2. Overview of TLS What is tumor lysis syndrome ? When does TLS arise?
Which tumors are associated with TLS ?
What is the pathophysiology of TLS?
What is the pathogenesis of hyperuricemia in TLS ?
Which patients are at the highest risk for TLS ?
What is the classification of cancers for the risk of TLS ?
Which agents may cause tumor lysis syndrome TLS ?
Which clinical conditions are rare causes of TLS ?
What is the global incidence of tumor lysis syndrome (TLS)?

3. definition
metabolic derangement resulting from abrupt and massive breakdown of malignant cells and the release of intracellular contents into the circulation which overwhelms the patient’sexcretory ability.
Characteristic LABORATORY findings of Tumor lysis syndrome include:
Hyperuricemia
Hyperkalemia
Hyperphosphatemia
Hypocalcemia

4. Guidelines for the Prevention of Tumour Lysis SyndromeVersion
Document Type: Clinical Practice GuidelineApproved on
Next Review Date:
Guidelines for the Prevention of Tumour Lysis SyndromeVersion

5. Although tumor lysis syndrome has been reported with virtually every type of tumor, it is typically associated with bulky, rapidly proliferating, treatment-responsive tumors —typically, acute leukemias and high-grade non-Hodgkin lymphomas such as Burkitt lymphoma.
The syndrome has also been reported with other hematologic malignancies and with solid tumors such as hepatoblastoma and stage IV neuroblastoma.

6. Because tumor lysis syndrome is potentially lethal, the main principles of management are (1) identification of high-risk patients with initiation of preventive therapy
(2) early recognition of metabolic and renal complications and the prompt administration of supportive care, including hemodialysis.

8. Agents reported to cause tumor lysis syndrome include the following:
Paclitaxel
Fludarabine
Etoposide
Thalidomide
Bortezomib
Zoledronic acid
Hydroxyurea
The development of tumor lysis syndrome is not limited to the systemic administration of agents; it can occur with intrathecal administration of chemotherapy and with chemo-embolization

11. TLS Incidence Today
Criscuolo M, et al. Expert Review of Hematology 2016; 9(2):

14. Risk Factors for the Tumor Lysis Syndrome.
1. Cancer mass:-
Risk Factor
Comment
Bulky tumor or
extensive metastasis
The larger the cancer mass have higher risk of
clinical TLS
Organ infiltration by
cancer cells
Hepatomegaly, splenomegaly, and nephromegaly generally
represent tumor infiltration into these organs and
a larger tumor burden
Bone marrow
involvement
Healthy adults have 1.4 kg of bone marrow
A marrow that has been replaced by leukemic cells
contains a cancer mass greater than 1 kg and
represents bulky disease.
Renal infiltration or
outflow-tract
obstruction
Decreased urine flow predispose to nephropathy from
other causes, such as the tumor lysis syndrome.

15. Risk Factors for the Tumor Lysis Syndrome.
2. Cell lysis potential:-
Risk Factor
Comment
High rate of
proliferation of
cancer cells
LDH is a surrogate for tumor proliferation.
The higher level is a risk of TLS
Cancer-cell
sensitivity to
anticancer therapy
Cancers that are more sensitive to therapy have
a higher rate of TLS
Intensity of initial
anticancer therapy
Preexisting nephropathy from hypertension, diabetes or
or other causes has a greater risk for acute kidney injury
and TLS

16. Risk Factors for the Tumor Lysis Syndrome.
3. Features on patient presentation:-
Risk Factor
Comment
Nephropathy before
diagnosis of cancer
Predisposes to TLS
Dehydration or
volume depletion
Dehydration decreases the rate of urine flow through renal
tubules and increases the level of solutes
Acidic urine
Uric acid has a lower solubility in acidic urine and therefore
crystallizes more rapidly
Hypotension
Hypotension decreases urine flow and increases the level of
solutes that can crystallize. Hypotension can also
independently cause acute kidney injury.
Exposure to
nephrotoxins
Vancomycin, aminoglycosides, contrast agents for diagnostic
imaging, and other potential nephrotoxins increase the risk
of acute kidney injury from lysis of cancer cells.

17. Comment Risk Factor Risk Factors for the Tumor Lysis Syndrome.
4. Supportive care
Risk Factor
Comment
Inadequate
hydration
Increases the risk of crystallization inside tubules
Exogenous
potassium
potassium should not be included in the intravenous fluids, and potassium from food or medications should be minimized until the risk of TLS has passed.

18. Risk Factors for the Tumor Lysis Syndrome.
4. Supportive care:-
Risk Factor
Comment
Exogenous phosphate
Restricting dietary phosphate and adding a phosphate
binder reduce the exogenous load of phosphate so that the
kidneys need only excrete the endogenous load of
phosphate released by cancer-cell lysis.
Delayed uric acid removal
Allopurinol prevents formation of new uric acid by inhibiting xanthine oxidase and preventing conversion of xanthine to uric acid.
Allopurinol does not remove existing uric acid and increases urinary excretion of xanthine, which can crystallize and cause “xanthine nephropathy“
Rasburicase rapidly removes uric acid by converting it to allantoin,which is highly soluble and readily excreted in the urine.

19. Timing of developing TLS
TLS occurs mainly after conventional chemotherapy.
However, corticosteroids, radiation, or monoclonal Abs may also cause a significant TLS.
Less frequent, spontaneous TLS can develop prior to initiation of anticancer therapy.
Even invasive procedures like biopsy, embolization and tumor surgery could lead to TLS.

20. ALL with > 100,000 or LDH of 2 ULN AML with WBC > 100,000
High-Risk Tumors
newly diagnosed/relapsed with Burkitt’s lymphoma
newly diagnosed with lymphoblastic lymphoma with advanced or bulky disease
ALL with > 100,000 or LDH of 2 ULN
AML with WBC > 100,000
DLBCL and bulky disease with an elevated LDH of 2 ULN
pre-existing renal impairment
Intermediate-Risk Tumors
AML with WBC between 25,000 and 100,000
ALL with WBC < 100,000 and a LDH of less than 2 ULN
DLBCL and LDH of 2 ULN but non-bulky disease
Early stage Burkitt lymphoma or leukemia with a LDH < 2 ULN
Highly chemotherapy sensitive solid tumours (e.g. neuroblastoma, germ cell tumour) with advanced or bulky disease
Low-Risk Tumors
Solid cancers
Indolent lymphomas
CML
AML with a WBC < 25,000 and LDH elevated to less than 2 ULN