Metabolism and action of purine nucleoside analogs

Plunkett, William; Saunders, Priscilla P.

doi:10.1016/0163-7258(91)90057-s

Cited by 135 publications

(69 citation statements)

References 215 publications

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“…For immunosuppression we used the combination of fludarabine and cyclophosphamide. The combination of the purin analog fludarabine, which produces lymphocytopenia and substantial immunosuppression, 29,30 and cyclophosphamide used in conventional myeloablative conditioning was shown to be very effective after non-myeloablative conditioning in enabling engraftment of donor hematopoietic stem cells and subsequent mixed donor/recipient chimeras. 9,10 As antileukemic components we used the combination of idarubicin and etoposide, which is part of the consolidation treatment in our ongoing protocol for elderly patients with AML.…”

Section: Discussionmentioning

confidence: 99%

Less intense conditioning with fludarabine, cyclophosphamide, idarubicin and etoposide (FCIE) followed by allogeneic unselected peripheral blood stem cell transplantation in elderly patients with leukemia

Schlenk

Hartmann²,

Hensel

et al. 2002

Leukemia

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The objective of this study was to assess toxicity and feasibility of achieving engraftment of allogeneic blood progenitor cells following nonmyeloablative conditioning according to the FCIE protocol (fludarabine 25 mg/m 2 /day, days −7 to −3; cyclophosphamide 200 mg/m 2 /day, days −7 to −3; idarubicin 12 mg/m 2 /day, days −7 to −5; etoposide 250 mg/m 2 /day, days −4 to −3) in elderly patients with leukemia. Eleven patients were included in the study: six patients with acute myeloid leukemia (AML) in complete remission (CR); three patients with refractory or relapsed AML; one patient with chronic myeloid leukemia; one patient with acute lymphoblastic leukemia. The median age of the patients was 62 years. All patients received blood progenitor cells from an HLA-identical sibling with 8.8 × 10 6 CD34 + cells/kg (median; range 4.7 to 26.2 × 10 6 /kg) and 5.5 × 10 8 CD3 + cells/kg (median; range 4.5 to 7.9 × 10 8 /kg). Graftversus-host disease (GVHD) prophylaxis consisted of cyclosporine and three courses of methotrexate. The median duration of white blood cell counts Ͻ1 × 10 9 /l was 17 days and of platelet counts Ͻ50 × 10 9 /l 20 days. In two patients acute GVHD grade I occurred. Nine of 10 patients analyzed developed mixed chimerism. Of seven patients transplanted in CR, three remained in CR 19 to 31 months after transplantation. Three patients with refractory leukemia did not achieve CR, while the patient with relapsed AML achieved a 3rd CR. After a median follow-up time of 22 months, chronic GVHD was mild and limited. The data from this pilot study in elderly patients with leukemia show that the combination of primarily immunosuppressive (FC) and antileukemic (IE) drugs for nonmyeloablative conditioning has moderate nonhematological toxicity and allows engraftment of allogeneic blood progenitor cells.

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Section: Discussionmentioning

confidence: 99%

Less intense conditioning with fludarabine, cyclophosphamide, idarubicin and etoposide (FCIE) followed by allogeneic unselected peripheral blood stem cell transplantation in elderly patients with leukemia

Schlenk

Hartmann²,

Hensel

et al. 2002

Leukemia

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“…[3][4][5] These are well-tolerated agents, with potent immunosuppressive effects, in addition to anti-tumor activity against a range of hematologic malignancies. 25 They have synergistic effects with alkylating agents. Purine analogues inhibit DNA repair systems responsible for repair of cellular damage induced by these agents.…”

Section: Nst Regimensmentioning

confidence: 99%

Non-myeloablative stem cell transplantation (NST): chimerism testing as guidance for immune-therapeutic manipulations

Shimoni

Nagler

2001

Leukemia

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“…81 Like other NA, it requires phosphorylation to its triphosphate form, F-ara-ATP for cytotoxic activity. 82,83 The initial step in this activation process is performed by dCK.…”

Section: Figurementioning

confidence: 99%