C linical Perspective Mary Ward RN BS CTR Objectives To increase the Cancer Registrars knowledge of the disease process of select cancers of the bone marrow from a clinical perspective Discuss the pathogenesis clinical evaluation and treatment options of AML APL MDS and Multiple Myelom ID: 792033
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Slide1
Cancers of the Bone Marrow: A Clinical Perspective
Mary Ward, RN, BS, CTR
Slide2Objectives
To increase the Cancer Registrar’s knowledge of the disease process of select cancers of the bone marrow from a clinical perspective
Discuss the pathogenesis, clinical evaluation and treatment options of AML, APL, MDS and Multiple Myeloma
Describe clinical distinctions that correspond with some of the ICD-0-3 codes for patients diagnosed with AML
Slide3What does the Bone Marrow Do?
Produces all the elements of the blood
RBCs
Platelets
WBCs
Proliferating marrow is found in certain areas of the body of adults
Slide4Cancers that Affect the Bone Marrow
Myelodysplastic
Syndromes
Leukemias
Lymphomas*
Plasma Cell Myelomas
Slide5Case Presentation: JF
68
yo
wmm
presents to PCP
c/o fatigue, malaise x
6 weeks,
ill-defined fevers and intractable infection
infection treated with
abx
x2;
weight loss of 10
lbs
, decreased appetite, easy bruising on his extremities
PE revealed
wm
in
no acute distress; presents with nonproductive cough, fever of 101.9
o
, no
lymphadeopathy
, noted several small bruises on LT arm and RT leg; no
ictera
, no jaundice;
Slide6Case Presentation: JF
Chest x-ray
CT
abd
Labs: CBC with differential and CMP
Peripheral blood smear
Slide7Case Presentation: JF
JF
is admitted to the inpatient oncology unit at Home Base Hospital
Ongoing diagnostic workup would include:
Uric Acid level
Bone Marrow biopsy and aspirate
Leukemia and Lymphoma panel
HLA typing
Type and Cross for transfusions
Consult to
Heme
/
Onc
AML: Defined
A group of hematopoietic neoplasms that affect the precursor cells of the myeloid cell line
The proliferation of the precursor cells causes a reduced capacity of the mature cells to develop
Slide9Epidemiology and Risk Factors
Most common acute leukemia in adults
Median age at diagnosis is 65 years old
Male to female ratio of 5:3
Slide10Risk Factors
Environmental
Chemicals
Radiation
Tobacco
chemotherapy drugs
Genetic abnormalities
Trisomy 21,
Fanconi’s
anemia, Bloom’s syndrome
Slide11AML: Diagnostic Workup
Peripheral blood smear
Bone marrow aspiration and biopsy*
Cytogenetics
*
Immunophenotyping
*
Slide12AML Classification
FAB
WHO
Histology
Code
M0
AML
with minimal differentiation
9872/3
M1
AML without maturation
9873/3
M2
AML with maturation
9874/3
M3
Acute
promeylocytic
leukemia with t(15:17) q(22;q12)
PML-RARA
9866/3
M4
Acute
myelomonocytic
leukemia
9867/3
M5a
Acute
monoblastic
/acute
monocytic
leukemia
9891/3
M5b
Acute
monoblastic
/acute
monocytic
leukemia
9891/3
M6
Acute
erythroid
leukemia
M7
Acute
megakaryoblastic
leukemia
9910/3
Slide13AML with Recurrent Genetic Abnormalities
AML with t(8;21)(q22;122),
RUNX1-RUNX1T1
Favorable prognosis in adults; seen in younger
adults overall
9896/3
AML with
inv
(16)(p13q22) or t(16;16)(p13;q22), CEFB-MYH11
Favorable prognosis with standard therapy
9871/3
AML
with t(9;11)(p22;q23); MLLT3-M-LL
Unusual age distribution-seen
in ¾ of children >1
yr
old; very poor prognosis
9897/3
AML with t(6;9)(p23;q34); DEK-NUP214
High rate of FLT3-ITD mutations which
is conveys a poor prognosis
9865/3
AML with
inv
(3)(q21q26:2) or t(3;3)(q21;126:2); RPN1-EV11
Commonly presents with increase
megakayocytes
, many morphologically
abnormal
9869/3
AML (
magakayoblastic
) with t(1;22)(p13;q13;q13);
RBN15-MKL1
Rare; sometimes presents as a mass and mimics sarcoma
9911/3
Slide14AML with Recurrent Genetic Abnormalities
Codes that do not need a 20% blast for definitive diagnosis:
AML with t(8;21)(q22;q22), RUNX1-RUNX1T1
AML with
inv
(16)(p13q22) or t(16)(p13;q22), CEFB-MYH11
APL with t(15;17)(q(22;112), PML-RARA
Slide15Treatment Planning
Standard Treatment
Induction chemotherapy 7+3 regimen
Cytarabine
plus an
anthracycline
Post Remission Treatment: based on Risk Stratification
Hematopoeitic
Stem Cell Transplant
Consolidation chemotherapy: HDAC: high-dose
Ara
-C,
cytarabine
-one dose every 28 days for 3-4 doses
Slide16Factor
Favorable
Unfavorable
Age
<50 years
>60 years
Leukemia
De novo
secondary
WBC
<25,000
>100,000
FAB subtype
M3, M4
M0, M5, M6, M7
Cytogenetics
T(15;17), t(8;21) in(16) normal: RUNX1-RUNX1T1;
Abnormalities of
chr.
5, 7, multiple, >3 abnormalities; 11q23, t (6;9);
inv
3
Extramedullary disease
Absent
present
Auer rods
Present
Absent
Phenotype
CD 34-
CD34+;CD56+
Other
Nucleophosmin
1 (NPM-1), CEBPA
FLT-3 mutation; KIT mutations
Slide17The Older Adult with AML
Factors that contribute to poor outcomes:
Poorer performance status
Higher incidence of multidrug resistance
Lower percentage of favorable
cytogenteics
Higher percentage of unfavorable
cytogenetics
Higher treatment-related morbidity and mortality
Higher incidence of treatment-resistant disease
Lower complete remission rates, shorter remission durations, shorter median overall survival
Fewer opportunities for
allo
HCT
Slide18Treating the Older Adult with AML
Favorable or intermediate risk patients
Induction therapy 7+3 regimen
Unfavorable risk or patients with significant comorbidities
Supportive care
Transfusions,
antibiotics, low-dose chemotherapy
Slide19AML Coding Tips
Histology Coding
Enter a provisional diagnosis, NOS, until a more specific diagnosis is made
There is no time limit
Treatment Coding
1
st
course treatment includes all remission-inducing and remission-maintaining therapies
Treatment can span a year or more
Supportive care is not coded as treatment
Slide20Acute Promyelocytic
Leukemia
Biologically and clinically distinct variant of AML
FAB classification of AML-M3
WHO classification: APL with t(15;17)(q24.1;q21.1); PML-
RARa
(9866/3)
Incidence: 5-8% of all AML cases
Age-predominately adults in mid-life
Slide21Clinical Manifestations of APL
Presents as a clinical emergency with a high rate of early mortality
Often due to hemorrhage from coagulopathy
Presenting symptoms typically secondary to pancytopenia: anemia, neutropenia, thrombocytopenia
Easy fatigability
Infections
Bleeding
Bleeding for APL patients may be secondary to DIC
Slide22APL and DIC
APL is often manifested by Disseminated Intravascular Coagulation
DIC is a cascade of bleeding and
micro clotting
that leads to a depletion of clotting factors and platelets
Ultimately it leads to hemorrhage in various
sites in the body
This is a medical emergency
Untreated it may lead to pulmonary or cerebral hemorrhage and possible death due to hemorrhage
May be present at diagnosis or at initiation of cytotoxic therapy
Induction of therapy improves condition
Slide23Diagnostic Criteria of APL
Suspected by the characteristic morphology of the leukemic cells
Presence of severe coagulopathy
The Non-granular form of APL presents with leukopenia
Diagnosis is confirmed by testing for the characteristic PML-RARA fusion gene or associated chromosomal translocation
Usually by FISH testing
Slide24Treatment of APL
May span 1-2 years total
Remission induction
Consolidation
Maintenance
Slide25Treatment of APL
Induction
Treatment should be initiated as soon as APL is suspected
Median survival of <1 month without treatment
ATRA-Retinoic Acid
Mechanism: induces tumor cell differentiation and
maturation
If the patient is found to have another type of leukemia, ATRA will be d/
c’d
Plus chemotherapy
An
anthracycline
and possibly
Cytarabine
Slide26Treatment of APL
Consolidation:
Arsenic Trioxide followed by a combination of an
antrhacycline
plus ATRA
Maintenance
ATRA daily for one year
Slide27Coding Tips for APL
APL is considered a distinct variant of AML and should be coded as such
Per the SEER Antineoplastic Drug Database
ATRA is coded
Code under “Other Treatment” and code as (1), Cancer treatment not otherwise assigned
Arsenic Trioxide is not a coded drug at this time
The precise mechanism of action has not been fully determined
Slide28Myelodysplastic
Syndromes
Slide29Myelodysplastic Syndromes
Group of heterogeneous malignant hematopoietic stem cell disorders
Characteristics
Dysplastic and ineffective blood cell proliferation
Variable risk of transformation to acute leukemia
May occur de novo or after exposure to mutagenic therapy (radiation, chemotherapy)
Slide30MDS: Epidemiology and Risk Factors
Age distribution
Median age at diagnosis: 65
Gender
Male predominance
Environmental risk factors:
Chemical exposure: benzene, radiation, tobacco, chemotherapy drugs)
Genetic risk factors
trisomy 21,
Fanconi
anemia, Bloom syndrome
Comorbid conditions as
risk factors
Benign hematologic diseases (paroxysmal nocturnal
hemagloinburia
, congenital
nuetropenia
)
Slide31Clinical Presentation of MDS
Non-specific signs and symptoms
Many patients are asymptomatic
Most common presenting signs are from a
cytopenia
Anemia is the most common
cytopenia
Infection is a less common presentation
Slide32Diagnostic Criteria of MDS
Clinical
evaluation with
pathologic
evaluation of peripheral blood and bone marrow
Unexplained changes at least one lineage that quantifies as a
cytopenia
Morphologic dysplasia on visual inspection
Blast forms <20% of total cells
Slide33Types of MDS
Refractory
anemia
<5% blasts; only anemia
9980/3
Refractory neutropenia
>10% dysplastic neutrophils
9991/3
Refractory
thrombocytopenia
>10%
dysplastic megakaryocytes; cytogenetic studies helpful
9992/3
Refractory anemia with ring
sideroblasts
>15%
ring
sideroblasts
in BM; <5% blasts in peripheral blood;
9982/3
Refractory anemia with
multilineage
dysplasia
Bi-
cytopenia
/pancytopenia
and dysplastic changes in 2 or more myeloid lines
9985/3
Refractory anemia with excess blasts
Multiple types based
on blast percentage from 1-19%
9983/3
MDS associate
d with isolated del 5q
Associated with specific genetic abnormality
9986/3
Slide34MDS: Chromosomal Abnormalities
Most common:
Del(5q), -7, trisomy 8, del (20q) and loss of the Y chromosome
Single or multiple chromosomal changes may be present at the time of diagnosis
Chromosomal changes may occur during the course of the disease
Do not change the coding of MDS once the initial diagnosis has been made
Slide35MDS: 5q-Syndrome
Distinctive profile
Median age at diagnosis is 65-70 years
Female predominance of 7:3
T
ypical presentation
refractory macrocytic anemia
normal or elevated platelets
absence of neutropenia
Benign course of disease
Projected median survival is 63 months
Likelihood of transformation to AML is low
Slide36Classification of MDS-IPSS-R
International Prognostic Scoring System-Revised
Calculates prognosis based on:
Bone marrow blast percentage
Karyotype (very good, good, intermediate, very poor)
Hemoglobin
Platelets
Absolute Neutrophil count
Stratifies patients into 5 risk categories
Survival and AML evolution
Slide37IPSS-R Scoring System
Risk Group
IPSS-R Score
Median Overall
Survival (years)
Median time to 25 percent AML evolution (years)
Very low
<1.5
8.8
>14.5
Low
>1.5 to 3.0
5.3
10.8
Intermediate
>3 to
4.5
3.0
3.2
High
>4.5 to 6
1.6
1.4
Very High
>6
0.8
0.7
Slide38Treatment of MDS
Asymptomatic disease: watch and wait
When patients develop transfusion* requirement or recurrent infections, this may herald the need for treatment
Slide39Treatment of MDS
Clinical trials
Supportive care, antibiotics, and transfusions
Low intensity chemotherapy
Hematopoietic growth factors,
azacitidine
,
decitabine
May improve QOL, but not curative
High intensity therapy
Combination chemotherapy and HCT
Slide40Treatment of MDS
Most treatment regimens continue until disease progression
Disease progression demonstrated by
Worsening
cytopenias
Increase in the percentage of bone marrow blasts
Progression to a more advanced MDS FAB subtype
Slide41MDS Coding Tips
Keep the initial diagnostic code of MDS once established
If transformation to AML occurs, this is a new primary
Often transfusions and growth factors are initial forms of treatment
Neither of these are currently coded for MDS
Slide42Therapy Related Myeloid Neoplasm (9920/3)
Occurs after treatment
Chemotherapy, radiation, stem cell transplant or bone marrow transplant,
Peripheral blood and bone marrow are principle sites
May present as either t-MDS or t-AML
WHO has one group
Must have MD statement
Slide43Multiple Myeloma: Plasma Cell Myeloma
Slide44Multiple Myeloma
Disease characteristic
Clinical manifestation
Neoplastic
proliferation of plasma cells in bone marrow
Bone pain;
anemia,
hypercalcemia
; pathologic fractures
Plasma
cell p
roduction of monoclonal immunoglobulin
Increased total serum
and/or urine concentration of M protein
Plasma cell infiltration of organs;
organ damage from immunoglobulin light chains
Kidney damage
Slide45Multiple Myeloma: Epidemiology
Race
African Americans:
Caucasian 2 to 3 times higher
Gender
Slightly more frequent
in men than women
Age
Average age at diagnosis: 66
Slide46Diagnostic Criteria
Clonal bone marrow plasma cells
>
10%
Or biopsy proven bony or soft tissue
plasmacytoma
PLUS one of the following:
Presence of related organ or tissue impairment:
Increased Calcium level
Renal insufficiency
Anemia
Bone lesions
Presence of a biomarker associated with end-organ damage
Slide47Symptoms of MM
Symptom
Cause
C
alcium levels increase (
hypercalcemia
)
Product
of osteoclast activating factors
R
enal dysfunction
Damage from
light chain infiltration; M globulin infiltration and damage to kidney
A
nemia
Secondary to bone marrow replacement
of normal
hematopoeitic
tissue by tumor and disruption of bone marrow microenvironment
B
one lesions,
osteolytic
The hallmark sign of MM; due to increased osteoclast activity with suppression
of osteoblasts
Slide48Diagnosis
Laboratory Testing
Protein electrophoresis of serum (SPEP)
Protein electrophoresis of aliquot of urine (UPEP)
Serum free light chain assay (FLC)
Urinalysis
Myeloma cast
uropathy
Peripheral smear
Bone marrow exam
IHC,
cytogenetics
, free light chain assay
Slide49Diagnosis
Radiographic Studies
Plain radiographs of the
humeri
and femoral bones
Key component to
pt
evaluation
CT, MRI and PET/CT scan
Bone scan is not a preferred method of evaluation
Slide50Related Conditions
MGUS
Smoldering MM*
Non-secretory MM*
Plasma cell leukemia*
Solitary
plasmacytoma
Solitary
extramedullary
plasmacytoma
Slide51Staging MM
Durie
-Salmon Staging
M-protein levels
Calcium levels
Bone damage
Hemoglobin
International Staging System
Beta-2
microglobulin
Serum albumin
Slide52Transplant Eligibility
Patients are considered ineligible for one of the following
Age
>
77
Bilirubin
>
2.0 mg/
dL
ECOG performance status 3 or 4
New York Heart Association functional status Class III or IV
Slide53Treatment for MM
High Risk
Intermediate Risk
Standard Risk
4 cycles of
VRd
or
VCd
Assess Response/collect Stem cells
Autologous HCT if eligible
Bortezomib
-based maintenance
4 cycles of
VCd
Autologous HCT if eligible
Bortezomib
-based maintenance
Eligible for transplant?
Yes
No
4 cycles of Rd or
VCd
Autologous HCT
Lenolidomide
--based maintenance
Rd until progression
Rajkumar
, S. Overview of the management of multiple myeloma
.
In:
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Slide54Multiple Myeloma Coding Tips
Dexamethasone is often part of the induction therapy
Maintenance therapy can go on for an extended period of time
Maintenance would not be considered subsequent treatment if it was planned
Slide55Summary
Coding histology should be as specific as possible for all these patients
Often a final diagnosis takes many weeks
Treatment for many hematologic malignancies can span a year or more
Treatment should be considered subsequent if it has not been considered as part of the initial treatment plan
Treatment would be considered subsequent if the patient showed signs of disease progression
Slide56How can you become an expert in abstracting any kind of bone marrow cancer?
Slide57http://seer.cancer.gov/seertools/hemelymph/
Slide58http://seer.cancer.gov/seertools/hemelymph/
Slide59http://seer.cancer.gov/seertools/hemelymph/
Slide60http://seer.cancer.gov/seertools/hemelymph/
Slide61Slide62AML, NOS, 9861/3
AML with
inv
(16)(p13.1q22) 9871/3
http://seer.cancer.gov/seertools/hemelymph/
Slide63“Any fool can know. The point is to understand.”
Albert Einstein
Slide64References
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Facility Oncology Registry Data Standards
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