Hematologic Malignancies. Kim Noonan, RN, ANP, AOCN

Transcription

1 Hematologic Malignancies Kim Noonan, RN, ANP, AOCN

2 Hematologic Malignancies Cancers that affect blood, bone marrow and lymphatic system. Liquid tumors vs solid tumors Leukemia Lymphoma Multiple Myeloma

3 Hematopoietic tree

4 Leukemia

5 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

6 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

7 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

8 Leukemia pathophysiology Malignant disorders of blood forming cells WBC Diffuse replacement of bone marrow Starts in bone marrow Myeloid vs lymphoid Chronic vs acute

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10 Leukemia diagnosis CBC Peripheral blood smear Bone marrow samples Aspiration Biopsy Flow cytometry

11 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)

12 Leukemia Incidence by Type ALL 6,250 new cases/year CLL 14,620 new cases/year AML 20,830 new cases/year CLL CML AML ALL American Cancer Society Facts & Figures 2015 CML 6,660 new cases/year

13 Hematopoietic tree -AML

14 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

15 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

16 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, % have a WBC <5,000 Auer rods are present in the peripheral smear Normocytic anemia with a decrease or normal reticulocyte count

17 Acute myelogenous leukemia (AML) Auer Rods

18 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

19 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

20 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 1 st remission when cytogenetic suggest poor prognosis In relapsed patients

21 Acute promyelogenous leukemia M3 - Induction Treatment All trans retinoic acid (ATRA) + cytarabine and daunarubicin Arsenic trioxide (ATO)+ ATRA

22 Hematopoietic tree - CML

23 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

24 Chronic myelogenous leukemia- Philadelphia chromosome

25 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

26 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

27 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

28 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

29 Hematopoietic tree - ALL

30 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

31 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

32 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

33 Acute lymphocytic leukemia clinical presentation Increase in WBC consisting of lymphoblasts Granulocytopenia Decrease in hemoglobin Decrease in platelets Increase in LDH

34 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

35 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

36 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

37 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

38 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

39 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

40 ALL- Maintenance 2-3 years Metheltrexate 6-mercaptopurine (6-MP) May include steroid and Vincristine Imatinib (Gleevec) + Philadelphia chromosome Adults - CNS prophylaxis

41 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

42 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

43 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

44 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, 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

45 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.

46 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)

47 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

48 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

49 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

50 Lymphoma Scientific Basis for Practice

51 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

52 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 Lymphomas All Other Cancers

53 Hematopoietic tree - Lymphoma

54 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

55 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 and age >60 1-year relative survival rate 92% 5-year and 10-year survival rates are about 85% and 80%, respectively

56 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

57 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

58 Hodgkin Lymphoma- diagnostics Biopsy Excisional or incisional biopsy Fine needle aspiration (FNA) or core needle biopsy Pathology Reed-Sternberg cell

59 Hodgkin Lymphoma- Ann Arbor staging

60 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

61 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

62 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

63 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)

64 Non-Hodgkin s Lymphoma - Subtypes Follicular - 22% Composite - 13% Small Lymphocytic - 6% Mantal Cell - 6% Peripheral T Cell - 6% Diffuse Large B Cell- 31% Other - 9% MALT - 5% Lymphoplasmacti c - 1% Marginal Zone T - 1%

65 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

66 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

67 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

68 Non-Hodgkin s Lymphoma staging

69 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

70 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

71 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

72 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

73 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

74 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

75 Multiple Myeloma Scientific Basis for Practice

76 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

77 Hematopoietic tree Multiple Myeloma

78 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%.

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

80 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

81 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

82 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

83 Multiple Myeloma survival International Staging System Stage I Stage II Stage III Median Survival 62 months ~5yr 44 months ~ 3.5yr 29 months ~ 2.5yr Poor Prognostic factors: Older age Kidney function IgA sub type Increased circulating peripheral plasma cells Chromosomal abnormalities

84 Progression of Multiple Myeloma

85 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

86 Multiple Myeloma interventions Chemotherapy Immunomodulating agents Steroids Bisphosphonates Radiation Surgery Plasmapheresis Kyphoplasty or Vertebroplasty Stem Cell Transplant Autologous Allogeneic

87 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

88 Multiple Myeloma Interventions Proteasome inhibitors - Bortezomib (Velcade) Side effects : Immunosuppression (Acyclovir) Cytopenias especially thrombocytopenia Peripheral neuropathy Diarrhea Constipation Rash Hypotension Asthenias- lack of strength

89 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

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