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Cancers of the Bone Marrow: A Cancers of the Bone Marrow: A

Cancers of the Bone Marrow: A - PowerPoint Presentation

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Cancers of the Bone Marrow: A - PPT Presentation

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

aml uptodate leukemia treatment uptodate aml treatment leukemia acute accessed bone post waltham mds marrow diagnosis clinical myeloid risk

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Slide1

Cancers of the Bone Marrow: A Clinical Perspective

Mary Ward, RN, BS, CTR

Slide2

Objectives

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

Slide3

What 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

Slide4

Cancers that Affect the Bone Marrow

Myelodysplastic

Syndromes

Leukemias

Lymphomas*

Plasma Cell Myelomas

Slide5

Case 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;

Slide6

Case Presentation: JF

Chest x-ray

CT

abd

Labs: CBC with differential and CMP

Peripheral blood smear

Slide7

Case 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

Slide8

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

Slide9

Epidemiology and Risk Factors

Most common acute leukemia in adults

Median age at diagnosis is 65 years old

Male to female ratio of 5:3

Slide10

Risk Factors

Environmental

Chemicals

Radiation

Tobacco

chemotherapy drugs

Genetic abnormalities

Trisomy 21,

Fanconi’s

anemia, Bloom’s syndrome

Slide11

AML: Diagnostic Workup

Peripheral blood smear

Bone marrow aspiration and biopsy*

Cytogenetics

*

Immunophenotyping

*

Slide12

AML 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

Slide13

AML 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

Slide14

AML 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

Slide15

Treatment 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

Slide16

Factor

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

Slide17

The 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

Slide18

Treating 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

Slide19

AML 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

Slide20

Acute 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

Slide21

Clinical 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

Slide22

APL 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

Slide23

Diagnostic 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

Slide24

Treatment of APL

May span 1-2 years total

Remission induction

Consolidation

Maintenance

Slide25

Treatment 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

Slide26

Treatment of APL

Consolidation:

Arsenic Trioxide followed by a combination of an

antrhacycline

plus ATRA

Maintenance

ATRA daily for one year

Slide27

Coding 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

Slide28

Myelodysplastic

Syndromes

Slide29

Myelodysplastic 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)

Slide30

MDS: 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

)

Slide31

Clinical 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

Slide32

Diagnostic 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

Slide33

Types 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

Slide34

MDS: 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

Slide35

MDS: 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

Slide36

Classification 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

Slide37

IPSS-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

Slide38

Treatment of MDS

Asymptomatic disease: watch and wait

When patients develop transfusion* requirement or recurrent infections, this may herald the need for treatment

Slide39

Treatment 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

Slide40

Treatment 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

Slide41

MDS 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

Slide42

Therapy 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

Slide43

Multiple Myeloma: Plasma Cell Myeloma

Slide44

Multiple 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

Slide45

Multiple 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

Slide46

Diagnostic 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

Slide47

Symptoms 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

Slide48

Diagnosis

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

Slide49

Diagnosis

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

Slide50

Related Conditions

MGUS

Smoldering MM*

Non-secretory MM*

Plasma cell leukemia*

Solitary

plasmacytoma

Solitary

extramedullary

plasmacytoma

Slide51

Staging MM

Durie

-Salmon Staging

M-protein levels

Calcium levels

Bone damage

Hemoglobin

International Staging System

Beta-2

microglobulin

Serum albumin

Slide52

Transplant 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

Slide53

Treatment 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:

UpToDate

, Post TW (Ed)

UpToDate

, Waltham, MA (accessed 2/12/15.)

Slide54

Multiple 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

Slide55

Summary

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

Slide56

How can you become an expert in abstracting any kind of bone marrow cancer?

Slide57

http://seer.cancer.gov/seertools/hemelymph/

Slide58

http://seer.cancer.gov/seertools/hemelymph/

Slide59

http://seer.cancer.gov/seertools/hemelymph/

Slide60

http://seer.cancer.gov/seertools/hemelymph/

Slide61

Slide62

AML, 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

Slide64

References

Acute Myeloid Leukemia, NCCN Clinical Practice Guidelines in Oncology, version 1.2015, (2015)NCCN.org.(Accessed 2/24/15)

Aster, J and Stone, R. Clinical manifestations and diagnosis of the

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syndromes. In:

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, Waltham, MA. (Accessed 2/12/15.)

www.cancedr.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-staging

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Facility Oncology Registry Data Standards

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Estey,E

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Larson, R. Post-remission therapy for acute myeloid leukemia in younger adults.

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Slide65

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