Hemoblastosis in Children

7/21/2019 Hemoblastosis in Children

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Hemoblastosis in children

Department of Pediatrics 2

The chief of department Prof.A.Volosovets

As.Karulina J.


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Hemoblastosis are tumorous diseases of

hematopoietic and lymphatic fabric.

Lymphohematopoietic cancers (i.e., acutelymphoblastic leukemia, lymphomas) account for

approximately 40% of childhood cancers.


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On the basis of structural peculiaritis of

leukaemias cells and their microscopic

peculiaritis acute leukaemia is di!ided by t"olar#e #roups$ cute lymphoblastic leukaemia

(LL) and cute myeloid leukaemia (&L).


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'he acute leukaemias

Acute lymphoblastic leukaemiacute lymphoblastic leukaemia is most common in the a#e

*0 years, "ith a peak at +4 years. 'he incidence then

decreases "ith increasin# a#e. n children it is the mostcommon mali#nant disease and accounts for -% ofchildhood leukaemia.

Acute myeloid leukaemia

cute myeloid leukaemia accounts for *0*% of childhood

leukaemia, but it is the commonest leukaemia of adulthood,particularly as chronic myeloproliferati!e disorders and

preleukaemic conditions such as myelodysplasia usually

pro#ress to acute myeloid leukaemia rather than acute

lymphoblastic leukaemia. 'he incidence increases "ith a#e.


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/isk factors of leukemia in children


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actors Predisposin! to "hildhood #eukemia

$ereditary Do%n&s syndrome 'loom&s syndrome anconi&s anaemia Ata(ia telan!iectasia

Kleinfelter&s syndrome )steo!enesis imperfecta *iskott+Aldrich syndrome #eukaemia in siblin!s "hemicals

"hronic ben,ene e(posure Alkylatin! a!ents -chlorambucil melphalan/ 0adiation Predisposin! haematolo!ical diseases -myeloproliferative disorders myelodysplasia and aplastic anaemia/

Viruses


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A' (renchmerican1ritish)

classification of acute myeloid leukaemia 1 Acute myeloid leukaemia %ith minimal evidence

of myeloid differentiation 13 Acute myeloblastic leukaemia %ithout maturation 12 Acute myeloblastic leukaemia %ith maturation 14 Acute promyelocytic leukaemia 15 Acute myelomonocytic leukaemia 16 Acute monocytic7monoblastic leukaemia 18 Acute erythroleukaemia 19 Acute me!akaryoblastic leukaemia


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'he cytolo#ic appearance of the blast cells is

!ariable and the no completely satisfactory

morpholo#ic classification has been de!ised. 'herenchmerican1ritish (1) inclused +

morpholo#ic subtypes 2 L* to L+.

L* lymphoblasts are predominantly smaal, "ith

little cytoplasm3

L cells are lar#e and pleomorphic "ith increased

cytoplasm, irre#ular nuclear shape, and prominent

nucleoli3L+ cells ha!e finely stippled and homo#eneous

nuclear chromatin, prominent nucleoli, and deep

blue cytoplasm "ith prominent !aculation.


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"ommon "hromosomal Abnormalities in the Acute

#eukemias of "hildhood

DISEASE

SUBTYPE

CHROMOSOMALABNORMALITY INFLUENCE ON PROGNOSIS

ALL Pre-B Trisomy 4 and 10 Favorable

t(12;21)

Pre-B t(4;11) Unfavorable Pre-B t(;22) Unfavorable

B-!ell t(";14) #one

$eneral %y&erdi&loidy Favorable

$eneral %y&odi&loidy Unfavorable

A'L '1* t(";21) Favorable

'4* inv(1+) Favorable

',* t(;1.) Favorable

$eneral del(.) Unfavorable

/nfant t(4;11) Unfavorable


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henotypically, surface markers sho" that about-% of cases of LL are deri!ed from pro#enitors

of 1 cells, about *% are deri!ed from ' cells, and

about *% are deri!ed from 1 cells. small

percenta#e of children dia#nosed "ith leukemiaha!e a disease characteri5ed by surface markers

of both lymphoid and myeloid deri!ation.

mmunophenotypes often correlate to disease

manifestations.


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"hromosomal abnormalitiesare found in most patients

"ith LL. 'he abnormalities, "hich may be related to

chromosomal number, translocations, or deletions, pro!ideimportant pro#nostic information. 'he identification of the

leukemiaspecific fusion#ene se6uences in archi!ed

neonatal blood spots of some children "ho de!elop LL at

a later date indicates the importance of in utero e!ents inthe initiation of the mali#nant process, but the lon# la#

period before the onset of the disease in some children,

reported to be as lon# as *4 yr, supports the concept that

additional #enetic modifications also are re6uired for

disease expression. 7pecific chromosomal findin#s, such

as the t(83) translocation, "hich expresses 19/1L

fusion protein, su##est a need for additional, molecular

#enetic studies.


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"#:;:"A# 1A;:

9ommon symptoms and si#ns at presentationresult from bone marro" failure or, less commonly,

or#an infiltration.

*. naemia can result in pallor, lethar#y, and

dyspnoea.. :eutropenia results in predominantly bacterial

infections of the mouth, throat, skin, chest or

perianal re#ion.

+. 'hrombocytopenia may present as spontaneous

bruisin#, menorrha#ia, bleedin# from

!enepuncture sites, #in#i!al bleedin#, or prolon#ed

nose bleeds.


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4. bone pain

. superficial lymphadenopathy

;. abdominal distension due to abdominal

lymphadenopathy and hepatosplenome#aly


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bnormalities of the hematopoieticsystem manifest aspallor, "hich indicates anemia3 bleedin# from orifices,

petechiae, purpura, and ecchymosis, "hich indicate

thrombocytopenia or disseminated intra!ascular

coa#ulation3 cellulitis or other e!idence of infection,"hich indicates leukopenia3 skin nodules, "hich indicate

leukocytosis3 and other abnormalities of the formed

elements of the blood. bnormalities of the lymphatic

system include lymphadenopathy, superior !ena ca!asyndrome, or respiratory distress "hen the patient is in a

supine position, su##estin# an upper anterior

mediastinal mass or thymic enlar#ement.


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D:A?;)=:=

Full blood countusually but not in!ariably sho"s reduced

haemo#lobin concentration and platelet count. 'he "hite cellcount can !ary from *,0=*08>l to 00=*08>l, and the differential

"hite cell count is often abnormal, "ith neutropenia and the

presence of blast cells. 'he anaemia is a normochromic,

normocytic anaemia, and the thrombocytopenia may be se!ere

(platelet count *0=*08>l).

Coagulation screeningmay yield abnormal results,

particularly in promyelocytic leukaemia (acute myeloid

leukaemia &+) "hen #ranules from the leukaemic blasts can

ha!e procoa#ulant acti!ity and tri##er a consumpti!ecoa#ulopathy.

Biochemical screeningis particularly important if the

leucocyte count is !ery hi#h, "hen there may be e!idence of

renal impairment and hyperuricaemia.


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Chest radiographyis mandatory to exclude the presence of a

mediastinal mass, "hich is present in up to


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Cytogenetics and molecular studiesoften detect abnormalities

"ithin the leukaemic clone that can ha!e dia#nostic orpro#nostic !alue?for example, the hiladelphia chromosome,

"hich is the product of a translocation bet"een chromosomes

8 and , the presence of "hich confers a !ery poor pro#nosis

in cases of acute lymphoblastic leukaemia.

Atraumatic lumbar puncture"ith cerebrospinal fluid cytospin

is an important initial sta#in# in!esti#ation in LL or &L "ith

neurolo#ical symptoms to detect leukaemic cells in the

cerebrospinal fluid, indicatin# in!ol!ement of the centralner!ous system.


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Differential dia!nosis of acute leukaemia

@ f lymphadenopathy$ infections such as infectiousmononucleosis or lymphoma

@ f hepatosplenome#aly$ myeloproliferati!e or

lymphoproliferati!e disorder, myelodysplasia, metabolic,

stora#e or autoimmune disorders(rarely, tropical disease, e#!isceral leishmaniasis)

@ f no peripheral leukaemic blasts but pancytopenia$ aplastic

anaemia or infiltrated bone marro" in!ol!ement from

nonhaemopoietic small round cell tumour@ &yelodysplasia

@ Lymphoblastic lymphoma$ lymphomatous presentation "ith %

of blasts in the marro" (distinction may be arbitrary as treatment

may be the same)


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"urrent chemotherapeutic re!imens for treatin! children

%ith A1# follo% five treatment principles>

*. ##ressi!e induction therapy impro!es induction success

rates as "ell as lon#term sur!i!al.

. 9onsolidation or intensification therapy after remission is

achie!ed is important for lon#term diseasefree sur!i!al.+. &aintenance therapy may #i!e results comparable "ith

the use of consolidation or intensification therapy, but it does

not ha!e a role in patients recei!in# a##ressi!e postremission

therapy.4. 'he type of treatment or prophylaxis for 9:7 leukemia

does not appear important in influencin# lon#term sur!i!al.

. 'ar#eted treatment of other extramedullary disease appears

not to affect lon#term sur!i!al.


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Principles of therapy


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&ost children "ith LL are treated on clinical trials conducted by

national or international cooperati!e #roups. n #eneral, the initial

therapy is desi#ned to eradicate the leukemic cells from thebonemarro"3 this is kno"n as remission induction.Aurin# this phase,

therapy usually is #i!en for 4 "k and consists of !incristine "eekly,

a corticosteroid such as dexamethasone or prednisone, and either

repeated doses of nati!e Laspara#inase or a sin#le dose of a

lon#actin#, pe#ylated aspara#inase preparation. ntrathecal

cytarabine or methotrexate, or both, also may be #i!en. atients

at hi#her risk also recei!e daunomycin at "eekly inter!als. Bith

this approach, 8-% of patients are in remissionas defined byC% blasts in the marro" and a return of neutrophil and platelet

counts to nearnormal le!els after 42 "k of treatment. ntrathecal

chemotherapy is usually #i!en at the start of treatment and once

more durin# induction.


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'he second phase of treatment focuses on ";=

therapyin an effort to pre!ent later 9:7 relapses.ntrathecal chemotherapy is #i!en repeatedly by lumbar

puncture in conDunction "ithintensi!e systemic

chemotherapy. 'he likelihood of later 9:7 relapse isthereby reduced to C%. small proportion of patients

"ith features that predict a hi#h risk of 9:7 relapse may

recei!e irradiation to the brain and spinal cord. 'his

includes those patients "ho, at the time of dia#nosis,ha!e lymphoblasts in the 97 and either an ele!ated

97 leukocyte count or physical si#ns of 9:7 leukemia,

such as cranial ner!e palsy.


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fter remission has been induced, many re#imens pro!ide *42-

"k of multia#ent therapy, "ith the dru#s and schedules used

!aryin# dependin# on the risk #roup of the patient. inally, patients

are #i!en daily mercaptopurine and "eekly methotrexate, usually

"ith intermittent doses of !incristine and a corticosteroid. 'his

period, kno"n as the maintenance phaseof therapy, lasts for 2

+ yr, dependin# on the protocol used. &any patients benefit from

administration of a delayed intensi!e phase of treatment (delayedintensification), approximately 2< mo after the be#innin# of

therapy, and after a relati!ely nontoxic phase of treatment (interim

maintenance) to allo" reco!ery from the initial intensi!e therapy.

small number of patients "ith particularly poor pro#nosticfeatures, principally those "ith the t(83) translocation kno"n as

the hiladelphia chromosome, may under#o bone marro"

transplantation durin# the first remission. n LL, this chromosome

is similar but not identical to the hiladelphia chromosome of

chronic myelo#enous leukemia (9&L).


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#ymphoma is the third most common cancer amon#

children, "ith an annual incidence of * per millionchildren E*4 yr of a#e. 'he t"o broad cate#ories of

lymphoma, Hod#kin disease (HA) and nonHod#kin

lymphoma (:HL).

emale predominance is found amon# youn# children,

"ith a ratio of 4 $ * for children +2< yr of a#e, + $ * for

children


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7e!eral studies su##est that infectious a#ents may be in!ol!ed,

such as human herpesvirus 8 cytome!alovirus and


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'he 0eed+=ternber! cell is a lar#e cell (*24 mm indiameter) "ith multiple or multilobulated nuclei.'his celltype is considered the hallmark of HA, althou#h similar

cells are seen in infectious mononucleosis and other

conditions. 'he /eed7ternber# cell is clonal in ori#in

and arises from the #erminal center 1 cells. HA is

characteri5ed by a !ariable number of /eed7ternber#

cells surrounded by an inflammatory infiltrate oflymphocytes, plasma cells, and eosinophils in different

proportions, dependin# on the HA histolo#ic subtype.


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"lassification =ystems for $od!kin Disease

:. 0< "#A==::"AT:); defines four maDorhistolo#ic subtypes$ Lymphocyte predominance

&ixed cellularity

:odular sclerosis

Lymphocyte depletion


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. ;


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nn rbor 7ta#in# 7ystem for Hod#kins Aisease

Stage IInvolvement of a sngle l!m"# no$e %egon o% a sngle e&t%al!m"#at'o%gan o% ste

Stage II Involvement of t(o o% mo%e l!m"#o$ %egons on t#e same s$e of o%gan

t#e $a"#%agm) o% lo'al*e$ nvolvement of an e&t%al!m"#at' o%gan o%ste an$ of one o% mo%e l!m"# no$e %egons on t#e same s$e of t#e$a"#%agm

Stage III Involvement of no$e %egons on +ot# s$es of t#e $a"#%agm, (#'# ma!+e a''om"ane$ +! lo'al*e$ nvolvement of an e&t%al!m"#at' o%gan o%

ste o% +! s"len' nvolvement

Stage I- Dff.se o% $ssemnate$ nvolvement of one o% mo%e e&t%al!m"#at'o%gan o% tss.es, (t# o% (t#o.t asso'ate$ l!m"# no$e enla%gement

I

Ann Arbor =ta!in! "lassification for $od!kin

Disease


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"#:;:"A# 1A;:*. ainless, nontender, firm, rubbery, cer!ical or supracla!icular

lymphadenopathy.

. ffected lymph nodes are firmer than inflammatory nodes. &ost

patients present "ithsome de#ree of mediastinal in!ol!ement.

+. 9linically detectable hepatosplenome#aly rarely is encountered.

4. 7ymptoms and si#ns of air"ay obstruction (dyspnea, hypoxia,

cou#h), pleural or pericardial effusion, hepatocellular dysfunction,

or bone marro" infiltration (anemia, neutropenia, orthrombocytopenia).

. 7ystemic symptomsare unexplained fe!er F+8J9, "ei#ht loss

F*0% total body "ei#ht o!er + mo, or drenchin# ni#ht s"eats.


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D:A?;)=:=


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"hemotherapy 0e!imens "ommonly Bsed for "hildren and

oun! Adults *ith $od!kin DiseaseCHEMOTHERAPYREGIMENS CORRESPONDING AGENTS

AB-D Do&o%.+'n /A$%am!'n0, +leom!'n, vn+lastne, $a'a%+a*ne

AB-E /DB-E0 Do&o%.+'n /A$%am!'n0, +leom!'n, vn'%stne, eto"os$e

-AMP -n'%stne, $o&o%.+'n /A$%am!'n0, met#ot%e&ate, "%e$nsone

OPPA 1 COPP/females0

-n'%stne /On'ovn0, "%e$nsone, "%o'a%+a*ne, $o&o%.+'n /A$%am!'n0,'!'lo"#os"#am$e, vn'%stne /On'ovn0, "%e$nsone, "%o'a%+a*ne

OEPA 1 COPP /males0 -n'%stne /On'ovn0, eto"os$e, "%e$nsone, $o&o%.+'n /A$%am!'n0,'!'lo"#os"#am$e, vn'%stne /On'ovn0, "%e$nsone, "%o'a%+a*ne

COPP2AB- C!'lo"#os"#am$e, vn'%stne /On'ovn0, "%e$nsone, "%o'a%+a*ne,$o&o%.+'n /A$%am!'n0, +leom!'n, vn+lastne

BEACOPP /a$van'e$

stage0

Bleom!'n, eto"os$e, $o&o%.+'n /A$%am!'n0, '!'lo"#os"#am$e,

vn'%stne /On'ovn0, "%e$nsone, "%o'a%+a*neCOPP C!'lo"#os"#am$e, vn'%stne /On'ovn0, "%e$nsone, "%o'a%+a*ne

CHOP C!'lo"#os"#am$e, $o&o%.+'n /A$%am!'n0, vn'%stne /On'ovn0,"%e$nsone

AB-E3PC /DB-E3PC0 Do&o%.+'n /A$%am!'n0, +leom!'n, vn'%stne, eto"os$e, "%e$nsone,'!'lo"#os"#am$e

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Hemoblastosis in Children