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Autografting

Autologous transplantation of chemotherapy-purged PBSC collections from high-risk leukemia patients: a pilot study

Abstract

We have recently demonstrated that the combination of the alkylating agent nitrogen mustard (NM) and etoposide (VP-16) is capable of eliminating, ex vivo, leukemic cells contaminating PBSC collections and this is associated with a significant recovery of primitive and committed hematopoietic progenitor cells. Based on these data a pilot study on autologous transplantation of NM/VP-16 purged PBSC for high-risk leukemic patients was recently initiated. Twelve patients (seven females and five males) with a median age of 46 years (range 18–57) have been treated. Two patients had acute myeloblastic leukemia (AML) resistant to conventional induction treatment, four patients had secondary AML in I complete remission (CR), one patient was in II CR after failing a previous autologous BM transplantation, while two additional AML individuals were in I CR achieved after three or more cycles of induction treatment. Two patients with high-risk acute lymphoblastic leukemia (ALL) in I CR and one patient with mantle cell lymphoma and leukemic dissemination were also included. Eight patients showed karyotypic abnormalities associated with a poor clinical outcome. The mobilizing regimens included cytosine arabinoside and mitoxantrone with (n = 6) or without fludarabine (n = 3) followed by subcutaneous administration of G-CSF (5 μg/kg/day until the completion of PBSC collection) and G-CSF alone (n = 3) (15 μg/kg/day). A median of two aphereses (range 1–3) allowed the collection of 7.2 × 108 TNC/kg (range 3.4–11.5), 5 × 106 CD34+ cells/kg (range 2.1–15.3) and 9.2 × 104 CFU-GM/kg (0.3–236). PBSC were treated with a constant dose of 20 μg of VP-16/ml and a median individual-adjusted dose (survival 5% of steady-state BM CFU-GM) of NM of 0.7 μg/ml (range 0.25–1.25). Eleven patients were reinfused after busulfan (16 mg/kg) and Cy (120 mg/kg) conditioning with a median residual dose of 0.3 × 104 CFU-GM/kg (0–11.5). The median time to neutrophil engraftment (>0.5 × 109/l) for evaluable patients was 25 days (range 12–59); the median time to platelet transfusion independence (>20 and >50 × 109/l) was 40 days (18–95) and 69 days (29–235), respectively. Hospital discharge occurred at a median of 25 days (18–58) after stem cell reinfusion. Four individuals are alive in CR (n = 3) or with residual nodal disease (n = 1 lymphoma patient) with a follow-up of 32, 26, 3 and 14 months, respectively. Seven patients died due to disease progression or relapse (n = 5) or extrahematological transplant toxicity (n = 2). Our data suggest that pharmacological purging of leukapheresis collections of leukemic patients at high-risk of relapse is feasible and ex vivo treated cells reconstitute autologous hematopoiesis.

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Lemoli, R., Visani, G., Leopardi, G. et al. Autologous transplantation of chemotherapy-purged PBSC collections from high-risk leukemia patients: a pilot study. Bone Marrow Transplant 23, 235–241 (1999). https://doi.org/10.1038/sj.bmt.1701576

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