Severe hypophosphatemia during hematopoietic reconstitution after allogeneic peripheral blood stem cell transplantation

Abstract

Summary:A patient suffering from acute myeloid leukemia (FAB M5a) received a PBSC allograft from a matched, related donor. On day 13 after transplantation severe hypophosphatemia (0.21 mmol/l) was first noted which persisted irrespective of intravenous phosphate administration, and within 2 days reached concentrations below 0.13 mmol/l. After repeated phosphate substitution serum phosphate returned to 1.40 mmol/l on day 17. Phosphate in urine, and calcium in serum were recorded as unchanged throughout. Clinical signs and symptoms due to severe hypophosphatemia were not observed except for paresthesia in the lower extremities. The precipitous fall in serum phosphate coincided with hematopoietic reconstitution as reflected by a steep rise in leukocyte count from 0.08 × 10 9 /l on day 10 to 5.94 × 10 9 /l on day 15 after transplantation. Thus, isolated hypophosphatemia was likely the result of excessive cellular phosphate uptake during hematopoietic reconstitution. Electrolyte monitoring after PBSCT should include serum phosphate to identify the hypophosphatemia associated with hematopoietic recovery. Bone Marrow Transplantation (2000) 25, 1015-1016. Keywords: hypophosphatemia; hematopoietic reconstitution; allogeneic PBSCT The reference range for inorganic serum phosphate is 0.80-1.30 mmol/l. Mild to moderate hypophosphatemia arbitrarily defined as 0.30-0.80 mmol/l is a frequently encountered laboratory finding in hospitalized patients, whereas severe hypophosphatemia quoted as a serum concentration below 0.30 mmol/l must be considered a rare but potentially life-threatening condition. 1 Severe hypophosphatemia leads to a wide range of clinical manifestations including cardiovascular, respiratory, neuromuscular, and hematological effects. Intravenous phosphate replacement may be required in these cases to correct the concentration of serum phosphate, thus ameliorating the risk of complications. 2 Although usually multifactorial in origin, the pathogenesis of hypophosphatemia includes the following mechanisms: inadequate phosphate intake, decreased intestinal absorption, gastrointestinal or renal phosphate loss, and redistribution of phosphate into cells. The latter mechanism might be the link between rapidly proliferating cells and severe hypophosphatemia as has been reported in patients suffering from hematological malignancies. 3,4 Similarly, low serum phosphate concentrations have been reported in patients undergoing stem cell harvesting 5 or bone marrow/ peripheral blood stem cell transplantation. 6,7 Case reportA 38-year-old male patient was diagnosed in December 1998 with acute myeloid leukemia FAB M5a. He was treated with courses of cytarabine, idarubicin/cytarabine, and mitoxantrone/cytarabine, and conditioning for stem cell transplantation including total body irradiation, VP16 and cyclophosphamide. 2.97 × 10 6 /kg body weight CD34 + peripheral blood stem cells from an HLA-identical related donor were given. Therapy-associated complications included mucositis (WHO grade IV), local skin toxicity after radi...

Severe metabolic abnormalities after allogeneic hematopoietic cell transplantation

“…Increased phosphate uptake by replicating neutrophils during the peri-engraftment period is thought to play a role in the occurrence of hypophosphatemia in HCT recipients. [27][28][29] Hypokalemia was also frequently encountered after HCT. This condition may be due to renal potassium wasting, which may result from long-term use of aminoglycoside antibiotics and amphotericin B, concomitant hypomagnesemia, and vomiting.…”

Cardiorenal Syndrome and the Role of the Bone-Mineral Axis and Anemia

“…Data on possible relations between the bone-mineral axis and iron are derived from associations between hypophosphatemia and stimulated erythropoiesis in some hematopoietic disorders 28,29 as well as after intravenous (IV) iron infusion. 30 Iron-induced hypophosphatemia may result from increased cellular uptake of phosphate during erythropoiesis, but renal phosphate wasting appears to be an important mechanism of iron-induced hypophosphatemia.…”

Hypophosphatemia and hypouricemia in pediatric allogeneic bone marrow transplant recipients

“…All patients received allogeneic stem cells from HLA identical or mismatched family donors except for one unrelated (five of six matched) donor. The patient diagnoses were chronic myeloid leukemia (6), acute myeloblastic leukemia (6), myelodysplastic syndrome (6), acute lymphoblastic leukemia (6), non‐Hodgkin's lymphoma (1), aplastic anemia (2), Fanconi anemia (1), thalassemia (5), Wiscott‐Aldrich syndrome (1), osteopetrosis (3), Griscelli syndrome (2), congenital ertyhropoietic porfiria (1), adrenoleukodystrophy (1), metakromatic leukodystrophy (2), globoid cell leukodystrophy (1), SCID (9), bare lymphocyte syndrome (1), leukocyte adhesion deficiency (1) and Omenn syndrome (1). All patients except six with SCID, received conditioning regimens consisting of either one of the following protocols: busulfan/cyclophosphamide (BuCy) (n = 26), BuCy + melphalan (n = 3), BuCy + ATG (n = 3), BuCy + etoposide (n = 12), Cy + ATG (n = 2), Cy + thoraco‐abdominal irradiation (n = 1), Cy + total lymphoid irradiation (n = 1), fludarabine + Cy + ATG (n = 2).…”