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Principles of
Treatment
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Treatment of children with canceris one of the most complexendeavors in pediatrics.
a. correct diagnosis (including subtype)
b. accurate and thorough staging of the extent ofdisease
c. determination of prognostic subgroup
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Team:
a. pediatric oncologists
b. Pathologists
c. Radiologists
d. Surgeons
e. Radiotherapists
f. Nurses
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g.various support staff :
nutritionists
social workers
psychologists,
pharmacistsother medical specialists
teachers trained to work withseriously ill children.
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DIAGNOSIS AND STAGING
Diagnostic imaging:
a. Evaluation pre and post treatment
b. Determine extent of diseasec. Appropriate therapy
d. Follow-up
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Example:
a. MRIb. CT
c. Ultrasonography
d. scintigraphy (nuclear medicine scans)
e. positron emission tomography
f. spectroscopy,
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DRUG MECHANIS
M OFACTION
INDICATION(
S)
ADVERSE REACTIONS MONITORY DRUG
LEVEL
DRUG LEVEL
COMMENTS
Methotrexate
Folic acidantagonist; inhibitsdihydrofol
atereductase
ALL non-Hodgkinlymphoma,osteosarco
ma,Hodgkinlymphoma,medulloblas toma
Myelosuppression,mucositis, stomatitis,dermatitis, hepatitis
Long Term:
Osteopenia and bonefractures
High dose:
Renal & CNS toxicity
IntrathecalAdministration:
Arachnoiditis,leukoencephalopathy,leukomyelopathy
Plasma levelsmust bemonitored withhigh-dose
therapy andwhen low dosesare administeredto patients withrenal dysfunctionand leucovorin
rescue appliedaccordingly
Systemicadministration may bePO, IM, or
IV;also maybe adminis-teredintrathe-cally
Common Chemotherapeutic Agents Used in Children
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DRUG MECHANISMOF ACTION
INDICATION(S)
ADVERSEREACTIONS
MONITORYDRUG LEVEL
DRUG LEVELCOMMENTS
6-Mercaptopurine(Purinethol)
Purineanalog;inhibitspurinesynthesis
ALL Myelosuppression, hepaticnecrosis,mucositis;allopurinolincreases toxicity
Therapeuticdrugmonitoringnot availableor indicated
Allopurinolinhibitsmetabolism
Cytarabine(Ara-C)
Pyrimidineanalog;inhibitsDNApolymerase
ALL, AML,non-Hodgkinlymphoma, Hodgkin
lymphoma
Nausea,vomiting,myelosuppression, conjunctivitis,mucositis,
central nervoussystemdysfunction
Therapeuticdrugmonitoringnot availableor indicated
Systemicadministrationmay be Po, IM,or IV;may alsobe
administeredintrathecally
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DRUG MECHANISM OF
ACTION
INDICATION(S)
ADVERSE REACTIONS MONITORY DRUGLEVEL
DRUGLEVELCOMMENTS
Cyclophosphamide(Cytoxan)
Alkylatesguanine;inhibitsDNAsynthesis
ALL, non-Hodgkinlymphoma,Hodgkinlymphoma, softtissue sarcoma,Ewing sarcoma
Nausea, vomiting,myelosuppression,hemorrhagic cystitis,pulmonary fibrosis,inappropriate ADHsecretion, bladder cancer,anaphylaxis
Therapeuticdrugmonitoringnotavailable orindicated
Requireshepaticactivationand thuslesseffective inpresence of
liverdysfunction
Ifosfamide (Ifex)
Alkylatesguanine;inhibits
DNAsynthesis
Non-Hodgkinlymphoma,Wilms tumor,
sarcoma, germcell andtesticulartumors
myelosuppression, Nausea,vomiting hemorrhagiccystitis, pulmonary fibrosis,
inappropriate ADHsecretion, bladder cancer,central nervous systemdysfunction, cardiac toxicity,anaphylaxis
Therapeuticdrugmonitoring
notavailable orindicated
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DRUG MECHANISM OF
ACTION
INDICATION(S) ADVERSE REACTIONS MONITORYDRUG LEVEL
DRUGLEVELCOMMENTS
Doxorubicin(Adriamycin)anddaunorubicin(Cerubidine)
Binds toDNA,intercalation
ALL, AML,osteosarcoma, Ewingsarcoma,Hodgkinlymphoma,non-Hodgkin
lymphoma,neuroblastoma
Nausea, vomiting,cardiomyopathy, redurine, tissuenecrosis onextravasation,myelosuppression,conjunctivitis,
radiation dermatitis,arrhythmia
Therapeuticdrugmonitoringnot availableor indicated
Dactinomycin
Binds toDNA,inhibitstranscription
Wilms tumor,rhabdomyosarcoma, Ewingsarcoma
Nausea, vomitingtissue necrosis onextravasation,myelosuppression,radiosensitizer,mucosal ulceration
Therapeuticdrugmonitoringnot availableor indicated
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DRUG MECHANISM OFACTION
INDICATION(S)
ADVERSE REACTIONS MONITORYDRUG LEVEL
DRUGLEVELCOMMENTS
Bleomycin(Blenoxane)
Binds toDNAcleavesDNAstrands
Hodgkindisease, non-Hodgkinlymphoma,germ cell
tumors
Nausea, vomiting,pneumonitis,stomatitis, Raynaudphenomenon,pulmonary fibrosis,
dermatitis
Therapeuticdrugmonitoringnot availableor indicated
L-Asparagin
ase
Depletionof L-
asparagine
ALL;AML,when used in
combinationwithasparaginase
Allergic reactionpancreatitis,
hyperglycemia,platelet dysfunctionand coagulopathy,encephalopathy
Therapeuticdrug
monitoringnot availableor indicated
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DRUG MECHANISM OF
ACTION
INDICATION(S) ADVERSEREACTIONS
MONITORYDRUG LEVEL
DRUGLEVELCOMMENTS
Vincristine(Oncovin)
Inhibitsmicrotubuleformation
ALL, non-Hodgkinlymphoma,Hodgkin disease,
Wilms tumor,Ewing sarcoma,
neuroblastomarhabdomyosarcoma
Local cellulitis,peripheralneuropathy,constipation, ileus,
jaw pain,inappropriate ADH
secretion, seizures,ptosis, minimalmyelosuppression
Therapeuticdrugmonitoringnot availableor indicated
IVadministrationonly;must notbe
allowed toextravasate
Vinblastine
(Velban)
Inhibitsmicrotub
uleformation
Hodgkin disease;Langerhans'cell
histiocytosis
Local cellulitis,leukopenia
Therapeuticdrugmonitoringnot availableor indicated
IVadministration only;must notbe allowedtoextravasate
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DRUG MECHANISM OFACTION
INDICATION(S)
ADVERSE REACTIONS MONITORYDRUG LEVEL
DRUGLEVELCOMMENTS
Etoposide(VePesid) Topoisomeraseinhibitor
ALL, non-Hodgkinlymphoma,germ celltumor
Nausea, vomiting,myelosuppression,secondary eukemia
Therapeuticdrugmonitoringnot availableor indicated
Etretinate(Tegison)(vitamin Aanalog) andtretinoin
Enhancesnormaldifferentiation
Acuteprogranuloc
yticleukemia;neuroblastoma
Dry mouth, hair loss,pseudotumor cerebri,premature epiphysealclosure
Therapeuticdrugmonitoringnot availableor indicated
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DRUG MECHANISM OF
ACTION
INDICATION(S)
ADVERSEREACTIONS
MONITORYDRUG LEVEL
DRUGLEVELCOMMENTS
Pegaspargase(Pegaspar)
Polyethylene glycolconjugateof L-asparagin
e
ALL Indicated forprolongedasparaginedepletion and forpatients with
allergy to L-asparaginase
Therapeuticdrugmonitoringnot availableor indicated
Carmustine(nitrosourea)
Carbamylation ofDNA;inhibitsDNAsynthesis
CNStumors,non-Hodgkinlymphoma,Hodgkindisease
Nausea, vomiting,delayedmyelosuppression(46 wk);pulmonary fibrosis,carcinogenicstomatitis
Therapeuticdrugmonitoringnot availableor indicated
Phenobarbitalincreasesmetabolism,decreases activity
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Infectious Complications of Malignancy
PREDISPOSINGFACTOR
ETIOLOGY SITE OFINFECTION
INFECTIOUS AGENTS
Splenectomy Staging of
Hodgkindisease
Sepsis,
shock,meningitis
Pneumococcus, Haemophilus
influenzae, meningococcus
Indwellingcentral venous
catheter
Nutrition,administration
ofchemotherapy
Line sepsis,tract of
tunnel, exitsite
S. epidermidis, S. aureus,Candida albicans, P. aeruginosa,
Aspergillus, CorynebacteriumJK, Streptococcus faecalis,Mycobacterium fortuitum,Propionibacterium acnes
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The Leukemias
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group of malignant diseases in which
genetic abnormalities in a
hematopoietic cell give rise to an
unregulated clonal proliferation of
cells.
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The progeny of these cells have a growth
advantage over normal cellular elements,because of their increased rate ofproliferation, and a decreased rate ofspontaneous apoptosis.
The result is a disruption of normal
marrow function and, ultimately, marrowfailure.
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Leukemias: Most common malignant neoplasms inchildhood,
41% of all malignancies that occur in children
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Acute Lymphoblastic
Leukemia
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EPIDEMIOLOGY
USA: Approx 2,000 children
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Among identical twins:
risk to the second twin if one develops leukemiais greater than that in the general population
risk is >70% if the first twin is diagnosed duringthe first year of life and the twins shared the same
(monochorionic) placenta
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ETIOLOGY
In virtually all cases, the etiology of ALL isunknown
several genetic and environmental factorsare associated with childhood leukemia
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Factors Predisposing to Childhood
LeukemiaGENETIC CONDITIONS
Down syndrome
Fanconi syndrome
Bloom syndrome
Diamond-Blackfan anemia
Schwachman syndrome
Klinefelter syndrome
Turner syndrome
Neurofibromatosis type 1 Ataxia-telangiectasia Severe combined immune deficiency
Paroxysmal nocturnal hemoglobinuria
Li-Fraumeni syndrome
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ENVIRONMENTAL FACTORS Ionizing radiation
Drugs
Alkylating agents
Nitrosourea
Epipodophyllotoxin Benzene exposure
Advanced maternal age
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CLINICAL MANIFESTATIONS
Initially: nonspecific and relatively brief.
Anorexia
FatigueIrritability
intermittent, low-grade fever
joint pain:lower extremities
URTI in the preceding 12 mo.
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As the disease progresses:
signs and symptoms of bone marrowfailure:
pallor
fatiguebruising
epistaxis
fever
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Physical examination
Bone Marrow Failure: Pallor
Listlessness
purpuric and petechial skin lesions
mucous membrane hemorrhage
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The proliferative nature:
Lymphadenopathy Splenomegaly
Hepatomegaly less common
bone or joint pain-
tenderness over the bone or objective evidence ofjoint swelling and effusion
with marrow involvement--deep bone pain may be
present but tenderness will not be elicited
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DIAGNOSIS
The diagnosis of ALL is stronglysuggested by peripheral bloodfindings indicative of bonemarrow failure.
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Anemia and thrombocytopenia are seen inmost patients.
Leukemic cells often are not observed in theperipheral blood in routine laboratory
examinations.Many patients with ALL present with total
leukocyte counts of
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Bone marrow aspiration alone usually is
sufficient But sometimes a bone marrow biopsy
---is needed to provide adequate tissue
for study or to exclude other possiblecauses of bone marrow failure
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ALL is diagnosed by a bone marrowevaluation that demonstrates >25% of thebone marrow cells as a homogeneouspopulation of lymphoblasts.
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Staging of ALL
- based partly on a cerebrospinal fluid
(CSF) examination
If lymphoblasts are found and the CSFleukocyte count is elevated, overt CNS ormeningeal leukemia is present.
This finding reflects a worse stage and
indicates the need for additional CNS andsystemic therapies
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TREATMENT
single most important prognostic
factor in ALL is the treatment:without effective therapy, the
disease is fatal
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Predictive Factors
age of the patient at the time ofdiagnosis
initial leukocyte count
speed of response to treatment
(i.e., how rapidly the leukemic cells can be clearedfrom the marrow or peripheral blood).
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Average Risk: age between 110 yr
leukocyte count of 10 yr of age
initial leukocyte count of >50,000/L
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Therapy
Remission Induction:therapy designed to eradicate the
leukemic cells from the bone marrow
therapy usually is given for 4 wk:a. vincristine weeklyb. corticosteroid such as dexamethasone or prednisone
c. repeated doses of native L-asparaginaseor single dose of a long-acting, pegylated asparaginasepreparation.
d. Intrathecal cytarabine or methotrexate, or both, also may begiven.
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Patients with higher risk:
daunomycin at weekly intervalsWith this approach, 98% of patients are in
remission
Remission:
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CNS therapy
to prevent later CNS relapses
Intrathecal chemotherapy is given repeatedly bylumbar puncture in conjunction with intensivesystemic chemotherapy.
CNS relapse is thereby reduced to
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Features that predict a high risk of CNS
relapse: patients who, at the time of diagnosis, have lymphoblastsin the CSF
either an elevated CSF leukocyte count or physical signs
of CNS leukemia, such as cranial nerve palsy.
CNS relapse may receive irradiation to the brain andspinal cord irradiation.
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Testicular relapse occurs in 12% of boys with ALL, usually after
completion of therapy. relapse presents as painless swelling of one or
both testes.
diagnosis is confirmed by biopsy of the affectedtestis
Treatment
a. systemic chemotherapyb. local irradiation.
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maintenance phase therapy: lasts for 23 yr,
depending on the protocol used.
After remission has been induced
many regimens provide 1428 wk of multi-agenttherapy
with the drugs and schedules used varying dependingon the risk group of the patient
daily mercaptopurineweekly methotrexate, usually with intermittent doses
of vincristine
corticosteroid.
Maintenance phase
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delayed intensification
approximately 57 mo after the beginning of therapy,and after a relatively nontoxic phase of treatment(interim maintenance) to allow recovery from the initial
intensive therapy.
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PROGNOSIS
Most children with ALL can now beexpected to have long-term survival
survival rate >80% at 5 yr fromdiagnosis
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Type of treatment chosen according
a. type of ALL
b. stage of diseasec. age of the patient
d. rate of response to initial therapy
Favorable: patient responds in
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Unfavorable: age 10 yr at diagnosis
leukocyte count of >100,000/L at diagnosis
slow response to initial therapy
Chromosomal abnormalities
Hypodiploidy
Philadelphia chromosome
MLL gene rearrangements and translocations[t(1:19) or t(4;11)], portend a poorer outcome.
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Acute Myelogenous
Leukemia
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EPIDEMIOLOGY
accounts for 11% of the cases of childhoodleukemia in the USA
approximately 370 children diagnosedwith AML annually.
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Several chromosomal abnormalitiesassociated with AML have beenidentified, but no predisposing genetic
or environmental factors can beidentified in most patients
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PATHOGENESIS
Characteristic feature of AML >30% of bone marrow cells on bone marrow aspiration or
biopsy touch preparations constitute a fairly
homogeneous population of blast cells
with features similar to those that characterize earlydifferentiation states of the myeloid-monocyte-
megakaryocyte series of blood cells..
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French-American-British (FAB) Classification ofAcute Myelogenous Leukemia
SUBTYPECOMMON NAME
M1 Acute myeloblastic leukemia without maturation
M2 Acute myeloblastic leukemia with maturation
M3 Acute promyeloblastic leukemia
M4 Acute myelomonocytic leukemia
M5 Acute monocytic leukemia
M6 Erythroleukemia
M7 Acute megakaryocytic leukemia
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CLINICAL MANIFESTATIONS
subcutaneous nodules or blueberry muffinlesions
infiltration of the gingiva
disseminated intravascular coagulation
discrete masses
chloromas or granulocytic sarcomas
CNS symptoms
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DIAGNOSIS
Analysis of bone marrow aspiration and biopsy
specimen--
features of a hypercellular marrow consisting of a
rather monotonous pattern of cells with features
that permit FAB subclassification of disease
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Special stains assist in identification ofmyeloperoxidase-containing cells-
confirming the origin of the leukemia and
the diagnosis.
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TREATMENT
Matched-sibling bone marrow or stem celltransplantation after remission has been shown toachieve long-term disease-free survival in 6070%of patients.
Continued chemotherapy for patients who do nothave a matched donor is less effective than
marrow transplantation but, nevertheless, iscurative in some patients.
CHROM ALT GENES USUAL PROGNOSI RECOMD TREATMENT
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ABN MORPH S
t(8;21) AML1-ETO FAB AML-M2 Favorable Intensive chemotherapy, includinghigh-dose cytarabine
inv(16),t(16;16)
CBFB-MYHIIFAB AML-M4Eo Favorable Intensive chemotherapy, includinghigh-dose cytarabine
t(15;17) PML-RARA FAB AML-M3 Favorable Intensive chemotherapy, includingATRA and anthracyclines
t(11;17) PLZF-RARA FAB AML-M3 Favorable Intensive chemotherapy, includingATRA and anthracyclines
11q23 abn. MLLrearrangements
FAB AML-M4or AML-M5
Unavorable Intensive chemotherapy, with high-
dose cytarabine and MRD HSCT
t(3;v) EVI1 MDS/AML Unavorable Intensive chemotherapy with orwithout HSCT
t(3;5) NPM-MLF MDS/AMS Unavorable Intensive chemotherapy with orwithout HSCT
del(7q), -7
Unknown MDS/FABAML-M0
Unavorable Intensive chemotherapy with or
without HSCT
del(5q), -
5
Unknown MDS/FAB
AML-M0
Unavorable Intensive chemotherapy with or
without HSCT
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Lymphoma
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Lymphoma is the third most commoncancer among children in the USA
annual incidence of 15 per million children
14 yr of age
Two categories of lymphoma
a. hodgkin disease (HD)
b. non-Hodgkin lymphoma (NHL)
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Hodgkin Disease
malignant process of the lymphoreticularsystem that constitutes 6% of childhood cancers
USA:about 5% of cancers in persons 14 yr of age
about 15% in persons 1519 yr of age
rare in children
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EPIDEMIOLOGY bimodal with regard to age early peak occurs in the middle to late 20s
second peak after 50 yr of age
developing countriesearly peak occurs before adolescence
male: female ratio
4 : 1 for children 37 yr of age
3 : 1 for children 79 yr of age
1.3 : 1 for children >10 yr of age
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infectious agents may be involved
a. human herpesvirus 6b. cytomegalovirus
c. Epstein-Barr virus (EBV)
Immunodeficiency
congenital- ataxia-telangiectasia,
acquired- HIV infection
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ETIOLOGY
Reed-Sternberg cell
large cell (1545 m in diameter) with multiple
or multilobulated nuclei hallmark of HD
arises from the germinal center B cells.
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RYE CLASSIFICATION
Lymphocyte predominanceaffects 1015% of patients
common among male and younger patients
presents as localized disease
Mixed cellularity
observed in 30% of patients
more common among children 10 yr of age
often presents as advanced disease with extranodalextension
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Nodular sclerosis
NS is the most common subtype
affecting 40% of younger patients and 70% ofadolescents
Lymphocyte depletionrare in children
common in patients with HIV infection
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NEW WHO/REAL CLASSIFICATION
Nodular lymphocyte predominance Classical Hodgkin lymphoma
Lymphocyte rich
Mixed cellularity Nodular sclerosis
Lymphocyte depletion
Anaplastic large cell lymphoma Hodgkin-like
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HD appears to arise in lymphoid tissue and
spreads to adjacent lymph node areas in arelatively orderly fashion
Hematogenous spread also occurs, leadingto involvement of the liver, spleen, bone,bone marrow, or brain, and usually is
associated with systemic symptoms
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CLINICAL MANIFESTATIONS
painless, non-tender, firm, rubbery, cervical orsupraclavicular lymphadenopathy
affected lymph nodes are firmer than inflammatorynodes
Signs & symptoms of airway obstruction
(dyspnea, hypoxia, cough)
pleural or pericardial effusion
hepatocellular dysfunction bone marrow infiltration
(anemia, neutropenia, or thrombocytopenia)
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Systemic symptoms classified as B symptoms:
a. unexplained fever >39C
b. weight loss >10% total body weight over 3 mo
c. drenching night sweatsd. some present as a fever of unknown origin.
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Less common and not considered of
prognostic significance: Pruritus
Lethargy
Anorexia pain that worsens after ingestion of alcohol.
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Immune system abnormalities
a. anergy to delayed-hypersensitivity skin tests
b. abnormal cellular immune response
c. slightly decreased CD4:CD8 ratiod. reduced natural killer cell cytotoxicity
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DIAGNOSIS
Any patient with persistent, unexplainedlymphadenopathy unassociated with anobvious underlying inflammatory orinfectious process should have a chestradiograph to identify the presence of amediastinal mass before undergoing node
biopsy
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Evaluation includes History
physical examination
imaging studies
chest radiograph
CT scans of the chestabdomen and pelvis
gallium scan
positron emission tomography (PET) scan.
L b t t di
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Laboratory studies
complete blood cell count (CBC
- to identify abnormalities that might suggestmarrow involvement
erythrocyte sedimentation rate (ESR)
serum copper and serum ferritin levels
-if abnormal at diagnosis, serve as a baseline toevaluate the effects of treatment
Li f ti t t
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Liver function tests
-influence treatment and treatment complications
chest radiograph
- for measuring the size of the mediastinal mass inrelation to the maximal diameter of the thorax
Chest CT
-defines the extent of a mediastinal mass if present
- identifies hilar nodes and pulmonary parenchymalinvolvement, which may not be evident on chestradiographs
Abdominal CT or MRI
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Abdominal CT or MRI
-identify gross subdiaphragmatic involvement of nodesand enlargement and defects in the liver and spleen
Bone marrow aspiration and biopsy
performed with advanced disease (stage III or IV) or B
symptoms (fever, weight loss, night sweats)
Bone scans
performed in patients with bone pain and/or elevatedalkaline phosphatase
ll
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Gallium-67 scan
- helpful in identifying areas of increased uptake, which
can then be re-evaluated at the end of treatment- especially in patients with mediastinal masses that donot resolve completely on chest radiographs or CT
Fluorodeoxyglucose (FDG)-PET
- has advantages over gallium-67 scanning because thescan is a 1-day procedure
- higher resolution, better dosimetry, and less intestinalactivity
-greater quantitation potential
Ann Arbor Staging Classification for Hodgkin
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Ann Arbor Staging Classification for Hodgkin
Disease
STAGE DEFINITIONI Involvement of a single lymph node (1) or of a
single extralymphatic organ or site (IE)II Involvement of two or more lymph node regions
on the same side of the diaphragm (II) or localizedinvolvement of an extralymphatic organ or site and one or morelymph node regions on the same side of the diaphragm (IIE)
III Involvement of lymph node regions on both sides ofthe diaphragm (III), which may be accompanied by involvementof the spleen (IIIS) or by localized involvement of an
extralymphatic organ or site (IIIE) or both (IIISE)
IV Diffuse or disseminated involvement of one or moreextralymphatic organs or tissues with or without associatedlymph node involvement
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STAGE DEFINITION
I Involvement of a single lymph node (1) or of a singleextralymphatic organ or site (IE)
II Involvement of two or more lymph node regions on the same sideof the diaphragm (II) or localized involvement of anextralymphatic organ or site and one or more lymph node regions
on the same side of the diaphragm (IIE)
III Involvement of lymph node regions on both sides of thediaphragm (III), which may be accompanied by involvement ofthe spleen (IIIS) or by localized involvement of an extralymphaticorgan or site (IIIE) or both (IIISE)
IV Diffuse or disseminated involvement of one or moreextralymphatic organs or tissues with or without associated lymphnode involvement
TREATMENT
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TREATMENT Chemotherapy and radiation therapy are effective in the
treatment of HD.
Pediatric patients
- combined chemotherapy with or without low-dose
involved field radiation therapy. determined largely by:
disease stage
age at diagnosis
presence or absence of B symptoms
presence of hilar lymphadenopathy or bulky nodaldisease.
Radiation therapy alone
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Radiation therapy alone
standard doses of 3,5004,000 cGy, initially
resulted in prolonged remissioncure rates of 4095% in patients with surgically low-staged HD
This treatment approach resulted in significant long-term morbidity in pediatric patients:
growth retardation
thyroid dysfunction cardiac and pulmonary toxicity
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The MOPP regimen(mechlorethamine [nitrogen mustard], vincristine,procarbazine, and prednisone)
introduced in 1964 was the first combinationchemotherapy
complete response rate of 7080% cure rate of 4050% at 10 yr in patients with advanced
stage disease
Associated with significant acute and long-term
toxicity.
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COPP/ABV
(cyclophosphamide, vincristine, procarbazine,prednisone/doxorubicin, bleomycin andvinblastine)
minimum of six cycles of chemotherapy
cumulative toxicity
second malignancies
sterility
cardiac and pulmonary dysfunction
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RELAPSE
occur within the first 3 yr from diagnosis
as late as 10 yr have been reported
Poor prognostic features
tumor bulk
stage at diagnosis
presence of B symptoms.
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Patients who never achieve remission or relapse
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PROGNOSIS
patients with favorable prognostic factors andearly-stage disease have
a. event-free survival (EFS) of 8590%
b. overall survival (OS) at 5 yr of 95%.
Patients with advanced stage disease have an EFS
and OS of 8085% and 90%, respectively
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Prognosis after relapse depends
a. time from completion of treatment to recurrenceb. site of relapse (nodal vs. extranodal)
c. presence of B symptoms at relapse
Patients who relapse >12 mo after chemotherapy aloneor combined modality therapy
a. best prognosis
b. usually respond to additional standard therapyc. resulting in a long-term survival of 6070%
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myeloablative autologous stem celltransplant in patients with refractorydisease or relapse within 12 mo of therapy
results in a long-term survival rate of 4050%.
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Non-Hodgkin
Lymphoma
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Non-Hodgkin Lymphoma approx. 60% of all lymphomas in children and
adolescents
represents 810% of all malignancies in children between519 yr of age
annual incidence in the USA of 750800 cases per year inchildren 19 yr of age
survival rates
9095% for localized disease6090% with advanced disease.
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EPIDEMIOLOGY
most children and adolescents with NHLpresent with de novo disease
small number of patients develop NHLsecondary to specific etiologies
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Inherited or acquired immune deficiencies
(e.g., severe combined immunodeficiencysyndrome, Wiskott-Aldrich syndrome)
viral etiologies (e.g., HIV, EBV)
genetic syndromes (e.g., ataxia-telangiectasia,
Bloom syndrome)
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