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Allogeneic stem cell transplantation after a fludarabine/busulfan-based reduced-intensity conditioning in patients with myelodysplastic syndrome or secondary acute myeloid leukemia.
Ann Hematol. 2003 Jun; 82(6):336-42.AH

Abstract

We report the feasibility and efficacy of a fludarabine/busulfan-based dose-reduced conditioning regimen followed by stem cell transplantation from related (n=19) or unrelated HLA-matched donors (n=18) in 37 patients with myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia (sAML) who were not eligible for a standard myeloablative conditioning regimen. The conditioning regimen consisted of fludarabine (120-180 mg/m(2)), busulfan (8 mg/kg p.o. or 6.4 mg/kg i.v.), and antithymocyte globulin (n=25). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (n=36) and a short course of methotrexate (n=29) or mycophenolate mofetil (n=3). The median age of the patients was 55 years (range: 23-72). The reasons to perform a dose-reduced conditioning were reduced performance status (n=14), age (n=12), prior autologous (n=5) or allogeneic (n=1) transplantation, or prior/active fungal infection (n=5). Diagnoses at transplantation were refractory anemia (RA) (n=8), refractory anemia with excess of blasts (RAEB) (n=6), RAEB in transformation (RAEB-T) (n=13), chronic myelomonocytic leukemia (CMML) (n=3), and sAML (n=7). Stem cell sources were peripheral blood stem cells (PBSC) (n=29) or bone marrow (n=8). One patient received a T-cell-depleted peripheral stem cell graft. Two primary graft failures were observed (6%). Engraftment of leukocytes (>1.0x10(9)/l) and platelets (>20x10(9)/l) was seen after a median of 14 days. Acute GVHD grade II-IV was seen in 37%, while severe grade III/IV GVHD was observed in six patients (17%). Chronic GVHD was seen in 13 patients (48%). There were ten deaths (27%) due to treatment (TRM). The probability of TRM was higher in patients with unrelated donors (45 vs 12%, p=0.03) and in patients with poor cytogenetics in comparison to those with a low or intermediate karyotype (75 vs 20%, p=0.009). During follow-up 12 patients relapsed (32%). Patients without chronic GVHD had a significantly higher probability of relapse compared to those with chronic GVHD (70 vs 15%, p=0.02). After a median follow-up of 20 months, the 3-year estimated disease-free survival (DFS) is 38% [95% confidence interval (CI): 21-55%] and the overall survival (OS) is 39% (95% CI: 22-56%). The OS and DFS after related and unrelated transplantations was 45% (95% CI: 19-71%) vs 31% (95% CI: 9-53%) (n.s.) and 51% (95% CI: 29-73%) vs 25% (95% CI: 4-47%) (n.s.), respectively. We conclude that dose-reduced conditioning followed by allogeneic stem cell transplantation from related or unrelated donors is an effective treatment approach in patients with MDS/sAML and might cure a substantial number of patients who are not eligible for a standard allogeneic transplantation.

Authors+Show Affiliations

Bone Marrow Transplantation, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. nkroeger@uke.uni-hamburg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study

Language

eng

PubMed ID

12728337

Citation

Kröger, N, et al. "Allogeneic Stem Cell Transplantation After a Fludarabine/busulfan-based Reduced-intensity Conditioning in Patients With Myelodysplastic Syndrome or Secondary Acute Myeloid Leukemia." Annals of Hematology, vol. 82, no. 6, 2003, pp. 336-42.
Kröger N, Bornhäuser M, Ehninger G, et al. Allogeneic stem cell transplantation after a fludarabine/busulfan-based reduced-intensity conditioning in patients with myelodysplastic syndrome or secondary acute myeloid leukemia. Ann Hematol. 2003;82(6):336-42.
Kröger, N., Bornhäuser, M., Ehninger, G., Schwerdtfeger, R., Biersack, H., Sayer, H. G., Wandt, H., Schäfer-Eckardt, K., Beyer, J., Kiehl, M., & Zander, A. R. (2003). Allogeneic stem cell transplantation after a fludarabine/busulfan-based reduced-intensity conditioning in patients with myelodysplastic syndrome or secondary acute myeloid leukemia. Annals of Hematology, 82(6), 336-42.
Kröger N, et al. Allogeneic Stem Cell Transplantation After a Fludarabine/busulfan-based Reduced-intensity Conditioning in Patients With Myelodysplastic Syndrome or Secondary Acute Myeloid Leukemia. Ann Hematol. 2003;82(6):336-42. PubMed PMID: 12728337.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Allogeneic stem cell transplantation after a fludarabine/busulfan-based reduced-intensity conditioning in patients with myelodysplastic syndrome or secondary acute myeloid leukemia. AU - Kröger,N, AU - Bornhäuser,M, AU - Ehninger,G, AU - Schwerdtfeger,R, AU - Biersack,H, AU - Sayer,H G, AU - Wandt,H, AU - Schäfer-Eckardt,K, AU - Beyer,J, AU - Kiehl,M, AU - Zander,A R, AU - ,, Y1 - 2003/05/01/ PY - 2003/03/19/received PY - 2003/04/01/accepted PY - 2003/5/3/pubmed PY - 2003/8/2/medline PY - 2003/5/3/entrez SP - 336 EP - 42 JF - Annals of hematology JO - Ann Hematol VL - 82 IS - 6 N2 - We report the feasibility and efficacy of a fludarabine/busulfan-based dose-reduced conditioning regimen followed by stem cell transplantation from related (n=19) or unrelated HLA-matched donors (n=18) in 37 patients with myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia (sAML) who were not eligible for a standard myeloablative conditioning regimen. The conditioning regimen consisted of fludarabine (120-180 mg/m(2)), busulfan (8 mg/kg p.o. or 6.4 mg/kg i.v.), and antithymocyte globulin (n=25). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (n=36) and a short course of methotrexate (n=29) or mycophenolate mofetil (n=3). The median age of the patients was 55 years (range: 23-72). The reasons to perform a dose-reduced conditioning were reduced performance status (n=14), age (n=12), prior autologous (n=5) or allogeneic (n=1) transplantation, or prior/active fungal infection (n=5). Diagnoses at transplantation were refractory anemia (RA) (n=8), refractory anemia with excess of blasts (RAEB) (n=6), RAEB in transformation (RAEB-T) (n=13), chronic myelomonocytic leukemia (CMML) (n=3), and sAML (n=7). Stem cell sources were peripheral blood stem cells (PBSC) (n=29) or bone marrow (n=8). One patient received a T-cell-depleted peripheral stem cell graft. Two primary graft failures were observed (6%). Engraftment of leukocytes (>1.0x10(9)/l) and platelets (>20x10(9)/l) was seen after a median of 14 days. Acute GVHD grade II-IV was seen in 37%, while severe grade III/IV GVHD was observed in six patients (17%). Chronic GVHD was seen in 13 patients (48%). There were ten deaths (27%) due to treatment (TRM). The probability of TRM was higher in patients with unrelated donors (45 vs 12%, p=0.03) and in patients with poor cytogenetics in comparison to those with a low or intermediate karyotype (75 vs 20%, p=0.009). During follow-up 12 patients relapsed (32%). Patients without chronic GVHD had a significantly higher probability of relapse compared to those with chronic GVHD (70 vs 15%, p=0.02). After a median follow-up of 20 months, the 3-year estimated disease-free survival (DFS) is 38% [95% confidence interval (CI): 21-55%] and the overall survival (OS) is 39% (95% CI: 22-56%). The OS and DFS after related and unrelated transplantations was 45% (95% CI: 19-71%) vs 31% (95% CI: 9-53%) (n.s.) and 51% (95% CI: 29-73%) vs 25% (95% CI: 4-47%) (n.s.), respectively. We conclude that dose-reduced conditioning followed by allogeneic stem cell transplantation from related or unrelated donors is an effective treatment approach in patients with MDS/sAML and might cure a substantial number of patients who are not eligible for a standard allogeneic transplantation. SN - 0939-5555 UR - https://www.unboundmedicine.com/medline/citation/12728337/Allogeneic_stem_cell_transplantation_after_a_fludarabine/busulfan_based_reduced_intensity_conditioning_in_patients_with_myelodysplastic_syndrome_or_secondary_acute_myeloid_leukemia_ L2 - https://dx.doi.org/10.1007/s00277-003-0654-9 DB - PRIME DP - Unbound Medicine ER -