Bone Marrow Failure Diseases: Including MDS, AA, PNH - PowerPoint Presentation

Slide1

Bone Marrow Failure Diseases: Including MDS, AA, PNH

Lauren

Cosolo

, RN, BScN, MN

Slide2

Outline

Review bone marrow failure and disease

Discuss

Myelodysplastic

syndrome, pathophysiology, clinical presentation, diagnosis, treatment

Discuss Aplastic Anemia,

clinical presentation, diagnosis,

treatment

Discuss PNH

, pathophysiology, clinical presentation, diagnosis,

treatment

Review nursing considerations for bone marrow failure diseases

Slide3

Bone Marrow Failure

Ineffective hematopoiesis causing pancytopenia and the inability to produce healthy blood cells

Pancytopenia= reduction in blood counts

 red cells, white cells, platelets

Image taken from: http://www.lookfordiagnosis.com/mesh_info.php?term=Myeloid+Cells&lang=1

Scheinberg

,

DeZern

,

Steensma

, 2016;

Hoffbrand

& Moss, 2016

Slide4

Bone Marrow Failure Diseases

Disorders resulting in

cytopenia

(low blood counts) due to decreased bone marrow production

Can be congenital (inherited) or acquired disorders

Young, 2014; Zhang, 2016

Slide5

Myelodysplastic Syndromes (MDS)

Clonal

disorders of hematopoietic stem cells characterized by increasing bone marrow failure in association with dysplastic changes (cells look abnormal) in one or more cell lineages

Simultaneous proliferation and apoptosis of hematopoietic cells (ineffective hematopoiesis) leading to

hypercellular

bone marrow but pancytopenia in peripheral blood

Pathologyoutline.com

Slide6

Pathophysiology of MDS

There is an abnormal regulation of proliferation, maturation and survival of hematopoietic stem cells due to genetic changes

A

number of genetic changes/mutations are associated with MDS

Changes in the expression of genes, such as

hypermethylation

contributes to the development or progression of MDSResulting in suppression of gene transcriptionAs the disease progresses, maturation of stem cells are further impaired with increased survival of myeloblasts

Slide7

Prevalence and Risk Factors

MDS usually develops in older adults >60 years old with median age of 72-76 years

More common in males than in females

MDS relatively common disease

4-7

estimated new

cases/100,000 each yearRisk Factors: Older ageMaleExposure to environmental factors (benzene)Smoking Previous chemotherapy or radiation treatment

Buckstein & Wells, 2008

Slide8

Etiology

Devine, 2013; Aster & Stone, 2018

Slide9

Clinical Presentation

Patients with MDS typically present with peripheral blood

cytopenias

Patients range from being asymptomatic with an incidental CBC finding to having symptoms and complications related to the previously unrecognized

cytopenia

Majority of MDS patients present with red cell lineage dysplasia (anemia)

Signs and Symptoms include: Fevers, infection from neutropeniaPetechiae, ecchymosis, bruising, bleeding from thrombocytopeniaFatigue, SOB, palpitations, weakness, exercise intolerance, dizziness, pale complexion, cognitive impairment as result of anemia

Slide10

Diagnosis

Diagnosis of MDS dependent on:

Quantitative changes in blood elements (

cytopenias

)

Evidence of dysplasia in peripheral blood smear and marrow

HistorySigns and symptoms Past medical history + comorbiditiesBlood transfusion historyPrior chemotherapy/radiation treatmentFamily historyMedicationsExposure to chemicals

Physical ExamInvestigating for evidence of cytopenias

Integumentary

Mucous membranes

Bleeding- epistaxis, gum bleeding, hemoptysis, hematuria, prolonged menstruation, melena

Fatigue

Vital signs

Presence of fevers, infections

Presence of splenomegaly

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Diagnostic Investigations

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WHO Classification of MDS

Subtype

Peripheral

blood

Bone marrow

% blasts

Refractory anemia

Anemia

Unilineage

erythroid

dysplasia

(in >10% cells)

<5

Refractory

neutropenia

Neutropenia

Unilineage

granulocytic

dysplasia

<5

Refractory thrombocytopenia

Thrombocytopenia

Unilineage

megakaryocytic dysplasia

<5

Refractory anemia with ring

sideroblasts

(RARS)

Anemia

Unilineage

erythroid

dysplasia

>15%

erythroid

precursors are ring

sideroblasts

<5

Refractory

cytopenia

with

multilineage

dysplasia (RCMD)

Cytopenia

Multilineage

dysplasia +/- ring

sideroblasts

<5

Refractory

anemia with excess blasts type 1 (RAEB-1)

Cytopenia

Unilineage

or

multilineage

dysplasia

5-9

Refractory anemia with excess blasts type

2 (RAEB-2)

Cytopenia

Unilineage

or

multilineage

dysplasia

10-19

MDS associated

with isolated del (5q-)

Anemia, normal

or high platelet count

5q31 deletion, anemia,

hypolobulated

megakaryocytes

<5

Slide13

IPSS-R

Parameter

Categories and Associated Scores

Cytogenetic risk group

Very good

Good

Intermediate

Poor

Very poor

0

1

2

3

4

Marrow

Blast proportion

≤2%

>2-<5%

5-10%

>10%

0

1

2

3

Hemoglobin

≥10g/

dL

8-<10g/

dL

<8 g/

dL

0

1

1.5

ANC≥0.8 x 109/L<0.8 x 109/L00.5Platelet Count≥100 x 109/L50 - 100 x 109/L<50 x 109/L00.51

Tool is only helpful at time of diagnosisTool is used to estimate life expectancy for NEWLY diagnosed patients with MDS

Risk Category

Risk

Score

Very low

≤1.5

Low

>1.5-3

Intermediate

>3-4.5

High

>4.5-6

Very high

>6

Slide14

IPSS-R

Slide15

Prognosis

Factors that predict outcome include:

WHO classification

Complex karyotype (>3 chromosome abnormalities)

Chromosome abnormalities

Blast proportion

Cytopenias Even low risk MDS has significant morbidity and mortality including transfusion requirements and associated complicationsWorsening of pancytopenia, acquisition of chromosomal abnormalities, increase in number of blasts are poor prognostic indicatorsTherapy related MDS is an extremely poor outlook

Slide16

Treatment

Dependent on:

Patient’s age

Performance status

Prognostic score

WHO classification comorbidities

Determine treatment goals with patient and family, including achieving hematologic improvement, reducing transfusion requirements, delaying transformation to leukemia, improving survival and maintaining quality of lifeDevine, 2013

Slide17

Low Risk MDS Treatment Options

(IPSS Low Risk/

Int

Risk-1)

For patients that are

asymptomatic

 watchful waiting and monitor Q3-6 monthsSymptomatic Treatment optionsMedications for anemia (ESA, lenalidomide), neutropenia (antibiotics, GCSF), thrombocytopenia (

antifibrinolytics)Immunosuppressive therapy (ATG, Cyclosporine)

Supportive Care (transfusion support, iron chelation)

Allo

-SCT assessment

Delayed

allo

-SCT offers maximal life expectancy as long as transplant occurs before transformation to leukemia

Eligibility ultimately decided by transplant center

Often SCT is not an option to due to patients’ older age or comorbidities

Mdsclearpath.org

Slide18

Disease Progression

Potential indicators of progression to high risk MDS

Worsening

cytopenia

New

cytopeniaAppearance of blasts

Rising LDHSystemic symptoms (fever, weight loss)Specific evaluation of higher risk MDSBone marrow aspiration and biopsyFlow cytometryCytogenetics

Mdsclearpath.org

Slide19

Treatment Options for High Risk MDS

Goal of treatment:

Change natural history of MDS

Defer AML transformation

Improve survival for patients with MDS

Treatment Options:

Hypomethylating agents (azacitidine, decitabine) (usually standard of care, however not a cure for MDS)Chemotherapy Allogeneic Stem Cell TransplantSupportive Care/ Palliative CareClinical TrialMdsclearpath.org

Slide20

Supportive Care

All patients should receive supportive care as it is adjunct to chosen therapy

Patients with

cytopenias

and associated symptoms can receive supportive care

Transfusion support

Red cells or plateletsCMV negativeNursing Management: Identify symptoms of anemia, monitor CBC, monitor for fluid overload and advocate for diureticAssess response to platelet transfusions (platelet refractoriness) and PRBCS (Hgb)Monitor for SE of transfusionsIron overload

Mdsclearpath.org

Slide21

Iron Overload Management

Iron Chelation Therapy

Deferoxamine

SC daily dose of 1,000–2,000 mg (20–40 mg/kg/day) should be administered over 8–24 hours, using a small portable pump capable of providing continuous mini-infusion.

SE: allergic reaction, ocular and ototoxicity, cardiac dysfunction

pretreatment hearing and visual exam

Defersirox Initial dose 20 mg/kg body weight daily, orally, taken on an empty stomach 30 minutes prior to meals. SE: GI hemorrhage, hepatic/renal failure, cytopenias

, diarrhea, n/v, abdo pain

Deferiprone

SE: agranulocytosis

Measure ANC, interrupt if ANC <1.5

Slide22

Impact of MDS on Patients/Families

Quality of life is complex, individually defined for patients living with MDS

Includes physical, social, emotional, practical and spiritual aspects

Aging, comorbidities, fatigue, and uncertain illness trajectory affects the quality of life of patients

Oncology nurses are in an appropriate position to monitor the impact of the illness and treatment on patients and their quality of life through systematic assessment, providing appropriate interventions, referrals and ongoing support

Thomas,

Crisp & Campbell,2012

Slide23

Aplastic Anemia

Pancytopenia (low blood counts) as a result of hypoplasia of bone marrow

Can be inherited or acquired, majority are acquired

Reduction in number of hematopoietic stem cells and an immune reaction or error in the remaining stem cells causing them to not divide or differentiate appropriately to populate bone marrow

Image: Medical-dictionary.thefreedictionary.com;

Hoffbrand

& Moss, 2016

Slide24

Prevalence and Etiology

Affects primarily children (with children, majority are inherited), young adults or adults >60

More common in people of Asian descent

2-12 new cases/million each year

Etiology:

Inherited or acquired

Most cases are idiopathicExposure to chemicals, drugs, viruses, radiation, immune diseasesIncekol & Ghadimi, 2015; Hoffbrand & Moss, 2016

Slide25

Clinical Features

Present with signs and symptoms of pancytopenia

Most frequent symptoms:

Bruising

Bleeding gums

Epistaxis

Menorrhagia Symptoms of anemia (Pallor, headache, palpitation, SOB/dyspnea, fatigue, foot swelling)Infections are common and frequently life threatening Incekol

& Ghadimi, 2015; Hoffbrand & Moss, 2016

Slide26

Diagnosis

Blood work

CBC with diff, B12, folic acid, LFT, LDH,

chem

panel,

coagsPancytopenia early on

Bone Marrow Aspirate and BiopsyBone marrow is profoundly hypocellular, marrow space is composed mostly of fat cells and marrow stroma Flow cytometry To detect coexisting disordersCytogenetics

Rule out MDS and congenital disorders

Slide27

Classification

Slide28

Treatment

very

severe & severe aplastic anemia stages require treatment as this category has a high mortality

rate

HCT

(

hematopoeitic stem cell therapy)Dependant on age, functional status and availability of donorImmunosuppressive therapyATG (Antithymocyte globulin)Horse ATG administered IV over 4 daysRequires pre-medication with tylenol

/ benadryl to decrease infusion reactions and serum sickness reactionRequires daily steroids to reduce risk of serum sickness

Risk for anaphylaxis- keep anaphylaxis kit at bedside during infusion

Cyclosporine

SE: HTN, renal insufficiency, Mg deficiency, gum hyperplasia

Requires BP, Cr monitoring, regular dental care

Larratt

,

powerpoint

; Longo, 2017

Slide29

Serum Sickness

Occurs 1-2 weeks after initiating treatment of ATG

F

lu-like illness, rash and arthralgia

Treatment: steroids

Slide30

Supportive Care

Transfusions

RBC, platelets

Irradiated Blood

Treatment of Infections

Empiric therapy with broad spectrum antibioticsGrowth factors as prophylaxis for repeated infections

Infection Prevention and MonitoringPatient education on preventing infections and monitoring for fever and signs and symptoms of infection

Slide31

Paroxysmal Nocturnal

Hemoglobinuria

(PNH)

Acquired hemolytic anemia

Characterized by:

Longo, 2017

Slide32

Pathophysiology

Acquired mutation in PIG-A gene in hematopoietic stem cell

If mutation proliferates the result is a clone that is deficient in cell surface proteins known as

glycosylphospatidylinositol

-anchored proteins (GPI-AP)

The GPI-AP proteins act as receptors, complement regulators and adhesion molecules

CD55 and CD59 which are two GPI-AP that protect red blood cells from complement activity are not present on the surface of the PNH red blood cells, which leaves these cells extremely sensitive to complement-mediated destruction Young et al., 2009

Slide33

Prevalence

Same frequency in men and women

Rare disease

Prevalence estimated at 5/1,000,000

Can present in small children or older adults, most patients are young adults

Slide34

Clinical Presentation

Brodsky, 2014

Slide35

Diagnosis

Blood work

CBC with diff

Liver profile, bilirubin

LDH

Reticulocyte countUrinalysis

HemoglobinuriaFlow CytometryIdentify the GPI-AP deficient peripheral blood cells Parker et al., 2005

Slide36

Treatment

Supportive Care

Transfusions

Folic acid/iron supplements

Treatment of complications (

eg. Thrombosis)

BiotherapyEcullizumab (Solaris) Allogenic SCT for young patient with severe PNHPrimary prophylaxis for thrombosisLongo, 2017

Slide37

Nursing Considerations for Bone Marrow Failure Diseases

Comprehensive assessment of patient and management of side effects

Monitoring for signs and symptoms of

cytopenias

including fatigue, bleeding, infection, etc

.

and providing appropriate interventionsAddressing patient’s supportive care needsEducation for patients and families on understanding the disease and its manifestations, treatment modalities and the adverse effects from treatment Connect to hospital and community resources

Slide38

AAMAC

Telephone and e-mail patient-to-patient support

Educational material on Aplastic Anemia, MDS & PNH

Quarterly newsletter

Patient Tracker

Local support group meetings

Grants for medical research and educationWebsite, Facebook, Marrowforums

http://www.aamac.ca/

Slide39

References

Devine, H. (2013).

Myelodysplastic

syndromes. In M. Olsen & L.

Zitella

(Eds.), Hematologic Malignancies in Adults

(51-74). Pittsburgh, Pennsylvania: Oncology Nursing Society.Buckstein, R. & Wells, R. (2008). Myelodysplastic syndromes (MDS). Retrieved from: https://sunnybrook.ca/uploads/Myelodysplastic_Syndromes.pdfBurgoyne, T. & Knight, A. (2000). Myelodysplastic syndromes. In M. Grundy (Ed.), Nursing in Hematological Oncology (21-30). London, UK: Baillere Tindall Royal College of Nursing

Celgene. (2010). Vidaza azacitidine for injection.

Thomas, M.L., Crisp, M., & Campbell, K. (2012). The importance of quality of life for patients living with

myelodysplastic

syndrome.

Clinical Journal of Oncology Nursing,

16(3), 47-57

Van de

Loosdrecht

, A. A., &

Westers

, T. M. (2014). Flow

Cytometric

Immunophenotyping

in

Myelodysplasia

: Discovery and Diagnosis. Blood, 124(21), SCI-24. Accessed June 24, 2018. Retrieved from http://www.bloodjournal.org/content/124/21/SCI-24.

Incekol

, D. &

Ghadimi

, L. (2015). Princess Margaret cancer

centre

: malignant hematology: self-learning booklet. 3

rd

edition.

Longo, D.L. (2017). Harrison’s hematology and oncology. New York: McGraw-Hill Education

Brodsky, R. A. (2014). Paroxysmal nocturnal

hemoglobinuria. Blood, 124, 2804-2811Parker, C. et al. (2005). Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood, 106, 3699-3709Young, N.S. et al. (2009). The management of paroxysmal nocturnal hemoglobinuria: recent advance in diagnosis and treatment and new hope for patients. Seminars in Hematology, 46(1), S1-S6

Slide40

References

Hoffbrand

, A.V. & Moss, P. A.H. (2016).

Hoffbrand’s

Essential

Haematology. West Sussex, UK: Wiley & Sons, Ltd.MDS Clear Path. Mdsclearpath.org

Scheinberg, P., DeZern, A.E. & Steensma, D.P. (2016). Acquired bone marrow failure syndromes: aplastic anemia, paroxysmal hemoglobinuria, and myelodysplastic syndromes. Retrieved from: http://ash-sap.hematologylibrary.org//content/2016/489.extract?utm_source=TrendMD&utm_medium=cpc&utm_campaign=American_Society_of_Hematology_Self-Assessment_Program_TrendMD_0

Young NS. Young N.S. Young, Neal S.Bone Marrow Failure Syndromes Including Aplastic Anemia and Myelodysplasia. In: Kasper D, Fauci

A, Hauser S, Longo D, Jameson J,

Loscalzo

J. Kasper D,

Fauci

A, Hauser S, Longo D, Jameson J,

Loscalzo

J Eds. Dennis Kasper, et

al.eds

.

Harrison's Principles of Internal Medicine, 19e

New York, NY: McGraw-Hill; 2014. http://accessmedicine.mhmedical.com/Content.aspx?bookid=1130&sectionid=79731602. Accessed August 01, 2018

.

Zhang, L. (2016). Inherited and acquired bone marrow failure syndromes: in the era of deep gene sequencing.

Journal of Leukemia, 4

(4)