2-5-10 Introduction to Acute Leukemia 1. Understand the general concepts of cancer and clonal proliferative diseases.

Cancer is a genetic disease associated with clonal genetic translocations Ex: 95 o! C"L #atients $and 25 o! ALL% ha&e the t$9'22% (hiladel#hia chromosome translocation )owell*s +,#othesis o! clonal cancer e&olution: se&eral #oints o! genetic damage -e!ore !inall, getting cancer. /nudson*s +,#othesis: multi#le $0two-hit1% hits are re2uired to cause cancer. 2. Understand the pathophysiology of leukemia. 3he two-hit model o! acute leukemogenesis: 1. 4i!!erentiation -lock: loss o! !unction o! transcri#tion !actors re2uired !or di!!erentiation 2. enhanced #roli!eration: gain o! !unction mutations o! t,rosine kinase 3ogether5 di!!erentiation -lock 6 enhanced #roli!eration 7 AC83E leukemia Leukemias are either myeloid $e&er,thing exce#t l,m#hoc,tes9granuloc,tes5 er,throc,tes5 #latelets% or lymphoid $: and 3 cells%' either acute or chronic. 3. Identify the differences between acute and chronic leukemias. Acute leukemia is de!ined -, a -lock in di!!erentiation #lus uncontrolled #roli!eration. 3hus5 ,ou get immature :LA;3;. <a#id onset and usuall, !atal within weeks to months without chemo. E&en with treatment5 mortalit, tends to -e higher. Acute leukemia #resentation: :one "arrow =ailure: anemia5 throm-oc,to#enia5 neutro#enia>leuco#enia ?rgan>tissue in!iltration: he#atos#lenomegal,5 l,m#h nodes5 gum h,#ertro#h,5 -one #ain5 C);5 testes5 others Constitutional s,m#toms: !e&er5 sweats5 weight loss Chronic leukemia: there*s no -lock in di!!erentiation5 -ut rather a lack o! a#o#tosis. 3hus5 there are mature o! di!!erentiated cells that do not die. Chronic onset. . Understand the basic diagnostic and treatment modalities of leukemia. Acute leukemia is de!ined -, the #resence o! @20 Con!irmation is done &ia immuno#henot,#ing: !low c,tometr,: C4 1A and C4AA: m,eloid C455 C4B5 C419: l,m#hoid molecular genetics c,togenetics $chromosomal a-normalities% -lasts in the :".

!. "iscuss basic characteristics of acute leukemia subtypes#acute myeloid leukemia and acute lymphoblastic leukemia. A$%: mainl, in adults5 more common in males5 #rognosis is #oor in adults ;ince A"L occurs #rimaril, in adults5 it has a &er, low cure rate $25 % Chat makes A"L #rognosis worseD I! #receded -, "4; $m,elod,s#lastic s,ndrome% Age @E5 at onset (rior chemo $eto#oside5 athrac,clines% and alk,lators also worsen #rognosis and can lead to "4; "ain !eatures: leukoc,tosis $raised w-c%5 c,togenetic5 molecular markers =L3A and )("1 Fross !eatures: gingi&al in!iltration and extramedullar, disease Acute &romyelocytic %eukemia 'A&%( is a s#eci!ic !orm o! A"L caused -, a t$15'1B% that #roduces a ("L-<A< !usion gene that causes maturation arrest. "or#holog,: lots o! #ur#le granules5 low !i-rinogen5 a-normal coag5 #ossi-le 4IC =low c,tometr,: C41A5 C4AA5 4< negati&e 90 cure rate due to A)*A -inding to ("L-<A< and o&ercoming maturation arrest A%%: mainl, in children' more common in males5 #rognosis is #oorer in adults Less common than A"L Chat makes ALL #rognosis worseD +igh risk: #re-3 and #ro-: ALL Age@A5,o. C-c @A0 in :-ALL5 @100 in 3-ALL $worr, a-out leukostasis% Ger, high risk: (hiladel#hia chromosome t$9'22% $causes a-out A0 o! ALL% 3 cell ALL 3reatments: intense #rolonged $26 ,ear% chemo with lots o! drugs5 C); co&erage5 and #rolonged maintenance 3reatments !or acute leukemia de#end on A"L &s ALL5 age5 and curati&e &s #alliati&e intent. Com-ination chemo: !irst achie&e com#lete remission5 then #re&ent rela#se A"L: induction5 then consolidation $#ost-remission thera#,% ALL: induction5 intensi!ication5 C); #ro#h,laxis5 maintenance +;C3 #ermits 0rescue1 !rom an otherwise toxic treatment regimen Autologous trans#lant is !rom the #atient themsel&es ;,ngeneic trans#lant: !rom a genetic twin Allogeneic trans#lant: !rom someone else5 whether related $"<4: matched related donor% or unrelated $"84: matched unrelated donor% 3here is an advantage o! gra!t-&s-leukemia e!!ect in allogeneic &s s,ngeneic or autologous trans#lants $cell mediated res#onse kee#s leukemia in check%. 3he tradeo!! is that allogeneic trans#lants are more toxic. Com#lications that arise in acute leukemia treatments are leukostasis5 4IC5 se#sis5 and tumor l,sis s,ndrome.