eMedicine Specialties > Hematology > Stem Cells and Disorders

Lymphoma, Non-Hodgkin: Follow-up

Author: Sanjay Vinjamaram, MD, MPH, Fellow in Hematology/Oncology, Roswell Park Cancer Institute
Coauthor(s): Francisco J Hernandez-Ilizaliturri, MD, Assistant Professor, Departments of Medicine and Immunology, Roswell Park Cancer Institute, State University of New York at Buffalo; Dolores A Estrada, MD, Consulting Staff, Hematology-Oncology, Cancer Care Specialists of Central Illinois; Lakshmi Rajdev, MD, Site Director, Jacobi Medical Center; Assistant Professor, Department of Radiation Oncology, Albert Einstein College of Medicine; Joseph A Sparano, MD, Professor of Medicine, Albert Einstein College of Medicine/Cancer Center; Program Director, Director of Breast Medical Oncology, Department of Internal Medicine, Division of Oncology, Montefiore Medical Center
Contributor Information and Disclosures

Updated: Sep 2, 2009

Follow-up

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.

Inpatient & Outpatient Medications

• 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.
  • Atherosclerosis: In a 3-year study, Bilora et al found evidence that patients receiving radiotherapy and chemotherapy for either Hodgkin or non-Hodgkin lymphoma are predisposed to early development of atherosclerosis.¹² In 96 patients, the investigators found increased thickness of the intima media at 1-year follow-up and decreased thickness at 3-year follow-up. Even with this change, over the course of the follow-up, however, the reduction in flow-mediated dilatation measured in the patients at 1 year had not improved by the second examination.¹²

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-C é ligny et al.¹³ 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

Medicolegal Pitfalls

• Ensure that the patient has a correct diagnosis before administering treatment. Non-Hodgkin lymphoma (NHL) should be distinguished from reactive lymph node hyperplasia, which only requires careful follow-up and supportive care and does not require chemotherapy, radiation therapy, or both.
• Determine the stage and specific subtype of NHL, ie, whether it is low-, intermediate-, or high-grade, because the type of treatment strongly depends on these 2 important parameters.
• NHL should also be distinguished from Hodgkin disease because the treatment strategy is different in these 2 neoplastic lymph node diseases.
• If NHL diagnosis is doubtful, acquire a second or third opinion from an expert hematopathologist before instituting therapy. Flow cytometry and cytogenetics should also be performed and can be especially helpful in difficult situations.
• Ensure that patients understand their diagnosis, treatment options, prognosis, and complications of therapy, which, in rare occasions, may result in a fatal event (eg, death secondary to severe infection in a patient with severe neutropenia who is unresponsive to antimicrobial therapy). Start the treatment only after the patient has signed an informed consent form.

Special Concerns

• Pediatric patients with NHL are best treated by pediatric oncologists.
• Pregnancy
  • NHL during pregnancy is uncommon; however, if diagnosed, this presents an ethical dilemma. Remission may be obtained with chemotherapy, but chemotherapy has potentially harmful effects to the fetus. Consider fetus exposure to transplacental chemotherapy when evaluating therapy options and carefully evaluate the timing of delivery.
  • For patients diagnosed with NHL during the second or third trimester of pregnancy, few literature reports suggest that they can be treated with chemotherapy without significant toxicity to the fetus. If possible, alkylating agents should be avoided. If the fetus can be delivered safely prior to administration of chemotherapy and a short wait will not affect the treatment outcome and prognosis of the patient, starting the treatment after the birth of the baby is better.
  • If the patient has high-grade NHL (eg, Burkitt or lymphoblastic lymphoma) diagnosed during the first trimester of pregnancy, immediate therapy institution is necessary; otherwise, the condition could be fatal. Discuss at length with the patient and family that chemotherapy treatment at this period of pregnancy is very risky for the fetus, and whether therapeutic termination of pregnancy should be performed before the patient is treated should be decided. Consultation with the ethical committee of the hospital should be obtained in these very difficult situations.

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