Veno-occlusive disease of the liver in children with solid tumors undergoing autologous hematopoietic progenitor cell transplantation: a high incidence in patients with neuroblastoma

Abstract

Summary:We retrospectively analyzed the incidence and risk factors for veno-occlusive disease (VOD) in 83 consecutive children with solid tumors, who underwent autologous blood or bone marrow (BM) transplantation at UCSF between 1992 and 2000. Forty-one patients were diagnosed with neuroblastoma and 42 had another solid tumor (Ewing's sarcoma, soft tissue sarcomas, germ cell tumors, etc). Patients with neuroblastoma were more likely than patients with other solid tumors (ST) to be р7 years of age, to have a decreased serum albumin level, and to have received abdominal radiation and surgery prior to transplant. Patients with neuroblastoma received a different conditioning regimen and a purged stem cell product. Twenty patients (24%) developed VOD. VOD was self-limited in 15 (75%) patients and severe in five (25%) patients. Univariate analysis identified the following risk factors for VOD: diagnosis of neuroblastoma (odds ratio 6.1, P Ͻ 0.01), abdominal radiation (odds ratio 4.1, P Ͻ 0.01), abdominal surgery (odds ratio 4.1, P Ͻ 0.01), and age р7 years of age (odds ratio 3.3, P = 0.02). Disease status at transplant, intensity of previous chemotherapy, conditioning regimen, progenitor cell source, ALT, AST, albumin level, renal function prior to transplant, or use of amphotericin, growth-factor or heparin during transplant, did not affect the incidence of VOD. On multivariate analysis, only the diagnosis of neuroblastoma remained significant (odds ratio 7.8, P = 0.03). Larger studies of patients with neuroblastoma are necessary in order to confirm our findings and better define the risk factors for VOD development in neuroblastoma patients.

Risk factors for hepatic veno-occlusive disease: a retrospective unicentric study in 116 children autografted after a high-dose BU-thiotepa regimen

“…8,16,21,22 Unlike Cesaro et al, 23 we found no correlation between age and HVOD. However, in their series, the BU-TTP combination was not used and in ours, the majority of the patients were very young (median age: 4.5 years).…”

“…Bouligand et al 33 however, showed that a high level of ferritin was a major risk factor for HVOD. The lack of significance of a high ferritin level in our multivariate analysis could be explained by the different types of tumors (brain tumors vs neuroblastoma) and/or the different conditioning regimens 21,22,30 or by the fact that our study was simply too underpowered to corroborate Bouligand's result.…”

“…The major risk factors identified are: previous hepatic alterations, previous abdominal irradiation, 7,16 recent use of vancomycin, 17 a second allogeneic graft, 17 TBI associated with CY, 18,19 grafts in children treated for neuroblastoma, 16,20,21 conditioning regimens combining BU and CY and/or melphalan (Mel). 8,16,21,22 Unlike Cesaro et al, 23 we found no correlation between age and HVOD.…”

“…Other studies suggest that neuroblastoma could be a risk factor. 16,21,22 Treatments performed before the conditioning regimen as well as the disease status before the graft were evaluated as possible risk factors. In this group of patients, only 1 of 47 irradiation treatments encompassed the abdomen, thus the importance of this modality could not be evaluated in this population.…”

Assessing the risk of transplant-related complications and individually tailoring the HSCT procedure in children and adolescents—is it possible?

“…7 Forced expiratory volume and forced vital capacity are the best tests to detect pulmonary abnormalities, both in symptomatic and in asymptomatic patients. 32, 43 Forced Table 1 Type and frequency in paediatric age of the most frequent early and late toxicities that occur after HSCT Euthyroid sick syndrome 13 Compensated or overt hypothyroidism (15-2.1) 14 Leydig cell failure (7) 15 Germ cell failure (after TBI 99) 16 Delayed menarche (after TBI 44) 15 Overt ovarian failure (after TBI 90) 16 Growth impairment Liver VOD (4.6-41) [17][18][19] Viral hepatitis (14-50), 20 iron overload (52) expiratory volume and forced vital capacity levels of less than 85% before transplant can predict pulmonary failure, and patients with pulmonary function test abnormalities should be carefully followed up, especially if they develop cGVHD.…”