Transient myeloproliferative disorder in a newborn with down syndrome treated with rasburicase for the risk of development of tumor lysis syndrome: A case report
© Tragiannidis et al; licensee BioMed Central Ltd. 2011
Received: 28 October 2010
Accepted: 24 August 2011
Published: 24 August 2011
Transient myeloproliferative disorder is a hematologic abnormality characterized by an uncontrolled proliferation of myeloblasts in peripheral blood and bone marrow that primarily affects newborns and babies with Down syndrome. Tumor lysis syndrome is rarely associated with transient myeloproliferative disorder.
Transient myeloproliferative disorder was diagnosed in a seven-day-old baby girl with Down syndrome, who was referred to our department due to hyperleukocytosis. Our patient developed tumor lysis syndrome, successfully treated with rasburicase, as a complication of transient myeloproliferative disorder resulting from rapid degradation of myeloid blasts after initiation of effective chemotherapy.
Tumor lysis syndrome is rarely reported as a complication of transient myeloproliferative disorder. To the best of our knowledge, this is the first case of a newborn with Down syndrome and transient myeloproliferative disorder treated with rasburicase for developing tumor lysis syndrome.
Transient myeloproliferative disorder (TMD) of Down syndrome (DS), also known as transient abnormal myelopoiesis, characteristically manifests in the first few days of life with numerous circulating blast cells exceeding the number of blast cells in the bone marrow and with spontaneous or no resolution within a few weeks [1–3]. Occasionally, however, TMD has preceded acute megakaryoblastic leukemia (AML-M7) after a period of remission lasting several months to years [4–6]. Tumor lysis syndrome (TLS) is rarely reported after initiation of effective chemotherapy as a complication of transient myeloproliferative disorder .
In this report, we present a case of a baby with DS and TMD who developed TLS successfully treated with rasburicase.
Laboratory hematological, biochemistry and coagulation test values from our patient on admission, on day four (initiation of rasburicase) and day 10 (end of rasburicase administration)
White blood cell count (cells/μL)
Total protein (g/dL)
Lactate dehydrogenase (IU/L)
Uric acid (mg/dL)
Alanine aminotransferase (IU/L)
Aspartate aminotransferase (IU/L)
Prothrombin time (seconds)
Activated partial thromboplastin time (seconds)
We describe the case of a newborn with DS and TMD who developed TLS that was successfully treated with rasburicase. To the best of our knowledge this is the first case of a newborn with DS and TMD treated with rasburicase for preventing the occurrence of TLS. Usually, transient leukocytosis associated with DS is generally diagnosed in the first few weeks of life. TMD, also known as transient leukemia, occurs in about 10% of neonates with DS . It is often accompanied by hepatosplenomegaly, pericardial and pleural effusions, hepatic disease, as in our patient and a pustular rash . Although TMD resolves in the majority of DS babies, 20% to 30% subsequently go on to develop AML-M7, usually within in the first 4 years of life [4, 6]. AML develops either by overt progression or after an apparent remission of TMD with AML arising many months later, presumably from a subcolony of persisting TMD cells that acquire a selective advantage.
Most neonates with TMD do not need chemotherapy as the clinical and laboratory abnormalities spontaneously resolve within three to six months after birth. However, symptomatic babies with TMD, especially those with high blast counts or liver dysfunction, may benefit from low-dose cytosine arabinoside. Chemotherapy is usually given at the treating physician's discretion and various groups have reported similar dosage schedules and response. In the Pediatric Oncology Group (POG) study 9481, 10 mg/m2 per dose or 1.2 to 1.5 mg/kg per dose was given subcutaneously or intravenously by slow injection twice a day for seven days . In the AML-BFM study, 0.5 to 1.5 mg/kg was administered for 3 to 12 days . As TMD blasts are highly sensitive to cytarabine, there is generally a rapid response, characterized by the disappearance of peripheral blasts by day seven of treatment. However this is not always the case, especially in babies with severe liver disease associated with fibrosis. Here, the response to chemotherapy is poor and overall there is a poor prognosis. Overall, TMD has been reported to have a mortality rate of approximately 20% [8, 9].
TLS is a group of metabolic complications that can occur after treatment for cancer, usually lymphomas and leukemias, and sometimes even without treatment. These metabolic complications include hyperkalemia, hyperphosphatemia, hyperuricemia and hyperuricosuria, hypocalcemia, and consequent acute uric acid nephropathy and acute renal failure . There are only few reports of TLS associated with TMD [10, 11]. Abe et al. reported the case of a neonate with DS who developed acute renal failure secondary to hypotension and TLS as a complication of TMD. The patient was treated with diuretics and pressor agents, but unfortunately died . Kato et al. reported the case of a baby with DS who developed TLS as a result of TMD, successfully treated with allopurinol and diuretics .
The clinical course of our patient indicates that TLS may develop in cases with DS and TMD. Intensive supportive and prophylactic therapy for preventing TLS should be given in cases of TMD showing prominent circulating blasts. To the best of our knowledge this is the first case of a newborn with DS and TMD treated with rasburicase for developing TLS.
Written informed consent was obtained from the patient's next-of-kin for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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