Brigitte Witz

Granulocyte Colony-Stimulating Factor After Intensive Consolidation Chemotherapy in Acute Myeloid Leukemia: Results of a Randomized Trial of the Groupe Ouest-Est Leucémies Aigues Myeloblastiques

PURPOSE Ten years after the first clinical studies, the clinical impact of myeloid growth factors in acute myeloid leukemia is still unclear. One of the objectives of the Groupe Ouest-Est Leucémies Aigues Myeloblastiques (GOELAM) 2 trial was to evaluate the benefit of granulocyte colony-stimulating factor (GCSF) given only after the two courses of intensive consolidation chemotherapy (ICC) used to maintain complete remission (CR). PATIENTS AND METHODS One hundred ninety-four patients who were in CR after induction treatment were randomly assigned to receive G-CSF (100 patients) or no G-CSF (94 patients) after two courses of ICC (ICC 1, high-dose cytarabine plus mitoxantrone; ICC 2, amsacrine plus etoposide). G-CSF (filgrastim) was administered from the day after chemotherapy until granulocyte recovery at a daily dose of 5 microg/kg. RESULTS In the G-CSF group, the median duration of neutropenia (< 0.5 x 10(9)/L) was dramatically reduced, both after ICC 1 (12 v 19 days, P <.001) and after ICC 2 (20 v 28 days, P <.001). The median duration of hospitalization was also significantly shorter in the G-CSF group (24 v 27 days after ICC 1, P <.001; 29 v 34 days after ICC 2, P <. 001). The median duration of intravenous antibiotics was significantly reduced after ICC 1 and ICC 2, and the median duration of antifungal therapy was significantly reduced after ICC 1. However, the incidence of microbiologically documented infections, the toxic death rate, the 2-year disease-free survival, and the 2-year overall survival were not affected by G-CSF administration. Moreover, the median interval between ICC1 and ICC2 was reduced by only 2 days, and the number of patients undergoing ICC2 was not increased in the G-CSF arm. CONCLUSION G-CSF should be administered routinely after ICC to reduce the duration of neutropenia and hospitalization. However, G-CSF did not seem to significantly increase the feasibility of this two-course program or modify overall outcome.

Hematologic recovery after autologous PBPC transplantation: importance of the number of postthaw CD34+ cells†

BACKGROUND: The implementation of a quality‐assurance program is a major requirement to ensure quality and safety of the final PBPC components intended for clinical use. It is not clear whether the quantification of CFU‐GM and CD34+ cells should be done on fresh components and after cryopreservation, which better represents the actual composition of the graft.

Early matched sibling hematopoietic-cell transplantation for adult AML in first remission using an age-adapted strategy: long-term results of a prospective GOELAMS study

The LAM2001 phase 3 trial, involving 832 patients with acute myeloid leukemia (AML; median: 46 years) proposed HLA-identical sibling allograft HSCT for all patients with an identified donor. The trial compared reduced-intensity conditioning (RIC) for patients older than 50 years of age (N = 47) and myeloablative conditioning for younger patients (N = 117). BM HSCT was performed in the younger patients, while the older ones received a consolidation course, followed by peripheral blood allo-HSCT using RIC. The incidence of grade II-IV acute GVHD, was 51.9% (95% confidence interval [CI]: 42.1-61.8) and 11.3% (1.6-21.2) after myeloablative or RIC, respectively (P < .0001) and that of chronic GVHD 45.8% (95% CI: 34.8-56.7) and 41.7% (24.7-58.6; NS). Cumulative incidence of nonrelapse mortality at 108 months was 15.8% (95% CI: 9.8-23.2) for myeloablative, and 6.5% (0.2-16.2) for RIC (NS). CI of relapse at 108 months was 21.7% (95% CI: 13.9-28.6) and 28.6% (16.5-43.4; NS). Overall survival at 108 months was 63.4% (95% CI: 54.6-72.2) and 65.8% (52.2-72.2), respectively, after myeloablative or RIC (NS). RIC peripheral blood stem cell allo-HSCT is prospectively feasible for patients between the ages of 51 and 60 years without excess of relapse or nonrelapse mortality, and compares favorably with myeloablative marrow allo-HSCT proposed to younger patients.

Persistence of lymphocyte function perturbations after granulocyte–colony‐stimulating factor mobilization and cytapheresis in normal peripheral blood stem cell donors

BACKGROUND: The short‐term effects of granulocyte–colony‐stimulating factor (G‐CSF) have been extensively studied, but recent reports of G‐CSF–induced genetic perturbations raised concerns regarding its long‐term safety. In this respect, duration of G‐CSF–induced perturbations has been less studied than short‐term effects and needs to be evaluated.

G-CSF-induced aneuploidy does not affect CD34+ cells and does not require cell division.

To the editor: Lymphocytes from granulocyte colony-stimulating factor (G-CSF)–mobilized donors display epigenetic and genetic alterations similar to those observed in leukemia patients.[1][1] To further evaluate the scope and duration of G-CSF–induced genetic alterations, 24 healthy donors were

Thawed autologous peripheral blood stem cells require modified quantification methods for hematopoietic progenitor cell evaluation

BACKGROUND AND OBJECTIVES The aim of this study was first, to analyze the post-thaw progenitor assays usually performed on peripheral blood stem cell autografts and second, to achieve standardization with improved flow cytometric and CFU-GM assays. MATERIALS AND METHODS In the first part of the study (n=79), recovery and Intraclass Correlation Coefficient (ICC) of total nucleated cells, CD34 and CFU-GM were analyzed before and after cryopreservation. In the second part (n=20), evaluation methods were modified : the washing step was suppressed in the flow cytometric method and 500 CD34 were plated compared to 4×10(4) total nucleated cells in the CFU-GM assay. The recovery rates were analyzed and the CFU-GM results were regarded as reliable when 30-100 colonies were observed, according to the manufacturer recommendation. RESULTS The analysis of the first part showed an ICC that was perfect for total nucleated cells (0.93), substantial for CD34 (0.67) and fair for CFU-GM (0.25). Median CD34 recovery was 112.6% (29.9-222%). The CFU-GM median recovery was 31.7% (0.19-142%) leading to reliable results for 27 grafts. In the second part, the median CD34 recovery was 85.75% (54-99%). No recovery over 100% was observed. The CFU-GM assay led to 18 out of 20 evaluable autografts when 500 CD34 were seeded, compared to 10 out of 20 when total nucleated cell were seeded. CONCLUSION Avoiding cell washing in the flow cytometric method limited the overestimate of the CD34 percentage. Plating 500 thawed CD34 improved reliability of the results and allowed a better standardization of the assay.