Peripheral-blood stem cells versus bone marrow from unrelated donors

Claudio Anasetti, Brent R Logan, Stephanie J Lee, Edmund K Waller, Daniel J Weisdorf, John R Wingard, Corey S Cutler, Peter Westervelt, Ann Woolfrey, Stephen Couban, Gerhard Ehninger, Laura Johnston, Richard T Maziarz, Michael A Pulsipher, David L Porter, Shin Mineishi, John M McCarty, Shakila P Khan, Paolo Anderlini, William I Bensinger, Susan F Leitman, Scott D Rowley, Christopher Bredeson, Shelly L Carter, Mary M Horowitz, Dennis L Confer, Blood and Marrow Transplant Clinical Trials Network, Mary M Horowitz, Shelly L Carter, Dennis L Confer, Nancy DiFronzo, Elizabeth Wagner, William Merritt, Roy Wu, Claudio Anasetti, Brent R Logan, Stephanie J Lee, Edmund K Waller, Daniel J Weisdorf, John R Wingard, Stephen Couban, Paolo Anderlini, William I Bensinger, Susan F Leitman, Scott D Rowley, Shelly L Carter, Catchada Karanes, Mary M Horowitz, Dennis L Confer, Colleen Allen, Colleen Colby, Cathy Gurgol, Kristin Knust, Amy Foley, Roberta King, Phyllis Mitchell, Stephen Couban, Michael A Pulsipher, Gerhard Ehninger, Laura Johnston, Shakila P Khan, Richard T Maziarz, John M McCarty, Shin Mineishi, David L Porter, Christopher Bredeson, Claudio Anasetti, Stephanie Lee, Edmund K Waller, John R Wingard, Corey S Cutler, Peter Westervelt, Ann Woolfrey, Brent R Logan, Shelly L Carter, Stephanie J Lee, Edmund K Waller, Claudio Anasetti, Brent R Logan, Stephanie J Lee, Edward Stadtmauer, John Wingard, Julie Vose, Hillard Lazarus, Mort Cowan, John Wingard, Peter Westervelt, Mark Litzow, Roy Wu, Nancy Geller, Shelly Carter, Dennis Confer, Mary Horowitz, Nancy Poland, Robert Krance, George Carrum, Edward Agura, Auayporn Nademanee, Indira Sahdev, Corey Cutler, Mitchell Eric Horwitz, Joanne Kurtzberg, Edmund K Waller, Ann Woolfrey, Scott Rowley, Joel Brochstein, Brian Leber, Parveen Wasi, Jean Roy, Jan Jansen, Patrick Joseph Stiff, Shakila Khan, Steven Devine, Richard Maziarz, Eneida Nemecek, Lothar Huebsch, Stephen Couban, Philip McCarthy, Laura Johnston, Paul Shaughnessy, Lynn Savoie, Edward Ball, William Vaughan, Morton Cowan, Bilijana Horn, John Wingard, Margarida Silverman, Sunil Abhyankar, Joseph McGuirk, Saul Yanovich, James Ferrara, Daniel Weisdorf, Edward Faber Jr, George Selby, Laura Marie Rooms, David Porter, Mounzer Agha, Paolo Anderlini, Jeffrey Lipton, Michael A Pulsipher, Michael A Pulsipher, John Shepherd, Cindy Toze, Adetola Kassim, Haydar Frangoul, John McCarty, David Hurd, John DiPersio, Peter Westervelt, Shalini Shenoy, Edward Agura, Elizabeth Culler, Frederick Axelrod, Linda Chambers, Eric Senaldi, Kim-Anh Nguyen, Edgar Engelman, Robert Hartzman, Laurie Sutor, Larry Dickson, Auayporn Nademanee, Ghada Khalife, Bruce A Lenes, Gretchen Eames, David Sibley, Peter Gale, Joseph Antin, Gerhard Ehninger, Neil R Newberg, Richard Gammon, Matthew Montgomery, Buff Mair, Susan Rossmann, Randal Wada, Dan Waxman, Robert Ranlett, Margarida Silverman, Geoffrey Herzig, Marek Fried, Elizabeth Atkinson, LeeAnn Weitekamp, Carolyn Bigelow, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, Thomas Price, Carolyn Young, Roger Hilbert, David Oh, Christian Cable, James W Smith, Norman D Kalmin, Karl Schultheiss, Thomas Beck, Michael W Lankiewicz, David Sharp, Claudio Anasetti, Brent R Logan, Stephanie J Lee, Edmund K Waller, Daniel J Weisdorf, John R Wingard, Corey S Cutler, Peter Westervelt, Ann Woolfrey, Stephen Couban, Gerhard Ehninger, Laura Johnston, Richard T Maziarz, Michael A Pulsipher, David L Porter, Shin Mineishi, John M McCarty, Shakila P Khan, Paolo Anderlini, William I Bensinger, Susan F Leitman, Scott D Rowley, Christopher Bredeson, Shelly L Carter, Mary M Horowitz, Dennis L Confer, Blood and Marrow Transplant Clinical Trials Network, Mary M Horowitz, Shelly L Carter, Dennis L Confer, Nancy DiFronzo, Elizabeth Wagner, William Merritt, Roy Wu, Claudio Anasetti, Brent R Logan, Stephanie J Lee, Edmund K Waller, Daniel J Weisdorf, John R Wingard, Stephen Couban, Paolo Anderlini, William I Bensinger, Susan F Leitman, Scott D Rowley, Shelly L Carter, Catchada Karanes, Mary M Horowitz, Dennis L Confer, Colleen Allen, Colleen Colby, Cathy Gurgol, Kristin Knust, Amy Foley, Roberta King, Phyllis Mitchell, Stephen Couban, Michael A Pulsipher, Gerhard Ehninger, Laura Johnston, Shakila P Khan, Richard T Maziarz, John M McCarty, Shin Mineishi, David L Porter, Christopher Bredeson, Claudio Anasetti, Stephanie Lee, Edmund K Waller, John R Wingard, Corey S Cutler, Peter Westervelt, Ann Woolfrey, Brent R Logan, Shelly L Carter, Stephanie J Lee, Edmund K Waller, Claudio Anasetti, Brent R Logan, Stephanie J Lee, Edward Stadtmauer, John Wingard, Julie Vose, Hillard Lazarus, Mort Cowan, John Wingard, Peter Westervelt, Mark Litzow, Roy Wu, Nancy Geller, Shelly Carter, Dennis Confer, Mary Horowitz, Nancy Poland, Robert Krance, George Carrum, Edward Agura, Auayporn Nademanee, Indira Sahdev, Corey Cutler, Mitchell Eric Horwitz, Joanne Kurtzberg, Edmund K Waller, Ann Woolfrey, Scott Rowley, Joel Brochstein, Brian Leber, Parveen Wasi, Jean Roy, Jan Jansen, Patrick Joseph Stiff, Shakila Khan, Steven Devine, Richard Maziarz, Eneida Nemecek, Lothar Huebsch, Stephen Couban, Philip McCarthy, Laura Johnston, Paul Shaughnessy, Lynn Savoie, Edward Ball, William Vaughan, Morton Cowan, Bilijana Horn, John Wingard, Margarida Silverman, Sunil Abhyankar, Joseph McGuirk, Saul Yanovich, James Ferrara, Daniel Weisdorf, Edward Faber Jr, George Selby, Laura Marie Rooms, David Porter, Mounzer Agha, Paolo Anderlini, Jeffrey Lipton, Michael A Pulsipher, Michael A Pulsipher, John Shepherd, Cindy Toze, Adetola Kassim, Haydar Frangoul, John McCarty, David Hurd, John DiPersio, Peter Westervelt, Shalini Shenoy, Edward Agura, Elizabeth Culler, Frederick Axelrod, Linda Chambers, Eric Senaldi, Kim-Anh Nguyen, Edgar Engelman, Robert Hartzman, Laurie Sutor, Larry Dickson, Auayporn Nademanee, Ghada Khalife, Bruce A Lenes, Gretchen Eames, David Sibley, Peter Gale, Joseph Antin, Gerhard Ehninger, Neil R Newberg, Richard Gammon, Matthew Montgomery, Buff Mair, Susan Rossmann, Randal Wada, Dan Waxman, Robert Ranlett, Margarida Silverman, Geoffrey Herzig, Marek Fried, Elizabeth Atkinson, LeeAnn Weitekamp, Carolyn Bigelow, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, John P Miller, Thomas Price, Carolyn Young, Roger Hilbert, David Oh, Christian Cable, James W Smith, Norman D Kalmin, Karl Schultheiss, Thomas Beck, Michael W Lankiewicz, David Sharp

Abstract

Background: Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia.

Methods: We conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37).

Results: The overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval [CI], 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P=0.29), with an absolute difference of 5 percentage points (95% CI, -3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P=0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P=0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse.

Conclusions: We did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD. (Funded by the National Heart, Lung, and Blood Institute-National Cancer Institute and others; ClinicalTrials.gov number, NCT00075816.).

Figures

Figure 1. Survival after Randomization in the…
Figure 1. Survival after Randomization in the Intention-to-Treat Analysis
The P value is from a stratified binomial comparison at the 2-year point. The P value from a stratified log-rank test was also not significant. A total of 75 patients in each group were still alive at 36 months.
Figure 2. Outcomes after Transplantation, According to…
Figure 2. Outcomes after Transplantation, According to Study Group
Panel A shows the rate of overall survival, and Panel B the rate of disease-free survival. Panel C shows the incidence of death unrelated to relapse. Panel D shows the incidence of relapse. Panel E shows the incidence of neutrophil engraftment (>500 neutrophils per cubic millimeter), and Panel F the incidence of platelet engraftment (>20,000 platelets per cubic millimeter, without platelet transfusion during the prior 7 days). Panel G shows the incidence of acute graft-versus-host disease (GVHD) of grades II to IV, and Panel H the incidence of chronic GVHD. P values for the between-group differences in overall survival (Panel A) and disease-free survival (Panel B) are from a stratified binomial comparison at the 2-year point; P values from stratified log-rank tests for survival and disease-free survival were also not significant. All other P values shown are from stratified log-rank tests.

Source: PubMed

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