eMedicine Specialties > Hematology > Stem Cells and Disorders
Lymphoma, Non-Hodgkin: Treatment & Medication
Updated: Sep 2, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
The treatment of non-Hodgkin lymphomas (NHLs) varies greatly depending on tumor stage, phenotype (B-, T- or NK/null-cell), histology (ie, whether low-, intermediate-, or high-grade), symptoms, performance status, patient's age, and comorbidities.
Indolent NHL
Follicular lymphoma (grade I-IIIa) comprises 70% of this group. Other entities in this group include small lymphocytic lymphoma (SLL), lymphoplasmacytoid lymphoma, and marginal zone lymphomas (MZL, nodal or extranodal).Indolent stage I and contiguous stage II NHL
Standard management consists of radiotherapy alone. Forty percent of patients with limited-stage disease remained disease-free at 10 years after radiation in a study done by Mac Manus and Hoppe.6 No randomized study has shown combined chemotherapy and radiation to be better than radiation alone. Radiation therapy (2500-4000 cGy) produces a 10-year failure-free survival (FFS) rate of 50-60%, with an overall survival (OS) rate of 60-80%. Offering adjuvant chemotherapy to selected patients with stage I-II NHL who have unfavorable prognostic factors (eg, B symptoms, >2 nodal sites), and to those with follicular mixed histology is not unreasonable. Early treatment in asymptomatic patients has not been shown to improve survival.
Indolent noncontiguous stage II, III, and IV NHL
The treatment of indolent B-cell lymphomas continues to evolve as newer therapies are becoming available with potent antitumor activity and limited toxicity. Monoclonal antibodies are changing the treatment paradigm of patients with B-cell lymphomas. However, controversies persist regarding the best treatment strategy and also the best time to initiate treatment.
The disease course of indolent lymphomas is characterized by a continuous decrease in the quality and the duration of response with each subsequent treatment or treatments. This effect is primarily due to the acquisition of chemotherapy resistance. Advanced indolent lymphomas have been accepted to be not curable with currently available therapies. However, sustained complete remissions can be achieved with various treatment modalities. The use of rituximab, a monoclonal antibody targeting CD20 antigen present in benign and malignant B-cells, in combination with systemic chemotherapy, has resulted in an improved duration of remission and survival for patients with indolent B-cell lymphomas when compared to chemotherapy. Prospective studies and 2 meta-analyses suggest that the rituximab-chemotherapy, also known as chemo-immunotherapy, may be changing the natural progression of indolent lymphomas.
Asymptomatic patients, especially older patients and patients with concomitant medical problems, deferred therapy with careful observation is an option. Early intervention in asymptomatic patients does not appear to prolong survival. The median time to progression is 4-6 years, and OS is 6-10 years.
The treatment of symptomatic patients with indolent lymphomas should be focused on achieving the best possible quality of response without producing excessive toxicity. Single-agent treatment with chlorambucil or cyclophosphamide (with or without prednisone) is useful in elderly patients with significant comorbidities. However, only a few achieve remission; most achieve palliation.
Combination chemotherapies are used in younger patients with the goal of achieving a complete remission. Frequently used combination regimens are CHOP (cyclophosphamide, hydroxydaunomycin, Oncovin-vincristine, and prednisone), CVP (cyclophosphamide, vincristine, and prednisone), and fludarabine alone or in combination (cyclophosphamide, mitoxantrone). Combination agents are useful in bulky and rapidly progressive disease and have increased response rates as compared to single agents, but there is no improvement in overall survival.7,8,9
Longer duration of remission, with more patients achieving a complete response and/or complete molecular response, has become possible with newer biological agents like rituximab. Czuczman et al reported a 95% overall response rate and increase in time to progression with addition of rituximab to CHOP chemotherapy.10 When used in combination with chemotherapy, rituximab has shown higher response rates, longer time to progression and longer survival than chemotherapy. Randomized trials have shown better responses when rituximab was combined with chemotherapy regimens (CHOP, CVP). Rituximab as a single agent is also useful in patients who are unable to tolerate chemotherapy or those patients who elect to undergo treatment in the absence of high tumor burden.
Bone marrow transplant may have a role in patients with relapsed high-risk disease. Allogenic transplant has lower relapse rates but an increase in transplant-related mortality as compared to autologous transplant.11 The precise role of transplantation in indolent lymphomas is still being investigated.
Aggressive NHL
Diffuse large B-cell lymphoma is the most common type of NHL. Other distinct entities in this group include immunoblastic, anaplastic, lymphoblastic, large-cell, Burkitt, and Burkitt-like lymphomas (high-grade lymphomas). Mantle-cell lymphomas also behave aggressively.
Aggressive stage I and contiguous stage II (nonbulky or <10 cm) NHL
Based on 2 large randomized trials (ie, Southwest Oncology Group [SWOG], Eastern Cooperative Oncology Group [ECOG]), the preferred treatment option for patients with intermediate-grade NHL is combination chemotherapy (3 cycles of CHOP) plus involved-field radiation therapy. According to SWOG data, patients who are treated with chemotherapy and involved-field radiation therapy have significantly better progression-free survival rates (ie, 77% versus 66%) and 5-year OS rates (ie, 82% versus 72%) compared to patients surviving 8 cycles of chemotherapy (ie, CHOP) alone. Patients with high-grade disease should be strongly considered for treatment with more aggressive regimens beyond CHOP.
Aggressive noncontiguous stage II, III, and IV NHL
Approximately 40-50% are cured with standard therapy, approximately 35-40% will respond but ultimately progress or relapse and the remainder will be primarily refractory. Scoring systems such the IPI score have been developed and validated to estimate the response rate or survival rate of a given patient with aggressive lymphomas (see Prognosis).
For many years, the treatment of aggressive lymphomas consisted of chemotherapy regimens using multiple drugs. Initial clinical studies were focused on investigating the use of more toxic regimens (higher doses or more drugs). A prospective randomized trial of 4 regimens (ie, [1] CHOP versus [2] prednisone, methotrexate, leucovorin, doxorubicin, cyclophosphamide, and etoposide [ProMACE]–cyclophosphamide, etoposide, Adriamycin, cytarabine, bleomycin, Oncovin, methotrexate, leucovorin, and prednisone [CytaBOM] versus [3] methotrexate, bleomycin, Adriamycin, cyclophosphamide, Oncovin, and dexamethasone [m-BACOD] versus [4] methotrexate-leucovorin, Adriamycin, cyclophosphamide, Oncovin, prednisone, and bleomycin [MACOP-B]) for patients with diffuse large cell lymphoma showed no difference in response rate (RR), OS, or time to treatment failure (TTF) at 3 years. The other 3 regimens were more toxic than CHOP therapy. However, non-CHOP regimens such as MACOP-B are used as first-line therapies in some subtypes of NHL such as primary mediastinal large B-cell NHL.
After more than 2 decades of scientific investigations, the treatment of aggressive lymphomas switched by the clinical development of rituximab. Currently, 6-8 cycles of CHOP chemotherapy in combination with rituximab is the standard of care in patients with advanced disease.
The GELA (Groupe d'Etude des Lymphomas de l'Adulte) study was the first phase III trial to investigate the efficacy of combining rituximab with standard doses of CHOP chemotherapy for elderly (those older than 60 y) patients with diffuse large B-cell lymphoma. In this landmark study, patients were randomized to receive either CHOP plus rituximab or CHOP alone. At 5-year follow-up, rituximab and CHOP improved OS from 46% to 58% compared with CHOP alone. The results of this study were further validated by other international randomized studies favoring the use of rituximab and chemotherapy in elderly patients with aggressive B-cell lymphomas.
Similar results were observed in younger patients, where the combination of rituximab and CHOP chemotherapy resulted in an improved survival. A large international study, the MabThera International Trial (MINT) addressed the role of rituximab-chemotherapy in young patients with aggressive B-cell lymphomas. The study, which has been presented only in an abstract form, was a phase III trial in which 823 diffuse large B-cell, CD20+, non-Hodgkin lymphoma (DLBCL) patients (ages 18-60 y) were randomized to receive either rituximab plus a standard anthracycline-containing chemotherapy regimen (standard chemotherapy) or standard chemotherapy alone as induction therapy. The rituximab plus standard chemotherapy regimens increased 2-year overall survival (OS) from 86% to 95% compared with standard chemotherapy alone and resulted in significant improvement in time to treatment failure and projected overall survival.
Ongoing research is being focused on identifying patients at risk for treatment failure and developing tailored treatment for patients with aggressive lymphoma based on clinical scores (IPI score) or gene profiles.
Patients at high risk of relapse (IPI intermediate or poor risk groups) might have an improved 5-year event-free survival/overall survival from autologous and allogeneic bone marrow or peripheral stem cell transplantation following chemotherapy.
CNS prophylaxis, usually with 4-6 injections of methotrexate intrathecally, is recommended for patients with paranasal sinus or testicular involvement, diffuse small noncleaved cell or Burkitt lymphoma, or lymphoblastic lymphoma. CNS prophylaxis for bone marrow involvement is controversial.
PET scanning is more sensitive than CT scan or gallium scan for staging and response assessment. Early PET negativity with 2-4 cycles correlates with durable remission and vice versa. After remission is achieved, patients are monitored with CT scans every 6 months for the first 2-3 years, as most recurrences occur in the first 3 years.
Treatment of acute lymphoblastic lymphoma, a very aggressive form of NHL, is usually patterned after acute lymphoblastic leukemia (ALL) therapy. Other subtypes of high-grade lymphomas are usually treated with more aggressive variations of CHOP chemotherapy, including the addition of high-dose methotrexate or other chemotherapy drugs and higher doses of cyclophosphamide.
Indolent recurrent NHL
In general, treatment with standard agents rarely produces a cure in patients who have relapsed. Sustained remissions after relapse can often be obtained in patients with indolent lymphomas, but relapse usually ensues. Favorable survival after relapse has been associated with age younger than 60 years, prior complete remission rather than partial remission, and duration of response longer than 1 year. For relapse that remains low grade, the following are possible treatment options:
- Single alkylating agents
- Combination chemotherapy - CVP, CHOP, and others
- Purine analogues - Fludarabine, 2-CDA
- Rituximab (results in a 40-50% RR in patients with relapsed/refractory indolent B-cell lymphomas) in standard or extended schedules of administration.
- Radioimmunotherapy - 131 I-rituximab radioimmunotherapy of relapsed or refractory indolent NHL achieves high overall response rates and complete response rates with minimal toxicity. Tositumomab (131 I murine IgG2a lambda monoclonal antibody directed against CD20 antigen). Ibritumomab (90 Y) also has been approved for use in relapsed indolent lymphoma. They typically are used only in patients with less than 25% bone marrow involvement with lymphoma and in patients refractory to rituximab.
- Local relapse can be treated with radiotherapy.
- High-dose chemotherapy plus stem cell transplantation is being investigated to determine whether it can produce significantly better survival rates compared with conventional chemotherapy.
Aggressive recurrent adult NHL
High-dose chemotherapy plus stem-cell transplantation is the treatment of choice for patients who have recurrent aggressive lymphomas. Preliminary studies indicate that approximately 20-40% of patients have a long-term disease-free status, but the precise percentage depends on patient selection and specific treatment used.
Second-line chemotherapy regimens such as ICE (ifosfamide, carboplatin, etoposide), DHAP (dexamethasone, high-dose cytarabine, cisplatin), or EPOCH (etoposide, vincristine, doxorubicin, cyclophosphamide, prednisone) are usually used with rituximab if CD20 positive.
Gemcitabine and Navelbine is also being attempted in these relapsed patients. Chemotherapy is usually followed by stem-cell transplantation.
In the Parma trial, the patients with relapse who were randomized to autologous bone marrow transplantation followed by involved-field radiation therapy did better than those randomized to conventional chemotherapy and involved-field radiation therapy. After a 5-year median follow-up study, the event-free survival (EFS) rate was significantly better with transplantation (ie, 46% versus 12%), and the OS rate was also better (ie, 53% versus 32%). In general, patients who respond to initial therapy and who respond to conventional salvage therapy prior to bone marrow transplantation have better survival outcomes. Patients who relapse late (>12 mo after diagnosis) have better OS than patients who relapse earlier. Patients who are not candidates for transplantation can be treated with chemotherapy with or without monoclonal antibodies. If possible, these patients should be enrolled into clinical trials.
- Tumor vaccines are still being investigated for use in patients with lymphoma.
- Novel biological agents are currently under study in these settings.
Surgical Care
The role of surgery in the treatment of patients with NHL is limited. Surgery is useful in selected situations (eg, GI lymphoma), particularly if the disease is localized or if risk of perforation, obstruction, and massive bleeding is present. Orchiectomy is part of the initial management of testicular lymphoma.
Consultations
- A hematologist-oncologist should treat patients with NHL.
- Consult a radiation oncologist for treatment of patients with localized or limited-stage low-grade lymphoma and for palliative radiation therapy (eg, for treatment of SVC syndrome, treatment of painful metastases [especially in the bones], as an adjunctive treatment for CNS lymphomas).
- Consult an infectious disease specialist for the management of patients with neutropenic fever who are not responding to the usual broad-spectrum antibiotics.
- Surgical consultation is needed for lymph node biopsy, palliative procedures, or placement of a venous access device (eg, Port-a-Cath, Hickman catheter) for blood drawing and chemotherapy access.
Diet
- Usually, a regular diet is adequate, except when the patient is neutropenic. Patients with neutropenia should not eat raw fruits or vegetables.
- Transplant patients who have severe mucositis, decreasing albumin levels, or both may be administered total parenteral nutrition (TPN) until they can tolerate oral feedings.
Activity
The following restrictions apply to patients who are neutropenic, thrombocytopenic, or both:
- Avoid exposure to or contact with other patients with communicable or infectious diseases. Ideally, patients with neutropenia should be admitted directly to a private room and should not stay long in the emergency department for evaluation. All persons should wash hands before and after examining these patients.
- Use a soft toothbrush during episodes of neutropenia and thrombocytopenia.
- Patients should not shave with a razor.
Medication
Multiple chemotherapeutic agents are active against non-Hodgkin lymphoma (NHL) and can be used alone or in combination, depending on the histology and stage of the disease and whether the patient can tolerate chemotherapy. Also, several biological therapies are currently available for these patients, including interferons, rituximab, and radiolabeled antibodies (the newest biological therapy).
Alkylating agents impair cell function by forming covalent bonds with DNA, ribonucleic acid (RNA), and proteins. These agents are not cell cycle phase–specific and are used for hematologic and nonhematologic malignancies.
Anthracycline antibiotics bind to nucleic acids by intercalation with base pairs of the DNA double helix, interfering with the DNA synthesis. They cause inhibition of DNA topoisomerases I and II.
Vinca alkaloids inhibit microtubule assembly, causing metaphase arrest in dividing cells. Vinca alkaloids are also cell cycle phase–specific at the M and S phase.
Glucocorticoids cause lysis of lymphoid cells, which led to their use against ALL, multiple myeloma, and NHL. These agents are also used as adjunctive antiemetic agents, to decrease vasogenic edema associated with tumors, and as prophylactic medication to prevent hypersensitivity reactions associated with some chemotherapeutic drugs.
Antimetabolites cause tumor cell death by inhibiting enzymes that are important in DNA synthesis.
Biological response modulators control the response of the patient's immune system to tumor cells, infecting organisms, or both.
Cytotoxic agents
These agents inhibit cell growth and proliferation.
Chlorambucil (Leukeran)
Alkylates and cross-links strands of DNA, inhibiting DNA replication and RNA transcription. Used mainly to treat indolent lymphomas, particularly CLL and Waldenström macroglobulinemia. May be preferable for elderly patients with serious comorbid medical problems who require treatment for lymphoma. Well-absorbed PO.
Adult
0.1-0.2 mg/kg/d PO or 3-6 mg/m2/d PO for 3-6 wk; adjust dose based on blood counts
Pediatric
Not established
None reported
Documented hypersensitivity; previous resistance to medication
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in patients with history of seizure disorder or bone marrow suppression; not to be administered within 1 mo of radiation or cytotoxic therapy; concomitant exposure to pneumococcal vaccine should be avoided
Cyclophosphamide (Cytoxan)
Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells. Can be used alone but is mostly used as a component of multiple combination chemotherapy regimens.
Adult
CVP: 300-400 mg/m2 PO on days 1-5
CHOP: 750 mg/m2 IV on day 1
Pediatric
Not established
Cyclophosphamide may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life of cyclophosphamide while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity of cyclophosphamide; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
Documented hypersensitivity; severely depressed bone marrow function
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis; maintain ample fluid intake and good urine output
Doxorubicin (Adriamycin)
Anthracycline antibiotic that can intercalate with DNA, affecting many of the 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 bodily tissues, including the heart, kidneys, lungs, liver, and spleen. Does not cross the blood-brain barrier and is excreted primarily in bile. Important part of multiple chemotherapeutic regimens for lymphomas, including CHOP.
Adult
CHOP: 50 mg/m2 IV on day 1
Pediatric
Not established
Increased toxicity with cyclophosphamide, cyclosporine, mercaptopurine, verapamil, streptozocin, paclitaxel, and progesterone; phenobarbital decreases effect; decreased toxicity with digoxin; phenytoin levels are decreased
Documented hypersensitivity; severe CHF; cardiomyopathy; preexisting myelosuppression; impaired cardiac function; complete cumulative doses of daunorubicin, doxorubicin, or idarubicin
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
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 characteristic of doxorubicin toxicity; monitor for drug-induced cardiomyopathy; mortality rate is greater than 50% once cardiomyopathy has developed; bone marrow suppression; necrosis at extravasation site; urine discoloration (red); obesity-reduced clearance
Vincristine (Oncovin)
Mechanism of action is uncertain. May involve a decrease in reticuloendothelial cell function or an increase in platelet production; however, neither of these mechanisms fully explains the effect in TTP and HUS. Used in hematologic and nonhematologic malignancies. A component of CHOP and other regimens for lymphoma.
Adult
1.4 mg/m2 IV; total dose not to exceed 2 mg IV; never administered intrathecally
Pediatric
<10 kg or BSA <1: 0.05 mg/kg IV; single dose not to exceed 2 mg
>10 kg or BSA >1: 1-2 mg/m2 IV; single dose not to exceed 2 mg
Acute pulmonary reaction may occur when taken concurrently with mitomycin-C
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in patients diagnosed with severe cardiopulmonary or hepatic impairment and patients with preexisting neuromuscular disease; extravasation of the drug can cause local tissue necrosis; patient receiving radiation to fields that include the liver
Fludarabine (Fludara)
Purine analogue that interferes with DNA synthesis by inhibiting ribonucleotide reductase. Also incorporated into RNA, causing inhibition of RNA and protein synthesis; however, its primary effect may result from activation of apoptosis.
Adult
25 mg/m2/d IV over 30 min qd for 5 d; repeat 5-d course q28d; adjust dose based on hematologic or nonhematologic toxicity
Pediatric
Not established
Combination with other purine analogs, such as pentostatin, is contraindicated because of unacceptably high incidence of pulmonary toxicity when used concomitantly
Documented hypersensitivity; breastfeeding women; bone marrow suppression
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Perform frequent peripheral blood counts to detect development of anemia, thrombocytopenia, and neutropenia; monitor for tumor lysis syndrome; adjust dose for renal impairment, severe bone marrow suppression, severe neurological effects, or life-threatening and fatal autoimmune hemolytic anemia
Immunomodulators
These drugs regulate key events responsible for immune reactions.
Interferon alfa-2a (Roferon-A) or alfa-2b (Intron A)
Protein product manufactured by recombinant DNA technology. Interferons are a family of proteins produced by the cells in response to viral infection or stimulation with double-stranded RNA, antigens, or mitogens. Have antitumor activity against various hematological (CML, NHL, hairy cell leukemia) malignancies and solid tumors (especially in melanoma and renal cell cancer). Evidence suggests that interferon prolongs time to disease progression in patients who have responded to an anthracycline-containing combination chemotherapy regimen.
Adult
5 million IU SC 3 times/wk for up to 18 mo in conjunction with or following anthracycline chemotherapy
Pediatric
Not established
Theophylline may increase interferon-alfa toxicity; cimetidine may increase antitumor effects; zidovudine and vinblastine may increase toxicity of interferon-alfa
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in brain metastases, severe hepatic or renal insufficiencies, seizure disorders, multiple sclerosis, or compromised CNS
Rituximab (Rituxan)
An 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 it is also under investigation for use in combination regimens for follicular, mantle cell, and diffuse aggressive NHL.
Adult
375 mg/m2 slow IV infusion (do not administer IV push or bolus) on days 1, 8, 15, and 22 as single agent for relapsed low-grade follicular NHL
Pediatric
Not established
May increase effects of antihypertensive agents administered up to 12 h before infusion
Documented hypersensitivity; patients with NHLs that do not express CD20
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Associated with hypersensitivity reactions that may respond to adjustments in the infusion rate; hypotension, bronchospasm, and angioedema may occur during infusion; interrupt rituximab infusion for severe reactions and resume at a 50% reduction in rate when symptoms have completely resolved; premedications with diphenhydramine and acetaminophen may reduce hypersensitivity reactions; medications for hypersensitivity reactions should be available for immediate use; discontinue infusions in the event of serious or life-threatening cardiac arrhythmias
Ibritumomab tiuxetan (Zevalin)
A murine monoclonal antibody that targets the CD20 antigen, which is chelated to the radioisotopes indium In 111 or yttrium Y 90. Used in conjunction with rituximab to treat B-cell NHL or rituximab-refractory follicular NHL. The regimen consists of 2 low doses of rituximab, an imaging dose, 2-3 whole body scans, and a therapeutic dose, which are delivered on an outpatient basis over 8 d.
Adult
Day 1: Rituximab (250 mg/m2) IV infused over 4-5 h; followed by ibritumomab 1.6 mg (5 mCi111 In) IV push over 10 min; followed by a whole body scan at 2-24 h
Day 3 or 4: Whole body scan at 48-72 h
Day 4-5: Whole body scan at 90-120 h (optional)
Day 7-9: Rituximab (250 mg/m2) IV infused over 4-5 h; followed by ibritumomab 0.4 mCi/kg of90 Y IV push over 10 min; not to exceed 32 mCi
Note that the dose of rituximab is lower when used with ibritumomab than as a single agent
Pediatric
Not established
Coadministration with antiplatelet or anticoagulant drugs may increase risk of cytopenias and bleeding
Documented hypersensitivity; prior sensitization to murine proteins
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause severe and prolonged cytopenias; do not administer to those with altered biodistribution (according to body scan results); use only as a single course of treatment; follow radionucleotide precautions; decrease Y-90 ibritumomab to 0.3 mCi/kg with mild thrombocytopenia (ie, 100,000-149,000 platelets/mm3); severe mucocutaneous reactions, some with fatal outcomes, have been reported with the therapeutic regimen
Tositumomab and iodine I131 (BEXXAR)
Tositumomab is a murine IgG2a lambda monoclonal antibody directed against the CD20 antigen, which is found on the surface of normal and malignant B lymphocytes. The radiolabeled tositumomab (ie, iodine I131 tositumomab) is administered following the nonradiotherapeutic version to direct treatment precisely to the malignancy. Possible mechanisms of action include apoptosis, complement-dependent cytotoxicity, antibody-dependent cytotoxicity, and ionizing radiation. Indicated for CD20-positive non-Hodgkin lymphoma that has recurred following chemotherapy and is refractory to rituximab.
Adult
Dosimetric step: Tositumomab 450 mg IV infused over 1 h, followed by iodine I131 tositumomab (5 mCi I-131 and 35 mg tositumomab) IV infused over 20 min
Therapeutic step (7-14 d following dosimetric step): Tositumomab 450 mg IV infused over 1 h, followed by iodine I131 (precise dose is dependent on current platelet count)
Pediatric
Not established
Live virus vaccines may not generate an immunologic response; because of frequency and duration of thrombocytopenia, antiplatelets or anticoagulants may cause exacerbation; coadministration with other drugs causing bone marrow suppression may cause additive effects
Documented hypersensitivity to tositumomab or murine antibodies
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
May cause severe or life-threatening cytopenias (ie, 71% experience grade 3 or 4); may cause hypersensitivity, including anaphylaxis; may cause secondary malignancies or hypothyroidism; infusion related symptoms (eg, fever, rigors, chills, sweating) may occur; 1 d prior to administration, administer protectant SSKI; administer acetaminophen and diphenhydramine on administration day
Corticosteroids
These drugs have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
Dexamethasone (Decadron, AK-Dex, Alba-Dex, Baldex)
Component m-BACOD regimen. Glucocorticoid acts as an immunosuppressant by stimulating the synthesis of enzymes needed to decrease the 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 of the adverse effects of corticosteroids are dose-dependent or duration-dependent.
Adult
20 mg IV qd (as an adjunctive anti-emetic agent)
6 mg/m2 PO on days 1-5 of a 21-day cycle (m-BACOD)
Pediatric
Variable, see protocol
Effects decrease with coadministration of barbiturates, phenytoin and rifampin; dexamethasone decreases effect of salicylates and vaccines used for immunization
Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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
Prednisone (Deltasone, Orasone, Meticorten)
Component of several regimens, such as CHOP and m-BACOD. Glucocorticoid acts as an immunosuppressant by stimulating the synthesis of enzymes needed to decrease the 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 of the adverse effects of corticosteroids are dose-dependent or duration-dependent.
Adult
100 mg PO on days 1-5 of a 21-d cycle (CHOP)
Pediatric
Variable, see protocol
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
Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective-tissue infections; fungal or tubercular skin infections; GI ulceration
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
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 may occur with glucocorticoid use
Nelarabine (Arranon)
Prodrug of the deoxyguanosine analogue 9-beta-D-arabinofuranosylguanine (ara-G). Converted to the active 5'-triphosphate, ara-GTP, a T-cell–selective nucleoside analog. Leukemic blast cells accumulate ara-GTP. This allows for incorporation into DNA, leading to inhibition of DNA synthesis and cell death.
Approved by FDA as orphan drug to treat persons with T-cell lymphoblastic lymphoma (a type of NHL) whose disease has not responded to or has relapsed with at least 2 chemotherapy regimens.
Adult
1500 mg/m2 IV (infuse over 2 h) on days 1, 3, and 5; repeat q21d
Pediatric
650 mg/m2 IV (infuse over 1 h) qd for 5 consecutive days; repeat q21d
None reported
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Common adverse effects include hematologic toxicity (eg, leukopenia, thrombocytopenia, anemia, neutropenia), hypokalemia, hypoalbuminemia, hyperbilirubinemia, fatigue, nausea, vomiting, and diarrhea; severe neurologic events reported and include extreme somnolence, convulsions, demyelination, ascending peripheral neuropathies similar to Guillain-Barré syndrome, and peripheral neuropathy ranging from numbness and paresthesia to motor weakness and paralysis; do not dilute prior to administration; preventive measures for hyperuricemia of tumor lysis syndrome (eg, hydration, urine alkalinization, allopurinol prophylaxis) must be taken
More on Lymphoma, Non-Hodgkin |
| Overview: Lymphoma, Non-Hodgkin |
| Differential Diagnoses & Workup: Lymphoma, Non-Hodgkin |
 Treatment & Medication: Lymphoma, Non-Hodgkin |
| Follow-up: Lymphoma, Non-Hodgkin |
| References |
| Further Reading |
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Further Reading
Related eMedicine Topics
- AIDS-Related Lymphomas
- HIV-1 Associated Opportunistic Neoplasms - CNS Lymphoma [in the Neurology section]
- Lymphoma, B-Cell
- Lymph oma, Bone [in the Radiology section]
- Lymphoma, Diffuse Large Cell
- Lymphoma, Follicular
- Lymphoma, High-Grade Malignant Immunoblastic
- Non-Hodgkin Lymphoma [in the Pediatrics: General Medicine section]
- Non-Hodgkin Lymphoma, Thoracic [in the Radiology section]
- Biobank Non-Hodgkin Lymphoma: Storing Blood for Analysis of DNA and Protein of Patients With Non-Hodgkin Lymphoma
- Dasatinib in Relapsed or Refractory Non-Hodgkin's Lymphoma
- Oral Clofarabine for Relapsed/Refractory Non-Hodgkin Lymphomas
- A Phase I Clinical Trial to Assess the Safety of SyB L-0501 in Combination With Rituximab to Patients With Aggressive B-Cell Non-Hodgkin's Lymphoma
- Pilot Study of Bortezomib, Bendamustine and Rituximab on Non-Hodgkin's Lymphoma
- A Study of Zevalin and Simultaneous Application of BEAM High-Dose Chemotherapy Followed by Autologous Stem Cell Transplantation in Refractory and Relapsed Aggressive Non-Hodgkin Lymphomas (escZ-BEAM)
National Guideline Clearinghouse
- Rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin's lymphoma. National Institute for Health and Clinical Excellence (NICE) - National Government Agency [Non-U.S.]. 2002 Mar (revised 2008 Feb). 29 pages. NGC:006360
- Staging laparoscopy for lymphoma. In: Diagnostic laparoscopy guidelines. Society of American Gastrointestinal and Endoscopic Surgeons - Medical Specialty Society. 1998 Apr (revised 2007 Nov). 4 pages. NGC:006837
- Treatment for anemia with erythropoietic agents in patients with non-myeloid hematological malignancies: a clinical practice guideline. Program in Evidence-based Care - State/Local Government Agency [Non-U.S.]. 2007 Jan 17. 32 pages. NGC:005525
- Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Clinical Oncology/American Society of Hematology clinical practice guideline update.
American Society of Clinical Oncology - Medical Specialty Society; American Society of Hematology - Medical Specialty Society. 2002 Apr 18 (revised 2008 Jan 1). 18 pages. NGC:006051
Keywords
non-Hodgkin lymphoma, non-Hodgkin's lymphoma, B-cell lymphoma, non-Hodgkin, lymphoma cancer, lymphomas, non-Hodgkin's lymphoma, non-Hodgkins lymphoma, large cell lymphoma, Burkitt's lymphoma, diffuse B-cell lymphoma, diffuse large B-cell lymphoma, large B-cell lymphoma, non-Hodgkin lymphoma, lymphoblastic lymphoma, Hodgkin disease, Hodgkin's disease, lymphoma, cell lymphoma, Revised European-American Lymphoma classification, REAL classification
lymphoid tissues, lymph node, hematopoietic neoplasm, mantle cell lymphoma, T/NK lymphoma, Burkitt lymphoma, indolent NHL, follicular lymphoma, small lymphocytic lymphoma, SLL, lymphoplasmacytoid lymphoma, marginal zone lymphoma, immunoblastic lymphoma, anaplastic lymphoma, lymphoblastic lymphoma, Burkitt-like lymphoma, Burkitt's-like lymphoma, malignant lymphoma, lymph node cancer, leukemia
