Background: Patients (pts) undergoing allogeneic hemopoietic stem cell transplant (alloHSCT) often have poor oral intake, which may result in micronutrient deficiencies. Currently, there are no standard guidelines for monitoring B12 or folate pre- or post-alloHSCT, and the true incidence of folate and B12 deficiencies in this population remains unknown. B12 or folate deficiencies may lead to cytopenias and serious adverse events. We aimed to evaluate B12 and folate deficiencies in alloHSCT pts and assess their association with delays in neutrophil or platelet engraftment.

Methods: We performed a single-center retrospective study (IRB-approved) including adult pts diagnosed with hematologic malignancy or aplastic anemia who underwent an alloHSCT between January 1, 2022 and December 31, 2023, with at least 30-day follow-up post-alloHSCT. 104 pts were eligible. All available B12 and folate levels from 90 days pre-HSCT through two years post-HSCT (Day +730) were collected, as well as platelet and neutrophil engraftment data. Patient demographic and clinical characteristics were also recorded. Data was distributed by post-transplant dates to align with typical post-alloHSCT follow up (Days +30, +60, +90, +120, +180, +365, +458, +730). Poisson regression analysis was used to determine if vitamin deficiencies were associated with delayed engraftment.

Results: Pre-alloHSCT (within 90 days) micronutrient screening frequency was low, with only 22 pts (21.2%) having B12 level and 12 pts (11.5%) having folate level checked. Post-alloHSCT, 90 (86.5%) pts had at least one B12 evaluation, and 11(10.6%) with B12 deficiency. 84(80.8%) pts had at least one folate evaluation, and 42(40.4%) with folate deficiency.

Folate deficiency was most prevalent in the early post-alloHSCT period (first 120 days), with frequencies of 33% (9 pts; up to Day +30), 34.2% (13 pts; Day +30-59), 23.1% (6 pts; Day +60-89), and 30.4% (14 pts; Day +90-120). Folate deficiency was less common after Day +120, with rates ranging from 3.2% to 15.4%. In contrast, zero pts had B12 levels below normal in the first 90 days post-HSCT. Beyond Day +90, the highest incidence of B12 deficiency occurred after Day +120 (up to 9.1%).

During early post-alloHSCT period (up to Day +120) where folate deficiency was most common, pts who had at least one folate-deficient lab value required 1.52 times longer to achieve platelet engraftment compared to pts without folate deficiency (p< 0.05). There was also a slight delay in neutrophil recovery (1.11 times longer, p=0.57). Across the entire study period, there was no observable association between B12 deficiency and platelet or neutrophil engraftment, though B12 deficiency rates were lower (0%-9.1%) when compared to folate deficiency.

Discussion: Our findings show that folate deficiency is common in the early post-alloHSCT period and may have a meaningful impact on hematopoietic recovery, specifically on platelets. Pts with folate deficiency in this critical window had a significantly prolonged time to platelet engraftment, raising the risks of serious bleeding and other complications. This suggests opportunities for standardized monitoring in the post-alloHSCT setting, particularly folate in early the post-alloHSCT course, and B12 in the later course. While retrospective design and non-standardized testing introduce selection bias (e.g., labs drawn due to symptoms or cytopenias), the strength of association with platelet recovery warrants further investigation. A prospective single-arm trial could better examine B12 and folate deficiency rates in a controlled setting, to correct for any situational or personal practice bias.  

Conclusion: Folate deficiency is common in early post-alloHSCT and is associated with significantly delayed platelet engraftment. These findings identify a potentially modifiable risk factor in the post-HSCT period and underscore the need for future research on the incidence and impact of micronutrient deficiencies in this setting.

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2025
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