Higher CD 34 Cell Doses Reduce Non Relapse Mortality (NRM) and Do Not Increase the Incidence of Graft Versus Host Disease (GVHD) Following Unrelated Donor Blood Stem Cell Transplantation (SCT).

Background: Higher CD34 cell doses have been shown to increase the incidence of acute (Przepiorka D et al, 1999) and extensive chronic GVHD (Zaucha et al, 2001) following HLA-matched sibling SCT. Less is known about the influence of CD 34 cell dose in the unrelated SCT setting.

Methods: A retrospective review was performed involving 81 consecutive adult patients (pts) who underwent unrelated donor G-CSF mobilised blood SCT in Vancouver between June 2000 and October 2006. NRM, relapse risk (RR) and overall survival (OAS) estimates were determined using a Kaplan-Meier technique and univariate and multivariate analyses were done to identify factors predictive of GVHD and outcome, with particular focus on cell dose administered.

Characteristics: There were 46 male and 35 female pts with a median age of 44 (range 17–58) years. Diagnoses included acute leukemia (39 pts), chronic leukemia (14 pts), lymphoma (15 pts) and other (13 pts). Conditioning was TBI-based in 80/81 pts and GVHD prophylaxis was with continuous infusion Cyclosporine and short-course Methotrexate (MTX) (15mg/m² d +1 and 10mg/m² d+3, d+6 and d+11). Fifty of 81 pts received >80% of the planned MTX dose. Forty three pts received SCT from a 10/10 high-resolution HLA-matched donor, 25 pts received a 1-antigen mismatched SCT, 12 pts received a 2-antigen mismatched SCT and 1 pt a 3-antigen mismatched SCT. The donor was male for 68 pts and female for 13 pts. Median CD 34 cell dose was 7.75x10⁶ (range−9.46x10⁴–33.6x10⁶)/kg.

Results: The estimated 3-year NRM, RR and OAS were 39% (95%CI 25%–50%), 30% (95%CI 17%–41%) and 43% (95%CI 31%–58%), respectively. In multivariate analysis, CD 34 cell dose >7.75x10⁶/kg was associated with faster neutrophil engraftment, p<0.001 and reduced NRM (28% vs. 49%, p=.019), but did not influence the incidence of either acute or chronic GVHD or OAS. Multivariate analysis showed that the most important predictor of grade 3–4 acute GVHD (49% vs. 22%, p=.005), NRM (65 vs. 30%, p=.006), and OAS (24% vs. 50%) was administration of >80% of the planned MTX dose. Although having a female donor predicted for an increase in NRM (p=.03), it also was associated with a decrease in RR (0/13 pts) and did not affect OAS.

Conclusion: A high CD34 cell dose in unrelated donor blood SCT is desirable in that it does not adversely influence the incidence of GVHD and is associated with faster neutrophil engraftment and a reduction in NRM. Delivery of at least 80% of the planned short-course MTX GVHD prophylaxis continues to be critical in producing a favourable outcome.