strategy.

The aim of this retrospective study was to test the residual humoral immunity to compulsory vaccines after the end of chemotherapy for acute lymphoblastic leukaemia in a cohort of 70 Italian children. All the patients, who had been immunised according to the Italian schedule prior to the disease, were tested for antibody levels against tetanus and hepatitis B at a median of 10 months after the end of therapy. Median age at diagnosis of leukaemia was 48 months, and median age at vaccine titration was 84 months. The protective level of antibodies for tetanus and hepatitis B was shown in 83% and 81% of patients, respectively; the remaining 17% and 19% were not protected against the two pathogens. Double negativity was observed in only four of 62 (6%) patients in the cohort. These data were comparable with published data regarding healthy children of the same age and from the same geographical areas. Therefore, given the direct and indirect costs of performing laboratory tests, as well as the cost of revaccination, our proposal is to continue the vaccination schedule according to the child's age without any titration screening 6 months after the end of therapy. Larger studies are needed to confirm these observations.