Overview of the

Diagnosis and

Treatment of

Lymphoma and

Leukemia

Kimberly Miller, BSN, RN, BMTCN™

Nebraska Medicine

• Discuss the different types of lymphoma and

leukemia, including presenting symptoms

• Discuss common treatments for lymphoma

and leukemia, including symptom

management

• Identify important genetic markers for each

disease and discuss the impact of these

genetic changes on treatment planning

Objectives

Lymphoma

Lymphoma

• A cancer of certain types

of white blood cells called

lymphocytes

• These cells circulate

throughout the body in the

blood stream and in the

lymphatic system, which is

part of the body’s immune

system

Lymphoma

Hodgkin Lymphoma

• Incidence: 9,050

• Deaths: 1,150

• Bimodal age distribution early to late 20’s and second peak 80’s

Non-Hodgkin Lymphoma

• Incidence: 71,850

• Deaths 19,790

• Increase incidence with age

• Most are B cell and express CD20

Incidence Rate

Malignancy Incidence –

US

Incidence -

IA

Non-Hodgkin

Lymphoma

19.2 22.5

SEER Fact Sheets

Epidemiology

• Hodgkin’s Lymphoma – Unknown, ? EBV

• Non-Hodgkin’s Lymphoma • Viral/Bacterial

• H. pylori – Gastric MALT NHL

• Epstein Barr Virus – Burkitt’s lymphoma

• Hepatitis C – some types indolent NHL (Lymphoplasmacytic, Marginal zone)

• HTLV-1 (Adult T-cell leukemia/lymphoma)

• Environmental/Occupational

• Pesticide/Herbicide exposure

• Leather workers, printers, medical professionals

• Autoimmune Diseases

• Rheumatoid arthritis, Sjogren’s Syndrome

Epidemiology

• Non-Hodgkin’s Lymphoma • Decreased immune system

• Immuosuppressive drugs – organ or bone marrow transplantation

• Prior chemotherapy and/or irradiation

• HIV /AIDS

• Hereditary - ? Environmental vs. truly hereditary factors

• Dietary

• Low vegetable intake – increased NHL

• Slight protective effect of moderate alcohol in female non-smokers

• Red meat – slight increase in NHL

Hematological Malignancies in Adults, 2013

Signs and Symptoms

All stages • Lymphadenopathy

• Often asymptomatic

• Fatigue

• Cough, SOB

• Abdominal pain, early

satiety

• B-symptoms

• Fever

• Weight loss

• Night sweats

Advanced Disease • Fatigue

• Anemia

• Tumor lysis

• Hydronephrosis

• Bowel obstruction

• Superior vena cava

syndrome

• Pleural effusions

Ansell et al, Mayo Clinic Proceedings, 2005;90:1087-1097; Kurtin, The Oncology Nurse, 2009;1(6):12,30

Lymphadenopathy

Diagnosis

• Physical exam

• Laboratory

• CBC with differential, LDH, Comprehensive Metabolic

Panel, Hepatitis B, HIV, uric acid

• Tissue biopsy

• Bone marrow aspirate and biopsy

• MUGA scan/echocardiogram

• CT or PET-CT

• Site specific – colonoscopy, lumbar puncture, MRI

Ansell et al, Mayo Clinic Proceedings, 2005;90:1087-1097; Kurtin, The Oncology Nurse, 2009;1(6):12,30

PET-CT

• Used for initial stating and evaluating response to

treatment

• Focal FDG uptake within bone or BM, liver, and

spleen is highly suggestive for involvement of

high grade lymphoma and may obviate the need

for BMBX

• PET-CT can miss low-volume BM involvement of

<20% and co-existent low-grade lymphoma

• End of treatment remission assessment is more

accurate with PET-CT than with CT alone for

patients with HL, DLBCL, and higher burden FL

• CT is indicated for non-avid histologies

• CLL/SLL, MZF, MF

Barrington et al, J Clin Oncol, 2014; Pfreundschuch, Blood 116 (24): 5103. 2010

Deauville Scale

1. No uptake

2. Uptake < mediastinum

3. Uptake > mediastinum < liver

4. Uptake moderately higher than liver

5. Uptake markedly higher than liver and/or

new lesions

X. New areas of uptake unlikely to be related

to lymphoma

Lymphoma Staging

Ann Arbor Staging System

For all stages

A No symptoms

B Weight loss >10% over 6 months, fever (380 C), drenching night sweats

Armitage JO. CA Cancer J Clin. 2005;55:368-376.

Stage I Stage II Stage III Stage IV

Single lymph node region

2 or more node regions, same side as diaphragm

Node regions, both sides of diaphragm

Diffuse extra- lymphatic involvement

Lungs

Liver

Bone

Non-Hodgkin

Lymphoma

Most Common Subtypes

of NHL

Percentages are of all NHLs. MALT=mucosa-associated lymphoid tissue; NK=natural killer.

Lichtman MA. Williams Hematology. 7th ed. New York, NY: McGraw Hill. 2006;1408.

T and NK cell

(12%)

Other subtypes

(9%)

Burkitt (2.5%)

Mantle cell (6%)

Diffuse large B cell

(DLBCL) (30%)

Follicular (25%)

Small lymphocytic

(7%) MALT-type

marginal-zone B cell (7.5%)

Nodal-type marginal-zone

B cell (<2%) Lymphoplasmacytic

(<2%)

WHO B-Cell NHL (85%)

• B-cell CLL/small lymphocytic lymphoma

• B-cell prolymphocytic leukemia

• Lymphoplasmacytic lymphoma (Waldenströms)

• Splenic marginal zone

• Hairy cell leukemia

• Extranodal marginal zone (MALT)

• Mantle Cell lymphoma

• Primary cutaneous follicle center cell lymphoma

• Nodal Marginal Zone

• Diffuse large B-cell

Hematological Malignancies in Adults, 2013

• Lymphomatoid granulomatosis

• Burkitt lymphoma

• Primary mediastinal (thymic) large B-cell

lymphoma

• Intravascular large B-cell lymphoma

• Alk+ large B-cell lymphoma

• Plasmablastic lymphoma

• Primary effusion lymphoma

• Follicular lymphoma

WHO B-Cell NHL (cont.)

Hematological Malignancies in Adults, 2013

T-cell NHL Types (15%)

• T-cell prolymphocytic leukemia

• T-cell large granular lymphocytic leukemia

• Sezary syndrome

• Aggressive NK cell leukemia

• Extranodal NK/T cell lymphoma – nasal and nasal type

• Mycosis fungoides

• Primary cutaneous anaplastic NK/T cell lymphoma

• Subcutaneous panniculitis-like T-cell lymphoma

• Enteropathy-type intestinal T-cell lymphoma

• Hepatosplenic gamma/delta T-cell lymphoma

• Angioimmunoblastic T-cell lymphoma

• Peripheral T-cell lymphoma (Unspecified)

• Anaplastic large cell lymphoma, systemic type

• Adult T-cell leukemia/lymphoma (HTLV-1+)

Hematological Malignancies in Adults, 2013

Diffuse Large B Cell Lymphoma

Intermediate and High Grade NHL

(Aggressive)

• Aggressive progression of disease

• Usually more sensitive to chemotherapy

• Higher response rates if treated

• 30%- 60% of patients can be cured

• Most relapses occur within first 2 years

• 1/3 have “B” symptoms

• Stage: ½ to ¾ are extensive

• Presentation: lymphadenopathy most common but 1/3 extranodal (GI, liver, spleen, Waldeyer’s ring, skin, bone marrow, thyroid, GU, CNS, sinuses)

Diffuse Large B-Cell Lymphoma

• Most common sub-type of NHL

• 31% of all cases

• More common with advanced age

• 54% of NHL cases in patients > 65 years

• Majority of patients have advanced

disease at the time of diagnosis

• Stage III or stage IV

• Chemotherapy + rituximab is the primary

treatment approach in this disease

Ansell et al, 2005; NCI, 2014.

Criteria (“APLES”)

• Age (60 vs >60 years)

• Performance status (0 or 1 vs 2)

• LDH (1 vs >1 times normal)

• Extranodal sites (1 vs >1)

• Stage (I or II vs III or IV)

Risk group Factors

Low 0-1

Low-intermediate 2

High-intermediate 3

High 4-5

International Prognostic Index

The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med. 1993;329:987.

Follicular Lymphoma

Low Grade NHL (Indolent)

• Presentation: painless, slow growing, peripheral lymph node enlargement which may have waxed and waned; +/- splenomegaly or cytopenias

• Median survival 10 years

• Stage: rarely limited, usually extensive

• High response rate to first treatment regimens

• Invariably followed by relapse

• After relapse, lower response rates, shorter duration of response

• Felt to be incurable

• May transform to intermediate or high-grade survival < 1 year

• Many controversies related to treatment standards

Follicular B-Cell Lymphoma

• Second most common NHL

• Adults middle aged and older

• 40-60% will eventually transform (poorer prognosis)

• BM involvement common

• Circulating cells

• Most are B-cell types and CD20 positive

• Cytogenetic abnormality t(14;18)

• Subdivided into 3 categories:

• Small cleaved cell type (grade 1)

• Mixed small and large cleaved cell type (grade 2)

• Large cells (grade 3) sometimes considered intermediate

Follicular Lymphoma

Morphology

Grade 11

0–5

Centroblasts/hpf;

Centrocytes

Predominate2

Grade 21

6–15

Centroblasts/hpf2

Grade 31

>15

Centroblasts/hpf;

Centroblasts

predominate2

indicates centroblast.

hpf=high-power field.

1. Grades of follicular lymphoma—high power. http://pleiad.umdnj.edu/~dweiss/follicular/hi_all3_img.html.

Accessed May 21, 2007.

2. Harris NL et al. Ann Oncol. 1999;10:1419-1432.

Follicular Lymphoma International Prognostic Index (FLIPI)

Prognosis

Number

of

Factors

Patients

(%)

5-

year

OS

(%)

10-

year

OS (%)

Good 0-1 36 91 71

Intermediate 2 37 78 51

Poor ≥3 27 53 36

Solal-Céligny P et al. Blood. 2004;104:1258-1265.

Criteria

• Nodal sites (4 vs >4)

• LDH ( normal vs > normal)

• Age ( 60 vs >60 years)

• Stage (I or II vs III or IV)

• Hemoglobin (12 g/dL vs

<12 g/dL)

Cervical

Pre-auricular Upper cervical Median or lower cervical Posterior cervical Supraclavicular

Axillary

Axillary

Mesenteric Celiac

Splenic (hepatic) hilar

Portal

Mesenteric

Inguinal Inguinal

Femoral

Mediastinal

Paratracheal

Mediastinal

Hilar

Retrocrural

Para-aortic

Para-aortic

Common iliac

External iliac

Others: epitrochlear, popliteal

FLIPI Nodal Map

Indications for Therapy in Follicular

Lymphoma

• Progressive local disease or change in

tempo

• Systemic or constitutional symptoms

• Cytopenias due to marrow involvement

• High tumor burden

• Leukemic phase

• Organ invasion

• High-risk disease based on FLIPI score

• Transformation

Tan et al, Hematol Oncol Clin N Am 22 (2008) 863-882; Vilolo et al, Critical Reviews in Oncology/Hematology 66 (2008) 248-261

Peripheral T-Cell Lymphoma

Peripheral T-cell Lymphoma

• 5% incidence

• 4 categories

• Nodal, Extranodal, Leukemic/Disseminated,

Cutaneous

• 22 subtypes

• Low overall disease free survival

• Presentation: enlarged lymph nodes,

necrotic nasal/facial lesions, systemic

illness or pulmonary symptoms

Treatment Options for Lymphoma

• Chosen based upon:

• Sub-type of lymphoma

• Stage of lymphoma

• Site of lymphoma involvement (CNS

involvement – needs additional

chemo)

• Age and other health problems

(Special drug toxicities)

• Convenience issues

Surgery

• Primary role in diagnosis

• Assist in staging of disease

• Not effective in treatment of lymphoma

Watch and Wait Approach

• Asymptomatic Low Grade (Indolent)

• Regular routine physician visits every 2-3 months with lab and/or CT Scan

• Symptomatic or the disease progressing then other treatment measures need considered

• Need to consider the patients feelings and emotions

Radiation

• May be used alone (low grade stage I or II) or in combination with chemotherapy

• Consolidative therapy post transplant for known areas of bulky disease

• Toxicities are related to the dose and volume of tissue treated

• Common areas that are frequently irradiated:

• Upper Abdominal Field

• Pelvic Area

• Total Body Irradiation

• Mantle Field

Chemotherapy

• Single Agents • Indolent lymphomas that become

symptomatic

• Progressive disease

• Cannot deal with the watch and wait approach

• Combination Chemotherapy Agents • Used for all lymphomas either initially or

relapse

• Important chemo given in full doses and without delay to maximize the full potential of the chemotherapy

• Drug resistance is a barrier in the treatment

Chemotherapy Agents

• Steroids

• Chlorambucil

• Cyclophosphamide

• Fludarabine

• Mitoxantrone

• Doxorubicin

• Vincristine

• Etoposide

• Oxaliplatin

• Gemcitabine

• Vinblastine

• Carmustine

• Ifosfamide

• Cytarabine

• Methotrexate

• Bleomycin

• Cisplatin

• Melphalan

• Bendamustine

Examples of Some Combination

Regimens Used for NHL

• CHOP

• CNOP

• ESHAP

• MINE

• ICE

• FND

• Hyper-CVAD

• McGrath

• COPP

• EPOCH

• ProMACE-CytaBOM

• DHAP

• CHOEP

• CVP

• M-BACOD

• MACOP-B

• MINE-ESHAP

• **Rituximab **

Chemotherapy Continued

• Can be given concurrent or before radiation

• Intrathecal chemotherapy should be given:

• CNS involvement

• Testicular or Sinus Involvement

• AIDS related lymphoma

• Prophylaxis in Lymphoblastic and Burkitt’s Lymphoma

Salvage Chemotherapy

• 30%- 60% patients will not receive a

CR with initial treatment or will relapse

• Sometimes salvage chemotherapy will

be given in preparation for a transplant

Bhatt VR, Vose JM. Hematol Oncol Clin N Am 28 (2014) 1073–1095

Treatment Related Toxicities

Treatment Related

• Cytokine release

syndrome

• Tumor flare reactions

• Tumor lysis syndrome

• Peripheral neuropathy

• GI toxicities

• Fatigue

• Hematological toxicities

Late and Long-Term Effects

• Shingles

• Cardiac

• Pulmonary

• Peripheral neuropathy

• Infertility

• Secondary malignancy

Leukemia

What is Leukemia?

• Leukemia is an abnormality in

the proliferation of blood cells

that causes uncontrollable

growth and development of

immature cells

Leukemia

• General term for 4 different types of blood

cancer

• AML, ALL, CML, CLL

• Clonal hematopoietic disorder

• Affect uncommitted or partially committed

(developing) hematopoietic stem cells

• Myeloid vs. Lymphoid (rarely biphenotypic)

• Further classified by morphology,

cytochemistry, immunophenotype,

cytogenetics, and molecular changes

Types of Leukemia

• Acute Myelogenous

Leukemia (AML)

• New Cases: 20,830

• Deaths: 10,460

• Acute Lymphocytic

Leukemia (ALL)

• New Cases: 6,250

• Deaths: 1,450

• Chronic Myelogenous

Leukemia (CML)

• New Cases: 6,660

• Deaths: 1,140

• Chronic Lymphocytic

Leukemia (CLL)

• New Cases: 14,620

• Deaths: 4,650

SEERS Data

Incidence Rate

Malignancy Incidence –

US

Incidence -

IA

Leukemia 13.2 15.2

SEER Fact Sheets

Acute Myelogenous Leukemia

Acute Myelogenous Leukemia

• Most common acute leukemia in adults

• Incidence higher in adults over 40 (mean age 70 years)

• Progresses rapidly and fatal if within weeks if left untreated

• Risk Factors:

• Chemical Exposure

• Benzene (chromosomal damage)

• Pesticide

• Prior Hematologic Disorders

• MDS, CML, primary myelofibrosis, polycythemia vera

• Prior Chemo/Radiation

• Treatment for Breast Cancer, NHL, HD

• Genetic Disorders

• Down Syndrome

• Fanconi’s Anemia

Clinical Symptoms

• Effects on hematopoiesis • Fatigue, bruising, bleeding, infections, fever

• Leukostasis-mental status changes, SOB, CP

• Physical Findings • Pallor, cutaneous lesions, gingival hyperplasia

• Metabolic Effects • Hyperuricemia—tumor lysis syndrome

• Coagulopathies

• Disseminated intravascular coagulation (DIC)

• Due to release or pro-coagulants from abnormal granules in tumor cells.

WHO Definitions AML

• >20% or more blast in the peripheral

blood or BM

• May have <20% blast in BM or in

peripheral blood if AML with recurrent

cytogenetic abnormality

• t(8;21), t(15;17), inv(16), 11q23

• If recurrent cytogenetic abnormality is

present the blast percentage is irrelevant

AML Diagnostic Work-up

• Laboratory

• CBC, Chemistry, LDH, Uric Acid, Coagulation and DIC panels

• EKG

• Chest X-Ray

• Bone Marrow Diagnostic Testing

• Morphology

• Determines the type and lineage of cells present in the BM (>20% blast

supports the diagnosis of AML)

• Immunophenotyping/Flow Cytometry

• Detects cell surface markers which helps type and characteristics of AML

• Differentiates between ALL vs. AML

• Cytogenetics

• Evaluation of the DNA and chromosomal makeup of the cells which assist

with classification, prognosis and treatment decisions

• Most important prognostic finding

• Molecular genetics

• Detect the presence of genetic mutations that play role in prognostic and

therapeutic decision making (ie: FLT3, NPM1, CEBPA genes)

• Fluorescence in situ hybridization (FISH)

• Detects gene rearrangements in leukemic cells, which is important for

treatment decisions

• Lumbar Puncture

AML Treatment Regimens

Induction/Re-induction • 7+3

• 5+2

• FLAG

• HiDAC

• CLAG (salvage)

• Azacitidine (older

adults/palliation)

• Decitabine (older

adults/palliation)

• MEC (salvage)

• Clofarabine (salvage)

AML Consolidation

• HiDAC/iDAC

• Low-dose cytarabine (age

> 60 or poor performance

status)

• Low-dose cytarabine plus

anthracycline (age > 60

or poor performance

status)

AML Treatment Regimens (cont.)

• Prophylaxis

• cytarabine

• methotrexate

• Treatment

• Triple therapy

• Liposomal cytarabine

• Brain irradiation

Intrathecal Treatment for CNS

AML-M3 (APL)

Characterized by t(15;17) resulting in PML/RARa

fusion gene and transcript

Auer rods

AML M3 (APL) Treatment

• All-trans retinoic acid (ATRA) is

essential component of induction

regimen

• Anthracyclines needed for

sustained remission, role of

cytarabine controversial

• Maintenance treatment improves

survival in selected patients (high

WBC at presentation)

AML M3 (APL) Treatment

• Special Consideration:

• Favorable prognosis

• DIC common at presentation

• Beware of differentiation syndrome

• WBC, fever, HA, wt. gain,

pulmonary infiltrates

• Treatment: Steroids and

antibiotics

• Follow-up should include monitoring

• qualitative PCR for PML/RARa

AML- Transplant Options

• Transplant

• Young age

• High risk disease

• Relapse disease

• Good

performance

status

• Donor available

• No transplant

• Older age

• Favorable

cytogenetics

• Poor performance

status

• No donor

Acute Lymphoblastic Leukemia

Acute Lymphocytic Leukemia

• Incidence 1.5 per 100,000

• 60 % cases seen in children

• Second peak in adults around 60

• Risk Factors

• Environmental exposure

• Genetics

• 85% of cases and most important

independent prognostic factor for

predicting outcome

• Most common is Philiadelphia

chromosome t(9;22) resulting in BCR-

ABL fusion present in 11-29% of adults

Clinical Symptoms

• Effects on hematopoiesis

• Fatigue, bruising, bleeding, infections,

• Leukostasis-mental status changes,

SOB, CP

• Physical Findings

• Hepatosplenomegaly,

lymphadenopathy, weakness,

headache, testicular asymmetric

enlargement

ALL-Diagnosis Work-up

• Laboratory

• CBC, Chemistry, LDH, Uric Acid

• Lumbar Puncture

• Cytology

• Bone Marrow Biopsy

• Flow Cytometry

• Differentiates between ALL vs. AML

• Cytogenetics

Classification of ALL

• Precursor B-cell ALL

• Most common type

• Philadelphia + ALL

• t(9;21)

• Poor prognosis

• Mature B-cell ALL

• Burkitt’s lymphoma/leukemia

• Common in HIV patients

• Precursor T-cell ALL

• Poor prognosis

• Associated with HTLV-1 infection

Prognostic Factors in ALL

• Age

• Presenting WBC

• Immunophenotype

• Cytogenetics

• Time to first CR

• Minimal residual disease

• Favorable < 35 years

• WBC >30,000 (B-cell)

• WBC>100,000 (T-cell)

• T-ALL more favorable than B-

ALL

• Cytogenetics varies

• Favorable if within 4 weeks

• No minimal disease after

induction

Thomas et al., 2010; Campana, et al, 2010

Treatment of ALL for Adults

• Chemotherapy

• Hyper CVAD

• CALGB protocols

• Tyrosine kinase inhibitors along with therapy

for Philadelphia positive t(9;21) disease

• Maintenance for B-cell (2 years)

• Prednisone, Vincristine, 6-MP,

Methotrexate

• Transplantation

Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia

• Most common form of chronic leukemia in

adults

• Proliferation of mature lymphocytes

• Autoimmune diseases common

• Often in elderly

• Sometimes considered a non-Hodgkin’s

Lymphoma (Small lymphocytic lymphoma)

• Richter’s Transformation

Clinical Symptoms

• Asymptomatic

• Effects on hematopoiesis

• Fatigue, bruising, bleeding, infections,

• WBC can be extreme high (almost 100%

lymphocytes)

• Physical Findings

• Hepatosplenomegaly, lymphadenopathy,

weakness, headache

CLL- Diagnostic Work-up

• Laboratory

• CBC, Chemistry, LDH

• Lymph Node Biopsy

• Bone Marrow Biopsy

• Flow Cytometry

• ZAP-70 and CD38

• Cytogenetics t(11;14); 13q14.3

• FISH

• Molecular

• IGHV gene mutation analysis

CLL Classification (RAI)

Stage Extent of Disease Risk Median Survival (yr)

0 Lymphocytosis of

BM (40%) and blood

Low 10

1 Stage 0 plus

lymphadenopahy

Intermediate 7

2 Stage 0 or 1 plus

splenomegaly

and/or

hepatomegaly

Intermediate 7

3 Stage 0,1, or 2 plus

anemia (Hgb

<11.0g/dL)

High 2

4 Stage 0,1,or 2 plus

thrombocytopenia

High 2

Treatment of CLL

• Watch and Wait

• Chemotherapy

• Bendamustine -Chlorambucil

• Fludarabine *combination regimens

• Monoclonal Antibodies

• Rituximab

• Alemtuzumab

• Ofatumumab

• BTK inhibitors

• ibrutinib

• Transplantation

Chronic Myelogenous Leukemia

Chronic Myelogenous Leukemia

• Present very high WBC, all stages of myeloid

maturation increased, no increase in blast

• Specific cytogenetic abnormality

• t(9;22) = Philadelphia chromosome

• Without treatment all patients develop blast

crisis within 5-10 years

CML- Diagnosis

• Laboratory

• CBC, Chemistry, LDH

• Bone Marrow Biopsy

• Flow Cytometry

• Cytogenetics t(9;22)

• BCR-ABL fusion gene

Phases of CML

• Chronic Phase:

• Asymptomatic but have a predominance of white blood cells

• 80% of patients diagnosed in this phase

• Survival is about 4-6 years (before tyrosine kinase inhibitor therapy)

• Accelerated Phase:

• Transition to this phase over about 1 year and last 4-6 months

• Progressive leukocytosis, thrombocytosis or thrombocytopenia, basophils, splenomegaly, fever, bone pain and thrombotic or bleeding complications can occur

• Blast Phase:

• Increasing blast (>30%)

• Progressive splenomegaly despite treatment

• Phase last only a few month and survival is poor if the patient are untreated

Treatment of CML

• Leukopheresis

• Initial Treatment:

• Imatinib mesylate

• Other Treatment: • Dasatinib

• Nilotinib

• Ponatinib

• Bosutinib Interferon-alpha

• Hydroxyurea

• Transplantation

***Gold Standard for molecular analysis of treatment

response and residual disease is monitoring qualitative

polymerase chain reaction for BCR-ABL

Criteria for Response in CML

Complete Hematologic

Response

• Complete normalization of

peripheral blood counts with

leukocyte count < 10,000

• Platelet count < 450,000

• No immature cells such as

myelocytes, promyelocytes, or

blasts in peripheral blood

• No signs or symptoms of

disease with disappearance of

palpable splenomegaly

Cytogenetic Response

• Complete: no Ph+ metaphases

• Partial: 1-35% Ph+

metaphases

• Major: 0-35% Ph+ metaphases

(complete +partial)

• Minor:> 35% Ph+ metaphases

Criteria for Response in CML (cont.)

Molecular Response

• Complete molecular

response: BCR-ABL

mRNA undetectable by

RT-PCR

• Major molecular

response: >3 log

reduction in International

Scale of BCR-ABL mRNA

Nursing Issues to Consider

• Psychosocial issues

• Co-morbidities

• Fertility Issues

• Treatment Related Factors

• Tumor Lysis Syndrome Prophylaxis

• DIC

• Hyperleukocytosis

• Infection

• Differentiation Syndrome

Nursing Issues to Consider

• Long-term Survivorship Issues

• Graft-versus-host disease

• Follow-up labs

• APL and CML especially with PCR

• Heart failure

• Radiation toxicities

• Secondary malignancies

Genetics

p

Centromere

q

Genetics Basics

• Oncogenes

• Normally promote cell growth

• Mutation/overexpression causes cells to

grow uncontrollably

• Mutations acquired – chromosome

rearrangement or gene duplication

• Gas pedal is stuck

• Tumor Suppressor Genes

• Cause apoptosis or slow cell division

• Mutation inactivates the gene

• Brakes are out

Inversion

Translocation

Deletion

Duplication

Methods to Identify Genetic Changes

• Chromosome analysis

(karyotyping)

• Addition

• Deletion

• Translocation

• FISH

• PCR

Chromosome Abnormalities in Cancer

• Translocations

• fusion proteins

• Overexpression of normal proteins

• Deletions

• Loss of tumor suppressor genes

• Amplification of genes

• Oncogene overexpression

Implications in Risk Stratification -

DLBCL

• BCL-2 rearrangement- t(14;18)(q32;q21)

• BCL-6 rearrangement -t(2;3)(q21;q27)

• “Double Hit Lymphoma” - transplant

• “Triple Hit Lymphoma” - transplant

Risk Stratification in AML According to

Cytogenetics and Molecular Genetics

• Favorable

• 27%

• Intermediate I-II

• 31-19%

• Unfavorable

• 23%

• inv 16 or t(16;16)

• t(8;21)

• t(15;17) --APL

• Mutated NPM1 without FLT3-ITD

• Mutated CEBPA

• Normal cytogenetics

• +8

• t(9;11)

• Mutated NPM1 and FLT3-ITD

• 5/5q-, -7/7q, AML M6

• Inv (3), t(3;3)

• complex (>3 abn)

• 11q23--non t(9;11)

• t(6;9)

• t(9;22)

• MLL rearranged

Adapted from Rolling et al., 2011

INTERGROUP study, Blood 2000

CML/ALL

Philadelphia Chromosome t(9;22) (q34;q11)

• Diagnostic for CML

• Poor prognosis for ALL in adults - transplant