SCI. SickKids-Caribbean Initiative Enhancing Capacity for Care in Paediatric Cancer and Blood Disorders

Transcription

1 1.0 Introduction The (SCI) is a not-for-profit collaboration between the Hospital for Sick Children (SickKids), Toronto, Canada, and seven Caribbean health care institutions across six countries that strive to improve the outcomes and quality of life for children with cancer and blood disorders. The initiative has established a strong and formal partnership between SickKids, represented by key healthcare professionals, and six countries in the Caribbean: The Bahamas, Barbados, Jamaica, St. Lucia, St. Vincent and the Grenadines and Trinidad and Tobago. Inter-professional leaders from government, hospitals and academia are working collaboratively to implement a comprehensive strategy to build sustainable capacity in the identification and management of children with cancer and blood disorders in the Caribbean. For the purposes of this Guidance Document, tumour lysis syndrome (TLS) is defined as metabolic derangement resulting from abrupt and massive breakdown of malignant cells and the release of intracellular contents into the circulation which overwhelms the patient s excretory ability. Both laboratory and clinical TLS have been described 1-4. Laboratory TLS results in high serum urate, potassium, phosphate and/or low calcium concentrations and rarely leads to clinical TLS (increased serum creatinine concentration, cardiac arrhythmia or seizure). Identification of patients at risk of developing TLS and prompt initiation of preventive interventions are critical to avoiding clinical TLS. This Guidance Document outlines the recommendations for the prevention of TLS in children diagnosed with cancer in the Caribbean. 1.1 Disclaimer This guidance document ( Guidance Document ) is intended solely for healthcare providers who are collaborators in the ( Collaborators ). The Guidance Document is a general guide to appropriate practice, to be followed only subject to the judgment of a patient's attending physician, taking into consideration all available information related to the condition of the patient and after review of the benefits and risks of the proposed course of action with the patient (if of an appropriate age) and/or the patient s parents or guardians. The Guidance Document has been specifically tailored for use at Collaborators institutions taking into consideration available health care resources and other relevant contextual factors in Collaborators countries. The Guidance Document is NOT intended for use by patients or their families and is not designed or intended to constitute medical advice or to be used for diagnosis. The Guidance Document is NOT a substitute for the personalized judgment and care provided by trained medical professionals. Every effort has been made to ensure that the information provided in the Guidance Document is accurate and in accordance with the standards accepted at the time it was created, however new research and experience may result in changes to these standards. In all cases, you, in your role as the patient s physician and the SCI lead physician for the relevant participating SCI country, are responsible for ensuring that the recommendations detailed below comply with all applicable local laws, statutes and regulations. By viewing and using any information derived from the Guidance Document, you, in your role as the patient s responsible physician, hereby waive any claims, causes of action and demands, whether in tort or contract, against any of the Collaborators (including their employees, physicians, directors and agents) in any way related Page 1 of 6

2 to use of the Guidance Document or the information derived from it. 2.0 Definitions and Abbreviations Tumour Lysis Syndrome: TLS Intravenous: IV 3.0 Clinical Practice Recommendation 3.1 Patients at risk of TLS Patients at high risk of developing TLS include children with: 3,5,8,9,11,14-16 newly diagnosed/relapsed with Burkitt lymphoma; newly diagnosed lymphoblastic lymphoma; or who present with: o a white blood cell count greater than or equal to 50 x 10 9 /L; o serum urate concentrations greater than 475 µmol/l or 7.98 mg/dl; or o pre-existing renal impairment (serum creatinine 1.5 times the upper limit of normal for age) Patients at low risk of developing TLS include children: diagnosed with: o non-haematological malignancies or o haematological malignancies with a low proliferative rate, e.g. CML in chronic phase, Hodgkin lymphoma. who present with: o a normal serum urate concentration (equal to or less than 360 µmol/l); o a white blood cell count below 20 x 10 9 /L; o no clinical evidence of significant tumour burden (e.g. no mediastinal mass, no hepato/splenomegaly); and o no pre-existing renal impairment.( serum creatinine 1.5 times the upper limit of normal for age) Other factors, which may be associated with an increased risk of developing TLS include: an elevated serum lactate dehydrogenase (LDH) concentration >2000 U/L, and dehydration. 3.2 Laboratory Investigations 3,13,15 Serum creatinine, urea, urate, potassium, sodium, phosphate, calcium, albumin, LDH concentrations and a white blood cell count with differential should be determined whenever a diagnosis of a malignancy is suspected. If Page 2 of 6

3 albumin is low, consider the need to determine serum ionized calcium concentrations. The frequency of bloodwork should be adapted according to local institution availability and anticipated turnaround time for results to be reported. It is recommended that, with the exception of LDH, these tests be repeated every 8 to 12h for patients at lower risk of TLS or every 4 to 6h for patients at higher risk of TLS until antineoplastic therapy is initiated and for at least 3 days thereafter. Bloodwork frequency may be reduced over this time as clinically determined. LDH need only be determined once at presentation. 3.3 Strategies aimed at preventing TLS Preventive strategies are aimed at minimizing laboratory TLS and preventing clinical TLS. These strategies should be continued until antineoplastic therapy has reduced the patient s tumour burden and serum creatinine and urate are stable. A period of 3 to 5 days following administration of initial antineoplastic therapy is usually required Hydration: 3,7,10,12,14,15 All patients newly diagnosed or relapsed with a malignancy that entails a risk of TLS other than those who present in acute renal failure or with oliguria should: receive IV hydration with 0.9% sodium chloride at 3L/m 2 /day (or 200mL/kg/day if the child is less than or equal to 10kg). Monitoring of serum sodium concentration (along with tumor lysis laboratory monitoring) is recommended to avoid hyper/hyponatremia, especially in the setting of impaired urine output. receive mannitol or furosemide to maintain a urine output of at least 80% of total fluid intake (i.e. at least 2.4 L/m 2 /day or 160 ml/kg/day in a patient less than or equal to 10kg). If requiring more than 3L/m 2 /day IV hydration, the urine output should be approximately 100% of total fluid intake. The maximum tolerated positive fluid balance in an afebrile patient is 600mL/m 2 /day. Diuretics should not be given if contraindicated (e.g. in the presence of hypovolemia); not receive potassium, calcium or phosphate in hydration fluids, at least initially, and have their weight assessed daily. Hydration should begin as soon as a risk of TLS is suspected, ideally, 24 to 48 hours prior to administration of antineoplastic therapy and should continue as clinically indicated Allopurinol: 3,6,14,15 Allopurinol prevents the metabolism of xanthine and hypoxanthine to uric acid by competitively inhibiting xanthine oxidase. Though allopurinol effectively prevents serum urate concentrations from increasing and decreases the incidence of uric acid nephropathy, it does not reduce the uric acid that is already present prior to administration of the drug. In addition, allopurinol results in increased concentrations of xanthine and hypoxanthine which in turn increases the risk of the precipitation of these 2 compounds, especially at higher ph; therefore, urinary alkalinization is NOT recommended. Allopurinol should be continued for at least 72 hours after the initiation of antineoplastic therapy and Page 3 of 6

4 discontinued only when serum urate concentrations are within normal limits and stable. 3, Rasburicase Rasburicase is a recombinant form of urate oxidase and catalyzes the conversion of uric acid into allantoin, a very soluble substance that is readily excreted in urine. Rasburicase reduces pre-existing uric acid. Serum urate concentrations have been shown to decrease more rapidly after rasburicase than after allopurinol administration. If available, rasburicase is recommended for the following patients: at high risk of developing TLS newly diagnosed/relapsed with leukemia or lymphoma and unable to take oral medications for physiological reasons newly diagnosed/relapsed with leukemia or lymphoma and present with significant renal impairment (serum creatinine greater than or equal to 1.5 times the upper limit normal for age) develop allergic reaction to allopurinol Rasburicase is contraindicated in patients with G6PD deficiency. If G6PD status is unknown it is suggested to send blood for G6PD assay prior to administering the first dose. If the first dose of rasburicase is administered prior to the G6PD result being available, the patient/family must be informed of the risk of hemolysis and monitored for this complication. Additional doses must be re-evaluated once the patient s G6PD status is known. Subsequent doses should be reevaluated every 24 hours. Rasburicase should not be prescribed if the serum urate is within normal limits. Rasburicase should not be given for longer than 7 days. If TLS prophylaxis is still required, allopurinol should be initiated. Antibodies to rasburicase are known to develop. Therefore, patients should be monitored for signs and symptoms of an allergic response. Patients re-treated with rasburicase following a relapse may be at increased risk of developing hypersensitivity reactions. Alkalinization is not recommended or required for the duration of rasburicase use but hydration should continue as clinically indicated. Blood samples for determination of urate concentration must be sent on ice for at least 96 hours following the administration of rasburicase. The urate concentrations of samples sent at room temperature will be reported as lower than actual. 3.5 Consideration for Nephrology Consult Consider a nephrology consult if a patient is having persistently elevated creatinine with or without decreased urine output and/or in cases of uncontrolled hyperkalemia, hyperphosphatemia and/or symptomatic hypocalcemia to assist with management. Page 4 of 6

5 4.0 References 1. Altman A. Acute tumor lysis syndrome. Seminars in Oncology 2001;28: Cairo MS. Prevention and treatment of hyperuricemia in hematological malignancies. Clinical Lymphoma 2002;3 Suppl 1:S Cairo MS, Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. British Journal of Haematology 2004;127: Cope D. Tumor lysis syndrome. Clinical Journal of Oncology Nursing 2004;8: Gobel BH. Management of tumor lysis syndrome: prevention and treatment. Seminars in Oncology Nursing 2002;18: Hagemeister F, Huen A. The status of allopurinol in the management of tumor lysis syndrome: a clinical review. Cancer Journal 2005;11 Suppl 1:S Koduri PR. Alkali therapy, hyperphosphatemia, and acute tumor lysis syndrome. Medical & Pediatric Oncology 1996;26: Locatelli F, Rossi F. Incidence and pathogenesis of tumor lysis syndrome. Contributions to Nephrology 2005;147: Mato AR, Riccio BE, Qin L, et al. A predictive model for the detection of tumor lysis syndrome during AML induction therapy.[see comment]. Leukemia & Lymphoma 2006;47: Pession A, Barbieri E. Treatment and prevention of tumor lysis syndrome in children. Experience of Associazione Italiana Ematologia Oncologia Pediatrica. Contributions to Nephrology 2005;147: Seidemann K, Meyer U, Jansen P, et al. Impaired renal function and tumor lysis syndrome in pediatric patients with non-hodgkin's lymphoma and B-ALL. Observations from the BFM-trials. Klinische Padiatrie 1998;210: Truini-Pittman L, Rossetto C. Pediatric considerations in tumor lysis syndrome. Seminars in Oncology Nursing 2002;18: Yarpuzlu AA. A review of clinical and laboratory findings and treatment of tumor lysis syndrome. Clinica Chimica Acta 2003;333: Tosi P, Barosi G, Lazzaro C, et al. Consensus conference on the management of tumor lysis syndrome. Haematologica 2008;93: Coiffier B, Altman A, Pui CH, Younes A, Cairo MS. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. Journal of Clinical Oncology 2008;26: Truong TH, Beyene J, Hitzler J, et al. Features at presentation predict children with acute lymphoblastic leukemia at low risk for tumor lysis syndrome. Cancer 2007;110: van de Berg H, Reintsema AM. Renal tubular damage in rasburicase: risks of alkalinisation. Annals of Oncology 2004; 15:175-6 Page 5 of 6

6 6.0 Guidance Document Group and Reviewers Guideline adapted from SickKids Clinical Practice Guideline (2010) Management of children with acute leukemia and an elevated white blood cell count at diagnosis hyperleukocytosis. Dr. Oussama Abla, MD, Staff Physician, Division of Haematology/Oncology Alicia Koo, RPh, PharmD, Clinical Pharmacy Manager, Division of Haematology/Oncology Strategic input to guide the development of this Guidance Document was solidified from and provided by the following Caribbean hospitals: Bustamante Hospital for Children, Kingston, Jamaica University Hospital of the West Indies, Kingston, Jamaica Milton Cato Memorial Hospital, Kingstown, St. Vincent and the Grenadines Victoria Hospital, St. Lucia Queen Elizabeth Hospital, Bridgetown, Barbados Princess Margaret Hospital, Nassau, The Bahamas Eric Williams Medical Sciences Complex, Trinidad and Tobago Page 6 of 6