Hematologic Malignancies

Kim Noonan, RN, ANP, AOCN

Hematologic Malignancies • Cancers that affect blood, bone

marrow and lymphatic system.

• Liquid tumors vs solid tumors

• Leukemia

• Lymphoma

• Multiple Myeloma

Hematopoietic tree

Leukemia

Leukemia objectives

• Identify risk factors for developing leukemia • Describe the pathophysiology of leukemia • Identify measures and tumor markers used to make a

diagnosis of leukemia • Outline how leukemia is classified • Describe the different types of treatments for leukemia

and identify nursing interventions appropriate to patient care

• Design a plan of care for individuals with leukemia, include planning related to side effects and other concerns regarding treatment

Leukemia epidemiology

• The American Cancer Society's estimates for leukemia in the United States for 2015 are: – About 54,270 new cases of leukemia (all kinds) and

24,450 deaths from leukemia (all kinds) • Leukemia occurs more often in adults than

children • Acute lymphocytic leukemia (ALL) is the most

common form in children • Acute myeloiod leukemia (AML) & Chronic

lymphocytic leukemia (CLL) are the most common forms in adults

Leukemia – risk factors

• Gender - Male > female • Age - Over 50 • Genetic predisposition

– Downs’s Syndrome – Ataxia telangiectasia – Fanconi anemia – Bloom syndrome

• Exposure to radiation

• Family history - CLL • Chemical exposure –

Benzene • Viruses – HIV, HTLV-1 &

EBV • History of cancer

therapy • Myelodysplastic/

myloproliferative disorders

Leukemia pathophysiology

• Malignant disorders of blood forming cells – WBC

• Diffuse replacement of bone marrow

• Starts in bone marrow • Myeloid vs lymphoid • Chronic vs acute

Leukemia diagnosis

• CBC • Peripheral blood smear • Bone marrow samples

– Aspiration – Biopsy

• Flow cytometry

Leukemia - types

• Rate of cell growth - Acute vs chronic • Type of cell - Myeloid vs lymphoid

– Acute myelogenous leukemia - AML – Chronic myelogenous leukemia -CML – Acute lymphocytic leukemia- ALL – Chronic lymphocytic leukemia -CLL – Hairy cell leukemia ( rare chronic leukemia)

Leukemia Incidence by Type

CLL CML AML ALL

CLL 14,620 new cases/year

ALL 6,250 new cases/year

AML 20,830 new cases/year

CML 6,660 new cases/year

American Cancer Society Facts & Figures 2015

Hematopoietic tree -AML

Acute myelogenous leukemia (AML) • Most common acute leukemia in adults – 80% • In 2014 about 18,860 new cases of acute myeloid leukemia

(AML). Most will be in adults. • In 2014 about 10,460 deaths from AML. Almost all will be in

adults. • Average age = 67 • Men > women • Increased risk of AML associated with:

– Smoking – Chemical exposure – benzene – MDS – Downs syndrome – RX with chemotherapy & radiation

Acute myelogenous leukemia (AML)

• Symptoms – Fatigue – Malaise – Weight loss – Fever/night sweats – Recurrent infections – Unexplained bleeding – Anorexia – Bone pain – Neuro (h/a, vomiting,

visual changes, Sz)

• Signs – Sudden onset – Rapid down hill course – Bone marrow failure – Anemia – Thrombocytopenia – Neutropenia – Hepatomegaly – Organ/gingival

infiltration – Pale skin, skin lesions

Acute myelogenous leukemia (AML) – Clinical Abnormalities

• 95% have circulating myeloblasts in the peripheral smear

• 75% have platelet counts <100,000 • 25% have platelet counts <25,000 • 20% have a WBC of >100,000 • 25-40% have a WBC <5,000 • Auer rods are present in the peripheral smear • Normocytic anemia with a decrease or normal

reticulocyte count

Acute myelogenous leukemia (AML) – Auer Rods

Acute myelogenous leukemia (AML) - Classification FAB – Classification

• M0 – Minimally differentiated • M1 – Undifferentiated

Myelocyte • M2 - Myelocytic • M3 - Promylecytic • M4 - Myelomonocytic • M5 - Monocytic • M6 - Erythroleukemia • M7 - Megakaraycytic

WHO - Classification • Genetic Abnormalities • Prognostic factors • Chromosome abnormalities • Gene mutations • Age • WBC count • Prior blood disorders or

cancers • Infection present • CNS involvement • Response to treatment

Acute myelogenous leukemia (AML) - Treatment

• Induction – initial high dose chemotherapy to achieve complete remission = bone marrow repopulation with normal cells (<5% blasts)

• Post-remission-given to reduce leukemic cell population – Consolidation- 1 or 2 cycles of same chemo used in

induction – Intensification – High dose chemo given shortly after

induction ( same or different drugs) – Maintenance- lower doses of same drugs as induction

given monthly for prolonged period to maintain disease free state

Acute myelogenous leukemia (AML) Treatment

• Induction high dose chemotherapy

– 7 +3 Cytarabine (Ara-c) + anthracycline (Daunorubicin) – Other Anthrcyclines – Decreased doses in patients older than 60 – Intrathecal cytarabine or methotrexate , with or without cranial

radiation, if CNS leukemia present – M4 • Consolidation

– Ara-C 3-4 cycles – Dose is age dependent

• Stem Cell Transplant – Allogeneic in 1st remission when cytogenetic suggest poor prognosis – In relapsed patients

Acute promyelogenous leukemia M3 - Treatment

• Induction – All trans retinoic acid (ATRA) + cytarabine and

daunarubicin – Arsenic trioxide (ATO)+ ATRA

Hematopoietic tree - CML

Chronic myelogenous leukemia • CML - 10% of all new cases of leukemia. • In 2015 about 6,660 new cases of CML will be

diagnosed. • In 2015 about 1,140 people will die of CML. • Men > women • Whites > African-Americans • The average age - 65 years ( rare in children) • Philadelphia chromosome – Chromosomes 9 & 22 • Increased risk of CML associated with:

– High dose radiation – Older age & male gender

Chronic myelogenous leukemia- Philadelphia chromosome

Chronic myelogenous leukemia

• Insidious Onset • Fatigue / Weakness • Pale skin • Night sweats • Weight loss • Fever • Bone pain • Spleenomegaly • Abdominal pain or a sense of "fullness” • Feeling full after eating even a small amount of food

Chronic myelogenous leukemia - phases • Chronic phase

– Excessive mature granulocytes ( < 10% blasts) – Mild symptoms (if any) – Philadelphia chromosome in 90% – Oral therapies

• Accelerated phase – Increase in immature blast cells - > 10% but < 20% blasts – Increase in basophil count- 20% of the WBCs – High WBC that do not respond treatment – Very high or very low platelet counts – New chromosome changes in the leukemia cells – SX: fever, poor appetite, and weight loss – Does not respond as well to treatment

• Blast phase (also called acute phase or blast crisis) – Bone marrow and/or blood samples > 20% blasts – tissues and organs infiltration – Resembles AML

Prognostic factors for chronic myeloid leukemia

• Adverse prognostic factors: – Accelerated phase or blast phase – Enlarged spleen – Areas of bone damage from growth of leukemia – Increased number of basophils and eosinophils – Very high or very low platelet counts – Age 60 years or older – Multiple chromosome changes in the CML cells

Chronic myelogenous leukemia - treatment

• Targeted therapies – Imatinib (Gleevec) – Dasatinib (Sprycel) – Nilotinib (Tasigna)

• Interferon alpha

• Chemotherapy – Hydroxyurea (Hydrea®) – Cytarabine (Ara-C) – Busulfan – Cyclophosphamide

(Cytoxan®) – Vincristine (Oncovin®)

• Splenectomy

• Radiation therapy – lytic bone lesions

• Bone marrow or peripheral blood stem cell transplant – Allogeneic stem cell

transplants- only cure

• Blast phase treated like acute leukemia

Hematopoietic tree - ALL

Acute lymphocytic leukemia • In 2015, about 6,250 new cases of ALL • In 2015, about 1,450 deaths from ALL • ALL represents the most common pediatric

malignancy • 60% of cases in patients < 20 years old • Cure rate more favorable in children than adults • Males > females • Whites > African-Americans

Acute lymphocytic leukemia – risk factors

• Radiation exposure • Chemical exposure –

benzene/ chemotherapy

• Male > female • White > black • Viral infections

– HTLV-1 – EBV

• Genetic – Down syndrome – Klinefelter syndrome – Fanconi anemia – Bloom syndrome – Ataxia-telangiectasia – Neurofibromatosis

Acute lymphocytic leukemia • Symptoms

– Fatigue – Malaise – Weight loss – Fever/night sweats – Recurrent infections – Unexplained bleeding – Anorexia – Bone pain – Neuro (h/a, vomiting,

visual changes, Seizures)

• Signs – Sudden onset – Rapid down hill course – Bone marrow failure – Anemia – Thrombocytopenia – Neutropenia – Hepatomegaly – Organ infiltration – Pale skin – Enlarged thymus- SVC – Lymphadenopathy – Splenomegaly

Acute lymphocytic leukemia – clinical presentation

• Increase in WBC consisting of lymphoblasts • Granulocytopenia • Decrease in hemoglobin • Decrease in platelets • Increase in LDH

Acute lymphocytic leukemia -classification • Morphology - FAB

– L1: childhood lymphoblasts (pre B and T cell) (85-89%) – L2: adult lymphoblasts (pre B and T cell) (11-14%) – L3: Burkitts’s type (B-cell)<1% poor prognosis

• B Cell ALL – Most common – About 85% are precursor B cell ALL – Markers: CD19, CD22, CD20 and CD79; CD10 and CD45

• T Cell ALL – Uncommon – Lymphadenopathy is common – Markers: CD3, CD2,CD5,CD1a, CD4 and/or CD8

Acute lymphocytic leukemia –prognostic indicators

• Age at diagnosis > 35 years • Initial WBC count • ALL subtype • CNS disease at diagnosis • Chromosomal abnormalities

– Translocation 11 q 23 – Philadelphia chromosome

• Response to chemotherapy

ALL – Induction treatment • Induction – 8 weeks

– Goal – cure – Combination Chemotherapy – 4 drug regimen

• Steriod • VinCRIStine (Oncovin®) • Anthracycline • +/- L-asparaginase (Elspar®) • And/or Cytoxan • Imatininb (Gleevec) with + Phildelphia chromosome

– Supportive care – 5% induction mortality • Symptom Management • Routine transfusions • Empiric broad spectrum antibiotics

ALL – Consolidation treatment • Post-remission/ Consolidation

– Must be in remission • Blast <5% • No S & S of ALL • No S & S of organ involvement • No S & S of CNS involvement

– Children intensification regimens • Methotrexate • L-asparaginase

– Adults • High dose chemotherapy • Allogenic stem cell transplant

ALL- CNS Prophylaxis

• Adults – Intrathecal methotrexate – High-dose IV methotrexate or cytarabine – Radiation therapy to the brain and spinal cord

• Children – Intrathecal Methotrexate – High dose chemotherapy

ALL – Bone marrow/ stem cell Transplantation

• Autologous stem cell transplant – Patient’s own stem cells – Will not reject – Cancer may continue to grow

• Allogeneic stem cell transplant – HLA matched donor 6/6 match

preferred • Synergistic – identical twin • Myeloablative HSCT

• Non-myeloablative – “mini” HSCT – Lower doses of chemo with

whole body RT – Allogenic HSCT – Graft vs tumor – Age >60 – Comorbidities

• Stem cell sources – Bone marrow – Peripheral stem cells – Umbilical cord blood – Placenta

ALL- Maintenance

• 2-3 years • Metheltrexate • 6-mercaptopurine (6-MP)

• May include steroid and Vincristine • Imatinib (Gleevec) + Philadelphia chromosome • Adults - CNS prophylaxis

ALL- Response Rates

• Children – The 5-year survival rate for children with ALL –

85%

• Adults – 80-90% achieve complete remission – 50% or more relaspe – 30-40% of adults treated with the conventional

ALL protocol will survive

Chronic lymphocytic leukemia • Characterized by accumulation of small mature

lymphocytes • Slow growing • Predominately in B cells • CLL accounts for about one-third of all leukemias. • In 2015 about 14,620 new cases of chronic lymphocytic

leukemia (CLL) • In 2015 about 4,650 deaths from CLL • Men > women • Family history • Average age - 72 years

Chronic lymphocytic leukemia Symptoms • Asymptomatic in early

stages • Weakness • Fatigue • Weight loss • Fever • Night sweats • Enlarged lymph nodes • Abdominal pain • Early satiety • Recurrent infections

Signs • Insidious onset • Splenomegaly • Hepatomegaly • Lymphadenopathy • Anemia • Thrombocytopenia • Hypogammaglobulinemia • Rashes

Chronic lymphocytic leukemia – staging- Rai system

• Rai system: This is used more often in the United States – The Rai system divides CLL into 5 stages:

• 0 - lymphocyte count > 10,000 • 1 - Lymphocytosis plus enlarged lymph nodes • 2 - Lymphocytosis plus an enlarged spleen (and possibly an

enlarged liver), +/- enlarged lymph nodes • 3 - Lymphocytosis plus anemia , + /- enlarged lymph nodes,

spleen, or liver • 4 - Lymphocytosis plus thrombocytopenia, +/- anemia,

enlarged lymph nodes, spleen, or liver

Chronic lymphocytic leukemia – staging- Binet system

• Binet system: This is used more widely in Europe – Stage A: Fewer than 3 areas of lymphoid tissue are

enlarged, with no anemia or thrombocytopenia. – Stage B: 3 or more areas of lymphoid tissue are

enlarged, with no anemia or thrombocytopenia. – Stage C: Anemia and/or thrombocytopenia are

present.

Chronic lymphocytic leukemia – Adverse prognostic factors

• Diffuse pattern of bone marrow involvement • Advanced age • Male gender • Increased proportion of large or atypical lymphocytes in the blood • Lymphocyte doubling time of less than 12 months • Deletions of parts of chromosomes 17 or 11 • High blood levels of certain substances, such as beta-2-microglobulin • CLL cells containing ZAP-70 (more than 20%) or CD38 (more than • 30%) • CLL cells with unchanged (not mutated) gene for the immunoglobulin

heavy chain variable region (IgVH)

Chronic lymphocytic leukemia - treatment

• Watchful waiting until symptomatic – Physical exam and blood counts every 3-6 months

• Goal – Control symptoms, reduce infections, QOL • Chemotherapy

– Purine analogs – fludarabine – Alkylating agents chlorambucil (Leukeran) and

cyclophosphamide (Cytoxan), bendamustine (Treanda) – Corticosteroids – Monoclonal antibodies – Rituximab, Alemtuzumab (Campath)

• Spleenectomy • Radiation therapy – painful lymphadenopathy

/spleenomegaly

Chronic lymphocytic leukemia – complications/nursing considerations

• Tumor lysis syndrome • Transformation to high grade non- Hodgkin's

Lymphoma • Hemolytic anemia and thrombocytopenia • Recurrent Infection

– Prophylactic support – Annual attenuated vaccinations

• Emotional impact of chronic disease

Nursing Considerations • Acute leukemia are very ill at diagnosis and hospitalized for

several weeks • Profound bone marrow suppression • Infection

– Sepsis – DIC

• Transfusional support • Side effect management • Tumor lysis syndrome • Psychological support • Oral adherence • Educational support

Lymphoma

Scientific Basis for Practice

Lymphoma - objectives

Identify risk factors for developing lymphoma Describe the pathophysiology of lymphoma Identify measures and tumor markers used to make a

diagnosis of lymphoma Outline how lymphoma is classified Describe the different types of treatments for lymphoma and

identify nursing interventions appropriate to patient care Design a plan of care for individuals with lymphoma, include

planning related to side effects and other concerns regarding treatment

Lymphoma

• Most common hematologic malignancy • Account for 5% of all cancers in U.S. • Two categories:

– Hodgkin’s lymphomas (Hodgkin’s Disease) – Non-Hodgkin’s lymphomas

All Other Cancers

Lymphomas

Hematopoietic tree - Lymphoma

Lymphoma

• Neoplasm of Lymphoid tissue – Lymph nodes, spleen,

thymus, adenoids, tonsils, GI tract, bone marrow

• Lymphocytes – B – cell -antibodies – T- cell- cellular

immunity • Non-Hodgkin’s

lymphoma • Hodgkin’s lymphoma

Hodgkin Lymphoma- (Hodgkin’s disease)

• Starts in lymphoid tissue, usually B cells • Spreads through lymph system in step wise orderly fashion • Reed Sternberg cell • In 2015, about 9,050 new cases will occur (3,950 in females

and 5,100 in males) • In 2015 about 1,150 people (490 females, 660 males) will

die of Hodgkin's Lymphoma • Bimodal age distribution – ages 15-34 and age >60 • 1-year relative survival rate – 92% • 5-year and 10-year survival rates are about 85% and 80%,

respectively

Hodgkin Lymphoma- risk factors • Viral

– Epstein-Barr virus infection/mononucleosis – HIV

• Age – bimodal incidence early adulthood (15-34) & late adulthood (>60)

• Gender - males > females • Geography • Family history • Socio-economic status

Hodgkin Lymphoma- signs & symptoms

• Painless enlargement of one or more lymph nodes

• B symptoms – Fever – Night sweats – Anorexia/weight loss

• Itching • Fatigue • Loss of appetite • Cough, SOB, chest pain

Hodgkin Lymphoma- diagnostics

• Biopsy – Excisional or incisional biopsy – Fine needle aspiration (FNA) or core needle biopsy

• Pathology – Reed-Sternberg cell

Hodgkin Lymphoma- Ann Arbor staging

Hodgkin’s Lymphoma– Adverse prognostic factors

• B symptoms or bulky disease • Age > 45 • Being male • WBC > 15,000 • Hemoglobin level < 10.5 • Lymphocyte count < 600 • Albumin level < 4

Hodgkin Lymphoma- treatment

• Goal – cure • Chemotherapy

– Adriamycin (doxorubicin) – Bleomycin – Vinblastine – Dacarbazine (DTIC)

• Radiation therapy – Involved field radiation – Extended field radiation

• Long tern side effects – Heart Disease – Stroke – Second malignancies – Hypothyroidism – Fertility issues

• Infections

Non-Hodgkin’s Lymphoma

• Most common hematologic cancer • In 2015, about 71,850 people (39,850 males

and 32,000 females) will be diagnosed with NHL.

• In 2015, about 19,790 people will die from this cancer (11,480 males and 8,310 females).

• Average risk 1 in 50 • 95% of case occur in adults

Non-Hodgkin’s Lymphoma • > 40 different types of NHL

• Malignancies of the B & T lymphocytes – B-cell lymphomas - 85% – T-cell lymphomas – 15%

• Indolent (slow growing) vs aggressive (fast –growing)

Non-Hodgkin’s Lymphoma - Subtypes

Composite - 13% Small Lymphocytic - 6%

Mantal Cell - 6% Peripheral T Cell -

6%

MALT - 5%

Other - 9%

Marginal Zone T -

1% Lymphoplasmacti

c - 1%

Diffuse Large B Cell- 31%

Follicular - 22%

Non-Hodgkin’s Lymphoma – risk factors

• Age • Gender • Race, ethnicity, and geography • Exposure to certain chemicals • Radiation exposure • Immune system deficiency • Autoimmune diseases • Certain infections

Non-Hodgkin’s Lymphoma – sign & symptoms

• Enlarged lymph nodes • Swollen abdomen • Nausea/vomiting/ abdominal pain • Feeling full after only a small amount of food • Chest pain or pressure • Shortness of breath or cough • Headache/neuro changes • B Symptoms:

– Fever – Weight loss – Night sweats

• Sx of Low blood counts

NonHodgkin Lymphoma- diagnostics • Biopsy

– Excisional or incisional biopsy – Fine needle aspiration (FNA) or core needle biopsy

• Pathology • Lab Tests

– Flow cytometry – Cytogenetic (chromosomal) analysis – Molecular studies

Non-Hodgkin’s Lymphoma – staging

Non-Hodgkin’s Lymphoma – International Prognostic Index

• IPI – Age > 60 – Stage III or IV – Number of extranodal sites >1 – Elevated LDH – ECOG Performance status > 2

• FLIPI – Follicular Lymphoma – Age > 60 – Stage III or IV – Elevated LDH – Hemoglubin < 12 g/dl – Number of extranodal sites >4

Non-Hodgkin’s Lymphoma- classification and grade

• REAL/WHO classification – Cell type

• B cell • T cell • Natural Killer cell

– Morphology – form & structure – Immunophenotype – type of protein expressed – Genetic

• Grade – Indolent - Survival of untreated disease = years

– Intermediate -Survival of untreated disease = months

– Aggressive - Survival of untreated disease = weeks

Non-Hodgkin’s Lymphoma – Indolent • Indolent low grade lymphoma – chronic disease

– Follicular – SLL/CLL – Marginal zone – Lymphoplasmacytic Lymphoma/Waldenstrom’s macroglobulinemia – Hairy Cell Leukemia

• Watchful waiting – Rapidly progressive disease – Organ impairment – Disease related symptoms

• Chemotherapy + Rituximab – R-CHOP – R-CVP – R-FC – Bendamustin (Treanda) + Rituximab

• Single agent Rituximab

Non-Hodgkin’s Lymphoma – Relapsed

• Retreatment with initial chemotherapy • New regimen • Stem cell transplantation • Clinical trials

– Benefit of maintenance Rituximab – Potential of cure with allogenic stem cell

transplant

Non-Hodgkin’s Lymphoma – Aggressive

• Aggressive high grade lymphomas – Diffuse Large B- Cell – Burkitt’s – highly aggressive, RX similar to ALL – Primary CNS – Mantle cell lymphoma – Peripheral T-cell lymphoma – Lymphoblastic lymphoma

• Immediate Treatment – R CHOP – ? Cycle length 21 days vs 14 days – Radiation therapy

• Respond well – can be curable • Relapsed disease

– High dose chemotherapy – Stem cell transplant

Lymphoma – Nursing Considerations

• Infusion reactions – Rituximab • Tumor lyses syndrome • Lung damage – Bleomycin

– Baseline pulmonary function tests

• Cardiac changes – Adriamycin – MUGA or ECHO

• Nausea/ vomiting • Diarrhea/constipation • Alopecia (hair loss) • Fatigue

• Bone marrow suppression – Infection prevention

• Bactrim/Acyclovir/Diflucan – Transfusions – Neulasta

• Mucositis • Peripheral Neuropathy • Sexual health & fertility • Cognitive dysfunction – “Chemo

brain” • Lymphodema

Multiple Myeloma

Scientific Basis for Practice

Multiple Myeloma - objectives • Identify risk factors for developing multiple myeloma • Describe the pathophysiology of multiple myeloma • Identify measures and tumor markers used to make a

diagnosis of multiple myeloma • Outline how multiple myeloma is classified • Describe the different types of treatments for multiple

myeloma and identify nursing interventions appropriate to patient care

• Design a plan of care for individuals with multiple myeloma, include planning related to side effects and other concerns regarding treatment

Hematopoietic tree – Multiple Myeloma

Multiple Myeloma • Incurable malignancy of plasma cells • Plasmacytoma • Myeloma cells prefer bone marrow • 1-2 % of all malignancies • 10-15% of hematologic malignancies • In 2015 about 26,850 new cases will be diagnosed

(14,090 in men and 12,760 in women). • In 2015 about 11,240 deaths are expected to occur

(6,240 in men and 5,000 in women). • The 5-year relative survival rate for multiple myeloma is

around 33%.

Multiple Myeloma – risk factors

• Age - > 65 years old. • Gender - Men >women. • Race - black Americans > white Americans • Radiation exposure • Environmental toxins • Viruses • Genetic factors

Multiple Myeloma – diagnosis • Laboratory tests • Imaging • Bone marrow biopsy • Diagnosis of Multiple Myeloma requires:

– A plasmacytoma (proven by biopsy) OR – 10% bone marrow = plasma cells. AND one of the following: – M protein present in blood and/or urine – Myeloma related organ dysfunction

Multiple Myeloma – signs & symptoms

• CRAB – C – serum Calcium elevation – R – Renal insufficiency (SCr >2 mg/dl) – A – Anemia (Hg , 10 g/dL) – B – Lytic Bone lesions

• Neuro S & S • Infections

Multiple Myeloma – staging • Durie-Salmon system • The International Staging System

– Stage I - Serum beta-2 microglobulin is less than 3.5 (mg/L) and the albumin level is above 3.5 (g/L)

– Stage II- Neither stage I or III – Stage III- Serum beta-2 microglobulin is

greater than 5.5

Multiple Myeloma – survival International Staging System Median Survival Stage I 62 months ~5yr Stage II 44 months ~ 3.5yr Stage III 29 months ~ 2.5yr

Poor Prognostic factors: – Older age – Kidney function – IgA sub type – Increased circulating peripheral plasma cells – Chromosomal abnormalities

Progression of Multiple Myeloma

Multiple Myeloma – treatment

• Observation with treatment at disease progression

• Indications for treatment – Symptomatic disease – Evidence of organ impairment

• Anemia • Hypercalcemia • Lytic bone leisions • Renal failure

Multiple Myeloma – interventions • Chemotherapy • Immunomodulating agents • Steroids • Bisphosphonates • Radiation • Surgery • Plasmapheresis • Kyphoplasty or Vertebroplasty • Stem Cell Transplant

– Autologous – Allogeneic

Multiple Myeloma – Interventions • Chemotherapy

– melphalan, vincristine, cyclophosphamide, carmustine, and doxorubicin (and liposomal doxorubicin).

• Corticosteroids • Immunomodulating agents

– Thalidomide • Side effects: drowsiness, fatigue, severe constipation, and

neuropathy, blood clots, serious birth defects – Lenalidomide (Revlimid)

• Side effects: thrombocytopenia, low WBCs, painful nerve damage, blood clots, serious birth defects

Multiple Myeloma – Interventions • Proteasome inhibitors - Bortezomib (Velcade)

– Side effects : • Immunosuppression (Acyclovir) • Cytopenias especially thrombocytopenia • Peripheral neuropathy • Diarrhea • Constipation • Rash • Hypotension • Asthenias- lack of strength

Multiple Myeloma - Biophosphonates • Zometa (Zoledronic acid) and Aredia

(Pamidronate Disodium) and Denosumab – Indication

• Hypercalcemia and bone strengthening – Mechanism of action –not fully understood

• Binds to bone matrix • Inhibition of bone resorption • Inhibition osteoclastic activity

• Complications: • Osteonecrosis of the jaw • Renal impairment • Hypocalcemia