Updates in the Management of Anemia in Cancer · Impaired production/hypoproliferative anemia ......
Transcript of Updates in the Management of Anemia in Cancer · Impaired production/hypoproliferative anemia ......
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Updates in the Management of Anemia in Cancer
Taylor M. Ortiz, MD
May 19, 2017
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Objectives
Recall common causes of anemia in patients with cancer
Understand risks/benefits of blood transfusion in patients with cancer
Understand the risks/benefits of erythropoiesis stimulating agents (ESAs) for anemia in patients with cancer
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Objectives
Recall common causes of anemia in patients with cancer
Understand risks/benefits of blood transfusion in patients with cancer
Understand the risks/benefits of erythropoiesis stimulating agents (ESAs) for anemia in patients with cancer
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Anemia in Cancer
Today’s focus is on anemia in patients with solid tumors or lymphoid malignancies
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Prevalence of Anemia
40%-63% of patients with cancer are anemic prior to treatment 32% of patients with Non-Hodgkin’s lymphoma
49% of patients with gynecologic malignancies
Degree of anemia correlates with Cancer stage
Inflammatory markers
Albumin, cholesterol, leptin
90% of patients treated with chemotherapy are anemic
Knight W, et al. Am J Med, 2004 Maccio A, et al. Haematologica, 2015
Stasi R, et al. Cancer, 2003 NCCN Guidelines, Cancer and Chemotherapy induced Anemia, v 2.2017
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Etiology of Anemia in Cancer Impaired production/hypoproliferative
anemia Low reticulocyte count
Nutritional deficiency
Malignancy-induced
Myelosuppressive chemotherapy or radiation-induced
Decreased erythropoietin production
Red cell destruction/decreased RBC survival High reticulocyte count
Intra/extra-vascular hemolysis
Blood loss Hemorrhage via intraluminal bleeding or RP/hepatic
internal bleeding
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Etiology of Anemia in Cancer Impaired production/hypoproliferative
anemia Low reticulocyte count
Nutritional deficiency
Malignancy-induced
Myelosuppressive chemotherapy or radiation-induced
Decreased erythropoietin production
Red cell destruction/decreased RBC survival High reticulocyte count
Intra/extra-vascular hemolysis
Blood loss Hemorrhage via intraluminal bleeding or RP/hepatic
internal bleeding
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Hypoproliferative anemia in cancer: Nutritional deficiencies
Cancer/chemotherapy-induced nausea and anorexia
Neoplastic-induced malabsorption Secondary to involvement of
duodenum/jejunum
Surgical resection Gastric tissue/terminal ileum -> B12 def
Gastrectomy->achlorhydria -> iron malabsorption
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Hypoproliferative anemia in cancer: Bone-marrow infiltration
Common in leukemia, lymphoma, plasma cell dyscrasia
Uncommon in solid tumor malignancies Can be seen in gastric and prostate
Ca.
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Bone marrow infiltration by
gastric carcinoma
Guner SI, J Ca Clin Trials, 2015
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Myelopthisis with
dacrocytes/ teardrop cells
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Hypoproliferative anemia in cancer: Anemia of inflammation
Cancers frequently produce IFN-α/β/γ, TGF-β, IL-1/6
Causes a block in iron utilization or erythropoietin production
Increased hepcidin
Iron sequestration within macrophage
Decreased duodenal absorption
Decreased mobilization of stored iron
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Girelli D, et al. Blood, 2016
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Hypoproliferative anemia in cancer: Myelosuppressive Chemotherapy Frequently accompanied by
thrombocytopenia and neutropenia
Expected timing of anemia varies by chemotherapy regimen, schedule Hgb trend is less dynamic than WBC/ANC
during chemotherapy; is more “cumulative”
Recent labs are critically important to determine expected change in hgb over subsequent days
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Example during one cycle of myelosuppressive chemotherapy
Adapted from www.neupogenhcp.com
Hemoglobin
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Hypoproliferative anemia in cancer: Myelosuppressive Chemotherapy Two common mechanisms for anemia
Direct suppression of RBC precursor synthesis in bone marrow
Usually through impaired DNA synthesis/mitosis
Decreased erythropoietin production
Nephrotoxicic effects
Ex: Cisplatin Platinum-containing DNA cross-linker
Interferes with RBC precursor synthesis
Also has direct nephrotoxic effects
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Etiology of Anemia in Cancer Impaired production/hypoproliferative anemia
Low reticulocyte count Nutritional deficiency
Malignancy-induced
Myelosuppressive chemotherapy or radiation-induced
Decreased erythropoietin production
Red cell destruction/decreased RBC survival High reticulocyte count
Autoimmune
Microangiopathic hemolysis
Blood loss Hemorrhage via intraluminal bleeding or RP/hepatic internal
bleeding
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Increased RBC destruction: Autoimmune Hemolytic Anemia
Can be seen in Chronic lymphocytic leukemia
Less frequently in Carcinoma Non-Hodgkin lymphoma Myelodysplastic syndrome Others
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Increased RBC destruction: Autoimmune Hemolytic Anemia
IgG or complement mediated Labs notable for
Elevated
Reticulocyte count
LDH
Indirect bili
Decreased Haptoglobin
Positive Coombs/DAT
Spherocytes
Cold-reacting autommune hemolysis is less common
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Direct Coombs Test/DAT
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Increased RBC destruction: Microangiopathic hemolysis
TTP, HUS, DIC Can be seen in liquid or
solid tumors Adenocarcinomas
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Schistocytes in microangiopathic hemolytic anemia
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Etiology of Anemia in Cancer Impaired production/hypoproliferative anemia
Low reticulocyte count Nutritional deficiency
Malignancy-induced
Myelosuppressive chemotherapy or radiation-induced
Decreased erythropoietin production
Red cell destruction/decreased RBC survival High reticulocyte count
Autoimmune
Microangiopathic hemolysis
Blood loss Hemorrhage via intraluminal bleeding or RP/hepatic internal
bleeding
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Acute and chronic hemorrhage
Intraluminal tumors (GI/GU tract)
Coagulopathies are common in cancer patients Many cancer patients are also treated with
anticoagulants
DIC in leukemias, mucinous adenocarcinomas
Stress and corticosteroids may contribute to gastric-mucosal erosive disease
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Initial Assessment of Cancer Patient with Anemia History
Symptoms, nutritional status, EtOH
Recent transfusions
Bleeding, menses
Medications (including anticoagulants/antiplatelet agents)
Timing/duration of chemo/radiotherapy treatment
Recent labs
Physical Examination Stool guaiac*
* Digital rectal exams are relatively contraindicated in patients with absolute neutrophil count less than 500/uL
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Laboratory evaluation
CBC MCV, platelets, other cytopenias
Reticulocyte count
Ferritin
B12, folate, TSH, iron/TIBC
Blood smear
PT/INR, PTT
Type and cross
Additional studies Haptoglobin
LDH
Fibrinogen, d-dimer
Coombs/DAT
Tbili/Dbili
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Objectives
Recall common causes of anemia in patients with cancer
Understand risks/benefits of blood transfusion in patients with cancer
Understand the risks/benefits of erythropoiesis stimulating agents (ESAs) for anemia in patients with cancer
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What is the goal hemoglobin?
There isn’t one Depends on
Timing of chemo/radiotherapy
Comorbidities
Symptoms
Recent labs are critical to predict the trend
In asymptomatic patients, short-term follow-up with repeat labs is reasonable
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PRBC transfusion in cancer: Clinical pearls Understanding trend of Hgb versus chemotherapy
administration guides transfusion Avoid transfusion in the setting of autoimmune
hemolysis Ferritin prior to transfusion Leukoreduced (and irradiated) RBCs reduce
Febrile non-hemolytic reaction
Alloimmunization/platelet refractoriness
Viral infection
1 unit should increase Hgb by ~1g/dL In a patient with previous stem cell transplant, consult
transplanter first
Sirchia G, et al. Transfusion, 1987
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Risks of RBC transfusion
Transfusion associated circulatory overload (TACO)
Transfusion reactions
Bacterial contamination/viral infection
Alloimmunization
Cancer and chemotherapy induced anemia, NCCN Guidelines, 2.2017
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Objectives
Recall common causes of anemia in patients with cancer
Understand risks/benefits of blood transfusion in patients with cancer
Understand the risks/benefits of erythropoiesis stimulating agents (ESAs) for anemia in patients with cancer
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Erythropoiesis-stimulating agents
ESAs (darbepoetin, epoetin alfa) may be suitable in patients with non-acute needs or who refuse PRBCs
Risks Increased thromboembolic events
Potential hastened progression of malignancy*
Breast, lung, lymphoid, head & neck, cervical cancers
Untch M, et al. JCO 2015 Hedenus M, et al. BJH, 2003 Henke M, et al, Lancet 2003
Leyland-Jones B, et al. JCO 2005 Overgaard J, et al. JCO, 2009
Smith RE, et al. JCO 2008 Wright JR, et al. JCO 2007
* FDA REMS in effect thru April 2017
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Epoetin alfa vs placebo in metastatic breast cancer
Leyland-Jones B, et al. JCO, 2005
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Epoetin-β vs placebo in head and neck cancer
Henke M, Lancet, 2003
Prog
ress
ion
free
sur
viva
l
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Anemia in cancer: Take-aways Start with a broad differential
Consider the categories of anemia
Important to understand the patient’s point in their treatment course
In patients on myelosuppressive chemotherapy, follow-up labs/visits and communication of lab results improves care
Transfuse leukoreduced PRBC when necessary
Avoid ESAs in patients with curable tumors
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References Prevalence of Anemia; Knight W, et al. Am J Med, 2004
Prevalence of Anemia; Maccio A, et al. Haematologica, 2015
Prevalence of Anemia; Stasi R, et al. Cancer, 2003
NCCN Guidelines, Cancer and Chemotherapy induced Anemia, v 2.2017
Bone marrow infiltration by gastric carcinoma; Guner SI, J Ca Clin Trials, 2015
Girelli D, et al. Blood, 2016
PRBC transfusion in cancer: Clinical pearls; Sirchia G, et al. Transfusion, 1987
Cancer and chemotherapy induced anemia, NCCN Guidelines, 2.2017
Erythropoiesis-stimulating agents; Untch M, et al. JCO 2015; Hedenus M, et al. BJH, 2003; Henke M, et al, Lancet 2003; Leyland-Jones B, et al. JCO 2005; Overgaard J, et al. JCO, 2009; Smith RE, et al. JCO 2008; Wright JR, et al. JCO 2007
Epoetin alfa vs placebo in metastatic breast cancer; Leyland-Jones B, et al. JCO, 2005
Epoetin-β vs placebo in head and neck cancer; Henke M, Lancet, 2003
Cancer- and chemotherapy-induced anemia, National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology, Version 2.2017, accessed February 21, 2017, https://www.nccn.org/professionals/physician_gls/f_guidelines.asp#site
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