ESHAP versus rituximab-ESHAP in frail patients with refractory diffuse large B-cell lymphoma.

BACKGROUND: Treatment for refractory lymphoma in frail patients (older, poor performance status, or concomitant diseases) has not been defined. PATIENTS AND METHODS: A total of 100 frail patients naive to rituximab therapy were allocated to be treated with ESHAP (etoposide, methylprednisolone, cytosine arabinoside, and platinum; 53 patients) or RESHAP (rituximab plus ESHAP; 47 patients). Granulocyte colony-stimulating factor was used to ameliorate the presence of severe granulocytopenia. RESULTS: Overall response rate (ORR) and complete response (CR) were similar among ESHAP and R-ESHAP (ORR, 33 patients [62%] and 28 patients [60%], respectively; CR, 20 patients [37%] and 18 patients [36%], respectively). Actuarial curves at 5 years showed that progression-free survival (PFS) and overall survival (OS) were similar: 51% and 31% in the ESHAP arm and 50% and 26%, respectively, in R-ESHAP. Toxicity was severe in both groups; grade 4 granulocytopenia was observed in 30% and 32% of ESHAP and R-ESHAP arms, respectively. Viral infections were more frequent in R-ESHAP (52 cases) than in ESHAP (3 cases). CONCLUSION: Frail patients, who generally have not been accepted in controlled clinical trials, can be treated with aggressive chemotherapy because tolerance is well and improvement in outcome is feasible. Although ESHAP retains the clinical efficacy previously reported in nonfrail patients, the addition of rituximab did not improve response rate, PFS, or OS.

In vitro proliferation and expansion of hematopoietic progenitors present in mobilized peripheral blood from normal subjects and cancer patients.

In the present study, we have assessed, in a comparative manner, the in vitro proliferation and expansion potentials of hematopoietic progenitor cells (HPC) present in mobilized peripheral blood from normal subjects (MPB-n; n = 18) and cancer patients (MPB-c; n = 18). The latter included patients with breast cancer (BrCa; n = 8), Hodgkin disease (HD; n = 4), non-Hodgkin lymphoma (NHL; n = 3), and acute myeloid leukemia (AML; n = 3). Progenitor cells from normal bone marrow (BM) and umbilical cord blood (UCB) were included as controls. HPC, enriched by a negative selection procedure, were cultured for 25 days, in serum-free liquid media in the presence of a cytokine combination including early- and late-acting cytokines. Our results demonstrate that the in vitro biological properties of progenitor cells present in MPB differ, depending on whether they are derived from healthy individuals, from patients with solid tumors, or from patients with hematological neoplasias. Among all cell sources analyzed, UCB-derived progenitors showed the greatest proliferation and expansion potentials (1000-fold increase in total cell numbers on day 15, and a 22-fold increase in myeloid progenitor cell numbers, at day 10). Progenitor cells present in MPB from hematologically normal individuals showed proliferation and expansion potentials comparable to those of HPC from normal BM (500-fold increase in total cell numbers on day 15, and a 14-fold increase in myeloid progenitor cell numbers, at day 10). The proliferation/expansion potentials of MPB progenitors from BrCa patients were also within the normal range, although in the lower levels (327-fold increase in total cell numbers, on day 15, and 11.8-fold increase in myeloid progenitors, at day 10). In contrast, progenitors present in MPB from patients with HD, NHL, and especially AML, showed reduced in vitro capacities (119-, 102-, and 51-fold increase in total cell numbers, respectively; and 8-, 4-, and 2.6-fold increase in myeloid progenitor cells, respectively). To our knowledge, this is the first report in which the in vitro proliferation and expansion potentials of HPC from MPB from normal subjects and cancer patients are assessed simultaneously in a comparative manner.