Hyperhydration is not necessary for high-dose melphalan in stem cell transplantation

TLDR: This study aimed to retrospectively compare the incidence and severity of acute renal impairment in patients who underwent an autologous HSCT for multiple myeloma between January 2015 and September 2017 and investigate any adverse events associated with the administration of hyperhydration such as clinical overload and pulmonary oedema.

Abstract: To the Editor, High-dose melphalan (120–200 mg/m) is widely used in preparative regimens for autologous and allogeneic haematopoietic stem cell transplantation (HSCT). This drug is often given with “hyperhydration” that usually means 4–6 litres (L) of 0.9% normal saline [1–3]. The practice of hyperhydration appears to be based on early studies using melphalan 200 mg/m (MEL200) in autologous HSCT for multiple myeloma (MM) [4, 5]. These studies used only 2L hydration, however described it as hyperhydration. Subsequent studies [6, 7] used 4–6 L of hyperhydration. Hyperhydration is usually given with highdose chemotherapy that is known to cause nephrotoxicity (e.g., cisplatin, methotrexate) or bladder toxicity (e.g., cyclophosphamide, ifosfamide). However, melphalan is not considered to be a renal or bladder toxic drug based on the limited evidence available. Pharmacokinetic studies have shown that melphalan is predominantly eliminated by spontaneous chemical hydrolysis and only 10% of the dose is excreted in the urine [1]. Given the absence of any data supporting hyperhydration and the potential morbidity and risk associated with the procedure, many institutions have opted not to use hyperhydration [8] while others continue the practice. The process of hyperhydration and subsequent forced diuresis can be exhausting and unpleasant for patients. In addition, patients may be at an increased risk of clinical fluid overload and pulmonary oedema after highdose melphalan and hyperhydration administration. Evidence is needed to inform best practice. This study aimed to retrospectively compare the incidence and severity of acute renal impairment in patients who underwent an autologous HSCT after MEL200 for multiple myeloma (MM), between institutes using hyperhydration and not using hyperhydration. An additional aim was to investigate any adverse events associated with the administration of hyperhydration such as clinical overload and pulmonary oedema. This study employed a retrospective cohort design. A chart review was performed on patients who had received a MEL200 autologous HSCT for MM between January 2015 and September 2017 at the Royal Brisbane and Women’s Hospital (RBWH) and The Townsville Hospital (TTH) in Queensland, Australia. These institutions were selected based on the similar in-patient treatment provided to HSCT patients, leading to reduced confounding when comparing the two groups. Both hospitals provided autologous HSCT as inpatients using standardised HDM protocols, provided similar supportive care, and took daily blood tests and weights. The main difference between the two institutions was the amount of fluid administered with melphalan (6L vs. 2L). Patients were included if they: (1) had a diagnosis of MM; and (2) underwent MEL200 autologous HSCT as in-patients. Patients who received all other types of HSCT were excluded. Ethical approval was obtained from the RBWH and TTH Human Research Ethics Committee (HREC/17/QRBW/ 364). Experienced health care professionals working at the RBWH and TTH collected data from the medical records. Collected data includes patients’ demography, daily creatinine (Cr) and weight, fluid overload (O/L), frusemide use, acute pulmonary oedema (APO), sepsis, and antibiotic use. Data was collected from admission (baseline) to Day 7 post HSCT. * Midori Nakagaki midori.nakagaki@health.qld.gov.au