Summary:There is limited experience on engraftment syndrome (ES) in children. The present study analyzes the characteristics of ES in pediatric patients undergoing autologous peripheral blood progenitor cells transplantation (PBPCT). From 1993 to 2001, 30 of 156 patients (19.2%) who underwent PBPCT developed ES (skin rash which involved more than 27% of the body surface and temperature Ͼ38.3؇C with no compatible infectious disease etiology, during neutrophil recovery). Of the 30 patients who developed ES, 20 (66%) developed hypoxia and/or pulmonary infiltrates, seven (23%) had hepatic dysfunction, six (20%) developed renal insufficiency, 16 (53%) showed weight gain and three (10%) experienced transient encephalopathy. Multivariate analysis showed that the only positive predictive factor for developing ES was mobilization with high-dose G-CSF (12 g/kg twice daily) (RR 3.88, CI 95% 1.73-8.67; P Ͻ 0.0005). The overall transplant-related mortality (TRM) was 8.33% and this was significantly higher in the patients who developed ES than in those who did not (23% vs 4.76%; P Ͻ 0.0001). We also found a higher morbidity in patients who developed ES, expressed as a statistically significant increase in supportive care (transfusion requirement, parenteral nutrition) and increase in the length of hospital stay. In summary, we have found ES to be the most important cause of morbidity and mortality in children undergoing autologous PBPCT.

Summary:This paper presents a state-of-the-art review of using mobilized-peripheral blood progenitor cells (PBPC) for transplantation in children. Our own data and those from Medline searches and meeting reports, are analyzed and presented for the different sections that involve transplantation. Recommendations concerning the choice of mobilization regimens, venous access, priming of separator extracorporeal line, anticoagulation, and number of CD34 + cells to infuse for rapid engraftment are proposed. In the allogeneic setting, we analyze ethical and safety aspects of pediatric donor mobilization and collection. Data from the literature suggest that the use of cytokine-mobilized PBPC for allogeneic transplantation appears to be safe both for pediatric donors and patients leading a rapid hematopoietic engraftment with a similar incidence of acute graftversus-host disease (GVHD). The high incidence of chronic GVHD and its management emerge as the most concerning aspect in allogeneic PBPC transplantation. Bone Marrow Transplantation (2000) 26, 1291-1298.

Summary:We conducted a prospective pilot study to assess the feasibility and safety of high-dose busulfan/melphalan as conditioning therapy prior to autologous PBPC transplantation in pediatric patients with high-risk solid tumors. From January 1995 to January 1999, 30 patients aged 2-21 years (median 8) were entered into the study. There were 14 females and 16 males. Diagnoses included neuroblastoma in 10 patients; Ewing's sarcoma and peripheral neuroectodermal tumor (PNET) in 15 patients and rhabdomyosarcoma in five patients. Treatment consisted of busulfan 16 mg/kg, orally over 4 days (from days ؊5 to ؊2) in 6 hourly divided doses, and melphalan at a dose of 140 mg/m 2 given by intravenous infusion over 5 min on day ؊1. G-CSF mobilized PBPC were used as autologous stemcell rescue. One patient developed a single generalized convulsion during busulfan therapy. The most relevant non-hematologic toxicity was gastrointestinal, manifesting as grade 2-3 mucositis and diarrhea in 12 patients. Two patients died of procedure-related complications, one from veno-occlusive disease of liver and multiorgan failure and the other from adult respiratory distress syndrome. Probability of treatment-related mortality was 6.6 ؎ 4.5%. With a median follow-up of 18 months (range, 1-48), 19 patients are alive and disease-free, the actuarial EFS at 4 years being 55 ؎ 12% for the whole group. We conclude that high-dose busulfan/melphalan for autologous transplantation in children with solid tumors is feasible even in small patients. It is well-tolerated, with an acceptable transplant-related mortality and has proven antitumor activity. Keywords: busulfan/melphalan; solid tumors; PBPC transplantation; children Children with advanced or recurrent solid tumor have a poor prognosis. High-dose chemotherapy followed by autologous hematopoietic cell rescue has improved this situation. 1 introduced as consolidation for pediatric patients with highrisk relapsed solid tumors. 2 However, the best conditioning regimen has not yet been established. High-dose chemotherapy regimens should consist of one or several agents that have dose-response-related anti-cancer activity and do not have overlapping extra-hematological toxicities. Busulfan is currently used at high doses in preparative regimens for hematopoietic transplantation. Liver toxicity is doselimiting for busulfan as a single agent. 3 Melphalan has demonstrated activity in high doses for relapsed or refractory solid tumors in children and its primary toxicity is myelosuppression. 4-5 A preparative regimen based on highdose busulphan and melphalan has been used for transplantation in patients with hematological malignancies in adults with low toxicity. 6-8 Based on previous experience, we conducted a pilot study to assess the feasibility and safety of high-dose busulfan and melphalan as conditioning therapy followed by mobilized peripheral blood progenitor cell (PBPC) support in pediatric patients with high-risk solid tumors. Patients and methods Patients

Summary:This multicenter study was designed to evaluate whether allo-PBPCT provides some advantages, if any, over BMT in terms of engraftment kinetics, acute and chronic GVHD incidence, TRM, relapse incidence and survival in acute lymphoblastic leukemia patients (ALL). From January 1995 to December 1999, 67 ALL patients (34 in the PBPCT group and 33 in the BMT group) were included in this study. Median age for both groups was 8 years (range, 1-18). There were 24 patients in first or second CR in the PBPCT group and 28 such patients in the BMT group. Preparatory regimens were TBI-based in 26/34 in the PBPC group and 25/33 in the BMT group. GVHD prophylaxis was CsA alone in 38 patients (18 PBPCT vs 20 BMT) and CsA plus short Mtx in 29 (16 PBPCT vs 13 BMT). Engraftment was achieved in all cases. Median days to neutrophil recovery was 10 (range, 7-18) after PBPCT vs 14 (range, 9-21) after BMT (P Ͻ 0.0001). Platelet engraftment (Ͼ50 ؋ 10 9 /l) was also faster for PBPCT patients (median 13 days, range, 9-40 vs 23 days, range, 15-165) (P Ͻ 0.0001). Acute GVHD grade II-IV incidence was similar in both groups (46.4 ؎ 8.8% vs 42.7 ؎ 8.6%) (P ‫؍‬ 0.45). Probability of chronic GVHD was 50.6 ؎ 12.2% after PBPCT vs 27.8 ؎ 9.2% after BMT (P ‫؍‬ 0.1). Probability of relapse was similar (28.7 ؎ 9.2% for PBPCT vs 27.1 ؎ 8.2% for BMT) (P ‫؍‬ 0.89). There were eight patients who died from transplantrelated complications after PBPCT vs 5 after BMT (P, NS). With a median follow-up of 25 months the eventfree survival probability was 53 ؎ 8.9% for PBPCT vs 54.9 ؎ 9.7% for BMT (P ‫؍‬ 0.54). Using PBPC for allogeneic transplantation in childhood ALL results in faster hematopoietic recovery compared to BM, with a similar incidence of aGVHD, TRM, relapse and disease-

Pseudotumor cerebri, an uncommon complication following BMT, has been generally associated with cyclosporin A neurotoxicity. However, it has not previously been reported as a clinical presentation of sinusitis in spite of its high incidence after BMT. We report a case of pseudotumor cerebri secondary to sinusitis in a child with acute lymphoblastic leukemia and who underwent unrelated bone marrow transplantation.