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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__
 
{{CMG}}; {{AE}} {{ABehjat}}


'''For patient information on this page, click [[Hypokalemia (patient information)|here]]'''
{{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>


{{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]]
==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.


{{SK}} Hypokalaemia; potassium levels low (plasma or serum); potassium - low; low blood potassium; potassium depletion
===Common Causes of AML===


==[[Hypokalemia overview|Overview]]==
*[[Gene mutations:FLT3, IDHI, IDH2, KRAS, DNMT3A, NPM1]]  
==Pathophysiology==
*[[Chromosomal translocations, deletions, and inversions]]
[[Potassium]] is one of the [[intracellular]] [[cations]]. 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 excitable. 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%).
*[[ 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>


==[[Hypokalemia historical perspective|Historical Perspective]]==


==[[Hypokalemia pathophysiology|Pathophysiology]]==
===Common Causes of ALL===
== Pathophysiology ==
*[[Radiation exposure]]
Hypokalemia can result from several conditions:
*[[Genetic disorders; e.g., Down syndrome, ataxia-telangiectasia, Fanconi anemia]]
* Trans-cellular shifts of potassium inside the cells (most common)
*[[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>
* [[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>
==FIRE==
A Focused Initial Rapid Evaluation (FIRE) should be performed to identify patients in need of immediate intervention.


{| style="cellpadding=0; cellspacing= 0; width: 900px;"
*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>:
|-
 
| 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'''
{{Family tree/start}}
|-
{{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>}}
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |
{{Family tree | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | |}}
* [[Metabolic alkalosis]] (K+/H+ exchanger)
{{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> }}
* [[Insulin]] (activates Na+/K+ ATPase)
{{Family tree | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | |}}
* [[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 ===
{{Family tree | | | | | | | | | | | | | | B01 | | | | | | | | | | | | | | |B01=<div style="float: left; text-align: left; line-height: 150% ">'''Hematologic evaluation:'''<br>
* The [[Kidneys]] play an important role in keeping the balance of [[potassium]].
❑ [[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>}}
* At the [[glomerulus]], potassium is freely filtered and reabsorbed mainly in the [[proximal tubule]] and thick ascending [[loop of Henle]] (>60 % of filtered potassium).
{{Family tree | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | |}}
* 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.


=== Factors Increasing Kidney Potassium Excretion ===
{{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>}}
*[[Aldosterone]]
{{Family tree | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | |}}
*High urine flow rate
{{Family tree | | | | | | | | | | | | | | E01 | | | | | | | | | | | | | | |E01=<div style="float: left; text-align: left; line-height: 150% ">''' ❑ [[Bone marrow aspiration]] and biopsy <br> </div>}}
*High distal sodium delivery
{{Family tree | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |}}
*[[Metabolic alkalosis]]
{{familytree/end}}


=== Some Factors Affecting Potassium Distribution Between the Cells and the Extracellular Fluid ===
*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>
*Na/K ATPase
*[[Insulin]]
*[[Catecholamines]]
*Plasma potassium concentration
*Extracellular pH
*[[Hyperosmolarity]]


=== The Physiologic Role of Potassium ===
{{Family tree/start}}
* Potassium is essential for many body functions, especially excitable cells such as [[muscle]] and [[nerve]] cells. 
{{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>}}
* Diet, mostly meats and fruits, 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> ❑ [[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> }}
* 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]].
{{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 electrochemical gradient of potassium between [[intracellular]] and [[extracellular]] space is essential for the function of [[Neurones|neurone]]<nowiki/>s; in particular, potassium is needed to repolarize the [[cell membrane]] to a resting state after an [[action potential]] has passed.
[[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>}}
* Decreased potassium levels in the extracellular space will cause [[hyperpolarization]] of the [[resting membrane potential]], i.e, it becomes more negative. This [[hyperpolarization (biology)|hyperpolarization]] is caused by the effect of the altered potassium gradient on [[resting membrane potential]], as defined by the [[Goldman equation]].  As a result, the cell becomes less sensitive to excitation, and a higher than standard stimulus is required for depolarization of the membrane in order to initiate an action potential. Clinically, this membrane hyperpolarization results in flaccid muscle paralysis, [[rhabdomyolysis]] (in severe hypokalemia) and paralytic ileus.
{{Family tree | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | |}}
* At the renal level, hypokalemia can cause metabolic alkalosis due to potassium/proton exchange across the cells and nephrogenic diabetes insipidus.


=== Pathophysiology of Hypokalemic Heart Arrhythmias ===
{{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>}}
* Potassium is essential to the normal muscular function, in both voluntary (i.e. skeletal muscle, e.g. the arms and hands) and involuntary muscle (i.e. smooth muscle in the intestines or cardiac muscle in the heart).    
{{Family tree | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | |}}
* Severe abnormalities in potassium levels can seriously disrupt [[heart|cardiac function]], even to the point of causing [[cardiac arrest]] and [[death]]. 
{{Family tree | | | | | | | | | | | | | | E01 | | | | | | | | | | | | | | |E01=<div style="float: left; text-align: left; line-height: 150% ">''' ❑ [[Bone marrow aspiration]] and biopsy <br> </div>}}
* As explained above, hypokalemia makes the resting potential of potassium [E(K)] more negative.  In certain conditions, this will make cells less excitable. However, in the heart, it causes [[myocytes]] to become hyperexcitable. This is due to two independent effects that may lead to aberrant cardiac conduction and subsequent arrhythmia:
{{Family tree | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | |}}
**There are more inactivated sodium (Na) channels available to fire.
{{Family tree | | | | | | | | | | | | | | E01 | | | | | | | | | | | | | | |E01=<div style="float: left; text-align: left; line-height: 150% ">''' ❑ [[Lumbar puncture]] <br> </div>}}
**The overall potassium permeability of the ventricle is reduced (perhaps by the loss of a direct effect of extracellular potassium on some of the potassium channels), which can delay ventricular repolarization.
{{Family tree | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree/end}}


=== Pathophysiology of Hypokalemic in GI system: ===
==Diagnosis==
* 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]] cause slow movement of GI system and illeus.
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}}


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<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.
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