AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

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

INTRODUCTION

Section 2 of 10  

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

Background

The term lymphoma describes a heterogenous group of malignancies with different biology and prognosis. In general lymphomas are divided into 2 large groups of neoplasms, namely non-Hodgkin lymphoma (NHL) and Hodgkin disease. About 85% of all malignant lymphomas are NHLs. The median age at diagnosis is the sixth decade of life, with some exceptions. (Burkitt lymphoma and lymphoblastic lymphoma occur in younger patients.) NHL includes many clinicopathologic subtypes, each with distinct epidemiologies; etiologies; morphologic, immunophenotypic, genetic, and clinical features; and responses to therapy.

Currently, several NHL classification schemas exist, reflecting the growing understanding of the complex diversity of the NHL subtypes. The Working Formulation, originally proposed in 1982, classified and grouped lymphomas by morphology and clinical behavior (ie, low, intermediate, or high grade). In the 1990s, the Revised European-American Lymphoma (REAL) classification attempted to apply immunophenotypic and genetic features in identifying distinct clinicopathologic NHL entities. The World Health Organization (WHO) classification further elaborates upon the REAL approach. This classification divides NHL into those of B-cell origin and those of T-cell and NK-cell origin.

For clinical oncologists, the most practical way of sorting the currently recognized types of NHL is according to their predicted clinical behavior; each classification schema contributes to a greater understanding of the disease, which dictates prognosis and treatment.

Pathophysiology

NHLs are tumors originating from lymphoid tissues, mainly of lymph nodes. Various neoplastic tumor cell lines correspond to each of the cellular components of antigen-stimulated lymphoid follicles.

NHL represents a progressive clonal expansion of B cells or T cells and/or natural killer (NK) cells arising from the accumulation of genetic lesions that affect proto-oncogenes or tumor suppressor genes, resulting in cell immortalization. These oncogenes can be activated by chromosomal translocations (ie, the genetic hallmark of lymphoid malignancies), or tumor suppressor loci can be inactivated by chromosomal deletion or mutation. In addition, the genome of certain lymphoma subtypes can be altered with the introduction of exogenous genes by various oncogenic viruses. Several cytogenetic lesions are associated with specific NHLs, reflecting the presence of specific markers of diagnostic significance in subclassifying various NHL subtypes.

Most NHLs are of B-cell origin (almost 85%); only 15% are derived from T/NK cells, and the small remainder stem from macrophages. These tumors are characterized by the level of differentiation, the size of the cell of origin, the origin cell's rate of proliferation, and the histologic pattern of growth. For many of the B-cell NHL subtypes, the pattern of growth and cell size may be important determinants of tumor aggressiveness. Tumors that grow in a nodular pattern, which vaguely recapitulate normal B-cell lymphoid follicular structures, are generally less aggressive than lymphomas that proliferate in a diffuse pattern. Lymphomas of small lymphocytes generally have a more indolent course than those of large lymphocytes, which may have intermediate-grade or high-grade aggressiveness. However, some subtypes of high-grade lymphomas are characterized by small cell morphology.

Frequency

United States

The American Cancer Society estimated that approximately 63,190 new cases of NHL would be diagnosed in 2007. Since the early 1970s, the incidence rates of NHL have nearly doubled. Although some of this increase may be attributable to earlier detection (resulting from improved diagnostic techniques and access to medical care), or possibly to HIV-associated lymphomas, for the most part the rise is unexplained.

International

NHL is the most prevalent hematopoietic neoplasm, representing approximately 4% of all cancer diagnoses and ranking seventh in frequency among all cancers. NHL is more than 5 times as common as Hodgkin disease.

Mortality/Morbidity

• Of the estimated 63,190 new cases of NHL in the United States in 2007, approximately 18,660 people are expected to die from the disease. The 5-year relative survival rate of patients with NHL is approximately 63%. Of interest, the survival rate for patients with Non-Hodgkin lymphomas has steadily improved over the last 2 decades. The improvement in medical and nursing care, development of novel therapeutic strategies (ie, monoclonal antibodies), validation of biomarkers of response, and the implementation of tailored treatment are some of the factors that have modified the life expectancy of patients with NHL.
• The potential for cure varies among the different histological subtypes and directly relates to the stage at presentation and patient response to initial therapy.
• In general, low-grade lymphomas are indolent tumors associated with a predicted median survival time of 5-10 years. Intermediate-grade and high-grade lymphomas are more aggressive but are more responsive to chemotherapy. They are associated with a predicted median survival time of 2-5 years and less than 2 years (unless cure is achieved), respectively.

Race

Incidence varies with race; white people have a higher risk than black and Asian American people.

Sex

In general, incidence is slightly higher in men than in women, with a male-to-female ratio of approximately 1.4:1, but the ratio may vary depending on the subtype of NHL; for example primary mediastinal diffuse large B-cell lymphoma occurs more frequently in females than in males.

Age

• The median age at presentation for all subtypes of NHL is older than 50 years, except for patients with high-grade lymphoblastic and small noncleaved lymphomas, which are the most common types of NHL observed in children and young adults.
• At diagnosis, low-grade lymphomas account for 37% of NHLs in patients aged 35-64 years but account for only 16% of cases in patients younger than 35 years. Low-grade lymphomas are extremely rare in children.

CLINICAL

Section 3 of 10  

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

History

In general, the clinical manifestations of patients with NHL depend on various factors such as the location of the lymphomatous process, the rate of tumor growth, and the function of the organ being compromised or displaced by the malignant process. 

The Working Formulation classification groups the subtypes of non-Hodgkin lymphoma (NHL) by clinical behavior, that is, low-grade, intermediate-grade, and high-grade. Because the Working Formulation is limited to classification based upon morphology, it cannot encompass the complex spectrum of NHL disease, excluding important subtypes such as mantle cell lymphoma or T/NK lymphomas. However, it continues to serve as a basis for understanding the clinical behavior of groups of NHLs.

• Low-grade lymphomas
• • Peripheral adenopathy that is painless and slowly progressive is the most common clinical presentation in these patients.
  • Spontaneous regression of enlarged lymph nodes can occur in low-grade lymphoma, potentially causing confusion with an infectious condition.
  • Primary extranodal involvement and B symptoms (ie, temperature >38°C, night sweats, weight loss >10% from baseline within 6 mo) are not common at presentation, but both are common in patients with advanced, malignant transformation (ie, evolution from a low-grade to a intermediate- or high-grade lymphoma) or end-stage disease.
  • Bone marrow is frequently involved and may be associated with cytopenia or cytopenias.
  • Fatigue and weakness are more common in patients with advanced-stage disease.
• Intermediate- and high-grade lymphomas
• • These types of lymphomas cause a more varied clinical presentation.
  • Most patients present with adenopathy.
  • More than one third of patients present with extranodal involvement; the most common sites are the GI tract (including the Waldeyer ring), skin, bone marrow, sinuses, genitourinary (GU) tract, thyroid, and CNS.
  • B-symptoms are more common, occurring in approximately 30-40% of patients.
  • Lymphoblastic lymphoma, a high-grade lymphoma, often manifests with an anterior-superior mediastinal mass, superior vena cava (SVC) syndrome, and leptomeningeal disease with cranial nerve palsies.
  • Patients with Burkitt lymphoma (occurring in the United States) often present with a large abdominal mass and symptoms of bowel obstruction.
  • Obstructive hydronephrosis secondary to bulky retroperitoneal lymphadenopathy obstructing the ureters can also be observed in these patients.
  • Primary CNS lymphomas are high-grade neoplasms of B-cell origin. Most lymphomas originating in the CNS are large cell lymphomas or immunoblastomas, and they account for 1% of all intracranial neoplasms. These lymphomas are more commonly observed in patients who are immunodeficient because of conditions such as Wiskott-Aldrich syndrome, transplantation, or AIDS.

Physical

• Low-grade lymphomas
• • Peripheral adenopathy
  • Splenomegaly: Splenomegaly is observed in approximately 40% of patients; the spleen is rarely the only involved site at presentation.
  • Hepatomegaly
• Intermediate- and high-grade lymphomas
• • Rapidly growing and bulky lymphadenopathy
  • Splenomegaly
  • Hepatomegaly
  • Large abdominal mass: This usually occurs in Burkitt lymphoma.
  • Testicular mass
  • Skin lesions: Lesions are associated with cutaneous T-cell lymphoma (mycosis fungoides), anaplastic large-cell lymphoma, and angioimmunoblastic lymphoma.
  • Chest radiograph: The chest radiograph may demonstrate a bulky mediastinal mass, which is associated with primary mediastinal large B-cell lymphoma or lymphoblastic lymphoma.

Causes

• Chromosomal translocations and molecular rearrangements play an important role in the pathogenesis of many lymphomas and correlate with histology and immunophenotype.
• • t(14;18)(q32;q21): This translocation is the most common chromosomal abnormality associated with NHL. This translocation occurs in 85% of follicular lymphomas and 28% of higher-grade NHLs. This translocation results in the juxtaposition of the bcl-2 apoptotic inhibitor oncogene at chromosome band 18q21 to the heavy chain region of the immunoglobulin (Ig) locus within chromosome band 14q32.
  • t(11;14)(q13;q32): This translocation has a diagnostic nonrandom association with mantle cell lymphoma. This translocation results in the overexpression of bcl-1 (cyclin D1/PRAD 1), a cell-cycle regulator on chromosome band 11q13.
  • 8q24 translocations: The 8q24 translocations lead to c-myc dysregulation. This is frequently observed in high-grade small noncleaved lymphomas (Burkitt and non-Burkitt types), including those associated with HIV infection.
  • t(2;5)(p23;q35): This translocation between the nucleophosmin (NPM) gene and the anaplastic lymphoma kinase (ALK1) gene results in the expression of an aberrant fusion protein found in a majority of anaplastic large cell lymphomas.
  • t(11;18)(q21;q21) and t(1;14)(p22;132): Two chromosomal translocations are associated with mucosa-associated lymphoid tissue (MALT) lymphomas. The more common (ie, t[11;18][q21;q21]) translocates the apoptosis inhibitor AP12 gene with the MALT1 gene, resulting in the expression of an aberrant fusion protein. The other translocation,  t(1;14)(p22;132), involves the translocation of the bcl-10 gene to the immunoglobulin gene enhancer region.
• Some viruses are implicated in the pathogenesis of NHL, probably because of their ability to induce chronic antigenic stimulation and cytokine dysregulation, which leads to uncontrolled B- or T-cell stimulation, proliferation, and lymphomagenesis. These viruses include the following:
• • Epstein-Barr virus (EBV) is a DNA virus that is associated with Burkitt lymphoma (especially the endemic form in Africa), Hodgkin disease, lymphomas in immunocompromised patients (eg, from HIV infection, organ transplantation), and sinonasal lymphoma.
  • Human T-cell leukemia virus type 1 (HTLV-1) causes a latent infection via reverse transcription in activated T-helper cells. This virus is endemic in certain areas of Japan and the Caribbean islands, and approximately 5% of carriers develop adult T-cell leukemia or lymphoma.
  • Hepatitis C virus (HCV) is associated with the development of clonal B-cell expansions and certain subtypes of NHL (ie, lymphoplasmacytic lymphoma, Waldenström macroglobulinemia), especially in the setting of essential (type II) mixed cryoglobulinemia.
  • Kaposi sarcoma–associated herpesvirus (KSHV) is associated with body cavity–based lymphomas in patients with HIV infection and in patients with multicentric Castleman disease.
• Environmental factors linked to the development of NHL include chemicals (eg, pesticides, herbicides, solvents, organic chemicals, wood preservatives, dusts, hair dye), chemotherapy, and radiation exposure.
• Congenital immunodeficiency states (eg, severe combined immunodeficiency disease [SCID], Wiskott-Aldrich syndrome), acquired immunodeficiency states (eg, AIDS), and induced immunodeficiency states (eg, immunosuppression) are associated with increased incidence of NHL and are characterized by a relatively high incidence of extranodal involvement, particularly of the GI tract, and with aggressive histology. Primary CNS lymphomas can be observed in about 6% of patients with AIDS.
• The chronic inflammation observed in patients with autoimmune disorders, such as Sjögren syndrome and Hashimoto thyroiditis, promotes the development of MALT and predisposes patients to subsequent lymphoid malignancies. Hashimoto thyroiditis, which occurs in 16-23% of middle-aged and elderly females, is a preexisting condition in 23-56% of primary thyroid lymphomas.
• Helicobacter pylori infection is associated with the development of primary GI lymphomas, particularly gastric MALT lymphomas.

DIFFERENTIALS

Section 4 of 10  

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

Other Problems to be Considered

The diagnosis of NHL relies on pathological confirmation following appropriate tissue biopsy.
A significant number of medical disorders can be manifested by either local or generalized lymph node enlargement.

The following are some of the conditions that can result in clinical manifestations similar to those observed in lymphoma patients:

• Solid tumor malignancies
• • Metastatic disease to lymph nodes secondary to carcinoma, melanoma, or sarcoma
• Other hematologic malignancies or lymphoproliferative disorders
• • Granulocytic sarcoma
  • Multicentric Castleman disease
• Benign lymph node infiltration or reactive follicular hyperplasia secondary to infection (eg, tuberculosis; other bacterial, fungal, and, rarely, viral infections), and collagen-vascular diseases

WORKUP

Section 5 of 10  

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

Lab Studies

• CBC count with differential and platelet count in patients with non-Hodgkin lymphoma (NHL) may show the following:
• • Counts within the reference range in the early stage of disease
  • Anemia secondary to bone marrow infiltration, autoimmune hemolysis (particularly associated with small lymphocytic lymphoma [SLL]/chronic lymphocytic leukemia [CLL]), bleeding, anemia of chronic disease
  • Thrombocytopenia, leukopenia, or pancytopenia secondary to bone marrow infiltration or autoimmune cytopenias
  • Lymphocytosis with circulating malignant cells (common in patients with low-grade lymphomas)
  • Thrombocytosis (paraneoplastic syndrome associated with lymphomas or reactive secondary to blood loss)
• Chemistries may show the following:
• • Elevated lactate dehydrogenase (LDH) - Poor prognostic factor, correlation with increased tumor burden
  • Abnormal liver function test (LFT) results - Secondary to hepatic involvement, hypermetabolic tumor growth, chronic inflammation
  • Hypercalcemia - In patients with acute form of adult T-cell lymphoma-leukemia (ATLL)
• Beta2-microglobulin may be elevated and correlates with a poor prognosis.
• Occasionally, NHL is associated with monoclonal gammopathy, positive Coombs test result (especially SLL/CLL), and hypogammaglobulinemia.
• HIV serology should be obtained, especially in patients with diffuse large cell immunoblastic or small noncleaved histologies.
• HTLV-1 serology should be obtained in patients with ATLL.

Imaging Studies

• CT scan of the neck, chest, abdomen, and pelvis is used to detect enlarged lymph nodes, hepatosplenomegaly, or filling defects in the liver and spleen. Currently, it is the most widely used test for initial staging, assessing treatment response, and conducting follow-up care.
• A chest radiograph yields positive information in approximately one fourth of patients with NHLs, including identification of hilar or mediastinal adenopathy, pleural or pericardial effusions, and parenchymal involvement.
• Bone scan is only ordered in patients with bone pain, elevated alkaline phosphatase, or both. Bone lesions are particularly associated with the acute form of ATLL and diffuse large B-cell lymphomas.
• Gallium scans (optional, selected cases) can detect initial sites of disease, reflect therapy response, and detect early recurrences. This scan is positive in nearly all patients with aggressive and highly aggressive lymphomas and in approximately 50% of patients with indolent lymphomas at diagnosis.
• Whole body F-18 2-deoxyglucose (FDG) positron emission tomography (PET) scan can be used for the initial evaluation of patients with NHL; however, this scan is more useful for posttreatment evaluation to differentiate early recurrences or residual disease from fibrosis or necrosis. This PET scan has a higher predictive value for relapse than classic CT scan imaging.
• Obtain an upper GI series with small bowel follow-through in patients with head and neck involvement (eg, tonsil, base of tongue, nasopharynx, Waldeyer ring) and those with a GI primary lesion.
• Obtain an ultrasound of opposite testis in male patients with a testicular primary lesion.
• Multiple gated acquisition (MUGA) scan should be performed to evaluate the left ventricular ejection fraction (LVEF) of patients who are being considered for treatment with anthracyclines. In general, anthracyclines should not be administered to those patients with LVEF of less than 50%.
• Obtain MRI of the brain and spinal cord of patients who are suspected to have primary CNS lymphoma, lymphomatous meningitis, paraspinal lymphoma, or vertebral body involvement by lymphoma. It can also be performed to identify focal areas of marrow involvement in those patients suspected to have bone marrow involvement but in whom random bone marrow biopsy findings have been negative.

Other Tests

• Immunophenotypic analysis of lymph node, bone marrow, peripheral blood (if positive for neoplastic cells), or a combination of these
• • This study compliments and confirms the results of routine tissue section and may be useful in resolving a diagnostic dilemma in patients with an atypical morphology.
  • Immunophenotypic analysis helps to distinguish reactive from neoplastic lymphoid infiltrates, lymphoid from nonlymphoid malignancies, and specific lymphoid neoplasms. bcl-2 expression distinguishes follicular lymphoma from reactive follicular hyperplasia. bcl-1 expression strongly favors a diagnosis of mantle cell lymphoma. CD30 expression is important for the recognition of anaplastic large cell lymphoma, and it can also be found in the majority of Hodgkin lymphomas.
  • This analysis provides information about lineage and clonality, which are complimentary to the histology of a given case.
  • Analysis is also useful for subclassifying certain lymphoma subtypes, which has therapeutic and prognostic importance.
• Cytogenetic studies
• • These studies have contributed to the understanding of the biology and prognosis of lymphoma.
  • Cytogenetic studies are critical to the discovery of oncogene abnormalities that now are known to be intimately involved in the pathogenesis of NHL.

Procedures

• Biopsy of peripheral (or most accessible) lymphadenopathy
• • Excisional lymph node biopsy is required because lymphoma diagnosis relies heavily on careful assessment of altered nodal architecture accompanying lymphomatous infiltrates.
  • Fine-needle aspiration (FNA) is insufficient for establishing a diagnosis; needle-core biopsies have a limited role in establishing a diagnosis of NHL.
  • A well-processed hematoxylin and eosin (H&E)–stained section of an excised lymph node is the mainstay of pathologic diagnosis.
• Bone marrow aspirate and biopsy
• • Perform this procedure for staging rather than diagnostic purposes.
  • Bilateral bone marrow aspirate and biopsy should be performed because bone marrow involvement is usually patchy. In bone marrow sections, the neoplastic cells may infiltrate in a focal (ie, paratrabecular or nonparatrabecular, depending on the type of lymphoma), interstitial, or diffuse pattern.
• Biopsy of extranodal sites
• • In approximately 30-35% of adult patients with NHL, the extranodal sites are the primary presenting sites, and the most common site is the GI tract.
  • Processing extranodal biopsy material for lymphoma protocol studies is important whenever suspicion of a hematolymphoid neoplasm exists.
• Lumbar puncture for cerebrospinal fluid (CSF) examination should be performed in patients with the following conditions:
• • Diffuse aggressive NHL with bone marrow, epidural, testicular, paranasal sinus, nasopharyngeal involvement, or patient with two or more extranodal sites of disease.
  • High-grade lymphoblastic lymphoma
  • High-grade small noncleaved cell lymphomas (eg, Burkitt and non-Burkitt types)
  • HIV-related lymphoma
  • Primary CNS lymphoma
  • Patients with neurologic signs and symptoms

Histologic Findings

NHLs are a heterogenous group of lymphoproliferative malignancies with varying morphologic features depending on the specific type of this disorder. The abnormal lymphocytes in the lymph node, bone marrow, or extranodal sites can be small cleaved or noncleaved, intermediate, or large cell and can have a follicular or diffuse pattern. In contrast with reactive follicular hyperplasia, lymphomas usually alter the lymph node architecture, and the capsule is usually involved.

Staging

Staging is important in selecting a treatment and also for prognosis. CT scans of the neck, chest, abdomen, and pelvis, as well as bilateral bone marrow aspirate and biopsy, are necessary to stage the lymphoma. Noncontiguous lymph node involvement, uncommon in Hodgkin disease, is more common among patients with NHL.

• The Ann Arbor staging system is the most commonly used staging system for patients with NHL.
• • Stage I NHL involves a single lymph node region (I) or localized involvement of a single extralymphatic organ or site (IE).
  • Stage II NHL involves 2 or more lymph node regions on the same side of the diaphragm (II) or localized involvement of a single associated extralymphatic organ in addition to criteria for stage II (IIE).
  • Stage III involves lymph node regions on both sides of the diaphragm (III) that also may be accompanied by localized involvement of an extralymphatic organ or site (IIIE), spleen (IIIS), or both (IIISE).
  • Stage IV represents disseminated or multifocal involvement of one or more extralymphatic sites with or without associated lymph node involvement or isolated extralymphatic organ involvement with distant (nonregional) nodal involvement.
  • Subscript letters designate involvement of extralymphatic organs, as follows: L, lung; H, liver; P, pleura; O, bone; M, bone marrow; and D, skin. The designation E is used when extranodal lymphoid malignancies arise in tissues that are separate from but near the major lymphatic aggregates.
  • In this system, stages I-IV can be appended by A or B designations. Patients with A disease do not have systemic symptoms. The B designation is applied in patients with any of the following symptoms: unexplained loss of more than 10% of body weight in the preceding 6 months before diagnosis, unexplained fever with temperature above 38°C, and drenching night sweats.

IPI and FLIPI score

In addition to staging, risk stratification is important in patients with NHL. Several scoring systems had been developed and validated prospectively in patients with diffuse large B-cell lymphoma (International Prognostic Index, IPI) or follicular B-cell lymphomas (Follicular Lymphoma International Prognostic Index, FLIPI) that can be used to predict the prognosis of patients with B-cell malignancies (see Prognosis).

TREATMENT

Section 6 of 10  

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

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

• 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 -   ¹³¹I-rituximab radioimmunotherapy of relapsed or refractory indolent NHL achieves high overall response rates and complete response rates with minimal toxicity. Tositumomab (¹³¹I murine IgG2a lambda monoclonal antibody directed against  CD20 antigen). Ibritumomab (⁹⁰Y) 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

Section 7 of 10  

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

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.

Drug Category: Cytotoxic agents

These agents inhibit cell growth and proliferation.

Drug Name	Cyclophosphamide (Cytoxan)
Description	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 Dose	CVP: 300-400 mg/m2 PO on days 1-5 CHOP: 750 mg/m2 IV on day 1
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; severely depressed bone marrow function
Interactions	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
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

Drug Name	Doxorubicin (Adriamycin)
Description	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 Dose	CHOP: 50 mg/m2 IV on day 1
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; severe CHF; cardiomyopathy; preexisting myelosuppression; impaired cardiac function; complete cumulative doses of daunorubicin, doxorubicin, or idarubicin
Interactions	Increased toxicity with cyclophosphamide, cyclosporine, mercaptopurine, verapamil, streptozocin, paclitaxel, and progesterone; phenobarbital decreases effect; decreased toxicity with digoxin; phenytoin levels are decreased
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

Drug Name	Vincristine (Oncovin)
Description	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 Dose	1.4 mg/m2 IV; total dose not to exceed 2 mg IV; never administered intrathecally
Pediatric Dose	<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
Contraindications	Documented hypersensitivity
Interactions	Acute pulmonary reaction may occur when taken concurrently with mitomycin-C
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

Drug Name	Fludarabine (Fludara)
Description	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 Dose	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 Dose	Not established
Contraindications	Documented hypersensitivity; breastfeeding women; bone marrow suppression
Interactions	Combination with other purine analogs, such as pentostatin, is contraindicated because of unacceptably high incidence of pulmonary toxicity when used concomitantly
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

Drug Category: Immunomodulators

These drugs regulate key events responsible for immune reactions.

Drug Name	Rituximab (Rituxan)
Description	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 Dose	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 Dose	Not established
Contraindications	Documented hypersensitivity; patients with NHLs that do not express CD20
Interactions	May increase effects of antihypertensive agents administered up to 12 h before infusion
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

Drug Name	Ibritumomab tiuxetan (Zevalin)
Description	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 Dose	Day 1: Rituximab (250 mg/m2) IV infused over 4-5 h; followed by ibritumomab 1.6 mg (5 mCi 111In) 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 of 90Y 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 Dose	Not established
Contraindications	Documented hypersensitivity; prior sensitization to murine proteins
Interactions	Coadministration with antiplatelet or anticoagulant drugs may increase risk of cytopenias and bleeding
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

Drug Name	Tositumomab and iodine I131 (BEXXAR)
Description	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 Dose	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 Dose	Not established
Contraindications	Documented hypersensitivity to tositumomab or murine antibodies
Interactions	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
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

Drug Category: Corticosteroids

These drugs have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Drug Name	Prednisone (Deltasone, Orasone, Meticorten)
Description	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 Dose	100 mg PO on days 1-5 of a 21-d cycle (CHOP)
Pediatric Dose	Variable, see protocol
Contraindications	Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective-tissue infections; fungal or tubercular skin infections; GI ulceration
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	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

Drug Name	Nelarabine (Arranon)
Description	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 Dose	1500 mg/m2 IV (infuse over 2 h) on days 1, 3, and 5; repeat q21d
Pediatric Dose	650 mg/m2 IV (infuse over 1 h) qd for 5 consecutive days; repeat q21d
Contraindications	Documented hypersensitivity
Interactions	None reported
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

FOLLOW-UP

Section 8 of 10  

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

Further Inpatient Care

• Further inpatient care depends on the patient's active problem, tumor type and stage, and overall prognosis.
• Admit patients with non-Hodgkin lymphoma (NHL) for complications of disease progression (eg, pain control for intractable pain) or adverse effects from chemotherapy (eg, neutropenic fever, dehydration secondary to diarrhea, vomiting requiring IV hydration, severe mucositis).
• Admit patients for infusional chemotherapy or high-dose chemotherapy followed by stem cell transplantation.

Further Outpatient Care

• Treatment and follow-up care of patients with NHL are usually performed on an outpatient basis.
• Monitoring the patient's blood cell count while receiving chemotherapy (eg, prior to each treatment cycle and 10-14 d after each treatment cycle) is important.
• Monitor adverse effects of chemotherapy with a detailed patient history, an examination, a CBC count, and chemistries (especially LFTs, electrolytes, LDH, BUN/creatinine).
• Treat symptomatic adverse effects such as nausea, vomiting, diarrhea, mucositis, anorexia, pain, and fatigue.
• Administer packed red blood cell (PRBC) transfusions for patients with symptomatic anemia and provide platelet transfusions for patients with a platelet count less than 10-20 k/CU mm.
• Provide growth factor (eg, granulocyte colony-stimulating factor [GCSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], erythropoietin) support as necessary.
• Perform a disease and response to treatment evaluation by obtaining patient history, physical examination (at intervals q2-3mo), and imaging studies (eg, CT scans at intervals q4-12mo).
• Provide psychosocial support for the patient and family.

In/Out Patient Meds

• Most of the chemotherapy, whether combination chemotherapy (eg, CHOP) or single-drug (eg, fludarabine) therapy, can be administered in an outpatient setting in the infusion clinic. In the infusion clinic, specially trained oncology nurses, who are supervised by oncologists, administer the chemotherapy.
• Growth factor support (eg, GCSF, GM-CSF, erythropoietin) is administered in an outpatient treatment setting.
• Infusional chemotherapy (eg, infusional cyclophosphamide, doxorubicin, and etoposide [CDE], which should be administered continuously for 4 d) should be administered as inpatient treatment.
• For the initial treatment of patients with intermediate- or high-grade lymphoma and patients with bulky disease, an inpatient setting is recommended in order to monitor for tumor lysis syndrome and to manage appropriately.
• Patients with fever during neutropenia should be admitted for broad-spectrum antibiotic therapy.
• High-dose chemotherapy and bone marrow and/or stem cell transplant treatment are administered in an inpatient setting of a transplant-approved center.

Transfer

Patients with NHLs who are being treated in community hospitals and need high-dose chemotherapy with stem-cell support should be transferred to tertiary hospitals with approved transplant centers.

Deterrence/Prevention

Currently, no proven prevention techniques are known for NHL. Avoiding long-term immunosuppression and other possible causes of NHLs possibly may help.

Complications

• Disease-related complications
• • Cytopenias (ie, neutropenia, anemia, thrombocytopenia) secondary to bone marrow infiltration: Anemia could also be secondary to autoimmune hemolytic anemia, which is observed in some types of NHL (eg, SLL/CLL).
  • Bleeding secondary to thrombocytopenia, disseminated intravascular coagulation (DIC), or vascular invasion by the tumor
  • Infection secondary to leukopenia, especially neutropenia
  • Cardiac problems secondary to large pericardial effusion or arrhythmias secondary to cardiac metastases
  • Respiratory problems secondary to pleural effusion and/or parenchymal lesions
  • SVC syndrome secondary to a large mediastinal tumor
  • Spinal cord compression secondary to vertebral metastases
  • Neurologic problems secondary to primary CNS lymphoma or lymphomatous meningitis
  • GI obstruction, perforation, and bleeding in a patient with GI lymphoma (may also be caused by chemotherapy)
  • Pain secondary to tumor invasion
  • Leukocytosis (lymphocytosis) in leukemic phase of disease
• Chemotherapy and other treatment-related complications
• • Cytopenias (ie, neutropenia, anemia, thrombocytopenia)
  • Nausea or vomiting
  • Infection
  • Fatigue
  • Neuropathy
  • Dehydration after diarrhea or vomiting
  • Cardiac toxicity from doxorubicin
  • Catheter-related sepsis
  • Catheter-related thrombosis
  • Secondary malignancies
  • Tumor lysis syndrome: Characterized by hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and renal failure, this syndrome commonly occurs after treatment of high-grade bulky NHLs because of their exquisite sensitivity to therapy, which is caused by their high proliferative capacity. Death from cardiac asystole can occur from hyperkalemia. Measures to prevent this complication include aggressive hydration, allopurinol administration, and urine alkalinization. Frequent monitoring of input and output, electrolytes, uric acid, and creatinine is necessary. Dialysis is sometimes required.

Prognosis

• Patient's response to treatment and prognosis depends on tumor histology (based on Working Formulation classification), tumor stage, patient's age, tumor bulk, performance status, serum LDH, beta2-microglobulin, and presence of extranodal disease. In general, these clinical characteristics are thought to reflect the following host or tumor characteristics:  
• • Tumor growth and invasive potential (eg, LDH, stage, tumor size, beta2-microglobulin, number of nodal and extranodal sites, bone marrow involvement)
  • Patient's response to tumor (eg, performance status, B symptoms)
  • Patient's tolerance of intensive therapy (eg, performance status, patient age, bone marrow involvement)
• Prognostic score for aggressive lymphomas: The International Prognostic Index (IPI), which was originally designed as a prognostic factor model for aggressive NHL, also appears to be useful for predicting the outcome of patients with low-grade lymphoma and mantle cell lymphoma. This index is also used to identify patients at high risk of relapse based on specific sites of involvement, including bone marrow, CNS, liver, testis, lung, and spleen. These patients may be considered for clinical trials that aim at improving the current treatment standard. An age-adjusted model for patients younger than 60 years has been proposed. In younger patients, stage III or IV, high LDH levels and nonambulatory performance status are independently associated with decreased survival rates. Clinical features included in the IPI that are independently predictive of survival include the following:
• • Age - Younger than 60 years versus older than 60 years
  • LDH level - Within the reference range versus elevated
  • Performance status - ECOG 0-1 versus 2-4
  • Ann Arbor stage - Stage I-II versus III-IV
  • Number of extranodal sites - 0-1 versus more than 1
  • Patients with 0-1, 2-3, and 4-5 risk factors have 75%, 50%, and 25% chance, respectively, of having a relapse-free and OS at 5 years.
• Prognostic score for follicular lymphomas: The FLIPI score was created by a collection of characteristics at diagnosis from 4167 patients with follicular lymphoma (FL) diagnosed between 1985 and 1992 from Solal-Celigny et al.³ Univariate and multivariate analyses were used to propose the prognostic index (PI). This index was then tested on 919 patients. Five adverse prognostic factors were selected: age (>60 y), Ann Arbor stage (III-IV), hemoglobin level (<12 g/dL), number of nodal areas (>4) and serum LDH level (above normal). Three risk groups were defined: low risk (0-1 adverse factor), intermediate risk (2 factors), and poor risk (3 or more adverse factors). FLIPI appeared more discriminant than the International Prognostic Index. FLIPI may be used for improving treatment choices, comparing clinical trials, and designing studies to evaluate new treatments.
• Biomarkers in tumor cells such as the expression of bcl-2 or bcl-6 proteins, and cDNA microarray provide useful prognostic information.
• Concomitant immunodeficiencies: Patients with congenital or acquired immunodeficiency have an increased risk of lymphoma and respond poorly to therapy.
• Other prognostic factors
• • Time to achieve CR and response duration: Patients who do not achieve complete remission by the third cycle of CHOP chemotherapy have a worse prognosis than those who achieve rapid CR.
  • Immunophenotype: Patients with aggressive T- or NK-cell lymphomas generally have worse prognoses than those with B-cell lymphomas, except the Ki-1 anaplastic large T- or null-cell lymphomas.
  • Cytogenetic abnormalities and oncogene expression: Patients with lymphomas with 1, 7, and 17 chromosomal abnormalities have worse prognoses than those with lymphomas without these changes.
• Low-grade lymphomas have indolent clinical behavior, are associated with a comparatively prolonged survival rate (median survival is 6-10 y), but have little potential for cure when the disease manifests in more advanced stages. They also have the tendency to transform to high-grade lymphomas.
• Approximately 70% of all patients with intermediate- and high-grade NHL relapse or never respond to initial therapy. Most recurrences are within the first 2 years after therapy completion.
• Patients with relapsed or resistant NHL have a very poor prognosis (<5-10% are alive at 2 y with conventional salvage chemotherapy regimens).

Patient Education

• Patients should receive a clear and detailed explanation of all the available treatment options, prognosis, and adverse effects of chemotherapy.
• Advise patients to call their oncologists as necessary and alert patients about oncologic emergencies that require an immediate emergency department visit.
• Suggest psychosocial counseling.
• 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 10  

• Authors and Editors