TY - JOUR
T1 - Low CD34 dose is associated with poor survival after reduced-intensity conditioning allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndrome
AU - Törlén, Johan
AU - Ringdén, Olle
AU - Le Rademacher, Jennifer
AU - Batiwalla, Minoo
AU - Chen, Junfang
AU - Erkers, Tom
AU - Ho, Vincent
AU - Kebriaei, Partow
AU - Keever-Taylor, Carolyn
AU - Kindwall-Keller, Tamila
AU - Lazarus, Hillard M.
AU - Laughlin, Mary J.
AU - Lill, Michael
AU - O'Brien, Tracey
AU - Perales, Miguel Angel
AU - Rocha, Vanderson
AU - Savani, Bipin N.
AU - Szwajcer, David
AU - Valcarcel, David
AU - Eapen, Mary
N1 - Funding Information:
The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID) U24-CA076518; a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and National Cancer Institute ; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); 2 Grants N00014-12-1-0142 and N00014-13-1-0039 from the Office of Naval Research ; and grants from * Actinium Pharmaceuticals ; Allos Therapeutics, Inc. ; ∗ Amgen, Inc. ; Anonymous donation to the Medical College of Wisconsin; Ariad Pharmaceuticals ; Be The Match Foundation ; ∗ Blue Cross and Blue Shield Association ; ∗ Celgene Corporation; Chimerix, Inc. ; Fred Hutchinson Cancer Research Center ; Fresenius-Biotech North America, Inc. ; ∗ Gamida Cell Teva Joint Venture Ltd. ; Genentech, Inc. ; ∗ Gentium SpA ; Genzyme Corporation; GlaxoSmithKline ; Health Research, Inc. Roswell Park Cancer Institute ; HistoGenetics, Inc. ; Incyte Corporation ; Jeff Gordon Children's Foundation ; Kiadis Pharma ; Medac GmbH ; The Medical College of Wisconsin; Merck & Co, Inc. ; Millennium: The Takeda Oncology Co. ; ∗ Milliman USA, Inc. ; ∗ Miltenyi Biotec, Inc. ; National Marrow Donor Program ; Onyx Pharmaceuticals ; Optum Healthcare Solutions, Inc. ; Osiris Therapeutics, Inc. ; Otsuka America Pharmaceutical, Inc. ; Perkin Elmer, Inc. ; ∗ Remedy Informatics ; ∗ Sanofi US ; Seattle Genetics ; Sigma-Tau Pharmaceuticals ; Soligenix, Inc. ; St. Baldrick's Foundation ; StemCyte , A Global Cord Blood Therapeutics Co. ; Stemsoft Software, Inc. ; Swedish Orphan Biovitrum ; ∗ Tarix Pharmaceuticals ; ∗ Terumo BCT ; ∗ Teva Neuroscience, Inc. ; ∗ Texas Instruments Inc. ; and ∗ WellPoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US Government.
PY - 2014/9
Y1 - 2014/9
N2 - Reduced-intensity conditioning/nonmyeloablative conditioning regimens are increasingly used in allogeneic hematopoietic cell transplantation (HCT). Reports have shown CD34+ dose to be important for transplantation outcome using myeloablative conditioning. The role of CD34+ dose of peripheral blood progenitor cells (PBPC) has not been previously analyzed in a large population undergoing reduced-intensity conditioning/nonmyeloablative HCT. We studied 1054 patients, ages 45 to 75years, with acute myeloid leukemia or myelodysplastic syndrome who underwent transplantation between 2002 and 2011. Results of multivariate analysis showed that PBPC from HLA-matched siblings containing <4×106 CD34+/kg was associated with higher nonrelapse mortality (hazard ratio [HR], 2.03; P=001), overall mortality (HR, 1.48; P=008), and lower neutrophil (odds ratio [OR], .76; P=03) and platelet (OR, .76; P=03) recovery. PBPC from unrelated donors with CD34+ dose < 6×106 CD34+/kg was also associated with higher nonrelapse (HR, 1.38; P=02) and overall mortality (HR, 1.20; P=05). In contrast to reports after myeloablative HCT, CD34+ dose did not affect relapse or graft-versus-host disease with either donor type. An upper cell dose limit was not associated with adverse outcomes. These data suggest that PBPC CD34+ doses >4×106 CD34+/kg and >6×106 CD34+/kg are optimal for HLA-matched sibling and unrelated donor HCT, respectively.
AB - Reduced-intensity conditioning/nonmyeloablative conditioning regimens are increasingly used in allogeneic hematopoietic cell transplantation (HCT). Reports have shown CD34+ dose to be important for transplantation outcome using myeloablative conditioning. The role of CD34+ dose of peripheral blood progenitor cells (PBPC) has not been previously analyzed in a large population undergoing reduced-intensity conditioning/nonmyeloablative HCT. We studied 1054 patients, ages 45 to 75years, with acute myeloid leukemia or myelodysplastic syndrome who underwent transplantation between 2002 and 2011. Results of multivariate analysis showed that PBPC from HLA-matched siblings containing <4×106 CD34+/kg was associated with higher nonrelapse mortality (hazard ratio [HR], 2.03; P=001), overall mortality (HR, 1.48; P=008), and lower neutrophil (odds ratio [OR], .76; P=03) and platelet (OR, .76; P=03) recovery. PBPC from unrelated donors with CD34+ dose < 6×106 CD34+/kg was also associated with higher nonrelapse (HR, 1.38; P=02) and overall mortality (HR, 1.20; P=05). In contrast to reports after myeloablative HCT, CD34+ dose did not affect relapse or graft-versus-host disease with either donor type. An upper cell dose limit was not associated with adverse outcomes. These data suggest that PBPC CD34+ doses >4×106 CD34+/kg and >6×106 CD34+/kg are optimal for HLA-matched sibling and unrelated donor HCT, respectively.
KW - Cellular content
KW - Hematological malignancy
KW - Peripheral blood graft
UR - http://www.scopus.com/inward/record.url?scp=84905586102&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84905586102&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2014.05.021
DO - 10.1016/j.bbmt.2014.05.021
M3 - Article
C2 - 24892261
AN - SCOPUS:84905586102
SN - 1083-8791
VL - 20
SP - 1418
EP - 1425
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 9
ER -