Fresh or Cryopreserved CD34+-Selected Mobilized Peripheral Blood Stem and Progenitor Cells for the Treatment of Poor Graft Function after Allogeneic Hematopoietic Cell Transplantation.
CD34+-selected stem cell boost (SCB) without conditioning has recently been utilized for poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation with promising results. Unfortunately, many patients have been unable to receive the boost infusion as their donors were unwilling or unable to undergo an additional stem cell collection. Therefore, we conducted this study utilizing either fresh or cryopreserved peripheral blood stem cell products to create CD34+-selected boost infusions for the treatment of PGF. Additionally, to explore relationship of CD34+dose and response, we included a cohort of donors mobilized with plerixafor in addition to the standard granulocyte colony-stimulating factor (G-CSF). Twenty-six patients with PGF were included in this study. Seventeen donor-recipient pairs were enrolled onto the prospective study; an additional 9 patients treated off protocol were reviewed retrospectively. Three different donor products were used for CD34+selection: (1) fresh mobilized product using G-CSF only, (2) fresh mobilized products using G-CSF and plerixafor, and (3) cryopreserved cells mobilized with G-CSF. CD34+cell selection was performed using a CliniMACS. The infusion was not preceded by administration of any chemotherapy or conditioning regimen. The primary objective was hematologic response rate and secondary objectives included CD34+yields, incidence and severity of acute and chronic graft-versus-host disease (GVHD), overall survival (OS), and relapse-free survival (RFS). The median post-selection CD34+counts per kilogram of recipient weight were 3.1 × 106, 10.9 × 106, and 1 × 106for G-CSF only, G-CSF plus plerixafor, and cryopreserved products, respectively. The median CD34+yields (defined as the number of CD34+cells after selection/CD34+cells before CD34+selection) were 69%, 66%, and 28% for G-CSF only, G-CSF plus plerixafor, and cryopreserved products, respectively. After SCB, 16 of the 26 recipients (62%) had a complete response, including 5 of 8 (63%) who received cryopreserved products. Five had a partial response (19%), resulting in an overall response rate of 81%. One-year RFS and OS were 50% and 65%, respectively. There was no treatment-related toxicity reported other than GVHD: 6 (23%) developed acute GVHD (2 grade I and 4 grade II) and 8 (31%) developed chronic GVHD (2 limited and 6 extensive). Cryopreserved products are viable alternatives to create SCB for the treatment of PGF. When collecting fresh products is an option, the addition of plerixafor increases CD34+yield over G-CSF alone; however, it is currently unclear if the CD34+cell dose impacts the efficacy of the SCB.
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. Electronic address: arminghobadi@wustl.edu.
Armin
A
Ghobadi
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Mark A
MA
Fiala
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Giridharan
G
Ramsingh
Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.
Feng
F
Gao
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Camille N
CN
Abboud
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Keith
K
Stockerl-Goldstein
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Geoffrey L
GL
Uy
Division of Laboratory and Genomic Medicine, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri.
Brenda J
BJ
Grossman
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Peter
P
Westervelt
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
John F
JF
DiPersio
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013234:Stem Cells / Q000378:metabolism*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods*
D018952:Antigens, CD34
Boost infusion; Cell therapy; Poor graft function; Stem cell boost