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Autologous transplantation of chemotherapy-purged PBSC collections from high-risk leukemia patients: a pilot study.
Bone Marrow Transplant. 1999 Feb; 23(3):235-41.BM

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 microg/kg/day until the completion of PBSC collection) and G-CSF alone (n = 3) (15 microg/kg/day). A median of two aphereses (range 1-3) allowed the collection of 7.2 x 10(8) TNC/kg (range 3.4-11.5), 5 x 10(6) CD34+ cells/kg (range 2.1-15.3) and 9.2 x 10(4) CFU-GM/kg (0.3-236). PBSC were treated with a constant dose of 20 microg of VP-16/ml and a median individual-adjusted dose (survival < or = 5% of steady-state BM CFU-GM) of NM of 0.7 microg/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 x 10(4) CFU-GM/kg (0-11.5). The median time to neutrophil engraftment (>0.5 x 10(9)/l) for evaluable patients was 25 days (range 12-59); the median time to platelet transfusion independence (>20 and >50 x 10(9)/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.

Authors+Show Affiliations

Institute of Hematology and Medical Oncology L & A Seràgnoli, University of Bologna, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10084254

Citation

Lemoli, R M., et al. "Autologous Transplantation of Chemotherapy-purged PBSC Collections From High-risk Leukemia Patients: a Pilot Study." Bone Marrow Transplantation, vol. 23, no. 3, 1999, pp. 235-41.
Lemoli RM, Visani G, Leopardi G, et al. Autologous transplantation of chemotherapy-purged PBSC collections from high-risk leukemia patients: a pilot study. Bone Marrow Transplant. 1999;23(3):235-41.
Lemoli, R. M., Visani, G., Leopardi, G., Motta, M. R., Rizzi, S., Testoni, N., Curti, A., & Tura, S. (1999). Autologous transplantation of chemotherapy-purged PBSC collections from high-risk leukemia patients: a pilot study. Bone Marrow Transplantation, 23(3), 235-41.
Lemoli RM, et al. Autologous Transplantation of Chemotherapy-purged PBSC Collections From High-risk Leukemia Patients: a Pilot Study. Bone Marrow Transplant. 1999;23(3):235-41. PubMed PMID: 10084254.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Autologous transplantation of chemotherapy-purged PBSC collections from high-risk leukemia patients: a pilot study. AU - Lemoli,R M, AU - Visani,G, AU - Leopardi,G, AU - Motta,M R, AU - Rizzi,S, AU - Testoni,N, AU - Curti,A, AU - Tura,S, PY - 1999/3/20/pubmed PY - 1999/3/20/medline PY - 1999/3/20/entrez SP - 235 EP - 41 JF - Bone marrow transplantation JO - Bone Marrow Transplant VL - 23 IS - 3 N2 - 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 microg/kg/day until the completion of PBSC collection) and G-CSF alone (n = 3) (15 microg/kg/day). A median of two aphereses (range 1-3) allowed the collection of 7.2 x 10(8) TNC/kg (range 3.4-11.5), 5 x 10(6) CD34+ cells/kg (range 2.1-15.3) and 9.2 x 10(4) CFU-GM/kg (0.3-236). PBSC were treated with a constant dose of 20 microg of VP-16/ml and a median individual-adjusted dose (survival < or = 5% of steady-state BM CFU-GM) of NM of 0.7 microg/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 x 10(4) CFU-GM/kg (0-11.5). The median time to neutrophil engraftment (>0.5 x 10(9)/l) for evaluable patients was 25 days (range 12-59); the median time to platelet transfusion independence (>20 and >50 x 10(9)/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. SN - 0268-3369 UR - https://www.unboundmedicine.com/medline/citation/10084254/Autologous_transplantation_of_chemotherapy_purged_PBSC_collections_from_high_risk_leukemia_patients:_a_pilot_study_ L2 - https://doi.org/10.1038/sj.bmt.1701576 DB - PRIME DP - Unbound Medicine ER -