AUTHOR AND EDITOR INFORMATION

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• Medication
• Follow-up
• Miscellaneous
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INTRODUCTION

Section 2 of 11  

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• Follow-up
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Background

Small noncleaved cell (SNCC) lymphomas are high-grade B-cell lymphoma. It is a historical term used to describe Burkitt lymphoma (BL). The World Health Organization Classification of lymphoid neoplasms identifies Burkitt lymphoma/leukemia as a highly aggressive mature B-cell neoplasm. It is further subdivided into endemic, sporadic, and immunodeficiency-associated variants. Some patients can also present with leukemia (L3 ALL).

Dennis Burkitt, a surgeon working in Kampala, Central Africa, first described BL in 1958. He noted children with lesions involving the face and jaw. Some children also had huge abdominal masses but no lymph node involvement. This condition was shown to be a lymphoma and named after him. It is a type of highly aggressive non-Hodgkin lymphoma (NHL), and it often presents in extranodal sites or as acute leukemia.

A few years later, Dr Burkitt met Dr Epstein, who was a pathologist. Dr Epstein and his colleagues identified Epstein-Barr virus (EBV) from the lymphoma samples Dr Burkitt provided establishing a role for EBV in the pathogenesis of Burkitt lymphoma.

The characteristic feature of this entity is the dysregulation and mutation of the c-MYC oncogene. It often resulted from translocation of chromosome 8 and 14 t(8:14). Other translocations are also reported causing c-MYC overexpression.

Burkittlike lymphoma (BLL) is morphologically different from BL. The Southwest Oncology Group (SWOG) published their experience with BLL. BLL is similar to BL with a high mitotic rate, prominent cytoplasmic basophilia, cytoplasmic vacuolation, and a starry sky pattern. Treatment is identical to protocols used to manage BL.

Epidemiologically BL is classified into sporadic, endemic, and HIV-associated varieties. The sporadic variant is present in North America and Europe, and the endemic variant is observed in equatorial Africa. HIV-associated BL accounts for about 30% of lymphoma patients with HIV. These lymphomas have a rapid and aggressive clinical course, commonly presenting in children and young adults, with frequent bone marrow and peripheral blood involvement. It is considered to be a medical emergency and requires immediate diagnostic and therapeutic intervention.

Pathophysiology

Burkitt lymphoma is a mature B-cell lymphoma. All the symptoms are caused by rapid turnover of the mature B lymphocytes and the involvement of extranodal sites and invasion of contiguous organs. C-MYC dysregulation is the basis for all the pathophysiology of Burkitt lymphoma. C-MYC is activated via its juxtaposition with immunoglobulin enhancers. The C-MYC is also mutated. Molecular epidemiology mapped the C-MYC mutation to several hotspots, which occurred in about 20% cases. The activation of C-MYC resulted in increased cell cycle progression, decreased apoptosis, increased cell growth and arrest of cell differentiation, increased cellular metabolism, and decreased cell adhesions.

Frequency

United States

Western Europe and United States

The incidence of sporadic BL is 2-3 cases per million individuals in the United States. It accounts for 1-2% of adult lymphoma cases, and up to 40% of lymphoma cases in children. The incidence of BLL is less frequent. The diagnosis has been problematic because of confusion regarding diagnostic criteria and changes in classification schemes. Thirty to forty percent of HIV-related non-Hodgkin lymphoma (NHL) cases are Burkitt lymphoma.

International

Incidence of endemic BL in African children is much higher than in the United States. The children are usually 4-7 years. It was estimated to be 50 times higher. EBV infection is found in nearly all cases.

Mortality/Morbidity

Approximately 90% of pediatric patients and up to 89% of adults with BL/BLL treated with current intensive chemotherapy regimens have long-term disease-free survival. For those experience relapse, as many as 25% of patients may be able to achieve a long-term disease-free survival through high-dose therapy with autologous hematopoietic stem-cell transplantation. The addition of rituximab to this therapeutic regimen may further increase the response rate.

Race

No racial predilection is reported, although the endemic BL observed primarily in equatorial Africa has primary jaw involvement (70% in children aged 4-7 years versus 15-20% in the sporadic US variety).

Sex

The male-to-female ratio is 2-3:1.

Age

Endemic BL is common in children (30% of non-African pediatric lymphomas), but it is rare in adults (1-2% of all cases of NHL). Twenty to thirty percent of NHL in HIV patients are BL. It can present as an AIDS-defining illness and does not correlate with the CD4 counts.

CLINICAL

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History

Three different clinical variants of Burkitt lymphoma (BL) are described: endemic, sporadic, and immunodeficiency related. Their presentations may vary.

The endemic form is most commonly seen in patients in equatorial Africa, with face and jaw involvement. Other clinical presentations include abdominal masses, and ileal, cecal, ovarian, and breast involvement have also been documented. The geographic distribution of the tumor corresponds to the epidemiologic distribution of malarial infections.

The sporadic forms most often present with abdominal tumors with bone marrow involvement.

Patients usually present with extranodal disease. It can also present as a leukemic type such as L3 lymphocytic leukemia.

Generalized lymphadenopathy is rare. Approximately 90% of patients with sporadic BL and 50% of patients with endemic BL have abdominal masses upon presentation.

Patients with BLL may have variable presentation compared with those with BL. Patients with BLL usually present in their fourth or fifth decade of life. Braziel et al (2001) have reported on the clinical features of BLL after review of SWOG data. Median age was reported as 67 years (range, 28-69 y), and 70% of the patients presented with bulky advance disease (II, III, or IV), with 60% of patients having 2 or more extranodal sites of lymphoma involvement.

Patients with BL may have the following common findings and symptoms:

• Face and jaw involvement in endemic BL
• • Abdominal masses can cause abdominal pain and distention, and ascites.
  • Nausea and vomiting
  • Loss of appetite and/or change in bowel habits
  • Gastrointestinal bleeding
  • Signs and symptoms of acute abdomen
  • Intestinal perforation
  • Right iliac fossa mass (40% of cases in the US National Cancer Institute [NCI] series)
  • Renal failure as a result of retroperitoneal disease and renal involvement
• Mandibular or maxillary mass
• • Most common presentation in the endemic variety
  • Jaw involvement much less frequently (It only occurs in 15-20% of sporadic cases.)
  • Maxillary tumors - More common, may involve the orbit
• Bone marrow involvement is common in BL.
• • CNS involvement is common, which includes the following:
    • Meningeal infiltration with or without cranial nerve (frequently third and seventh nerve) involvement - Most common mode of presentation with CNS disease
    • Headaches, visual impairment, and paraplegia from spinal involvement - May be initial presenting features in some cases
• "B" systemic symptoms
• • Fever, weight loss, night sweats, fatigue
  • Although uncommon, may be associated with other presenting symptoms

Physical

The physical examination findings depend on the sites of extranodal involvement by BL.

• Abdominal tenderness
• Ascites
• Abdominal mass
• Hepatosplenomegaly
• Palpable tumor of the mandibulomaxillary region
• Ecchymosis and/or petechiae (as a result of thrombocytopenia)
• Meningeal signs (from CNS disease)
• Painless lymphadenopathy

Causes

The following are considered etiologic factors that are implicated in the pathogenesis of BL:

• Viral: EBV is associated with 95% of endemic SNCC lymphomas and 20-30% of sporadic BL cases.
• c-MYC oncogene activation: The classic t(8;14)(q24;q32) reciprocal translocation (85%) results in the transposition of the c-MYC proto-oncogene on chromosome 8 with one of the immunoglobulin genes on chromosome 14, which results in activation of the c-MYC gene and is considered responsible for tumor proliferation. The variant translocations involving c-MYC transposition to the other immunoglobulin genes, t(2;8) and t(8;22), are also found in BL. C-MYC mutations are also presented.
• P53 gene: Abnormalities in P53 genes have also been reported and are thought to be associated with the pathogenesis of BL.

DIFFERENTIALS

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WORKUP

Section 5 of 11  

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Lab Studies

• Flow cytometry of biopsied tissue or bone marrow may reveal expression of immunoglobulin M (IgM) surface immunoglobulins (most common) as well as other mature B-cell markers such as CD19, CD20, CD22, CD79a, and CD10. Tdt, CD5, CD23, and CD34 negative.
• Cytogenetic studies may reveal one of 3 reciprocal chromosomal translocations: t(8;14)(q24;q32) in 85% of cases, t(2;8)(p12;q24), and t(8;22)(q24;q11).
• Complete blood counts may reveal pancytopenia (anemia, thrombocytopenia, and/or leukopenia) due to the involvement of the bone marrow.
• Serum chemistries
• • Electrolyte imbalances occur as a result of renal infiltration with lymphoma. The rapid turnover of the Burkitt lymphoma (BL) cells may cause primary tumor lysis.
  • Oliguric renal failure may be a presenting feature of patients with a high tumor burden, resulting in uric acid nephropathy.
• Serum lactate dehydrogenase (LDH) level, if elevated, corresponds with tumor burden and the extent of disease. It is also a useful indicator of the patient's response to treatment and can be used as an early nonspecific indicator of disease relapse.
• Liver function test results, if abnormal, may be indicative of visceral involvement with lymphoma.
• Beta2 microglobulin is a predictor of the extent of disease and is used as a surrogate marker for early relapse.
• Serum uric acid levels, if high, reflect the high-grade nature of the disease and correlate with the probability of tumor lysis syndrome with initiation of cytotoxic therapy.

Imaging Studies

• CT scan of the abdomen and pelvis can be used to evaluate for abdominal and pelvic lymphadenopathy, masses, and visceral involvement. This helps in determining the extent of the disease and may aid in determining the most suitable site for biopsy. CT scanning of the chest should be performed to complete the staging workup.
• CT scan or MRI of the brain or spinal cord is indicated if neurologic signs are present.
• Findings on gallium scan provide an estimate of the extent of disease, and gallium scan is used as a follow-up tool in assessing sites of relapse.

Other Tests

• ECG is indicated for possible arrhythmia resulting from cardiac involvement.
• Multigated angiogram (MUGA) is used to evaluate the ejection fraction prior to chemotherapy; anthracyclines have a potential cardiotoxic effect.

Procedures

• Laparotomy was indicated for initial diagnosis and for resection of the disease years ago; it is not recommended by current guidelines.
• The diagnosis of BL or BLL is made by obtaining a biopsy of the tumor mass for histopathology, immunochemistry, and flow cytometry. Cytogenetic studies to identify C-Myc mutation will aid in the diagnosis.
• Bone marrow aspirate and biopsy: The aspirate should be sent for cytogenetic studies. If lymphoma cells are present in the aspirate, flow cytometry/immunophenotyping should be ordered to further characterize the disease.
• • Bone marrow is involved in 20% of sporadic cases and 8% of endemic cases.
  • Obtaining bilateral biopsy and aspirate specimens is highly recommended.
• Lumbar puncture (LP) is considered part of the staging workup. LP should be performed to ascertain meningeal involvement. The CSF should be sent for cytology and, possibly, flow cytometry in addition to the usual studies. Intrathecal chemotherapy is usually given at the time of initial LP.

Histologic Findings

Extranodal involvement shows monotonous morphology with cells of uniform size and shape. The cytoplasm is scanty, and the nucleus is round or slightly irregular with slightly coarse chromatin and several nucleoli. Mitotic figures are frequently seen. The description of "starry sky appearance" is because of the scattered macrophages with phagocyte cell debris under the microscope. However, the starry sky pattern is not pathognomonic for BL and may be observed in other highly proliferative lymphomas. Immunophenotype and cytogenetic studies are aiding the diagnosis of BL.

Staging

Ann Arbor system and Jude/Murphy staging are commonly used.

• Stage I
• • Single tumor (extranodal)
  • Single anatomic area (nodal)
• Stage II
• • Single tumor (extranodal) with regional node involvement
  • Primary gastrointestinal tumor
  • Lymphoma involving sites on the same side of the diaphragm
• Stage III - Lymphoma involving sites both above and below the diaphragm
• Stage IV - Any of the above with CNS or bone marrow involvement at presentation

TREATMENT

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Medical Care

Patients in whom BL is suspected should be admitted to the hospital. These patients experience rapidly progressive of extranodal sites; therefore, a diagnostic workup should be completed as soon as possible. Consultation with a hematologist and hematopathologist should be obtained as soon as possible. Measures should be taken to prevent tumor lysis syndrome, including the following:

• Maintain adequate hydration through intravenous fluids, starting 24-48 hours prior to chemotherapy.
• Maintain high urine outflow (200-250 mL/m²/h).
• Administer allopurinol (600 mg loading dose and then 300 mg daily) in divided doses, starting 24-48 hours prior to chemotherapy.
• Monitor serum electrolyte levels for hyperkalemia, hyperphosphatemia, and hyperuricemia.
• Monitor renal function closely to screen for uric acid nephropathy.

Surgical Care

The role of surgical debulking in patients with BL has become controversial because of improved response rates (ie, up to 90%) with combination chemotherapy alone. Historically, most patients who presented with large masses, particularly abdominal disease, underwent an exploratory laparotomy, at which time an effort was made to debulk as well. With newer sophisticated interventional radiology approaches, an adequate diagnosis can be reached in almost all patients without major surgical intervention.

In current clinical practice, effective and durable responses are observed with combination chemotherapy, obviating the role of surgical debulking.

• Tracheotomy is indicated if the patient's airway is compromised from the physical pressure of a large tumor mass.
• Exploratory laparotomy due to bowel obstruction (often before the diagnosis was made)
• • Patients with uncontrolled gastrointestinal bleeding also may need exploratory laparotomy or endoscopic procedures for hemostasis.
  • Pericardiocentesis is indicated for patients presenting with cardiac tamponade.
• Paracentesis is indicated if large ascites is one of the presenting complaints.
• An excisional lymph node biopsy is usually necessary to reach an accurate diagnosis.
• A semipermanent intravenous catheter such as a peripherally inserted central catheter (PICC) line or medicine port should be arranged with interventional radiology or surgery to aid chemotherapy, medications, blood products, and fluid management.

Consultations

Various subspecialty consultations may be required as indicated by clinical situations.

• Renal consultation for patients presenting with, or developing, renal failure (uric acid nephropathy) that may require dialysis
• Surgical consultation for the reasons mentioned above
• Interventional radiology consultation for diagnostic fine-needle aspiration or core needle biopsy procedures and for placement of indwelling central venous access devices

Diet

• Regular diet is continued as tolerated.
• Institute a neutropenic diet during neutropenic periods after chemotherapy.

Activity

No limitations on activity are necessary.

MEDICATION

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Systemic combination chemotherapy is the treatment of choice for all stages of Burkitt lymphoma (BL). It should be started as soon as possible as the diagnosis is made. With current short, intensive chemotherapy approaches, cure rates have been reported in the range of 90% for children and up to 89% in adults.

Various chemotherapy regimens have been used. An effective regimen is composed of an alkylating agent, usually high-dose cyclophosphamide and/or ifosfamide, combined with vinca alkaloids, steroids, and an anthracycline.

Most protocols incorporate cyclophosphamide, methotrexate, vincristine, and doxorubicin, with or without corticosteroids. Two to 3 months of treatment is now considered sufficient depending on the stage of disease, with reported cure rates of 90-100%. The Children's Cancer Study Group (CCSG) conducted a randomized trial comparing 6 months of therapy versus the traditional 18 months of chemotherapy and found equivalent efficacy with the abbreviated course of chemotherapy. Further trials conducted in Europe and the United States reported favorable results with only 2-3 months of therapy. Radiation has no role in the management of any stage of disease. BL is considered to be a systemic disease.

Based on the extent of disease and LDH level and cytogenetic studies, patients can be stratified into low-risk and high-risk categories.

Low-risk category: Patients have low tumor burden, as determined by low LDH level, completely resected abdominal disease, or a single extra-abdominal site of disease. In such cases, combination chemotherapy (preferably via a clinical trial) should be considered.

High-risk category: Patients have high tumor burden, as determined by a high LDH level, and extensive abdominal or extra-abdominal disease. These patients are at high risk for relapse. Combination chemotherapy in the setting of a clinical trial is the recommended way to treat these patients. High-dose methotrexate, anthracyclines, alkylating agents, and intrathecal chemotherapy are usually used. Patients who have CNS or bone marrow disease should be considered for enrollment in clinical trials involving consolidation with high-dose chemotherapy with autologous stem cell rescue.

Various protocols used for the treatment of BL (both adults and children)

• LMB protocol of the Societe Francaise d'Oncologie Pediatrique (Soussain, 1995)
  • Complete responses - 89%
  • Relapse rate - 12%
  • Disease-free survival - 74%
• Hyper-CVAD protocol (Todeschini)
  • Complete responses - 100%
  • Relapse rate - 15%
  • Disease-free survival - 75%
• NCI 89-C-41 protocol (Magrath, 1996)
  • Complete responses - 100%
  • Relapse rate - 0%
  • Disease-free survival - 100%
• Vanderbilt protocol (McMaster, 1991)
  • Complete responses - 85%
  • Relapse rate - 15%
  • Disease-free survival - 65%

CNS prophylaxis

CNS prophylaxis is warranted in all patients except those in stage I with minimal disease or those with completely resected stage I abdominal disease, in whom the incidence of CNS relapse is minimal. A combination of intrathecal cytarabine (Ara-C) and methotrexate, along with high-dose systemic methotrexate or Ara-C, is the regimen usually used.

The Cancer and Leukemia Group B (CALGB) launched a multidrug regimen pilot study (9251) of high-intensity, brief-duration chemotherapy. A brief schema of this protocol is discussed here; the results of this study are still not published, and, therefore, this regimen does not represent standard therapy for SNCC NHL.

(Note: Courses II, IV, and VI are similar, and courses III, V, and VII are similar and described together.)

• Course I - Cyclophosphamide 200 mg/m²/d IV on days 1-5; prednisone 60 mg/m²/d PO for 7 d on days 1-7
• Courses II, IV, and VI
  • Ifosfamide 800 mg/m² IV qd for 5 d (cycles II, IV, and VI); MESNA 200 mg/m² IV (with ifosfamide) qd for 5 d (in cycles II, IV, and VI); methotrexate (MTX) 1.5 g/m² IV (in cycles II, IV, and VI); leucovorin 50 mg/m² IV starting 36 h after methotrexate, then 12 mg/m² q6h until MTX levels are less than 5 X 10^-8 M; vincristine 2 mg IV bolus (in cycles II, IV, and VI); Ara-C 150 mg/m²/d continuous infusion over 48 h (cycles II, IV, and VI); etoposide 80 mg/m² qd for 2 d (cycles II, IV, and VI); dexamethasone 10 mg/m² PO qd for 5 d (cycles II, IV, and VI)
  • Intrathecal - MTX 15 mg plus Ara-C 40 mg plus hydrocortisone 50 mg (cycles II, IV, and VI)
• Courses III, V, and VII
  • Cyclophosphamide 200 mg/m² IV for 5 d; MTX 1.5 g/m² IV (over 24 h); leucovorin 50 mg/m² IV starting 36 h after MTX and then 12 mg/m² until MTX level is less than 5 X 10^-8 M; vincristine 2 mg IV push; Adriamycin 25/m² IV for 2 d; dexamethasone 10 mg/m² PO qd for 5 d
  • Intrathecal - MTX 15 mg plus Ara-C 40 mg plus hydrocortisone 50 mg for 1 dose (each cycle)
  • Cranial radiation (only for those patients with prior bone marrow involvement) - 2400 cGy in 12 fractions administered 21 days after the start of course VII

Relapsed small noncleaved cell lymphoma

Patients usually experience relapse within 8 months of therapy, if at all. Those who remain free from disease at 8-10 months are considered cured, although reports of delayed relapse, ie, as long as a few years, have been described in the African population and in patients with concurrent HIV infection. Most patients in this group respond poorly to salvage therapy, although some patients are reported to have long-term survival. The salvage regimen typically incorporates chemotherapeutic agents to which the patient has had no prior exposure. The DHAP (dexamethasone at 40 mg PO for 4 d, high-dose Ara-C at 2000 mg/m² q12h for 2 doses, and cisplatin at 100 mg/m² for 1 dose) regimen often is used as salvage therapy. Among these patients, those whose disease demonstrates some chemosensitivity are then referred for high-dose chemotherapy and autologous stem-cell/bone marrow transplantation or allogeneic stem-cell transplantation via clinical protocols.

Bone marrow transplantation

The use of high-dose chemotherapy plus stem-cell transplantation has decreased because of the high rate of remission achieved with current regimens.

High-dose chemotherapy plus autologous stem-cell transplantation may be considered for patients who have not responded to (primary refractory) or have relapsed after first-line conventional chemotherapy. The outcome for adult patients treated with a short, intensive regimen is less favorable than the outcome in children. Up to 40% of the patients treated on the LMB81 and LMB84 regimens experienced relapse. Current indications for treatment of these patients with high-dose chemotherapy plus autologous stem-cell transplantation remain similar to those of the pediatric group.

• Primary refractory disease: Patients with primary refractory disease do not respond well to high-dose chemotherapy plus autologous stem-cell transplantation. The duration of responses in these patients is often short, with eventual relapse in most reported series. Alternative approaches, including allogeneic bone marrow/stem-cell transplantation or salvage regimens in the setting of a clinical trial, should be considered in these cases.
• Partial remission: Patients in first partial remission should be considered for high-dose chemotherapy plus autologous stem-cell transplantation. The outcome of treatment in these patients with conventional chemotherapy regimens is usually poor. Philip and Biron (1986) reported the results of bone marrow transplantation in patients with NHL, including BL, in partial remission. In this series, a 70% survival rate at 2 years (in BL) was reported. Subsequent randomized studies in aggressive NHL have failed to clearly show an advantage. Currently, patients with BL whose disease demonstrates chemosensitivity and who achieve a good partial remission after front-line therapy should be considered for high-dose chemotherapy plus autologous stem-cell transplantation.
• Clinical remission: Patients in first clinical remission with poor prognostic features have been considered for consolidation therapy with high-dose chemotherapy plus autologous stem-cell transplantation. Published data to date do not support the use of this approach outside of a clinical trial.
• Relapse: The French group has reported improved survival rates in patients with relapsed aggressive NHL who were treated with high-dose chemotherapy plus autologous stem-cell transplantation. The only significant prognostic factor noted was sensitivity to reinduction chemotherapy at the time of relapse. A 3-year survival rate of 36% in sensitive relapse (SR) versus 14% in resistant relapse (RR) was reported. Subsequent studies have reported similar outcomes. Patients with relapsed BL with chemosensitive disease should be considered for high-dose chemotherapy plus autologous stem-cell transplantation; alternative therapies should be considered for those with RR.

The role of allogeneic stem-cell transplant and graft versus leukemia effect in BL or BLL remains investigational. Many transplant centers consider this option for patients at high risk and for those with refractory disease. Recently, case reports have suggested a possible role of nonablative and cord blood transplantation in relapsed heavily treated patients.

Supportive medications

These are used to help control the adverse effects of chemotherapy, such as nausea, vomiting, tumor lysis syndrome, and infections.

Drug Category: Alkylating agents

These agents inhibit cell growth and proliferation.

FOLLOW-UP

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Further Inpatient Care

• Intravenous antibiotics for neutropenic fevers
• Growth factors (granulocyte-macrophage colony-stimulating factor [GM-CSF] or granulocyte colony-stimulating factor [G-CSF]) to help decrease the duration of neutropenia
• Transfusions (red blood cells or platelets), as clinically indicated for anemia and thrombocytopenia
• Anticoagulation and possible inferior vena cava (IVC) filter placement for patients presenting with intraluminal thrombosis

Further Outpatient Care

• After remission induction, patients' cases should be followed every 2 months during the first year, then every 3 months the following year, and every 6 months thereafter.
• During follow-up visits, a complete physical examination should be performed and CBC and serum electrolyte levels should be obtained. LDH and beta2 microglobulin may be helpful in detecting early relapse.
• Repeat staging with CT scan is performed during and after completion of treatment to ascertain disease response and document achievement of complete remission.

In/Out Patient Meds

• For patients with HIV, highly active antiretroviral therapy (HAART) should be started with the chemotherapy.

Deterrence/Prevention

• During the neutropenic phase, patients should avoid flowers and potted plants and thoroughly wash fresh fruits and vegetables.

Complications

• Complications from disease (The likelihood of complications increases with extent of disease.)
• • Renal failure from tumor infiltration of the kidneys
  • External compression of ureters causing obstructive uropathy, and compression of loops of bowel causing bowel obstruction
• Complications from chemotherapy
• • Tumor lysis syndrome
  • Cardiomyopathy (anthracycline related)
  • Infections (during neutropenia postchemotherapy)
  • Gonadal dysfunction (chemotherapy-related sterility)
  • Secondary leukemias (exposure to alkylating agents), a late potential complication generally occurring more than 5 years after alkylator therapy

Prognosis

• Limited disease (stage I and II) - Cure rate of 90-100%
• Extensive disease (stage III and IV) - Cure rate of 50-90%
• Relapse disease - Long-term survival rate of 20-50%

Patient Education

• Patients should be educated about the following:
• • Febrile neutropenia
  • Postchemotherapy thrombocytopenia and the tendency to bleed with minimal trauma
  • Chemotherapy-associated alopecia
  • Avoidance of pregnancy in women of childbearing age
  • Chemotherapy-induced nausea and vomiting
  • Chemotherapy-associated menstrual dysregulation (females) and the possibility of sexual dysfunction
  • Fatigue
  • Sperm banking
• For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education article Lymphoma.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Accurate and expeditious diagnosis is necessary. Patients presenting with B symptoms should have a thorough examination, and a biopsy should be obtained immediately for any suspicious mass. Failure to diagnose this high-grade lymphoma can lead to long-term sequelae and, possibly, death.
• Failure to inform patients about the potential long-term sequelae of chemotherapeutic agents:
• • Secondary leukemias and myelodysplastic syndrome
  • Infertility
  • Possible anaphylactic reactions
  • Serious and potentially fatal infections
• Failure to clearly explain transfusions (both red blood cells and platelets) and their associated complications
• Failure to inform patients who require high-dose chemotherapy and stem-cell transplantation that long-term complications of higher doses of chemoradiotherapy and a mortality rate of 3-5% from the conditioning regimen are possible

Special Concerns

• BL and BLL have an aggressive clinical course; therefore, management should be directed toward an expeditious diagnosis followed by prompt institution of definitive therapy.
• Initial treatment should be started in an inpatient setting.
• Renal failure as a result of tumor lysis syndrome from therapy is a potential risk in all patients, especially those with high tumor burden. Aggressive management of this potentially life-threatening complication should be clearly addressed. Hemodialysis should be considered in these patients early to prevent long-term renal dysfunction.

MULTIMEDIA

Section 10 of 11  

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Media file 1:  Gallium scans of a patient diagnosed with small noncleaved cell lymphoma (SNCCL). Scans show a prominent area of increased uptake in the right cervical region suggestive of gallium avid tumor.
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Media file 2:  Patient with large left-sided axillary mass from which a biopsy was obtained. Biopsy findings were consistent with small noncleaved cell non-Hodgkin lymphoma.
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Media type:  CT

Media file 3:  Right-sided pleural effusion in a patient with small noncleaved cell lymphoma (SNCCL) non-Hodgkin lymphoma.
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Media type:  CT

Media file 4:  Postchemotherapy CT scan of a patient diagnosed with small noncleaved cell lymphoma (SNCCL) (see Image 1), showing regression of left axillary mass.
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Media type:  CT

Media file 5:  Gallium scan of patient who presented with a large right-sided neck mass (see Image 6).
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Media file 6:  Coronal section of a patient with large neck mass (see Image 5). Biopsy findings showed Burkittlike non-Hodgkin lymphoma (NHL). MRI was performed to assess for cord involvement.
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Media type:  MRI

Media file 7:  Sagittal section of the neck area showing a large mass invading the cervical spine with epidural encroachment. MRI was performed to rule out cord compression. Image 1 shows the gallium scan of this patient that correlates with the site of the tumor.
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Media type:  MRI

Media file 8:  Hematoxylin and eosin (H&E) stain. Sheets of monotonous-appearing lymphoid cells with one or more prominent nucleoli and an area of pale staining resulting from the presence of benign macrophages reveal a starry sky pattern.
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Media type:  Photo

Media file 9:  The 2-dimensional flow cytometry demonstrates the highlighted cells to be CD5 negative and CD23 negative as well as lambda negative. Cells typically are CD19+, CD20+, CD22+, and CD10+.
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Media type:  Image

REFERENCES

Section 11 of 11

• Authors and Editors
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• Appelbaum FR, Deisseroth AB, Graw RG, et al. Prolonged complete remission following high dose chemotherapy of Burkitt's lymphoma in relapse. Cancer. Mar 1978;41(3):1059-63. [Medline].
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Article Last Updated: Sep 29, 2004