Life threatening hypophosphatemia and/or phosphate depletion in a patient with acute lenfoblastic leukemia: A rare case report Yasemin Soyoral, Mehmet Aslan, Senar Ebinc, Yaren Dirik, Cengiz Demir PII: DOI: Reference:
S0735-6757(14)00255-1 doi: 10.1016/j.ajem.2014.04.011 YAJEM 54241
To appear in:
American Journal of Emergency Medicine
Received date: Accepted date:
27 March 2014 1 April 2014
Please cite this article as: Soyoral Yasemin, Aslan Mehmet, Ebinc Senar, Dirik Yaren, Demir Cengiz, Life threatening hypophosphatemia and/or phosphate depletion in a patient with acute lenfoblastic leukemia: A rare case report, American Journal of Emergency Medicine (2014), doi: 10.1016/j.ajem.2014.04.011
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Life threatening hypophosphatemia and/or phosphate depletion in a patient with acute lenfoblastic leukemia: A rare case report
RI P
T
Yasemin Soyoral*1, Mehmet Aslan2, Senar Ebinc2, Yaren Dirik2, Cengiz Demir3
1*
Yuzuncu Yil University, Medical Faculty, Department of Nephrology, Van, Turkey
Yuzuncu Yil University, Medical Faculty, Department of Internal Medicine, Van, Turkey
3
Yuzuncu Yil University, Medical Faculty, Department of Hematology, Van, Turkey
MA NU
SC
2
Running Title: Severe hypophosphatemia in relapsed ALL
Dr. Yasemin Usul Soyoral
ED
*1Author for Correspondence:
PT
Yuzuncu Yil University, Medical Faculty,
CE
Department of Internal Medicine, Division of Nephrology, 65000, Van, Turkey
AC
Tel: +90 0432 215 0473
Fax: +90-(432)-216 7519 E-mail: [email protected]
Abstract Acute severe hypophosphatemia can be life-threatening and is associated with mortality and impaired cardiac and respiratory function. Several conditions including decreased absorption or increased urinary phosphate excretion, shifts from the extracellular to intracellular compartments and phosphate consumption by rapidly proliferating cells are
1
ACCEPTED MANUSCRIPT known to induce moderate to severe acute hypophosphatemia. Although hypophosphataemia and/or phosphate depletion in patients with acute or chronic myeloid leukemia have been
T
reported in the literature, hypophosphataemia due to acute lymphoblastic leukemia (ALL) is
RI P
very rare. We report a case of history of ALL complicated by life-threatening hypophosphataemia manifesting as generalized muscle weakness, fatigue, acute shortness of
SC
breath, difficulty in standing up and walking for 3 days. Serum inorganic phosphate levels were consistently low (0.06 mmol/l). The patient was hospitalized and thought to have a
MA NU
relapsed ALL. Anti-cancer agents and oral phosphate (660 mg/twice daily) were administered. On the second day of treatment, the patient began to improve, and the patient gradually fully recovered within five days. We suggested that this hypophosphataemia was induced by a shift of phosphorus into leukemic cells that rapidly replicated in the tissues and
ED
excessive cellular phosphate consumption by rapidly proliferating cells. Serum phosphate
PT
levels should always be monitored, especially in suspected life-threatening manifestation in
CE
relapsed ALL.
AC
Keywords: Relapsed acute lenfoblastic leukemia, severe hypophosphatemia
Introduction
Leukemia is a disease characterized by progressive and excessive production of immature leukocytes in the bone marrow, whose immature forms start circulating in blood (1). Acute lymphocytic leukemia (ALL) is a most common cancer type diagnosed in patients younger than 15 years, accounting for 26% of all cancers and 80% of leukemias (2). ALL also represents about 20% of adult acute leukaemias (3). ALL results in uncontrolled and excessive production of lymphoid blasts, hindering the normal production of red and white
2
ACCEPTED MANUSCRIPT cells, as well as platelets. The chances of survival have increased with advances in anticancer treatment modalities (1).
T
Hypophosphatemia is caused by inadequate intake, decreased intestinal absorption,
RI P
excessive urinary excretion, or a shift of phosphate from the extracellular to the intracellular compartments (4). Certain populations are likely to include a greater proportion of
SC
hypophosphatemic patients such as alcoholics, septic patients, and patients with diabetic ketoacidosis (5). Severe hypophosphatemia (≤1.0 mg/dl) might affect as few as 0.43% of
MA NU
hospitalized patients. Severe hypophosphatemia can cause respiratory failure, delay weaning from the ventilator, and increase the duration of intensive care and hospitalization (5). Hypophosphataemia are commonly seen in patients with acute leukemia. The postulated mechanism of this patient's hypophosphataemia is uptake by the rapidly dividing
ED
leukemic cells (6).
PT
Several case reports reported severe symptomatic hypophsopahatemia in patients with acute myelomonocytic leukemia (7-9), acute myeloid leukemia (10,11) and chronic
CE
myelogenous leukemia (12). On the other hand, Osoria et al. (13) observed
AC
hypophosphatemia in patients with chronic myeloid leukemia treated with imatinib. To our knowledge, Benitez et al. (14) described hypophosphatemia in children with ALL during remission induction. However, hypophosphatemia associated with ALL has rarely been reported in the literature (15,16). Therefore, we want to report our case. Case report A 45-year-old women patient was admitted to the emergency service with generalized muscle weakness, fatigue, acute shortness of breath, difficulty in standing up and walking. Her complaints began about 3 days prior to admission. The patients had a past medical history of an ALL diagnosed in June 2012.
3
ACCEPTED MANUSCRIPT On admission, his general status was moderate. Physical examination revealed a body temperature 37oC, blood pressure 120/80 mmHg, heart rate 96/min, respirature rate 24/min
T
and SpO2 80% (breathing room air). On physical examination, bronchial breath sounds were
RI P
normal and there was no heart-murmur. Abdomen was soft and non-tender. Neurological examination was normal.
SC
The patient’s laboratory results were as follows: Hemoglobin 9 g/dl (normal range: 1118 g/dl), hematocrit 28% (normal range: 35-55%), white blood cell 100.000 mm3 (normal
MA NU
range: 4.000-11.000 mm3), platelet count 48.000 per cubic millimeter (normal range: 150.000-400.000), blood urea nitrogen 28 mg/dl (normal range: 6 to 20 mg/dl), creatinine 0.4 mg/dl (normal range: 0.7 to 1.3 mg/dl), uric acide 4 mg/dl (normal range: 0-7 mg/dl), sodium 142 mmol/L (normal range: 136-145 mmol/L), potassium 3.4 mmol/L (normal range: 3.5-5.1
ED
mmol/L), magnesium 1.8 mg/dl (normal range:1.5-2.5 mg/dl), calcium 8.8 mg/dl (normal
PT
range: 8.4-10.7 mg/dl), alkaline phosphatase 223 IU/L (normal range: 0 to 270 IU/L), alanine aminotransferase (ALT) 16 IU/L (normal range: 0 to 41 IU/L), aspartate aminotransferase
CE
(AST) 12 IU/L (normal range: 0 to 37 IU/L), lactic dehydrogenase (LDH) 4980 IU/L (normal
AC
range: 240 to 480 IU/L), albumin 3.9 g/dl (normal range: 3.5 to 5.2 g/dl), direct bilirubin 0.37 mg/dl (normal range: 0.0-0.4 mg/dl), indirect bilirubin 0.4 mg/dl (normal range:0.0-0.8 mg/dl) and parathormone: 63 pg/ml (normal range:15-68.3 pg/ml). 24 h urinary phosphorus and calcium excretion were 0.25 g/24 hour (normal range: 0.4-1.3 g/24 hour) and 100 mg/24hour (normal range: 100-200 mg/24hour); respectively. Arterial blood gases on room air revealed a pH 7.52 (normal range: 7.38-7.42), PaCO2 32 kPa (normal range: 4.5-6.1), PaO2 38 kPa (normal range: 10.0-13.3), bicarbonate 26 mmol/l (normal range: 21-24). Her chest X-ray revealed a small heart size and clear lung fields. The electrocardiogram was normal. The patient was taking no drugs and was not consuming
4
ACCEPTED MANUSCRIPT alcohol at that time. Life-threatening asthma, pulmonary embolus and pneumothorax were all excluded.
T
Serum inorganic phosphate levels were consistently low (0.06 mmol/l). An acute rise
RI P
in peripheral lymphoblast cell counts due to recurrence of ALL was observed. A diagnosis of severe hypophosphataemia in patients with relapsed ALL was made.
SC
She was treated with anti-cancer agents and oral monobasic sodium phosphate (660 mg/twice daily). On the second day of treatment, the patient began to feel better, and her
MA NU
clinical status completely resolved in line with the rise in her serum phosphate within five days. Discussion
This report describes a patient with severe hypophosphatemia in patients with relapsed
ED
ALL. In our case, hypophosphatemia could be ascribed to a combination of factors, mainly to
shift of phosphate.
PT
excessive cellular phosphate consumption by rapidly proliferating cells and the transcellular
CE
Phosphate is involved in a variety of processes including acid-base buffering, post
(17).
AC
receptor signaling, energy transfer, and information storage and translation in DNA and RNA
Hypophosphatemia can be acute or chronic. Acute hypophosphatemia with phosphate depletion is common in the hospital setting and results in significant morbidity and mortality. Acute hypophosphatemia may be mild (phosphorus levels, 2-2.5 mg/dL), moderate (1-1.9 mg/dL) and severe (
S0735-6757(14)00255-1 doi: 10.1016/j.ajem.2014.04.011 YAJEM 54241
To appear in:
American Journal of Emergency Medicine
Received date: Accepted date:
27 March 2014 1 April 2014
Please cite this article as: Soyoral Yasemin, Aslan Mehmet, Ebinc Senar, Dirik Yaren, Demir Cengiz, Life threatening hypophosphatemia and/or phosphate depletion in a patient with acute lenfoblastic leukemia: A rare case report, American Journal of Emergency Medicine (2014), doi: 10.1016/j.ajem.2014.04.011
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Life threatening hypophosphatemia and/or phosphate depletion in a patient with acute lenfoblastic leukemia: A rare case report
RI P
T
Yasemin Soyoral*1, Mehmet Aslan2, Senar Ebinc2, Yaren Dirik2, Cengiz Demir3
1*
Yuzuncu Yil University, Medical Faculty, Department of Nephrology, Van, Turkey
Yuzuncu Yil University, Medical Faculty, Department of Internal Medicine, Van, Turkey
3
Yuzuncu Yil University, Medical Faculty, Department of Hematology, Van, Turkey
MA NU
SC
2
Running Title: Severe hypophosphatemia in relapsed ALL
Dr. Yasemin Usul Soyoral
ED
*1Author for Correspondence:
PT
Yuzuncu Yil University, Medical Faculty,
CE
Department of Internal Medicine, Division of Nephrology, 65000, Van, Turkey
AC
Tel: +90 0432 215 0473
Fax: +90-(432)-216 7519 E-mail: [email protected]
Abstract Acute severe hypophosphatemia can be life-threatening and is associated with mortality and impaired cardiac and respiratory function. Several conditions including decreased absorption or increased urinary phosphate excretion, shifts from the extracellular to intracellular compartments and phosphate consumption by rapidly proliferating cells are
1
ACCEPTED MANUSCRIPT known to induce moderate to severe acute hypophosphatemia. Although hypophosphataemia and/or phosphate depletion in patients with acute or chronic myeloid leukemia have been
T
reported in the literature, hypophosphataemia due to acute lymphoblastic leukemia (ALL) is
RI P
very rare. We report a case of history of ALL complicated by life-threatening hypophosphataemia manifesting as generalized muscle weakness, fatigue, acute shortness of
SC
breath, difficulty in standing up and walking for 3 days. Serum inorganic phosphate levels were consistently low (0.06 mmol/l). The patient was hospitalized and thought to have a
MA NU
relapsed ALL. Anti-cancer agents and oral phosphate (660 mg/twice daily) were administered. On the second day of treatment, the patient began to improve, and the patient gradually fully recovered within five days. We suggested that this hypophosphataemia was induced by a shift of phosphorus into leukemic cells that rapidly replicated in the tissues and
ED
excessive cellular phosphate consumption by rapidly proliferating cells. Serum phosphate
PT
levels should always be monitored, especially in suspected life-threatening manifestation in
CE
relapsed ALL.
AC
Keywords: Relapsed acute lenfoblastic leukemia, severe hypophosphatemia
Introduction
Leukemia is a disease characterized by progressive and excessive production of immature leukocytes in the bone marrow, whose immature forms start circulating in blood (1). Acute lymphocytic leukemia (ALL) is a most common cancer type diagnosed in patients younger than 15 years, accounting for 26% of all cancers and 80% of leukemias (2). ALL also represents about 20% of adult acute leukaemias (3). ALL results in uncontrolled and excessive production of lymphoid blasts, hindering the normal production of red and white
2
ACCEPTED MANUSCRIPT cells, as well as platelets. The chances of survival have increased with advances in anticancer treatment modalities (1).
T
Hypophosphatemia is caused by inadequate intake, decreased intestinal absorption,
RI P
excessive urinary excretion, or a shift of phosphate from the extracellular to the intracellular compartments (4). Certain populations are likely to include a greater proportion of
SC
hypophosphatemic patients such as alcoholics, septic patients, and patients with diabetic ketoacidosis (5). Severe hypophosphatemia (≤1.0 mg/dl) might affect as few as 0.43% of
MA NU
hospitalized patients. Severe hypophosphatemia can cause respiratory failure, delay weaning from the ventilator, and increase the duration of intensive care and hospitalization (5). Hypophosphataemia are commonly seen in patients with acute leukemia. The postulated mechanism of this patient's hypophosphataemia is uptake by the rapidly dividing
ED
leukemic cells (6).
PT
Several case reports reported severe symptomatic hypophsopahatemia in patients with acute myelomonocytic leukemia (7-9), acute myeloid leukemia (10,11) and chronic
CE
myelogenous leukemia (12). On the other hand, Osoria et al. (13) observed
AC
hypophosphatemia in patients with chronic myeloid leukemia treated with imatinib. To our knowledge, Benitez et al. (14) described hypophosphatemia in children with ALL during remission induction. However, hypophosphatemia associated with ALL has rarely been reported in the literature (15,16). Therefore, we want to report our case. Case report A 45-year-old women patient was admitted to the emergency service with generalized muscle weakness, fatigue, acute shortness of breath, difficulty in standing up and walking. Her complaints began about 3 days prior to admission. The patients had a past medical history of an ALL diagnosed in June 2012.
3
ACCEPTED MANUSCRIPT On admission, his general status was moderate. Physical examination revealed a body temperature 37oC, blood pressure 120/80 mmHg, heart rate 96/min, respirature rate 24/min
T
and SpO2 80% (breathing room air). On physical examination, bronchial breath sounds were
RI P
normal and there was no heart-murmur. Abdomen was soft and non-tender. Neurological examination was normal.
SC
The patient’s laboratory results were as follows: Hemoglobin 9 g/dl (normal range: 1118 g/dl), hematocrit 28% (normal range: 35-55%), white blood cell 100.000 mm3 (normal
MA NU
range: 4.000-11.000 mm3), platelet count 48.000 per cubic millimeter (normal range: 150.000-400.000), blood urea nitrogen 28 mg/dl (normal range: 6 to 20 mg/dl), creatinine 0.4 mg/dl (normal range: 0.7 to 1.3 mg/dl), uric acide 4 mg/dl (normal range: 0-7 mg/dl), sodium 142 mmol/L (normal range: 136-145 mmol/L), potassium 3.4 mmol/L (normal range: 3.5-5.1
ED
mmol/L), magnesium 1.8 mg/dl (normal range:1.5-2.5 mg/dl), calcium 8.8 mg/dl (normal
PT
range: 8.4-10.7 mg/dl), alkaline phosphatase 223 IU/L (normal range: 0 to 270 IU/L), alanine aminotransferase (ALT) 16 IU/L (normal range: 0 to 41 IU/L), aspartate aminotransferase
CE
(AST) 12 IU/L (normal range: 0 to 37 IU/L), lactic dehydrogenase (LDH) 4980 IU/L (normal
AC
range: 240 to 480 IU/L), albumin 3.9 g/dl (normal range: 3.5 to 5.2 g/dl), direct bilirubin 0.37 mg/dl (normal range: 0.0-0.4 mg/dl), indirect bilirubin 0.4 mg/dl (normal range:0.0-0.8 mg/dl) and parathormone: 63 pg/ml (normal range:15-68.3 pg/ml). 24 h urinary phosphorus and calcium excretion were 0.25 g/24 hour (normal range: 0.4-1.3 g/24 hour) and 100 mg/24hour (normal range: 100-200 mg/24hour); respectively. Arterial blood gases on room air revealed a pH 7.52 (normal range: 7.38-7.42), PaCO2 32 kPa (normal range: 4.5-6.1), PaO2 38 kPa (normal range: 10.0-13.3), bicarbonate 26 mmol/l (normal range: 21-24). Her chest X-ray revealed a small heart size and clear lung fields. The electrocardiogram was normal. The patient was taking no drugs and was not consuming
4
ACCEPTED MANUSCRIPT alcohol at that time. Life-threatening asthma, pulmonary embolus and pneumothorax were all excluded.
T
Serum inorganic phosphate levels were consistently low (0.06 mmol/l). An acute rise
RI P
in peripheral lymphoblast cell counts due to recurrence of ALL was observed. A diagnosis of severe hypophosphataemia in patients with relapsed ALL was made.
SC
She was treated with anti-cancer agents and oral monobasic sodium phosphate (660 mg/twice daily). On the second day of treatment, the patient began to feel better, and her
MA NU
clinical status completely resolved in line with the rise in her serum phosphate within five days. Discussion
This report describes a patient with severe hypophosphatemia in patients with relapsed
ED
ALL. In our case, hypophosphatemia could be ascribed to a combination of factors, mainly to
shift of phosphate.
PT
excessive cellular phosphate consumption by rapidly proliferating cells and the transcellular
CE
Phosphate is involved in a variety of processes including acid-base buffering, post
(17).
AC
receptor signaling, energy transfer, and information storage and translation in DNA and RNA
Hypophosphatemia can be acute or chronic. Acute hypophosphatemia with phosphate depletion is common in the hospital setting and results in significant morbidity and mortality. Acute hypophosphatemia may be mild (phosphorus levels, 2-2.5 mg/dL), moderate (1-1.9 mg/dL) and severe (
