In myelodysplastic syndromes (MDS), anemia responds to recombinant human erythropoietin (rHuEPO) alone and in combination with recombinant human granulocyte-colony-stimulating factor (rHuG-CSF) in 10% to 20% and in 35% to 40% of patients, respectively. We randomly divided 60 patients with low-grade anemic MDS and serum EPO levels lower than 500 IU/L (500 mU/mL) into 2 groups: rHuEPO ؉ rHuG-CSF (arm A) and supportive care (arm B). After 12 weeks, those who had erythroid responses were given rHuEPO alone for 40 additional weeks.They were also given rHuG-CSF if they had relapses. A response was considered major if the hemoglobin (Hb) level was 115 g/L (11.5 g/dL) or higher and minor Hb increase was 15 g/L (1.5 g/dL) or more or if it remained stable without transfusion. Ten of 24 patients responded in arm A, and 0 of 26 responded in arm B (P ‫؍‬ .01). Eight patients in arm A continued rHuEPO therapy alone, and 6 had relapses. Responses were always restored when rHuG-CSF was reintroduced. IntroductionMyelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by ineffective hematopoiesis, peripheral cytopenia, and increased risk for acute myelogenous leukemia (AML). Approximately two thirds of patients with MDS have anemia at diagnosis, and it develops in nearly all the rest as the disease progresses. Many MDS patients require frequent transfusions, leading to secondary hemochromatosis and risk for viral infections. In low-risk MDS, anemia is often the major clinical problem. Anemia significantly affects quality of life and causes significant morbidity in older patients. Cardiovascular diseases are often aggravated. Treatment of anemia with recombinant human erythropoietin (rHuEPO) alone is effective only in a small percentage of MDS patients. A meta-analysis of 205 patients with MDS showed that 16% responded to rHuEPO alone. 1 Patients who responded to treatment had no or limited transfusion requirements. Granulocytecolony-stimulating factor (G-CSF) and granulocyte macrophagecolony-stimulating factor (GM-CSF) increase neutrophil counts, do not increase the risk for leukemia, and have no effect on survival. [2][3][4] When combined with myeloid cytokines, rHuEPO can have synergistic effects on erythropoiesis in vitro. 5,6 Some clinical studies have shown that the combination of rHuG-CSF and rHuEPO has a better response rate (40%-50%) than rHuEPO alone. [7][8][9][10][11][12] However, none of these clinical trials were randomized, and cost analyses and quality-of-life evaluations are lacking. In one randomized study, the response rate was similar with GM-CSF plus EPO and with placebo 4 In these studies, only a small proportion of subjects with baseline serum EPO concentrations exceeding 500 IU/L (500 mU/mL) responded to treatment. 9 Therefore, we designed a multicenter randomized trial comparing treatment with rHuEPO plus rHuG-CSF and supportive care in patients with MDS who had serum EPO concentrations lower than or equal to 500 IU/L (500 mU/mL) to determine the effect of this Patients, materials...

Summary. Biphenotypic acute leukaemia (BAL) patients represented 8% of the 287 de novo consecutive adult acute leukaemias (23 BAL, 230 acute myeloid leukaemia (AML) and 34 acute lymphoblastic leukaemia (ALL)) referred to our department during the last 4-year period. Of these 23 BAL patients, 14 patients showed myeloid morphology and nine cases lymphoid morphology according to FAB criteria. There were no differences between lymphoid and myeloid BAL according to clinical and biological presentation and treatment outcome. We confirm the poor prognosis of BAL when compared to AML or ALL seen during the same period of time, in terms of complete remission (47%, 62% and 82% respectively, BAL v AML, NS and BAL v ALL, P ¼ 0·006) and 4-year overall survival (8·1%, 25·8% and 23·8% respectively, BAL v AML, P ¼ 0·05 and BAL v ALL, P ¼ 0·003). Comparing adult BAL patients with AML patients, we found an increase in poor prognostic factors: CD34 þ phenotype (82% v 60% respectively, P ¼ 0·03), unfavourable karyotype (60% v 20%, P < 0·0001) and Pgp over-expression by RT-PCR (0·705 v 0·107, P < 0·0001) and flow cytometry (0·824 v 0·391, P ¼ 0·0001). MRP and LRP were not found to be poor prognostic factors. Comparing BAL patients with ALL patients, we found also an increase in poor prognostic factors: age (51 v 39, P ¼ 0·003) and CD34 þ phenotype (82% v 50%, P ¼ 0·02). We conclude that BAL patients need a more aggressive treatment procedure, including high-dose AraC or the use of Pgp modulators for first-line therapy.

A B S T R A C T PurposeTo compare the antitumor efficacy of three different anthracyclines in combination with cytarabine and etoposide in adult patients with newly diagnosed acute myeloid leukemia (AML). Patients and MethodsWe randomly assigned 2,157 patients (age range, 15 to 60 years) to receive intensive induction-consolidation chemotherapy containing either daunorubicin, idarubicin, or mitoxantrone. After achieving complete remission (CR), patients were assigned to undergo either allogeneic or autologous stem-cell transplantation (SCT), depending on the availability of a sibling donor. ResultsThe overall CR rate (69%) was similar in the three groups. Autologous SCT was performed in 37% of cases in the daunorubicin arm versus only 29% and 31% in mitoxantrone and idarubicin, respectively (P Ͻ .001). However, the disease-free survival (DFS) and survival from CR were significantly shorter in the daunorubicin arm: the 5-year DFS was 29% versus 37% and 37% in mitoxantrone and idarubicin, respectively. The proportion of patients who underwent allogeneic SCT (22%) was equivalent in the three treatment groups, and the outcome was similar as well: the 5-year overall survival rates were 34%, 34%, and 31%, respectively. ConclusionIn adult patients with AML who do not receive an allogeneic SCT, the use of mitoxantrone or idarubicin instead of daunorubicin enhances the long-term efficacy of chemotherapy.

The role of glycosylated recombinant human granulocyte colony-stimulating factor (G-CSF) in the induction treatment of older adults with acute myeloid leukemia (AML) is still uncertain. In this trial, a total of 722 patients with newly diagnosed AML, median age 68 years, were randomized into 4 treatment arms: (A) no G-CSF; (B) G-CSF during chemotherapy; (C) G-CSF after chemotherapy until day 28 or recovery of polymorphonuclear leukocytes; and (D) G-CSF during and after chemotherapy. The complete remission (CR) rate was 48.9% in group A, 52.2% in group B, 48.3% in group C, and 64.4% in group D. Analysis according to the 2 ؋ 2 factorial design indicated that the CR rate was significantly higher in patients who received G-CSF during chemotherapy (58.3% for groups B ؉ D vs 48.6% for groups A ؉ C; P ‫؍‬ .009), whereas no significant difference was observed between groups A ؉ B and C ؉ D (50.6% vs 56.4%, P ‫؍‬ .12). In terms of overall survival, no significant differences were observed between the various groups. Patients who received G-CSF after chemotherapy had a shorter time to neutrophil recovery (median, 20 vs 25 days; P < .001) and a shorter hospitalization (mean, 27.2 vs 29.7 days; P < .001). We conclude that although priming with G-CSF can improve the CR rate, the use of G-CSF during and/or after chemotherapy has no effect on the long-term outcome of AML in older patients. (Blood. 2005;106:27-34)

BackgroundThe microenvironment plays a major role in the onset and progression of metastasis. Epithelial ovarian cancer (EOC) tends to metastasize to the peritoneal cavity where interactions within the microenvironment might lead to chemoresistance. Mesothelial cells are important actors of the peritoneal homeostasis; we determined their role in the acquisition of chemoresistance of ovarian tumours.Methodology/Principal FindingsWe isolated an original type of stromal cells, referred to as “Hospicells” from ascitis of patients with ovarian carcinosis using limiting dilution. We studied their ability to confer chemoresistance through heterocellular interactions. These stromal cells displayed a new phenotype with positive immunostaining for CD9, CD10, CD29, CD146, CD166 and Multi drug resistance protein. They preferentially interacted with epithelial ovarian cancer cells. This interaction induced chemoresistance to platin and taxans with the implication of multi-drug resistance proteins. This contact enabled EOC cells to capture patches of the Hospicells membrane through oncologic trogocytosis, therefore acquiring their functional P-gp proteins and thus developing chemoresistance. Presence of Hospicells on ovarian cancer tissue micro-array from patients with neo-adjuvant chemotherapy was also significantly associated to chemoresistance.Conclusions/SignificanceThis is the first report of trogocytosis occurring between a cancer cell and an original type of stromal cell. This interaction induced autonomous acquisition of chemoresistance. The presence of stromal cells within patient's tumour might be predictive of chemoresistance. The specific interaction between cancer cells and stromal cells might be targeted during chemotherapy.