Retrospective Analysis of 111 Cases with Chronic Myeloproliferative Disorders: Clinical Features and Survival
AABBSS TTRRAACCTT OObbjjeeccttiivvee:: In this retrospective study, the clinical features, treatment modalities and survival durations of 111 patients with chronic myeloproliferative disorders (MPDs) were ana- lyzed. MMaatteerriiaall aanndd MMeetthhooddss:: The medical records of 111 MPD patients including 58 patients with polycythemia vera (PV), 32 with essential thrombocythemia (ET), and 21 with idiopathic myelofi- brosis (IMF) who presented to our center between 1987-2006 were evaluated. RReessuullttss:: Among all of the patients, 57 were female and 54 were male (female/male ratio, 1.1). The median age at the time of diagnosis was 61 years (range, 28-81 years). Thrombotic events were more common than bleeding in patients with PV (thrombotic/hemorrhagic events: 34/16) and ET (thrombotic/hem- orrhagic events: 21/11) whereas bleeding was slightly more common than thrombotic events in pa- tients with IMF (thrombotic/hemorrhagic events: 4/5). Arterial thrombotic events predominated over venous events and involved primarily cerebral and coronary arteries. The majority of bleed- ing manifestations affected the skin, mucous membranes, and the gastrointestinal system. Kaplan- Meier curves showed that mean survival time was 21.3 ± 3.6 years (1-29) in PV patients and 12.7
± 0.3 years (1-13) in ET patients while IMF patients had a mean survival time of 7.4 ± 1.5 years (0.5- 12). Survival was shortened with advanced age (p< 0.05), anemia (p< 0.05) and male gender (p>
0.05). CCoonncclluussiioonn:: MPDs share many overlapping clinical and laboratory features but exhibit dif- ferent survival rates being highest for PV and lowest for IMF. The relatively high frequency of thromboembolic complications in this study cohort emphasizes the importance of using an an- tithrombotic preventive strategy in MPD patients.
KKeeyy WWoorrddss:: Polycythemia vera; thrombocythemia, essential Ö
ÖZZEETT AAmmaaçç:: Bu retrospektif çalışmada, kronik miyeloproliferatif hastalığı (MPH) olan 111 olgunun klinik özellikleri, tedavi şekilleri ve yaşam süreleri incelendi. GGeerreeçç vvee YYöönntteemmlleerr:: 1987- 2006 yılları arasında merkezimize başvuran 58 polistemia vera (PV), 32 esansiyel trombositoz (ET) ve 21 idiyopatik miyelofibrozis (IMF) olgusunu içeren 111 MPH hastasının tıbbi kayıtları değerlendirildi. BBuullgguullaarr:: Olguların 57’si kadın, 54’ü erkek (kadın/erkek oranı, 1.1) idi. Tanı sırasında hastaların ortanca yaşları 61 (28-81 yaş aralığı) idi. PV ve ET’li olgularda trombotik olaylar, hemorajik olaylardan daha sık gelişirken (trombotik/hemorajik olay oranları PV ve ET alt gruplarında sırasıyla 34/16 ve 21/11), IMF’li olgularda hemorajik olaylar, trombotik olaylardan hafifçe daha yüksek oranda bulunmuştur (trombotik/hemorajik olay oranı 4/5). Arteriyel trombotik olaylar venöz olaylardan daha sık olup başlıca serebral ve koroner arterlerde gelişmiştir.
Hemorajik olaylar çoğunlukla cilt, mukoz membranlar ve gastrointestinal sistemi etkilemiştir.
Kaplan-Meier eğrisine göre ortalama sağkalım süresi PV’li olgularda 21.3 ± 3.6 yıl (1-29 yıl), ET’li olgularda 12.7 ± 0.3 yıl (1-13 yıl) iken IMF’li olgularda 7.4 ± 1.5 yıl (0.5-12 yıl) olarak gösterildi.
İleri yaşta (p< 0.05), anemisi olan olgularda (p< 0.05) ve erkek cinsiyette (p> 0.05) sağkalım daha kısa bulundu. SSoonnuuçç:: MPH’ler birçok örtüşen klinik ve laboratuvar özellikleri paylaşırken; PV’de en yüksek ve IMF’de en düşük olmak üzere farklı sağkalım oranları göstermektedir. Çalışma grubumuzdaki oldukça yüksek tromboembolik komplikasyon oranı, MPH’li olgularda antitrombotik profilaktik tedavi kullanımının önemini vurgulamaktadır.
AAnnaahh ttaarr KKee llii mmee lleerr:: Polistemia vera; esansiyel trombositoz
Olga Meltem AKAY, MD,a Nazife Şule YAŞAR, MD,a Hava ÜSKÜDAR TEKE, MD,a Fezan ŞAHİN MUTLU, MD,b Zafer GÜLBAŞ, MDa
Departments of aHematology,
bBiostatistics Eskişehir Osmangazi University Faculty of Medicine, Eskişehir
Ge liş Ta ri hi/Re ce i ved: 18.05.2008 Ka bul Ta ri hi/Ac cep ted: 21.10.2008 Ya zış ma Ad re si/Cor res pon den ce:
Zafer GÜLBAŞ, MD
Eskişehir Osmangazi University Faculty of Medicine,
Department of Hematology, Eskişehir, TÜRKİYE/TURKEY
ye lop ro li fe ra ti ve di sor ders (MPDs) are clo nal he ma to lo gi cal ma lig nan ci es that ari se from the trans for ma ti on of a mul ti - po tent he ma to po i e tic stem cell. MPD com pri ses the con di ti ons chro nic mye lo id le u ke mi a (CML), PV, ET, IMF and in the re vi sed World He alth Or- ga ni za ti on (WHO) clas si fi ca ti on al so inc lu des ra re en ti ti es such as chro nic ne ut rop hi lic le u ke mi a.1 The se di se a ses in the past ha ve be en po orly un der- s to od ex cept for CML, which is ge ne ti cally cha rac - te ri zed by the pre sen ce of the Phi la delp hi a (Ph) chro mo so me and the bcl/abl fu si on ge ne.2Ho we - ver, the iden ti fi ca ti on of a mu ta ti on in the Ja nus ki- na se 2 (JAK2) de tec tab le in the ma jo rity of pa ti ents rep re sen ted a ma jor ad van ce in our un ders tan ding of the mo le cu lar pat ho ge ne sis of MPDs.1
The dis tinc ti on bet we en sub gro ups is ba sed on the pre sen ce or ab sen ce of par ti cu lar cli ni cal and la - bo ra tory fe a tu res. PV is de fi ned pri ma rily by an el- e va ted red cell mass, ET by high pla te let co unts and IMF by subs tan ti al bo ne mar row fib ro sis and ex tra - me dul lary he ma to po i e sis.3As a gro up, all MPDs are pre le u ke mic and are pre dis po sed to clo nal evo lu ti - on and di se a se trans for ma ti on.4The pro pen sity to trans form in to acu te mye lo id le u ke mi a dif fers bet - we en sub gro ups, be ing hig hest for CML and lo west for ET. Anot her bi o lo gic comp li ca ti on sha red among the MPDs is the throm bo tic and ble e ding ten dency that sig ni fi cantly inf lu en ces upon prog no- sis and qu a lity of li fe.1Be ca u se of the va ri ab le risks of blas tic trans for ma ti on and throm bo sis-as so ci a ted de aths, ove rall sur vi val in the MPDs ran ges from a ne ar-nor mal li fe ex pec tancy in pa ti ents with ET to a me di an of less than 5 ye ars in pa ti ents with IMF.5 This ret ros pec ti ve sing le-cen ter study analy - zed 111 pa ti ents with MPDs, inc lu ding PV, ET, and IMF only. He re, we pre sent da ta on the comp li ca - ti ons, tre at ment mo da li ti es and sur vi val.
MA TE RI AL AND MET HODS
In this study, we iden ti fi ed 111 pa ti ents with MPD for whom cli ni cal da ta and fol low-up in for ma ti on co uld be ob ta i ned from the re cords of the De part - ment of In ter nal Me di ci ne, Di vi si on of He ma to - logy, Es ki şe hir Os man ga zi Uni ver sity Faculty of
Medicine bet we en 1987-2006. For the di ag no sis of PV, ra i sed cell mass ≥36 mL/kg for ma les and ≥32 for fe ma les in the ab sen ce of hypo xe mi a (ar te ri al oxy gen sa tu ra ti on ≥92%) and in the pre sen ce of sple no me galy we re used as ma jor cri te ri a. A di ag - no sis of ET was ma de with pe rip he ral throm bocy - to sis (>600 x 109/L), cha rac te ris tic mar row fe a tu res with sta i nab le mar row iron sto res as des cri bed by Murphy et al.3The di ag no sis of IMF was ba sed on cha rac te ris tic bo ne mar row his to logy with sple no - me galy, le u co eryt hrob las tic sme ar and the ab sen ce of ot her ca u ses of mye lo fib ro sis.6
In the analy sis of throm bo em bo lic comp li ca ti - ons, occ lu si ve events in the ar te ri al or ve no us sys- tem and in the mic ro cir cu la ti on inc lu ding eryt hro me lal gi a and Ray na ud’s phe no me na we re inc lu ded. In the analy sis of he morr ha gic events, ma jor he morr ha ge and pro lon ged mu co cu ta ne o us ble e dings we re re cor ded.
Statistical Analysis
Sta tis ti cal tests we re per for med using SPSS for Win dows 15.0 soft wa re pac ka ge and Sig mas tat 3.1 soft wa re pac ka ge; dif fe ren ces with a p va lu e be low 0.05 we re con si de red sig ni fi cant. The Sha pi ro-Wilk test was per for med for tes ting nor ma lity. The chi- squ a re test was used to com pa re ca te go ri cal va ri ab - les and the Krus kal Wal lis test for con ti nu o us va ri ab les not nor mally dis tri bu ted, fol lo wed by Dunn’s post hoc test. Sur vi val was as ses sed using the Kap lan-Me i er analy sis; the log-rank test was used for uni va ri a te com pa ri sons. The ef fect of prog- nos tic fac tors on sur vi val was analy zed by Cox pro- por ti o nal ha zards reg res si on mo dels.
RE SULTS
The cha rac te ris tics of 111 pa ti ents inc lu ded in this study are sum ma ri zed in Tab le 1. 54 pa ti ents we re ma le and 57 fe ma le; the ir ages at di ag no sis ran ged from 28 to 81 ye ars (me di an 61 ye ars). 58 pa ti ents we re clas si fi ed as PV, 32 as ET, and 21 as IMF. Sple - no me galy was pre sent in 44 of 56 (79%), 10 of 32 (31%), and 21 of 21 (100%) pa ti ents with PV, ET and IMF, res pec ti vely (p< 0.001). The sple en was mildly en lar ged in pa ti ents with ET and PV and mas si vely en lar ged in the IMF sub gro up.
PV ET AMM p value Clinical Characteristics
No. of patients (n) 58 32 21
Female 29 14 14
Male 29 18 7
Age (mean ± SD) 59.7 ± 11.0 58.3 ± 14.0 63.0 ± 10.00
Splenomegaly (%) 44/56 (79) 10/32 (31) 21/21 (100) < 0.001
Laboratory Characteristics (Median, Range)a
Hematocrit (%) 54 (20-67) 37 (21-47) 31 (11-52) < 0.001
Leucocyte count (x 109/1) 15.1 (5.0-51.7) 13.2 (3.6-50.4) 9.3 (3.2-21.9) NS
Platelet count (x 109/1) 609 (116-3480) 1412 (699-3100) 284 (15-942) < 0.001
Patientsb with pseudohyperkalemia (%) 15/54 (28) 14/31 (45) 2/19 (11) < 0.05
Patients with increased LDH (%) 36/52 (69) 21/27 (78) 16/19 (84) NS
TABLE 1: Clinical and laboratory characteristics of 111 patients with MPDs.
aAvailable before the onset of any treatment modalities.
PV: Polycythemia vera, ET: Essential thrombocythemia, IMF: Idiopathic myelofibrosis, MPDs: Myeloproliferative disorders.
At the ti me of di ag no sis, the me di an he ma toc - rit co unt was 54% (ran ge 20-67) in PV pa ti ents and the me di an pla te let co unt was 1412 x 109/L (ran ge 699-3100) in ET pa ti ents. The he ma to lo gi cal pa ra - me ters at ini ti al di ag no sis dif fe red sig ni fi cantly among MPD sub gro ups as shown in Tab le 1. He - ma toc rit was ele va ted in PV (p< 0.001) and pla te - let co unt was hig hest in ET (p< 0.001) whi le le u cocy te co unt sho wed no dif fe ren ce bet we en sub gro ups. 30% of pa ti ents had a po tas si um le vel of gre a ter than 5.5 meq/L (ran ge 3.5-5.5 meq/L) at di ag no sis and LDH le vel ex ce e ded 480 U/L (ran ge 240-480 U/L) in 74%.
Hydrox yu re a was the most com monly pre fer - red agent in PV and ET sub gro ups whi le an dro gens
ti ents with IMF. Only thre e pa ti ents we re pres cri - bed in ter fe ron-α. Ph le bo tomy was the usu al ini ti - al tre at ment for most pa ti ents with PV to re du ce the he ma toc rit and risk of throm bo sis. As pi rin the - rapy and al ter na ti ve an ti ag re ga ting agents we re used in the pre ven ti on of throm bo sis whe re as oral an ti co a gu lants we re ad mi nis te red for se con dary proph yla xis af ter a first throm bo tic event. Fi ve pa- ti ents with IMF who had ex ces si ve trans fu si on re- qu i re ments and se ve re throm bocy to pe ni a un der went sple nec tomy (Tab le 2).
Throm bo he morr ha gic events and ot her comp - li ca ti ons are shown in Tab le 3. We ob ser ved 59 throm bo tic and 32 he morr ha gic events in the se 111 pa ti ents. Throm bo tic events we re mo re com mon
PV ET AMM
Cytoreductive Therapy (patients, %)
Hydoxyurea 47 (81) 29 (91) 7 (33)
Androgens 1 (2) - 11 (52)
Alkylating agents 11 (19) 10 (31) -
Interferon-α 2a 2 (3) 1 (3) -
None 2 (3) - 3 (14)
Antithrombotic Therapy (patients, %)
Anti-aggregantsa 28 (48) 17 (53) -
Anticoagulantsb 6 (10) 4 (13) 1 (5)
Phlebotomy 46 (79) - 2 (10)
Splenoctomy (patients, %) 3 (5) 3 (9) 5 (24)
TABLE 2: Treatment modalities in 111 patients with MPDs.
a Aspirin and dipyridamole, bWarfarin and heparin
PV: Polycythemia vera, ET: Essential thrombocythemia, IMF: Idiopathic myelofibrosis, MPDs: Myeloproliferative disorders.
morr ha gic events: 34/16) and ET (throm bo tic/he - morr ha gic events: 21/11) whe re as ble e ding was slightly mo re com mon than throm bo tic events in pa ti ents with IMF (throm bo tic/he morr ha gic events:
4/5). In ge ne ral, ar te ri al events (78%) pre do mi na ted over ve no us events. Ma jor ar te ri al events inc lu ded, in des cen ding or der of fre qu ency, ce reb ro vas cu lar ac ci dents, co ro nary he art di se a se (an gi na pec to ris or myo car di al in farc ti on) and eryt hro me lal gi a. Lo wer ex tre mity de ep ve no us throm bo sis (DVT) and pul- mo nary em bo lism ac co un ted for the ma jo rity of ve- no us events. Less com mon si tes of ve no us throm bo sis we re the por tal, sple nic and me sen te ric ve ins. The re was no sig ni fi cant cor re la ti on bet we en the oc cur ren ce of throm bo sis and he ma to lo gic in di - ces such as he ma toc rit, le u cocy te, and pla te let co unt in PV and ET pa ti ents. 14 (36%) of pa ti ents ex pe ri - en cing throm bo tic events, had con ven ti o nal risk fac- tors inc lu ding di a be tes mel li tus, hyper li pi de mi a, hyper ten si on, and/or smo king.
Ble e ding ma ni fes ta ti ons in vol ved pri ma rily skin and mu co us mem bra nes (epis ta xis, ecch ymo - sis, me norr ha gi a and gin gi val he morr ha ge) and gas- tro in tes ti nal system. 42% of all he morr ha gic epi so des we re se con dary to the cli ni cally in di ca ted
use of an ti co a gu lants or an ti ag gre ga ting agents. Du - ring the fol low-up, one PV and one ET pa ti ent evol ved in to acu te le u ke mi a, 6 ye ars and 7 ye ars af - ter di ag no sis, res pec ti vely. Both pa ti ents had be en ex po sed to hydrox yu re a and alk yla ting agents.
Mye lo fib ro sis de ve lo ped in one pa ti ent with PV at 3 ye ars af ter di ag no sis.
The eva lu a ti on of the Kap lan-Me i er cur ves sho wed that the me an sur vi val ti me was 21.3 ± 3.6 ye ars (1-29) in PV pa ti ents and 12.7 ± 0.3 ye ars (1- 13) in ET pa ti ents whi le IMF pa ti ents had a me - an sur vi val ti me of 7.4 ± 1.5 ye ars (0.5-12) (Figure 1). Ove rall sur vi val ti me in MPD pa ti ents was 19.9
± 2.5 ye ars (0.5-29). We eva lu a ted the as so ci a ti on bet we en sur vi val ti me and gen der, age (<60 ye ars and ≥60 ye ars) and he mog lo bin le vel (<10 g/dL and
≥10 g/dL) by cox reg res si on analy sis. Cox reg res si - on analy sis sho wed that sur vi val was shor te ned 5.8-fold with ad van ced age (p= 0.044; ha zard ra ti o of 5.8, [95% Cl 1.1-31.6]), 2.9-fold with ma le gen- der (p= 0.230; ha zard ra ti o of 0.3, [95% Cl 0.1-2.0]), and 10.3-fold with ane mi a (p= 0.018; ha zard ra ti o of 0.1, [95% Cl 0.01-0.7]). Throm bo tic and he mor- r ha gic events and con ven ti o nal risk fac tors had no inf lu en ce on the length of sur vi val. We eva lu a ted
PV ET AMM
Tromboembolic Events (Absolute Numbers) 34 21 4
Atreial 28 15 3
Cerebral 12 6 -
Cardiac 4 3 1
Extremity 1 2 -
Raynaud’s phenomenon 3 - -
Erythromelalgia 8 4 2
Venous 6 6 1
Extremity 3 3 1
Pulmonary embolism 3 - -
Othersa - 3 1
Hemorrhageb 16 11 5
Epistaxis 6 6 4
Other mucocutaneousc 7 1 1
Gastrointestinal 3 4 -
Leukemic Transformation 1 1 -
Secondary Myelofibrosis - 1 -
TABLE 3: Hemostatic and other complications in 111 patients.
a Mesenteric, portal and splenic thrombosis,
b42% of all events observed in anticoagulated patients,
cHematoma, oral bleeding and menorrhagia.
PV: Polycythemia vera, ET: Essential thrombocythemia, IMF: Idiopathic myelofibrosis, MPDs: Myeloproliferative disorders.
the as so ci a ti on bet we en sur vi val ti me and he mog - lo bin le vel (<10 g/dL and ≥10 g/dL) and pla te let co - unt (<100 x 109/L ≥) in a se pa ra te da ta of IMF pa ti ents and no ti ced that the se pa ra me ters did not inf lu en ce sur vi val in pa ti ents with IMF.
DISCUSSION
This sing le-cen ter ret ros pec ti ve study ai med to com pa re cli ni cal fe a tu res, tre at ment mo da li ti es and sur vi val du ra ti ons in a co hort of 111 pa ti ents with MPDs.
Throm bo he morr ha gic events we re the most fre qu ent comp li ca ti ons sha red among the 111 MPD pa ti ents. The fre qu ency of throm bo sis was gre a ter than that of ble e ding be ing hig hest in PV pa ti ents fol lo wed by ET and IMF pa ti ents. Ar te ri al events pre do mi na ted over ve no us events in all sub gro ups oc cur ring com monly in ce reb ral ar te ri es, co ro nary ar te ri es, and mic ro cir cu la tory lo ca ti ons. The in ci - den ce of eit her throm bo sis or he morr ha ge is dif fi - cult to es tab lish in MPDs. Pub lis hed da ta des cri be a wi de ran ge of va lu es for the re la ti ve fre qu ency of throm bo he morr ha gic epi so des, pro bably du e to fac tors inc lu ding pa ti ent se lec ti on, de fi ni ti ons of events, ac cu racy in da ta re por ting and the ef fect of the rapy.7Re gard less, the fre qu ency of throm bo sis (ar te ri al, ve no us and mic ro cir cu la tory) has be en con sis tently gre a ter than ble e ding.8 The pro- throm bo tic ef fect of an ele va ted he ma toc rit is well es tab lis hed in the pat ho ge ne sis of throm bo sis. The
and dec re a sed ce reb ral blo od flow ra te was shown in vi vo.9
In cre a sing age and a his tory of vas cu lar events pro ved to be ot her in de pen dent pre dic tors of throm bo sis in pa ti ents with PV.10Le u cocy to sis is al so a risk fac tor for throm bo sis in PV and ET thro - ugh re cently dis co ve red mec ha nisms of ac ti va ti on and in te rac ti on with pla te lets and en dot he li al cells.11-13High JAK2 V617F mu ta ti on al le le bur den is be ing cur rently in ves ti ga ted for ad di ti o nal prog- nos tic va lu e in vas cu lar events.10Alt ho ugh this da - ta co uld not show any cor re la ti on bet we en the oc cur ren ce of vas cu lar events and he ma to lo gic in- di ces (ie, he ma toc rit, le u cocy te, and pla te let co unt), our fin dings de mons tra ted the dif fe ren ces in the kind and lo ca li za ti on of he morr ha gic and throm- bo em bo lic comp li ca ti ons in MPD subt ypes. The re - la ti vely high fre qu ency of throm bo em bo lic comp li ca ti ons in this study co hort sug gests that mo re strin gent throm bop roph yla xis may be in di - ca ted for MPD pa ti ents.10
Hydrox yu re a was the most com monly used agent in PV and ET sub gro ups whe re as as pi rin the - rapy was pre fer red for the pre ven ti on of throm bo - sis. In high-risk pa ti ents for throm bo sis, the be ne fits of mye lo sup pres si ve the rapy out we igh the po ten ti al risk of to xi city.7Cur rent evi den ce sup- ports the use of hydrox yu re a as the ini ti al cho i ce of cyto re duc ti ve agent be ca u se of its pro ven ef fi - cacy.14,15As pi rin furt her re du ces throm bo tic risk in PV pa ti ents whe re as ret ros pec ti ve ob ser va ti ons sug gest that it might be si mi larly be ne fi ci al in ET pa ti ents.16-19The cur rent da ta sup ports the the ra - pe u tic va lu e of hydrox yu re a and as pi rin in pa ti ents with PV and ET.
Anot her bi o lo gic comp li ca ti on sha red among our pa ti ents was di se a se trans for ma ti on. Trans for - ma ti on in to a mye lo fib ro tic sta ge de ve lops in ap- pro xi ma tely 12% of PV pa ti ents, but ra rely oc curs in ET pa ti ents. The pro pen sity to trans form in to acu te le u ke mi a dif fers among the sub gro ups, be ing hig hest for IMF and le ast for ET.20 Ra di o ac ti ve phosp ho rus (32P) and cyto re duc ti ve agents such as bu sul fan and hydrox yu re a are tho ught to play a ca - u sa ti ve ro le in the pat ho ge ne sis of le u ke mic trans-
FI GU RE 1: Kap lan Me i er sur vi val cur ves of 111 pa ti ents with mye lop ro li fe - ra ti ve di sor ders.
trans for med to acu te le u ke mi a af ter re ce i ving hy- drox yu re a and an alk yla ting agent, which is al so men ti o ned in le u ke mic trans for ma ti on of ET.22,23
We ob ser ved that sur vi val was hig hest in PV and lo west in IMF. Sur vi val of pa ti ents in this co- hort was fa vo rably com pa rab le with pre vi o us re- ports. PV has a sur vi val ra te bet we en 10 and 20 ye ars, whi le IMF has the worst prog no sis with a me di an sur vi val of 3.5 to 5.5 ye ars among MPDs.24,25The sur vi val ra te for MPDs va ri es, de- pen ding on the type of di sor der and the kind of symptoms ex pe ri en ced by each in di vi du al. Prog- no sis is highly de pen dent on the oc cur ren ce of throm bo he morr ha gic comp li ca ti ons.26The ot her fac tors as so ci a ted with shor ter sur vi val inc lu de age (>60), sex (ma le), sple no me galy, ane mi a, le u cocy - to sis or le u cocy to pe ni a, throm bocy to pe ni a, in cre - a sed blasts in the pe rip he ral blo od and the pre sen ce of symptoms.27-29It is no tab le that se ve ral prog nos - tic sco ring systems ha ve be en es tab lis hed and wi - dely used for sur vi val in IMF pa ti ents.30-33In the cur rent study, we de mons tra ted an un fa vo rab le prog nos tic im pact of ma le gen der, age, and ane mi - a, sup por ting the pre dic ti ve va lu e of cli ni cal and la -
bo ra tory va ri ab les for de fi ning sur vi val in MPD pa- ti ents.
Be ing a ret ros pec ti ve study, the ma in li mi ta ti - on of our study was that di ag nos tic cri te ri a for PV, ET, and IMF we re ba sed on cli ni cal and morp ho lo - gic fin dings. Re cent dis co ve ri es of mye lop ro li fe ra - ti ve di se a se spe ci fic mo le cu lar mar kers, inc lu ding JAK2 mu ta ti on ha ve ope ned a new era in our un- ders tan ding of the se di se a ses and furt her mo re the di ag nos tic cri te ri a for MPDs ha ve be en re vi sed by in cor po ra ting JAK2 mu ta ti on scre e ning.34,35
In conc lu si on, MPDs sha re many over lap ping cli ni cal and la bo ra tory fe a tu res but ex hi bit dif fe - rent sur vi val ra tes be ing hig hest for PV and lo west for IMF. The re la ti vely high oc cur ren ce of throm- bo em bo lic comp li ca ti ons sug gests a ra ti o na le for the use of an an tit hrom bo tic pre ven ti ve stra tegy in pa ti ents with MPD. The cur rent study sup ports the use of prog nos tic mar kers to aid furt her both physi- ci ans and pa ti ents in tre at ment re com men da ti ons and in for med de ci si ons ma king, res pec ti vely. Fi- nally, much lar ger gro up of pa ti ents is re qu i red to es tab lish new in ter na ti o nal prog nos tic mo dels for MPD.
1. Va inc hen ker W, Cons tan ti nes cu SN. A uni qu - e ac ti va ting mu ta ti on in JAK2 (V617F) is at the ori gin of polyc ythe mi a ve ra and al lows a new clas si fi ca ti on of mye lop ro li fe ra ti ve di se a ses.
He ma to logy Am Soc He ma tol Educ Prog ram 2005:195-200.
2. No well PC, Hun ger ford DA. Chro mo so me stu - di es on nor mal and le u ke mic hu man le u kocy - tes. J Natl Can cer Inst 1960;25:85-109.
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