Impact of donor marrow cellularity on outcome of allogeneic stem cell transplantation

Background

Outcomes of allogeneic hematopoietic stem cell transplant (HSCT) are affected by a number of donor and patient related factors like extent of human leucocyte antigen mismatch, age, source of stem cells, female donor to male recipient and stem cell dose. All of these factors have been extensively investigated; however, effect of donor bone marrow cellularity on HSCT outcomes has not been evaluated.

Methods

This was a prospective study carried out at Armed forces bone marrow transplant center (AFBMTC/NIBMT) from January 2018 to December 2022. Bone marrow cellularity of donors was determined by separate assessment by two experienced Hematopathologists and classified as normocellular, hypocellular or hypercellular according to donor age. Total nucleated cells (TNC) were assessed by automated hematology analyzer and stem cell quantification was done by flowcytometric assay based on CD34, CD45 and 7-AAD immunophenotyping markers. Primary outcome measures were time to achieve neutrophil and platelet engraftment. Secondary outcome measures assessed were overall survival (OS), disease free survival (DFS) and graft versus host disease (GVHD). Frequency and percentage were calculated for categorical variables while Chi-square test was used for quantitative variables. Multivariate Cox regression analysis was used to determine significance of different variables and effect of cellularity on them. Kaplan Meier estimates with group differences were calculated using log rank tests for OS and DFS. A p value of 0.05 or less was considered statistically significant.

Results

Cellularity of 95 donors was assessed, 39 (41.1 %) had normocellular marrow while 56 (58.9 %) were hypocellular for age. Median time from diagnosis to transplant was 13 months. In 38 (40 %) the indication for donation was for patients with bone marrow failure syndromes, 23 (24.2 %) for hematological malignancies, 21(22.1 %) for beta thalassemia major and 13 (13.6 %) for miscellaneous disorders including immune deficiencies. Median stem cell / CD 34 dose was 6 × 106/kg and median TNC dose was 5.09 × 108/kg. Median time of neutrophil engraftment was 13.6 days while that of platelet engraftment was 27.1 days. Mean OS was 84.2 %. OS for normocellular donors was 84.6 % and that for hypocellular donors was 83.9 % (p 0.995). DFS for normocellular donors was 84.6 % and for hypocellular donors was 83.9 % (p 0.96). No statistically significant association between the disease group and transplant type with donor marrow cellularity (p value 0.32 and 0.358 respectively) was determined. Multivariate logistic regression model and Backwald test showed no significant association between donor marrow cellularity and CD 34 dose (p 0.65), TNC (p 0.78), neutrophil engraftment (p 0.23), platelet engraftment (p 0.27), Acute GVHD (p 0.83), and chronic GVHD (p 0.44).

Conclusion

Majority of the donors had hypocellular bone marrow. Bone marrow cellularity had no statistically significant impact on the CD34 and TNC doses obtained; neither did it affect post-transplant neutrophil and platelet engraftment, OS, and DFS. Further population-based studies are required to confirm normal marrow cellularity in Pakistani population and the effects of various genetic and environment factors that make it hypocellular.