Factors affecting neutrophil and platelet reconstitution following T cell-depleted bone marrow transplantation: differential effects of growth factor type and role of CD34+ cell dose

Abstract

Summary:We have performed univariate and multivariate analysis to determine the factors that affect the kinetics of neutrophil and platelet recovery in 546 recipients of T cell-depleted (TCD) marrow allografts. All patients received marrow depleted of mature CD3 ؉ T cells by complement-mediated lysis using T 10 B 9 -1A3 (n = 489) or Muromonab-Orthoclone OKT3 (n = 57) monoclonal antibodies. Neutrophil engraftment to 0.5 ؋ 10 9 /1 and platelet engraftment to 20 ؋ 10 9 /l were assessed as endpoints. Factors significantly affecting neutrophil or platelet engraftment in the univariate analysis included patient age, T cell dose, anti-thymocyte globulin use, gender, diagnosis at transplant, CMV serostatus, HLA mismatch, CD34 cell dose (n = 249), and growth factor use and type. These variables were included in the multivariate Cox proportional hazards regression model. The results showed that a faster rate of neutrophil engraftment was independently associated with CD34 + cell dose у5 ؋ 10 6 /kg and most strongly with growth factor administration. Faster platelet engraftment was associated with transplantation for chronic leukemia, CD34 + cell dose Ն2 ؋ 10 6 /kg, an HLA matched related donor, and the absence of growth factor use. G-CSF had a higher relative risk (RR) of enhancing neutrophil engraftment than GM-CSF and significantly delayed platelet engraftment. The combined use of G-CSF ؉ GM-CSF was similar to G-CSF alone. The enhancing effect of G-CSF for neutrophil recovery was most striking for patients who engrafted to 0.5 ؋ 10 9 /1 at or before day 12 (RR = 9.5, P Ͻ 0.0001) compared to patients who received no growth factor. Conversely, the delaying effect of G-CSF on platelet engraftment was strongest for patients engrafting on or before day 25 (RR = 0.4, P = 0.0004). Of the independent variables affecting engraftment kinetics in recipients of TCD marrow allografts only growth factor, and to a limited extent, CD34 ؉ cell dose can be controlled by the

Unmanipulated HLA‐mismatched/haploidentical peripheral blood stem cell transplantation for high‐risk hematologic malignancies

“…The numbers of CD34+ cells and MNCs in the graft are critical for engraftment. 18,25,26 Thus, the lower engraftment rate reported by Xu and colleagues 13 appears to be in some degree associated with the lower stem cell number and does not actually reflect inferiority of unmanipulated HLA-mismatched/haploidentical PBSCT to G-BM/PB transplantation. 26 Because extra marrow is needed in the G-BM/PB protocol, the procedure became more sophisticated and potential donors became more likely to refuse donation.…”

“…In addition, the median numbers of MNC (7.14 × 10 8 /kg) and CD34+ cells (2.54 × 10 6 /kg) in 14 patients at transplantation in the report by Xu and colleagues 13 are markedly lower than those in 21 patients (10.15 × 10 8 and 4.81 × 10 6 /kg, respectively) at transplantation in our study. The numbers of CD34+ cells and MNCs in the graft are critical for engraftment 18,25,26 . Thus, the lower engraftment rate reported by Xu and colleagues 13 appears to be in some degree associated with the lower stem cell number and does not actually reflect inferiority of unmanipulated HLA‐mismatched/haploidentical PBSCT to G‐BM/PB transplantation 26 .…”

Prolonged Thrombocytopenia Following Allogeneic Hematopoietic Stem Cell Transplantation and Its Association with a Reduction in Ploidy and an Immaturation of Megakaryocytes

“…Both transplanted CD34 1 cell dose and cytomegalovirus infection have been reported as important factors that correlate with platelet recovery after hematopoietic stem cell transplantation. A larger transplanted CD34 1 cell count has been positively correlated with rapid platelet engraftment [26,27]. Therefore, a lower number of transplanted CD34 1 cells may affect the maturation process of marrow MKs in allo-HSCT patients with prolonged thrombocytopenia and lead to an increase in the number of lower-ploidy MKs; however, this scenario needs to be further examined.…”

HLA-identical stem cell transplantation: is there an optimal CD34 cell dose?

“…Also not included in this review are allogeneic transplants involving manipulated components (eg CD34 enrichment or T-cell depletion) or nonmyeloablative conditioning regimens. [34][35][36][37] The relation between CD34 cell dose and clinical outcomes is likely to be different in those settings. In a few cases, supplemental results from recent analyses done with the Fred Hutchinson Cancer Research Center's (FHCRC) large database of matched related and matched unrelated donors have been incorporated into this review to illustrate specific points.…”