Long-term disease-free survival after nonmyeloablative cyclophosphamide/ fludarabine conditioning and related/unrelated allotransplantation for acute myeloid leukemia/myelodysplasia

Robert Nelson, M. Yu, J. E. Schwartz, Michael Robertson, R. Hromas, C. A. Fausel, Gail Vance, Stephen Dlouhy, J. A. Baute, E. A. Cox, L. L. Wood, S. Srivastava, Kent Robertson, Paul Haut, Sherif Farag, Rafat Abonour, Kenneth Cornetta, Larry Cripe

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13 Citations (Scopus)

Abstract

A total of 50 consecutive patients (median age, 57.5 years) with AML (n30) or myelodysplasia (MDS, n20) underwent HLA matched related donor (MRD, n27) or unrelated donor (MUD, n23) peripheral blood hematopoietic cell transplantation after nonmyeloablative CY/fludarabine (Flu) conditioning. GVHD prophylaxis included CsA (n19)mycophenolate mofetil (n31). At a median follow-up of 59 months, 21 patients (42%) were alive without evidence of disease. By Kaplan-Meier analysis, year 1-4 disease-free survival (DFS) and OS estimates were 0.50/0.58, 0.40/0.46, 0.37/0.43 and 0.37/0.41. MUD recipients were engrafted quickly (13.5 days) compared to MRD recipients (16 days) and relapsed/progressed less frequently (P0.005). Overall grade 3/4 acute GVHD (aGVHD) occurred in 26% in the absence of antecedent mucositis and was associated with chronic GVHD (cGVHD) and poor OS. Extensive cGVHD developed in 51.2% of 100 day survivors. Rates of aGVHD, cGVHD and survival were similar between MRD and MUD recipients. Of 14 survivors with cGVHD, 5 (35.7%) experienced resolution off immunosuppression, suggesting that tolerance with HLA matched grafts is possible at an advanced age by this method. This study provides further evidence for prolonged DFS after CY/Flu MRD allotransplantation for AML/MDS, and extends the findings to older patients and those with unrelated donors.

Original languageEnglish
Pages (from-to)1300-1308
Number of pages9
JournalBone Marrow Transplantation
Volume45
Issue number8
DOIs
StatePublished - Aug 2010

Fingerprint

Acute Myeloid Leukemia
Cyclophosphamide
Disease-Free Survival
Unrelated Donors
Survivors
Mycophenolic Acid
Mucositis
Cell Transplantation
Kaplan-Meier Estimate
Immunosuppression
Blood Cells
Tissue Donors
Transplants
Survival
fludarabine

Keywords

  • leukemia
  • minimal intensity
  • myelodysplasia
  • nonmyeloablative
  • transplantation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

@article{45d422a0d8e14f388ef6652a7474c7ba,
title = "Long-term disease-free survival after nonmyeloablative cyclophosphamide/ fludarabine conditioning and related/unrelated allotransplantation for acute myeloid leukemia/myelodysplasia",
abstract = "A total of 50 consecutive patients (median age, 57.5 years) with AML (n30) or myelodysplasia (MDS, n20) underwent HLA matched related donor (MRD, n27) or unrelated donor (MUD, n23) peripheral blood hematopoietic cell transplantation after nonmyeloablative CY/fludarabine (Flu) conditioning. GVHD prophylaxis included CsA (n19)mycophenolate mofetil (n31). At a median follow-up of 59 months, 21 patients (42{\%}) were alive without evidence of disease. By Kaplan-Meier analysis, year 1-4 disease-free survival (DFS) and OS estimates were 0.50/0.58, 0.40/0.46, 0.37/0.43 and 0.37/0.41. MUD recipients were engrafted quickly (13.5 days) compared to MRD recipients (16 days) and relapsed/progressed less frequently (P0.005). Overall grade 3/4 acute GVHD (aGVHD) occurred in 26{\%} in the absence of antecedent mucositis and was associated with chronic GVHD (cGVHD) and poor OS. Extensive cGVHD developed in 51.2{\%} of 100 day survivors. Rates of aGVHD, cGVHD and survival were similar between MRD and MUD recipients. Of 14 survivors with cGVHD, 5 (35.7{\%}) experienced resolution off immunosuppression, suggesting that tolerance with HLA matched grafts is possible at an advanced age by this method. This study provides further evidence for prolonged DFS after CY/Flu MRD allotransplantation for AML/MDS, and extends the findings to older patients and those with unrelated donors.",
keywords = "leukemia, minimal intensity, myelodysplasia, nonmyeloablative, transplantation",
author = "Robert Nelson and M. Yu and Schwartz, {J. E.} and Michael Robertson and R. Hromas and Fausel, {C. A.} and Gail Vance and Stephen Dlouhy and Baute, {J. A.} and Cox, {E. A.} and Wood, {L. L.} and S. Srivastava and Kent Robertson and Paul Haut and Sherif Farag and Rafat Abonour and Kenneth Cornetta and Larry Cripe",
year = "2010",
month = "8",
doi = "10.1038/bmt.2009.348",
language = "English",
volume = "45",
pages = "1300--1308",
journal = "Bone Marrow Transplantation",
issn = "0268-3369",
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T1 - Long-term disease-free survival after nonmyeloablative cyclophosphamide/ fludarabine conditioning and related/unrelated allotransplantation for acute myeloid leukemia/myelodysplasia

AU - Nelson, Robert

AU - Yu, M.

AU - Schwartz, J. E.

AU - Robertson, Michael

AU - Hromas, R.

AU - Fausel, C. A.

AU - Vance, Gail

AU - Dlouhy, Stephen

AU - Baute, J. A.

AU - Cox, E. A.

AU - Wood, L. L.

AU - Srivastava, S.

AU - Robertson, Kent

AU - Haut, Paul

AU - Farag, Sherif

AU - Abonour, Rafat

AU - Cornetta, Kenneth

AU - Cripe, Larry

PY - 2010/8

Y1 - 2010/8

N2 - A total of 50 consecutive patients (median age, 57.5 years) with AML (n30) or myelodysplasia (MDS, n20) underwent HLA matched related donor (MRD, n27) or unrelated donor (MUD, n23) peripheral blood hematopoietic cell transplantation after nonmyeloablative CY/fludarabine (Flu) conditioning. GVHD prophylaxis included CsA (n19)mycophenolate mofetil (n31). At a median follow-up of 59 months, 21 patients (42%) were alive without evidence of disease. By Kaplan-Meier analysis, year 1-4 disease-free survival (DFS) and OS estimates were 0.50/0.58, 0.40/0.46, 0.37/0.43 and 0.37/0.41. MUD recipients were engrafted quickly (13.5 days) compared to MRD recipients (16 days) and relapsed/progressed less frequently (P0.005). Overall grade 3/4 acute GVHD (aGVHD) occurred in 26% in the absence of antecedent mucositis and was associated with chronic GVHD (cGVHD) and poor OS. Extensive cGVHD developed in 51.2% of 100 day survivors. Rates of aGVHD, cGVHD and survival were similar between MRD and MUD recipients. Of 14 survivors with cGVHD, 5 (35.7%) experienced resolution off immunosuppression, suggesting that tolerance with HLA matched grafts is possible at an advanced age by this method. This study provides further evidence for prolonged DFS after CY/Flu MRD allotransplantation for AML/MDS, and extends the findings to older patients and those with unrelated donors.

AB - A total of 50 consecutive patients (median age, 57.5 years) with AML (n30) or myelodysplasia (MDS, n20) underwent HLA matched related donor (MRD, n27) or unrelated donor (MUD, n23) peripheral blood hematopoietic cell transplantation after nonmyeloablative CY/fludarabine (Flu) conditioning. GVHD prophylaxis included CsA (n19)mycophenolate mofetil (n31). At a median follow-up of 59 months, 21 patients (42%) were alive without evidence of disease. By Kaplan-Meier analysis, year 1-4 disease-free survival (DFS) and OS estimates were 0.50/0.58, 0.40/0.46, 0.37/0.43 and 0.37/0.41. MUD recipients were engrafted quickly (13.5 days) compared to MRD recipients (16 days) and relapsed/progressed less frequently (P0.005). Overall grade 3/4 acute GVHD (aGVHD) occurred in 26% in the absence of antecedent mucositis and was associated with chronic GVHD (cGVHD) and poor OS. Extensive cGVHD developed in 51.2% of 100 day survivors. Rates of aGVHD, cGVHD and survival were similar between MRD and MUD recipients. Of 14 survivors with cGVHD, 5 (35.7%) experienced resolution off immunosuppression, suggesting that tolerance with HLA matched grafts is possible at an advanced age by this method. This study provides further evidence for prolonged DFS after CY/Flu MRD allotransplantation for AML/MDS, and extends the findings to older patients and those with unrelated donors.

KW - leukemia

KW - minimal intensity

KW - myelodysplasia

KW - nonmyeloablative

KW - transplantation

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