BMT Case Study

1. BMT Case Study By Lark Duncan

2. Patient Overview • 53 YOWM • Relapsed Non-Hodgkins Lymphoma • Diet: Immuno • PMH: Large-cell malignant lymphoma, Hepatitis B & C, HTN, erosive esophagitis • Ht: 70” • Admit Wt: 84.1kg • Most Current Wt: 85.2kg

3. Patient Overview • Patient Received: • Chemo • Kills all or most fast growing cells such as bone marrow, hair cells, some GI cells, etc. • ALLO MUD • Allogenic transplant from a matched unrelated donor. • Higher risk of complications • Significant Labs that were altered: • AST/ALT/Alk Phos • Albumin • WBC/Platelets

4. What is Non-Hodgkins Lymphoma? • Non-Hodkins Lymphoma is a cancer that begins in the cells of the immune system: • Lymph vessels • Lymph • Lymph Nodes • Other parts such as spleen or tonsils • Usually it is found in a lymph node first

5. What is Non-Hodgkins Lymphoma? • Risk Factors: • Weakened Immune System • Inherited, Organ transplant • Certain Infections • HIV, H. pylori, Hep C • Age • Most people are over 60

6. What is Non-Hodgkins Lymphoma? • Symptoms • Swollen lymph nodes • Weight loss • Fever • Night Sweats • Coughing, trouble breathing, chest pain • Weakness

7. What is Non-Hodgkins Lymphoma? • Types of NHL: • Indolent – slow growing • Aggressive (intermediate or high grade) – fast growing • Stages of NHL: • Stage I – lymphoma cells are in one lymph node group or in one organ (not liver or bone marrow) • Stage II – lymphoma cells are found in at least 2 lymph nodes on the same side of the diaphragm • Stage III – lymphoma cells both above and below diaphragm • Stage IV – lymphoma in several parts of one or more organs or tissues or is in the liver, blood, or bone marrow • Recurrent – the disease returns after treatment

8. Treatment • Side effects of chemotherapy: • Blood cells lowers – both red and white cells are lowered making the patient tired and weak. • Blood can be given or Rx to help the body make more cells • Hair loss • Loss of proper GI function – often poor appetite, nausea, vomiting, diarrhea, trouble swallowing, taste changes, or mouth and lip sores.

9. Treatment • Bone Marrow Transplant • Autologous stem cell transplant – uses the patient’s own stem cells • Allogenic stem cell transplant – donor cells are used from a relative or an unrelated donor • Syngenic stem cell transplant – cells from the patient’s healthy identical twin

10. Drug-Nutrient Interactions • Xanax – caution with grapefruit, decr. appetite, decr. weight, incr. weight • Magnesium Oxide – may need AL supplement • Phenergan – for Nausea • Acyclovir – Anorexia • Benicar HCT – Caution with K supplement or salt substitution • Zofran – for Nausea • Zocor – avoid grapefruit/related citrus

11. Drug-Nutrient Interactions • Celexa – incr. weight, incr. appetite • Clonazepam – decr. weight, incr appetite, incr. weight • Lexapro – incr. weight, incr. appetite • Epivir – Anorexia, N/V • Bactrim – Anorexia, N/V • Fludara – Anorexia, stomatitis, N/V • Actigall – N/V/D/C

12. Drug Nutrient Interactions • Levofloxacin – N/D, take with water • Cefepime – May need Vit K supplement • Vancomycin – nausea • Tacrolimus – Anorexia, incr. appetite, decr Fe • Oxycodone – Anorexia, N/V/C • Decadron – high BG

13. Nutritional Implications • Loss of appetite – encourage protein and kcal intake and explain importance for strength and healing • Taste changes – provide food preferences, make suggestions on the menu from prior experiences • Mouth sores – provide foods that are soft and low acid • Nausea/Vomiting – provide bland foods, TPN

14. Nutritional Implications • Oral Feedings • Enteral Feedings • GI issues are common with chemo and BMT patients • TPN • Higher risk of infection • Low plate count • Central line in place • GI issues

15. Medical Terminology • Allogenic Stem Cell Transplant – patient receives bone marrow cells from a genetically similar, but not identical donor. • B-cell – a white blood cell that comes from bone marrow. It makes antibodies and fights infection. • Blood transfusion – administration of blood or blood products into a blood vessel. • Large-cell lymphoma – type of B-cell NHL that is usually aggressive.

16. Nutrition Intervention • Diet Rx: Immunosuppressive Diet • Helps prevent infection • Education: Immuno Diet, Importance of Protein/Kcal • Diet well accepted, followed • Willing to try new foods to increase Pro/Kcal • Supplements: Ensure Plus TID • Tried to drink at least two a day

17. Significant Events • 7/8: Admission Date • 7/9: Start Chemo • 7/12: Minimal toxicity – nausea • 7/14: Fever, rigors, chills, headache • 7/16: Transplant today, transfuse platelets, acute onset of abdominal pain from thickening/edema of the ileum, NPO for the night • 7/18: Rash from serum sickness

18. Significant Events • 7/19: Platelet transfusion • 7/21: Liver labs elevated, grade 2 toxicity • 7/22: Liver labs more elevated (very high), noted depression • 7/24: Liver labs still very high, continued toxicity • 7/26: Liver labs begin to normalize • 8/3: Liver labs normal

19. Significant Events • Patient had no signs of GVHD • Can effect: • Liver • Skin • Mucosa • GI

20. Review of Literature • TNFAIP3/A20 functions as a novel tumor suppressor gene in several subtypes of non-Hodgkins lymphoma. • The deletion of chromosome 6q is associated with tumorigenesis of lympoid malignancies. • The NK-kB pathway is the primary target for 6q deletion in B-cell • TNFAIP3/A20 is a negative regulator of the NF-kB pathway. • Findings: By increasing the activation of TNFAIP3/A20 there was an association with resistance to apoptosis

21. Review of Literature • Distinctive natural history in hepatitis C virus postive diffuse large B-cell lymphoma: analysis of 156 patients from northern Italy. • Hepatitis C virus (HCV) infection has been associated with increased risk of developing B-cell lymphoproliferative disorders. • Findings: HCV patients had a more frequently elevated LDH and were older at diagnosis. • They had favorable outcomes. • There was a high occurrence of spleen involvement. • In comparison to patients without HCV, these patients had a distinctive presentation and natural history.

22. Review of Literature • High-Dose Celecoxib and Metronomic “Low-dose” Cyclophosphamide Is an Effective and Safe Therapy in Patients with Relapsed and Refractory Aggressive Histology Non-Hodgkin’s Lymphoma. • Angiogenesis is increased in aggressive histology non-Hodgkin’s lymphoma and may be a target with selective cyclooxygenase-2 inhibition and metronomic chemotherapy. • Most common toxicity was skin rash • Gastrointestinal side effects were uncommon • Survival rate is comparable to other chemo regiments • Findings: This regiment is a safe way to treat relapsed Non-Hodgkins, especially due to the minor side effects.

23. Review of Literature • Upfront high-dose sequential therapy (HDS) versus VACOP-B with or without HDS in aggressive non-Hodgkin’s lymphoma: long-term results by the NHLCSG. • Because there is not univocal concordance for using high-dose sequential therapy (HDS) for NHL, this study evaluates the usefullness of HDS followed by high-dose therapy (HDT). • Arm A – 12 weeks usual treatment and then HDS/HDT if disease was persistant • Arm B – 8 weeks usual treatment plus HDS/HDT • Findings: Complete response rate for Arm A was 75% and 72.6% for Arm B. Aggressive NHL patients do not benefit from upfront HDS/HDT.

24. Review of Literature • Sequential high dose chemotherapy as initial treatment for aggressive types of Non-Hodgkin Lymphoma: results of international randomized phase III trial (MISTRAL). • Sequential high dose (SHD) chemotherapy with stem cell support has been shown to prolong the event-free survival in patients with diffuse large B-cell lymphoma. • Patients were randomized to receive either CHOP of SHD. • Overall survival rate after 3 years was 46% for SHD and 53% for CHOP. • Findings: SHD did not confer any survival benefit in these patients.

25. Review of Literature • Overweight and Obesity at Different Times in Life as Risk Factors for Non-Hodgkin’s Lymphoma: The Multiethnic Cohort. • Obesity may increase the risk for non-Hodgkin’s lymphoma through an inflammatory pathway. • Body weight and BMI at age 21 were stronger predictors of NHL risk than anthropometric characteristics at baseline. • At 21, men and women at the highest quartile were at substantially higher risk than others, whereas there was no association at baseline. • Findings: weight at age 21 may represent lifetime adiposity better than body weight at cohort entry. • Weight may at age 21 may be more relevant for the etiology of NHL.

26. References • U.S. Department of Health and Human Services. What You Need to Know about Non-Hodgkin Lymphoma. September 2007. • Honma K, Tsuzuki S, Nakagawa M, Tagawa H, Nakamura S, Morishima Y, Seto M. TNFAIP3/A20 functions as a novel tumor suppressor gene in several subtypes of non Hodgkin lymphomas. Blood. Published online July 16, 2009. • Visco C, Arcaini L, Brusamolino E, Burcheri S, Ambrosetti A, Merli M, Bonoldi E, Chilosi M, Viglio A, Lazzarino M, Pizzolo G, Rodeghiero F. Distinctive natural history in hepatitis C virus positive diffuse large B-cell lymphoma: analysis of 156 patients from northern Italy. Annals of Oncology. 2006;17:1434-1440. • Buckstein R, Kerbel R, Shaked Y, Nayar R, Foden C, Turner R, Lee C, Taylor D, Zhang L, Man S, Baruchel S, Stempak D, Bertolini F, Crump M. High-Dose Celecoxib and Metronomic “Low-dose” Cyclophosphamide Is an Effective and Safe Therapy in Patients with Relapsed and Refractory Aggressive Histology Non-Hodgkin’s Lymphoma. Clinical Cancer Research. 2006;12(17): 5190-5198. • Olivieri A, Santini G, Patti C, Chisesi T, De Souza C, Rubagotti, Aversa S, Billio A, Porcellini A, Candela M, Centurioni R, Congiu A, Brunori M, Nati S, Spriano M, Vimercati R, Marino G, Contu A, Tedeschi L, Majolino I, Crugnola M, Sertoli M. Upfront high-dose sequential therapy (HDS) versus VACOP-B with or without HDS in aggressive non Hodgkin’s lymphoma: long-term results by the NHLCSG. Annals of Oncology. 2005; 16: 1941-1948. • Betticher D, Martinelli G, Radford J, Kaufmann M, Dyer M, Kaiser U, Aulitzky W, Beck J, von Rohr A, Kovascovics T, Cogliatti S, Cina S, Malbach R, Cerny T, Linch D. Sequential high dose chemo therapy as initial treatment for aggressive sub-types of Non-Hodgkin Lymphoma: results of the international randomized phase III trials (MISTRAL). Annals of Oncology. 2006; 17: 1546-1552. • Maskarinec G, Erber E, Gill J, Cozen W, Kolonel N. Overweight and Obesity at Different Times in Life as Risk Factors for Non-Hodgkin’s Lymphoma: The Multiethnic Cohort. Cancer Epidemiol Biomarkers. 2008; 17: 196-203.