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The literature contains a substantial amount of information about factors that adversely influence the linear growth in up to 85% of patients undergoing haematopoietic SCT (HSCT) with TBI and/or cranial irradiation (CI) for acute leukaemia (AL). By contrast, only a few studies have evaluated the impact of growth hormone (GH) therapy on growth rate and final height (FH) in these children. We evaluated growth rates during the pre- and post-transplant periods to FH in a group of 25 children treated with HSCT (n=22), TBI (n=21) or/and CI (n=8) for AL and receiving GH therapy. At the start of GH treatment, the median height Z-score was -2.19 (-3.95 to 0.02), significantly lower than at AL diagnosis (P

International audience; Our purpose was to assess success rates in children of achieving optimal hematopoietic progenitor cells (HPCs) harvest after mobilization with 300 microg/kg pegfilgrastim. Between January 2005 and January 2007, 26 children with solid malignancies who were referred for HPC collection were consecutively included. Hematopoietic progenitor cell mobilization consisted of one s.c. injection of 300 microg/kg body weight (BW) of pegfilgrastim. The success criterion was defined as at least 5 x 10(6) CD34+ cells/kg during the first standard apheresis (less than 3 blood volumes processed (BVP)). After 26 inclusions, the Bayesian analysis gave a mean estimated success rate of 60.7% (95% credibility interval: 42.0-78.0%). The first apheresis allowed the collection of 8.3 x 10(6) CD34+ cells/kg BW (range 0.6-37.8), with a median of 2.8 BVP (range 1.4-3.0). Overall, the median of CD34+ cells collected was 12.4 x 10(6)/kg (range 2.7-37.8). The cumulative dose of anthracyclin was the only variable associated with the total number of CD34+ collected cells (P or =3 occurred. We conclude that a single injection of 300 microg/kg pegfilgrastim in the hematological steady state is an efficient and well-tolerated method of HPC mobilization in children with solid malignancies.

New concepts of allogeneic hematopoietic SCT (allo-HSCT) for neuroblastoma and other solid tumors do not rely on escalation of chemotherapy intensity and tumor load reduction but rather on a graft-vs-tumor effect. At this point, this is still an investigational and unusual application of allogeneic transplant, with 78 neuroblastoma patients reported to the European Group for Blood and Marrow Transplantation activity survey from 2002 to 2007 and less than 100 published cases. Two trends can be observed in the reviewed data: some teams have used allo-HSCT in children with refractory or progressive disease and significant tumor burden and other teams in children with CR, PR or minimal residual disease earlier in their disease process. Early studies of allo-HSCT in children with high-risk neuroblastoma suggest that this is a feasible approach that may improve outcome in this deadly disease. However, the proper timing for allo-HSCT during the disease course remains to be determined.

The kinetics of peripheral blood progenitor cell (PBPC) release induced by G-CSF-alone at 10 μg/kg/day were monitored daily in 42 children with solid tumors and leukemias. Median 16- and 27-fold enrichment of circulating CD34 + cells and granulocyte-macrophage colony-forming units (CFU-GM) was noted with peak values occurring after the 4th or the 5th G-CSF dose. Individual values of PBCD34 + cell levels in patients with solid tumors were not significantly different after the 4th and after the 5th dose. The day-of-collection PBCD34 + cell concentration was related to the harvested CD34+ cell (P = 0.0001) and CFU-GM numbers (P = 0.0001). No correlations were found between PBPC enrichment and either patient age, body weight, diagnosis or pre-mobilization treatment duration. The median numbers of 1.1 X 10 6 CD34 + cells/kg and 28.1 x 10 4 CFU-GM/kg were derived from one patient's blood volume processed. Nineteen patients received G-CSF-alone primed grafts and had successful engraftment. Our data indicate that in 88% of children a single standard leukapheresis is sufficient to obtain a minimum graft (2 x 10 6 CD34 + cell and/or 10 x 10 4 CGU-GM per kg) whether undertaken after the 4th dose of G-CSF or the 5th.

To evaluate the feasibility and efficacy of CD34+ cell immunoselection from routine peripheral blood stem cell (PBSC) harvests in very small children a prospective study was performed in 15 children with advanced neuroblastoma weighing 20 kg or less. Products of two consecutive leukaphereses carried out on a COBE Spectra separator after G-CSF alone mobilization were pooled for immunoselection on Ceprate column. The median number of CD34+ cells and total CFU-GM collected were respectively 5.9 x 10(6)/kg (range 2.3-23.4) and 126.9 x 10(4)/kg (range 52.9-559.9). After separation the median number of CD34+ cells in the adsorbed fraction was 2.6 x 10(6)/kg (range 1-9.8) with a median purity of 54% (range 21-82) and a median of 95.7-fold (range 35-250) enrichment. Thirteen patients underwent autografts with CD34+ PBSCs after a busulfan 600 mg/m2 + melphalan 180 mg/m2 preparative regimen. The median number of days to achieve an absolute granulocyte count of 0.5 x 10(9)/l and a platelet count of 20 x 10(9)/l were respectively, 12 (range 10-24) and 35 (range 25-43). The median number of platelet transfusions was nine (range 2-15). We conclude that safe and effective immunoselection and transplantation of CD34+ PBSC can be accomplished in children with low body mass.

Pediatric experience with extracorporeal photochemotherapy (ECP) for graft-versus-host disease (GvHD) has mainly been reported by Italian and French groups. Data concerning 41 children with acute GvHD and 63 children affected by chronic GvHD are available. In 73 and 63% of them, respectively, improvement was observed, with addition of ECP to their immunosuppressive regimen. Treatment with ECP was associated with minimal side effects, even in the smallest of patients. In all responded pediatric patients, both with acute and chronic GvHD, ECP allowed progressive reduction or discontinuation of the concomitant pharmacological immunosuppressive therapy without an increase in GvHD acitivity. These data show that ECP is a useful therapy for children affected by GvHD resistant to conventional treatment and can be safely used.

The purpose of this multicenter study was to compare the long-term impact of a preparative regimen with either BUBU or TBI on health status and quality of life (QoL) in childhood acute leukemia survivors treated with hematopoietic SCT (HSCT). Two-hundred and forty patients were included. Sixty-six had received BU, while 174 had received TBI. Median follow-up from HSCT was 10.1 years. Multivariate analyses were performed to assess the occurrence of late effects according to treatment. QoL was assessed in 130 adults using SF-36 questionnaires. Patients developed fewer late complications after BU (2.35 vs 3.01, P=0.03) while the risk to present with at least one complication was equivalent in both groups (87.9% after BU and 93.1% after TBI, P=0.66). Detailed multivariate analyses revealed a lower risk of height growth failure (OR=0.2), cataract (OR=0.1) and iron overload (OR=0.2) after BU, and an increased risk of overweight (OR=3.9) and alopecia (OR=11.2). SF-36 mental and physical composite scores were similar in both treatment groups and proved significantly lower than French norms. Late effects induced by BU might differ from those experienced after TBI. Although less frequent, they are still of considerable importance and may affect patients' QoL.

We report French prospective experience with reduced-intensity conditioning-allo-SCT in 46 patients (median age: 15.5 years, 4.8-20.2) presenting high-risk AL (n=11), Hodgkin's lymphoma (n=15) or solid tumors (n=20). Graft sources were BM (n=21), PBSC (n=20) and cord blood (CB; n=5) from related (n=20) or unrelated (n=26) donors. For CB grafts, only one patient out of five achieved sustained engraftment. For PBSC/BM grafts, engraftment rate was 95%, hematopoietic recovery times were not significantly different between BM, PBSC, sibling or unrelated grafts, day+100. Full donor chimerism was achieved in 94% of patients, and incidences of primary acute GVHD and chronic GVHD were 49% and 14%, respectively. Underlying disease was fatal in 39% of patients. TRM was 6.9%. Three-year OS was 49.15%. OS and EFS were not significantly different between patients transplanted with different grafts and with or without primary GVHD. Patients with solid tumor or measurable disease at transplant had poorer outcomes. Three-year EFS: 33.3% for ALL, 75.0% for AML, 51.8% for Hodgkin's lymphoma, 28.6% for neuroblastoma and 22.2% for sarcoma patients. This multicentre study concluded that Bu/fludarabine/anti-thymocyte globulin conditioning with PB or BM, related or unrelated grafts in patients with various malignancies at high-risk for transplantation toxicity results in high engraftment rates, low TRM and acceptable survival.

Peripheral blood CD34+ cell samples from eight children with advanced neuroblastoma and from 10 healthy adult donors were seeded at 5 x 10(4) cells/ml in stroma-free, serum-free medium with FL, SCF, MGDF (100 ng/ml each), G-CSF, IL6 (10 ng/ml each) and IL3 (5 ng/ml), and incubated for 10 days. The levels of expansion of PBCD34+ cells observed in neuroblastoma patients, with up to 214-fold expansion for total nucleated cells, 39-fold for CD34+ cells, 79-fold for CFU-GM and nine-fold for LTC-IC were identical to those obtained with PBCD34+ cells of healthy donors (P/=0.5). All samples from patients with neuroblastoma and five donor's PBCD34+ cell samples contaminated with IMR-32 neuroblasts, were screened for the number of tyrosine hydroxylase (TH) mRNA transcript using LightCycler software. In all samples, progressive 1.9-4.4 log decreases in the number of TH transcripts were observed between days 0 and 10 of expansion. Our results show that in extensively pretreated children with neuroblastoma, the culture conditions that were effective for BM and CB cell expansion can generate an expansion of PBCD34+ cells and provide a purge of tumour cells.

To assess the place of allogeneic hematopoietic stem cell transplantation (HSCT) in the advanced stage of acute myeloid leukemia (AML), we retrospectively analyzed 379 consecutive patients who underwent allogeneic HSCT for advanced AML. The median follow-up of the entire cohort was 7.5 years. Sixty-nine patients (18%) were transplanted with primary resistant disease. Three hundred and ten (82%) were relapsed patients, 94 (30%) of whom were in untreated relapse, 67 (22%) in refractory relapse and 149 (48%) in 2nd or 3rd complete remission at time of transplantation. The 5-year probabilities of overall survival (OS), disease-free survival (DFS), and transplant-related mortality (TRM) were 22 ± 4% 20 ± 4%, 45 ± 6%, respectively. In multivariate analysis, we demonstrated the favorable impact on OS, DFS and TRM of two factors over which we have no control (age

Immunological and molecular detection of tumor contamination in leukapheresis products from children with disseminated neuroblastoma: implication for evaluation of tumor cell depletion after CD34 selection