Delayed Neutrophil Engraftment in Autologous Transplant Patients with Very High CD34+ Cell Collections in a Single Apheresis

Background: The number of CD34+ cells infused during autologous hematopoietic stem cell transplantation (auto-HSCT) is the most important determinant of the speed of engraftment and neutrophil recovery. Increasing the infused CD34+ cell doses results in faster neutrophil recovery, but infusion of more than 5-10 x 10⁶/kg CD34+ cells typically does not hasten engraftment any further. In contrast, we have noticed cases of delayed engraftment when the number of CD34+ cells collected has been extraordinarily high. We report a single center experience of engraftment in auto-HSCT patients with very high CD34+ cell numbers collected in a single apheresis session (typically 20 L blood volume).

Methods: Utilizing the database of the Stem Cell Transplantation and Cell Therapy Program and the Mathews Center for Cellular Therapy, we studied apheresis and engraftment data on patients undergoing auto-HSCT for hematologic malignancies at Northwestern Memorial Hospital from January 2000 through June 2022. Inclusion criteria were age ≥18 years, ≥20 x 10⁶/kg CD34+ cells collected in a single aphaeresis session, and available neutrophil engraftment data. Time to neutrophil engraftment was defined as days from stem cell infusion to the first of three consecutive days of absolute neutrophil count ≥0.5 x 10⁹/L. Delayed engraftment was defined as ≥20 days to neutrophil recovery. Fisher's exact test of independence was utilized to determine the statistical significance of the difference between variables.

Results: We identified 214 patients with a yield of ≥20 x 10⁶/kg CD34+ cells in one apheresis session. Patients were divided into two groups depending on the number of CD34+ cells collected; ≥20 but <50 (group A; n=93) and ≥50 (group B; n=121). Group A had a median collection of 31.1 x 10⁶/kg CD34+ cells and group B had 66.8 x 10⁶/kg. For group A, the median time to neutrophil recovery was 12 days, compared with 11 days for group B. Zero out of 93 patients in group A had delayed engraftment compared with 7 of the 121 patients (6%) in group B (P=0.022). All 7 patients with delayed engraftment were mobilized with single-agent granulocyte-colony stimulating factor. Four patients had myeloma, 2 acute promyelocytic leukemia (APL), and 1 Waldenstrom's macroglobulinemia (WM) (Table 1). Patients with myeloma and WM (all in first partial remission) received high-dose melphalan conditioning and patients with APL (both in second complete remission) received busulfan-cyclophosphamide. For the 7 patients with delayed engraftment, the median number of CD34+ cells infused was 14.5 x 10⁶/kg (range 9.5-19.6) with a median time to neutrophil engraftment of 24 days (range 20-38).

Conclusions: We describe an uncommon phenomenon of delayed engraftment in some patients with very high CD34+ cell yields in a single apheresis. Additional studies on stored autologous stem cells are needed to elucidate the cause of this peculiar finding.

Winter:Servier: Consultancy, Other: For Spouse; CVS/Caremark: Consultancy, Other: For Spouse; Astellas: Other: For Spouse, to University of Chicago, Research Funding; Forty Seven/Gilead: Other: For Spouse, to University of Chicago, Research Funding; Rafael: Other: For Spouse, to University of Chicago, Research Funding; Novartis: Consultancy, Other: for Spouse, to the University of Chicago, Research Funding; Daiichi Sankyo: Other: for Spouse, to the University of Chicago, Research Funding; Cellectis: Other: for Spouse, to the University of Chicago, Research Funding; Merck & Co., Inc.: Honoraria, Research Funding. Karmali:Morphosys/Incyte: Consultancy, Other: Advisory Board, Speakers Bureau; Calithera: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; Genentech/Roche: Consultancy, Other: Advisory Board; Pharmacyclics: Consultancy, Other: Advisory Board; BMS/Celgene: Consultancy, Research Funding; Takeda: Research Funding; Kite: Consultancy, Other: Advisory Board, Research Funding, Speakers Bureau; Karyopharm: Consultancy; Eusa: Consultancy; AstraZeneca: Other: Advisory Board, Speakers Bureau; BeiGene: Consultancy, Other: Advisory Board, Research Funding, Speakers Bureau. Gordon:BMS: Research Funding; Janssen: Other: DSMB; Ono Pharmaceuticals: Consultancy; Zylem: Current equity holder in private company, Current equity holder in publicly-traded company, Patents & Royalties: Patent on nanoparticles for lymphoma therapy. Moreira:CTI BioPharma: Consultancy; Ingenio Rx: Consultancy.