Negative immunomagnetic ex vivo purging combined with high-dose chemotherapy with peripheral blood progenitor cell autograft in follicular lymphoma patients: evidence for long-term clinical and molecular remissions.

The feasibility and efficacy of a novel immunomagnetic ex vivo negative purging method was evaluated on peripheral blood progenitor cells (PBPC) from 13 non-Hodgkin's lymphoma patients (eight follicular, FL; three mantle cell, MCL; two FL with histologic transformation). A peculiar feature of the study was the collection of PBPC after prolonged tumor debulking. Our method included a stem cell enrichment phase followed by cell incubation with anti-B cell MoAbs (anti-CD19, CD20, CD22, CD23), addition of immunobeads, and then positive cell removal by passage on a Max-Sep (Baxter Immunotherapy) cell separator.

In vitro growth and quantification of early (CD33-/CD38-) myeloid progenitor cells: stem cell factor requirement and effects of previous chemotherapy.

Background And Objective: All culture systems exploring the early (pre-CFU) hematopoietic compartment are generally complex, time-consuming and unsuitable for routine application. The aim of our study was to develop a stroma-free culture system to quantify early bone marrow (BM) myeloid progenitor cells.

Design And Methods: Low density, progenitor cell enriched BM cells underwent a double cytotoxic treatment with CD38 and CD33 monoclonal antibodies + rabbit complement, which depleted 99% of CFU-GM and BFU-E.

Hemopoietic progenitor cell mobilization and harvest following an intensive chemotherapy debulking in indolent lymphoma patients.

An in vivo purging with intensive debulking chemotherapy prior to peripheral blood progenitor cell (PBPC) collection may reduce the risk of tumor contamination of the harvest products; however, it is usually associated with a marked reduction in PBPC mobilization. These issues have been considered while designing an adapted version of the high-dose sequential regimen for patients with lymphoid malignancies and bone marrow involvement. To reduce tumor contamination risks, PBPC collection was postponed to the end of the high-dose phase; however, in order to enhance progenitor cell mobilization, a chemotherapy-free lag period was introduced prior to the final mobilizing course.

A single step density gradient separation for large scale enrichment of mobilized peripheral blood progenitor cells collected for autotransplantation.

Peripheral blood leukocytes are becoming the preferred source of hematopoietic progenitor/stem cells for autologous transplantation. However, in vitro purging procedures are complex and expensive when applied to peripheral blood progenitor cells harvests. This is mainly due to the large quantities of nucleated cells present in leukapheresis collections.

Peripheral blood progenitor cell mobilization in patients with primary refractory lymphoma or at first relapse: comparison with patients at diagnosis and impact on clinical outcome.

Peripheral blood progenitor cell (PBPC) mobilization was evaluated in 53 patients receiving the high-dose sequential (HDS) regimen: 27 had non-Hodgkin's lymphoma or Hodgkin's disease, primary refractory or at first relapse, 26 had non-Hodgkin's lymphoma at diagnosis. Mobilization was assessed following either 7 g/m2 cyclophosphamide (48 patients) or 2 g/m2 etoposide, both followed by G-CSF (filgrastim) at 5 microg/kg/d. PBPC mobilization was significantly higher in patients at diagnosis compared to refractory/relapsed patients (median peak values of circulating CFU-GM: 25,209/ml v 4270/ml, P < 0.

Molecular monitoring of minimal residual disease in follicular and mantle cell non-Hodgkin's lymphomas treated with high-dose chemotherapy and peripheral blood progenitor cell autografting.

Minimal residual disease (MRD) was evaluated in 30 patients with follicular or mantle cell non-Hodgkin's lymphoma (NHL) undergoing an intensive treatment with high-dose sequential (HDS) chemotherapy and peripheral blood progenitor cell (PBPC) autografting. To minimize the potential tumor cell contamination, PBPC harvests were scheduled at the end of HDS pretransplant phase. All patients had advanced-stage disease and most of them presented with bone marrow (BM) involvement.

Both early and committed haemopoietic progenitors are more frequent in peripheral blood than in bone marrow during mobilization induced by high-dose chemotherapy + G-CSF.

Haemopoietic growth factor administration following high-dose chemotherapy markedly amplifies progenitor cell pool in the peripheral blood (PB). Collection and reinfusion of these cells enable rapid haemopoietic reconstitution following autograft. Less is known on engraftment potentiality of bone marrow (BM) cells taken under analogous conditions.

Circulating progenitors following high-dose sequential (HDS) chemotherapy with G-CSF: short intervals between drug courses severely impair progenitor mobilization.

Sequential administration of high-dose chemotherapy courses possibly allows extensive in vivo purging before circulating progenitor collection for autograft. To evaluate whether progenitor cell mobilization was negatively affected by repeated high-dose chemotherapy courses, we studied 23 lymphoma patients undergoing the HDS regimen. The scheme includes the sequential administration of cyclophosphamide (CY) given at 7 g/m2 and etoposide (VP16) given at 2 g/m2, each followed by G-CSF (filgrastim) at 5 micrograms/kg/day.

Haematological support of high-dose sequential chemotherapy: clinical evidence for reduction of toxicity and high response rates in poor risk lymphomas.

The toxicity and feasibility of a high-dose sequential (HDS) chemotherapy programme delivered with growth factor support were evaluated in patients with intermediate and high-grade non-Hodgkin's lymphoma (NHL) or with progressive Hodgkin's disease. The scheme includes the sequential administration of single cytotoxic drugs at very high doses followed by intensified treatment with circulating progenitor autograft. In some instances, the original HDS scheme, initially designed at the Milan Cancer Center, was partially modified and intensified with a preliminary debulking phase.

Selection and characterization of early hematopoietic progenitors using an anti-CD71/S06 immunotoxin.

Most recently reported methods to select early hematopoietic cells basically rely on the depletion of committed progenitors. This task is generally accomplished by laborious procedures, which are sometimes difficult to reproduce. To simplify the selection method, we took advantage of the expression of the transferrin receptor (CD71) by proliferating committed progenitors and the lack of CD71 on noncycling immature progenitors.