Purging of G-CSF-mobilized peripheral autografts in acute leukemia with mafosfamide and amifostine to protect normal progenitor cells

Abstract

Summary:In the present study the in vitro growth of CFU-GM from PBPC of patients with AML (n = 11), purged with mafosfamide alone or a combination of mafosfamide and amifostine, was compared to historical controls of mafosfamide-purged bone marrow (AML CR1, n = 16). Two patients were transplanted with mafosfamide and mafosfamide/amifostine pretreated PBPC autografts. The in vitro experiments demonstrated a significantly higher resistance of peripheral blood derived CFU-GM to mafosfamide (median ID 95 190 g mafosfamide/ml) compared with bone marrow derived CFU-GM (median ID 95 130 g/ml). Preincubation with amifostine significantly further increased the median ID 95 to 245 g/ml. The clinical results showed short recovery times for neutrophils Ͼ500/ l (9 and 13 days) and platelets Ͼ20 000/ l (12 and 21 days) and stable long-term engraftment with one relapse at day ؉118 and one patient in CR at day 760 after transplantation. The in vitro results show a significant advantage of PBPC over bone marrow-derived progenitors for purging with mafosfamide. Furthermore, a protective effect from mafosfamide of amifostine on normal progenitors could be demonstrated. The clinical results demonstrate the clinical feasibility of using mafosfamide-purged autologous PBPCT without impairing the short-term and longterm repopulating capacities of the autografts. Bone Marrow Transplantation (2000) 25, 831-836.

Mafosfamide-Purged Peripheral Blood Stem Cell Harvest: Case Report of a 54-Year-Old Patient with Relapsed Acute Myeloid Leukemia

“…In the future, we will optimize the procedure in accordance to GMP to obtain a higher level of safety and reproducibility. In summary, our results demonstrate the feasibility of in vitro mafosfamide purging of leukapheresis products which confirmed very recently published data from Fauth et al [9]. The increasing use of mobilized PBSCs instead of bone marrow in autologous transplantations might contribute to a higher demand for mafosfamide purging, in particular for those stem cell harvests having a high risk of contaminating leukemic blasts which could not depleted by CD34+ selection.…”

“…We are reporting one of the first patients with AML (FAB M1, CD34+) treated with mafosfamide-purged autologous PBSCs instead of bone marrow after total-body irradiation and HDC, confirming very recently published data by Fauth et al [9]. The results presented here show the feasibility of ex vivo drug treatment of stem cell products in principle although there is an urgent need to optimize steps of procedure such as the MNC separation and drug incubation to receive higher cell recovery and to be in line with the good manufacturing practice (GMP) guidelines.…”

Purging of Contaminating Breast Cancer Cells From Hematopoietic Progenitor Cell Preparations Using Activation Enhanced Cell Death

“…These observations have led to the development of ex-vivo approaches for removing contaminating tumor cells, or purging, of stem cell products. A number of approaches including the use of che-motherapeutic agents (4-hydroxycyclophosphamide) [14][15][16][17] and positive enrichment of hemopoietic progenitor cells using CD34 + immunoseparation, have been attempted with variable success [18][19][20]. More effective methods of purging hematopoietic stem cell products are an important part of the ongoing research to determine the place of ASCT in the treatment of breast cancer and, would also be of relevance for the treatment of other cancers in which high dose chemotherapy is a treatment option.…”

Autologous stem cell transplantation for acute myeloid leukemia

“…Experience in two patients suggests that engraftment will not be markedly delayed. 49 However, experience is limited, and some anecdotal reports create concern about engraftment problems (Miller CB, personnel communication).…”