Tumor lysis syndrome resident survival guide: Difference between revisions

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__NOTOC__
__NOTOC__
{{CMG}}; {{AE}} {{TS}}
{{CMG}}; {{AE}} {{TS}}; {{Rim}}


==Definition==
==Overview==
Tumor lysis syndrome (TLS) is a group of metabolic abnormalities resulting from rapid lysis of malignant cells and massive release of cell breakdown products into the blood among patients with hematologic malignancies treated with chemotherapy.  Metabolic complications include [[hyperkalemia]], [[hyperphosphatemia]], [[hyperuricemia]], [[hypocalcemia]] and [[hyperuricosuria]].<ref name="pmid18509186">{{cite journal| author=Coiffier B, Altman A, Pui CH, Younes A, Cairo MS| title=Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. | journal=J Clin Oncol | year= 2008 | volume= 26 | issue= 16 | pages= 2767-78 | pmid=18509186 | doi=10.1200/JCO.2007.15.0177 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18509186  }} </ref>
Tumor lysis syndrome (TLS) is a group of metabolic abnormalities resulting from rapid lysis of malignant cells and massive release of cell breakdown products into the blood among patients with hematologic malignancies treated with chemotherapy.  Metabolic complications include [[hyperkalemia]], [[hyperphosphatemia]], [[hyperuricemia]], [[hypocalcemia]] and [[hyperuricosuria]].<ref name="pmid18509186">{{cite journal| author=Coiffier B, Altman A, Pui CH, Younes A, Cairo MS| title=Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. | journal=J Clin Oncol | year= 2008 | volume= 26 | issue= 16 | pages= 2767-78 | pmid=18509186 | doi=10.1200/JCO.2007.15.0177 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18509186  }} </ref>


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* [[Non-Hodgkin's lymphoma]]
* [[Non-Hodgkin's lymphoma]]


==Classification==
==Management==
Cairo and Bishop classified and graded TLS as laboratory tumor lysis syndrome (LTLS) and clinical tumor lysis syndrome (CTLS).


====Cairo and Bishop Definition for Laboratory Tumor Lysis Syndrome (LTLS)<ref name="pmid18509186">{{cite journal| author=Coiffier B, Altman A, Pui CH, Younes A, Cairo MS| title=Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. | journal=J Clin Oncol | year= 2008 | volume= 26 | issue= 16 | pages= 2767-78 | pmid=18509186 | doi=10.1200/JCO.2007.15.0177 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18509186  }} </ref>====
===Prevention===
LTLS is considered to be present if 2 or more of the following serum abnormalities are present within 3 days before or 7 days after [[cytotoxic]] therapy.
Shown below is an algorithm summarizing the approach to tumor lysis syndrome according to the guidelines by American Society of Clinical oncology and an expert TLS panel consensus.<ref name="Cairo-2010">{{Cite journal  | last1 = Cairo | first1 = MS. | last2 = Coiffier | first2 = B. | last3 = Reiter | first3 = A. | last4 = Younes | first4 = A. | last5 = Cairo | first5 = MS. | last6 = Coiffier | first6 = B. | last7 = Reiter | first7 = A. | last8 = Younes | first8 = A. | last9 = Baruchel | first9 = A. | title = Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus. | journal = Br J Haematol | volume = 149 | issue = 4 | pages = 578-86 | month = May | year = 2010 | doi = 10.1111/j.1365-2141.2010.08143.x | PMID = 20331465 }}</ref><ref name="pmid18509186">{{cite journal| author=Coiffier B, Altman A, Pui CH, Younes A, Cairo MS| title=Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. | journal=J Clin Oncol | year= 2008 | volume= 26 | issue= 16 | pages= 2767-78 | pmid=18509186 | doi=10.1200/JCO.2007.15.0177 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18509186  }} </ref>
{|Class="wikitable"
|-
|style="border-bottom:3px solid grey;" align="center" width="200" style="background:#efefef;"|'''Element''' ||style="border-bottom:3px solid grey;" align="center" width="200" style="background:#efefef;"|'''Value''' ||style="border-bottom:3px solid grey;" align="center" width="200" style="background:#efefef;"|'''Change from baseline'''
|-
|[[Uric acid]] ||≥476 μmol/L or 8 mg/dL ||25 % increase
|-
|[[Potassium]] ||≥6 mmol/L or 6mg/L || 25 % increase
|-
|[[Phosphorus]] ||≥2.1 mmol/L for children<br>≥1.45 mmol/L for adults ||25 % increase
|-
|[[Calcium]] ||≤1.75 mmol/L || 25% decrease
|-
|}
====Cairo and Bishop Definition and Grading for Clinical Tumor Lysis Syndrome (CTLS)<ref name="pmid18509186">{{cite journal| author=Coiffier B, Altman A, Pui CH, Younes A, Cairo MS| title=Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. | journal=J Clin Oncol | year= 2008 | volume= 26 | issue= 16 | pages= 2767-78 | pmid=18509186 | doi=10.1200/JCO.2007.15.0177 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18509186  }} </ref>====
Clinical tumor lysis syndrome is said to be present if LTLS is present plus 1 or more of the following clinical correlations:
{|Class="wikitable"
|-
|style="background:#efefef;" align="center"|'''Complication'''||style="background:#efefef;" colspan="6" align="center"|'''Grade'''
|-
| ||0||1||2||3||4||5
|-
|[[Creatinine]]||≤1.5×ULN||1.5×ULN||>1.5-3.0×ULN||>3-6×ULN||>6×ULN||[[Death]]
|-
|[[Cardiac arrhythmia]]||None|| Intervention not indicated||'''Medical intervention''' indicated,<br> but '''not urgently'''||Controlled with a device or<br> symptomatically and incompletely<br> controlled medically||Life threatening||Death
|-
|[[Seizure]]||None||-||One well controlled generalized seizure OR<br>infrequent multiple focal motor seizures <br> not affecting activities of daily living||poorly controlled seizure disorder,<br>seizure with altered consciousness||[[Status epilepticus]],<br> intractable [[epilepsy]]|| Death
|-
|}
ULN: Upper limit of normal
 
==Prevention==
Shown below is an algorithm summarizing the approach to <nowiki>tumor lysis syndrome</nowiki> according to the guidelines by American Society of Clinical oncology and an expert TLS panel consensus.<ref name="Cairo-2010">{{Cite journal  | last1 = Cairo | first1 = MS. | last2 = Coiffier | first2 = B. | last3 = Reiter | first3 = A. | last4 = Younes | first4 = A. | last5 = Cairo | first5 = MS. | last6 = Coiffier | first6 = B. | last7 = Reiter | first7 = A. | last8 = Younes | first8 = A. | last9 = Baruchel | first9 = A. | title = Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus. | journal = Br J Haematol | volume = 149 | issue = 4 | pages = 578-86 | month = May | year = 2010 | doi = 10.1111/j.1365-2141.2010.08143.x | PMID = 20331465 }}</ref><ref name="pmid18509186">{{cite journal| author=Coiffier B, Altman A, Pui CH, Younes A, Cairo MS| title=Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. | journal=J Clin Oncol | year= 2008 | volume= 26 | issue= 16 | pages= 2767-78 | pmid=18509186 | doi=10.1200/JCO.2007.15.0177 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18509186  }} </ref>


{{familytree/start |summary=PE diagnosis Algorithm.}}
{{familytree/start |summary=PE diagnosis Algorithm.}}
{{familytree | | | | | | | | | | | A01 | | | A01= '''Risk assessment''' of patients for '''TLS'''}}
{{familytree | | | | | A01 | | | A01= '''Risk assessment of patients for TLS'''}}
{{familytree | | | | | |,|-|-|-|-|-|+|-|-|-|-|-|.| | }}
{{familytree | |,|-|-|-|+|-|-|-|.| | }}
{{familytree | | | | | B01 | | | | B02 | | | | B03 | | | B01= <div style="float: left; text-align: left; height: 25em; width: 20em; padding:1em;"> '''Low Risk Disease (LRD):'''<br>
{{familytree | B01 | | B02 | | B03 | | B01= <div style="float: left; text-align: left; height: 25em; width: 20em; padding:1em;"> '''Low Risk Disease (LRD):'''<br>
----
----
❑ Solid tumors <br> ❑ [[Multiple myeloma]] <br> ❑ Indolent [[Non-Hodgkin's lymphoma]] <br>❑ [[Hodgkin's lymphoma]]<br> ❑ [[AML]] with WBC count ≤25,000 cells/μL and LDH < 2× ULN <br> ❑ [[CLL]] with WBC count < 50,000 cells/μL, treated only with [[alkylating agents]] <br> ❑ [[CML]]<br>
❑ Solid tumors <br> ❑ [[Multiple myeloma]] <br> ❑ Indolent [[Non-Hodgkin's lymphoma]] <br>❑ [[Hodgkin's lymphoma]]<br> ❑ [[AML]] with WBC count ≤25,000 cells/μL and LDH < 2× ULN <br> ❑ [[CLL]] with WBC count < 50,000 cells/μL, treated only with [[alkylating agents]] <br> ❑ [[CML]]<br>
</div>|B02=<div style="float: left; text-align: left; height: 27em; width: 20em; padding:1em;"> '''Intermediate Risk Disease (IRD):'''<br>
</div>|B02=<div style="float: left; text-align: left; height: 27em; width: 20em; padding:1em;"> '''Intermediate Risk Disease (IRD):'''<br>
----❑ Bulky or advanced stage solid tumors <br> ❑ [[Plasma cell leukemia]] <br> ❑ Stage III/IV [[Non-Hodgkin's lymphoma]] with LDH > 2xULN <br> ❑[[AML]] with WBC count ≤25,000 cells/μL and LDH > 2× ULN OR [[AML]] with WBC count 25,000-100,000 cells/μL <br> ❑ [[CLL]] treated with [[fludarabine]] or [[rituximab]] or CML with WBC count > 50,000 cells/μL <br> ❑ [[ALL]] with WBC < 100,000 cells/μL and LDH > 2xULN<br>❑ [[Burkitt's lymphoma]] stage I/II with LDH < 2x ULN<br>
----❑ Bulky or advanced stage solid tumors <br> ❑ [[Plasma cell leukemia]] <br> ❑ Stage III/IV [[Non-Hodgkin's lymphoma]] with LDH > 2xULN <br> ❑ [[AML]] with WBC count ≤25,000 cells/μL and LDH > 2× ULN OR [[AML]] with WBC count 25,000-100,000 cells/μL <br> ❑ [[CLL]] treated with [[fludarabine]] or [[rituximab]] or CML with WBC count > 50,000 cells/μL <br> ❑ [[ALL]] with WBC < 100,000 cells/μL and LDH > 2xULN<br>❑ [[Burkitt's lymphoma]] stage I/II with LDH < 2x ULN<br>
❑ [[Lymphoblastic lymphoma]] stage I/II with LDH < 2x ULN<br>
❑ [[Lymphoblastic lymphoma]] stage I/II with LDH < 2x ULN<br>
❑ [[Diffuse large B cell lymphoma]]</div>|B03=<div style="float: left; text-align: left; height: 25em; width: 20em; padding:1em;">'''High Risk Disease (HRD):'''<br>
❑ [[Diffuse large B cell lymphoma]]</div>|B03=<div style="float: left; text-align: left; height: 25em; width: 20em; padding:1em;">'''High Risk Disease (HRD):'''<br>
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❑ [[AML]] with WBC count > 100,000 cells/μL <br> ❑ [[ALL]] with WBC >100,000 cells/μL AND/OR LDH > 2xULN <br> ❑ [[Burkitt's lymphoma]] stage III/IV with LDH ≥ 2x ULN <br> ❑ [[Lymphoblastic lymphoma]] stage III/IV with LDH ≥ 2x ULN <br>❑ IRD with renal dysfunction<br>❑ IRD with uric acid, potassium or phosphate above ULN<br>
❑ [[AML]] with WBC count > 100,000 cells/μL <br> ❑ [[ALL]] with WBC >100,000 cells/μL AND/OR LDH > 2xULN <br> ❑ [[Burkitt's lymphoma]] stage III/IV with LDH ≥ 2x ULN <br> ❑ [[Lymphoblastic lymphoma]] stage III/IV with LDH ≥ 2x ULN <br>❑ IRD with renal dysfunction<br>❑ IRD with uric acid, potassium or phosphate above ULN<br>
</div>}}
</div>}}
{{familytree | | | | | |!| | | | | |!| | | | | |!| | | | | | | | | | | | | | | | | |}}
{{familytree | |!| | | |!| | | |!| | |}}
{{familytree | | | | | |!| | | | | |!| | | | | |!| | | | | | | | | | | | | | | | | |}}
{{familytree | C01 | | C02 | | C03 | |C01=<div style="float: left; text-align: left; height: 21em; width: 20em; padding:1em;">❑ Provide hydration with 2-3 L/m²/day IV of a one quarter NS/5%dextrose<br>❑ Monitor urine output (80-100 ml/m²/hr)<br>❑ Record the fluid balance <br>❑ Monitor [[electrolyte]]s and [[creatinine]] daily</div>|C02=<div style="float: left; text-align: left; height: 21em; width: 20em; padding:1em;">❑ Monitoring for laboratory or clinical TLS criteria for 24-72 hrs<br>
{{familytree | | | | | C01 | | | | C02 | | | | C03 | | | | | | | | | | | | | | | | |C01=<div style="float: left; text-align: left; height: 21em; width: 20em; padding:1em;">❑ Provide hydration with 2-3 L/m²/day IV of a one quarter NS/5%dextrose<br>❑ Monitor urine output (80-100 ml/m²/hr)<br>❑ Record the fluid balance <br>❑ Monitor [[electrolyte]]s and [[creatinine]] daily</div>|C02=<div style="float: left; text-align: left; height: 21em; width: 20em; padding:1em;">❑ Monitoring for laboratory or clinical TLS criteria for 24-72 hrs<br>
❑ Provide hydration with 2-3 L/m²/day IV of a one quarter NS/5%dextrose<br>❑ Monitor urine output (80-100 ml/m²/hr)<br>❑ Record the fluid balance <br>❑ Monitor [[electrolyte]]s and [[creatinine]] every 8-12 hours<br>
❑ Provide hydration with 2-3 L/m²/day IV of a one quarter NS/5%dextrose<br>❑ Monitor urine output (80-100 ml/m²/hr)<br>❑ Record the fluid balance <br>❑ Monitor [[electrolyte]]s and [[creatinine]] eevry 8-12 hours<br>
❑ Administer [[allopurinol]]*<br>
❑ Administer [[allopurinol]]*<br>
❑ Add 0.15 mg/kg [[rasburicase]] in pediatric patients with uric acid level ≥ 7.5 mg/dl for 1-7 days (average 3 days)
❑ Add 0.15 mg/kg [[rasburicase]] in pediatric patients with uric acid level ≥ 7.5 mg/dl for 1-7 days (average 3 days)
</div>| C03=<div style="float: left; text-align: left; height: 21em; width: 20em; padding:1em;">❑ Provide hydration with 2-3 L/m²/day IV of a one quarter NS/5%dextrose<br>❑ Monitor urine output (80-100 ml/m²/hr)<br>❑ Record the fluid balance <br>❑ Monitor [[electrolyte]]s and [[creatinine]] every 4-6 hours<br>❑ Ensure continuous cardiac monitoring <br>❑ Consult [[nephrology]]<br>❑ Delay tumor therapy (individual clinical judgement)<br>
</div>| C03=<div style="float: left; text-align: left; height: 21em; width: 20em; padding:1em;">❑ Provide hydration with 2-3 L/m²/day IV of a one quarter NS/5%dextrose<br>❑ Monitor urine output (80-100 ml/m²/hr)<br>❑ Record the fluid balance <br>❑ Monitor [[electrolyte]]s and [[creatinine]] every 4-6 hours<br>❑ Ensure continuous cardiac monitoring <br>❑ Request renal consult<br>❑ Delay tumor therapy (individual clinical judgement)<br>
❑ Administer 0.20 mg/kg [[rasburicase]] in pediatric patients with uric acid level > 7.5 mg/dl for 1-7 days (average 3 days)</div> }}
❑ Administer 0.20 mg/kg [[rasburicase]] in pediatric patients with uric acid level > 7.5 mg/dl for 1-7 days (average 3 days)</div> }}
{{familytree | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |}}
 
{{familytree/end}}
{{familytree/end}}


<nowiki>* </nowiki>'''[[Allopurinol]] administration:'''<br>
<nowiki>*</nowiki> '''[[Allopurinol]] administration:'''<br>
* '''In pediatric patients:'''
* '''In pediatric patients:'''
** 50-100 mg/m2 every 8 hours, orally, maximum dose of 300 mg/m2/d, OR
** 50-100 mg/m2 every 8 hours, orally, maximum dose of 300 mg/m2/d, OR
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** 100 mg/m2/dose every 8 hours (10 mg/kg/d divided every 8 hours), orally, maximum dose of 800 mg/d, OR
** 100 mg/m2/dose every 8 hours (10 mg/kg/d divided every 8 hours), orally, maximum dose of 800 mg/d, OR
** 200-400 mg/m<sup>2</sup>/d, 1 to 3 IV doses, maximum dose 600 mg/d (when oral allopurinol can not be administered)<ref name="pmid18509186">{{cite journal| author=Coiffier B, Altman A, Pui CH, Younes A, Cairo MS| title=Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. | journal=J Clin Oncol | year= 2008 | volume= 26 | issue= 16 | pages= 2767-78 | pmid=18509186 | doi=10.1200/JCO.2007.15.0177 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18509186  }} </ref>
** 200-400 mg/m<sup>2</sup>/d, 1 to 3 IV doses, maximum dose 600 mg/d (when oral allopurinol can not be administered)<ref name="pmid18509186">{{cite journal| author=Coiffier B, Altman A, Pui CH, Younes A, Cairo MS| title=Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. | journal=J Clin Oncol | year= 2008 | volume= 26 | issue= 16 | pages= 2767-78 | pmid=18509186 | doi=10.1200/JCO.2007.15.0177 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18509186  }} </ref>
<br>
===General Management===
Shown below is an algorithm summarizing the initial management of tumor lysis syndrome.<ref name="pmid18509186">{{cite journal| author=Coiffier B, Altman A, Pui CH, Younes A, Cairo MS| title=Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. | journal=J Clin Oncol | year= 2008 | volume= 26 | issue= 16 | pages= 2767-78 | pmid=18509186 | doi=10.1200/JCO.2007.15.0177 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18509186  }} </ref><ref name="Cairo-2010">{{Cite journal  | last1 = Cairo | first1 = MS. | last2 = Coiffier | first2 = B. | last3 = Reiter | first3 = A. | last4 = Younes | first4 = A. | last5 = Cairo | first5 = MS. | last6 = Coiffier | first6 = B. | last7 = Reiter | first7 = A. | last8 = Younes | first8 = A. | last9 = Baruchel | first9 = A. | title = Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus. | journal = Br J Haematol | volume = 149 | issue = 4 | pages = 578-86 | month = May | year = 2010 | doi = 10.1111/j.1365-2141.2010.08143.x | PMID = 20331465 }}</ref><ref name="pmid21561350">{{cite journal| author=Howard SC, Jones DP, Pui CH| title=The tumor lysis syndrome. | journal=N Engl J Med | year= 2011 | volume= 364 | issue= 19 | pages= 1844-54 | pmid=21561350 | doi=10.1056/NEJMra0904569 | pmc=PMC3437249 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21561350  }} </ref>


==Initial Approach==
{{Family tree/start}}
{{Family tree/start}}
{{familytree  | | | | | B01 | | | | | B01=<div style="float: left; text-align: left; height: 22em; width: 17em; padding:1em;"> '''Characterize the symptoms:'''<br>
{{familytree  | | | | | B01 | | | | | B01=<div style="float: left; text-align: left; height: 21em; width: 17em; padding:1em;"> '''Characterize the symptoms:'''<br>
----
----
❑ [[Nausea]] <br> ❑ [[Vomiting]] <br> ❑ [[Anorexia]]  <br> ❑ [[Lethargy]]  <br> ❑ [[Diarrhea]]  <br> ❑ [[Hematuria]]  <br> ❑ [[Seizures]]  <br> ❑ Muscle cramps<br> ❑ [[Syncope]]<br>❑ [[Flank pain]]<br>❑ [[Heart failure]]<br>❑ [[Tetany]]<br>❑ [[Arrhythmia]]</div>}}
❑ [[Nausea]] <br> ❑ [[Vomiting]] <br> ❑ [[Anorexia]]  <br> ❑ [[Lethargy]]  <br> ❑ [[Diarrhea]]  <br> ❑ [[Hematuria]]  <br> ❑ [[Seizures]]  <br> ❑ Muscle cramps<br> ❑ [[Syncope]]<br>❑ [[Flank pain]]<br>❑ [[Heart failure]]<br>❑ [[Tetany]]<br>❑ [[Arrhythmia]]</div>}}
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----
----
❑ Order an [[EKG]]</div>}}
❑ Order an [[EKG]]</div>}}
{{familytree  | | | | | |!| | | | | |}}
{{familytree  | | | | | D01 | | | | |D01='''Does the patient have the criteria for the diagnosis of tumor lysis syndrome?'''}}
{{familytree  | |,|-|-|-|+|-|-|-|.| |}}
{{familytree  | |,|-|-|-|+|-|-|-|.| |}}
{{familytree  | E01 | | E02 | | E02 | | E01= |E02= | E03= }}
{{familytree  | E01 | | E02 | | E03 | | E01= '''No TLS''' |E02= '''Laboratory TLS'''| E03= '''Clinical TLS''' <br> }}
{{familytree  | |!| | | |!| | | |!| | | }}
{{familytree  | |!| | | |!| | | |!| | | }}
{{familytree  | F01 | | F02 | | F03 | |F01=<div style="width:15em;">❑ Stratify the patient by the risk of developing TLS <br> ❑ Initiate the appropriate preventive measures (see the algorithm above)</div>|F02= | F03=<div style="float: left; text-align: left; height: 16em; width: 17em; padding:1em;"> ❑ Intensive care in [[ICU]]<br>❑ Continuous cardiac monitoring<br>❑ Renal consult<br>❑ Above mentioned laboratory tests every 4-6 hours<br>❑ Normalize electrolyte abnormalities<br>❑ [[Rasburicase]] 0.2 mg/kg<br>❑ Hydration ± loop diuretic</div>}}
{{familytree  | F01 | | F02 | | F03 | |F01=<div style="float: left; text-align: left; height: 16em; width: 17em; padding:1em;">❑ Stratify the patient by the risk of developing TLS <br> ❑ Initiate the appropriate preventive measures (see the algorithm above)</div>|F02= <div style="float: left; text-align: left; height: 16em; width: 17em; padding:1em;"> ❑ Provide hydration with 2-3 L/m²/day IV of a one quarter NS/5%dextrose <br> ❑ Monitor urine output (80-100 ml/m²/hr)<br> ❑ Record the fluid balance <br>❑ Monitor [[electrolyte]]s and [[creatinine]] every 4-6 hours<br> ❑ Ensure continuous cardiac monitoring<br> ❑ Request a renal consult<br> ❑ Normalize electrolyte abnormalities<br>❑ Administer [[rasburicase]]* 0.2 mg/kg</div>| F03=<div style="float: left; text-align: left; height: 24em; width: 17em; padding:1em;"> ❑ Admit to the intensive care in [[ICU]]<br>❑ Provide hydration with 2-3 L/m²/day IV of a one quarter NS/5%dextrose<br>❑ Monitor urine output (80-100 ml/m²/hr)<br>❑ Record the fluid balance <br>❑ Monitor [[electrolyte]]s and [[creatinine]] every 4-6 hours<br> ❑ Ensure continuous cardiac monitoring<br>❑ Request a renal consult <br> ❑ Normalize electrolyte abnormalities<br>❑ Administer [[rasburicase]]* 0.2 mg/kg<br>❑ Hydration ± loop diuretic</div>}}
{{familytree/end}}
{{familytree/end}}


==Management of the Complications==
<nowiki>*</nowiki> [[Rasburicase]] is not FDA approved for the use in the prophylaxis or treatment of tumor lysis syndrome in adults.  It is only approved by the FDA for its use in the pediatric population.
<br>
 
===Management of Electrolyte Disturbances===
Shown below is an algorithm summarizing the management of the electrolytes disturbances in tumor lysis syndrome.<ref name="pmid18509186">{{cite journal| author=Coiffier B, Altman A, Pui CH, Younes A, Cairo MS| title=Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. | journal=J Clin Oncol | year= 2008 | volume= 26 | issue= 16 | pages= 2767-78 | pmid=18509186 | doi=10.1200/JCO.2007.15.0177 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18509186  }} </ref><ref name="Cairo-2010">{{Cite journal  | last1 = Cairo | first1 = MS. | last2 = Coiffier | first2 = B. | last3 = Reiter | first3 = A. | last4 = Younes | first4 = A. | last5 = Cairo | first5 = MS. | last6 = Coiffier | first6 = B. | last7 = Reiter | first7 = A. | last8 = Younes | first8 = A. | last9 = Baruchel | first9 = A. | title = Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus. | journal = Br J Haematol | volume = 149 | issue = 4 | pages = 578-86 | month = May | year = 2010 | doi = 10.1111/j.1365-2141.2010.08143.x | PMID = 20331465 }}</ref>
 
{{familytree/start}}
{{familytree/start}}
{{familytree  | | | | | | | | A01 | | | | | | | A01= '''Complications of TLS'''}}
{{familytree  | | | | | A01 | | | A01= <div style="float: left; height: 2em; width:17em; padding:1em;">'''Management of electrolyte disturbances in TLS'''</div>}}
{{familytree  | | | | | | | | |!| | | | | | | |}}
{{familytree  | |,|-|-|-|+|-|-|-|.| | }}
{{familytree  | | |,|-|-|-|v|-|^|-|v|-|-|-|.| |}}
{{familytree  | G01 | | G02 | | G03 | G01=[[Hyperphosphatemia]]|G02=[[Hypocalcemia]]|G03=[[Hyperkalemia]]}}
{{familytree  | | |!| | | |!| | | |!| | | |!| | |}}
{{familytree  | |!| | | |!| | | |!| | }}
{{familytree  | | G01 | | G02 | | G03 | | G04 | | |G01=[[Hyperphosphatemia]]|G02=[[Hypocalcemia]]|G03=[[Hyperkalemia]]|G04=[[Hyperuricemia]]}}
{{familytree  | H01 | | H02 | | H03 | |H01=<div style="float: left; text-align: left; height: 28em; width:17em; padding:1em;"> '''Moderate ( ≥2.1 mmol/L)'''<br>
{{familytree  | | |!| | | |!| | | |!| | | |!| | |}}
{{familytree  | | H01 | | H02 | | H03 | | H04 | |H01=<div style="float: left; text-align: left; height: 26em; width:
19em; padding:1em;"> '''Moderate ( ≥2.1 mmol/L)'''<br>
----
----
❑ Avoid phosphate in IV solutions<br> ❑ Provide adequate hydration<br>
❑ Avoid phosphate in IV solutions<br> ❑ Provide adequate hydration<br>
❑ Administer [[phosphate binders]]:<br>
❑ Administer [[phosphate binders]]:<br>
: ♦ [[Aluminium hydroxide]]: 50-150 mg/kg/day every 6 hrs, orally or by NG tube<br>
: ♦ [[Aluminium hydroxide]]: 50-150 mg/kg/day every 6 hrs, orally or by NG tube<br>
: ♦ [[Calcium carbonate]]: 30-40 mg/kg with each meal
: ♦ [[Calcium carbonate]]
: ♦ [[Lanthanum carbonate]]: 500-1000 mg with each meal
: ♦ [[Lanthanum carbonate]]
: ♦ [[Sevelamer]]<br>
: ♦ [[Sevelamer]]<br>
----
'''Severe'''<br>
'''Severe'''<br>
----
----
❑ [[Hemodialysis]]<br>❑ [[Peritoneal dialysis]]<br>❑ Continuous venovenous hemofiltration </div>|H02=<div style="float: left; text-align: left; height: 26em; width: 19em; padding:1em;">'''Asymptomatic'''<br>
❑ [[Hemodialysis]]<br>❑ [[Peritoneal dialysis]]<br>❑ Continuous venovenous hemofiltration </div>|H02=<div style="float: left; text-align: left; height: 28em; width: 17em; padding:1em;">'''Asymptomatic'''<br>
----
----
❑ No treatment required<br>
❑ No treatment required<br>
'''Symptomatic'''<br>
'''Symptomatic'''<br>
----
----
❑ [[Calcium gluconate]] 50-100 mg/kg IV, given slowly with EKG monitoring<br>
Administer [[calcium gluconate]] 50-100 mg/kg IV, given slowly with EKG monitoring<br>
If [[phosphate]] levels are high<br>
Request a renal consult if [[phosphate]] level is high </div>|H03=<div style="float: left; text-align: left; height: 28em; width: 17em; padding:1em;">'''Asymptomatic ( ≥ 6.0 mmol/L)'''<br>
: ♦ Renal consult </div>|H03=<div style="float: left; text-align: left; height: 26em; width: 19em; padding:1em;">'''Asymptomatic ( ≥ 6.0 mmol/L)'''<br>
----
----
❑ Avoid IV or oral [[potassium]] intake<br>❑  [[Sodium polystyrene sulfonate]] 1 g/kg with 50 % [[sorbitol]]<br>❑ Cardiac monitoring<br>
❑ Avoid IV or oral [[potassium]] intake<br>❑  Administer [[sodium polystyrene sulfonate]] 1 g/kg with 50 % [[sorbitol]]<br>❑ Ensure cardiac monitoring<br>
----
----
'''Severe ( > 7 mmol/L)/ Symptomatic:'''<br>
'''Severe ( > 7 mmol/L)/ Symptomatic:'''<br>
----
----
Above mentioned actions plus:<br>❑ Rapid acting insulin 0.1 U/kg IV plus glucose infusion (25 % dextrose 2 ml/kg)<br>❑ Calcium gluconate 100-200 mg/kg/dose slow infusion with ECG monitoring for arrhythmias.<br>❑ [[Sodium bicarbonate]] 1-2 mEq/kg IV push<br>❑ [[Albuterol]] inhalation<br>❑ [[Hemodialysis]]</div>|H04=<div style="float: left; text-align: left; height: 26em; width: 19em; padding:1em;">'''Established [[hyperuricemia]]'''<br>
Perform the above mentioned actions<br>❑ Administer regular insulin 0.1 U/kg IV plus glucose infusion (25 % dextrose 2 ml/kg)<br>❑ Administer calcium gluconate 100-200 mg/kg/dose slow infusion with ECG monitoring for arrhythmias<br>❑ Administer [[sodium bicarbonate]] 1-2 mEq/kg IV push<br> ❑ [[Hemodialysis]]</div>}}
----
{{familytree  | |`|-|-|-|+|-|-|-|'| | |}}
❑ Hydration<br>
{{familytree  | | | | | I01 | | | | | | | I01=❑ Monitor the patient}}
: ♦ 2-3 L/m²/day IV of a one quarter NS/5%dextrose<br>
{{familytree  | | | |,|-|^|-|.| | }}
: ♦ Urine out maintained up to 80-100 ml/m²/hr<br>
{{familytree  | | | Z01 | | Z02 | | | Z01=No improvement <br>Renal dysfunction| Z02=Improvement}}
❑ [[Allopurinol ]] administration</div>}}
{{familytree  | | | |!| | | |!| | }}
{{familytree  | | |`|-|-|-|^|-|v|-|^|-|-|-|'| |}}
{{familytree  | | | J01 | | J02 | | J01=<div style="float: left; text-align: left; height: 7em; width: 15em; padding:1em;">❑ Ensure fluid and electrolyte management<br> ❑ Order [[dialysis]]<br> ❑ Adjust the dose of drugs excreted by the kidneys</div>| J02=<div style="float: left; text-align: left; height: 7em; width: 12em; padding:1em;">❑ Continue treatment<br>❑ Continue laboratory monitoring<br>❑ Continue cardiac monitoring</div>}}
{{familytree  | | | | | | | | I01 | | | | | | | I01=Patient responds?}}
{{familytree  | | | | Z01 |-|-|^|-|-| Z02 | | | Z01=No| Z02=Yes}}
{{familytree  | | | | |!| | | | | | | |!| | | |}}
{{familytree  | | | | J01 | | | | | | | J02 | |J02=<div style="float: left; text-align: left; height: 10em; width: 12em; padding:1em;">❑ Continue treatment<br>❑ Continue laboratory monitoring<br>❑ Continue cardiac monitoring</div>|J01=Renal dysfunction (Uremia)}}
{{familytree  | | | | |!| | | | | | | | | | | |}}
{{familytree  | | | | K01 | | | | | | | | | | | K01=<div style="float: left; text-align: left; height: 26em; width: 19em; padding:1em;">❑ Fluid and electrolyte management<br>❑ Uric acid and phosphate management<br>❑ [[Hemodialysis]]<br>❑ [[Peritoneal dialysis]]<br>❑ [[Hemofiltration]]<br> ❑ Adjust the dose of drugs excreted by the kidneys</div>}}
{{familytree/end}}
{{familytree/end}}
<br>
<br>
==Cairo and Bishop Definition for Laboratory Tumor Lysis Syndrome (LTLS)==
Laboratory tumor lysis syndrome (LTLS) is considered to be present if 2 or more of the following serum abnormalities are present within 3 days before or 7 days after [[cytotoxic]] therapy.  Shown below is a table summarizing the Cairo and Bishop definitions for laboratory tumor lysis syndrome.<ref name="pmid18509186">{{cite journal| author=Coiffier B, Altman A, Pui CH, Younes A, Cairo MS| title=Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. | journal=J Clin Oncol | year= 2008 | volume= 26 | issue= 16 | pages= 2767-78 | pmid=18509186 | doi=10.1200/JCO.2007.15.0177 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18509186  }} </ref>
{|Class="wikitable"
|-
|style="border-bottom:3px solid grey;" align="center" width="200" style="background:#efefef;"|'''Element''' ||style="border-bottom:3px solid grey;" align="center" width="200" style="background:#efefef;"|'''Value''' ||style="border-bottom:3px solid grey;" align="center" width="200" style="background:#efefef;"|'''Change from baseline'''
|-
|[[Uric acid]] ||≥476 μmol/L or 8 mg/dL ||25 % increase
|-
|[[Potassium]] ||≥6 mmol/L or 6mg/L || 25 % increase
|-
|[[Phosphorus]] ||≥2.1 mmol/L for children<br>≥1.45 mmol/L for adults ||25 % increase
|-
|[[Calcium]] ||≤1.75 mmol/L || 25% decrease
|-
|}
==Cairo and Bishop Definition and Grading for Clinical Tumor Lysis Syndrome (CTLS)==
Clinical tumor lysis syndrome is said to be present if LTLS is present in addition to 1 or more of the following clinical correlations summarized in the table below.<ref name="pmid18509186">{{cite journal| author=Coiffier B, Altman A, Pui CH, Younes A, Cairo MS| title=Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. | journal=J Clin Oncol | year= 2008 | volume= 26 | issue= 16 | pages= 2767-78 | pmid=18509186 | doi=10.1200/JCO.2007.15.0177 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18509186  }} </ref>
<span style="font-size:85%"> '''Abbreviation:''' '''ULN:''' upper limit of normal </span>
{|Class="wikitable"
|-
|style="background:#efefef;" align="center"|'''Complication'''||style="background:#efefef;" colspan="6" align="center"|'''Grade'''
|-
| ||0||1||2||3||4||5
|-
|[[Creatinine]]||≤1.5×ULN||1.5×ULN||>1.5-3.0×ULN||>3-6×ULN||>6×ULN||[[Death]]
|-
|[[Cardiac arrhythmia]]||None|| Intervention not indicated||'''Medical intervention''' indicated,<br> but '''not urgently'''||Controlled with a device or<br> symptomatically and incompletely<br> controlled medically||Life threatening||Death
|-
|[[Seizure]]||None||-||One well controlled generalized seizure OR<br>infrequent multiple focal motor seizures <br> not affecting activities of daily living||Poorly controlled seizure disorder,<br>seizure with altered consciousness||Prolonged seizure such as<br> [[status epilepticus]] or <br>intractable [[epilepsy]]|| Death
|-
|}


==Do's==
==Do's==
Line 185: Line 183:
* Alkalinization is currently not recommended for prevention or treatment of TLS.
* Alkalinization is currently not recommended for prevention or treatment of TLS.
* Do not administer [[rasburicase]] in patients with [[G6PD deficiency]], pregnant women, lactating women or in the case of a history of anaphylactic reaction.
* Do not administer [[rasburicase]] in patients with [[G6PD deficiency]], pregnant women, lactating women or in the case of a history of anaphylactic reaction.
* Do not treat with allopurinol treatment after a course of rasburicase.
* Do not treat with allopurinol after a course of rasburicase.
* Do not administer sodium bicarbonate and calcium through the same IV line.
* Do not administer sodium bicarbonate and calcium through the same IV line.



Latest revision as of 19:34, 17 March 2014

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Twinkle Singh, M.B.B.S. [2]; Rim Halaby, M.D. [3]

Overview

Tumor lysis syndrome (TLS) is a group of metabolic abnormalities resulting from rapid lysis of malignant cells and massive release of cell breakdown products into the blood among patients with hematologic malignancies treated with chemotherapy. Metabolic complications include hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia and hyperuricosuria.[1]

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. Tumor lysis syndrome is a life-threatening condition and must be treated as such irrespective of the causes.

Common Causes

Management

Prevention

Shown below is an algorithm summarizing the approach to tumor lysis syndrome according to the guidelines by American Society of Clinical oncology and an expert TLS panel consensus.[2][1]

 
 
 
 
Risk assessment of patients for TLS
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low Risk Disease (LRD):

❑ Solid tumors
Multiple myeloma
❑ Indolent Non-Hodgkin's lymphoma
Hodgkin's lymphoma
AML with WBC count ≤25,000 cells/μL and LDH < 2× ULN
CLL with WBC count < 50,000 cells/μL, treated only with alkylating agents
CML

 
Intermediate Risk Disease (IRD):

❑ Bulky or advanced stage solid tumors
Plasma cell leukemia
❑ Stage III/IV Non-Hodgkin's lymphoma with LDH > 2xULN
AML with WBC count ≤25,000 cells/μL and LDH > 2× ULN OR AML with WBC count 25,000-100,000 cells/μL
CLL treated with fludarabine or rituximab or CML with WBC count > 50,000 cells/μL
ALL with WBC < 100,000 cells/μL and LDH > 2xULN
Burkitt's lymphoma stage I/II with LDH < 2x ULN

Lymphoblastic lymphoma stage I/II with LDH < 2x ULN

Diffuse large B cell lymphoma
 
High Risk Disease (HRD):

AML with WBC count > 100,000 cells/μL
ALL with WBC >100,000 cells/μL AND/OR LDH > 2xULN
Burkitt's lymphoma stage III/IV with LDH ≥ 2x ULN
Lymphoblastic lymphoma stage III/IV with LDH ≥ 2x ULN
❑ IRD with renal dysfunction
❑ IRD with uric acid, potassium or phosphate above ULN

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Provide hydration with 2-3 L/m²/day IV of a one quarter NS/5%dextrose
❑ Monitor urine output (80-100 ml/m²/hr)
❑ Record the fluid balance
❑ Monitor electrolytes and creatinine daily
 
❑ Monitoring for laboratory or clinical TLS criteria for 24-72 hrs

❑ Provide hydration with 2-3 L/m²/day IV of a one quarter NS/5%dextrose
❑ Monitor urine output (80-100 ml/m²/hr)
❑ Record the fluid balance
❑ Monitor electrolytes and creatinine every 8-12 hours
❑ Administer allopurinol*
❑ Add 0.15 mg/kg rasburicase in pediatric patients with uric acid level ≥ 7.5 mg/dl for 1-7 days (average 3 days)

 
❑ Provide hydration with 2-3 L/m²/day IV of a one quarter NS/5%dextrose
❑ Monitor urine output (80-100 ml/m²/hr)
❑ Record the fluid balance
❑ Monitor electrolytes and creatinine every 4-6 hours
❑ Ensure continuous cardiac monitoring
❑ Request renal consult
❑ Delay tumor therapy (individual clinical judgement)
❑ Administer 0.20 mg/kg rasburicase in pediatric patients with uric acid level > 7.5 mg/dl for 1-7 days (average 3 days)
 

* Allopurinol administration:

  • In pediatric patients:
    • 50-100 mg/m2 every 8 hours, orally, maximum dose of 300 mg/m2/d, OR
    • 10 mg/kg/day divided every 8 hours, orally, maximum dose of 800 mg/d
  • In adults:
    • 100 mg/m2/dose every 8 hours (10 mg/kg/d divided every 8 hours), orally, maximum dose of 800 mg/d, OR
    • 200-400 mg/m2/d, 1 to 3 IV doses, maximum dose 600 mg/d (when oral allopurinol can not be administered)[1]


General Management

Shown below is an algorithm summarizing the initial management of tumor lysis syndrome.[1][2][3]

 
 
 
 
Characterize the symptoms:

Nausea
Vomiting
Anorexia
Lethargy
Diarrhea
Hematuria
Seizures
❑ Muscle cramps
Syncope
Flank pain
Heart failure
Tetany
Arrhythmia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Order tests:

Uric acid
Potassium
Calcium
Phosphate
LDH
Creatinine


❑ Order an EKG
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No TLS
 
Laboratory TLS
 
Clinical TLS
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Stratify the patient by the risk of developing TLS
❑ Initiate the appropriate preventive measures (see the algorithm above)
 
❑ Provide hydration with 2-3 L/m²/day IV of a one quarter NS/5%dextrose
❑ Monitor urine output (80-100 ml/m²/hr)
❑ Record the fluid balance
❑ Monitor electrolytes and creatinine every 4-6 hours
❑ Ensure continuous cardiac monitoring
❑ Request a renal consult
❑ Normalize electrolyte abnormalities
❑ Administer rasburicase* 0.2 mg/kg
 
❑ Admit to the intensive care in ICU
❑ Provide hydration with 2-3 L/m²/day IV of a one quarter NS/5%dextrose
❑ Monitor urine output (80-100 ml/m²/hr)
❑ Record the fluid balance
❑ Monitor electrolytes and creatinine every 4-6 hours
❑ Ensure continuous cardiac monitoring
❑ Request a renal consult
❑ Normalize electrolyte abnormalities
❑ Administer rasburicase* 0.2 mg/kg
❑ Hydration ± loop diuretic
 

* Rasburicase is not FDA approved for the use in the prophylaxis or treatment of tumor lysis syndrome in adults. It is only approved by the FDA for its use in the pediatric population.

Management of Electrolyte Disturbances

Shown below is an algorithm summarizing the management of the electrolytes disturbances in tumor lysis syndrome.[1][2]

 
 
 
 
Management of electrolyte disturbances in TLS
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hyperphosphatemia
 
Hypocalcemia
 
Hyperkalemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate ( ≥2.1 mmol/L)

❑ Avoid phosphate in IV solutions
❑ Provide adequate hydration
❑ Administer phosphate binders:

Aluminium hydroxide: 50-150 mg/kg/day every 6 hrs, orally or by NG tube
Calcium carbonate
Lanthanum carbonate
Sevelamer

Severe


Hemodialysis
Peritoneal dialysis
❑ Continuous venovenous hemofiltration
 
Asymptomatic

❑ No treatment required
Symptomatic


❑ Administer calcium gluconate 50-100 mg/kg IV, given slowly with EKG monitoring

❑ Request a renal consult if phosphate level is high
 
Asymptomatic ( ≥ 6.0 mmol/L)

❑ Avoid IV or oral potassium intake
❑ Administer sodium polystyrene sulfonate 1 g/kg with 50 % sorbitol
❑ Ensure cardiac monitoring


Severe ( > 7 mmol/L)/ Symptomatic:


❑ Perform the above mentioned actions
❑ Administer regular insulin 0.1 U/kg IV plus glucose infusion (25 % dextrose 2 ml/kg)
❑ Administer calcium gluconate 100-200 mg/kg/dose slow infusion with ECG monitoring for arrhythmias
❑ Administer sodium bicarbonate 1-2 mEq/kg IV push
Hemodialysis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Monitor the patient
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No improvement
Renal dysfunction
 
Improvement
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Ensure fluid and electrolyte management
❑ Order dialysis
❑ Adjust the dose of drugs excreted by the kidneys
 
❑ Continue treatment
❑ Continue laboratory monitoring
❑ Continue cardiac monitoring
 



Cairo and Bishop Definition for Laboratory Tumor Lysis Syndrome (LTLS)

Laboratory tumor lysis syndrome (LTLS) is considered to be present if 2 or more of the following serum abnormalities are present within 3 days before or 7 days after cytotoxic therapy. Shown below is a table summarizing the Cairo and Bishop definitions for laboratory tumor lysis syndrome.[1]

Element Value Change from baseline
Uric acid ≥476 μmol/L or 8 mg/dL 25 % increase
Potassium ≥6 mmol/L or 6mg/L 25 % increase
Phosphorus ≥2.1 mmol/L for children
≥1.45 mmol/L for adults
25 % increase
Calcium ≤1.75 mmol/L 25% decrease

Cairo and Bishop Definition and Grading for Clinical Tumor Lysis Syndrome (CTLS)

Clinical tumor lysis syndrome is said to be present if LTLS is present in addition to 1 or more of the following clinical correlations summarized in the table below.[1]

Abbreviation: ULN: upper limit of normal

Complication Grade
0 1 2 3 4 5
Creatinine ≤1.5×ULN 1.5×ULN >1.5-3.0×ULN >3-6×ULN >6×ULN Death
Cardiac arrhythmia None Intervention not indicated Medical intervention indicated,
but not urgently
Controlled with a device or
symptomatically and incompletely
controlled medically
Life threatening Death
Seizure None - One well controlled generalized seizure OR
infrequent multiple focal motor seizures
not affecting activities of daily living
Poorly controlled seizure disorder,
seizure with altered consciousness
Prolonged seizure such as
status epilepticus or
intractable epilepsy
Death

Do's

  • Consider additional risk factors that place the patient in a higher risk group:
  • Consider the following during the administration of allopurinol:
    • Start treatment 1-2 days before induction therapy and continue till 3-7 after the chemotherapy or until the serum values are normalized.
    • Reduce dose by 50 % in cases of renal insufficiency.
    • Reduce doses of 6-mercaptopurine and azathioprine by 65-75% if administered with allopurinol.
    • Also adjust doses of dicumarol, uricosuric drugs, cytotoxic drugs and thiazide diuretics if they are administered with allopurinol.
  • Administered IV rasburicase over 30 min.
    • Note that rasburicase is not approved for adults and geriatric population in United States.
  • Immediately initiate hyperkalemia management in case of severe (>7 mg/dl) hyperkalemia, or if the EKG shows widening of QRS complex.
  • Ensure that dialysis should be accessible to all high risk disease patients before cytotoxic chemotherapy is started.
  • Request a renal consult for all high risk disease patients.

Dont's

  • Do not administer calcium, phosphate and potassium with the initial hydration fluids.
  • Alkalinization is currently not recommended for prevention or treatment of TLS.
  • Do not administer rasburicase in patients with G6PD deficiency, pregnant women, lactating women or in the case of a history of anaphylactic reaction.
  • Do not treat with allopurinol after a course of rasburicase.
  • Do not administer sodium bicarbonate and calcium through the same IV line.

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Coiffier B, Altman A, Pui CH, Younes A, Cairo MS (2008). "Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review". J Clin Oncol. 26 (16): 2767–78. doi:10.1200/JCO.2007.15.0177. PMID 18509186.
  2. 2.0 2.1 2.2 Cairo, MS.; Coiffier, B.; Reiter, A.; Younes, A.; Cairo, MS.; Coiffier, B.; Reiter, A.; Younes, A.; Baruchel, A. (2010). "Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus". Br J Haematol. 149 (4): 578–86. doi:10.1111/j.1365-2141.2010.08143.x. PMID 20331465. Unknown parameter |month= ignored (help)
  3. Howard SC, Jones DP, Pui CH (2011). "The tumor lysis syndrome". N Engl J Med. 364 (19): 1844–54. doi:10.1056/NEJMra0904569. PMC 3437249. PMID 21561350.


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