Changes in Red Blood Cell Mean Corpuscular Volume after Pediatric HSCT

Background:While it has been noted clinically that the mean corpuscular volume (MCV) for HSCT recipients may tend to increase over time, literature describing changes to mean corpuscular volume (MCV) following pediatric HSCT is very limited. Macrocytosis is of clinical interest because it may signal underlying bone marrow dysfunction. Consequently, understanding the natural course of changes in the MCV over time is important.

Methods: We conducted a retrospective chart review of all pediatric patients undergoing allogeneic (allo) or autologous (auto) HSCT at the Medical University of South Carolina during July 1, 2007-June 30, 2012 who have survived for >1 year after transplant without relapse.  The sample included 16 auto-HSCT patients (10 patients with incomplete data) and 32 allo-HSCT patients. Baseline MCV values were recorded both at baseline (PBSC collection date for auto patients, HSCT admission date for allo patients) and at specific intervals post-HSCT. Data was analyzed to identify the presence of macrocytosis based on age-specific normal values, the trend of MCV changes with time, and the time of maximum change in MCV. Linear regression was used to evaluate associations between factors and MCV changes. Statistical significance was accepted at P<0.05.

Results: Macrocytosis was present at baseline in 19% of the allo patients and 0% of the auto patients. Maximum mean MCV change for allo and auto patients was at 90 days post-HSCT. At day 90, allo patients had a mean increase in MCV of 5.77 fl (95% CI 2.77- 8.77), and auto patients had a mean increase in MCV of 8.33 fl (95% CI 2.80-13.87). For allo patients, 56%, 32%, and 40% were macrocytic at days 90, 365, and 730 post-HSCT. For auto patients, 67%, 40%, and 40% were macrocytic at days 90, 365, and 730 post-HSCT. For allo patients, MCV changes were associated with ABO incompatibility (p=0.043) but not with age, sex, diagnosis, disease status at HSCT, prep regimen, graft source, cell dose, GVHD, neutrophil engraftment, or platelet engraftment. Compared to patients with no ABO incompatibility, the mean change in MCV at day 90 was 14.38 fl less for patients with minor ABO incompatibility but was not significantly different for patients with major ABO incompatibility. For auto patients, MCV changes had a positive association with neutrophil engraftment (p=0.049) with a trend towards an association with cell dose (p=0.071) but not with age, sex, diagnosis, initial chemotherapy, disease status at HSCT, prep regimen, or platelet engraftment. For each additional day increase in neutrophil engraftment, the mean change in MCV at day 90 is expected to increase by 1.91 fl.

Conclusion: Macrocytosis develops and persists up to two years post-HSCT in a substantial proportion of allo and auto HSCT patients. Macrocytosis may be related to bone marrow microenvironment injury from prep regimens.