Amy Pierre, RN, MSN, ANP-BC, from the Research Oncology Division for Flatiron Health and the Memorial Sloan Kettering Cancer Center, discusses how myelosuppression may present and how it can be managed in patients with multiple myeloma.
Hello! I’m Amy Pierre, and welcome to the Multiple Myeloma Center for Nurses. This video will explore the causes, appropriate monitoring, interventions, and management of myelosuppression in patients with myeloma.
Myeloma, a plasma cell malignancy, grows in the bone marrow, causing suppression of normal hematopoiesis, the process of new blood formation.1,2 This inability of the marrow to make blood cells is called myelosuppression.1 Several drugs used to treat myeloma can also cause myelosuppression.1 The reduction in blood cell production can cause various complications, such as anemia, neutropenia, and thrombocytopenia.2
Anemia results from decrease in production of red blood cells. It is a clinical feature found in approximately 75% of patients when they are first diagnosed.2 These patients may present with malaise, generalized weakness, and/or dyspnea.2
Neutropenia results from a decrease in production of neutrophils, which make up approximately 60% of all white blood cells and provide immune defense against bacterial and fungal infections.1 Febrile neutropenia is a condition marked by a single temperature of >38.3° C, or 101° F, or a sustained temperature of at least 38° C, or 100.4° F, for more than 1 hour, and an absolute neutrophil count less than 1000 per cubic millimeter.3 It is a life-threatening complication reported with some myeloma regimens that requires emergency intervention.4,5
The third complication is thrombocytopenia, which results from a decrease in the production of platelets, resulting in a decrease in the ability of the blood to clot after an injury.1 Symptoms include bruising; bleeding that doesn’t stop with pressure; and small red or purple spots on the body, called petechiae, caused by bleeding into the skin.1
If myelosuppression is not properly managed, it can interfere with quality of life and with the ability to receive the optimal dosing schedule of therapy, and can become life-threatening.2 Early intervention and appropriate management of myelosuppression and its consequences are important to improve patient outcomes, overall outlook, and survival.2
The International Myeloma Foundation’s Nurse Leadership Board developed a consensus statement that includes toxicity grading, strategies for monitoring and managing myelosuppression, and educational recommendations for patients and their caregivers.6 It is important to understand that anemia, neutropenia, and thrombocytopenia are expected side effects of myeloma and are associated with varying degrees with different myeloma regimens. They’re manageable with appropriate interventions and education.1,2,5,6
Now, let’s discuss guidelines for anemia. Anemia results from the lack of sufficient healthy red blood cells to carry oxygen to the body’s tissues and is best defined by reduction in blood hemoglobin levels.2 Common signs and symptoms include skin pallor, fatigue and lethargy, shortness of breath, and heart palpitations.2 The Common Terminology Criteria for Adverse Events, known as the CTCAE, provide a 5-point toxicity grading system that can measure the severity of a patient’s condition.3 Hemoglobin values reported as part of a complete blood count, or CBC, decrease with each of the 5 grades of anemia from grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, life-threatening; and grade 5, death related to anemia.3
A performance status interview should be done to identify quality-of-life symptoms. Fatigue, dyspnea, pallor, light-headedness, hypotension, tachycardia, reduced cognitive function, and emotional distress should be assessed.2 Vital signs, including temperature, blood pressure, pulse, respiratory rate, and oxygen saturation should be monitored.2 Nutritional status should be determined to exclude iron, folate, and vitamin B12 deficiency as causes of anemia.2
Fatigue is one of the most frequently reported symptoms in cancer patients.6 Severity and impact of fatigue can be rapidly assessed using a validated tool, called the Brief Fatigue Inventory, that measures 9 items on a 10-point numeric scale. On average, the inventory takes less than 3 minutes to complete.7
Anemia as a result of the myeloma itself, where patients are asymptomatic or minimally symptomatic, may improve as the myeloma’s controlled by treatment. These patients should be observed initially without intervention.2 If symptoms from anemia are reducing quality of life, then blood transfusions may be needed to correct moderate to severe anemia in the short-term.2 Alternatively, a course of an erythropoiesis-stimulating agent, abbreviated ESA, may help to increase red blood cell production and improve anemia.2 Treatment-induced anemia may be improved or corrected by reducing the dose of treatment or temporarily discontinuing treatment. If symptoms continue, patients may need to undergo blood transfusions.2
Now, let’s discuss guidelines for neutropenia. Neutrophil counts are monitored as part of a differential white blood cell count.3 The absolute neutrophil count, abbreviated ANC, in a sample of a patient’s blood, will determine if the patient is neutropenic and, if so, what their grade level of neutropenia is according to the Common Terminology Criteria for Adverse Events, abbreviated CTCAE.3 Neutropenia itself does not cause any symptoms, but it is important to assess if a patient with neutropenia has an infection, as neutropenic patients are at a greater risk of infection.2 Patient assessment should include the following: fever, chills, myalgia, malaise, nausea, hypotension, hypoxia, and a history of infections. Conduct a physical exam, including respiratory, urinary, and gastrointestinal symptoms.6
Neutropenia as a result of the myeloma may improve with antimyeloma treatment, but those with treatment-related neutropenia should be dose-reduced in the first instance and given granulocyte-colony stimulating factor, abbreviated G-CSF, if infection is recurrent.2
Neutropenic patients are at a greater risk of infection with Streptococcus pneumonia, Hemophilus influenzae, and gram-negative bacilli.2 Infection causing a febrile episode must be handled as an emergency situation and IV broad-spectrum antibiotics that cover these pathogens should be administered to prevent sepsis.2 Treatment should continue until neutrophil count has recovered and fever has abated. IV hydration and antipyretics should also be considered, where necessary.2 Routine antibiotic prophylaxis is only recommended in patients at high risk of infection,8 such as, in the stem-cell transplant setting. General prophylactic use has the potential for increasing Clostridium difficile infection and inducing antibiotic resistance, so it is not recommended in other settings.
Now, let’s discuss guidelines for thrombocytopenia. Platelet counts are monitored as part of a CBC. Thrombocytopenia is graded according to the CTCAE as shown in the Table.3 A patient with mild thrombocytopenia will likely not need treatment.9 A patient with thrombocytopenia is likely to present with 1 or more of the following signs2:
In addition to a family history, physical exam, and monitoring vital signs, a coagulation screen may be indicated to assess prothrombin time and partial thromboplastin time.2
As with anemia and neutropenia, myeloma-related thrombocytopenia may improve with antimyeloma treatment. Transient thrombocytopenia is common with antimyeloma treatment, but patients should be observed closely.2 If platelet counts fall below 25 x 103/µL, treatment should be withheld until platelet counts rise, and dose reduction should be considered for subsequent cycles. Alternatively, patients may continue with the same dose and be supported by platelet transfusions.2
Now, let’s review some areas where hematology-oncology nurses can play a pivotal role.2
Make sure that CBC values are taken at regular intervals, dependent on treatment and stage of myeloma.
Make sure that the results of other relevant tests are available, such as, blood cultures to determine source of infection, and oxygen saturation to determine severity of anemia.
Be vigilant for signs and symptoms of anemia, neutropenia, and/or thrombocytopenia, and report them to the hematologist; manage the signs of febrile neutropenia immediately to prevent sepsis.
Ask patients questions on a regular basis to assess their performance status, psychological well-being, and quality of life.
Discuss with patients the importance of blood count monitoring and the potential consequences of myelosuppression.
Inform patients and families about the importance of early detection and reporting of symptoms related to anemia, infection, and thrombocytopenia.
Educate patients and families on effective preventive measures to reduce the risk of infection and bleeding.
Discuss the risks and benefits associated with the different interventions for anemia, neutropenia, and thrombocytopenia.
Coordinate referral to other healthcare professionals, where appropriate.
Stay current with new developments in preventing, treating, and managing myelosuppression, and be aware of novel treatments that may cause myelosuppression.
This concludes the Myelosuppression video. Be sure to explore this site for more informational videos and resources.
References
1. International Myeloma Foundation. Myelosuppression. https://www.myeloma.org/myelosuppression. Accessed May 18, 2021.
2. Myeloma Academy. Best Practice Guide: Myelosuppression. https://academy.myeloma.org.uk/wp-content/uploads/2015/03/Myeloma-Academy-Best-Practice-Myelosuppression-Jan-15-RCN.pdf. Accessed May 18, 2021.
3. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, November 2017. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf. Accessed May 18, 2021.
4. BMJ Best Practice 2019. Febrile neutropenia. https://bestpractice.bmj.com/topics/en-us/950. Accessed May 18, 2021.
5. Leleu X, Gay F, Flament A, Allcott K, Delforge M. Incidence of neutropenia and use of granulocyte colony-stimulating factors in multiple myeloma: is current clinical practice adequate? Ann Hematol. 2018;97(3):387-400. doi:10.1007/s00277-017-3191-7
6. Miceli T, Colson K, Gavino M, et al. Myelosuppression associated with novel therapies in patients with multiple myeloma: consensus statement of the IMF Nurse Leadership Board. Clin J Oncol Nursing. (3 suppl 12):13-20. doi: 10.1188/08.CJON.S1.13-19
7. Brief Fatigue Inventory. (c) The University of Texas MD Anderson Cancer Center, 1999. https://www.ons.org/sites/default/files/2017-06/BriefFatigueInventory_English_1.pdf. Accessed August 31, 2021.
8. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma V.2.2022. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed October 26, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
9. Thrombocytopenia. National Heart, Lung, and Blood Institute. https://www.nhlbi.nih.gov/health-topics/thrombocytopenia. Accessed September 9, 2021.
