Page 498 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

482 PART 6 ■ Neoplastic Disorders

P tients with secon ry MDS or those who were pre-

viously i gnose with MDS n tre te will prob bly BOX 24.1

receive tre t ent to relieve sy pto s o the ise se (e.g.,

ne i or blee ing). P rticip tion in clinic l tri l o che-

other py or biologic l ther py y lso be n option Categories of Myelodysplastic Syndrome/

(www.clinic ltri ls.gov). Myeloproliferative Neoplasms (MDS/ MPN)

re t ent consi er tions ust weigh the risk o ther py ■ CMML 0, 1, 2, Chronic yelo onocytic leuke i

versus the risk o proble s ssoci te with existing cytope- ■ CML, Atypic l chronic yeloi leuke i

ni s s well s the likelihoo n i inence o leuke ic ■ JMML, Juvenile yelo onocytic leuke i

tr ns or tion. P tients whose ise se is ore severe or get- ■ MDS/MPN-U, Myelo yspl stic syn ro e/Myelopro-

ting worse ore quickly y be tre te with che other py. li er tive neopl s s, uncl ssif ble

In p tients with AML tr ns or ing ro MDS, the clini- ■ RARS- , Re r ctory ne i with ringe si erobl sts

c l responses to the st n r ther py re poor. T e gre tly n thro bocytosis

ecre se he topoiesis in these p tients is consi ere

responsible or their clinic l picture. Leuke i - ssoci te

inhibitory ctivity, which inhibits hu n GM progenitors,

y be responsible or the suppression o nor l gr nu- Pathophysiology

locytopoiesis in so e p tients. In ition, the pro oun T e p thophysiology o MDS/MPN-U involves bnor li-

er nge ent o nor l he topoietic c p bility in these ties in the regul tion o yeloi p thw ys or cellul r proli -

c ses y be bec use o ultiple co plex ctors. Although er tion, tur tion, n surviv l.

MDS is r re in chil ren, these represent so e o the ost i - Isoenzy e n cytogenetic n lyses suggest th t the

f cult yscr si s to tre t. Chil ren tre te or MDS respon p thogenesis o these clon l isor ers is ultistep pro-

poorly to convention l che other py. In requently, chil ren cess beginning with the est biliz tion o the ultipotenti l

y chieve re ission with intensive ther py n llogeneic progenitor cell, c using proli er tion o ivergent clone o

bone rrow tr nspl nt tion. genetic lly unst ble pluripotenti l ste cells th t pro uce

orphologic lly v ri ble but clon lly rel te progeny. T is

MYELODYSPLASTIC SYNDROMES/ type o berr tion beco es per nent when the cquisition

MYELOPROLIFERATIVE NEOPLASMS o clon l chro oso e bnor lity exists.

(MDS/MPN) I the cell bnor lity persists, ition l subclones with
recurrent chro oso e bnor lities e erge. T is prece es

T e MDS/MPN exist t the interph se o phenotypic lly either ilure o e ective he topoiesis or cute tr ns or -

opposing bone rrow lign ncies. T ey re ch r cter- tion (clon l esc pe) to cute yelogenous leuke i (AML)

ize by the si ult neous e tures o bone rrow ilure n or both. He topoiesis is yspl stic bec use o ine cient

yeloproli er tion usu lly with poor prognosis. tur tion o slowly exp n ing or so eti es st ble popu-

Te co bine MDS/MPN c tegory in WHO 2016 h s l tion o bloo cell precursors.

fve subtypes with new olecul r genetic criteri n new

entity, RARS- . T e MDS/MPNs cl ssif c tion (Box 24.1) Clinical Signs and Symptoms

inclu es clon l yeloi neopl s s th t t initi l present - Clinic l sy pto s re c use by co plic tions resulting

tion h ve so e clinic l, l bor tory, or orphologic f n - ro

ings th t support i gnosis o MDS n other f n ings

th t re ore consistent with MPN (see Ch pter 23). T e ■ Cytopeni (s)

bloo picture is hybri with t le st one elev te n one ■ Dyspl stic cells th t unction bnor lly

re uce he topoietic line ge. P tients pl ce in this c t- ■ Leuke ic inf ltr tion o v rious org n syste s

egory, or ex ple, CMML, usu lly e onstr te hyper- ■ Gener l constitution l sy pto s, such s ever n l ise

cellul r bone rrow bec use o proli er tion o one or

ore cell lines. Etiology

P tients with re r ctory ne i with ring si erobl sts T e etiology o MDS/MPN-U is not known.

n thro bocytosis re provision lly inclu e in this c t-

egory s MDS/MPNs-U, uncl ssif ble. T e jority o Incidence

these p tients e onstr te ut tion JAK2 V617F. T e

threshol o pl telets in this c tegory h s been lowere ro Te inci ence o MDS/MPN-U v ries wi ely, r nging ro

600 × 10 /L to 450 × 10 /L. Other l bor tory ch r cteristics pproxi tely 3 per 100,000 in ivi u ls ol er th n 60 ye rs
9
9
inclu e ne i n rig si erobl sts in the bone rrow n nnu lly or chronic yelocytic- onocytic leuke i to s

orphologic lly bnor l eg k ryocytes th t re si il r ew s 0.13 per 100,000 chil ren ro birth to 14 ye rs nnu-

to essenti l thro bocythe i n pri ry yelof brosis lly or juvenile yelocytic- onocytic leuke i (JMML).

(see Ch pter 23). Te inci ence o MPN-U is unknown.