Page 437 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

CHAPTER 22 ■ Lymphoid and Plasma Cell Neoplasms 421

(MRD) neg tivity n er ic tion o MRD up to 20% o

p tients with re r ctory ise se. Regi ens consisting o

co bin tions o u r bine with onoclon l ntibo ies

(e.g., rituxi b n le tuzu b) re highly pro ising

tre t ents to chieve co plete olecul r re ission.

Newer Treatm ents

Initi l tre t ent o CLL p tients requires ssess ent using
the gui elines o the Intern tion l Workshop on Chronic

Ly phocytic Leuke i or “ ctive ise se.” A er clinic l
ev lu tion or f tness, p tients re require to h ve FISH

n lysis or 17p13 eletion (17p−) n ut tion n lysis o

A P53. A ition l consi er tions inclu e response to previ-

ous tre t ent or p tients with rel pse /re r ctory CLL.
Newer tre t ents inclu e the use o onoclon l nti-

bo ies such s ben ustine. re t ent o CLL p tients
h s ch nge r tic lly over the p st ew ye rs with the

vent o the B-cell receptor (BCR) sign ling nt gonists or
rel pse ise se. In 2014, the Foo n Drug A inistr tion

(FDA) pprove two novel or l kin se inhibitors or p tients
with rel pse or re r ctory CLL. T ese inhibitors re:

■ Bruton’s tyrosine kin se (B K) inhibitor, ibrutinib
B ■ Phosphoinositi e-3 kin se (PI3K) inhibitor, i el lisib

FIGURE 22.3 A. Hyperleukocytosis le . B. Micro rr y n ly-

sis in chronic ly phocytic leuke i (CLL) le ; the expression o Allogeneic Hem atopoietic Stem Cell

C247 sign ture genes right . Di erenti tion o CLL p tients into Transplantation

those with or without ut tions o the Ig V gene by the expres-
sions o 56 genes n Ig I unoglobulins. (Reprinte ro Greer Allogeneic he topoietic ste cell tr nspl nt tion

JP, et l. Wintrobe’s Clinical Hematology, 11th e , Phil elphi , PA: ( lloHSC ) is the only potenti lly cur tive tre t ent v il ble

Lippincott Willi s & Wilkins, 2004, with per ission.) or p tients with CLL. Myelo bl tive high- ose che other py,
with subsequent utologous or llogeneic ste cell tr nspl nt

(SC ), is n option or young n physic lly f t p tients with
e onstr te higher response r tes th n lkyl ting gents to rel pse ise se, but this is not n option or the jority o

provi e or longer progression- ree surviv l. re t ent with CLL p tients.

purine n logues lone oes not ppe r to i prove surviv l.

T e in verse re ctions to purine n logues re yelo- MicroRNA

suppression n ly phocytopeni .

Purine n logues in co bin tion with other cytotoxic MicroRNA y potenti lly be use in ther py or CLL. In the

rugs ( lkyl tors) were intro uce s tre t ent str tegy in uture, p tient-specif c ther peutic rugs y be esigne

the 1990s. An esti te 35% o p tients chieve co plete or CLL p tients h rboring bnor lities in iRNA expres-

re ission. sion in their lign nt cells. iRNAs re potenti l t rgets

More recently, u r bine, cyclophosph i e, n ritux- or ther py s well, s knocking own overexpression o

i b (FCR) co bin tion ther py h s pro uce the l rgest pro- iRNAs n in ucing expression o silence iRNAs in

portion o co plete responses ever reporte in CLL p tients. c ncer cells y contribute to selective tu or killing. Loss o

FCR bec e the new “gol st n r ” or CLL ther py. iRNA expression in CLL p tients y selectively suppress

CD52+ is expresse by nor l n B ly phocytes n pro poptotic p thw ys, provi ing such lign ncies with

l ost ll CLL cells. Anti-CD52 h s been use pri rily in surviv l v nt ge.

p tients who h ve h rel pse n , in so e c ses, s pos-

tre ission consoli tion ther py. T is hu nize onoclo- Minim al Residual Disease

n l ntibo y h s pro uce signif c nt responses in p tients PCR-b se n ow cyto etry–b se ss ys re use to

with resi u l ise se er che other py. Bone rrow is- ssess MRD in CLL. Re l-ti e PCR h s beco e co on

e se w s er ic te ore requently th n no l ise se, n or qu ntif c tion by PCR.

olecul r re issions were chieve .

Monoclon l ntibo ies h ve i erent ech nis o

ction th n cytotoxic che other peutic gents. T ey pl y NOTE: This is a good time to complete Review Questions

signif c nt role in tt in ent o minimal residual disease related to preceding content.