AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Immunoblastic lymphoma (IBL), also known as diffuse histiocytic lymphoma, is a malignant disorder of the B cell.

Earlier classifications subdivided diffuse large B-cell lymphomas (DLBCLs) either by morphology or by the biological behavior.

• Kiel's classification subdivides large B-cell lymphoma into immunoblastic and centroblastic lymphomas.
• In the Working Formulation, IBL is classified with lymphoblastic and small noncleaved-cell lymphoma as a high-grade non-Hodgkin lymphoma (NHL).
• The International Lymphoma Study group uses all available information, morphology, immunophenotype, genetic features, and clinical features, to define a disease entity.

The World Health Organization (WHO) consensus classification should replace all existing classifications. The WHO classification of hematologic malignancies uses an updated version of the Revised European-American Lymphoma (REAL) classification for lymphoid neoplasms.

Although initially IBL was considered a more aggressive variety of lymphoma with a poor prognosis when compared with diffuse large-cell NHL (DLCL), newer combination chemotherapeutic approaches now associate IBL with a similar overall survival rate when compared with DLCL.

IBL is a fatal disease if untreated and is potentially curable with intensive chemotherapy. The success of treatment depends on the extent of disease at the time of presentation, associated B symptoms, initial therapeutic choice, and response to therapy.

Pathophysiology

IBL can originally derive from B or T cells. The Working Formulation differentiates subtypes of IBL by cell of origin. The subtypes include plasmacytoid, clear cell, polymorphous, and epithelial cell component. From a clinical point of view, this subclassification has little value; B- or T-cell origin cannot be predicted based on morphology.

In the REAL classification, except in morphologic descriptions, the schema includes immunologic, cytogenetic, and molecular information in order to define distinct lymphoma entities. The DLBCLs are considered in the REAL classification as the classic DLCL of B-cell origin defined by the Working Formulation.

Frequency

United States

The frequency rate in the United States is approximately 9% of all NHLs. Of these, 70% are of B-cell origin and 25% are of T-cell origin.

Mortality/Morbidity

• The International Prognostic Index is now commonly used to assess the prognosis of aggressive NHL. Based on these pretreatment risk factors, the complete remission (CR) rate and 5-year overall survival rate of patients who are at low risk is 87% and 73%, respectively, compared to 44% and 26% in the high-risk group.
• Patients undergoing combination chemotherapy may experience long-term morbidity primarily associated with the chemotherapeutic agents.

Race

• No difference exists among races.

Sex

• No difference exists between the sexes.

Age

• IBL can appear in persons of any age but appears most commonly in persons who are middle-aged or older.
• IBL is commonly observed in patients of any age who are immunocompromised.

CLINICAL

Section 3 of 11  

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History

Most patients present with advanced disease; only as few as 30% present with limited-stage disease (I or II). Symptoms vary and depend on the site of involvement.

• Painless lymphadenopathy
• • This is the most common presenting feature.
  • Occasionally, pain might be associated with aggressive tumor growth.
  • Adenopathy is usually marked and may involve any site; often, it is generalized.
• B symptoms
• • Patients report profuse night sweats.
  • Fever is usually low grade (range 100-101°F).
  • Patients may report unintentional weight loss of more than 10% in 6 months.
• Fatigue (anemia)
• Neurologic deficit (CNS involvement)

Physical

• Lymphadenopathy
• Pallor (anemia)
• Hemorrhage: Petechiae, ecchymoses, epistaxis, and bleeding gums may be present.
• Hepatosplenomegaly: This may be present as a result of organ involvement.
• Common sites of extranodal IBL
• • Gastrointestinal tract
  • Bone
  • Testis
  • Central nervous system
• Unilateral or bilateral tonsillar enlargement: This may be present and typically is refractory to antibiotic treatment.
• Skin lesions: Rarely, patients may present with skin lesions.

Causes

• Environmental - Previous radiation exposure or exposure to pesticides and herbicides
• Infectious - HIV infection (Patients with AIDS have a higher incidence of IBL.)
• Autoimmune
• • Sjögren syndrome - Associated with IBL
  • Solid organ transplant or bone marrow transplant - Associated with a higher risk of developing IBL

DIFFERENTIALS

Section 4 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

WORKUP

Section 5 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Complete blood cell count and peripheral blood smear
• Serum chemistry, including lactate dehydrogenase (LDH), liver function tests, serum electrolytes, and renal function tests
• Beta-2 microglobulin: Elevated levels are associated with a poor prognosis.
• Cytogenetic studies
• • Cytogenic studies are generally used to help exclude other types of NHL.
  • Chromosomal aberrations, such as del(6q),+X, are associated with IBL but are not exclusive for this type. Mutations or allelic losses of the p53 tumor suppressor gene are common in the immunoblastic type.
  • Yunis et al (1989) observed that rearrangement of BCL2 in patients with IBL correlates with poor response to therapy.
  • Immunoblastic morphology is characterized by MUM1 expression and infrequent bcl6 expression.
• Coagulation profile: This is performed prior to any surgical intervention (eg, tissue biopsy, placement of a venous access port).
• Serum protein electrophoresis (not performed routinely): This may show presence of monoclonal proteins or an increase in immunoglobulins.

Imaging Studies

• Radiologic staging studies
• • Chest radiographs are used for staging purposes.
  • Computed tomography (CT) scan of the chest, abdomen, and pelvis to evaluate nodal and extranodal involvement is usually part of the staging workup. CT scan of the head is performed only if neurologic symptoms are present.
• Gallium scan: Although a nonspecific test, a gallium scan is often useful in follow-up evaluations for patients with initial gallium-avid disease. Therefore, gallium scan is performed as part of the initial staging workup. Clinical correlation with CT scan results is always recommended in patients with abnormal gallium scan results.
• Positron emission tomography (PET) scan: Most of the studies evaluating PET scan results were performed mainly in cases of DLCL. PET scans may be more sensitive compared with other imaging modalities, including gallium, when used for lymphoma staging.
• MRI of the spine and brain: This study may be performed for patients with a paraspinal mass to assess for epidural involvement and cord compression. Patients with signs or symptoms suggestive of intracranial disease also may require an MRI.
• Bone scan: This should be performed only if the patient has unexplained bone pain and a high alkaline phosphatase level.
• Multigated angiogram (MUGA) scan: This is usually performed to assess the cardiac ejection fraction prior to starting potentially cardiotoxic chemotherapy.

Procedures

• Bilateral iliac crest bone marrow biopsy and aspiration is performed as part of the staging evaluation.
• Excisional lymph node biopsy is preferred over fine-needle aspiration in patients suggested to have lymphoma. Adequate tissue should be obtained for histopathological and flow cytometric examination.
• Skin biopsy may be indicated, although rarely, if lesions suggestive of cutaneous involvement are present.
• Lumbar puncture and cerebrospinal fluid examination are warranted in patients with a paraspinal or paranasal mass, a concurrent HIV infection, involvement of the Waldeyer ring, testicular involvement, or bone marrow involvement.

Histologic Findings

These lymphomas have varying morphologic characteristics, ranging from plasmacytoid features to more pleomorphic characteristics. Generally, they comprise immunoblasts (>90%), with centrally located nucleoli, and centroblasts (must be <10%).

Staging

The Ann Arbor Staging Classification designed for Hodgkin disease is now used (with certain limitations) for NHL classification. This classification does not recognize disease of bulk, which has prognostic and therapeutic importance.

• Stage I - Single lymph node involvement
• Stage IE - Single extranodal site or organ involvement
• Stage II - Two or more lymph nodes involved on the same side of the diaphragm
• Stage IIE - Localized involvement of an extranodal site or organ and involvement of one or more lymph node regions on the same side of the diaphragm
• Stage III - Involvement of lymph node regions on both sides of diaphragm, which might be accompanied by localized involvement of an extranodal organ or site (stage IIIE), the spleen (stage IIIS), or both (stage IIISE)
• Stage IV - Diffuse or disseminated involvement of one or more distant extranodal organs, with or without associated lymph node involvement

TREATMENT

Section 6 of 11  

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• Treatment
• Medication
• Follow-up
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Medical Care

As discussed earlier, IBL is classified as an intermediate-grade NHL and is treated using therapeutic guidelines similar to those used for DLCL.

The current standard of treatment is combined-modality treatment in the limited stage and chemotherapy only in the advanced stage. Patients can be further subclassified as having bulky or nonbulky disease and low, intermediate, or high risk based on the International Prognostic Index.

• Limited stage I and II
• • Nonbulky disease and no adverse risk factors: Use the cyclophosphamide, hydroxydaunomycin, Oncovin (vincristine), prednisone, and rituximab (CHOP+R) chemotherapy regimen for 3-4 cycles and involved-field radiation therapy.
  • Bulky disease (tumor >10 cm in the greatest dimension) and adverse risk factor present: Use the CHOP+R chemotherapy regimen for 6-8 cycles and involved-field radiation therapy.
  • In a randomized study, CHOP+R therapy (rituximab administered on day 1 of CHOP) has emerged to become the standard initial treatment for DLBCL in the United States.
  • The benefit of irradiation is still controversial. Chemotherapy followed by consolidation radiotherapy has a 5-year overall survival rate and progression-free survival rates of up to 80%. Rituximab-based chemotherapy and the observation that radiation does not improve overall survival incline for chemotherapy alone.
• Advanced stage III and IV
• • Low-intermediate risk: Use 6-8 cycles of the CHOP+R chemotherapy regimen.
  • High-intermediate/high risk: Use 6-8 cycles of the CHOP+R chemotherapy regimen or offer enrollment in a clinical trial.
• Chemotherapy follow-up guidelines
• • Follow up periodically with patients who respond to chemotherapy and achieve a complete response.
  • Those who have a partial remission should either be treated with a new non–cross-resistant chemotherapy regimen or considered for the best supportive care.
• High-dose chemotherapy and stem cell transplant
• • Patients with primary resistant or relapsed disease who show some chemosensitivity with second-line salvage therapy should be considered for high-dose chemotherapy (HDC) and autologous stem cell transplant (ASCT).
  • Current recommendations are to consider HDC and ASCT for patients in their first relapse, after chemoresponsiveness is established with a second-line salvage therapy. The role of HDC plus ASCT in first CR for patients who have a slow initial response to front-line chemotherapy, those with poor initial prognostic factors, or as up-front therapy has not been clearly defined and remains controversial.
• Salvage regimens for primary resistant or refractory cases
• • The dexamethasone, cisplatin, and cytarabine (DHAP) regimen may be used.
  • Alternatively, consider using the etoposide, methylprednisolone, cisplatin, and cytarabine (ESHAP) regimen.
  • Finally, consider using the methotrexate, bleomycin, Adriamycin, cyclophosphamide, Oncovin, and dexamethasone (M-BACOD) regimen every 3 weeks.

Surgical Care

NHL is treated with chemotherapy, with or without radiation. The surgical procedures are limited to diagnostic or palliative purposes or for placement of an indwelling central venous catheter.

Consultations

The following consultations may be needed during the course of treatment:

• Surgeon - To obtain a tissue biopsy sample or an excisional lymph node biopsy sample for initial diagnosis
• Interventional radiologist - For placement of an indwelling venous catheter or subcutaneous port for venous access
• Radiation oncologist - For patients who have limited disease or those with bulky disease who do not require radiotherapy
• Dietary specialist
• Social services counselor

Diet

Patients with neutropenia should avoid undercooked meat, and fruits and vegetables should be either cooked or peeled.

Activity

In most instances, no special activity restrictions are required. Special circumstances may require some intervention.

• Patients with neutropenia
• • All personnel and visitors should wash their hands. Avoid contact with persons known to have ongoing viral or bacterial infections.
  • Avoid potted plants and flowers because these may be a source of fungal spores.
• Patients with thrombocytopenia
• • Pay special attention to oral hygiene, including frequent rinsing and brushing of teeth only with a toothette sponge.
  • Take precautions to avoid falls.
  • Avoid strenuous physical activity.

MEDICATION

Section 7 of 11  

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The goals of pharmacotherapy are to induce remission, to prevent complications, and to reduce morbidity.

Drug Category: Chemotherapeutic agents

Used in advanced stages of disease. CHOP+R regimen is therapy of choice. All others are used as salvage treatment.

Drug Name	Doxorubicin (Adriamycin)
Description	Anthracycline antibiotic that can intercalate with DNA, affecting many functions of DNA, including synthesis. Forms DNA-cleavable complexes by interaction with topoisomerase II, which is responsible for the cytocidal activity of the drug. Administered IV and distributes widely into tissues, including heart, kidneys, lungs, liver, and spleen. Does not cross blood brain barrier and is excreted primarily in bile.
Adult Dose	CHOP: 50 mg/m2 IV on day 1 M-BACOD: 45 mg/m2 IV on day 1
Pediatric Dose	CHOP: 40 mg/m2 IV on day 1
Contraindications	Documented hypersensitivity; severe CHF; cardiomyopathy; preexisting myelosuppression; complete cumulative doses of daunorubicin, doxorubicin, and idarubicin
Interactions	May decrease phenytoin and digoxin plasma levels; phenobarbital may decrease plasma levels; cyclosporine may induce coma or seizures; mercaptopurine, verapamil, streptozocin, paclitaxel, and progesterone increase toxicity; cyclophosphamide increases cardiac toxicity
Pregnancy	D - Unsafe in pregnancy
Precautions	May produce severe local toxicity in irradiated tissues, even when the 2 therapies are not administered concomitantly; caution in patients who have received radiotherapy; cardiomyopathy is a well-known adverse effect, monitor for drug-induced cardiomyopathy; mortality rate is >50% once cardiomyopathy has developed; extravasation may result in severe local tissue necrosis; reduce dose in patients with impaired hepatic function

Drug Name	Vincristine (Oncovin, Vincasar PFS)
Description	Mechanism of action is uncertain. May involve a decrease in reticuloendothelial cell function or an increase in platelet production.
Adult Dose	CHOP: 1.4 mg/m2 IV M-BACOD: 1 mg/m2 IV on day 1
Pediatric Dose	1.5 mg/m2 (not to exceed 2 mg) IV qwk for 6 doses
Contraindications	Documented hypersensitivity
Interactions	Acute pulmonary reaction may occur when taken concurrently with mitomycin-C
Pregnancy	D - Unsafe in pregnancy
Precautions	Caution in patients diagnosed with severe cardiopulmonary or hepatic impairment and patients with preexisting neuromuscular disease

Drug Name	Prednisone (Deltasone, Orasone, Meticorten, Sterapred)
Description	Glucocorticoid that acts as an immunosuppressant by stimulating the synthesis of enzymes needed to decrease inflammatory response. Also acts as an anti-inflammatory agent by inhibiting the recruitment of leukocytes and monocyte-macrophages into affected areas via inhibition of chemotactic factors and factors that increase capillary permeability. Readily absorbed via the GI tract and metabolized in the liver. Inactive metabolites are excreted via the kidneys. Most adverse effects are dose- or duration-dependent.
Adult Dose	100 mg PO for 4 d
Pediatric Dose	40 mg/m2/d PO for 28 d
Contraindications	Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease
Interactions	Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Abrupt discontinuation may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Drug Name	Dexamethasone (Decadron)
Description	Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability.
Adult Dose	DHAP: 40 mg PO/IV on days 1-4 M-BACOD: 6 mg/m2 PO on days 1-5
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; active bacterial or fungal infection
Interactions	Effects decrease with coadministration of barbiturates, phenytoin, and rifampin; decreases effect of salicylates and vaccines used for immunization
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Increases risk of multiple complications, including severe infections; monitor adrenal insufficiency when tapering drug; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections are possible complications of glucocorticoid use

Drug Name	Cisplatin (Platinol)
Description	Inhibits DNA synthesis and, thus, cell proliferation by causing DNA crosslinks and denaturation of double helix.
Adult Dose	DHAP: 100 mg/m2/d IV infusion on day 1 ESHAP: 25 mg/m2/d IV infusion on days 1-4
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; preexisting renal insufficiency; myelosuppression; hearing impairment
Interactions	Increases toxicity of bleomycin and ethacrynic acid
Pregnancy	D - Unsafe in pregnancy
Precautions	Administer adequate hydration before and 24 h after dosing to reduce risk of nephrotoxicity; myelosuppression, ototoxicity, nausea, and vomiting may occur

Drug Name	Cytarabine (Cytosar-U)
Description	Converted intracellularly to active compound, cytarabine-5'-triphosphate, which inhibits DNA polymerase. This inhibition, in turn, halts viral replication.
Adult Dose	DHAP: 2000 mg/m2 IV q12h for 2 doses on day 2 ESHAP: 2000 mg/m2 IV on day 5
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Decreases effects of gentamicin and flucytosine; other alkylating agents and radiation increase toxicity
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	If significant increase in bone marrow suppression, reduce number of treatment days; patients with hepatic or renal insufficiencies are at higher risk for CNS toxicity after a high dose (reduce dose)

Drug Name	Etoposide (Toposar, VePesid)
Description	Inhibits topoisomerase II and causes DNA strand breakage, causing cell proliferation to arrest in late-S or early-G2 portion of cell cycle.
Adult Dose	ESHAP: 60 mg/m2 IV on days 1-4
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; IT administration may cause death
Interactions	May prolong effects of warfarin and increase clearance of methotrexate; cyclosporine and etoposide have additive effects in cytotoxicity of tumor cells
Pregnancy	D - Unsafe in pregnancy
Precautions	Bleeding and severe myelosuppression may occur

Drug Name	Methylprednisolone (Adlone, Solu-Medrol, Depo-Medrol, Depopred)
Description	Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Adult Dose	ESHAP: 500 mg IV on days 1-4
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; viral, fungal, or tubercular skin infections
Interactions	Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use

Drug Name	Methotrexate (Folex PFS, Rheumatrex)
Description	Antimetabolite that inhibits dihydrofolate reductase, thereby hindering DNA synthesis and cell reproduction in malignant cells. Satisfactory response observed 3-6 wk following administration. Adjust dose gradually to attain satisfactory response.
Adult Dose	M-BACOD: 3000 mg/m2 IV on day 15
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); renal insufficiency
Interactions	Oral aminoglycosides may decrease absorption and blood levels of concurrent PO MTX; charcoal lowers levels; coadministration with etretinate may increase hepatotoxicity; folic acid or derivatives contained in some vitamins may decrease response; coadministration with NSAIDs may be fatal; indomethacin and phenylbutazone can increase plasma levels; may decrease phenytoin serum levels; probenecid, salicylates, procarbazine, and sulfonamides (including TMP-SMZ) may increase effects and toxicity; may increase plasma levels of thiopurines
Pregnancy	D - Unsafe in pregnancy
Precautions	Monitor CBC counts monthly and liver and renal function every 1-3 mo during therapy (monitor more frequently during initial dosing, dose adjustments, or when risk of elevated levels, eg, dehydration); has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if significant drop in blood counts; aspirin, NSAIDs, or low-dose steroids may be administered concomitantly (possibility of increased toxicity with NSAIDs, including salicylates, has not been tested)

Drug Name	Bleomycin (Blenoxane)
Description	Glycopeptide antibiotic that inhibits DNA synthesis. For palliative measure in the management of several neoplasms.
Adult Dose	M-BACOD: 4 mg/m2 IV on day 1
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; significant renal function impairment; compromised pulmonary function
Interactions	May decrease plasma levels of digoxin and phenytoin; cisplatin may increase toxicity when administered systemically
Pregnancy	D - Unsafe in pregnancy
Precautions	Caution in renal impairment; possibly secreted in breast milk; may cause mutagenesis and pulmonary toxicity (10%); idiosyncratic reactions similar to anaphylaxis (1%) may occur; monitor for adverse effects during and after treatment; vasoocclusive phenomenon with distal necrosis of digit; permanent damage to nail matrix may occur

Drug Name	Rituximab (Rituxan)
Description	Unconjugated chimeric monoclonal antibody that binds with high affinity to the CD20 antigen found on the surface of most (>90%) B-cell lymphomas. Mediates complement-dependent cell lysis and antibody-dependent cellular toxicity. Approved as a single agent in the treatment of relapsed low-grade follicular NHL and is also under investigation for use in combination regimens for follicular, mantle cell, and diffuse aggressive NHL.
Adult Dose	With CHOP regimen: 375 mg/m2 slow IV infusion (do not administer IV push or bolus) on day 1
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; IgE-mediated reaction to murine proteins
Interactions	Coadministration with cisplatin is known to cause severe renal toxicity including acute renal failure; may interfere with immune response to live-virus vaccine (MMR) and reduce efficacy (do not administer within 3 mo of vaccine)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Use with caution in patients with dormant infections, such as hepatitis B, hepatitis C, or CMV, because of risk of reactivation; hypotension, bronchospasm, and angioedema may occur; premedication with acetaminophen and diphenhydramine may decrease incidence; discontinue treatment if life-threatening cardiac arrhythmias occur; must administer by slow IV infusion, do not administer IV push or bolus

FOLLOW-UP

Section 8 of 11  

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• Follow-up
• Miscellaneous
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Further Inpatient Care

• Admit for chemotherapy-related toxicity or febrile neutropenia.
• Those patients who may require HDC and autologous bone marrow transplant (ABMT) require inpatient care until their counts recover and engraftment is achieved posttransplant.

Further Outpatient Care

• While on chemotherapy, patients should be monitored very carefully, including complete blood cell counts and serum chemistry evaluations.
• Patients with indwelling catheters may require daily heparin flushes to prevent clotting.
• Elderly patients may require home health services because chemotherapy may compromise their performance status.
• Growth factors may be required, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), or recombinant erythropoietin. These are administered subcutaneously and can usually be administered by the patients themselves in an outpatient setting.
• For patients who develop severe anemia or thrombocytopenia as a result of chemotherapy, outpatient transfusions may be required.
• For patients with concomitant diabetes mellitus, home monitoring of blood glucose may be required while undergoing chemotherapy because these patients often develop electrolyte imbalances from nausea/vomiting or hyperglycemia from steroids, which are administered as part of the chemotherapy regimen (eg, CHOP).
• Posttreatment periodic follow-up evaluation is essential in these patients because a substantial number of patients may relapse, especially those categorized as intermediate-high risk or high risk. A complete physical examination, CBC count, and CT scans are initially performed every 3 months for the first year; the frequency can then be decreased to every 4-6 months depending on the initial risk category of the lymphoma.

In/Out Patient Meds

• Antibiotics may be needed in episodes of fever postchemotherapy. The choice of antibiotics is usually based on the clinical presentation and clinical findings upon presentation. In cases in which no identifying source is found, broad-spectrum coverage should be started empirically. Most patients require hospitalization and intravenous administration of antibiotics.
• Antiemetic agents are usually prescribed for both acute and delayed onset of nausea and vomiting.
• Allopurinol is usually started in patients with a high tumor burden to prevent tumor lysis syndrome.
• In the hospital, intravenous hydration may be warranted in patients with a high tumor burden who are at high risk for tumor lysis syndrome.

Transfer

• Patients may require transfers in following situations:
• • Patients may be transferred to tertiary care centers if HDC and ABMT are being considered for therapy.
  • Patients who have refractory or relapsed disease and have poor performance status, thus, not candidates for further therapy, may need to be transferred to a terminal care facility.
  • Transfer to a rehabilitation center may be required posttherapy.
  • Home-based nursing care may be required.

Deterrence/Prevention

• Sterile technique should be emphasized in patients who are prescribed growth factors postchemotherapy at home.
• Patients with indwelling catheters should be instructed about daily heparin flushes under aseptic conditions.
• Neutropenic diet should be recommended during periods of expected neutropenia.
• Patients should be instructed to seek immediate medical attention if fever develops postchemotherapy.

Complications

• Neutropenic fever and opportunistic infections
• • In many cases, even if treated properly, neutropenic fever can be fatal.
  • Shortening the neutropenic phase with cytokines and early induction of prophylactic antibiotics is helpful.
• Tumor lysis syndrome (ie, hyperuricemia, hyperkalemia, hyperphosphatemia)
• • Recognizing the patients who are at risk (high uric acid level, high tumor burden) is important.
  • Before chemotherapy, allopurinol, intravenous hydration, and urine alkalization should be started. Renal function should be monitored carefully.
• Growth factors (eg, recombinant erythropoietin, interleukin 11, GM-CSF, G-CSF) - May be indicated in some patients

Prognosis

• The International Prognostic Index, established by the International Non-Hodgkin's Lymphoma Prognostic Factors Project from 1993, is a predictive model for patients with NHL based on 5 pretreatment characteristics.
• • Age - Older than 60 years
  • Tumor stage - Stages III and IV
  • Number of extranodal sites involved by NHL - More than one
  • Patient performance status - Two or more
  • LDH - Elevation above normal values
• From the evaluation of these 5 characteristics, patients are classified into 4 categories.
• • High-risk patients - Four or 5 adverse factors
  • High-intermediate–risk patients - Three adverse factors
  • Low-intermediate–risk patients - Two adverse factors
  • Low-risk patients - No or one adverse factor

Patient Education

• Patients should receive information about the following:
• • Potential short- and long-term adverse effects of chemotherapy
  • Neutropenic fever
  • Chemotherapy-associated thrombocytopenia and risk of bleeding
  • Avoidance of pregnancy and use of adequate birth control methods in reproductive-aged men or women
  • Sperm banking and other methods to ensure future fertility
  • Possible alteration in menstrual cycles during and after chemotherapy
  • Chemotherapy-induced fatigue
• For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education article Lymphoma.

MISCELLANEOUS

Section 9 of 11  

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Medical/Legal Pitfalls

• Failure to properly diagnose and stage the lymphoma
• Failure to clearly explain the short- and long-term adverse effects of chemotherapy agents
• Failure to clearly explain and discuss issues related to chemotherapy-associated infertility
• Failure to discuss procedure-related adverse effects and failure to obtain informed consent
• Adequate pathological diagnosis
• History of allergic reaction to medications
• Risk and hazards associated with blood product transfusions
• Cases in which an HDC and ABMT are required: Discussion of the risk of mortality and morbidity associated with regimen-related toxicity and the long-term follow-up is essential.

Special Concerns

• Preferably, an experienced hematopathologist should review pathology findings.
• Carefully select patients for HDC and ABMT.
• Adequately educate patients regarding neutropenic fevers, and emphasize seeking early medical attention in case of fever that may develop postchemotherapy.
• Discuss catheter-related complications and daily flushes to prevent clotting.

MULTIMEDIA

Section 10 of 11  

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• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Lymph node biopsy (hematoxylin and eosin stain) showing diffuse involvement with loss of architecture in a patient with immunoblastic non-Hodgkin lymphoma (NHL).
	View Full Size Image
Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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Article Last Updated: Aug 8, 2006