In hematopoietic stem cell transplantation (HSCT), oral intake is severely impaired by preparative regimen-induced mucosal toxicity and nausea. Therefore, parenteral nutrition (PN) is usually administered. The vitamin preparation accompanying PN therapy is based on the FDA recommendation proposed in 2000. However, it remains unknown whether this preparation retains adequateness for HSCT recipients who undergo strenuous conditioning regimens and immunological reactions, which put them in a hyper catabolic state. Additionally, almost no study has been conducted to examine the relevance of standard regimen of mineral microelements supplementation during HSCT.
In this prospective observational study, we measured the blood level of selected vitamins (vitamin B1, B6, C, K, E, and folate) and mineral microelements (iron, zinc, copper, and selenium) during the peri-HSCT period (measured weekly from 1 week before until 4 weeks after HSCT). Oral and parenteral total energy amounts, administration of multivitamin preparation, and mineral supplementation, were recorded. The subjects were 15 adult patients who received allogeneic HSCT for hematological malignancies (AML: 7, ALL: 1, CML: 1, MPN: 2, MDS: 2, NHL: 2) at The University of Tokyo Hospital. Eight of them received CY/TBI-based full conditioning and the others received fludarabine-based reduced intensity regimens. All the patients received PN with vitamin and mineral preparations when their oral intake decreased to less than 700 Kcal/day. PN was modified adequately in case of organ dysfunctions. Engraftment was observed in all but one patient, and one died before day 28 due to sepsis. The most striking finding was the marked deficiency of vitamin C, a major antioxidant vitamin. Vitamin C levels dropped just after conditioning regimens started, and reached a nadir (2.1+-1.49 microgram/mL, normal range: 5.5–16.8) at day 14. The deficiency levels at day 7 and day 14 were significantly correlated with increase of acute phase inflammatory proteins (p=0.03 for C-reactive protein and p=0.004 for ferritin, at day 7), which suggests that the current vitamin C complement regimen is insufficient for patients who suffer from intense inflammation. On the other hand, vitamin E, another antioxidant vitamin, remained within the normal level during the surveillance period. Selenium is a microelement that assists antioxidative effect and has attracted attention because emerging evidence suggests its relevance for critically ill condition. Although it is not contained in the standard PN preparations, our results indicated no sign of shortage. Selenium is abundant in normal diet, and short suspension of oral intake does not induce selenium depletion. Marked excess of vitamin K was another point of note. The average vitamin K level continued to rise after the start of the conditioning regimen, and exceeded 10 times of the normal upper level (0.15 – 1.25 ng/mL) at day14 (12.8 +- 5.6 ng/mL), day 21 (17.4 +- 17.9), and day 28 (12.1+- 25.0). These abnormal rises were observed especially in patients with prolonged administration of PN, suggesting overdosing of vitamin K in the standard vitamin preparations. Vitamin K excess would be problematic because it causes hypercoagulability; however, it was not clinically correlated with the onset of thrombotic microangiopathy in our cohort. Vitamin B1 was slightly but significantly below the normal lower limit. Its deficiency started before the conditioning regimen and persisted through day14. Considering increased requirement of vitamin B1 during a debilitating state, this shortage should be corrected with active supplementation before the patients undergo a stressful conditioning process. Other substances (folate, zinc, iron, and copper) remained almost within a normal range.
In conclusion, the nourishment status during peri-HSCT period is characterized by marked depletion of vitamin C and excess of vitamin K, and other aberrations with less degree of deviation. These results indicate that normal PN is not adequate for HSCT patients. Development of vitamin and microelement preparation that is optimized for HSCT setting should be discussed.
Nannya:Otsuka Seiyaku Koujyou: Research Funding.
Asterisk with author names denotes non-ASH members.