Fresh or Cryopreserved CD34 + -Selected Mobilized Peripheral Blood Stem and Progenitor Cells for the Treatment of Poor Graft Function after Allogeneic Hematopoietic Cell Transplantation

Abstract

CD34+-selected stem cell boost (SCB) without conditioning have recently been utilized for poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) 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 G-CSF. Twenty six patients with poor graft function were included in this study. Seventeen donor-recipient pairs were enrolled onto the prospective study; 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. Primary objective was hematologic response rate and secondary objectives included CD34+ yields, incidence and severity of acute and chronic GVHD, overall survival (OS), and relapse-free survival (RFS). The median post-selection CD34+ count per kg of recipient weight was 3.1×106, 10.9×106, and 1×106 for 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 prior to CD34+ selection) was 69%, 66%, and 28% for G-CSF only, G-CSF plus plerixafor, and cryopreserved products, respectively. Following 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%. There was no treatment related toxicity reported other than graft-versus-host-disease (GVHD); six (23%) developed acute GVHD (2 grade I and 4 grade II), Eight (31%) 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.

Cryopreservation of adult unrelated donor products in hematopoietic cell transplantation: the OneMatch experience and systematic review of the literature

“…No apparent difference in time to platelet (PLT) recovery (10 studies reporting median days to PLT count of >20 × 10 9 /L; five studies reporting median days to PLT count of >50 × 10 9 /L) or neutrophil engraftment (18 studies reporting median days to neutrophil count of >0.5 × 10 9 /L) was reported in any of the studies in comparison to controls (Table ). Moreover, no apparent difference in CD34+ cells infused (eight studies) was reported for patients receiving cryopreserved products compared to controls receiving fresh products (Table ). The yield of CD34+ cells available after thawing was 31% to 100% (data reported in eight studies).…”

“…Moreover, no apparent difference in CD34+ cells infused (eight studies) was reported for patients receiving cryopreserved products compared to controls receiving fresh products (Table ). The yield of CD34+ cells available after thawing was 31% to 100% (data reported in eight studies).…”

“…The 32 studies that met the inclusion criteria described a total of 993 patients, and half of these studies were published before 2000 . The studies were from groups in North America (12), Europe (15), Asia (four), and elsewhere (one).…”

“…Moreover, 57% of study participants were males. Some studies have been published as abstracts only or letter to the editor, while a majority of the included studies were full publications …”

Robust Selections of Various Hematopoietic Cell Fractions on the CliniMACS Plus Instrument

“…In prior studies, we and others have found that the CliniMACS Plus immunomagnetic selection method has shown superior CP and VCR compared with other technologies, particularly with regard to CD34+ cell selection from mobilized peripheral blood [5,11]. Since then, this technique has been successfully applied to CD34+ cell selections on bone marrow collections and umbilical cord blood, as well as on cryopreserved and thawed cells [12][13][14][15]. Further, other cell subtypes, including monocytes, NK cells and T-lymphocytes selected on the instrument have also been utilized in early phase clinical studies [8,[16][17][18].…”