Looking at lymphoma and leukemia

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Looking at lymphoma and leukemia
BARBARA ROGERS CRNP, AOCN, MN


Abstract
Learn the signs and symptoms of these liquid tumors and how to help patients manage them.


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LYMPHOMA AND LEUKEMIA, two blood-related cancers, can produce similar signs and symptoms. Both may follow a chronic or very aggressive course. The terms lymphoma and leukemia encompass multiple diseases, each posing unique challenges for patients—and for you, the nurse caring for them.

According to American Cancer Society statistics, lymphoma will account for 5% of all cancer diagnoses in 2005; leukemia will account for almost 3%. In this article, I'll discuss each disorder in detail and take a close look at current treatment protocols and nursing interventions.

LYMPHOMA: MALIGNANT LYMPHOCYTES
A lymphoma is a neoplastic disease in which lymphocytes undergo malignant change and produce tumors in lymphoid tissue. Sharing the common characteristic of lymphadenopathy, various lymphomas are classified as Hodgkin's disease and non-Hodgkin's lymphoma (NHL). Enlarged lymph nodes are a hallmark of both types; the patient also may experience fatigue, weight loss, fever, or night sweats. Some patients complain of severe itching, possibly caused by cytokines from the malignant cells.

Biopsy of an enlarged lymph node establishes the diagnosis. When biopsy shows the presence of Reed-Sternberg cells, distinctive giant cells with one or two large nuclei, the diagnosis is Hodgkin's disease. The diagnosis is NHL when biopsy shows infiltration of malignant B cells or T cells in the lymph system.

Once diagnosed with Hodgkin's disease or NHL, the patient undergoes further diagnostic tests to stage the disease. (See Staging Hodgkin's and non-Hodgkin's lymphoma for details.) Lymphoma is further identified as “A” (no symptoms) or “B” (the patient has such signs and symptoms as fever, chills, night sweats, and weight loss).

Tests performed to stage lymphoma include chest X-ray and computed tomography (CT) scans of the head and neck, chest, abdomen, and pelvis. Positron emission tomography (PET) of the entire body may help the clinician identify hypermetabolic areas that suggest malignancy and assist staging.

The patient's blood work will probably include a complete blood cell (CBC) count to assess for anemia, a sedimentation rate, and a beta-2 microglobulin level. He may also have a bone marrow biopsy to stage the disease. Lactate dehydrogenase levels are nonspecific markers that may be used to determine prognosis in NHL.

Treating Hodgkin's disease
Spread through the lymphatic system, Hodgkin's disease accounts for about 12% of lymphomas. Its etiology is unknown, but reduced immunity and infection with certain viral diseases have been implicated. The overall survival rate 10 years after diagnosis of Hodgkin's disease is 77%.

Hodgkin's disease is treated with radiation therapy, chemotherapy, or both.

Radiation therapy is a common treatment choice for patients with stage IA or IIA nonbulky (less than 9 cm) Hodgkin's disease. More than 95% of these patients achieve complete remission, and 90% survive beyond 20 years.

Chemotherapy is appropriate for anyone with more advanced stage IIIB or IV disease, bulky disease (involving a large part of the chest and mediastinum), four or more sites of involvement, or extranodal disease. The standard regimen, known as ABVD, includes A driamycin (doxorubicin), b leomycin, v inblastine, and d acarbazine. A patient who achieves a partial response with chemotherapy may have a complete response after undergoing radiation therapy to sites of residual disease.

From 20% to 30% of patients with Hodgkin's disease never achieve complete remission (all signs and symptoms eliminated) or partial remission (cancer shrinking but not disappearing). Another 20% to 30% achieve complete remission, then have a relapse. If your patient requires a second round of therapy, the duration of his response to initial therapy helps determine what he'll receive next.

If Hodgkin's disease recurs within 12 months of initial therapy, the patient is more likely to have a poor outcome. Someone with a relapse more than 12 months after initial therapy can generally be treated successfully with combination chemotherapy. A patient who has a relapse after receiving radiation therapy alone has a 50% to 80% likelihood of long-term disease-free survival if he receives chemotherapy with ABVD for the recurrence. In someone who relapses after responding to chemotherapy, the clinician will consider high-dose therapy with autologous bone marrow or peripheral blood stem cell support.

The downside of therapy
Adverse reactions to chemotherapy for Hodgkin's disease and other malignancies depend on the regimen. (See Managing problems associated with chemotherapy for specific recommendations.) Therapy with ABVD may cause infertility, especially in males, although this is a smaller risk than with earlier regimens such as MOPP ( m echlorethamine, O ncovin [vincristine], p rocarbazine, and p rednisone). Chemotherapy also can cause sperm abnormalities and birth defects, so talk with your patient about the need to prevent pregnancy and the option of banking sperm or ova before starting treatment. Oncologists generally recommend that women avoid pregnancy for 2 years and men use contraception for 6 months after treatment.

Teach your patient that receiving radiation or chemotherapy for Hodgkin's disease increases the risk of another type of lymphoma, so he'll continue to need monitoring after he finishes treatment. After 5 disease-free years, however, his risk becomes close to normal. Radiation therapy also increases the risk of developing a solid malignancy, such as a breast or lung tumor, or thyroid disease if the radiation field during treatment included these regions.

Non-Hodgkin's lymphoma: Aggressive or indolent
Scientists don't understand how NHL begins, but they do know that the incidence has increased about 7% annually over the past 20 years, primarily in older adults. Spread through the bloodstream, NHL is classified as aggressive or indolent.

Aggressive NHL is fast growing, so patients typically are sicker at diagnosis. Because the disease is discovered in the early stages, a cure is more likely. Aggressive NHL is divided into intermediate and high grades; although treated differently, both are curable.

Indolent NHL is slow growing and poses more of a challenge to cure. Also known as low-grade NHL, the disease progresses slowly, so it's typically widely disseminated before being discovered. Even after treatment, most patients with indolent NHL have relapses.

What causes NHL is unclear, but factors that increase risk are long-term immunosuppressant therapy, bone marrow transplantation, inherited immune defects, rheumatoid arthritis, and previous treatment for Hodgkin's disease. Lymphoma related to human immunodeficiency virus (HIV), now recognized as a separate entity, is treated differently than other types of NHL.

Treatment options for NHL
A patient with NHL may receive radiation, chemotherapy, or both, depending on the disease grade and stage. Monoclonal antibodies such as rituximab (Rituxan) may be used to enhance the effects of chemotherapy. For someone with recurrent NHL, stem cell transplantation may be an option.

Combating aggressive NHL.
The standard treatment for intermediate-grade NHL has been CHOP chemotherapy ( c yclophosphamide, h ydroxydaunomycin, O ncovin [vincristine], and p rednisone), producing a cure in about 40% of patients treated. Recent data show that 60% of patients who also receive rituximab have long-term survival without relapse, so adding rituximab to the regimen (CHOP-R) has become the standard of care. The patient may receive radiation therapy too if he has only a partial response to chemotherapy or to prevent recurrence at sites of previous bulky disease.

Typically, a patient with high-grade NHL requires combination chemotherapy, but radiation also plays a role in combating this disease. Studies suggest that receiving fewer chemotherapy treatments and radiation can be equally effective and less toxic than more courses of chemotherapy alone. Someone with clinical stage I high-grade NHL has a greater than 80% chance of cure with radiation to either the involved field or an extended field.



Figure. Maturity matters
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Combating indolent NHL.
If your patient has localized low-grade NHL, radiation therapy alone offers a 60% to 80% chance of 10-year survival and possibly a full cure. However, in disseminated low-grade NHL, early intervention doesn't appear to prolong survival, so “watch and wait” is an acceptable approach. The reason to delay is that the patient may remain stable for years without treatments that could cause adverse reactions and decrease quality of life.

If your patient chooses to watch and wait, the practitioner will monitor him and prescribe therapy if adenopathy and disease-related symptoms increase or if he develops organ compromise or bone marrow suppression. Multiple chemotherapy options are available if he wants a more aggressive approach.

When treatment for low-grade NHL is necessary, numerous options include single or combination alkylating agents and the addition of an anthracycline (an anticancer antibiotic such as doxorubicin), radiation therapy, or biologic agents (such as monoclonal antibodies). The choice depends on the extent of disease, the patient's signs and symptoms, and major organ dysfunction due to other medical conditions. Because biologic agents produce a slower response, the patient may need chemotherapy for significant symptoms. Adding biologic agents to various chemotherapy regimens may enhance the response.

Generally, a shorter initial response to chemotherapy means shorter survival. After subsequent treatments, each remission is typically shorter and of less quality than the preceding one. Although the histologic features of disease at relapse are typically the same as at diagnosis, the disease could transform into a more aggressive type.

High-dose chemotherapy with autologous stem cell transplantation (ASCT) is a treatment option for someone with a recurrence. Considered a bone marrow “rescue,” ASCT is a standard approach to treating patients with relapsed disease who previously responded to chemotherapy. Allogeneic bone marrow transplant may be an option for someone with more resistant disease.

LEUKEMIA: CANCER IN THE MARROW
A malignancy of bone marrow cells, leukemia occurs when cells arising from stem cells lose the ability to differentiate into white blood cells (WBCs), red blood cells (RBCs), and platelets. (See Maturity matters .) Instead, one type of abnormal WBC prevails and normal cell line development declines.

Acute and chronic leukemias are classified as lymphocytic or myelogenous according to the predominant cell type. Biphenotypic leukemia is a name given to acute leukemia with both lymphocytic and myelogenous features.

No single factor has been pinpointed as a cause of leukemia, although genetics, drugs, and environmental and occupational exposures have been implicated. In most cases, signs of leukemia are evident in CBC count results, but a bone marrow biopsy is necessary for a definitive diagnosis.

Acute leukemias progress rapidly and are characterized by ineffective, immature cells in the bone marrow crowding out and preventing development of normal cells. Acute myelogenous leukemia (AML) accounts for most acute leukemias in adults; acute lymphocytic leukemia (ALL) is more common in children.

Some initial signs and symptoms of acute leukemia are nonspecific. Rising numbers of immature cells can affect all the blood cell lines—RBCs, WBCs, and platelets—so signs and symptoms are related to anemia, neutropenia, and thrombocytopenia. These include pallor, headache, fatigue, malaise, loss of appetite, weight loss, tachycardia, shortness of breath, petechiae, ecchymoses, and splenomegaly.

Bleeding or easy bruising after minor trauma, a characteristic sign of leukemia, stems from thrombocytopenia. Bone tenderness of the long bones, ribs, and sternum also may occur as leukemic cells expand the intramedullary space or invade the periosteum.

Chronic leukemias progress more slowly and rarely affect people under age 20. Allowing development of more normal cells, chronic leukemia may not affect the patient's health as severely until the advanced stages. Chronic myelogenous leukemia (CML) typically strikes between ages 40 and 50, with slightly more men affected than women. Chronic lymphocytic leukemia (CLL) typically develops after age 40 and is most common in older men.

Recognizing and treating leukemia
Now let's look at each leukemia type in detail.

Acute myelogenous leukemia.
Stem cells destined to develop in the myelogenous line of cells normally mature into neutrophils, monocytes, eosinophils, RBCs, and platelets. But when these cells overwhelmingly commit to one type—most commonly neutrophils—AML develops. Bone marrow biopsy is necessary to make the diagnosis.

Several clinical characteristics of AML influence prognosis. Factors in the patient's favor are age under 60 years, spontaneous rather than secondary leukemia, a WBC count less than 10,000/mm 3 , and the achievement of complete remission with one cycle of chemotherapy.

Treatment for AML consists of induction and maintenance therapy.

* Induction chemotherapy usually consists of cytosine arabinoside and an anthracycline. The goal of induction therapy is to attain complete remission by eliminating leukemic cells from the bone marrow.
* Postinduction therapy (consolidation) is necessary to prevent relapse after remission. However, the optimal regimen hasn't yet been determined. From 25% to 35% of patients have a long-term remission after postinduction chemotherapy. Therapy with high-dose cytarabine has improved the duration of first remission in most young patients with AML.
The options for consolidation therapy are more standard-dose chemotherapy or a transplant of the patient's own stem cells (autologous) or stem cells from a human-leukocyte-antigen (HLA) matched sibling or unrelated donor (allogeneic). Whether ASCT improves the rate of long-term remission is unclear. Allogeneic transplants from HLA-matched donors have produced a cure in 50% to 60% of patients in consolidation therapy. The regimen that precedes allogeneic transplant is so harsh that this option is usually reserved for patients younger than 55 years, who are more likely to survive the adverse effects of treatment.

Acute lymphocytic leukemia.
Rapidly developing immature lymphocytes crowding out normal cells indicate ALL. In adults with ALL, the Philadelphia chromosome, the hallmark of CML, is the most common chromosome abnormality detected. Cytogenic testing on the bone marrow specimen identifies this marker.

Poor prognostic factors for ALL include a high WBC count (25,000/mm 3 or greater) at presentation, presence of the Philadelphia chromosome, age over 50 years, and slow first remission (longer than 4 weeks).

The primary goal of ALL therapy is complete remission with restoration of normal hematopoiesis.

* Induction chemotherapy is administered in two phases. The first consists of daunorubicin, vincristine, and prednisone with L-asparaginase. The second phase, administered soon after the first, includes cyclophosphamide, cytarabine, and 6-mercaptopurine and prophylaxis with intrathecal methotrexate or cytosine arabinoside.
* Maintenance therapy must follow induction to prevent relapse. Several alternating regimens may be used for up to 36 months. The patient's risk factors determine the duration of treatment.
Chronic myelogenous leukemia
Characterized by the presence of the Philadelphia chromosome and development of too many neutrophils, CML consists of three clinical phases:

* The chronic phase follows an indolent course during which the patient may have mild symptoms and respond to standard treatments. The percentage of blasts in bone marrow is usually less than 10%.
* The accelerated phase is characterized by spleen enlargement and progressive signs and symptoms, such as intermittent fevers, night sweats, and unexplained weight loss. The typical patient doesn't respond to treatment as readily, and his bone marrow contains 10% to 30% blasts and promyelocytes. The accelerated phase typically lasts 6 to 12 months.
* The blast phase indicates a transformation to a very aggressive acute leukemia. The bone marrow contains more than 30% blasts, and promyelocytes and blasts commonly spread to other tissues and organs. Most patients die when CML reaches this phase.
The kinase inhibitor imatinib (Gleevec) is the current treatment of choice for CML. Most effective at inducing remission in the early stages, it's also well tolerated. Trials are under way to combine imatinib with other agents to enhance the response rate and duration.

Other agents used to treat patients with CML include interferon alpha, which has been shown to reduce growth and division of leukemia cells in 55% to 60% of treated patients. Because interferon alpha causes major adverse reactions, it's no longer the drug of choice to combat CML. Another agent, hydroxyurea, may prolong the chronic phase of CML but hasn't been shown to affect cell growth and development.

Stem cell transplant from a compatible donor achieves long-term survival in many patients, but the risk of dying during the first 100 days is 20%. This intervention is most successful early in the chronic phase of CML.

Chronic lymphocytic leukemia
The course of CLL depends on the disease stage. Median survival ranges from less than 19 months for patients with advanced disease to more than 10 years for those with early-stage disease.

An indolent disease characterized by lymphocytosis, lymphadenopathy, and hepatosplenomegaly, CLL eventually poses a risk of death from recurrent bacterial and viral infections as the disease advances.

Treatment of CLL with standard chemotherapy can produce remissions but can't cure the disease. Because CLL isn't curable and therapy may cause harsh adverse reactions, treatment is usually delayed until the patient develops signs and symptoms. The options include the alkylating agent chlorambucil with or without prednisone, the antimetabolite fludarabine, and combined chemotherapy such as CVP (cyclophosphamide/vincristine/prednisolone). Rituximab is frequently combined with chemotherapy to enhance the response. The patient also may receive radiation therapy to sites of bulky lymphadenopathy.

Skilled care, teaching, emotional support
Anyone with lymphoma or leukemia requires skilled nursing care to cope with the diagnosis and to minimize adverse reactions to treatment. Remind your patient that most adverse effects of therapy can be managed and that many people continue working during treatment. To help him manage immediate and long-term problems, teach him about the following effects of his illness and therapy.

* Emotional issues. Encourage him to discuss his feelings; provide reassurance and support when he does. Teach him relaxation techniques and encourage him to seek help through a support group or counselor. If he's taking prednisone, advise him to take it with breakfast or lunch to prevent insomnia and to notify the oncologist/hematologist if he has mood changes, which can occur with prednisone therapy.
* Infection. Teach him about infection risk. Review the signs and symptoms and tell him to contact the oncologist/hematologist if he develops signs of infection.
* Hair loss and skin changes. Tell the patient about the potential for hair loss and explain that his hair will probably grow back after he finishes therapy. Encourage him to purchase a wig or hat before his first chemotherapy infusion. Tell him that his skin may dry and become more sensitive to sunlight so he may need to apply sunblock and wear protective clothing in the sunshine. He may also notice changes in his nails.
* Fatigue. Encourage your patient to pace his activities, rest frequently, and get help with activities of daily living.
* Reproductive issues. Discuss the potential for chemotherapy-induced sterility. For a male, review the need to prevent pregnancy in his partner because chromosome damage to sperm can negatively affect the fetus. Discuss sperm banking and provide resource information if he chooses this option. Teach a female patient that treatment can cause menstrual changes and menopause-like symptoms and make her susceptible to vaginal infections.
* Stomatitis. Encourage your patient to see a dentist before starting chemotherapy. Teach him to rinse his mouth with a solution of salt and baking soda in water to prevent infection and advise him to avoid drinking alcohol. Tell him to call the oncologist/hematologist if he develops mouth sores.
* Bladder and bowel changes. Advise your patient to drink plenty of fluids and to void frequently to prevent cystitis. Teach him to check his urine for blood and to call his health care provider if he develops frequency or discomfort with urination. Teach him to include fiber in his diet and encourage him to use a laxative if he can't move his bowels every 2 days. Tell him to call his health care provider if he develops diarrhea. Monitor his response to antidiarrheal medication and assess him for dehydration.
* Gastric irritation. If your patient takes prednisone, tell him to take it with food or milk. If he reports midepigastric distress, ask the oncologist/hematologist to prescribe medication to prevent gastrointestinal irritation.
Keeping current
By keeping current on the various treatments for lymphomas and leukemias, you can prepare your patient for treatment, answer his questions, and help him manage problems caused by his disease or therapy.

Barbara Rogers is a nurse practitioner in adult hematology/oncology at Fox Chase Cancer Center in Philadelphia, Pa.

The author has disclosed that she has no significant relationship with or financial interest in any commercial companies that pertain to this educational activity.

SELECTED WEB SITES
Gilda's Club http://www.gildasclub.org

National Marrow Donor Program http://www.marrow.org/index.html

Planet Cancer: Support for Young Adults with Cancer http://www.planetcancer.org

The Leukemia & Lymphoma Society http://www.leukemia-lymphoma.org/hm_lls

Last accessed on June 2, 2005.

Staging Hodgkin's and non-Hodgkin's lymphoma
Stage I
Involvement of a single lymph node or localized involvement:
Stage II
Involvement of two or more lymph node regions on the same side of the diaphragm:
Stage III
Involvement of several lymph node regions on both sides of the diaphragm:
Stage IV
Involvement of extralymphatic tissue, such as the bone marrow

Managing problems associated with chemotherapy
Follow these guidelines to help your patient overcome adverse reactions.

Myelosuppression
* Monitor complete blood cell count before each treatment.
* Administer packed red blood cells (RBCs) as ordered.
* Administer growth factors as prescribed: granulocyte colony-stimulating factor, to decrease duration of nadir and epoetin alfa (Procrit) or darbepoetin alfa (Aranesp) to increase RBC production.
* Assess the patient for signs and symptoms of infection. Educate him about decreased absolute neutrophil count and infection risk.
* Monitor temperature daily. Call the oncologist/hematologist if the patient's oral temperature exceeds 100.5°F (38°C).
Pulmonary toxicity
* Obtain baseline pulmonary function tests.
* Assess the patient's pulmonary status before each infusion.
* Teach him to report cough, dyspnea, or shortness of breath.
* Hold bleomycin if he reports any symptoms of altered pulmonary status.
Cardiac toxicity
* Make sure that the patient undergoes a MUGA (multiple-gated acquisition) scan or an echocardiogram to determine adequate left ventricular ejection fraction before his first chemotherapy dose.
* Teach him to report shortness of breath or palpitations.
* Monitor his total doxorubicin dose.
* Perform ongoing assessments for signs and symptoms of heart failure, including dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, and fatigue.
Nausea and vomiting
* Administer antiemetics before administering chemotherapy.
* Assess the patient's level of nausea and vomiting with each treatment and modify his antiemetic regimen as indicated.
* Teach him how to use his prescribed antiemetic to prevent or treat delayed nausea and vomiting.
Extravasation
* Assess your patient's veins before and during each chemotherapy infusion.
* Teach him about the benefits of a central venous access device if peripheral access is poor.
* Assess blood return frequently during administration of vesicants such as doxorubicin, vinblastine, and dacarbazine.
* Treat extravasation promptly, according to facility policy.
Hypersensitivity reactions
* Assess your patient's baseline vital signs. Bleomycin in particular can cause fever.
* Administer premedications such as acetaminophen and steroids before therapy and have emergency equipment readily available in case of anaphylactic or anaphylactoid reaction.
* Teach him to promptly report any unusual symptoms such as dizziness, itching, or pain.
* Monitor his vital signs throughout the infusion. Increase the infusion rate every 30 minutes only if his vital signs remain stable and he doesn't develop signs of an adverse reaction.
* Stop the infusion if he develops a reaction.
Neuropathy
* Assess him for sensory and perceptual changes before each treatment.
* Notify the oncologist of any changes (peripheral, gastrointestinal) that develop after he receives vinca alkaloids.
Pain at injection site: ABVD
* Administer dacarbazine in 100 to 250 ml of I.V. fluid and infuse slowly over 1 hour.
* Apply heat or ice above the injection site.
Flulike syndrome
* Premedicate with acetaminophen.
* Encourage the patient to drink plenty of fluids.
Hyperglycemia
* Monitor his serum glucose level.
* Increase monitoring frequency if he has diabetes. The prescriber may need to modify his antihyperglycemic therapy.
SELECTED REFERENCES
American Cancer Society: Cancer Facts & Figures. Atlanta, Ga., American Cancer Society, 2005.

Cheson B. Hodgkin's disease and the non-Hodgkin's lymphomas. In R Lenhard, et al., The American Cancer Society's Clinical Oncology . Atlanta, Ga., American Cancer Society, 2001.

Harris N, et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: Report of the clinical advisory committee meeting-Arlie House, Virginia. Journal of Clinical Oncology. 17(12):3835–3849, November 1999.

Lowenberg B, et al. Acute myelogenous leukemia. The New England Journal of Medicine . 341(14):1051–1062, September 30, 1999.

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Nursing2005
July 2005
Volume 35 Number 7

© 2005 Lippincott Williams & Wilkins, Inc. Volume 35(7), July 2005, p 56–63
Looking at lymphoma and leukemia
[ARTICLE]
ROGERS, BARBARA CRNP, AOCN, MN


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