Transplantation in Remission Improves the Disease-Free Survival of Patients with Advanced Myelodysplastic Syndromes Treated with Myeloablative T Cell-Depleted Stem Cell Transplants from HLA-Identical Siblings

Hugo Castro-Malaspina, Ann A. Jabubowski, Esperanza B. Papadopoulos, Farid Boulad, James W. Young, Nancy A. Kernan, Miguel A. Perales, Trudy N. Small, Katharine Hsu, Michelle Chiu, Glenn Heller, Nancy H. Collins, Suresh C. Jhanwar, Marcel van den Brink, Stephen D Nimer, Richard J. O'Reilly

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Abstract

From 1985 to 2004, 49 patients with advanced myelodysplastic syndromes (MDS) (≥5% blasts) or acute myeloid leukemia (AML) transformed from MDS underwent T cell depleted bone marrow or peripheral blood hematopoietic stem cell transplantation (HSCT) from HLA-identical siblings following conditioning with a myeloablative regimen that included total body irradiation (44 patients) or busulfan (5 patients). Thirty-six patients received chemotherapy (3 low dose and 33 induction doses) before conditioning, and 13 patients did not receive any chemotherapy. Prior to transplantation, 22 of the 36 treated patients were in hematologic remission; 4 were in a second refractory cytopenia phase (26 responders); 8 had failed to achieve remission; and 2 of the responders had progression or relapse of their MDS (10 failures). No post-transplantation pharmacologic prophylaxis for graft-versus-host disease (GVHD) was given. The median age was 48 yrs (range 13-61). Forty-five of the 49 patients engrafted; 2 had primary graft failure; and 2 died before engraftment. Only 3 patients developed acute GVHD (aGVHD) (grades I and III) and 1 chronic GVHD (cGVHD). At 3 yrs post-transplantation, the overall survival (OS) was 54% in the responders; 31% in the untreated group; and 0% in the failure group (P=.0004). The disease free survival (DFS) was 50%, 15% and 0% in each group respectively (P=.0008). In multivariate analysis, disease status before cytoreduction remained highly correlated with DFS (P<.001). The cumulative incidence (CI) of relapse at 2-yrs post-transplantation for the responders was 23%; for the untreated group was 38%; and for the failures was 50%. The CI of non-relapse mortality at 2-yrs post-transplantation, for the responders was 23%; for the untreated group was 38%; and for the failures was 40%. All survivors achieved a Karnofsky Performance Status (KPS) of ≥90. These results indicate that patients with advanced MDS who achieve and remain in remission or a second refractory cytopenia phase with chemotherapy before conditioning can achieve successful long-term remissions following a myeloablative T cell depleted allogeneic HSCT.

Original languageEnglish
Pages (from-to)458-468
Number of pages11
JournalBiology of Blood and Marrow Transplantation
Volume14
Issue number4
DOIs
StatePublished - Apr 1 2008
Externally publishedYes

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Myelodysplastic Syndromes
Disease-Free Survival
Siblings
Stem Cells
Transplantation
T-Lymphocytes
Transplants
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Drug Therapy
Karnofsky Performance Status
Peripheral Blood Stem Cell Transplantation
Recurrence
Busulfan
Whole-Body Irradiation
Incidence
Acute Myeloid Leukemia
Survivors
Multivariate Analysis
Bone Marrow

Keywords

  • Hematopoietic stem cell transplantation
  • Myelodysplastic syndromes
  • T cell depletion

ASJC Scopus subject areas

  • Transplantation

Cite this

Transplantation in Remission Improves the Disease-Free Survival of Patients with Advanced Myelodysplastic Syndromes Treated with Myeloablative T Cell-Depleted Stem Cell Transplants from HLA-Identical Siblings. / Castro-Malaspina, Hugo; Jabubowski, Ann A.; Papadopoulos, Esperanza B.; Boulad, Farid; Young, James W.; Kernan, Nancy A.; Perales, Miguel A.; Small, Trudy N.; Hsu, Katharine; Chiu, Michelle; Heller, Glenn; Collins, Nancy H.; Jhanwar, Suresh C.; van den Brink, Marcel; Nimer, Stephen D; O'Reilly, Richard J.

In: Biology of Blood and Marrow Transplantation, Vol. 14, No. 4, 01.04.2008, p. 458-468.

Research output: Contribution to journalArticle

Castro-Malaspina, H, Jabubowski, AA, Papadopoulos, EB, Boulad, F, Young, JW, Kernan, NA, Perales, MA, Small, TN, Hsu, K, Chiu, M, Heller, G, Collins, NH, Jhanwar, SC, van den Brink, M, Nimer, SD & O'Reilly, RJ 2008, 'Transplantation in Remission Improves the Disease-Free Survival of Patients with Advanced Myelodysplastic Syndromes Treated with Myeloablative T Cell-Depleted Stem Cell Transplants from HLA-Identical Siblings', Biology of Blood and Marrow Transplantation, vol. 14, no. 4, pp. 458-468. https://doi.org/10.1016/j.bbmt.2008.02.006
Castro-Malaspina, Hugo ; Jabubowski, Ann A. ; Papadopoulos, Esperanza B. ; Boulad, Farid ; Young, James W. ; Kernan, Nancy A. ; Perales, Miguel A. ; Small, Trudy N. ; Hsu, Katharine ; Chiu, Michelle ; Heller, Glenn ; Collins, Nancy H. ; Jhanwar, Suresh C. ; van den Brink, Marcel ; Nimer, Stephen D ; O'Reilly, Richard J. / Transplantation in Remission Improves the Disease-Free Survival of Patients with Advanced Myelodysplastic Syndromes Treated with Myeloablative T Cell-Depleted Stem Cell Transplants from HLA-Identical Siblings. In: Biology of Blood and Marrow Transplantation. 2008 ; Vol. 14, No. 4. pp. 458-468.
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abstract = "From 1985 to 2004, 49 patients with advanced myelodysplastic syndromes (MDS) (≥5{\%} blasts) or acute myeloid leukemia (AML) transformed from MDS underwent T cell depleted bone marrow or peripheral blood hematopoietic stem cell transplantation (HSCT) from HLA-identical siblings following conditioning with a myeloablative regimen that included total body irradiation (44 patients) or busulfan (5 patients). Thirty-six patients received chemotherapy (3 low dose and 33 induction doses) before conditioning, and 13 patients did not receive any chemotherapy. Prior to transplantation, 22 of the 36 treated patients were in hematologic remission; 4 were in a second refractory cytopenia phase (26 responders); 8 had failed to achieve remission; and 2 of the responders had progression or relapse of their MDS (10 failures). No post-transplantation pharmacologic prophylaxis for graft-versus-host disease (GVHD) was given. The median age was 48 yrs (range 13-61). Forty-five of the 49 patients engrafted; 2 had primary graft failure; and 2 died before engraftment. Only 3 patients developed acute GVHD (aGVHD) (grades I and III) and 1 chronic GVHD (cGVHD). At 3 yrs post-transplantation, the overall survival (OS) was 54{\%} in the responders; 31{\%} in the untreated group; and 0{\%} in the failure group (P=.0004). The disease free survival (DFS) was 50{\%}, 15{\%} and 0{\%} in each group respectively (P=.0008). In multivariate analysis, disease status before cytoreduction remained highly correlated with DFS (P<.001). The cumulative incidence (CI) of relapse at 2-yrs post-transplantation for the responders was 23{\%}; for the untreated group was 38{\%}; and for the failures was 50{\%}. The CI of non-relapse mortality at 2-yrs post-transplantation, for the responders was 23{\%}; for the untreated group was 38{\%}; and for the failures was 40{\%}. All survivors achieved a Karnofsky Performance Status (KPS) of ≥90. These results indicate that patients with advanced MDS who achieve and remain in remission or a second refractory cytopenia phase with chemotherapy before conditioning can achieve successful long-term remissions following a myeloablative T cell depleted allogeneic HSCT.",
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T1 - Transplantation in Remission Improves the Disease-Free Survival of Patients with Advanced Myelodysplastic Syndromes Treated with Myeloablative T Cell-Depleted Stem Cell Transplants from HLA-Identical Siblings

AU - Castro-Malaspina, Hugo

AU - Jabubowski, Ann A.

AU - Papadopoulos, Esperanza B.

AU - Boulad, Farid

AU - Young, James W.

AU - Kernan, Nancy A.

AU - Perales, Miguel A.

AU - Small, Trudy N.

AU - Hsu, Katharine

AU - Chiu, Michelle

AU - Heller, Glenn

AU - Collins, Nancy H.

AU - Jhanwar, Suresh C.

AU - van den Brink, Marcel

AU - Nimer, Stephen D

AU - O'Reilly, Richard J.

PY - 2008/4/1

Y1 - 2008/4/1

N2 - From 1985 to 2004, 49 patients with advanced myelodysplastic syndromes (MDS) (≥5% blasts) or acute myeloid leukemia (AML) transformed from MDS underwent T cell depleted bone marrow or peripheral blood hematopoietic stem cell transplantation (HSCT) from HLA-identical siblings following conditioning with a myeloablative regimen that included total body irradiation (44 patients) or busulfan (5 patients). Thirty-six patients received chemotherapy (3 low dose and 33 induction doses) before conditioning, and 13 patients did not receive any chemotherapy. Prior to transplantation, 22 of the 36 treated patients were in hematologic remission; 4 were in a second refractory cytopenia phase (26 responders); 8 had failed to achieve remission; and 2 of the responders had progression or relapse of their MDS (10 failures). No post-transplantation pharmacologic prophylaxis for graft-versus-host disease (GVHD) was given. The median age was 48 yrs (range 13-61). Forty-five of the 49 patients engrafted; 2 had primary graft failure; and 2 died before engraftment. Only 3 patients developed acute GVHD (aGVHD) (grades I and III) and 1 chronic GVHD (cGVHD). At 3 yrs post-transplantation, the overall survival (OS) was 54% in the responders; 31% in the untreated group; and 0% in the failure group (P=.0004). The disease free survival (DFS) was 50%, 15% and 0% in each group respectively (P=.0008). In multivariate analysis, disease status before cytoreduction remained highly correlated with DFS (P<.001). The cumulative incidence (CI) of relapse at 2-yrs post-transplantation for the responders was 23%; for the untreated group was 38%; and for the failures was 50%. The CI of non-relapse mortality at 2-yrs post-transplantation, for the responders was 23%; for the untreated group was 38%; and for the failures was 40%. All survivors achieved a Karnofsky Performance Status (KPS) of ≥90. These results indicate that patients with advanced MDS who achieve and remain in remission or a second refractory cytopenia phase with chemotherapy before conditioning can achieve successful long-term remissions following a myeloablative T cell depleted allogeneic HSCT.

AB - From 1985 to 2004, 49 patients with advanced myelodysplastic syndromes (MDS) (≥5% blasts) or acute myeloid leukemia (AML) transformed from MDS underwent T cell depleted bone marrow or peripheral blood hematopoietic stem cell transplantation (HSCT) from HLA-identical siblings following conditioning with a myeloablative regimen that included total body irradiation (44 patients) or busulfan (5 patients). Thirty-six patients received chemotherapy (3 low dose and 33 induction doses) before conditioning, and 13 patients did not receive any chemotherapy. Prior to transplantation, 22 of the 36 treated patients were in hematologic remission; 4 were in a second refractory cytopenia phase (26 responders); 8 had failed to achieve remission; and 2 of the responders had progression or relapse of their MDS (10 failures). No post-transplantation pharmacologic prophylaxis for graft-versus-host disease (GVHD) was given. The median age was 48 yrs (range 13-61). Forty-five of the 49 patients engrafted; 2 had primary graft failure; and 2 died before engraftment. Only 3 patients developed acute GVHD (aGVHD) (grades I and III) and 1 chronic GVHD (cGVHD). At 3 yrs post-transplantation, the overall survival (OS) was 54% in the responders; 31% in the untreated group; and 0% in the failure group (P=.0004). The disease free survival (DFS) was 50%, 15% and 0% in each group respectively (P=.0008). In multivariate analysis, disease status before cytoreduction remained highly correlated with DFS (P<.001). The cumulative incidence (CI) of relapse at 2-yrs post-transplantation for the responders was 23%; for the untreated group was 38%; and for the failures was 50%. The CI of non-relapse mortality at 2-yrs post-transplantation, for the responders was 23%; for the untreated group was 38%; and for the failures was 40%. All survivors achieved a Karnofsky Performance Status (KPS) of ≥90. These results indicate that patients with advanced MDS who achieve and remain in remission or a second refractory cytopenia phase with chemotherapy before conditioning can achieve successful long-term remissions following a myeloablative T cell depleted allogeneic HSCT.

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KW - Myelodysplastic syndromes

KW - T cell depletion

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