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Sustained remissions of high-risk acute myeloid leukemia and myelodysplastic syndrome after reduced-intensity conditioning allogeneic hematopoietic transplantation: chronic graft-versus-host disease is the strongest factor improving survival.
J Clin Oncol. 2008 Feb 01; 26(4):577-84.JC

Abstract

PURPOSE

Reduced-intensity conditioning (RIC) for allogeneic stem-cell transplantation (allo-SCT) reduces nonrelapse mortality (NRM). This reduction makes it possible for patients who are ineligible for high-dose myeloablative conditioning allo-SCT to benefit from graft-versus-leukemia reaction. In this multicenter, prospective study of patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), we investigated the efficacy of RIC allo-SCT from a human leukocyte antigen-identical sibling by using a regimen that uses fludarabine and busulfan.

PATIENTS AND METHODS

Ninety-three patients with AML (n = 59) and MDS (n = 34) were included, and the median age was of 53 years. Follow-up for survivors was 43 months (range, 3 to 89 months). The conditioning regimen consisted of fludarabine (150 mg/m(2)) and oral busulfan (8 to 10 mg/kg). All except one patient received mobilized peripheral blood stem cells. Graft-versus-host disease (GVHD) prophylaxis consisted of cyslosporine and methotrexate or mycophenolate mofetil.

RESULTS

The 100-day, 1-year, and 4-year incidences of NRM were 8, 16%, and 21%, respectively. The 1- and 4-year relapse cumulative incidences were 23% and 37%, respectively, and leukemia recurrence was the main cause of death. The 4-year disease-free survival (DFS) and overall survival (OS) rates were 43% and 45%, respectively. The 4-year cumulative incidence of chronic GVHD was 53% (45% extensive), and its development was the major factor associated with lower relapse incidence and improved DFS and OS.

CONCLUSION

Our results confirm the capacity of this RIC regimen to obtain long-term remissions in patients ineligible for a conventional allo-SCT. The results suggest an important role of the development of chronic GVHD in reducing relapse and improving DFS and OS.

Authors+Show Affiliations

Hospital de la Santa Creu i Sant Pau, Universitat Autonoma Barcelona, Barcelona, Spain. dvalcarcel@santpau.esNo 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 availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18086801

Citation

Valcárcel, David, et al. "Sustained Remissions of High-risk Acute Myeloid Leukemia and Myelodysplastic Syndrome After Reduced-intensity Conditioning Allogeneic Hematopoietic Transplantation: Chronic Graft-versus-host Disease Is the Strongest Factor Improving Survival." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, vol. 26, no. 4, 2008, pp. 577-84.
Valcárcel D, Martino R, Caballero D, et al. Sustained remissions of high-risk acute myeloid leukemia and myelodysplastic syndrome after reduced-intensity conditioning allogeneic hematopoietic transplantation: chronic graft-versus-host disease is the strongest factor improving survival. J Clin Oncol. 2008;26(4):577-84.
Valcárcel, D., Martino, R., Caballero, D., Martin, J., Ferra, C., Nieto, J. B., Sampol, A., Bernal, M. T., Piñana, J. L., Vazquez, L., Ribera, J. M., Besalduch, J., Moraleda, J. M., Carrera, D., Brunet, M. S., Perez-Simón, J. A., & Sierra, J. (2008). Sustained remissions of high-risk acute myeloid leukemia and myelodysplastic syndrome after reduced-intensity conditioning allogeneic hematopoietic transplantation: chronic graft-versus-host disease is the strongest factor improving survival. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 26(4), 577-84.
Valcárcel D, et al. Sustained Remissions of High-risk Acute Myeloid Leukemia and Myelodysplastic Syndrome After Reduced-intensity Conditioning Allogeneic Hematopoietic Transplantation: Chronic Graft-versus-host Disease Is the Strongest Factor Improving Survival. J Clin Oncol. 2008 Feb 1;26(4):577-84. PubMed PMID: 18086801.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sustained remissions of high-risk acute myeloid leukemia and myelodysplastic syndrome after reduced-intensity conditioning allogeneic hematopoietic transplantation: chronic graft-versus-host disease is the strongest factor improving survival. AU - Valcárcel,David, AU - Martino,Rodrigo, AU - Caballero,Dolores, AU - Martin,Jesus, AU - Ferra,Christelle, AU - Nieto,Jose B, AU - Sampol,Antonia, AU - Bernal,M Teresa, AU - Piñana,Jose L, AU - Vazquez,Lourdes, AU - Ribera,Jose M, AU - Besalduch,Joan, AU - Moraleda,Jose M, AU - Carrera,Dolores, AU - Brunet,M Salut, AU - Perez-Simón,Jose A, AU - Sierra,Jorge, Y1 - 2007/12/17/ PY - 2007/12/19/pubmed PY - 2008/2/20/medline PY - 2007/12/19/entrez SP - 577 EP - 84 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JO - J Clin Oncol VL - 26 IS - 4 N2 - PURPOSE: Reduced-intensity conditioning (RIC) for allogeneic stem-cell transplantation (allo-SCT) reduces nonrelapse mortality (NRM). This reduction makes it possible for patients who are ineligible for high-dose myeloablative conditioning allo-SCT to benefit from graft-versus-leukemia reaction. In this multicenter, prospective study of patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), we investigated the efficacy of RIC allo-SCT from a human leukocyte antigen-identical sibling by using a regimen that uses fludarabine and busulfan. PATIENTS AND METHODS: Ninety-three patients with AML (n = 59) and MDS (n = 34) were included, and the median age was of 53 years. Follow-up for survivors was 43 months (range, 3 to 89 months). The conditioning regimen consisted of fludarabine (150 mg/m(2)) and oral busulfan (8 to 10 mg/kg). All except one patient received mobilized peripheral blood stem cells. Graft-versus-host disease (GVHD) prophylaxis consisted of cyslosporine and methotrexate or mycophenolate mofetil. RESULTS: The 100-day, 1-year, and 4-year incidences of NRM were 8, 16%, and 21%, respectively. The 1- and 4-year relapse cumulative incidences were 23% and 37%, respectively, and leukemia recurrence was the main cause of death. The 4-year disease-free survival (DFS) and overall survival (OS) rates were 43% and 45%, respectively. The 4-year cumulative incidence of chronic GVHD was 53% (45% extensive), and its development was the major factor associated with lower relapse incidence and improved DFS and OS. CONCLUSION: Our results confirm the capacity of this RIC regimen to obtain long-term remissions in patients ineligible for a conventional allo-SCT. The results suggest an important role of the development of chronic GVHD in reducing relapse and improving DFS and OS. SN - 1527-7755 UR - https://www.unboundmedicine.com/medline/citation/18086801/Sustained_remissions_of_high_risk_acute_myeloid_leukemia_and_myelodysplastic_syndrome_after_reduced_intensity_conditioning_allogeneic_hematopoietic_transplantation:_chronic_graft_versus_host_disease_is_the_strongest_factor_improving_survival_ L2 - https://ascopubs.org/doi/10.1200/JCO.2007.11.1641?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -