Leukemia cell mobilization with G-CSF plus plerixafor during busulfan-fludarabine conditioning for allogeneic stem cell transplantation

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Abstract

We hypothesized that during conditioning chemotherapy for allogeneic stem cell transplant (allo-SCT), the disruption of stromal-leukemia interactions using G-CSF in combination with the CXCR4-specific inhibitor, plerixafor, may promote the release of leukemic cells from the niche and increase tumor elimination. In a phase 1/2 investigation, we treated 45 AML/myelodysplastic syndrome (MDS)/CML patients (34 AML, 7 MDS and 4 CML) with G-CSF (10 μg/kg daily for 6 days starting on day-9) plus plerixafor (doses of 0, 80, 160 or 240 μg/kg daily for 4 days starting on day-7) along with the busulfan-fludarabine (Bu-Flu) conditioning regimen. In the phase 1 part, we determined that G-CSF plus plerixafor is safe in this setting. We compared the clinical effects and outcomes of AML/MDS study patients (n=40) with 164 patients from a historical data set who received Bu-Flu alone before allo-SCT by stratifying on cytogenetics and disease status to correct for bias. Study patients had increased myeloid chimerism and lower rates of GvHD. There was no significant difference in relapse-free survival or overall survival. The G-CSF plus plerixafor combination increased circulating WBCs, CD34+ cells and CXCR4+ cells, and preferentially mobilized FISH+ leukemic cells.

Original languageEnglish (US)
Pages (from-to)939-946
Number of pages8
JournalBone marrow transplantation
Volume50
Issue number7
DOIs
StatePublished - Jul 3 2015

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Busulfan
Stem Cell Transplantation
Granulocyte Colony-Stimulating Factor
Myelodysplastic Syndromes
Leukemia
Stem Cells
Transplants
Chimerism
Survival
Cytogenetics
Recurrence
Drug Therapy
JM 3100
fludarabine
Neoplasms

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

@article{12685cbe16fa433093f76422f5542c3a,
title = "Leukemia cell mobilization with G-CSF plus plerixafor during busulfan-fludarabine conditioning for allogeneic stem cell transplantation",
abstract = "We hypothesized that during conditioning chemotherapy for allogeneic stem cell transplant (allo-SCT), the disruption of stromal-leukemia interactions using G-CSF in combination with the CXCR4-specific inhibitor, plerixafor, may promote the release of leukemic cells from the niche and increase tumor elimination. In a phase 1/2 investigation, we treated 45 AML/myelodysplastic syndrome (MDS)/CML patients (34 AML, 7 MDS and 4 CML) with G-CSF (10 μg/kg daily for 6 days starting on day-9) plus plerixafor (doses of 0, 80, 160 or 240 μg/kg daily for 4 days starting on day-7) along with the busulfan-fludarabine (Bu-Flu) conditioning regimen. In the phase 1 part, we determined that G-CSF plus plerixafor is safe in this setting. We compared the clinical effects and outcomes of AML/MDS study patients (n=40) with 164 patients from a historical data set who received Bu-Flu alone before allo-SCT by stratifying on cytogenetics and disease status to correct for bias. Study patients had increased myeloid chimerism and lower rates of GvHD. There was no significant difference in relapse-free survival or overall survival. The G-CSF plus plerixafor combination increased circulating WBCs, CD34+ cells and CXCR4+ cells, and preferentially mobilized FISH+ leukemic cells.",
author = "Marina Konopleva and Benton, {Christopher Brent} and Thall, {Peter F} and Zhihong Zeng and Elizabeth Shpall and Ciurea, {Stefan Octavian} and Partow Kebriaei and Alousi, {Amin Majid} and Popat, {Uday R} and Paolo Anderlini and Yago Nieto and Simrit Parmar and W. Qiao and J. Chen and Gabriela Rondon and B. McMullin and Wang, {R. Y.} and Huifang Lu and W. Schober and G. Woodworth and A. Gulbis and R. Cool and Michael Andreeff and Champlin, {Richard E}",
year = "2015",
month = "7",
day = "3",
doi = "10.1038/bmt.2015.58",
language = "English (US)",
volume = "50",
pages = "939--946",
journal = "Bone Marrow Transplantation",
issn = "0268-3369",
publisher = "Nature Publishing Group",
number = "7",

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T1 - Leukemia cell mobilization with G-CSF plus plerixafor during busulfan-fludarabine conditioning for allogeneic stem cell transplantation

AU - Konopleva, Marina

AU - Benton, Christopher Brent

AU - Thall, Peter F

AU - Zeng, Zhihong

AU - Shpall, Elizabeth

AU - Ciurea, Stefan Octavian

AU - Kebriaei, Partow

AU - Alousi, Amin Majid

AU - Popat, Uday R

AU - Anderlini, Paolo

AU - Nieto, Yago

AU - Parmar, Simrit

AU - Qiao, W.

AU - Chen, J.

AU - Rondon, Gabriela

AU - McMullin, B.

AU - Wang, R. Y.

AU - Lu, Huifang

AU - Schober, W.

AU - Woodworth, G.

AU - Gulbis, A.

AU - Cool, R.

AU - Andreeff, Michael

AU - Champlin, Richard E

PY - 2015/7/3

Y1 - 2015/7/3

N2 - We hypothesized that during conditioning chemotherapy for allogeneic stem cell transplant (allo-SCT), the disruption of stromal-leukemia interactions using G-CSF in combination with the CXCR4-specific inhibitor, plerixafor, may promote the release of leukemic cells from the niche and increase tumor elimination. In a phase 1/2 investigation, we treated 45 AML/myelodysplastic syndrome (MDS)/CML patients (34 AML, 7 MDS and 4 CML) with G-CSF (10 μg/kg daily for 6 days starting on day-9) plus plerixafor (doses of 0, 80, 160 or 240 μg/kg daily for 4 days starting on day-7) along with the busulfan-fludarabine (Bu-Flu) conditioning regimen. In the phase 1 part, we determined that G-CSF plus plerixafor is safe in this setting. We compared the clinical effects and outcomes of AML/MDS study patients (n=40) with 164 patients from a historical data set who received Bu-Flu alone before allo-SCT by stratifying on cytogenetics and disease status to correct for bias. Study patients had increased myeloid chimerism and lower rates of GvHD. There was no significant difference in relapse-free survival or overall survival. The G-CSF plus plerixafor combination increased circulating WBCs, CD34+ cells and CXCR4+ cells, and preferentially mobilized FISH+ leukemic cells.

AB - We hypothesized that during conditioning chemotherapy for allogeneic stem cell transplant (allo-SCT), the disruption of stromal-leukemia interactions using G-CSF in combination with the CXCR4-specific inhibitor, plerixafor, may promote the release of leukemic cells from the niche and increase tumor elimination. In a phase 1/2 investigation, we treated 45 AML/myelodysplastic syndrome (MDS)/CML patients (34 AML, 7 MDS and 4 CML) with G-CSF (10 μg/kg daily for 6 days starting on day-9) plus plerixafor (doses of 0, 80, 160 or 240 μg/kg daily for 4 days starting on day-7) along with the busulfan-fludarabine (Bu-Flu) conditioning regimen. In the phase 1 part, we determined that G-CSF plus plerixafor is safe in this setting. We compared the clinical effects and outcomes of AML/MDS study patients (n=40) with 164 patients from a historical data set who received Bu-Flu alone before allo-SCT by stratifying on cytogenetics and disease status to correct for bias. Study patients had increased myeloid chimerism and lower rates of GvHD. There was no significant difference in relapse-free survival or overall survival. The G-CSF plus plerixafor combination increased circulating WBCs, CD34+ cells and CXCR4+ cells, and preferentially mobilized FISH+ leukemic cells.

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DO - 10.1038/bmt.2015.58

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