Optimizing Patient Outcomes in Non-Hodgkin Lymphoma: An Update for Oncology Nurses

1
Optimizing Patient Outcomes in Non-Hodgkin
Lymphoma An Update for Oncology Nurses

• Barbara Barnes Rogers, CRNP, MN, AOCN, ANP-BC
• Adult Hematology-Oncology Nurse Practitioner
• Fox Chase Cancer Center

2
Disclosure of Conflicts of Interest

• Barbara B. Rogers has an affiliation with
  Celgene (Advisory Board) and Allos, Cephalon,
  Seattle Genetics, and Millennium (Speakers
  Bureaus).

3
Learning Objectives

• After completing this activity, the participant
  should be better able to
• Discuss the classification, presentation, and
  diagnosis of NHL
• Explain the prognosis of NHL using established
  prognostic models
• Identify the different classes and mechanisms of
  therapeutic agents for treating NHL
• Recognize the signs and symptoms of side effects
  and complications associated with chemotherapy
• Manage chemotherapy side effects and
  complications in patients with NHL

4
Non-Hodgkin Lymphoma

• A heterogeneous group of lymphoid tumors that
  have distinct clinical and biologic behaviors
• Accurate diagnosis of specific NHL subtype
  important to understand management
• Biological and clinical heterogeneity can be
  noted within each subtype

5
Incidence of NHL

• Incidence rising
• Faster than that of all other malignancies except
  lung cancer in women, melanoma and prostate
  cancer
• Age-adjusted incidence in US increased from 11.1
  per 100,000 in 1975 to 19.8 per 100,000 in 2008
• Reason for rising incidence
• NHL in patients with acquired immunodeficiency
  syndrome (AIDS)
• Improvements in diagnosis
• Other reasons (most likely primary cause)
• Estimated new cases in the US in 2011 is 66,360
• Race
• 30 higher in whites than blacks
• Blacks gt whites age less than 50
• Whites gt blacks age over 55
• Greer J, Williams M. Wintrobes Clinical
  Hematology (12th Ed). Philadelphia Wolters
  Kluwer/Lippincott Williams Wilkins, 2009.
• American Cancer Society Cancer facts and figures
  2011.

6
Epidemiology

• Variable world-wide distribution
• More common in males than females
• Represent 10 of all childhood cancers in
  developed countries
• More common in adults than children
• Steady increase in incidence from childhood
  through age 80 years
• Seventh most common malignancy in US
• Represent 4 of all cancers

7
Risk Factors

• Abnormality of immune function
• HIV infection
• Iatrogenic immune suppression
• Autoimmune diseases
• Congenital immune deficiencies
• Wiskott-Aldrich
• X-linked lymphoproliferative disorder
• Infectious agents
• Gamma herpes viruses
• Epstein-Barr virus - associated with African
  Burkitt lymphoma, AIDS-related DLBCL, NK/T-cell
  nasal type lymphoma
• Kaposis sarcoma-associated herpes virus (human
  herpes virus 8) - linked to primary effusion
  lymphomas and multicentric Castlemans disease
• Human T-lymphotropic virus I (HTLVI) - adult
  T-cell leukemia/lymphoma
• Helicobacter pylori - gastric malt
• Hepatitis C virus - spenic marginal zone
  lymphoma other B-cell lymphomas
• Campylobacter jejuni - immunoproliferative small
  intestinal disease
• Borrelia burgdorferi - primary cutaneous B-cell
  lymphoma
• Chlamydia psittaci - ocular adnexal lymphoma

8
Environmental Factors Associated with NHL

• Environmental and occupational exposures
• Organic compounds (organophosphate insecticides)
• Drug exposure
• Phenytoin
• Carbamazepine
• Methotrexate
• TNF-a inhibitors - etanercept, infliximab,
  adalimumab
• Toxic chemical exposure
• Greer J, Williams M. Wintrobes Clinical
  Hematology (12th Ed). Philadelphia Wolters
  Kluwer/Lippincott Williams Wilkins, 2009.

9
Clinical Features of NHL

• Painless adenopathy - more common in cervical,
  axilla, or groin
• B symptoms - fevers, night sweats, weight loss
• Extranodal disease can be detected in up to 40
  of patients
• GI tract most common site
• Skin
• CNS involvement
• Ocular
• Significant cytopenias rare
• Hepatosplenomegaly - common feature of advanced
  disease manifested by upper abdominal pain

10
Where Do B-Cell Lymphomas Originate?
Jaffe E, et al. Blood. 20081124384-4399.
11
Classifications of NHL

• B-cell vs T-cell
• B-cell NHL - 88 of all NHLs
• T-cell NHL - 12 of all NHLs
• Indolent vs Aggressive
• WHO classification includes
• Immunophenotypic
• Molecular
• Genetic
• Clinical elements

12
Diagnostic Work-Up

History and Physical
CBC with diff/plts
Viral Testing HIV, HTLV-1, Hepatitis
Metabolic Panel with LDH
B2 microglobulin
CXR
CT of neck, chest, abdomen, pelvis
PET/CT
Biopsy with flow cytometry and cytogenetics
Bone marrow aspirate and biopsy
Lumbar puncture with cytology, if indicated
GI endoscopy in those with GI symptoms
13
Indications for Lumbar Puncture

• Small non-cleaved cell NHL
• Lymphoblastic lymphomas
• NHL of certain sites
• Nasopharynx
• Epidural space
• Testes
• Large cell with marrow involvement
• HIV

Greer J, Williams M. Wintrobes Clinical
Hematology (12th Ed). Philadelphia Wolters
Kluwer/Lippincott Williams Wilkins, 2009.
14
Subtypes of NHL
Mantle cell (6)
MALT-type marginal-zone B cell (7.5)
Lichtman MA. Williams Hematology. (7th Ed). New
York, NY McGraw Hill, 20061408.
15
Antigen Expression Associated with B-Cell NHL
Bone Marrow
Periphery (Spleen, Lymph Node)
Memory B
Pro-B
Pre-B
Immature B
Mature B
GC B
Mature B
Plasmablast
Plasma Cell
CD19
CD10 /
CD20 /
CD38
CD22 ?
CD52
CD80
Activated B-cells
ALL
CLL, PLL
MM
WM
Burkitts, FL, DLBCL, HCL
ALL acute lymphoblastic leukemia FL
follicular lymphoma HCL hairy cell leukemia
CLL chronic lymphocytic leukemia DLBCL
diffuse large B-cell lymphoma MM multiple
myeloma PLL prolymphocytic leukemia WM
Waldenströms macroglobulinemia Jaffe ES, et
al, eds. World Health Organization Classification
of Tumours. 2001. Hale G, et al. Tissue Antigens.
199035118-127. Freeman GJ, et al. J Immunol.
19891432714-2722.
16
Molecular Indices in Lymphocytic Malignancies
Lymphoma Subtype Morphology Immunophenotyping Favorable f Unfavorable u Common Cytogenetic Abnormalities Molecular Testing
Diffuse large B-cell (DLBCL) Diffuse pattern with distortion of the normal architecture of the lymph node or extranodal site CD20, CD45, CD3- t(1418), t(3v), t(814) Testing for bcl-2, bcl-1, c-myc All offer a survival advantage to the lymphoma cells u
Follicular lymphoma (FL) Nodal lymphoma with a follicular growth pattern CD10,CD20, sIg, CD23/-, CD22, CD25/- t(1418)(q32q21) 85 IgH re-arrangement with bcl-2 expression which leads to cellular resistance to apoptosis u
Small lymphocytic lymphoma/ chronic lymphocytic leukemia Usually appear normal, may be large, smudge cells may be present, pro-lymphocytes are common CD5, CD20dim, sIgdim, CD23, CD22-, CD25-() CD38 u Trisomy 12 t(11qv) u del(11q) u del(17p) u del(13q) f Patients with variable region Ig mutations have a more favorable prognosis u
Mantle cell lymphoma (MCL) Cells populating the mantle zone of the follicle CD5, CD20, sIg, CD22, CD45 CD10-, CD23-, CD25- Cyclin D1 t(1114)(q13q32) de-regulates cyclin D1 expression interfering with cell cycle regulation IgH re-arrangement with bcl-1 (increased cell proliferation), and bcl-6 expression (resistance to apoptosis) u
Peripheral T-cell lymphoma (PTLC) Peripheral T-cells and no features of other subtypes CD4, CD7-, CD8- Clonal re-arrangements of the receptor genes seen in non-cancerous T-cell disease are common
Kurtin S. Oncology Nurse. 20081(5)1-2.
17
Differences Between Childhood and Adult
Non-Hodgkin Lymphomas
Children Adults
Incidence Rare Common
Median Age 10-15y 55-70y
Presentation Extranodal gt nodal Nodal gt extranodal
Most common histologic diagnoses B cell Burkitt, diffuse large cell T cell Lymphoblastic ALK anaplastic large cell B cell diffuse large cell (DLBCL), small cleaved (follicular center) cell T cell Peripheral T-cell unspecified anaplastic large cell angioimmunoblastic
Immunophenotype 50-70 B cell 85-90 B cell (US Europe)
Paraprotein None Rare (lt5)
Clinical course Aggressive Variable - often indolent
Curability 70-90 lt30 except 40-70 in aggressive subtypes, particularly DLBCL
Greer J, Williams M. Wintrobes Clinical
Hematology (12th Ed). Philadelphia Wolters
Kluwer/Lippincott Williams Wilkins, 2009.
18
Indolent NHL

• Long median survival
• Slow but continuous decline in survival
• Usually advanced stage at presentation
• Respond to therapy but relapse
• May transform to aggressive lymphoma
• Rarely, can spontaneously regress

19
Indolent Lymphoma Subtypes

• Follicular lymphoma
• Small lymphocytic lymphoma
• Lymphoplasmacytic lymphoma (Waldenström
  macroglobulinemia)
• Marginal zone lymphoma
• Splenic marginal zone lymphoma
• Primary cutaneous anaplastic large cell lymphoma
• Mycosis fungoides (Sézary syndrome)

National Cancer Institute Adult Non-Hodgkin
Lymphoma Treatment (PDOR), cellular
classification of adult NHL.
20
Aggressive Lymphomas

• Present acutely or sub-acutely with
• A rapidly growing mass
• Systemic B symptoms
• Fever
• Night sweats
• Weight loss
• Elevated serum LDH (lactate dehydrogenase)
• Elevated uric acid
• Examples
• Diffuse large B cell lymphoma
• Burkitt lymphoma
• Adult T cell leukemia/lymphoma
• Precursor B and T lymphoblastic leukemia/lymphoma
• Mantle cell lymphoma

Greer J, Williams M. Wintrobes Clinical
Hematology (12th Ed). Philadelphia Wolters
Kluwer/Lippincott Williams Wilkins, 2009.
21
Peripheral T-cell Lymphoma Subtypes
ALCL anaplastic large-cell lymphoma ALK
anaplastic lymphoma kinase PTCL peripheral
T-cell lymphoma.
OLeary. Curr Opin Hematol. 200916292. Internati
onal T-Cell Lymphoma Project. J Clin Oncol.
2008264124. de Leval. Hematology Am Soc Hematol
Educ Program. 2008272.
22
Ann Arbor Staging System
Stage Description
I Single lymph node region or single extralymphatic organ or site
II Two or more lymph node regions on the same side of the diaphragm or single exanodal site with adjacent nodes
III Nodal regions on both sides of the diaphragm or involving single extranodal site with adjacent nodes, or spleen or both
IV Diffuse or disseminated involvement of one or more extralymphatic organs, bone marrow, liver, brain involvement
A No symptoms
B Fevers, chills, night sweats, weight loss
E Extranodal involvement
X Bulky
S Spleen involvement
23
Prognostic Indexes
IPI AA-IPI FLIPI MIPI PIT
Age gt60 years Performance Status 2 or more Age gt60y Age Age
Performance Status LDH above normal Stage III/IV Performance Status Performance Status
LDH above normal Stage III or IV Hemoglobin lt12 g/L LDH LDH
Two or more extranodal sites Number of nodal areas gt4 Leukocyte count BM Involvement
Stage III or IV LDHgt normal

IPI International Prognostic Index AA-IPI Age
Adjusted IPI FLIPI Follicular Lymphoma IPI MIPI
Mantle Cell IPI PIT Peripheral T cell NHL IPI
The International Non-Hodgkins Lymphoma
Prognostic Factor Project. N Engl Med.
1993329987-994. Solal-Celigny, et al. Blood.
20041041258-1265. Gallamini A, et al. Blood.
20041032474-2479. Geisler C, et al. Blood.
20101151530-1533.
24
Progression-Free Survival Based on IPI
Sehn L, et al. Blood. 20071091857-1861.
25
Overall Survival of Patients with PTCL Based on
Prognostic Index for PTCL (PIT)
Group 1 - 0 risk factors Group 2 - 1 risk
factor Group 3 - 2 risk factors Group 4 - 3-4
risk factors
Gallamini A, et al. Blood. 20041032474-2479.
26
Treatment Related Issues

• Ability of patient to tolerate treatment
  dependent on
• Age
• Performance status
• Immunodeficiency from pre-lymphomatous condition
• Higher mortality in elderly
• Increased treatment related toxicities
• Death from unrelated causes are increased
• Greater lymphoma related mortality

27
Management of Indolent LymphomaTreatment Options

• Watchful waiting
• Local radiation for limited stage disease
• Chemotherapy
• Alkylating agent
• Nucleoside analog
• Combination chemotherapy
• Immunotherapy
• Unconjugated monoclonal antibody
• Radioimmunotherapy
• Interferons
• Interleukins
• Vaccines

• Combined modality therapy
• Chemotherapy and radiation therapy
• Chemotherapy and immunotherapy
• Transplantation
• Autologous
• Allogeneic
• Myeloablative
• Non-myeloablative
• Selective therapies
• Antibiotics in selected maltomas
• Splenectomy

Greer J, Williams M. Wintrobes Clinical
Hematology (12th Ed). Philadelphia Wolters
Kluwer/Lippincott Williams Wilkins, 2009.
28
Management of Diffuse Large B-Cell Lymphoma
(DLBCL)

• Initial R-CHOP /- IFRT
• Management of aggressive (high Ki67) DLBCL
• Relapsed /- autologous transplant
• RICE
• R-DHAP
• R-ESHAP
• R-GemOx
• R-MINE
• R-GDP

NCCN. Non-Hodgkins Lymphoma. Version 2.2012.
29
Management of Follicular Non-Hodgkins Lymphoma
Frontline Bendamustine/Rituximab R-CHOP R-CVP Rituximab R-Fludarabine Clinical Trial
Relapsed Rituximab Bendamustine/Rituximab R-CHOP R-CVP Lenolidomide Radioimmunotherapy Clinical Trial
NCCN. Non-Hodgkins Lymphoma. Version 2.2012.
30
Management of Peripheral T-Cell Lymphoma
Frontline CHOP Hyper CVAD Clinical Trial Autologous Peripheral Stem Cell Transplant as consolidation
Recurrent/Refractory DHAP ESHAP GDP ICE Pralatrexate Romidepsin Brentuximab vedotin Alemtuzumab Cyclosporine Bortezomib Denileukin diftitox Gemcitabine Clinical Trial
Foss F, et al. Blood. 20111176756-6767.
31
Role of Transplant in the Management of NHL

• Outcomes dependent on
• Disease State
• Type of lymphoma
• Remission status - best outcome in patients in
  first CR or have minimal disease before
  transplant
• Patients with disease that is responsive to
  therapy have 30-60 salvage rate
• Patients with resistant relapse have 0-15
  salvage rate
• Patient factors
• Age
• Performance Status
• Source of stem cells
• Autologous
• Allogeneic - higher mortality rate
• No superior preparative regimen

32
Overall Survival in PTCL The International PTCL
and NK/T-Cell Lymphoma Study
PTCL Subtypes PTCL Subtypes PTCL Subtypes PTCL Subtypes PTCL Subtypes PTCL Subtypes PTCL Subtypes
ALK ALCL ALK ALCL PTCL-NOS AITL NK/T-Cell Lymphoma ATLL
5-Yr OS Rate () 70 49 32 32 32 14
ATLL adult T-cell leukemia/lymphoma OS
overall survival.
International T-Cell Lymphoma Project, 2008.
Vose J, et al. J Clin Oncol. 2008264124-4130.
33
Side Effects of Agents Used in the Treatment of
B-Cell Lymphomas- CHOP
Cyclophosphamide - hemorrhagic cystitis, nausea and vomiting, anorexia, stomatitis, diarrhea, hepatotoxicity, neutropenia, alopecia, sexual dysfunction, SIADH, pulmonary toxicity. Doxorubicin - neutropenia, thrombocytopenia, cardiac toxicity, nausea and vomiting, anorexia, stomatitis, alopecia, radiation recall, nail and skin changes, drug extravasation, sexual dysfunction.
Vincristine - peripheral neuropathy, constipation, alopecia, mild neutropenia, mild thrombocytopenia, impotence. Prednisone - gastric irritation, decreased carbohydrate metabolism, hyperglycemia, edema, fluid and electrolyte alterations, immunosuppression, cushingoid changes, cataracts, glaucoma, ocular infections, behavioral changes, muscle weakness.
Wilkes G, Barton-Burke M. Oncology Nursing Drug
Handbook (2011 Ed). Sudbury, MA Jones and
Bartlett Publishers, 2011.
34
Side Effects of Agents Used in the Management of
NHL
Rituximab - infusion reactions, tumor lysis, lymphopenia, mucocutaneous reactions, reactivation of hepatitis B, nausea and vomiting, pruritus, myalgias. Fludarabine - neutropenia, thrombocytopenia, pulmonary toxicity, nausea and vomiting, diarrhea.
Bendamustine - neutropenia, anemia, thrombocytopenia, infusion reaction, tumor lysis, nausea and vomiting, diarrhea, rash. Lenalidomide - neutropenia, thrombocytopenia, anemia, rash, fatigue, light headedness, leg cramps, diarrhea, constipation, nausea, electrolyte imbalance, birth defects.
Wilkes G, Barton-Burke M. Oncology Nursing Drug
Handbook (2011 Ed). Sudbury, MA Jones and
Bartlett Publishers, 2011.
35
Side Effects of Agents Used in the Treatment of
B-Cell Lymphomas-Radioimmunotherapy
90Y Ibritumomab tiuxetan (Zevalin) - infusion reaction, neutropenia, anemia, thrombocytopenia, nausea, abdominal pain, headache, secondary malignancies. 131I tositumomab (Bexxar) - infusion reaction, neutropenia, anemia, thrombocytopenia, secondary malignancies, thyroid dysfunction.
Wilkes G, Barton-Burke M. Oncology Nursing Drug
Handbook (2011 Ed). Sudbury, MA Jones and
Bartlett Publishers, 2011.
36
Side Effects of Agents Used in the Management of
T-Cell NHL
Romidepsin - anemia, leukopenia, neutropenia, thrombocytopenia, infection, EKG changes, asthenia, decreased appetite, headache, cough, rigors, weight loss. Pralatrexate - stomatitis, thrombocytopenia, nausea, fatigue, anemia, neutropenia, dyspnea, hypokalemia, altered LFTs, abdominal pain, leukopenia, febrile neutropenia, sepsis, hypotension.
Brentuximab vedotin - peripheral neuropathy, nausea, fatigue, pyrexia, diarrhea, rash, constipation, neutropenia.
Alemtuzumab - anemia, neutropenia, thrombocytopenia, fever, infection, viremia (CMV, EBV), hypotension, rash, urticaria, diarrhea, nausea, vomiting, myalgias, insomnia, anxiety, bronchospasm, dyspnea. Denileukin Diftitox - fever, fatigue, rigors, nausea, headache, edema, cough, dyspnea, pruritus, rash, hypotension, back pain, myalgia, chest pain, tachycardia, hypoalbuminemia, asthenia, altered LFTs, capillary leak syndrome, infusion reactions, visual impairment.
Wilkes G, Barton-Burke M. Oncology Nursing Drug
Handbook (2011 Ed). Sudbury, MA Jones and
Bartlett Publishers, 2011.
37
Management of Side Effects of Agents Used in the
Management of NHL
Toxicity Interventions
Myelosuppression (neutropenia, anemia, thrombocyopenia) Assess baseline CBC Assess CBC throughout therapy Assess for signs/symptoms of infection or bleeding Teach patient the signs and symptoms of infection or bleeding and to report these immediately Teach patient self-care measures to minimize risk of infection and bleeding Transfuse as necessary Discuss need for dose modifications with prescriber/physician
Wilkes G, Barton-Burke M. Oncology Nursing Drug
Handbook (2011 Ed). Sudbury, MA Jones and
Bartlett Publishers, 2011.
38
Management of Side Effects of Agents Used in the
Management of NHL
Nausea and vomiting Teach patient to take antiemetic as needed Administer antiemetic prior to administration of chemotherapy Encourage patient to eat small, frequent meals Teach dietary modifications as needed Teach patient to notify healthcare professionals if antiemetics not successful in relieving nausea
Peripheral Neuropathy Assess sensory/motor changes prior to each treatment Notify prescriber/physician of alterations in neurologic function Discuss need for dose modifications Teach patient about potential for neuropathy and need to notify healthcare providers for difficulty in performing ADLs
Wilkes G, Barton-Burke M. Oncology Nursing Drug
Handbook (2011 Ed). Sudbury, MA Jones and
Bartlett Publishers, 2011.
39
Management of Side Effects of Agents Used in the
Management of NHL
Stomatitis Perform oral assessment prior to each treatment Teach patient to perform good oral hygiene and use mouthwash with salt water or salt and soda mouthwash Recommend patient have dental exam prior to starting treatment Teach patient to contact health professional for any mouth discomfort
Wilkes G, Barton-Burke M. Oncology Nursing Drug
Handbook (2011 Ed). Sudbury, MA Jones and
Bartlett Publishers, 2011.
40
Management of NHL in the Elderly

• Over half of new cases occur in those over the
  age of 60 years
• Prognosis poor in the elderly
• Poor performance status
• Reduced vital organ reserve
• Comorbid diseases
• Biologic features of lymphoma

41
Management of NHL in Pregnancy

• Lymphoma during pregnancy is rare (about 100
  reported cases)
• Therapy is based on histologic type and the point
  of gestation at diagnosis
• Most women who develop NHL during pregnancy have
  aggressive histologies and advanced-stage disease
• Unusually high incidence of breast, ovarian,
  uterine and cervix involvement - most likely due
  to hormonal influenced and increased blood flow
  to these organs
• Placental involvement rare
• Transmission to fetus uncommon
• Staging studies are limited due to concerns about
  radiation exposure during pregnancy
• CXR can be done
• MRI can be used but to be avoided during first
  trimester
• Ultrasound and echocardiograms can be useful
• PET can be performed after delivery but since FDG
  is concentrated in breast tissue, patients should
  avoid breast feeding for 72 hours after the scan
• Prognosis for mother relatively poor
• EFS 40-45
• Due to aggressive nature of disease and advanced
  stage

Brenner B, et al. Lancet. 2012379580-587.
42
Management of NHL During Pregnancy

• Abortion should be considered when aggressive
  lymphoma is diagnosed during first trimester
  unless localized above diaphragm
• In that situation, can use involved field
  radiation therapy (with abdominal shielding)
• Radiation should be avoided until third trimester
• Combination chemotherapy can be given in second
  or third trimester
• Anthracyclines have been given without untoward
  effects to mother or fetus but should be avoided
  if possible
• Rituximab plus chemotherapy has been given
  without evidence of harm
• Early delivery should be considered
• Avoid myelosuppression
• To initiate intensive chemotherapy
• Complete staging after delivery
• Low-grade lymphomas can be observed until after
  delivery

Brenner B, et al. Lancet. 2012379580-587.
43
Long-term Effect of Therapy

• Not as well defined as in HL
• Appear to be similar to HL and depend on
• Therapy used
• Age of patient
• Comorbid illnesses
• Long-term effect
• Endocrine - infertility, hypothyroid,
  panhypopituitarism, growth retardation
• Psychosocial issues
• Transfusion - induced viral infections
• Second neoplasms
• Radiation is main cause of endocrine and
  neurologic toxicities and secondary solitary
  neoplasms
• Cardiotoxicity from anthracyclines is manifested
  as CHF
• Cumulative incidence of cardiovascular disease in
  NHL treated with anthracycline was
• 12 at 5 years
• 22 at 10 years

44
Secondary Malignancies

• Increased risk over time for
• AML
• Bladder cancer
• Kidney cancer
• Lung cancer
• Malignant melanoma
• HL
• Up to 10 of patients with NHL treated with
  chemotherapy or autologous transplant may develop
  MDS or AML within 10 years of their initial
  therapy

Greer J, Williams M. Wintrobes Clinical
Hematology (12th Ed). Philadelphia Wolters
Kluwer/Lippincott Williams Wilkins, 2009.
45
Key Takeaways

• NHL is a heterogeneous group of malignancies that
  have distinct morphologic and molecular
  differences
• The distinct subtypes of NHL require specific
  management
• There are multiple prognostic indexes that can be
  used to calculate the level of risk of the
  patients lymphoma
• The prognosis is poorer in the elderly diagnosed
  with NHL than in younger patients
• Nursing interventions can assist patients in
  managing side effects from their treatment