St.

John Providence Health System Fall 2013

Clinical Nutrition Case Study: Myelofibrosis

Michelle Baker
B.S. in Dietetics Student Coordinated Program in Dietetics Wayne State University

Table of Contents I. II. Introduction/Patient Profile page 2 Disease Background page 3 A. Description page 3 B. Epidemiology, Etiology, and Pathophysiology page 3 C. Symptoms and Diagnosis page 5 D. Prognosis page 6 E. Medical Treatment page 8 F. Nutrition Intervention page 9 III. IV. Present Illness and Medical Treatment page 9 Nutrition Care Process page 12 A. Nutrition Assessment page 12 1. Anthropometric Measurements page 12 2. Biochemical Data page 13 3. Nutrition-Related Physical Findings page 14 4. Client History page 15 5. Food- and Nutrition-Related History page 16 B. Nutrition Diagnosis page 18 C. Nutrition Intervention page 18 D. Nutrition Monitoring and Evaluation page 20 V. Conclusion page 20

References page 22 Appendices Appendix A Nutrition Needs Calculations Appendix B Initial ADIME Documentation Appendix C Teaching Plan

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I. Introduction/Patient Profile M.L.J. is a 62-year old Caucasian female who lives with her husband in a middle-class Northeastern suburb of Metro-Detroit. On September 19, 2013 around 5:00 PM she arrived at St. John Macomb Hospital via wheelchair with her spouse, following a referral from her primary care physician. The patient was alert and fully oriented, and presented with hypotension, tachycardia, generalized weakness, and fever with chills. Prior to this year, the patients medical history was significant for class III obesity, rheumatoid arthritis, hypothyroidism, gout, borderline type 2 diabetes mellitus, heart disease, hypertension, asthma, and anxiety. Despite these issues, she was relatively active and worked full-time, until she began to experience significantly increased pain and fatigue around November 2012, which had been attributed to rheumatoid arthritis and her obesity. Shortly after this time she began experiencing rapid unintentional weight loss and weakness. M.L.J.s medical records show a history of hospitalizations in 2013 prior to the current admission, the first of which lasted from February 23rd March 15th. During this time she was hospitalized for hyponatremia, dehydration, and aching bone pain, which were later accompanied by ventilator-dependent respiratory failure and sepsis during her stay. On March 6th she had a bone marrow aspiration and biopsy and was diagnosed with myelofibrosis, a serious disorder in which bone marrow is replaced with fibrotic tissue. Another bone marrow biopsy was later performed, and on March 15th she was also diagnosed with multiple myeloma, a hematological cancer of the plasma cells that originates in the bone marrow, where plasma cells begin formation. She was then transferred from the hospital to a care facility for one month for strength rehabilitation. Upon discharge from this facility, she began chemotherapy for her multiple myeloma. M.L.J. completed four cycles of chemotherapy from April through July, and

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as of August 2013 re-evaluation found the multiple myeloma to be in complete remission. Upon her arrival to the hospital on September 19th, M.L.J. had blood analysis performed, which found her white blood cell, red blood cell, and platelet levels all significantly low; her neutrophils were considered especially severe. She was admitted to the oncology floor in reverse isolation with a diagnosis of pancytopenia and febrile neutropenia secondary to myelofibrosis. Her admission plan included septic workup, broad-spectrum I.V. antibiotics, transfusional support, and growth factor support. II. Disease Background A. Description Myelofibrosis (MF) is a rare hematological disorder in which the bone marrow becomes hard and fibrotic, resembling scar tissue. Bone marrow contains the stem cells that develop into each main component of blood red blood cells, white blood cells, and platelets. Fibrosis of the marrow can lead to inadequate production of these important blood constituents, among other serious complications such as splenomegaly and cachexia. Myelofibrosis is also known by the names myeloid metaplasia, myelosclerosis, chronic idiopathic myelofibrosis, or primary myelofibrosis. This disorder belongs to a group of related stem cell-derived bone marrow disorders called myeloproliferative neoplasms (MPNs). As these neoplasms are malignant, the Leukemia and Lymphoma Society have labeled MPNs (including myelofibrosis) cancer to the public, though most researchers and clinicians opt not to use term as the disorders are unique hematological malignancies that are not dysplastic in nature and do not utilize the typical cancer staging system1, 2. B. Epidemiology, Etiology, and Pathophysiology Myelofibrosis is rare, occurring actively in approximately 1.5 out of every 100,000

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people each year, and it comes with a poor prognosis2. The condition affects both men and women equally and median age of diagnosis is in the mid-60s, though it may occur at any age. The vast majority of patients are in their 50s-70s2. Myelofibrosis can occur on its own or develop secondary to the other MPNs. More than 50% of those diagnosed with myelofibrosis test positive for a mutation of the gene Janus kinase 2 (JAK2), though it has been found that dysregulation of the JAK pathway may occur even in those patients who tested negative for the mutation2, 3. There is no inheritance pattern of the disorder, meaning the mutation does not tend to run in families, and cause of the mutation is widely unknown; therefore, there is currently no known prevention for myelofibrosis. However, it has been suggested that the risk of developing MF may be increased for people exposed to petrochemicals such as benzene and toluene or ionizing radiation1. Researchers are still attempting to determine the exact mechanism of how this disease occurs, but discovery of the JAK2 mutation has been greatly beneficial for developing treatment options. Normal bone marrow is soft tissue that exists inside the cavities created by networked cancellous or spongy bone. The main defining feature of myelofibrosis is the fibrotic tissue accumulation within the bone marrow. This abnormal tissue is composed of reticulin and collagen fibers, and advanced build up of these materials is often accompanied by elevated density of the spongy bone4. It appears that megakaryocytes, the giant cells in the marrow that are precursors to platelets, are abnormal in people with myelofibrosis and release high levels of cytokines, as these proinflammatory chemicals are noticeably elevated in serum labs of MF patients. Inflammatory cytokines may be at levels greater even than seen in inflammatory disorders such as rheumatoid arthritis3. It is speculated that these cytokines, along with influences from the JAK2 pathway and growth factor, stimulate synthesis of collagen fibers in

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the marrow5. This fibrotic tissue accumulates and inhibits erythropoiesis, causing anemia. Ineffective blood cell formation stimulates extramedullary hematopoiesis, in which growth of blood cells occurs in organs other than the marrow; this most commonly takes place in the spleen and liver, though the lungs, lymph nodes, vertebral column among other sites can also be involved1. Due to extramedullary hematopoiesis, enlargement of the involved organs is found in a majority of people with myelofibrosis. This is most often presents in MF patients in the spleen, causing splenomegaly to be a main identifying sign of the disease. C. Symptoms and Diagnosis As explained by the mechanisms above, clinical signs of the disease are most often anemia and palpable splenomegaly or hepatomegaly. As the myelofibrosis progresses, patients become hypercatabolic with increasing development of constitutional symptoms. The most prevalent symptoms are fatigue, lethargy, unintentional weight loss, drenching night sweats, fever, abdominal pain and fullness, early satiety, pruritus (itching), and bone pain. Bruising and shortness of breath, although less common, were also identified in more than 30% of patients in a large review6. A complete blood count on a myelofibrotic patient frequently shows anemia and leukopenia; about one third of patients will have platelet levels above normal limits and about one third of patients will have platelet levels below normal limits (due to the abnormal physiology of the megakaryotes in MF1). Microscopic examination of the blood may show immature cells and teardrop-shaped red blood cells, along with circulating dwarf megakaryotes and giant platelets. Along with blood tests, diagnostic testing is done to determine if the findings are indicative of myelofibrosis. Other diseases that affect the blood such as leukemia and lymphoma must be ruled out. Bone marrow biopsy and aspiration is performed to assess for fibrotic

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changes in structure and abnormal cell findings. Even if reticulin and collagen fibrosis is not significant yet, stains can highlight certain cells that are characteristic of the disorder. However, advanced disease progression often means tissue is too completely fibrotic and hardened to obtain an adequate sample2. Genetic mutation testing is usually performed as well; a positive finding for a myelofibrosis-related mutation such as JAK2 will help confirm a diagnosis, though a lack of mutation will not rule out the condition. Complete bone scans and MRIs are performed to assess for areas of increased bone density and organomegaly. Diagnostic criteria for myelofibrosis are set by the World Health Organization (WHO) and were last updated in 2008. Criteria guidelines are demonstrated in the chart below; WHO states that all three major criteria listed and two of the minor criteria must be met for a proper diagnosis2,7.
Table 1: Diagnostic Criteria2,7

WHO Diagnostic Criteria for Primary Myelofibrosis Megakaryocyte proliferation and atypia accompanied by either reticulin and/or collagen fibrosis -OR- in the absence of significant reticulin fibrosis, megakaryocyte changes must be accompanied by increased marrow cellularity, granulocytic proliferation and often decreased erythropoiesis (i.e. pre-fibrotic cellular phase disease) Not meeting WHO criteria for PV, CML, MDS, or other myeloid neoplasms Positive for JAK2 V617F or other associated mutations (i.e. MPL W515K/L) -OR- in the absence of positive mutations, no evidence that marrow fibrosis is secondary to another disease state Minor criteria (need 2) Anemia Splenomegaly Leukoerythroblastosis Increased serum LDH level

Major criteria (need all 3)

Abbreviations: WHO - World Health Organization; PV polycythemia vera; CML chronic myelogenous leukemia; MDS myelodysplastic syndrome; MPL myeloproliferative leukemia; LDH lactate dehydrogenase

D. Prognosis Unfortunately, prognosis of patients diagnosed with myelofibrosis is generally poor, though median length of survival varies based on disease severity. Median survival of all

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patients has been approximated to be around six years after diagnosis6. A tool called the Dynamic International Prognostic Scoring System-plus (DIPSS-plus) can be used at any point in the disease to determine what level of risk the patient is7. Risk stratification is based on several factors found to be independent predictors of decreased survival, and length of survival is based on how many of these risk factors are present. Using this model, patients are categorized as either low, intermediate-1, intermediate-2, or high-risk. Table 2 shows DIPPS-plus criteria and risk stratification with predicted survival.
Table 2: DIPPS-plus Prognostic Model7

Risk Factors Age > 65 years Hemoglobin < 10 g/dL Leukocytes > 25 x 109/L Circulating blasts 1% Constitutional symptoms Red cell transfusion dependency Platelet count < 100 x 109/L Unfavorable karyotype

Risk Stratification Low Intermediate-1 Intermediate-2 High

Number of Risk Factors Present 0 1 2-3 4

Median Survival in Years 15.4 6.5 2.9 1.3

As the disease progresses, many complications can emerge. Around 20% of myelofibrosis cases will transform into acute myeloid leukemia (AML), a rapidly progressing marrow cancer7. Patients are also likely to suffer from development of gout and portal hypertension with ascites or bleeding from esophageal varices1, 7. Severe anemia often accompanies myelofibrosis, and debilitating fatigue occurs in a vast majority of people with the disorder. The splenomegaly often caused by extramedullary hematopoiesis leads to abdominal pain, bloating, and early satiety as the enlarged spleen may encroach upon the stomach. The high amount of cytokines produced also may cause patients to develop a hypercatabolic state, and many become cachectic6. The combination of early satiety with hypercatabolism puts patients at profound nutrition risk. Main causes of death in people with myelofibrosis are Myelofibrosis | 7

reported to be hematologic progression (including development of AML), infections, thromboembolic events, hemorrhages/bleeding, and cachexia3. E. Medical Treatment The only curative treatment for myelofibrosis is allogeneic stem cell transplant (ASCT), but it is dangerous; about half of those who receive ASCT have transplant-related death or severe morbidity7. In the largest published study on the topic, only 30-50% of recipients survived three years after transplant8. Treatment, therefore, is largely palliative in manner, focused on improving quality of life and providing relief of the many symptoms and complications listed above. Anemia may be treated by periodic red blood cell transfusions, corticosteroids, androgens, injection of erythropoietin hormone or growth factor, and immunomodulators (such as interferon, thalidomide, lenalidomide, or pomalidomide). Splenomegaly, another cause of many symptoms, may be treated by the chemotherapy agent hydroxyurea, radiation therapy, or surgical removal (another risky procedure linked to high morbidity and mortality1, 2). Discovery of the Janus kinase gene and JAK pathway has helped researchers recently develop new possibilities for drug therapies. Ruxolitinib, a JAK inhibitor, was FDA-approved in 2011 and is currently the only approved drug intended to treat intermediate- or high-risk myelofibrosis. Clinical trials have shown that in at least half of patients, ruxolitinib can provide a sustained reduction in spleen size and substantial improvements in constitutional symptoms, cachexia, transfusion dependence, and progression to AML. However, the drug is likely to cause dizziness, headaches, and low platelet counts, and discontinuation causes symptoms to return1, 2. Several other JAK inhibitor medications in testing are showing promise that treatments for myelofibrosis will be improving in the near future8.

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F. Nutrition Intervention People with myelofibrosis are likely to benefit from a nutrition plan tailored to each patient depending on progression of disease. Intermediate- and high-risk myelofibrotic patients with splenomegaly present are at especially high risk for malnutrition due to the combination of early satiety and increased nutrient needs. Due to the hypercatabolic nature of the disease, foods should be dense in calories and protein and be dispersed throughout the day in small, frequent meals to optimize intake. As extreme fatigue is often an issue, patients are likely to consume more if foods are easy to obtain, prepare, and eat. To manage cachexia, patients may benefit from a combination of nutrition intervention and pharmacologic agents, such as appetite stimulants, metabolic agents, or anabolic agents. In addition, patients with myelofibrosis may have a low white blood cell count, thus they need to be especially careful to avoid any risk of food-borne illness9. III. Present Illness and Medical Treatment Following a referral from her physician, M.L.J. arrived to St. John Macomb Hospital on Thursday, September 19th around 5:00 P.M., pushed in a wheelchair by her husband. Upon arrival she appeared extremely weak; she was found to be hypotensive and somewhat tachycardic, and blood was drawn for laboratory assessment. Analysis revealed M.L.J. to have very low counts of red blood cells and platelets, and significantly depleted white blood cells. Hemoglobin and hematocrit were only 7 g/dL and 21%, respectively. Neutrophils were found to be severely depleted at only 500 per mm3. A history and physical revealed her home medication regimen to be positive for lenalidomide, an immunomodulator used in both treatment of myelofibrosis as well as part of a maintenance regimen for multiple myeloma in remission. She was admitted to the oncology unit that evening with a diagnosis of pancytopenia and neutropenia

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secondary to myelofibrosis. On the unit, M.L.J. was placed in a standard single room in reverse isolation, which encouraged anybody entering to wear a gown, facial mask, and gloves for her protection due to inability to fight foreign bacteria. She was started on cefepime (a broad-spectrum IV antibiotic) and IV fluids, given a magnesium sulfate injection since her serum magnesium had been low, Xanax for anxiety, and potassium chloride as part of her usual evening regimen. She was also started on Neupogen, a growth factor that stimulates WBC and neutrophil production and activity. The admitting physician determined M.L.J. to be in need of tranfusional support, and in the early hours of Friday, September 20th she had two bags of packed red blood cells infused. Friday, M.L.J. was noted to be febrile with a fever of 100.1F, and had complaints of chills and frequency of urination. She was seen by the registered dietitian and started on a neutropenic/low microbial diet with a nutritional supplement with each meal. She developed nausea and vomiting that afternoon, believed to be caused by the cefepime, which was discontinued and replaced with vancomycin and ciprofloxacin antibiotics; emesis resolved following antibiotic change and treatment with oral antiemetics. Blood work showed hemoglobin to have improved to 9.6 g/dL and hematocrit to 28.4% post-transfusion. WBCs improved to 1100 mm3 and neutrophils to 700 mm3, though both levels were still significantly low. That evening she was given another dose of growth factor to help improve these numbers, along with a new fentanyl analgesic patch for the aching bone pain she experienced chronically as part of her disease. M.L.J.s usual regimen of levothyroxine, potassium chloride, pantoprazole, and metoprolol was also given (medications are explained in further detail in Table 3). Continued on page 12

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Table 3: Patient Medications9 Medication Alprazolam/Xanax (1 mg BID PRN) * Drug Class Benzodiazepine, anti-anxiety Action Presumed to bind at stereospecific receptors at several sites within the CNS Replenishes electrolyte balance in the blood Control of T4 DNA transcription and protein synthesis Possible Adverse Effects Drowsiness, lightheadedness, depression, headache, confusion, insomnia, dry mouth, constipation, diarrhea, N/V, tachycardia/palpitations, blurred vision, nasal congestion Hyperkalemia, GI effects (obstruction, bleeding, ulceration), N/V, abdominal pain, flatulence, diarrhea Fatigue, increased appetite, weight loss, heat intolerance, headache, hyperactivity, irritability, insomnia, palpitations, arrhythmias, dyspnea, hair loss, menstrual irregularities Headache, diarrhea, N/V, abdominal pain, flatulence, dizziness Bradycardia, tiredness, dizziness, depression, SOB, diarrhea, pruritus, rash, heart block, heart failure, hypotension, dry mouth Nutrition Effects Avoid alcohol, use caution with grapefruit & herbal supplements; caffeine may lessen effects Avoid K+-containing salt supplements

Potassium Chloride/KDur (20 mEq BID) * Levothyroxine/Synthroid (75 mcg QD) *

Electrolyte supplement

Thyroid replacement hormone for hypothroidism

Pantoprazole/Protonix (40 mg QD) * Metoprolol/Lopressor (50 mg QD) *

Proton pump inhibitor, antiGERD, antisecretory Selective betablocker, antihypertensive, antiangina

Suppresses gastric acid production

Fentanyl (25 mcg patch q72h) *

Opioid analgesic

Lenalidomide/Revlimid (QD 3 weeks on with 7 days off in between) *

Ciprofloxacin IV (BID)

Antineoplastic, immunomodulatory, & antiangiogenic; for treatment of transfusiondependent anemia in myelodysplastic syndrome Fluoroquinolone/ broad-spectrum antibiotic

Reduced sympathetic outflow to periphery and suppression of renin activity Interacts with the opioid -receptor in the brain, spinal cord, & other tissues Thalidomide analog; activation of T cells & natural killer cells, increased NKT cells, inhibition of cytokines Inhibits enzymes required for bacterial DNA replication, transcription, repair, and recombination Stimulates proliferation & activation of hematopoietic cells

Respiratory depression, N/V, constipation, diarrhea, headache, pruritus, abdominal pain, dizziness, insomnia, somnolence, fatigue, anorexia Thrombocytopenia, neutropenia, DVT, PE, pruritus, rash, diarrhea, constipation, nausea, nasopharyngitis, arthralgia, cough, pyrexia, peripheral edema, dizziness

Decrease absorption with soy, cotton seed meal, walnuts, dietary fiber, iron, calcium, magnesium; caution with grapefruit May decrease absorption of iron & vit B12; avoid alcohol Take separately from orange juice, avoid natural licorice; dietary calcium and sodium may decrease absorption Avoid alcohol

>2-3 L/d fluid recommended; avoid alcohol

Hepatotoxicity, musculoskeletal symptoms, arthralgia, N/V, diarrhea, abdominal pain, neurological events, rhinitis, abnormal LFTs, rash, arthropathy

Increased effect of caffeine; may decrease natural gut flora

Filgrastim/Neupogen (480 mcg QD at HS)

Granulocyte/WBC colony stimulating factor; increase production & activity of neutrophils

N/V, skeletal pain, diarrhea, neutropenic fever, mucositis, fatigue, anorexia, dyspnea, headache, cough, splenomegaly, thrombocytopenia, stomatitis, hemorrhagic events

None noted

* Indicates this medication is to be included in M.L.J.s home medication regimen

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The next day, a urine culture was positive for gram-negative bacilli and WBCs. The infectious disease specialist saw the patient, and the physician impression was that a urinary tract infection likely triggered the neutropenic fever. Her fever persisted throughout the day but fortunately blood cultures were found negative for bacteria and the infection remained localized to the urinary system; this is of utmost importance in this patient as neutropenic sepsis puts immunocompromised patients at high risk for mortality. She continued to receive growth factor support and close monitoring. Sunday, the final report of the urine culture showed no appearance of any gram-positive bacteria, justifying discontinuation of the vancomycin. Growth factor support was continued and a complete blood count showed M.L.J.s neutrophil count to be improving accordingly. Her spleen was palpable but fever was controlled, and she reported feeling better. The following morning, on Monday, September 23rd, she was decided to be in stable condition and was discharged home. Discharge orders recommended she continue taking ciprofloxacin orally for one month and maintain neutropenic precautions, which included avoiding crowded places and maintaining safe hygiene and sanitation practices. IV. Nutrition Care Process A. Nutrition Assessment Anthropometric Measurements An R.D. consult was originally ordered for M.L.J. due to report of unintentional weight loss and decreased/poor appetite during the nurses nutrition screening. When asked about this, M.L.J., at 5-feet-6-inches tall, stated she was 259 pounds for years until last November 2012 when symptoms of her condition began to appear and her weight just started dropping. Weight history in the electronic medical record for the patient showed that in late February 2013 she weighed 205 lbs., in June was 156 lbs., and in late July was 144 lbs. She reported that she was Myelofibrosis | 12

down to 136 lbs., but a standing scale at admission weighed her at 134 pounds on September 19th. Considering usual body weight was 259 lbs. prior to November 2012 and was 134 lbs. in September 2013, this put her at unintentional weight loss of 48.4% over eleven months, which can unquestionably be considered severe weight loss. Her BMI was 21.7, which is normal at her current age of 62-years-old, but could be considered underweight if she were a mere three years older. Ideal body weight for any woman of 56 is 130 lbs., so she was at 103% of IBW (normal). Biochemical Data M.L.J.s blood analysis revealed many abnormal results due to her myelofibrotic tissues inability to produce an adequate blood cell supply. As discussed in section III, her red blood cells, hemoglobin, and hematocrit were deficient enough to require transfusion of two bags of packed RBCs, while her white blood cells, including absolute neutrophil count, absolute lymphocyte count, and absolute monocyte count were all drastically depleted. Platelets were found quite low as well. Total lymphocyte count (TLC) was calculated through use of WBC and percent lymphocytes values to compare to the absolute lymphocyte count generated during analysis; TLC was calculated to be only 175 cells/mm3,whereas a value less than 1500 cells/mm3 is considered to be at nutrition risk. This very low value was of course due to her myelofibrosis, but it is possible a protein-energy deficiency in M.L.J.s diet may have exacerbated this. As discussed above, her absolute neutrophil count of a mere 500 cells/mm3 put her in a very immunocompromised state in which any foodborne pathogen could cause her great harm. Other nutritionally-relevant labs were abnormal as well; sodium, calcium, and magnesium were all found slightly depleted, which may have been caused by overhydration, but considering M.L.J.s hypotension this may have been caused by inadequate mineral and

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electrolyte intake as well. BUN and creatinine appeared slightly elevated, which may possibly be attributed to the stress of a urinary tract infection on her system. A lab that was not performed on M.L.J. that may provide benefit would be a urea urinary nitrogen test to see the degree of catabolism occurring in her body (though this would not be appropriate at the time due to her urinary tract infection).
Table 4: MLJ's Initial Lab Values

Substance WBC RBC Hgb Hct Platelet % Neutro % Lymph Calc. TLC % Mono Abs Neutro Abs Lymph Abs Mono

Ref. Range 4.3-10 Thou/mm 4-5.5 Mill/mm 12-15 g/dL 37-47% 100-450 Thou/mm 40-60% 20-40% >1500 cells/mm 2-10% 1.8-8 Thou/mm3 1.1-5 Thou/mm
3 3 3 3 3 3

Value 0.7 (L) 2.57 (L) 7.0 (L) 21 (L) 60 (L) 56 25 175 (L) 9 0.5 (L) 0.2 (L) 0.1 (L)

Substance Glucose BUN Creatinine Sodium Potassium Chloride Calcium Magnesium AST ALT Total Protein Albumin

Ref. Range 70-120 mg/dL 7-21 mg/dL 0.6-1.1 mg/dL 136-145 mmol/L 3.5-5 mmol/L 98-107 mmol/L 8.4-10.2 ng/dL 1.3-2.5 mg/dL 0-35 U/L 4-36 U/L 6.4-8.3 g/dL 3.5-5 g/dL

Value 70 28 (H) 1.21 (H) 127 (L) 4.8 99 8 (L) 1 (L) 34 15 6.6 2.1 (L)

0.2-1.1 Thou/mm

Nutrition-Related Physical Findings Upon discussion with M.L.J. and her spouse about her weight loss, her husband enthusiastically divulged her license photograph as evidence of how she looked one year ago. The woman pictured had a very rotund face with rosy cheeks and chestnut-brown hair. The same woman in the hospital bed however, despite having the same eyes, nose, and mouth as the woman in the photograph, gave the appearance that she had aged numerous years over this span. M.L.J. appeared friendly and smiling, though very fatigued and pale, with prominent cheekbones and hair that was very thin, sparse, and lacking color. She was visibly shaking with chills despite

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having blankets pulled up to her chin. Physical assessment of M.L.J. demonstrated ample folds of loose skin. She had slightly dark orbital circles with a somewhat hallow look to her eyes and a triceps pinch gave some depth to the pinch but not an ample amount. Hollow, scooping depression of her temples was evident, her shoulder bones protruded slightly, and her scapula bones were prominent with significant muscle deficit. Her thighs were very thin with depression of quadriceps and lack of definition, her knees prominent, and calves not well developed. Her hands presented a somewhat depressed interosseous area between the thumb and forefinger. Client History As has been described previously, M.L.J. was an active working woman with class III obesity, hypertension, and borderline type 2 diabetes mellitus up until November 2012 when fatigue, weakness, and pain began to intensify, later accompanied by decreased appetite. She had been diagnosed with rheumatoid arthritis (RA) in September 2012; her medical record was also positive for gout, hypothyroidism, gastroesophageal reflux disease, asthma, and anxiety. Surgical history was positive for cholecystectomy, tonsillectomy, and hysterectomy. For several months her aching pain and weakness had been attributed to rheumatoid arthritis. In late February she was hospitalized for pneumonia and pancytopenia (credited to her RA medication), and computed tomography of her abdomen showed splenomegaly. During this extended hospital stay she had a bone marrow aspiration and biopsy performed, along with genetic testing for the JAK2 mutation. In early March she was found negative for the mutation but results of the aspiration and biopsy found increased reticulin and atypical megakaryotes, which combined with her splenomegaly, pancytopenia, and other symptoms to lead to diagnosis of myelofibrosis. Almost concurrently, she was also found to have multiple myeloma, or plasma cell cancer. Due

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to the infrequency of myelofibrosis and the increased rarity of MF with coexistent multiple myeloma, the conditions were seen as independent entities. In Mid-March, she was sent from the hospital to an extended care rehabilitation facility where she stayed for one month, following which she had a MediPort inserted and was sent home to start chemotherapy. From April through July she completed four cycles of bortezomiband dexamethasone-based chemotherapy. During this period she was hospitalized once in June for pancytopenia requiring transfusional support, believed to be secondary to chemotherapy and/ or myelofibrosis. In August she was reported to be in complete remission of the multiple myeloma. It is unclear at what point throughout the year M.L.J. began the lenalidomide to treat her myelofibrosis. Her current admission appears to be the first time she was identified as having significant neutropenia, though this is not certain. At the time of current hospitalization, the patient lived with her husband, who is very involved and concerned in the care and wellbeing of the patient. She was also known to have an adult daughter who is active in her life though she lives away from home. M.L.J.s husband reported that he switched jobs to work at their building complex so he could assist her at times when she is too weak to ambulate on her own and needs help getting to the bathroom. Her mobility and activity tolerance seem to be increasingly limited. Food- and Nutrition-Related History M.L.J. admitted her appetite has been basically nonexistent since December 2012. She described early satiety secondary to splenomegaly, declaring that her spleen presses against her stomach and causes her to feel full all the time. She is too weak and fatigued for meal preparation, but her husband asserted that he likes to cook. She stated that every day she makes herself eat five times. She described typical daily intake as consuming four 4-ounce Health

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Shakes and typically three to four bites of chicken pot pie or cereal with two-percent milk. Two unopened Health Shake cartons from home were seen in a clean bedpan full of ice on the bedside table. She stated her previous chemotherapy caused her to have many taste changes and aversions, and she cannot tolerate meat. She had tried Ensure but she found them too metallictasting and too sweet. The interview with the patient also revealed a shellfish allergy. It appeared that M.L.J. may have had previous medical nutrition therapy with a dietitian during a previous hospitalization since the Health Shakes she was consuming at home are analogous to the MightyShakes supplied by the hospital to patients with increased needs. She had attempted compliance by utilizing these shakes while at home, though they were likely not intended to be her sole source of nutrition. Four of these Health Shakes provide 800 calories and 24 grams of protein. It can be assumed she was not consuming much more energy from the few bites of her last meal each day. She had already lost a great amount of weight and muscle from the combining effects of myelofibrosis and multiple myeloma on her system; even though the multiple myeloma is in remission, her myelofibrosis remains active and it can be an incredibly catabolic disease. M.L.J.s nutrient needs were therefore calculated to be upwards of 2150-2400 calories and 90120 grams of protein per day, which she was clearly not meeting. Fluid needs were calculated to be around 1850 mL/day according to the age method, but ideally she should be exceeding this since the lenalidomide she takes recommends drinking 2000-3000 mL/day. During her current admission the patient had been prescribed a regular neutropenic/low microbial diet, though the majority of her home diet was not too far from this as each shake comes individually packaged and sterile until opened if refrigerated properly. Preferably she should be attempting to consume a high calorie/high protein diet to ensure no further losses

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occur and to build her bodys protein stores. The protein she is able to take in needs to be of high biological value if she is not capable of consuming large amounts. The patients husband was enthusiastic to attempt whatever he can to improve her nutrition and comply with her immunological status; the patient appears slightly doubtful that she will be able to make changes but was very willing to try. B. Nutrition Diagnosis Assessment of the patient revealed that a main concern with M.L.J. was that she was only taking in less than 50% of her protein and energy needs each day over many months. This put her at profound nutrition risk, especially since cachexia is one of the main contributing causes of death in myelofibrosis3. Physical assessment of the patient revealed moderate fat loss and severe muscle wasting, which in combination with her poor intake and severe weight loss gave her an indubitable diagnosis of malnutrition. M.L.J. was given the nutrition diagnosis of malnutrition (severe malnutrition in the context of chronic disease) related to increased energy needs due to catabolic illness, poor appetite, and early satiety as evidenced by severe unintentional weight loss of 48.4% over 11 months, intake of <50% of her estimated energy needs over 11 months, moderate fat loss, severe muscle wasting, and myelofibrosis. Neutropenic diet precautions due to her immunocompromised state were also a nutritional concern for M.L.J., though a separate nutrition diagnosis was not needed for this at the time. C. Nutrition Intervention As M.L.J. needed to increase her nutrient intake as soon as possible, the dietitian encouraged her to order small, frequent meals continuously throughout the day while at the hospital. Her diet order was maintained as regular with neutropenic/low microbial precautions. The R.D. ordered MightyShake supplements to be sent up from the kitchen three times per day,

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and arranged for the current shakes in her room to be refrigerated and retrieved upon request. Diet education was determined necessary for the neutropenic diet and for a high calorie and high protein diet. The R.D. made a note to ask the physician to consider prescribing the patient an appetite stimulant. The R.D. also requested that the physician consider supplemental enteral feedings, and to consider if the patient may be a candidate for a PEG or PEJ tube once her condition was stabilized. Education for the patient focused on neutropenic diet components and increasing calorie and protein intake. Educational materials obtained from the Academy of Nutrition and Dietetics Nutrition Care Manual (similar to those found in Appendix D) were provided to the patient to take home, along with the dietitians business card and department contact information in case questions arose later. The neutropenic diet instruction addressed safe food handling and storage along with which foods may be unsafe for patient consumption. With special regard to the patients usual intake of chicken pot pie, she was informed to only consume leftovers within 24 hours and to first reheat them thoroughly. Both the patient and her husband verbalized their understanding, and compliance to neutropenic recommendations was expected to be high. High protein and high calorie diet advice was also supplied. The R.D. verbalized this instruction during the initial visit and returned that afternoon to provide handouts including recipes and tips for how to increase calorie and protein density of foods. The R.D. discussed with the M.L.J. and her husband the importance of maintaining adequate intake. They were encouraged to incorporate extra protein and fat into what she was already eating by utilizing whole milk and whey protein powder. M.L.J.s husband suggested he could incorporate these into the sauce that he prepares for the chicken potpies. He appeared very motivated to make any changes he could to improve his wifes nutrition status, and she agreed to try the changes.

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Appendix D offers further details about the teaching plan for the patient. D. Nutrition Monitoring and Evaluation At the time of assessment on M.L.J.s first full day at the hospital, the R.D. set parameters to be monitored throughout the course of her stay. Acceptance of the hospitals MightyShakes along with percentage of meals and supplements consumed was requested to be documented by the attending nurse. A new medication order for an appetite stimulant was monitored and unfortunately never materialized. The patient was monitored for weight changes and gastrointestinal profile was watched closely. M.L.J. developed nausea and vomiting from the antibiotics after the R.D.s visit, but with help of antiemetic medications and a switch in antibiotics, this resolved quickly. Hydration status was monitored by tracking her intake and output and assessing for signs of dehydration or edema. The course of her infection, along with her blood count status, was surely monitored as well. Ideally, as she was malnourished and fighting a catabolic disease, M.L.J. would have a follow-up evaluation after being home for some time, perhaps by an outpatient or home-care dietitian. This follow up would evaluate if she had any weight gain or further losses, her adherence to neutropenic precautions (if still deemed necessary at the time), and her adherence to and acceptance of increased protein and calorie food modifications. After some time at home with the new modifications, her need and/or desire for supplemental enteral nutrition would also be evaluated. V. Conclusion Unfortunately even the closest adherence to nutrition recommendations wouldnt mitigate all the painful symptoms of her disease, but improving her nutrition status could possibly enhance M.L.J.s quality of life and potentially even length of life. It is hoped that her home

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physician is able to address the malnutrition and cachectic processes still occurring due to myelofibrosis (and not only her prior chemotherapy) before they advance beyond hope. Myelofibrosis is a quite rare but very serious condition that can easily affect a patients entire well-being. As evident by M.L.J., symptoms can appear quickly and severely. Advanced treatments are still being researched, but with the recent discovery of certain genetic links it is hoped that the disease will be better controlled in the very near future. M.L.J.s recent visit represented a typical myelofibrotic patient whose blood production became too insufficient and required transfusional and growth factor support. When this occurs it is possible for even a small amount bacterial invasion, in an area such as the urinary tract, to become a huge threat to the patient. Myelofibrosis also puts patients at profound nutrition risk since it can be a very catabolic disorder, as M.L.J. exemplifies. As a dietetic student still gaining experience in the medical world, I was very grateful to be included in this interesting case. It astounded me how drastically M.L.J.s entire life and physique changed over a matter of months. The friendliness, enthusiasm, and optimism given off by M.L.J. and her husband in the face of such serious and debilitating illness really touched me. It was disappointing to realize we, the dietetic staff, could not do much for her in terms of more aggressive nutrition intervention without the interest and support of a physician, who may not consider that a top priority. As this case was both medically fascinating and empathyinducing, I feel it is one that will stay in my mind long after my clinical rotation has completed.

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References 1. Myelofibrosis Facts; http://www.lls.org/content/nationalcontent/resourcecenter/freeedcationmaterials/mpd/pdf/idiopathicmyelofibrosis.pdf. L.L.Society, Editor 2012. 2. Kim J, Haddad R, Atallah E, Myeloproliferative neoplasms. Dis Mon. 2012; 58 (4): 177- 94. 3. Pieri L, Loiacono I, Vannucchi A, The burden of symptoms in myelofibrosis: from patientreported outcomes to health economics. Leuk Res. 2013: 37(8): 855-856. 4. Tefferi A, Myeloproliferative neoplasms 2012: the John M. Bennett 80th birthday anniversary lecture. Leuk Res. 2012: 36(12): 1481-1489. 5. Della Porta M.G, Malcovati L, Myelodysplastic syndromes with bone marrow fibrosis. Haematologica. 2011:96(2): 180-183. 6. Debanjali M, Kaye J, Piecoro L, et al. Symptom burden and splenomegaly in patients with myelofibrosis in the United States: a retrospective medical record review. Cancer Medicine. 2013:2(5): 1-9. 7. Tefferi A, Primary myelofibrosis: 2013 update on diagnosis, risk-stratification, and management. Am J Hematol. 2013:88(2): 141-150. 8. Vannucchi A.M, Management of myelofibrosis. Am Soc Hematol. 2011: p. 222-230. 9. Mahan LK, Escott-Stump S, Raymond JL, Krause's Food and the Nutrition Care Process. 13th ed. St. Louis, MO: Elsevier Saunders; 2012.

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