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! style="padding: 0 5px; font-size: 80%; background: #A8A8A8;" align="center" |{{fontcolor|#2B3B44|Acute leukemia<BR>Resident Survival Guide}}
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! style="font-size: 80%; padding: 0 5px; background: #DCDCDC; border-radius: 5px 5px 5px 5px;" align="left" |[[{{PAGENAME}}#Overview|Overview]]
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! style="font-size: 80%; padding: 0 5px; background: #DCDCDC; border-radius: 5px 5px 5px 5px;" align="left" |[[{{PAGENAME}}#Causes|Causes]]
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! style="font-size: 80%; padding: 0 5px; background: #DCDCDC; border-radius: 5px 5px 5px 5px;" align="left" |[[{{PAGENAME}}#FIRE: Focused Initial Rapid Evaluation|FIRE]]
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! style="font-size: 80%; padding: 0 5px; background: #DCDCDC; border-radius: 5px 5px 5px 5px;" align="left" |[[{{PAGENAME}}#Complete Diagnostic Approach|Diagnosis]]
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! style="font-size: 80%; padding: 0 5px; background: #DCDCDC; border-radius: 5px 5px 5px 5px;" align="left" |[[{{PAGENAME}}#Treatment|Treatment]]
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! style="font-size: 80%; padding: 0 5px; background: #DCDCDC; border-radius: 5px 5px 5px 5px;" align="left" |[[{{PAGENAME}}#Do's|Do's]]
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| <figure-inline><figure-inline>[[File:Siren.gif|link=Hypokalemia resident survival guide|41x41px]]</figure-inline></figure-inline>|| <br> || <br>
! style="font-size: 80%; padding: 0 5px; background: #DCDCDC; border-radius: 5px 5px 5px 5px;" align="left" |[[{{PAGENAME}}#Don'ts|Don'ts]]
| [[Hypokalemia resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
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{{Hypokalemia}}
__NOTOC__
 
'''For patient information on this page, click [[Hypokalemia (patient information)|here]]'''
 
{{CMG}}'''; Associate Editor-In-Chief:''' {{CZ}}; {{AIDA}} [[User:Aditya Govindavarjhulla|Aditya Govindavarjhulla, M.B.B.S.]] [mailto:agovi@wikidoc.org] ; '''Assistant Editor(s)-In-Chief:''' [[User:Jack Khouri|Jack Khouri]]
 
{{SK}} Hypokalaemia; potassium levels low (plasma or serum); potassium - low; low blood potassium; potassium depletion
 
==[[Hypokalemia overview|Overview]]==
==Pathophysiology==
 
 


{{CMG}}; {{AE}} {{ABehjat}}


[[Potassium]] is the principal [[intracellular]] [[cation]], with a [[concentration]] of about 145 mEq/L, as compared with a normal value of 3.5 - 5.0 mEq/L in extracellular fluid, including blood. Any disorder of potassium serum levels can disturb the transmembrane [[potential]] and renders excitable cells ([[nerve]] and [[muscle]]) [[Hyperpolarization (biology)|hyperpolariz]]<nowiki/>ed and less sensitive. However, [[Cardiac|cardiac cells]] don't obey this rule and become hyperexcitable. [[Potassium]] regulation is essential to maintain a normal activity in cells. Any impairment in potassium serum levels will have severe consequences on several organs especially the [[heart]] and the [[nervous system]]. Typically, total potassium excretion in the stool is low and most ingested potassium is absorbed. The [[Kidney|kidne]]<nowiki/>y is the primary regulator of potassium balance through excretion (the kidney excretes 90-95% of dietary potassium); the gut excretes a minimal amount of dietary potassium (approximately 10%).
{{SK}} Acute lymphocytic leukemia, Acute myeloid leukemia, ALL, AML
==Overview==
Acute Leukemia is a malignancy of bone marrow myeloid and lymphoblastic precursor cells, in which these poorly differentiated hematopoietic cells proliferate rapidly. Hence, their accumulation would disrupt the performance of bone marrow to produce normal blood cells
<div align="center"><gallery heights="200" widths="200">
Image:AML_(2).png
Image:ALL2.png
</gallery>
</div>


==[[Hypokalemia historical perspective|Historical Perspective]]==
==Causes==
 
AML and ALL are life-threatening diseases, which would result in death if left untreated. In the majority of cases, etiology is not apparent.
== Pathophysiology ==
Hypokalemia can result from several conditions:
* Trans-cellular shifts of potassium inside the cells (most common)
* [[Renal]] loss of [[potassium]]
** Increased distal Na delivery
** Increased urine flow
** [[Metabolic alkalosis]]
** Increased [[aldosterone]] level
* Gastrointestinal (GI) loss of potassium
* Increased [[hematopoiesis]] (increased cellular use of potassium)
* Decreased intake of potassium (least common)
 
Shown below is a table summarizing the different pathophysiological processes that can lead to hypokalemia.<ref name="pmid24139581">{{cite journal |vauthors=Daly K, Farrington E |title=Hypokalemia and hyperkalemia in infants and children: pathophysiology and treatment |journal=J Pediatr Health Care |volume=27 |issue=6 |pages=486–96; quiz 497–8 |date=2013 |pmid=24139581 |doi=10.1016/j.pedhc.2013.08.003 |url=}}</ref> <ref name="pmid21278718">{{cite journal |vauthors=Unwin RJ, Luft FC, Shirley DG |title=Pathophysiology and management of hypokalemia: a clinical perspective |journal=Nat Rev Nephrol |volume=7 |issue=2 |pages=75–84 |date=February 2011 |pmid=21278718 |doi=10.1038/nrneph.2010.175 |url=}}</ref> <ref name="pmid22169581">{{cite journal |vauthors=Cheungpasitporn W, Suksaranjit P, Chanprasert S |title=Pathophysiology of vomiting-induced hypokalemia and diagnostic approach |journal=Am J Emerg Med |volume=30 |issue=2 |pages=384 |date=February 2012 |pmid=22169581 |doi=10.1016/j.ajem.2011.10.005 |url=}}</ref> <ref name="pmid24053336">{{cite journal |vauthors=Bisogni V, Rossi GP, Calò LA |title=Apparent mineralcorticoid excess syndrome, an often forgotten or unrecognized cause of hypokalemia and hypertension: case report and appraisal of the pathophysiology |journal=Blood Press. |volume=23 |issue=3 |pages=189–92 |date=June 2014 |pmid=24053336 |doi=10.3109/08037051.2013.832967 |url=}}</ref>   
 
 
{| style="cellpadding=0; cellspacing= 0; width: 900px;"
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF;" align="center" |'''Trans-cellular shifts''' || colspan="2" style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF;" align="center" |'''Renal loss''' || style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF;" align="center" |'''GI loss'''|| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF;" align="center" |'''Increased hematopoiesis''' || style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF;" align="center" |'''Decreased intake of potassium'''
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |
* [[Metabolic alkalosis]] (K+/H+ exchanger)
* [[Insulin]] (activates Na+/K+ ATPase)
* [[Catecholamine]] (activates Na+/K+ ATPase)
* [[Hypokalemic thyrotoxic periodic paralysis]]
* [[Hypothermia]]
* [[Chloroquine]]
* [[Barium]] intoxication
* [[Cesium]] intoxication
* [[Antipsychotic]] overdose
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |
'''''Subject is normo or hypotensive'''''<br>
''Associated with acidosis''
* [[Diabetic ketoacidosis]]
* [[Renal tubular acidosis type 1]]
* [[Renal tubular acidosis type 2]]
''Associated with alkalosis''
* [[Diuretics]]
* [[Vomiting]] (increase in [[aldosterone]])
* [[Bartter's syndrome]] (dysfunction of in loop of Henle)
* [[Gitelman's syndrome]] (dysfunction in distal convoluted tubules)
''Variable acid/base status''
* [[Hypomagnesemia]]
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |
'''''Subject is hypertensive'''''<br>
''Primary hyperaldosteronism''
* Conn's syndrome
''Secondary hyperaldosteronism''
* Renovascular disease
* Renin secreting tumor
''Non aldosterone increase in mineralcorticoid''
* [[Cushing's disease]]
* [[Congenital adrenal hyperplasia]]
* Increased [[mineralcorticoid]]s
* Licorice ingestion
* [[Liddle's syndrome]]
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |
''Associated with metabolic acidosis''
* [[Diarrhea]]
* [[Laxative abuse]]
* [[Villous adenoma]]
''Associated with metabolic alkalosis''
* [[Vomiting]]
* [[Nasogastric tube]] drainage
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |
* [[Megaloblastic anemia]]
* Treatment of [[anemia]]
* Crisis of [[AML]]
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |
* Tea and toast diet
* [[Anorexia nervosa]]
* [[Alcoholism]]
|}


=== The Role of the Kidney ===
===Common Causes of AML===  
* The [[Kidneys]] play an important role in keeping the balance of [[potassium]].
* At the [[glomerulus]], potassium is freely filtered and reabsorbed mainly in the [[proximal tubule]] and thick ascending [[loop of Henle]] (>60 % of filtered potassium).
* The cortical [[collecting duct]] receives 10–15% of filtered potassium and constitutes the kidney’s primary site of potassium excretion.
* Potassium excretion at the cortical collecting duct depends on the amount of sodium delivered there and the activity of [[aldosterone]].
* The absorption of sodium by the principal cells of the cortical collecting ducts is mediated by the apical epithelial [[sodium channels]] (ENaC); when the amount of [[sodium]] delivered to the cortical [[collecting duct]] is very high, the absorption of sodium increases without concomitant absorption of the accompanying anions (e.g., [[Bicarbonates|bicarbonate]]<nowiki/>s and chloride ions) which are not easy to absorb. This physiologic process causes the formation of a negative charge within the cortical collecting duct lumen, causing potassium and proton secretion.
* [[Aldosterone]] increases sodium absorption at the cortical collecting duct by means of enhancing the activity of Na-K-ATPase pumps and augmenting the number of the ENaC channels.


*[[Gene mutations:FLT3, IDHI, IDH2, KRAS, DNMT3A, NPM1]]
*[[Chromosomal translocations, deletions, and inversions]]
*[[ Benzene or radiation exposure chronically]]<ref name="pmid23634996">{{cite journal| author=Cancer Genome Atlas Research Network. Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ | display-authors=etal| title=Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. | journal=N Engl J Med | year= 2013 | volume= 368 | issue= 22 | pages= 2059-74 | pmid=23634996 | doi=10.1056/NEJMoa1301689 | pmc=3767041 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23634996  }} </ref> <ref name="pmid8361504">{{cite journal| author=Thirman MJ, Gill HJ, Burnett RC, Mbangkollo D, McCabe NR, Kobayashi H | display-authors=etal| title=Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations. | journal=N Engl J Med | year= 1993 | volume= 329 | issue= 13 | pages= 909-14 | pmid=8361504 | doi=10.1056/NEJM199309233291302 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8361504  }} </ref>




{{#ev:youtube|gQ39BX-NXsc}}
===Common Causes of ALL===
*[[Radiation exposure]]
*[[Genetic disorders; e.g., Down syndrome, ataxia-telangiectasia, Fanconi anemia]]
*[[Certain infections: e.g., HTLV-1]] <ref name="pmid23523389">{{cite journal| author=Inaba H, Greaves M, Mullighan CG| title=Acute lymphoblastic leukaemia. | journal=Lancet | year= 2013 | volume= 381 | issue= 9881 | pages= 1943-55 | pmid=23523389 | doi=10.1016/S0140-6736(12)62187-4 | pmc=3816716 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23523389  }} </ref>


=== Factors Increasing Kidney Potassium Excretion ===
==FIRE==
*Increased [[aldosterone]]
A Focused Initial Rapid Evaluation (FIRE) should be performed to identify patients in need of immediate intervention.
*High urine flow rate
*High distal sodium delivery
*[[Metabolic alkalosis]]
*High extracellular fluid K+ concentration


=== Some Factors Affecting Potassium Distribution Between the Cells and the Extracellular Fluid ===
*Focused Initial Rapid Evaluation (FIRE) in AML <ref name="TallmanWang2019">{{cite journal|last1=Tallman|first1=Martin S.|last2=Wang|first2=Eunice S.|last3=Altman|first3=Jessica K.|last4=Appelbaum|first4=Frederick R.|last5=Bhatt|first5=Vijaya Raj|last6=Bixby|first6=Dale|last7=Coutre|first7=Steven E.|last8=De Lima|first8=Marcos|last9=Fathi|first9=Amir T.|last10=Fiorella|first10=Melanie|last11=Foran|first11=James M.|last12=Hall|first12=Aric C.|last13=Jacoby|first13=Meagan|last14=Lancet|first14=Jeffrey|last15=LeBlanc|first15=Thomas W.|last16=Mannis|first16=Gabriel|last17=Marcucci|first17=Guido|last18=Martin|first18=Michael G.|last19=Mims|first19=Alice|last20=O’Donnell|first20=Margaret R.|last21=Olin|first21=Rebecca|last22=Peker|first22=Deniz|last23=Perl|first23=Alexander|last24=Pollyea|first24=Daniel A.|last25=Pratz|first25=Keith|last26=Prebet|first26=Thomas|last27=Ravandi|first27=Farhad|last28=Shami|first28=Paul J.|last29=Stone|first29=Richard M.|last30=Strickland|first30=Stephen A.|last31=Wieduwilt|first31=Matthew|last32=Gregory|first32=Kristina M.|last33=Hammond|first33=Lydia|last34=Ogba|first34=Ndiya|title=Acute Myeloid Leukemia, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology|journal=Journal of the National Comprehensive Cancer Network|volume=17|issue=6|year=2019|pages=721–749|issn=1540-1405|doi=10.6004/jnccn.2019.0028}}</ref><ref>{{cite book | last = Jameson | first = J | title = Harrison's principles of internal medicine | publisher = McGraw-Hill Education | location = New York | year = 2018 | isbn = 978-1259643996 }}</ref>:
*Na/K ATPase
*[[Insulin]]
*[[Catecholamines]]
*Plasma potassium concentration
*Extracellular pH
*[[Hyperosmolarity]] <ref>{{cite book | last = Hall | first = John | title = Guyton and Hall textbook of medical physiology | publisher = Elsevier | location = Philadelphia, PA | year = 2016 | isbn = 978-1-4557-7005-2 }} </ref>


=== The Physiologic Role of Potassium ===
{{Family tree/start}}
* Potassium is essential during numerous body functions, particularly for excitable cells such as muscle and nerve cells. 
{{Family tree | | | | | | | | | | | | | | A01 | | | | | | | | | | | | | | |A01=<div style="float: left; text-align: left; line-height: 150% ">'''Obtain patient's medical history and focus on these signs and symptoms:''' <br> ❑ [[Fatigue]] <br> ❑ [[Weight loss]] <br> ❑ [[Anorexia]] <br> ❑ [[Bone pain]] <br> ❑ [[Bleeding]]  <br> ❑ [[Early satiety]] <br> ❑ History of specific and chronic exposures such as alkylating agents, benzene, radiation, or previous chemotherapy <br> ❑ [[Headache]] <br> ❑ [[History of recurrent fever]]</div>}}
* Diet, mostly fruits and vegetables, is the major source of potassium for the body. 
{{Family tree | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | |}}
* Potassium is the principal [[intracellular]] [[cation]], with a concentration of about 145 mEq/L, as compared with a normal value of 3.5 - 5.0 mEq/L in [[extracellular]] fluid, including blood. 
{{Family tree | | | | | | | | | | | | | | F01 | | | | | | | | | | | | | | |F01=<div style="float: left; text-align: left; line-height: 150% ">'''Examine the patient:''' <br> ❑ [[Fever]] <br>  ❑ [[Ecchymosis]] <br>  ❑ [[Lymphadenopathy]] <br>❑ [[Splenomegaly]] <br> ❑ [[Hepatomegaly]]<br> ❑ Mediastinal mass  <br>❑ Abnormalities in cranial nerve examination <br> ❑ [[Skin Petechiae]]<br> ❑ Testicular enlargement < <br>  </div> }}
* More than 98% of the body's potassium is [[intracellular]]; measuring it from a blood sample is relatively insensitive, with small fluctuations in the blood corresponding to substantial changes in the total bodily reservoir of [[potassium]].<ref name="pmid23674806">{{cite journal| author=Weaver CM| title=Potassium and health. | journal=Adv Nutr | year= 2013 | volume= 4 | issue= 3 | pages= 368S-77S | pmid=23674806 | doi=10.3945/an.112.003533 | pmc=3650509 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23674806  }} </ref>
{{Family tree | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | |}}


=== The Cellular Effect of Hypokalemia ===
{{Family tree | | | | | | | | | | | | | | B01 | | | | | | | | | | | | | | |B01=<div style="float: left; text-align: left; line-height: 150% ">'''Hematologic evaluation:'''<br>
The normal ratio of intracellular to extracellular potassium in the body is vital for the generation of action potential and results in appropriate cardiac and neuromuscular cells performance. By decreasing the potassium concentration in extracellular space, the amount of the potassium gradient across the cell membrane is risen and results in hyperpolarization. This alteration moves the resting membrane potential from the threshold to a higher level; hence, a bigger than standard stimulus is necessary to generate an action potential. Consequently, reduced excitability in the neurons and muscle cells would appear and cause flaccid muscle paralysis, [[rhabdomyolysis]] (in severe hypokalemia), and paralytic ileus.<ref name="PalmerClegg2016">{{cite journal|last1=Palmer|first1=Biff F.|last2=Clegg|first2=Deborah J.|title=Physiology and pathophysiology of potassium homeostasis|journal=Advances in Physiology Education|volume=40|issue=4|year=2016|pages=480–490|issn=1043-4046|doi=10.1152/advan.00121.2016}}</ref>
❑ [[CBD including platelets and WBCs)]] <br> ❑ [[Uric acid]], [[BUN]], [[Cr]], [[Liver function test]]s, [[bilirubin]],[[Ca]], [[P]], [[Sodium]], [[potassium]], <br> ❑ [[amylase]], and [[lipase]] <br> ❑ [[Lactate dehydrogenase]] <br> ❑ [[PT]], [[PTT]] <br> ❑ [[D-dimer]], [[fibrinogen]] <br>  ❑ [[Viral antibodies]], [[(varicella-zoster]], [[CMV]]), [[HSV-1]] ❑ Peripheral blood smear</div>}}
{{Family tree | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | |}}


{{Family tree | | | | | | | | | | | | | | B02 | | | | | | | | | | | | | | | B02= <div style="float: left; text-align: left; line-height: 150% ">'''Radiologic assessment:''' <br> ❑ '''[[CXR]] (PA and lateral)  <br> ❑ [[PET]] or [[CT scan]] (if [[extramedullary disease]] is doubted based on symptoms and physical exam)  <br>  ❑  [[CT]], or [[MRI]], and other  imaging methods to diagnose [[ICH]], [[brain]] or [[spinal cord tumor]]s, and [[leptomeningeal disease]] (if patient presenting notable CNS signs and symptoms <br> </div>}}
{{Family tree | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | |}}
{{Family tree | | | | | | | | | | | | | | E01 | | | | | | | | | | | | | | |E01=<div style="float: left; text-align: left; line-height: 150% ">''' ❑ [[Bone marrow aspiration]] and biopsy <br> </div>}}
{{Family tree | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree/end}}


[[Image:Hypokalemia .png|right|400px]]
*Focused Initial Rapid Evaluation (FIRE) in ALL:<ref name="pmid23523389">{{cite journal| author=Inaba H, Greaves M, Mullighan CG| title=Acute lymphoblastic leukaemia. | journal=Lancet | year= 2013 | volume= 381 | issue= 9881 | pages= 1943-55 | pmid=23523389 | doi=10.1016/S0140-6736(12)62187-4 | pmc=3816716 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23523389  }} </ref> <ref name="pmid31910389">{{cite journal| author=Brown P, Inaba H, Annesley C, Beck J, Colace S, Dallas M | display-authors=etal| title=Pediatric Acute Lymphoblastic Leukemia, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. | journal=J Natl Compr Canc Netw | year= 2020 | volume= 18 | issue= 1 | pages= 81-112 | pmid=31910389 | doi=10.6004/jnccn.2020.0001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31910389  }} </ref> <ref name="pmid25060251">{{cite journal| author=Rose-Inman H, Kuehl D| title=Acute leukemia. | journal=Emerg Med Clin North Am | year= 2014 | volume= 32 | issue= 3 | pages= 579-96 | pmid=25060251 | doi=10.1016/j.emc.2014.04.004 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25060251  }} </ref>


=== Pathophysiology of Hypokalemic Heart Arrhythmias ===
{{Family tree/start}}
* Hypokalemia in neurons and muscle cells reduces the membrane responsiveness and causes hyperpolarization. But in cardiac cells, specifically in the conducting system, depolarization is observed. The main reason is the alteration of ion selectivity of TWIK-1 K+ channels, which in standard situation leak potassium. During pathological hypokalemia, these channels transport sodium inward the cells, leading to paradoxical depolarization and may result in cardiac arrhythmias.
{{Family tree | | | | | | | | | | | | | | A01 | | | | | | | | | | | | | | |A01=<div style="float: left; text-align: left; line-height: 150% ">'''Take a precise medical history and focus on these signs and symptoms:''' <br> ❑ [[Fatigue]] <br>  ❑ [[Anorexia]] <br> ❑ [[Bone and joint pain]] <br> ❑ [[Bleeding]]  <br> ❑ [[Weakness and lethargy]] <br> ❑ History of  prior exposures with alkylating agents, radiation, or previous chemotherapy (less prevalent than AML) <br> ❑ [[Headache]] <br> ❑ [[History of bleeding or unexplained bruising]] <br> ❑ History of congenital syndroms <br> ❑ [[Night sweats, weight loss and fever(B symptoms)]] <br>❑ [[Abdominal distention]] <br></div>}}
{{Family tree | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | |}}
{{Family tree | | | | | | | | | | | | | | F01 | | | | | | | | | | | | | | |F01=<div style="float: left; text-align: left; line-height: 150% ">'''Examine the patient:''' <br> ❑ [[Fever]] <br> ❑ [[Tachycardia]]<br>  ❑ Mediastinal mass <br>  ❑ [[Lymphadenopathy]] <br>❑ [[Splenomegaly]] <br> ❑ [[Hepatomegaly]]<br> ❑ Abnormalities in cranial nerve examination <br> ❑ [[Skin Petechiae]] <br> ❑Testicular enlargement (rare) <br> </div> }}
{{Family tree | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | |}}


* Decreased extracellular potassium also suppresses the activity of some potassium channels conductance, and in turn, it delays ventricular repolarization. Prolonged repolarization could also predispose re-entrant arrhythmias.
{{Family tree | | | | | | | | | | | | | | B01 | | | | | | | | | | | | | | |B01=<div style="float: left; text-align: left; line-height: 150% ">'''Hematologic evaluation:'''<br>
❑ [[CBD including platelets and WBCs)]] <br> ❑ [[Uric acid]], [[BUN]], [[Cr]], [[Liver function test]]s, [[bilirubin]] <br> ❑ [[Lactate dehydrogenase]] , potassium, phosphates, and calcium <br> ❑ d-dimer, fibrinogen, PT, and PTT <br> ❑ Peripheral blood smear <br> </div>}}
{{Family tree | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | |}}


* Moreover, Hypokalemia can inhibit Na+-K+ ATPase activity, leading to intracellular Na+ And Ca2+ increase. The accumulation of intracellular ca2+ activates calmodulin kinase and, in turn, induces late Na+ and Ca2+ currents and causes a further reduction in repolarization reserve. This would result in early after-depolarization (EAD)–mediated arrhythmias.<ref name="MaZhang2011">{{cite journal|last1=Ma|first1=L.|last2=Zhang|first2=X.|last3=Chen|first3=H.|title=TWIK-1 Two-Pore Domain Potassium Channels Change Ion Selectivity and Conduct Inward Leak Sodium Currents in Hypokalemia|journal=Science Signaling|volume=4|issue=176|year=2011|pages=ra37–ra37|issn=1945-0877|doi=10.1126/scisignal.2001726}}</ref> <ref name="WeissQu2017">{{cite journal|last1=Weiss|first1=James N.|last2=Qu|first2=Zhilin|last3=Shivkumar|first3=Kalyanam|title=Electrophysiology of Hypokalemia and Hyperkalemia|journal=Circulation: Arrhythmia and Electrophysiology|volume=10|issue=3|year=2017|issn=1941-3149|doi=10.1161/CIRCEP.116.004667}}</ref>
{{Family tree | | | | | | | | | | | | | | B02 | | | | | | | | | | | | | | | B02= <div style="float: left; text-align: left; line-height: 150% ">'''Radiologic assessment:''' <br> ❑ '''[[CXR]] (PA and lateral) to rule out mediastinal masses  <br>  ❑  Brain CT scan and MRI  with contrast if neurologic signs and symptoms have existed <br> ❑ Scrotal ultrasound for assessing testicular involvement <br> ❑ Echocardiogram or cardiac scan <br>  A whole body PET or CT scan when lymphoblastic lymphoma is doubted </div>}}
{{Family tree | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | |}}
{{Family tree | | | | | | | | | | | | | | E01 | | | | | | | | | | | | | | |E01=<div style="float: left; text-align: left; line-height: 150% ">''' ❑ [[Bone marrow aspiration]] and biopsy <br> </div>}}
{{Family tree | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | |}}
{{Family tree | | | | | | | | | | | | | | E01 | | | | | | | | | | | | | | |E01=<div style="float: left; text-align: left; line-height: 150% ">''' ❑ [[Lumbar puncture]] <br> </div>}}
{{Family tree | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree/end}}


=== Pathophysiology of Hypokalemic in GI system: ===
==Diagnosis==
* A low level of potassium  [[Category:Electrophysiology]] [[Category:Cardiology]] [[Category:Endocrinology]] [[Category:Emergency medicine]] [[Category:Nephrology]] [[Category:Electrolyte disturbance]] [[Category:Blood tests]] [[Category:Intensive care medicine]]  causes dysfunctional gastrointestinal smooth muscle performance, the slow movement of the GI system, constipation, and paralytic ileus. The primary rationale behind them is the impairment of normal action potential in the muscle cell membrane, which disturbs favorable contraction and cellular depolarization. <ref name="StreetenWilliams1952">{{cite journal|last1=Streeten|first1=D. H. P.|last2=Williams|first2=E. M. Vaughan|title=Loss of cellular potassium as a cause of intestinal paralysis in dogs|journal=The Journal of Physiology|volume=118|issue=2|year=1952|pages=149–170|issn=00223751|doi=10.1113/jphysiol.1952.sp004782}}</ref> <ref name="PalmerClegg2016">{{cite journal|last1=Palmer|first1=Biff F.|last2=Clegg|first2=Deborah J.|title=Physiology and pathophysiology of potassium homeostasis|journal=Advances in Physiology Education|volume=40|issue=4|year=2016|pages=480–490|issn=1043-4046|doi=10.1152/advan.00121.2016}}</ref>
Diagnostic criteria of acute myeloid leukemia and acute lymphoblastic leukemia are similar to one another.
*According to the 2016 WHO criteria observing ≥20% blasts in the bone marrow biopsy or peripheral blood smear is diagnostic for AML. These genetic abnormalities in AML are diagnostic even with less than 20% marrow blasts: inv(16), t(16;16), t(8;21), and t(15;17).<ref name="pmid10643532">{{cite journal| author=Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J | display-authors=etal| title=The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997. | journal=Ann Oncol | year= 1999 | volume= 10 | issue= 12 | pages= 1419-32 | pmid=10643532 | doi=10.1023/a:1008375931236 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10643532  }} </ref>


==[[Hypokalemia causes|Causes]]==
*Presenting ≥20% of leukemic lymphoblasts in bone marrow aspirate and biopsy would prove ALL.<ref name="pmid25408859">{{cite journal| author=Chiaretti S, Zini G, Bassan R| title=Diagnosis and subclassification of acute lymphoblastic leukemia. | journal=Mediterr J Hematol Infect Dis | year= 2014 | volume= 6 | issue= 1 | pages= e2014073 | pmid=25408859 | doi=10.4084/MJHID.2014.073 | pmc=4235437 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25408859  }} </ref>


==[[Hypokalemia differential diagnosis|Differentiating Hypokalemia from other Diseases]]==
==Treatment==  


==[[Hypokalemia epidemiology and demographics|Epidemiology and Demographics]]==
{{familytree/start |summary=Sample 6}}
{{familytree | | | | | | | | | | | | | | | | | | A01 |A01= <div style="float: left; text-align: left; width: 25em; padding:1em;">'''Treatment of a patient with definitive AML'''<ref name="pmid26376137">{{cite journal| author=Döhner H, Weisdorf DJ, Bloomfield CD| title=Acute Myeloid Leukemia. | journal=N Engl J Med | year= 2015 | volume= 373 | issue= 12 | pages= 1136-52 | pmid=26376137 | doi=10.1056/NEJMra1406184 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26376137  }} </ref> <ref name="pmid27895058">{{cite journal| author=Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T | display-authors=etal| title=Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. | journal=Blood | year= 2017 | volume= 129 | issue= 4 | pages= 424-447 | pmid=27895058 | doi=10.1182/blood-2016-08-733196 | pmc=5291965 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27895058  }} </ref> <ref>{{cite book | last = Jameson | first = J | title = Harrison's principles of internal medicine | publisher = McGraw-Hill Education | location = New York | year = 2018 | isbn = 978-1259643996 }}</ref>
</div>}}
{{familytree | | | | | | | | | |,|-|-|-|-|-|-|-|-|^|-|-|-|-|-|-|-|-|-|-|-|-|-|-|-|-|-|-|-|.| | | }}
{{familytree | | | | | | | | | B01 | | | | | | | | | | | | | | | | | | | | | | | | | | | B02 | |B01=<div style="float: left; text-align: left; width: 25em; padding:1em;">'''Treating for the first time(new case)''' </div>|B02= <div style="float: left; text-align: left; width: 25em; padding:1em;">'''Cases with relapsed/refractory AML''' </div>}}
{{familytree  | |,|-|-|-|-|-|-|-|+|-|-|-|-|-|-|-|-|-|-|.| | | | | | | | | | | | | | | | | |!| | }}
{{familytree  | C01 | | | | | | C02 | | | | | | | | | C03 | | | | | | | | | | | | | | | | C04 |C01= <div style="float: left; text-align: left; width: 25em; padding:1em;">'''Favorable-Risk Cytogenetics''' </div>|C02= <div style="float: left; text-align: left; width: 25em; padding:1em;">'''Intermediate-Risk Cytogenetics''' </div>
|C03= <div style="float: left; text-align: left; width: 25em; padding:1em;">'''Poor-Risk Cytogenetics|C04= <div style="float: left; text-align: left; width: 25em; padding:1em;">'''Salvage therapy''' </div>}}
{{familytree | |!| | | | | | | |!| | | | | | | | | | |!| | | | |!| | | | | | | | | | | | |!| | }}
{{familytree | D01 | | | | | | D02 | | | | | | | | | D03 | | | | | | | | | | | | | | | | D04 | |D01= Select one of these therapies: <br> ❑ 1. Induction treatment: Cytarabine-based regimen + Daunorubicin. If a complete remission is achieved, postremission consolidation therapy as maintenance should be started: intermediate  dose of Cytarabine) <br> ❑ 2.Investigational drugs(clinical trial): for cases aged younger than 60 years, a standard chemotherapy regimen including a backbone of Cytarabine + Anthracycline has been recommended. After complete remission, postremission therapy have to be regarded.
|D02=Select one of these treatments: <br>
❑ 1. Investigational therapy: for patients older than 65 or have more comorbidities and high-risk illnesses or cases who cannot tolerate Cytarabine-based regimen + Daunorubicin, changing their regiments to an investigational therapy could be regarded. (administrate one chemotherapy drug or combine their treatment with non-intensive medications fitting with the patient such as decitabine, azacitidine). After complete remission, postremission therapy have to be regarded.<br> ❑ 2. Induction treatment: Cytarabine-based regimen + Daunorubicin (could be suitable for young and elderly patients). If complete remission(CR) is achieved, postremission consolidation therapy as maintenance should be started to prevent relapse, including: <br>
:*  Allogenic hematopoietic cell transplantation, which is the preferred treatment, or <br>
:*  If the patient is younger than 60 years autologous hematopoietic cell  transplantation is recommended, or <br> 
:*  Intermediate  dose of Cytarabine
||D03= Select one of these therapies:<br> 1. Induction treatment: Cytarabine-based regimen + Daunorubicin (could be suitable for both young and elderly patients). After complete remission(CR) achieved, postremission consolidation therapy should be started to prevent relapse, including Allogenic hematopoietic cell transplantation, which is the preferred treatment. When there is not any accessible HLA-matched donor, using an alternate donor has been recommended. <br> 2. Investigational therapy: for patients older than 65 or have more comorbidities and high-risk illnesses or cases who cannot tolerate Cytarabine-based regimen + Daunorubicin, changing their regiments to an investigational therapy could be regarded. (administrate one chemotherapy drug or combine their treatment with non-intensive medications fitting with the patient such as decitabine, azacitidine). After complete remission, postremission therapy has to be regarded.<br> |D04=Patients with relapsed and refractory AML who has an HLA-matched donor accessible for allogenic HCT or cases who attained second complete remission after salvage therapy while there is an available appropriate donor should undergo allogenic hematopoietic cell  transplantation. Those who do not have these conditions have to be treated based on clinical trials (investigational therapy).  }}
{{familytree/end}}


==[[Hypokalemia risk factors|Risk Factors]]==


==[[Hypokalemia natural history|Natural History, Complications and Prognosis]]==
Treatment of acute lymphoblastic leukemia includes three phases:<ref name="pmid21220592">{{cite journal| author=Bassan R, Hoelzer D| title=Modern therapy of acute lymphoblastic leukemia. | journal=J Clin Oncol | year= 2011 | volume= 29 | issue= 5 | pages= 532-43 | pmid=21220592 | doi=10.1200/JCO.2010.30.1382 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21220592  }} </ref>


==[[Hypokalemia Diagnosis|Diagnosis]]==
:*Induction therapy, i.e., prednisolone, vincristine, cytarabine <br>
[[Hypokalemia laboratory findings#Diagnostic Algorithm|Diagnostic Algorithm]] | [[Hypokalemia history and symptoms | History and Symptoms]] | [[Hypokalemia physical examination|Physical Examination]] | [[Hypokalemia laboratory findings | Laboratory Findings]] | [[Hypokalemia electrocardiogram | Electrocardiogram]] | [[Hypokalemia other diagnostic studies|Other Diagnostic Studies]]
:*Administrating Central Nervous System prophylaxis, i.e., methotrexate
:*Chemotherapy as a maintenance treatment for two years
:*Stem cell transplantation in adults who are eligible while there is a suitable donor


==[[Hypokalemia treatment|Treatment]]==
==Do's==
[[Hypokalemia medical therapy| Medical Therapy]] | [[Hypokalemia primary prevention|Primary Prevention]] | [[Hypokalemia secondary prevention|Secondary Prevention]] | [[Hypokalemia cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Hypokalemia future or investigational therapies|Future or Investigational Therapies]]
:* Before starting the therapy, taking a precise history and physical examination have to be done to diagnose any kind of comorbidities ,i.e. heart failure or renal diseases that affect the prognosis and treatment choices.


==Case Studies==
:*HLA-typing evaluation have to be done for all of the AML cases In the pretreatment assessment.
[[Hypokalemia case study one|Case #1]]
:*Seven days after the induction phase of chemotherapy ended, bone marrow biopsy must be done in order to assess the remission situation.
:* In the induction chemotherapy process of AML for most of the cases, cytarabine IV infusion should be administrated for seven days consecutively + anthracycline on days one to three.(known as "7+3" regimens)<ref name="pmidhttps://pubmed.ncbi.nlm.nih.gov/9045305">{{cite journal| author=Bishop JF| title=The treatment of adult acute myeloid leukemia. | journal=Semin Oncol | year= 1997 | volume= 24 | issue= 1 | pages= 57-69 | pmid=https://pubmed.ncbi.nlm.nih.gov/9045305 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9045305  }} </ref> <ref name="TallmanWang2019">{{cite journal|last1=Tallman|first1=Martin S.|last2=Wang|first2=Eunice S.|last3=Altman|first3=Jessica K.|last4=Appelbaum|first4=Frederick R.|last5=Bhatt|first5=Vijaya Raj|last6=Bixby|first6=Dale|last7=Coutre|first7=Steven E.|last8=De Lima|first8=Marcos|last9=Fathi|first9=Amir T.|last10=Fiorella|first10=Melanie|last11=Foran|first11=James M.|last12=Hall|first12=Aric C.|last13=Jacoby|first13=Meagan|last14=Lancet|first14=Jeffrey|last15=LeBlanc|first15=Thomas W.|last16=Mannis|first16=Gabriel|last17=Marcucci|first17=Guido|last18=Martin|first18=Michael G.|last19=Mims|first19=Alice|last20=O’Donnell|first20=Margaret R.|last21=Olin|first21=Rebecca|last22=Peker|first22=Deniz|last23=Perl|first23=Alexander|last24=Pollyea|first24=Daniel A.|last25=Pratz|first25=Keith|last26=Prebet|first26=Thomas|last27=Ravandi|first27=Farhad|last28=Shami|first28=Paul J.|last29=Stone|first29=Richard M.|last30=Strickland|first30=Stephen A.|last31=Wieduwilt|first31=Matthew|last32=Gregory|first32=Kristina M.|last33=Hammond|first33=Lydia|last34=Ogba|first34=Ndiya|title=Acute Myeloid Leukemia, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology|journal=Journal of the National Comprehensive Cancer Network|volume=17|issue=6|year=2019|pages=721–749|issn=1540-1405|doi=10.6004/jnccn.2019.0028}}</ref>


==Related Chapters==
==Don'ts==
* [[Hypomagnesemia]]
:*If the patient with AML has a coagulopathy disorder and is susceptible to bleeding, do not have to undergo lumbar puncture in the workup process before correcting that.
* [[Hyperkalemia]]
:*Without the assessment of cardiac symptoms and echocardiogram, chemotherapy medications which are cardiotoxic should not be administrated. <ref name="TallmanWang2019">{{cite journal|last1=Tallman|first1=Martin S.|last2=Wang|first2=Eunice S.|last3=Altman|first3=Jessica K.|last4=Appelbaum|first4=Frederick R.|last5=Bhatt|first5=Vijaya Raj|last6=Bixby|first6=Dale|last7=Coutre|first7=Steven E.|last8=De Lima|first8=Marcos|last9=Fathi|first9=Amir T.|last10=Fiorella|first10=Melanie|last11=Foran|first11=James M.|last12=Hall|first12=Aric C.|last13=Jacoby|first13=Meagan|last14=Lancet|first14=Jeffrey|last15=LeBlanc|first15=Thomas W.|last16=Mannis|first16=Gabriel|last17=Marcucci|first17=Guido|last18=Martin|first18=Michael G.|last19=Mims|first19=Alice|last20=O’Donnell|first20=Margaret R.|last21=Olin|first21=Rebecca|last22=Peker|first22=Deniz|last23=Perl|first23=Alexander|last24=Pollyea|first24=Daniel A.|last25=Pratz|first25=Keith|last26=Prebet|first26=Thomas|last27=Ravandi|first27=Farhad|last28=Shami|first28=Paul J.|last29=Stone|first29=Richard M.|last30=Strickland|first30=Stephen A.|last31=Wieduwilt|first31=Matthew|last32=Gregory|first32=Kristina M.|last33=Hammond|first33=Lydia|last34=Ogba|first34=Ndiya|title=Acute Myeloid Leukemia, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology|journal=Journal of the National Comprehensive Cancer Network|volume=17|issue=6|year=2019|pages=721–749|issn=1540-1405|doi=10.6004/jnccn.2019.0028}}</ref>


[[Category:Electrophysiology]]
==References==
[[Category:Cardiology]]
[[Category:Endocrinology]]
[[Category:Emergency medicine]]
[[Category:Nephrology]]
[[Category:Electrolyte disturbance]]
[[Category:Blood tests]]
[[Category:Intensive care medicine]]


{{reflist|2}}


{{WikiDoc Help Menu}}
[[Category:Disease]]
{{WikiDoc Sources}}
[[Category:Oncology]]
<references />
[[Category:Medicine]]
[[Category:Resident survival guide]]

Latest revision as of 19:00, 3 November 2020

Acute leukemia
Resident Survival Guide
Overview
Causes
FIRE
Diagnosis
Treatment
Do's
Don'ts


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alieh Behjat, M.D.[2]

Synonyms and keywords: Acute lymphocytic leukemia, Acute myeloid leukemia, ALL, AML

Overview

Acute Leukemia is a malignancy of bone marrow myeloid and lymphoblastic precursor cells, in which these poorly differentiated hematopoietic cells proliferate rapidly. Hence, their accumulation would disrupt the performance of bone marrow to produce normal blood cells

Causes

AML and ALL are life-threatening diseases, which would result in death if left untreated. In the majority of cases, etiology is not apparent.

Common Causes of AML


Common Causes of ALL

FIRE

A Focused Initial Rapid Evaluation (FIRE) should be performed to identify patients in need of immediate intervention.

  • Focused Initial Rapid Evaluation (FIRE) in AML [4][5]:
 
 
 
 
 
 
 
 
 
 
 
 
 
Obtain patient's medical history and focus on these signs and symptoms:
Fatigue
Weight loss
Anorexia
Bone pain
Bleeding
Early satiety
❑ History of specific and chronic exposures such as alkylating agents, benzene, radiation, or previous chemotherapy
Headache
History of recurrent fever
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Examine the patient:
Fever
Ecchymosis
Lymphadenopathy
Splenomegaly
Hepatomegaly
❑ Mediastinal mass
❑ Abnormalities in cranial nerve examination
Skin Petechiae
❑ Testicular enlargement <
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Radiologic assessment:
CXR (PA and lateral)
PET or CT scan (if extramedullary disease is doubted based on symptoms and physical exam)
CT, or MRI, and other imaging methods to diagnose ICH, brain or spinal cord tumors, and leptomeningeal disease (if patient presenting notable CNS signs and symptoms
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Bone marrow aspiration and biopsy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  • Focused Initial Rapid Evaluation (FIRE) in ALL:[3] [6] [7]
 
 
 
 
 
 
 
 
 
 
 
 
 
Take a precise medical history and focus on these signs and symptoms:
Fatigue
Anorexia
Bone and joint pain
Bleeding
Weakness and lethargy
❑ History of prior exposures with alkylating agents, radiation, or previous chemotherapy (less prevalent than AML)
Headache
History of bleeding or unexplained bruising
❑ History of congenital syndroms
Night sweats, weight loss and fever(B symptoms)
Abdominal distention
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Examine the patient:
Fever
Tachycardia
❑ Mediastinal mass
Lymphadenopathy
Splenomegaly
Hepatomegaly
❑ Abnormalities in cranial nerve examination
Skin Petechiae
❑Testicular enlargement (rare)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematologic evaluation:
CBD including platelets and WBCs)
Uric acid, BUN, Cr, Liver function tests, bilirubin
Lactate dehydrogenase , potassium, phosphates, and calcium
❑ d-dimer, fibrinogen, PT, and PTT
❑ Peripheral blood smear
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Radiologic assessment:
CXR (PA and lateral) to rule out mediastinal masses
❑ Brain CT scan and MRI with contrast if neurologic signs and symptoms have existed
❑ Scrotal ultrasound for assessing testicular involvement
❑ Echocardiogram or cardiac scan
A whole body PET or CT scan when lymphoblastic lymphoma is doubted
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Bone marrow aspiration and biopsy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Diagnosis

Diagnostic criteria of acute myeloid leukemia and acute lymphoblastic leukemia are similar to one another.

  • According to the 2016 WHO criteria observing ≥20% blasts in the bone marrow biopsy or peripheral blood smear is diagnostic for AML. These genetic abnormalities in AML are diagnostic even with less than 20% marrow blasts: inv(16), t(16;16), t(8;21), and t(15;17).[8]
  • Presenting ≥20% of leukemic lymphoblasts in bone marrow aspirate and biopsy would prove ALL.[9]

Treatment

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment of a patient with definitive AML[10] [11] [12]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treating for the first time(new case)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cases with relapsed/refractory AML
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Favorable-Risk Cytogenetics
 
 
 
 
 
Intermediate-Risk Cytogenetics
 
 
 
 
 
 
 
 
Poor-Risk Cytogenetics
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Salvage therapy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Select one of these therapies:
❑ 1. Induction treatment: Cytarabine-based regimen + Daunorubicin. If a complete remission is achieved, postremission consolidation therapy as maintenance should be started: intermediate dose of Cytarabine)
❑ 2.Investigational drugs(clinical trial): for cases aged younger than 60 years, a standard chemotherapy regimen including a backbone of Cytarabine + Anthracycline has been recommended. After complete remission, postremission therapy have to be regarded.
 
 
 
 
 
Select one of these treatments:

❑ 1. Investigational therapy: for patients older than 65 or have more comorbidities and high-risk illnesses or cases who cannot tolerate Cytarabine-based regimen + Daunorubicin, changing their regiments to an investigational therapy could be regarded. (administrate one chemotherapy drug or combine their treatment with non-intensive medications fitting with the patient such as decitabine, azacitidine). After complete remission, postremission therapy have to be regarded.
❑ 2. Induction treatment: Cytarabine-based regimen + Daunorubicin (could be suitable for young and elderly patients). If complete remission(CR) is achieved, postremission consolidation therapy as maintenance should be started to prevent relapse, including:

  • Allogenic hematopoietic cell transplantation, which is the preferred treatment, or
  • If the patient is younger than 60 years autologous hematopoietic cell transplantation is recommended, or
  • Intermediate dose of Cytarabine
 
 
 
 
 
 
 
 
Select one of these therapies:
1. Induction treatment: Cytarabine-based regimen + Daunorubicin (could be suitable for both young and elderly patients). After complete remission(CR) achieved, postremission consolidation therapy should be started to prevent relapse, including Allogenic hematopoietic cell transplantation, which is the preferred treatment. When there is not any accessible HLA-matched donor, using an alternate donor has been recommended.
2. Investigational therapy: for patients older than 65 or have more comorbidities and high-risk illnesses or cases who cannot tolerate Cytarabine-based regimen + Daunorubicin, changing their regiments to an investigational therapy could be regarded. (administrate one chemotherapy drug or combine their treatment with non-intensive medications fitting with the patient such as decitabine, azacitidine). After complete remission, postremission therapy has to be regarded.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patients with relapsed and refractory AML who has an HLA-matched donor accessible for allogenic HCT or cases who attained second complete remission after salvage therapy while there is an available appropriate donor should undergo allogenic hematopoietic cell transplantation. Those who do not have these conditions have to be treated based on clinical trials (investigational therapy).
 


Treatment of acute lymphoblastic leukemia includes three phases:[13]

  • Induction therapy, i.e., prednisolone, vincristine, cytarabine
  • Administrating Central Nervous System prophylaxis, i.e., methotrexate
  • Chemotherapy as a maintenance treatment for two years
  • Stem cell transplantation in adults who are eligible while there is a suitable donor

Do's

  • Before starting the therapy, taking a precise history and physical examination have to be done to diagnose any kind of comorbidities ,i.e. heart failure or renal diseases that affect the prognosis and treatment choices.
  • HLA-typing evaluation have to be done for all of the AML cases In the pretreatment assessment.
  • Seven days after the induction phase of chemotherapy ended, bone marrow biopsy must be done in order to assess the remission situation.
  • In the induction chemotherapy process of AML for most of the cases, cytarabine IV infusion should be administrated for seven days consecutively + anthracycline on days one to three.(known as "7+3" regimens)[14] [4]

Don'ts

  • If the patient with AML has a coagulopathy disorder and is susceptible to bleeding, do not have to undergo lumbar puncture in the workup process before correcting that.
  • Without the assessment of cardiac symptoms and echocardiogram, chemotherapy medications which are cardiotoxic should not be administrated. [4]

References

  1. Cancer Genome Atlas Research Network. Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ; et al. (2013). "Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia". N Engl J Med. 368 (22): 2059–74. doi:10.1056/NEJMoa1301689. PMC 3767041. PMID 23634996.
  2. Thirman MJ, Gill HJ, Burnett RC, Mbangkollo D, McCabe NR, Kobayashi H; et al. (1993). "Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations". N Engl J Med. 329 (13): 909–14. doi:10.1056/NEJM199309233291302. PMID 8361504.
  3. 3.0 3.1 Inaba H, Greaves M, Mullighan CG (2013). "Acute lymphoblastic leukaemia". Lancet. 381 (9881): 1943–55. doi:10.1016/S0140-6736(12)62187-4. PMC 3816716. PMID 23523389.
  4. 4.0 4.1 4.2 Tallman, Martin S.; Wang, Eunice S.; Altman, Jessica K.; Appelbaum, Frederick R.; Bhatt, Vijaya Raj; Bixby, Dale; Coutre, Steven E.; De Lima, Marcos; Fathi, Amir T.; Fiorella, Melanie; Foran, James M.; Hall, Aric C.; Jacoby, Meagan; Lancet, Jeffrey; LeBlanc, Thomas W.; Mannis, Gabriel; Marcucci, Guido; Martin, Michael G.; Mims, Alice; O’Donnell, Margaret R.; Olin, Rebecca; Peker, Deniz; Perl, Alexander; Pollyea, Daniel A.; Pratz, Keith; Prebet, Thomas; Ravandi, Farhad; Shami, Paul J.; Stone, Richard M.; Strickland, Stephen A.; Wieduwilt, Matthew; Gregory, Kristina M.; Hammond, Lydia; Ogba, Ndiya (2019). "Acute Myeloid Leukemia, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology". Journal of the National Comprehensive Cancer Network. 17 (6): 721–749. doi:10.6004/jnccn.2019.0028. ISSN 1540-1405.
  5. Jameson, J (2018). Harrison's principles of internal medicine. New York: McGraw-Hill Education. ISBN 978-1259643996.
  6. Brown P, Inaba H, Annesley C, Beck J, Colace S, Dallas M; et al. (2020). "Pediatric Acute Lymphoblastic Leukemia, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology". J Natl Compr Canc Netw. 18 (1): 81–112. doi:10.6004/jnccn.2020.0001. PMID 31910389.
  7. Rose-Inman H, Kuehl D (2014). "Acute leukemia". Emerg Med Clin North Am. 32 (3): 579–96. doi:10.1016/j.emc.2014.04.004. PMID 25060251.
  8. Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J; et al. (1999). "The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997". Ann Oncol. 10 (12): 1419–32. doi:10.1023/a:1008375931236. PMID 10643532.
  9. Chiaretti S, Zini G, Bassan R (2014). "Diagnosis and subclassification of acute lymphoblastic leukemia". Mediterr J Hematol Infect Dis. 6 (1): e2014073. doi:10.4084/MJHID.2014.073. PMC 4235437. PMID 25408859.
  10. Döhner H, Weisdorf DJ, Bloomfield CD (2015). "Acute Myeloid Leukemia". N Engl J Med. 373 (12): 1136–52. doi:10.1056/NEJMra1406184. PMID 26376137.
  11. Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T; et al. (2017). "Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel". Blood. 129 (4): 424–447. doi:10.1182/blood-2016-08-733196. PMC 5291965. PMID 27895058.
  12. Jameson, J (2018). Harrison's principles of internal medicine. New York: McGraw-Hill Education. ISBN 978-1259643996.
  13. Bassan R, Hoelzer D (2011). "Modern therapy of acute lymphoblastic leukemia". J Clin Oncol. 29 (5): 532–43. doi:10.1200/JCO.2010.30.1382. PMID 21220592.
  14. Bishop JF (1997). "The treatment of adult acute myeloid leukemia". Semin Oncol. 24 (1): 57–69. PMID https://pubmed.ncbi.nlm.nih.gov/9045305 Check |pmid= value (help).