Side effects related to hematopoietic stem cell transplantation (HSCT) conditioning can lead to severe mucositis, impair oral intake, chewing, and swallowing, and suggest a need of special nutritional support for these patients [1]. Mucositis lesions are common occurrences in oncology patients, with a reported incidence of 40 % in those receiving chemotherapy and 76 % in patients undergoing hematopoietic stem cell transplantation (HSCT). This high prevalence frequently leads to poor tolerance of oral or enteral feeding routes [2] and so the parenteral route is preferred.

Parenteral nutrition (PN), although a vital lifeline for patients undergoing hematological recovery, is associated with numerous complications with mineral disorders having emerged as a prominent concern [3]. Mineral disorders in patients receiving PN predominantly arise from two key factors. First, patients undergoing HSCT often require complex regimens of medications to manage their underlying conditions [4]. These medications typically include immunosuppressants to prevent graft-versus-host disease (GvHD), antibiotics to prevent infections, and other drugs to manage post-transplant complications. Unfortunately, these drugs can significantly disrupt the delicate balance of essential electrolytes in the body, leading to imbalances in minerals such as potassium, magnesium, and phosphorus. These imbalances can have far-reaching consequences, affecting the patient's overall health and potentially hindering the success of the hematological recovery process [5]. The second factor contributing to mineral disorders in HSCT patients is the risk of Refeeding syndrome, particularly within the initial days after starting PN. Refeeding syndrome is a severe metabolic disturbance characterized by rapid shifts in mineral levels, particularly potassium, phosphorus, and magnesium, as the body adapts to increased nutritional intake after a period of malnutrition or fasting [6]. When HSCT patients, who are often in a compromised nutritional state before transplantation, begin PN abruptly, they are particularly susceptible to Refeeding syndrome. This condition can lead to various complications, including cardiac arrhythmias, respiratory distress, and neuromuscular disturbances [7]. The correct management of the mineral disorders in these vulnerable patients is paramount to ensuring successful hematological recovery while minimizing the potential complications associated with PN.

This study evaluated the prevalence of hypophosphatemia, hypokalemia, and hypomagnesemia before and within the first 24 days of PN infusion in adult patients who underwent HSCT.

A total of 77 adult patients who underwent HSCT were included in this study. The mean age of the patients was 46.4 years and 50.6 % were male. Most patients had myeloid malignancies (50.6 %) and lymphoid malignancies (44.2 %). Autologous HSCT transplantation was performed in 41.6 % of cases, human leukocyte antigen (HLA) matched related and unrelated HSCT in 50.6 % and 6.5 %, respectively, and HLA-mismatched related transplantation in 1.3 %. The conditioning regimen types included high doses without total-body irradiation (81.8 %), high doses with total-body irradiation (1.3 %), and reduced intensity (16.9 %). Platelet engraftment occurred at a median of 18 days (interquartile range [IQR]: 16–22 days), and neutrophil engraftment occurred at a median of 14 days (IQR: 11–17 days) (Table 1).

The mean BMI was 25.6 kg/m2 with 40.3 % of patients overweight and 13.0 % obese. Among the patients, 14.3 % died with PN administered for a mean duration of 1.4 days. The main reason for PN indication was grade IV mucositis (88.3 %) (Table 2).

Energy intake per day varied across different periods, ranging from 23.1–36.8 kcal/kg. Protein intake per day also varied across the study period, ranging from 0.96–1.62 g/kg. The non-protein calorie/g of the nitrogen ratio was also evaluated, with values below and above the recommended target values observed during different periods (Table 3).

Table 4 provides information on the occurrence of mineral disorders during the HSCT detailed by period (P1–P6). The prevalence of hypophosphatemia ranged from 21.1–40.3 % with the highest occurrence observed in P2. Hypokalemia was observed in 10.5–31.2 % of patients with the highest occurrence in P1. The incidence of hypomagnesemia ranged from 50.0–62.3 % with the highest incidence in P1. Severe hypophosphatemia events were observed in 1.6 % of patients in P2. Severe hypokalemia was observed in 2.6 % and 2.7 % of patients in P2 and P4, respectively. Severe hypomagnesemia occurred in 1.3 % and 1.8 % of patients in P1 and P3, respectively.

There was a high number of mild intracellular mineral disorders. Disorders of intracellular minerals are noteworthy for their frequency. Hypokalemia, hypomagnesemia, and hypophosphatemia have been reported during the PN period; this phenomenon might be explained by the release of insulin associated with the parenteral energy infusion [16]. However, both hypokalemia and hypomagnesemia occurred in almost half of the samples during the first four days of PN when the amount of energy offered was still low; therefore, it is likely that, in addition to refeeding, there was tubulopathy caused by pre-transplant chemotherapy. A study of patients undergoing HSCT observed an incidence of acute kidney injury of 64 %, occurring more frequently in those with hypoalbuminemia [17].

Electrolyte disturbances are often associated with patients taking antineoplastic agents; this can lead to serious or fatal clinical manifestations [18]. In this study, hypokalemia and hypomagnesemia were found in 31.2 % and 62.3 % of patients, respectively. These disorders frequently occurred concomitantly, which may be explained by the association between proximal tubule damage and the blockage of the TRPM6/EGF/EGFR pathway. This blockage impairs magnesium reabsorption in the distal tubule, thereby preventing the maintenance of normal serum magnesium and calcium levels [18]. Although drug-induced tubulopathy can explain hypokalemia and hypomagnesemia, patients undergoing HSCT often experience a period of low food intake and reduced lean body mass due to processes related to the neoplasia. An underlying inflammatory process is present, characterized by anorexia and insufficient energy and protein intake. This condition is further exacerbated by the metabolic redirection of protein stores toward the synthesis of pro-inflammatory factors [19]. Thus, these factors may have contributed to hypokalemia and hypomagnesemia associated with drug tubulopathy. However, considering the prevalence of hypokalemia and hypomagnesemia during the first week of PN, it is not possible to separate the effects of tubulopathy from what can be attributed to refeeding caused mainly by PN [3].

Phosphorus is another intracellular mineral and is, therefore, characteristically depleted in the Refeeding syndrome. In the current study, the drop in this anion was most evident after the fourth day of PN (40.3 % of patients). Therefore, it can be understood that the fact that phosphorus had a more significant drop in plasma levels during the second period of PN is probably attributable to cellular Theft syndrome, given that the amount of energy administered, although without hyperalimentation, was already increased during this period [3,20]

Although there was a high prevalence of mineral depletion throughout the study, few patients had severe levels of mineral depletion. This can be directly attributed to the fact that rigorous monitoring of both the nutritional and metabolic issues occurred daily, owing to the presence of an NMTT. Notably, the patients managed to achieve their target, indicating the active involvement of the team [21].

In the 77 patients studied, Grade IV mucositis was present in 88.3 % of the cases as expected given that the patients had to receive PN as their main source of nutrition. Patients with Grade IV mucositis experience significant discomfort when eating because of intense inflammation and ulceration with necrotic lesions; however, the use of enteral tubes remains controversial [22].

In the present cohort, the use of PN was effective in meeting energy and protein needs with the amount of energy offered reaching 36.8 kcal/kg/day, and protein reaching 1.62 g/kg/day. It has been previously reported that the amount of energy needed after HSCT increases by 30–50 %, and the amount of protein should reach approximately 1.5 g/kg/day [23]. This was only possible because the place where this research was conducted by the NMTT was prepared to prescribe customized PN, with the possibility of optimizing the number of amino acids prescribed. Studies have shown that the presence of an NMTT facilitates this type of approach [24,25].

Patients undergoing HSCT are at risk of developing mineral disturbances during the engraftment period. Although these factors diminish over time, disorders remain prevalent in all periods. Therefore, rigorous daily monitoring of these patients by a team specializing in PN is warranted.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.