Detection of monoclonality in bone marrow plasma cells by flow cytometry: limitations for minimal residual disease detection

We would like to add to the recent correspondence regarding severe hypophosphataemiain autograft recipients reported by Raanani et al (1995). We too have noticed severe hypophosphataemia in two patients undergoing bone marrow transplantation (BMT). Case 1 was a 62-year-old male with acute myeloid leukaemia who underwent an autograft using cyclophosphamide/busulphan conditioning. He developed severe hypophosphataemia (plasma phosphate 0.29 mmol/l) within 1 week of his BMT. Case 2 was a 35-year-old male with a teratoma of the testis who underwent BMT with cyclophosphamide and busulphan conditioning. He also developed severe hypophosphataemia of 0.26 mmol/l within 1 week of his BMT. There are two major points that need to be emphasized in the context of severe hypophosphataemia and bone marrow transplantation. Firstly, hypophosphataemia can result in many clinical abnormalities (Betro & Pain, 1972). In many cases the effects are either the result of impaired cellular energy pathways that involve ATP or are due to reduced erythrocyte 2,3-DPG (Knochel, 1977). Rhabdomyolysis can occur, as may impaired skeletal muscle function, including weakness and myopathy. Cardiomyopathy is another possible complication. The nervous system can also be affected with seizures, perturbed mental state, and paraesthesia. Hypophosphataemia can lead to osteomalacia and, if prolonged, renal tubular impairment and acute tubular necrosis (Stoff, 1982). The haematological effects caused by severe hypophosphataemia include impaired leucocyte phagocytosis and chemotaxis. Haemolysis may occur, as can erythrocyte 2,3DPG depletion, resulting in a shift in the haemoglobin/oxygen dissociation curve to the left, i.e. haemoglobin has a greater affinity for oxygen (Knochel, 1977). This is of fundamental importance to a patient undergoing bone marrow transplantation, particularly as their haematological state is already compromised. Secondly, care is required when giving intravenous phosphate. This is usually not necessary unless the plasma phosphate concentration is <0.30 mmol/l or the patient is symptomatic. A Lancet editorial (1981) suggested that severe hypophosphataemia should be treated. The recommendation in severe hypophosphataemia was to use intravenous phosphate replacement by the Vannatta regime (Vannatta et al, 1981). This gives 9 mmol of monobasic potassium phosphate in half-normal saline by continuous intravenous infusion over 12 h. However, this should not be given to patients with hypercalcaemia, because of the risk of metastatic calcification, nor to patients with hyperkalaemia. Plasma phosphate, ionized calcium, magnesium and potassium should be closely monitored, and the infusion stopped once the plasma phosphate concentration exceeds 0.30 mmol/l (Coyle et al, 1992). Monitoring urine output is also important. Recently there has been continued debate about the treatment of severe hypophosphataemia,illustrated by a patient who had been given 50 mmol/l of intravenous phosphate as was earlier recommended in the British National Formulary in preference to the Vannatta regime (Young et al, 1993). This patient developed severe hyperphosphataemia with hypocalcaemia and needed haemodialysis. Clearly, attention should be paid to the safest phosphate replacement regimen in bone marrow transplant patients manifesting severe hypophosphataemia, so as to avoid possible iatrogenic complications.