Lymphoma, diffuse large cell

Author: Andre M Kallab, MD, Clinical Associate Professor of Oncology, Medical College of Georgia; Consulting Staff, Department of Oncology, Northeast Georgia Diagnostic Clinic
Andre M Kallab, MD, is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Clinical Oncology, and American Society of Hematology
Editor(s): Michael Paul Kosty, MD, Associate Director, Associate Professor, Department of Internal Medicine, Divisions of Supportive Care Services and Hematology and Oncology, Ida M and Cecil H Green Cancer Center, Scripps Clinic; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Wendy Hu, MD, Consulting Staff, Department of Hematology/Oncology and Bone Marrow Transplantation, Huntington Memorial Medical Center; Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems; and Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Thomas Jefferson University, Jefferson Medical College

Disclosure
INTRODUCTION Section 2 of 11
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography
Background: The non-Hodgkin lymphomas (NHLs) constitute a heterogeneous group of lymphoid system neoplasms with varying presentation, natural history, and response to therapy.

During the past 15 years, considerable progress has been made in NHL classification. In 1982, the National Cancer Institute introduced the International Working Formulation, a translation system for other older classifications, including the Rappaport and the immunologically oriented Lukes-Collins and Kiel systems. The working formulation provided a conceptual framework that groups lymphomas as low-grade (indolent), intermediate-grade, or high-grade with respect to their natural histories.

In 1994, the International Lymphoma Study Group proposed the Revised European-American Lymphoma (REAL) classification schema. It classifies NHLs as being derived from B or T/NK-cells, and it includes new disease entities that were not part of the working formulation.

The diffuse large cell lymphoma (DLCL) of the REAL classification combines the large cell and the immunoblastic categories of the working formulation. These lymphomas currently are considered a single group because they behave similarly and, therefore, have similar prognoses. DLCL is the most common lymphoma, representing 31% of NHLs, and is rapidly fatal if untreated.

Pathophysiology: Under the International Working Formulation in the classification of intermediate-grade DLCLs, approximately 79% of DLCLs were of B-cell origin, 16% of T-cell origin, and 5% were unclassifiable. Exceptional cases expressed both B-cell and T-cell markers.

Incorporation of the REAL classification system for lymphomas has been strongly encouraged. In addition to morphologic descriptions, this schema includes immunologic, cytogenetic, and molecular information in order to define distinct lymphoma entities. Currently, the diffuse large B-cell lymphomas are considered in the REAL classification as the classic DLCL of B-cell origin defined by the working formulation. Lymphomas of T-cell or NK-cell origin exhibit biological and clinical features distinct from diffuse large B-cell lymphomas.

B-cell restricted markers (CD19, CD20, CD22) are expressed consistently. Activation antigens are variably expressed by B-cell DLCLs, with HLA-DR being the most frequent and CD23 being expressed uncommonly (0-25%). The presence of CD10 or CD5 suggests that at least one third of DLCLs may have transformed from follicular lymphomas or a small lymphocytic lymphoma.

The majority of B-cell DLCLs demonstrate rearrangements of the immunoglobulin genes by DNA hybridization techniques, proving their B-cell lineage.

Mutations or allelic losses of the p53 tumor suppressor gene or 17p13.1 are common in DLCLs, particularly in the immunoblastic type. Changes of p53 appear especially involved in the evolution of follicular lymphoma to DLCL. A number of cytogenetic abnormalities have been reported in DLCLs, including t(14;18), t(8;14), trisomy 12, and deletion of 6q.


Frequency:


In the US: The incidence of NHL has been increasing more rapidly than many other malignancies. Overall, the incidence has increased more than 73% between 1973 and 1991. The current US age-adjusted rate is 15.1 cases per 100,000 person-years for both sexes. The estimated rate for DLCLs is approximately 4.68 cases per 100,000 person-years.
Internationally: In general, age-adjusted incidence is higher in developed countries. For men, it varied from 3.7-14 cases per 100,000 persons per year from 1983-1987. Over the past 2 decades, rates for both men and women have increased by 50% or more in 20 different countries. The rates by subtype, such as Burkitt lymphoma (Epstein-Barr virus–associated) and human T-cell leukemia virus type 1–related lymphoma/leukemia, also vary widely in different geographic areas and are much more frequent in endemic areas.
Mortality/Morbidity:

Mortality rates have increased significantly in each race/sex group. Rates of change are highest in areas where HIV is epidemic and in patients with posttransplant lymphoproliferative diseases.
Recent data suggest that 5-year survival rates are higher for Caucasians compared to people of African descent, which may or may not reflect socioeconomic factors.
Women have a better survival outcome, as do patients younger than 65 years.
Race:

Incidence varies by race.
Caucasians have higher rates than people of African or Asian descent.
The Surveillance, Epidemiology, and End Results registry demonstrates rates in white men that are 49% higher than in African Americans, 54% higher than in Japanese Americans, and 27% higher than in Chinese Americans. These differences also apply to women.
Sex:

The male-to-female disease incidence ratio is 1.3:1.
Age:

Although DLCLs can occur at any age, in general, they occur in middle-aged and older adults.

 

History:
  • The clinical manifestations of DLCLs are diverse and depend on the site of disease involvement.
  • These tumors have a rapid growth rate.
  • They present as masses, causing symptoms when they infiltrate tissues or obstruct organs.
  • Pain in an enlarged lymph node or organ may be noted if the lymphomatous mass enlarges rapidly.
  • As with other types of NHL, DLCLs can present with B symptoms, including fever, drenching night sweats, and weight loss. Generalized pruritus also may be present.

Physical:

  • Most frequently, DLCLs appear in lymphoreticuloendothelial tissues, which include the lymph nodes, spleen, liver, and bone marrow. However, any extranodal site may be primarily or secondarily involved, including the central nervous system (CNS), lungs, gastrointestinal tract, genitourinary tract, and the bones.
  • Involvement of sanctuary sites, including the CNS and testicles, is more frequently associated with Burkitt and non-Burkitt lymphoma, HIV-associated lymphoma, human T-cell leukemia virus type 1–associated lymphoma, primary CNS lymphoma, and primary testicular DLCL.
  • Involvement of the cerebrospinal fluid (CSF) with DLCL is observed more frequently with advanced-stage disease and bone marrow involvement.

Causes:

  • NHLs have been associated with the following conditions:
    • Hereditary immunodeficiency disorders such as ataxia-telangiectasia syndrome, Bruton-type agammaglobulinemia, severe combined immunodeficiency, Wiskott-Aldrich syndrome, Duncan syndrome, and Chediak-Higashi syndrome
    • Infections such as HIV, Epstein-Barr virus (EBV), Helicobacter pylori infection, hepatitis C, human T-cell leukemia virus (HTLV), and human herpes virus–type infections
    • Autoimmune disorders such as rheumatoid arthritis, Sjögren syndrome, and systemic lupus erythematosus
    • Use of drugs such as immunosuppressants and chemotherapeutic agents
    • Exposure to environmental toxins such as herbicides, vinyl chloride, and organic solvents
Lab Studies:
 
  • After histology and immunology confirm the diagnosis of DLCL, a pretreatment staging evaluation should be performed.
  • At minimum, patients should have routine blood counts and blood chemistries, particularly a lactate dehydrogenase (LDH) level, which is a prognostic parameter.
  • Carefully examine the peripheral blood smear for any abnormal lymphoid cells.

Imaging Studies:
 

  • Radiologic staging studies include chest radiograph and CT scan of the chest, abdomen, and pelvis.
  • Upper and lower gastrointestinal series, in conjunction with appropriate endoscopic studies, are indicated in patients with gastrointestinal symptoms but need not be performed routinely in asymptomatic patients.
  • Additional studies, such as bone scans, gallium scans, positron emission tomography (PET) scans, and plain films, may be helpful in selected patients.
    • Patients with unexplained bone pain or elevated alkaline phosphatase levels should be evaluated with a bone scan. Obtain plain radiographs of any abnormal area on the bone scan to check for lymphomatous involvement of the skeleton.
    • Gallium-67 scans are valuable in the staging of DLCLs. Gallium uptake correlates with disease activity and is useful as an indicator of response and prognosis. Uptake of gallium-67 occurs in approximately 50% of indolent lymphomas and in most aggressive and highly aggressive types.
    • PET scans increasingly are being used to stage disease by using fructose diphosphate glucose as a measure of disease metabolic activity. PET scanning may be more sensitive than gallium scans for more indolent lymphoproliferative diseases, but definitive data comparing gallium to PET scanning in lymphomas are not available.

Procedures:
 

  • An excisional lymph node biopsy should be performed.
  • Bilateral iliac crest bone marrow biopsies should be performed as a part of the staging.
  • Because bone marrow involvement increases the likelihood of lymphomatous involvement of the meninges, in patients with advanced stage disease, a lumbar puncture for cytologic and chemical analysis of the CSF may be necessary.
Staging: The Ann Arbor staging system, originally designed for Hodgkin disease, traditionally is used to assess extent of disease involvement by NHL.
  • Stage I is disease involvement of a single lymph node region or of a single extranodal organ or site (I E).
  • Stage II is involvement of 2 or more lymph node regions on the same side of the diaphragm or localized involvement of an extranodal site or organ (II E) and involvement of 1 or more lymph node region on the same side of the diaphragm.
  • Stage III is involvement of lymph node regions on both sides of the diaphragm, which may be accompanied by localized involvement of an extranodal organ or site (III E), the spleen (III S), or both (III SE).
  • Stage IV is diffuse or disseminated involvement of 1 or more distant extranodal organ, with or without associated lymph node involvement.
  • The presence of systemic symptoms, including fever higher than 38°C, night sweats, and/or weight loss of more than 10% of body weight in the 6 months preceding diagnosis, are denoted by the suffix B. Staging of asymptomatic patients is denoted by the suffix A.
Medical Care: Therapy for aggressive NHL has evolved significantly in the last 25 years. The CHOP (cyclophosphamide, Adriamycin, vincristine, prednisone) regimen was among the first combinations to produce complete response (CR) rates and long-term survivors. New treatments to increase CRs have not yet shown improvement in survival. Recently, high-dose chemotherapy in the setting of stem cell/bone marrow transplantation has become a useful treatment modality in the management of this disease.
  • Treatment of early stage DLCL (stage IA and IIA, nonbulky)

     

    • Current data suggest that either 6 cycles of CHOP or 3-4 cycles of CHOP followed by involved-field radiation therapy (IFRT) is reasonable treatment of early-stage nonbulky DLCL. The best approach to early-stage disease remains to be defined.

       

    • In patients treated with IFRT alone, relapses occur in nodal sites within and outside the irradiated field. In addition, relapses in the bone marrow and other parenchymal organs suggest the presence of microscopic disease in these organs at the time of diagnosis. As a result, radiation therapy as the sole treatment of early-stage disease has been abandoned. Treatment with either chemotherapy alone or a combination of chemotherapy and IFRT is considered the standard of care.

       

    • When the CHOP regimen was established as effective therapy for advanced-stage disease, some pursued the use of this regimen for early-stage disease. Connors and associates conducted a prospective study employing 3 cycles of CHOP followed by IFRT in 78 patients. Approximately 99% of these patients achieved a CR, and 86% remained free of disease with a median follow-up of 30 months. The actuarial survival rate for the entire group was 84%. Tordini and colleagues reported similar results in a large series of patients.

       

    • The South West Oncology Group (SWOG) conducted a randomized trial in patients with localized intermediate-grade or high-grade NHL, comparing 8 cycles of CHOP versus 3 cycles of CHOP followed by IFRT. The main objective was to compare 2 curative approaches with respect to differences in survival, time to treatment failure, and toxicity. Five-year estimated overall survival rates were 72% for CHOP (8 cycles) and 82% for CHOP (3 cycles) plus radiation. Progression-free survival also was significantly different in the 2 groups (P = 0.03). This SWOG study concluded that 3 cycles of CHOP plus IFRT is more effective and less toxic than 8 cycles of CHOP alone for early-stage DLCL.
  • Treatment of advanced-stage DLCL (stages II bulky, III, and IV)

     

    • The CHOP regimen produced a CR rate of 45-62% in aggressive lymphomas. With up to 14 years of follow-up, CHOP was found to be curative to 32% of patients with advanced DLCL.

       

    • New and more complex regimens, such as M-BACOD (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone, leucovorin), PROMACE-MOPP (prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, mechlorethamine, vincristine, procarbazine, leucovorin), and PROMACE-CYTABOM (prednisone, doxorubicin, cyclophosphamide, etoposide, cytarabine, bleomycin, vincristine, methotrexate, leucovorin), were developed in the 1970s and 1980s and are referred to as second-generation and third-generation regimens. Initial reports of single-institution pilot studies with third-generation regimens suggest 68-86% CR rates and 58-69% survival rates. The survival rates decreased with longer follow-ups.

       

    • Conclusions about the efficacy of the new regimens awaited results of prospective randomized trials. The SWOG conducted a randomized trial comparing standard CHOP to M-BACOD, PROMACE-CYTABOM, or MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, bleomycin, prednisone). After 6 years, no difference in response rate, time to treatment failure, or overall survival was observed among the groups. However, the cost and toxicity of the new regimens were higher. Thus, CHOP remains the best available standard of care for most subtypes of DLCL. However, the newer-generation regimens have demonstrated benefit in selected subgroups of patients with DLCL.

       

    • Because CHOP cures less then 50% of patients with DLCL, new treatments are needed. Current investigations to improve treatment outcome include the following 3 goals:

       

      1. Identification of new active therapies: Rituximab (Rituxan), a chimeric antibody that targets CD20+ B cells, produces a 48% response rate in patients with low-grade lymphomas. It also has activity in DLCL. A phase II pilot study of rituximab in combination with CHOP in patients with previously untreated DLCL or high-grade NHL was reported. The overall response rate was 97% (32 of 33 patients), with a 61% complete remission rate, a 36% partial remission rate, and a 3% progressive disease rate. Severe adverse events were similar to those observed with CHOP alone. These results are encouraging, and randomized studies currently are underway to determine if the addition of rituximab to standard chemotherapy should be considered the standard of care.

         

      2. Intensification of current drugs with colony-stimulating factor support: The SWOG is undertaking a randomized phase II study of dose-intensified CHOP with growth factor support.

         

      3. Risk stratification: The use of prognostic factors can help identify patients with a high risk of relapse who will benefit from more aggressive therapy, such as high-dose chemotherapy with bone marrow or peripheral stem cell transplant.
  • Prognostic factors

     

    • The International Non-Hodgkin Lymphoma Prognostic Factors Project developed a predictive model of outcome for aggressive NHL. The project found 5 pretreatment characteristics that were independently statistically significant for higher-risk disease. They are (1) age older than 60 years, (2) tumor stage III or IV (advanced), (3) more than 1 extranodal site involved by disease, (4) patient performance status of 2 or more, and (5) LDH elevation above the reference range. Based on these 5 characteristics, patients were stratified into 4 categories, as follows:

       

      • Low-risk patients had 0 or 1 adverse factors.

         

      • Low-risk to intermediate-risk patients had 2 factors.

         

      • High-risk to intermediate-risk patients had 3 factors.

         

      • High-risk patients had 4 or 5 factors.

       

    • When patient outcomes were analyzed by risk stratification, they had different outcomes with regard to CR, disease-free survival, and overall survival. For example, patients with a low risk had a CR rate of 87% and a 5-year survival rate of 73%, as compared to a CR rate of 44% and a 5-year survival rate of 26% in the high-risk group.

       

    • Subsequent studies have confirmed the reproducibility of the International Prognostic Index for predicting clinical outcome for patients with DLCL. Currently, poor-risk patients (despite achieving CR) may be considered for aggressive therapy with high-dose chemotherapy and peripheral stem cell/bone marrow transplantation in first remission.
  • Treatment of primary refractory disease

     

    • Up to 10% of patients with DLCL do not respond to induction chemotherapy (stable or progressive disease). These patients have a poor outcome.

       

    • Therapies that produce responses in 10% or fewer of these cases include (1) salvage chemotherapy with DHAP (dexamethasone, high-dose cytarabine, and cisplatin), (2) ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin), (3) MIME (mesna, ifosfamide, methotrexate, and etoposide), and (4) high-dose therapy with autologous bone marrow/stem cell support.

       

    • Patients who achieve only a partial response with standard conventional therapy but are considered to have chemosensitive disease should be evaluated for high-dose therapy and autologous stem cell support. These patients may have better outcomes than those with primary refractory disease.

     

  • Treatment of relapse
    • Of patients with DLCLs who achieve an initial CR, 20-50% experience disease relapse. Numerous second-line salvage regimens have been used to induce a second remission. In general, 20-35% of patients who relapse achieve a second CR using a combination chemotherapy regimen, including DHAP, ESHAP, MIME, or IMVP-16 (ifosfamide, methotrexate, etoposide). However, the duration of the second CR frequently is less than 1 year, and patients treated with salvage chemotherapy at conventional doses are considered incurable unless treated with high-dose therapy and autologous transplantation.
    • A multicenter randomized trial evaluated patients with chemosensitive relapsed aggressive lymphomas treated with 2 cycles of DHAP. These patients were randomized to receive an additional 4 cycles of DHAP or high-dose chemotherapy followed by autologous bone marrow transplant. The patients in the transplant arm had a superior event-free survival rate (46% vs 12% at 5 y, P = 0.001) and overall survival rate (53% vs 32% at 5 y, P = 0.04) compared to those patients receiving conventional salvage therapy. Based on this study, transplantation for patients who experience relapse and have chemosensitive DLCL is considered the standard of care. Most series demonstrate that approximately 10-15% of patients with chemotherapy-resistant relapse also may benefit from this strategy.

Surgical Care:

  • The role of surgery in DLCLs usually is limited. Treatment of these tumors is primarily with cytotoxic agents, with or without radiation therapy.
  • Surgery can be helpful in obtaining tissue for diagnosis or, rarely, to palliate a complication.

Consultations:

  • A surgical oncologist may be consulted if an open biopsy is needed for the diagnosis or to treat a complication such as perforated viscus.
  • A radiation oncologist may be consulted if the primary therapy involves a combination of chemotherapy and radiotherapy. In addition, an initial large lymphoma mass or a large residual mass following completion of chemotherapy may be considered for IFRT.

Diet:

  • No specific diet is recommended, except a salt restriction when steroids are administered as part of the chemotherapy regimen.
  • Patients undergoing cytotoxic chemotherapy may develop severe neutropenia, as defined by an absolute neutrophil count of less than 500/microliter. These patients should be advised to maintain a low microbial diet for the expected duration of neutropenia.

Activity:

  • No specific limitation of activity is necessary unless the patient is thrombocytopenic, in which case activity restriction may be necessary to avoid traumatic bleeding or bruising.
The CHOP regimen given for 6-8 cycles remains the standard treatment of DLCLs. More complicated regimens, as discussed in Medical Care, generally fail to improve overall survival.
 

Drug Category: Antineoplastic agents -- Inhibit cell growth and proliferation

Drug Name
 		 Cyclophosphamide (Cytoxan, Neosar) -- This is a prototypical alkylator drug that is cell-cycle independent. 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.
Adult Dose 750 mg/m2 IV q3wk for 4-6 cycles
Pediatric Dose Not established
Contraindications Documented hypersensitivity; severely depressed bone marrow function
Interactions Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones
Chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
Pregnancy D - Unsafe in pregnancy
Precautions Myelosuppression, nausea, vomiting, hemorrhagic cystitis, impaired hepatic function, impaired renal function, SIADH, pulmonary fibrosis, carcinogenesis, mutagenesis, and impaired fertility may occur; regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis
Drug Name
 		 Doxorubicin (Adriamycin, Rubex) -- Intercalates between DNA and inhibits topoisomerase I and II and produces free radicals, which may cause the destruction of DNA. The combination of these 2 events can, in turn, inhibit the growth of neoplastic cells.
Adult Dose 50 mg/m2 IV q3wk for 4-6 cycles
Pediatric Dose Not established
Contraindications Documented hypersensitivity; severe heart failure, cardiomyopathy, impaired cardiac function, preexisting myelosuppression
Interactions May decrease phenytoin and digoxin plasma levels; phenobarbital may decrease plasma levels; cyclosporine may induce coma or seizures; mercaptopurine increases toxicity; cyclophosphamide increases cardiac toxicity
Pregnancy D - Unsafe in pregnancy
Precautions Irreversible cardiac toxicity and myelosuppression may occur; extravasation may result in severe local tissue necrosis; reduce dose in patients with impaired hepatic function
Drug Name
 		 Vincristine (Oncovin, Vincasar) -- Binds to microtubular protein of the mitotic spindle, inhibiting key steps in the cell cycle.
Adult Dose 1.4 mg/m2 IV q3wk for 4-6 cycles, not to exceed 2 mg
Pediatric Dose Not established
Contraindications Documented hypersensitivity; patients with demyelinating form of Charcot-
Marie-Tooth syndrome
Interactions Acute pulmonary reaction may occur when taken concurrently with mitomycin-C
Pregnancy D - Unsafe in pregnancy
Precautions Hypersensitivity, constipation, abdominal cramps, nausea, vomiting, paralytic ileus, urinary retention, and neuropathy may occur; caution in patients diagnosed with severe cardiopulmonary or hepatic impairment and patients with preexisting neuromuscular disease
Drug Category: Corticosteroids -- These are used in combination with cytotoxic drugs to reduce inflammatory reactions.
Drug Name
 		 Prednisone (Meticorten, Orasone, Deltasone) -- May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Adult Dose 100 mg PO qd for 5 d; repeat q3wk in combination with above mentioned drugs for 4-9 cycles
Pediatric Dose Not established
Contraindications Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI disease
Interactions Coadministration with estrogens may decrease prednisone 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 - Safety for use during pregnancy has not been established.
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
 
Further Inpatient Care:
 
  • Admit the patient if a treatment complication arises.
  • Chemotherapy usually is given on an outpatient basis.

Further Outpatient Care:
 

  • Follow patients very carefully while they are receiving chemotherapy.
  • Treatment is administered every 3 weeks.
  • Complete blood counts and chemistries are ordered frequently for outpatient monitoring.
  • Patients are seen immediately if they develop any chemotherapy-related adverse effects.

In/Out Patient Meds:
 

  • Antiemetics are always prescribed prior to and after the administration of chemotherapy.
  • Intravenous fluids are given as necessary.
  • Supportive care with analgesics and growth factors are provided as necessary.
  • Patients often are started on allopurinol with the induction of chemotherapy to avoid acute renal failure from tumor lysis syndrome (TLS) and uric acid nephropathy.

Transfer:
 

  • Transfer may be necessary for further diagnostic evaluation and medical or surgical interventions.

Complications:
 

  • TLS is a potential complication.
    • It manifests as a rapid rise in potassium, phosphorus, and uric acid and a drop in calcium.
    • It can lead to a sudden death from electrolyte abnormalities.
    • Aggressive intravenous hydration, alkalinization of the urine, and the administration of allopurinol usually prevents TLS. Occasionally, patients with significant tumor volume and rapidly growing disease can avoid TLS by receiving dose-modified or attenuated chemotherapy as the first treatment, followed by conventional chemotherapy in subsequent treatment cycles.
  • Uric acid nephropathy, with or without TLS, usually can be prevented by administering allopurinol or alkalinizing the urine.
  • Neutropenic fevers and sepsis are the most common potentially serious complications of chemotherapy. If not recognized and treated aggressively, these infections can cause rapid deterioration of the patient's condition, which could lead to death. The use of cytokines (granulocyte colony-stimulating factors or granulocyte-macrophage colony-stimulating factors) has been helpful in preventing infections by shortening, and in some cases preventing, the neutropenic period. More recently, the use of prophylactic antibiotics (especially with the fluoroquinolones [eg, ciprofloxacin, levofloxacin]) has been shown to be effective in preventing neutropenic infections.

Prognosis:
 

  • The prognosis of patients with DLCLs can be assessed by applying the 5 lymphoma prognostic factors as described by the International Prognostic Index. These are as follows:
    • Age
    • Tumor stage
    • Number of extranodal sites involved
    • Performance status
    • LDH value
  • Patients with low risk, ie, 0 or 1 adverse factors, have a 5-year survival rate of 73%.
  • In the high-risk group, ie, people with 4-5 adverse factors, 5-year survival rate drops to 26%.
Medical/Legal Pitfalls:
 
  • Failure to completely stage the patient
  • Failure to initiate treatment as soon as possible
  • Failure to prevent uric acid nephropathy and TLS
  • Failure to recognize and treat neutropenic sepsis
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