Fludarabine versus cyclophospamide in combination with myeloablative total body irradiation as conditioning for patients with acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation. A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
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Fludarabine versus cyclophospamide in combination with myeloablative total body irradiation as conditioning for patients with acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation. A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. / Giebel, Sebastian; Labopin, Myriam; Schroeder, Thomas; Swoboda, Ryszard; Maertens, Johan; Bourhis, Jean Henri; Grillo, Giovanni; Salmenniemi, Urpu; Hilgendorf, Inken; Kröger, Nicolaus; Poiré, Xavier; Cornelissen, Jan J; Arat, Mutlu; Savani, Bipin; Spyridonidis, Alexandros; Nagler, Arnon; Mohty, Mohamad.
In: AM J HEMATOL, Vol. 98, No. 4, 04.2023, p. 580-587.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Fludarabine versus cyclophospamide in combination with myeloablative total body irradiation as conditioning for patients with acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation. A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
AU - Giebel, Sebastian
AU - Labopin, Myriam
AU - Schroeder, Thomas
AU - Swoboda, Ryszard
AU - Maertens, Johan
AU - Bourhis, Jean Henri
AU - Grillo, Giovanni
AU - Salmenniemi, Urpu
AU - Hilgendorf, Inken
AU - Kröger, Nicolaus
AU - Poiré, Xavier
AU - Cornelissen, Jan J
AU - Arat, Mutlu
AU - Savani, Bipin
AU - Spyridonidis, Alexandros
AU - Nagler, Arnon
AU - Mohty, Mohamad
N1 - © 2023 Wiley Periodicals LLC.
PY - 2023/4
Y1 - 2023/4
N2 - Total body irradiation (TBI) at a dose of 12 Gy combined with cyclophosphamide (CyTBI12Gy) is one of the standard myeloablative regimens for patients with acute myeloid leukemia (AML) treated with allogeneic hematopoietic cell transplantation (allo-HCT). In clinical practice, cyclophosphamide may be substituted with fludarabine (FluTBI12Gy) to reduce toxicity. We retrospectively compared outcomes of CyTBI12Gy with FluTBI12Gy for patients with AML treated in complete remission (CR) with allo-HCT from either a matched sibling or unrelated donor. Of 1684 adults who met inclusion criteria, 109 patients in each group were included in a matched-pair analysis. The cumulative incidence of relapse at 2 years was 25% in the FluTBI12Gy compared to 28% in the CyTBI12Gy group (p = .44) while non-relapse mortality (NRM) was 17% versus 19%, (p = .89) respectively. The rates of leukemia-free survival and overall survival were 65% versus 54% (p = .28) and 70% versus 60.5% (p = .17). Cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) was significantly lower for FluTBI12Gy than CyTBI12Gy (16% vs. 34%, p = .005), while the incidences of grade 3-4 acute GVHD and chronic GVHD did not differ significantly. The probability of GVHD and relapse-free survival was 49% in the FluTBI12Gy and 41% in the CyTBI12Gy group (p = .17). We conclude that for patients with AML treated with allo-HCT in CR, cyclophosphamide may be substituted with fludarabine in a regimen based on TBI at a dose of 12 Gy without negative impact on the efficacy. FluTBI12Gy is associated with reduced risk of grade 2-4 acute GVHD and encouraging survival rates.
AB - Total body irradiation (TBI) at a dose of 12 Gy combined with cyclophosphamide (CyTBI12Gy) is one of the standard myeloablative regimens for patients with acute myeloid leukemia (AML) treated with allogeneic hematopoietic cell transplantation (allo-HCT). In clinical practice, cyclophosphamide may be substituted with fludarabine (FluTBI12Gy) to reduce toxicity. We retrospectively compared outcomes of CyTBI12Gy with FluTBI12Gy for patients with AML treated in complete remission (CR) with allo-HCT from either a matched sibling or unrelated donor. Of 1684 adults who met inclusion criteria, 109 patients in each group were included in a matched-pair analysis. The cumulative incidence of relapse at 2 years was 25% in the FluTBI12Gy compared to 28% in the CyTBI12Gy group (p = .44) while non-relapse mortality (NRM) was 17% versus 19%, (p = .89) respectively. The rates of leukemia-free survival and overall survival were 65% versus 54% (p = .28) and 70% versus 60.5% (p = .17). Cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) was significantly lower for FluTBI12Gy than CyTBI12Gy (16% vs. 34%, p = .005), while the incidences of grade 3-4 acute GVHD and chronic GVHD did not differ significantly. The probability of GVHD and relapse-free survival was 49% in the FluTBI12Gy and 41% in the CyTBI12Gy group (p = .17). We conclude that for patients with AML treated with allo-HCT in CR, cyclophosphamide may be substituted with fludarabine in a regimen based on TBI at a dose of 12 Gy without negative impact on the efficacy. FluTBI12Gy is associated with reduced risk of grade 2-4 acute GVHD and encouraging survival rates.
KW - Adult
KW - Humans
KW - Retrospective Studies
KW - Whole-Body Irradiation
KW - Bone Marrow
KW - Busulfan/therapeutic use
KW - Leukemia, Myeloid, Acute/drug therapy
KW - Hematopoietic Stem Cell Transplantation/adverse effects
KW - Cyclophosphamide/therapeutic use
KW - Acute Disease
KW - Graft vs Host Disease/etiology
KW - Recurrence
KW - Transplantation Conditioning/adverse effects
U2 - 10.1002/ajh.26825
DO - 10.1002/ajh.26825
M3 - SCORING: Journal article
C2 - 36626592
VL - 98
SP - 580
EP - 587
JO - AM J HEMATOL
JF - AM J HEMATOL
SN - 0361-8609
IS - 4
ER -
