Nucleated Cell (NC) Dose of Autologous (Auto) Marrow Graft Is Not Predictive of Engraftment after Auto-Bone Marrow Transplant (auto-BMT) Following Failed Peripheral Blood Stem Cell (PBSC) Mobilization.

BACKGROUND: Auto-PBSC transplant has replaced auto-BMT. 10–30% of patients (pts) fail to mobilize adequate PBSCs. Previous studies have shown a correlation between infusion of marrow NC doses >2×10⁸/kg recipient body weight and improved marrow engraftment as well as improved disease free survival (DFS).

HYPOTHESIS: NC dose in auto-BMT following failed PBSC mobilization is not predictive of marrow engraftment.

METHODS: Consecutive pts undergoing high-dose chemotherapy (HDC) and auto-BMT after failed PBSC mobilization were evaluated in this retrospective study. NC dose, CD34+ cell dose, time to neutrophil (ANC) engraftment, time to platelet (Plt) engraftment, and survival were reviewed. Spearman’s correlation was computed. Overall survival (OS) and progression free survival (PFS) were evaluated using Kaplan-Meier plots.

RESULTS: 22 pts failed to mobilize PBSC and underwent bone marrow harvest followed by HDC and auto-BMT from 2001 to 2006. 3 pts failed G-CSF and 19 failed cyclophosphamide and G-CSF mobilization. The median age at transplant was 56 yrs (range, 9–69). The diagnoses included Non-Hodgkin lymphoma (NHL;14,64%), Hodgkin lymphoma (4,18%), acute myeloid leukemia (AML;3,14%), and multiple myeloma (MM;1,4%). The median number of salvage regimens prior to attempted PBSC mobilization was 1 (range, 0–4). The median NC and CD34+ cell doses of the marrow stem cell product infused were 3.7×10⁸/kg (range, 1.4–6.8) and 1.0×10⁶/kg (range, 0.3–3.0), respectively. All pts achieved ANC engraftment with G-CSF support at a median time of 20.5 days (range, 13–43). Only 55% (12/22) of the pts achieved Plt engraftment with a median time of 46.5 days (range, 23–92). The NC cell and CD34+ cell dose did not differ significantly in patients with ANC engraftment (≤20 days or >20 days), Plt engraftment (≤45 days or >45 days) or number of salvage regimens (≤1 or >1). There was no correlation between NC dose and time to either ANC engraftment (rho=−0.05, P=0.8) or Plt engraftment (rho=0.6, P=0.9). CD34+ cell dose did not correlate with time to ANC engraftment (rho=−0.2, P=0.4) or Plt engraftment (rho=−0.2, P=0.4). Median follow up was 322 days (range, 53 to 1700). Median overall survival (OS) was 1140 days and median PFS was 509 days (95% CI, 368 to 649). OS and PFS were not impacted by the number of salvage regimens prior to transplant. Overall mortality (OM) was 36% (8/22). Causes of death were progressive disease (6/8,75%) and treatment related mortality (2/8,25%). 10/22 (45%) pts are alive without post-transplant relapse (PTR) at a median follow-up time of 276 (range, 53 to 649). 6 of these 10 pts continue to have Plt counts <100×10⁹/L.

CONCLUSIONS: NC or CD34+ cell doses of auto-marrow graft do not correlate with engraftment in pts undergoing HDC and auto-BMT after failed PBSC mobilization. Caution should be exercised in interpreting marrow cell doses in this population. These pts have a high OM and should be appropriately counselled.