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Ancestim (r-MetHuSCF) is available in France for compassionate use in patients who are candidates for high-dose chemotherapy and autologous transplantation, and who failed in previous attempts at mobilization and collection. We report here data from 513 adult patients who benefited from this program, between January 1998 and July 2007. Given with systematic premedication, ancestim was generally well tolerated, although severe but not life-threatening adverse events were reported in 12 individuals. Overall, a graft was obtained or completed for 235 patients (46%). The median number of collected CD34+ cells was 3.00 × 106/kg (range: 0.03-39.50). The target threshold of 2 × 106 CD34+ cells/kg was reached in 161 patients (31%). Factors associated with collection were diagnosis of myeloma, no previous autologous transplant, no more than one previous failed attempt and a mobilization regimen including cytotoxic agents. A total of 207 patients (40%) proceeded to high-dose chemotherapy and autologous transplantation. The median time to reach 0.5 × 109/L neutrophils and 20 × 109/L platelets was 12 (6-40) and 13 (0-31) days, respectively. We conclude that a combination of ancestim with filgrastim successfully mobilized CD34+ cells in peripheral blood, and allowed adequate collection in preparation for autologous transplantation in approximately one-third of poorly mobilizing patients. [ABSTRACT FROM AUTHOR]

Cord blood (CB) units are increasingly used for allogeneic transplantation. Cell dose, a major factor for CB selection, is evaluated before freezing by each CB bank, using various techniques. This may introduce variability and affect the prediction of cell recovery after thawing, or haematopoietic reconstitution. Forty-two children were transplanted at the same institution with unrelated CB units. All units were thawed and evaluated at the same cell therapy facility, using standard procedures. We investigated: (i) factors that affect cell loss after thawing, and (ii) the importance of CD34+ cell doses. Prefreeze and post-thaw CD34+ cell doses were statistically correlated, thus suggesting that variability in numeration techniques used by different CB banks does not compromise the biological and clinical value of these figures. CD34+ cell recovery appeared to be correlated with the absolute number of CD34+ cells per frozen bag. Infused CD34+ is the cell dose that better correlates with platelet reconstitution delay; in addition, when using a quartile comparison, haematopoietic recovery appeared to be related with prefreeze and post-thaw CD34+ cell doses. We conclude that enumeration of CD34+ cells in CB units is of biological significance, and may help select CB units and identify patients at risk of delayed recovery.Bone Marrow Transplantation (2007) 39, 453–460. doi:10.1038/sj.bmt.1705618; published online 5 March 2007 [ABSTRACT FROM AUTHOR]

Since low T cell counts evaluated 1 month after allogeneic bone marrow transplantation (BMT) are associated with an increased risk of leukemia relapse (Powles et al., Blood 1998; 91: 3481–3486), we compared, in a randomized multicentric clinical study, the peripheral blood cells obtained 30 days after allogeneic BMT vs allogeneic G-CSF-mobilized peripheral blood stem cell transplantation (BCT) in an HLA-identical setting. T cell counts were higher 30 days after BCT (718 ± 142 cells/μl, n = 20) than after BMT (271 ± 53 cells/μl, n = 26, P = 0.006). However, T cells were less activated after BCT than after BMT, as demonstrated by a lower expression level of CD25 and a lower percentage of HLA-DR+ and CD95+ T cells. Furthermore, CD4+, CD8+and CD45RA+ post-BCT T cell counts correlated with the number of cells infused with the PBSC graft, while such a correlation was not observed between post-BMT counts and BM graft cell numbers, suggesting that the intensity of post-transplant peripheral lymphoid expansion and/or deletion differed between BCT and BMT. A comparison of the input of T cells expressing different CD45 isoforms with the post-transplant cell recovery further confirmed that, within the CD4+ T cell subset, post-transplant expansions occurred at a higher level after BMT than after BCT, affecting mainly the CD4+ CD45RO+subset. Altogether, our data demonstrate for the first time in a randomized setting that homeostasis of the T cell pool is less altered early after BCT than after BMT. This may have a strong impact on the graft-versus-leukemia (GVL) effect and subsequent relapse rate. Bone Marrow Transplantation (2001) 27, 167–175. [ABSTRACT FROM AUTHOR]

Although infants with stage 4 neuroblastoma (NB) usually have a good prognosis, metastatic relapses after 1 year of age and amplification of the N-myc oncogene are established poor prognostic factors. In order to improve the survival of patients with such high-risk factors, we performed consolidation with a busulfan (600 mg/m2)-melphalan (140 mg/m2)-containing regimen followed by autologous stem cell transplantation (SCT). From 1986 to 1998, 12 patients were treated according to this strategy. Their median age at diagnosis was 9 months (1–11). Consolidation was performed after a metastatic relapse in five children, because of persistent bone metastases in one and as first-line consolidation in six patients whose tumor exhibited N-myc amplification. The 5-year EFS rate is 64.5% (36–85%) with a median follow-up of 92 months (20–126). One toxicity-related death occurred in a very heavily pretreated patient. Hepatic veno-occlusive disease was the major side-effect that occurred in nine of 12 children. This busulfan-melphalan combination appears to dramatically improve the prognosis of these high-risk infants with metastatic NB. Given its high toxicity, indications for this consolidation must be restricted to high-risk infants and a lower dose of busulfan (480 mg/m2) is recommended in children weighing less than 10 kg. Bone Marrow Transplantation (2000) 25, 937–942. [ABSTRACT FROM AUTHOR]

Allogeneic peripheral blood hematopoietic stem cell transplantation (PBSCT) is presently being evaluated in a French randomized study comparing peripheral blood vs bone marrow. cases of potentially lethal acute hemolysis have recently been reported after allogeneic pbsct in the presence of a ‘minor’ abo incompatibility. patients were frequently transfused with recipient-compatible and donor-incompatible rbc and usually did not receive methotrexate in addition to cyclosporin a for graft-versus-host disease (gvhd) prophylaxis. in order to homogenize immuno-hematological (ih) assessment and transfusion practices within our protocol, we made proposals to 25 allo-transplant french centers on the following aspects: pre-inclusion ih assessment, ih exclusion criteria, transfusion rules, post-transplant ih surveillance and treatment of hemolysis. analysis of responses to our proposals led to the elaboration of guidelines which were approved and implemented by the french bone marrow transplantation society (sfgm). pre-inclusion ih testing includes mandatory detection and titration of anti-rbc allo-ab, as well as titration of anti-a and anti-b ab. the presence in the donor of an anti-a (group a or ab recipients), anti-b (group b or ab recipients) ab with a titer >1/32 or the presence of allo-Ab against Rh, Kell, Fya, Fyb, Jka, Jkb, Ss Ag present on recipient RBC is an exclusion criterion for the protocol. ABO and RhD compatibility of RBC blood products with both HSC donor and recipient is mandatory. A similar compatibility is also required for Rh (other than D) and Kell Ag. If not possible, compatibility of RBC blood products with the HSC donor is mandatory. Lastly, guidelines regarding post-transplantation IH follow-up as well as acute hemolysis treatment have been elaborated. The implementation of these guidelines should contribute to enhancing the quality of transfusion practice after PBSCT. Such an approach will be applied to other aspects of transfusion... [ABSTRACT FROM AUTHOR]

The purpose of this paper is to study prognostic factors in neuroblastoma patients treated with high-dose chemotherapy and hematopoietic stem cell transplantation. Two hundred and eighteen children over 1 year of age and treated for stage 4 neuroblastoma were enrolled in this study. The median age at diagnosis was 39 months, the sex ratio 1.5 and 84% of patients had an abdominal primary tumor. Skeletal disease was detected in 79% of cases and bone marrow involvement in 93%. N-myc oncogene amplification was present in 27% of the patients studied. The probability of event-free survival at 5 years post-diagnosis was 29% in this series. Three major favorable prognostic factors were significant and independent in the multivariate analysis: age under 2 years at diagnosis (P < 0.01), absence of bone marrow metastases at diagnosis (P < 0.04) and the high-dose conditioning regimen containing busulfan–melphalan combination (P = 0.001). The quality of response to conventional primary chemotherapy was close to significance (P = 0.053). We conclude that factors related to the patient (age) and extent of disease are predictive of outcome in patients with neuroblastoma treated with conventional chemotherapy followed by surgical excision of the primary and consolidation with high-dose chemotherapy. They should be taken into account in future prospective studies. Moreover, the type of conditioning regimen appears to be the most important prognostic factor. This should encourage new investigations into innovative drug combinations. [ABSTRACT FROM AUTHOR]

From 1987 to 1995, 22 children with refractory solid tumors entered a phase II study of high-dose thiotepa (HDT) (900 mg/m2) followed by stem cell transplantation (SCT) in the Pediatrics Department of the Institut Gustave Roussy. Tumor types were rhabdomyosarcoma (eight), osteosarcoma (seven), neuroblastoma (three), Ewing’s sarcoma (three) and Burkitt’s lymphoma (one). Before HDT, all had been extensively treated with conventional chemotherapy, surgical resection of the primary tumor (13/22) and of metastases (6/22), and radiotherapy of the primary tumor in three patients. All had measurable disease, at the site of the primary tumor (3 patients), of the metastases (9 patients) or both (10 patients). Toxicity from the HDT was severe but acceptable. No toxicity-related death occurred. The median duration of neutropenia and thrombocytopenia was 18 days (5–37) and 30 days (7–377), respectively. Septicemia was documented in four patients. Severe diarrhea was observed in seven patients. Mild hepatic toxicity occurred 18 times. No CR and 11/22 PR were documented: osteosarcoma 4/7, rhabdomyosarcoma 4/8, Ewing’s sarcoma 2/3; 1/1 Burkitt’s lymphoma progressed. We conclude that at a dose of 900 mg/m2 followed by SCT support in these heavily pretreated children, the main toxicity induced by thiotepa was digestive. The response rate observed, especially in sarcoma, is particularly encouraging. Thiotepa should be further evaluated in HDC regimens either in combination with other alkylating agents or in rapidly cycled courses of HDC with SCT. [ABSTRACT FROM AUTHOR]