TUMOR LYSIS SYNDROME ISU Dietetic Intern Mini Case Topic - - PowerPoint PPT Presentation

TUMOR LYSIS SYNDROME

Jenni Wolf

ISU Dietetic Intern Mini Case Topic Presentation March 2017

OBJECTIVES:

I. Basics of TLS II. Pathophysiology III. Classification

• IV. Metabolic Abnormalities and Clinical

Manifestation of TLS V. TLS Management

I. Assessing TLS Risk in Patients II. Treatment III. Monitoring

• VI. Relevance to Clinical RDs
• VII. Future of TLS Research

▪Define tumor lysis syndrome (TLS) and understand its pathophysiology ▪Identify patients at risk for TLS ▪Understand clinical characteristics of TLS and current medical treatment ▪Identify appropriate MNT approach to care for these patients ▪Gain insight into goals of continued tumor lysis research

OUTLINE:

TUMOR LYSIS SYNDROME: DEFINED

▪Oncologic condition characterized by:

▪electrolyte abnormalities ▪acute kidney injury ▪cardiac arrhythmias ▪seizures ▪death

▪Occurs most commonly after initiation of cancer treatment via chemotherapy in hematological patients

PATHOPHYSIOLOGY

▪TLS = direct consequence of the rapid release of intracellular components from lysed cells ▪Malignant cells are rich in purines, potassium, and phosphorus

▪Release into ECF

▪Hyperuricemia, hyperkalemia, hyperphosphatemia, secondary hypocalcemia

• Increases serum burden

▪Rapid onset

• 12 -72 hours after initiation of treatment
• AKI within 24 hours

CLASSIFICATION

▪Laboratory TLS

• Asymptomatic
• Only detectable through lab work
• ≥ 2 of below abnormalities within 3 days

before, or 7 days after, beginning chemotherapy

▪Clinical TLS

• Symptomatic clinical manifestations present

Via American Society of Nephrology

HYPERURICEMIA

▪Malignant cells contain purines – Adenine, Guanine ▪Released into ECF ---> uric acid ▪Uric acid crystallization and blockage of renal tubules ---> risk of AKI

• Acute uric acid nephropathy
• Increased UA load may affect nephron’s ability to autoregulate
• CKD further exacerbates

Purines Hypoxanthine Xanthine Uric Acid

HYPERKALEMIA

▪Rapid release of k+ into ECF ▪Uptake capacity of liver and muscle is overwhelmed ▪AKI, CKD further exacerbates the condition ▪Symptoms: fatigue, muscle weakness, cardiac arrhythmias

• EKG/ECG to assess severity

HYPERPHOSPHATEMIA

+HYPOCALCEMIA

▪Massive release of phosphorus into ECF

• Malignant cells can contain up to 4x more phosphorus than healthy, normal cells

▪Clearance moderated by kidney function

• Hyperphosphatemia may affect nephron’s ability to autoregulate
• Exacerbated by AKI, CKD

▪Symptoms: nausea, vomiting, diarrhea, fatigue and lethargy ▪Phosphate binds calcium ions ---> secondary hypocalcemia

• Calcium-phosphate precipitates when solubility product is exceeded contributing to AKI

ACUTE KIDNEY INJURY

▪Urate nephropathy = most common cause ▪Additional contributing mechanisms to reduce kidney function within TLS:

• Calcium-phosphate precipitates
• Volume depletion – promotes acidic pH, decreasing solubility of UA
• Cytokine-mediated responses and changes
• CKD
• Hx of AKI

▪AKI further exacerbates the key electrolyte abnormalities of TLS and therefore renal function is the focus of prevention and treatment measures

N Engl J Med.

TLS MANAGEMENT

▪“The best treatment is prevention.”

• Screening
• Prophylaxis
• Treatment
• Monitoring

SCREENING: WHO’S AT RISK?

▪Hematological malignancies

• Acute lymphoblastic leukemia
• Non-Hodgkins lymphoma
• Burkitt’s lymphoma

▪Advanced stage malignancies ▪Advanced age ▪Medication use

▪NSAIDs, angiotensin receptor blockers, ACE inhibitors

▪Dehydration

Via American Society of Nephrology

PROPHYLAXIS & TREATMENT

▪Attention to renal function

▪Hydration – cornerstone of TLS management

▪IV volume expansion for all patients 2 days prior to tx ▪Hydration to achieve target urine output of ≥ 2 mL/kg/h ▪Pt at risk for volume overload may require loop diuretics

▪Pharmacotherapy if intermediate or high risk

▪Allopurinol ▪Rasburicase

• Allantoin is 5-10x more soluble than UA

▪Febuxostat

N Engl J Med.

PROPHYLAXIS & TREATMENT

▪Electrolyte management

• Reduce/remove k+ and phosphorus from TPN, TF, PO

intake during time of risk

• Phosphate-binders
• Kayexalate or hypertonic glucose + insulin
• Hypocalcemia NOT treated unless severe and

symptomatic

• Frequent monitoring

▪Renal Replacement Therapy

▪Intermittent hemodialysis ▪Continuous renal replacement therapies ▪May begin RRT prophylactically – hx of AKI or CKD

MONITORING

▪Essential aspect of TLS prevention and management ▪Interdisciplinary approach: oncology, ICU team, nephrology, cardiovascular, nutrition ▪Monitor labs and assess renal sufficiency prior to, during, and after treatment

• Urine output
• Electrolytes
• UA

▪Frequency dependent on risk severity

RELEVANCE TO CLINICAL RDS

▪Assess nutritional status and risk for malnutrition ▪Diet restrictions

• Evaluate, formulate and identify appropriate TPN,

TFs, supplements

• Diet education

▪Electrolyte monitoring ▪Fluid status ▪Interdisciplinary team member

LOOKING AHEAD:

THE FUTURE OF TLS RESEARCH

▪Crucial to develop universal, standard definition and diagnostic criteria ▪Improve risk assessment and identification ▪Specific nutritional needs – protein ▪Incidence of TLS

• Spontaneous, radiation, solid tumor patients

REFERENCES

Belay, Y., Yirdaw, K., & Enawgaw, B. (2017). Tumor lysis syndrome in patients with hematological malignancies. Journal of Oncology, 2017, 1-9. http://doi.org/10.1155/2017/9684909 Davidson, M.B, Thakkar, S., Hix, J.K., Bhandarkar, N.D., Wong, A., & Schreiber, M.J. (2004). Pathophysiology, clinical consequences, and treatment of tumor lysis syndrome. Am J Med, 116, 546-554. http://doi.org/10.1016/j.amkmed.2003.09.045 Edeani, A. & Shirali, A. (2016). Chapter 4: Tumor Lysis Syndrome. The American Society of Nephrology. Retrieved from https://www.asn-online.org/education/distancelearning/curricula/onco/Chapter4.pdf Escott-stump, S. (2012). Nutrition and diagnosis-related care (7th ed.). Baltimore, MD: Lippincott Williams & Wilkins. Garimella, P.S., Balakrishnan, P., Ammakkanavar, N.R., Patel, S., Patel, A., Konstantinidis, I.,… Nadkarni, G. (2017). Impact of dialysis requirement on outcomes in tumor lysis syndrome. Nephrology, 22,(2017), 85-88. http://doi.org/10.111/nep.12806 Howard, S.C., Jones, D.P., & Pui, C. (2011). The tumor lysis syndrome. N Engl J Med, 364(19), 1844-1854. http://www.nejm.org/doi/full/10.1056/NEJMra0904569 Mirrakhimov, A.E., Voore, P., Khan, M., & Ali, A.M. (2015). Tumor lysis syndrome: A clinical review. World Journal of Critical Care, 4(2), 130-138. http://doi.org/10.5492/wjccm.v4.i2.130 National Comprehensive Cancer Network. (2017). NCCN clinical practice guidelines in oncology: B-cell lymphomas. Retrieved from https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf The University of Texas MD Anderson Cancer Center. (2016). [Practice algorithm for tumor lysis in adult patients.] Retrieved from https://www.mdanderson.org/documents/for-physicians/algorithms/clinical-management/clin-management-tumor-lysis- web-algorithm.pdf

QUESTIONS?