Giorgio Dini

Impact of cumulative anthracycline dose, preparative regimen and chronic graft-versus-host disease on pulmonary and cardiac function in children 5 years after allogeneic hematopoietic stem cell transplantation: a prospective evaluation on behalf of the EBMT Pediatric Diseases and Late Effects Working Parties

This prospective study focused on risk factors and clinical outcome of pulmonary and cardiac late effects after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We prospectively evaluated 162 children by pulmonary function tests (PFTs) and cardiac shortening fraction (SF) before allo-HSCT and yearly up to the 5th year of follow-up. The 5-year cumulative incidence of lung and cardiac impairment was 35 (hazard rate=0.03) and 26% (hazard rate=0.06), respectively. Patients presenting abnormal PFTs and SF at last follow-up were 19 and 13%, respectively, with a median Lansky performance status of 90% (70–100). Chronic graft-versus-host disease (c-GVHD) was the major risk factor for reduced lung function in univariate (P=0.02) and multivariate analysis (P=0.02). Total body irradiation (TBI) alone and TBI together with pre-transplant anthracycline administration were significant risk factors for reduced cardiac function in univariate analysis, only (P=0.04 and 0.004, respectively). In conclusion, our prospective study demonstrates an asymptomatic post-allo-HSCT deterioration of pulmonary and cardiac function in some long-term survivors, who had been transplanted in childhood, and thus emphasizes the need for lifelong cardiopulmonary monitoring and the development of new strategies both to reduce pre-transplant cardiotoxic regimens and to treat more efficiently c-GVHD.

Prevention and treatment of acute GvHD.

GvHD remains a source of significant morbidity and mortality in the setting of allogeneic haematopoietic SCT. Improving outcomes in stem cell transplant recipients requires additional therapeutic modalities for GvHD, especially for patients who fail to respond to initial therapy with steroids. Moreover, while the absence of acute GvHD (aGvHD) is associated with a higher risk of relapse of the underlying malignant disease, severe aGvHD usually induces the occurrence of life-threatening complications such as severe infections. This article summarizes the current state of aGvHD prophylaxis and treatment.

Herpes simplex virus and oral mucositis in children with cancer

The relationship between herpes simplex virus (HSV) and oral mucositis was investigated in children undergoing antineoplastic chemotherapy. HSV culture was performed in 20 children with stomatitis developing after antineoplastic chemotherapy. Viral isolates were typed and susceptibility to acyclovir was investigated. The virus was isolated from oral lesions in 10 of 20 children with severe oral mucositis. Viral reactivation was the most likely explanation in most cases, since HSV was isolated in 9 of 13 seropositive patients (and in 1 patient with unknown anti-HSV serology), but in no seronegative patient. HSV type 1 was isolated more frequently than HSV type 2 (8 versus 2). Acyclovir showed standard in vitro activity against all isolates. Our results suggest that oral mucositis in children receiving antineoplastic treatment is probably multifactorial in origin and that HSV can be an important cofactor, especially in children who are seropositive for HSV. In our Centre, acyclovir remains active in vitro against this opportunistic pathogen and could be employed in prophylaxis and therapy.

Processing of Human Cord Blood by Three Different Procedures for Red Blood Cell Depletion and Mononuclear Cell Recovery

Background and Objectives: Human cord blood (CB) is an important source of stem cells which may be used for hematopoietic reconstitution as an alternative to bone marrow transplantation. Banking of CB would be accomplished by removing red blood cells (RBC) and plasma from CB collections. Our aim was to compare three different procedures for CB processing. Materials and Methods: Poligeline, hydroxyethyl starch gel (HES) and gelatin were used as separation media in processing 79 CB units for RBC depletion and mononuclear cell (MNC) recovery. Results: The best MNC recoveries were obtained performing the HES– and the gelatin–based procedures (80.9 and 84.7%, respectively), but the gelatin procedure allowed us to obtain the highest RBC depletion (96.4%); CD34+ cell recovery was higher using HES or gelatin as separation media (85.6 and 85.9%, respectively). Conclusion: The best results, as far as RBC removal and MNC recovery are concerned, were obtained by using gelatin as RBC sedimentation medium. Gelatin is a low–cost, animal–derived reagent, which has been successfully used for CB transplantation; the procedure is simple to perform and appears to be suitable for large–scale banking in view of CB transplantation.

Osteochondroma after Hematopoietic Stem Cell Transplantation in Childhood. An Italian Study on Behalf of the AIEOP-HSCT Group

A retrospective study was conducted among Italian children treated with hematopoietic stem cell transplant (HSCT) to evaluate the incidence and risk factors in the development of osteochondroma (OC). OC occurred in 27 patients who received autologous or allogeneic HSCT. The estimated 5-, 10-, and 15-year cumulative risk of developing OC was 0.5%, 3.2%, and 6.1%, respectively. Analysis of cumulative risk stratified by the various risk factors revealed that male sex (P=.026), autologous HSCT (P=.001), age at HSCT (< or =3 years) (P < .0001), and total body irradiation (TBI) (P <.0001) significantly affected the risk of OC. Multivariate analysis, restricted only to tumor types with at least 1 case of OC, showed that earlier age at HSCT (P =.0004) and TBI (P < .0001) were the only factors that were significantly associated with OC.

HIGH-DOSE CISPLATIN AND ETOPOSIDE IN ADVANCED MALIGNANCIES OF CHILDHOOD

Thirty-two children with poor-prognosis solid tumors were treated with a combination of high-dose cisplatin (CDDP) (200 mg/m2 over 5 days) and VP16. In the 30 children evaluable for antitumor effect, there were 7 complete, 12 partial, and 3 minor tumor responses. Wilms tumor and rhabdomyosarcoma responded best. There were no therapy-related deaths. Severe neutropenia (PMN less than 500/mmc) developed after 29 out of the 45 evaluable courses and lasted a median of 8 days; during periods of neutropenia 8 episodes of fever occurred, 1 of which was caused by streptococcal sepsis. Platelet levels were depressed to less than 50,000/mmc after 17/45 cycles and this thrombocytopenia lasted a median of 8 days. No neurological toxicity occurred. One case developed acute renal failure. A hearing deficit for high frequencies was documented in 14/22 patients evaluated after the first cycle and in all cases after the subsequent cycles; the deficits correlated with the total dose of CDDP administered. High-dose cisplatin and VP16 is an effective association in children with advanced cancer, but cumulative dosage is limited by ototoxicity.

SCT for Wilms' tumour

Thanks to advances in treatment, approximately 85–90% of patients suffering from Wilms’ tumour are now cured. However, success rate after relapse is significantly lower, ranging from 25 to 45%. Several different re-induction approaches, more or less intensive according to first-line therapy and characteristics of relapse, have been proposed. A number of adverse prognostic factors related to a bad outcome after relapse have been identified and are used as inclusion criteria for entering in a programme including high-dose chemotherapy (HCT). HCT followed by autologous haematopoietic stem cell rescue has been used in small numbers of patients worldwide and promising results have been reported. Information from the European Group for Blood and Marrow Transplantation Database regarding more than 300 transplants have been gathered. In addition, literature data on rescue therapy and HCT will be discussed, such as recent treatment proposals currently under discussion within European and US cooperative groups.

Feasibility of integrated home/hospital physiotherapeutic support for children with cancer

PurposeChildren suffering from cancer often have to undergo physiotherapy that either extends the duration of in-patient hospitalisation or requires more frequent visits to the outpatient clinic. To improve care and to decrease the length of hospitalisation of children being treated at the Dept. of Haematoloy/Oncology of the Gaslini Children’s Hospital, a programme of Home Care was set up in April 2000.Materials and methodsIn June 2003, rehabilitation was added to the procedures that were feasible at home and included i.v. therapy administration, blood examinations, transfusion and/or psychological support, as well as palliative care for terminally ill children. The physiotherapy sessions were done in the ward, in the Rehabilitation Unit Gym, or at home, depending on the clinical conditions and the needs of the child and the family.ResultsBetween June 2003 and May 2005, 46 children, whose median age was 7xa0years (range 6xa0months–21xa0years) suffering from CNS tumours (13), leukaemia (13), neuroblastoma (7), bone tumours (6), sarcoma (4) and lymphoma (3), underwent 1,398 physiotherapy sessions for neuro-motor re-education (534), motor rehabilitation (485), strain re-education and training (250), respiratory care (79), or to improve comfort during the terminal phase of the disease (50). To maintain continuity of care, the treatments were performed at home (931), in the hospital ward (282), or in the gymnasium of our Physiotherapy Service (185).ConclusionThe physiotherapist was able to start or to continue assistance at home or in the hospital, and to keep up the programme based on the child’s needs. Integrated home/hospital physiotherapy for children suffering from cancer is feasible and is useful for maintaining continuity of treatment without lengthening hospitalisation.

Prophylaxis of streptococcal bacteraemia with oral penicillin V in children undergoing bone marrow transplantation.

The work described aimed to evaluate the incidence of streptococcal bacteraemia in children undergoing bone marrow transplantation and receiving prophylaxis with penicillin V. From January 1991 to December 1993 oral penicillin V was administered as prophylaxis for streptococcal bacteraemia to patients undergoing bone marrow transplantation at G. Gaslini Childrens Hospital, Genoa, Italy. The data were compared with those from a similar population receiving bone marrow transplantation from September 1984 to July 1990 and not receiving this kind of prophylaxis. Streptococcal bacteraemia was diagnosed in 7/17 (41%) episodes of bacteraemia observed in the period January 1991 to December 1993, while it accounted for 71% of all bacteraemias in the period from September 1984 to July 1990 and was especially frequent from January 1988 to July 1990, comprising 13/15 (87%) of observed bacteremias. The decrease of this complication observed after the beginning of the prophylaxis programme was statistically significant. Oral penicillin V is effective as prophylaxis of streptococcal bacteraemias in children receiving bone marrow transplantation in a centre with a high incidence of this complication.

Isolated intracranial metastasis of neuroblastoma 2 years after completion of therapy

Metastatic neuroblastoma in the brain without evidence of intracranial or extracranial disease elsewhere, is a very rare event. The pattern of spread is believed to be via the hematogenous route or cerebrospinal fluid. A child with a cystic neuroblastoma mass in the right temporal lobe 23 months following completion of therapy for the initial disease is described here. Chemotherapy with the protocol ‘eight drugs in 1 day’ was initially effective for this patient.