eMedicine Specialties > Hematology > Stem Cells and Disorders

Lymphoma, Malignant Anaplastic (Ki 1+)

Delong Liu, MD, PhD, Associate Professor of Medicine, Division of Oncology/Hematology, New York Medical College; Chief of Hematology, Phelps Memorial Hospital Center; Director of Non-ablative Allogeneic Stem Cell Transplantation Program, Westchester Medical Center; Editor-in-Chief, Journal of Hematology and Oncology
Koyamangalath Krishnan, MD, FRCP, FACP, Paul Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, Program Director, Hematology-Oncology Fellowship, James H Quillen College of Medicine at East Tennessee State University; Christine Urbanski, MD, Consulting Staff, Hematology/Oncology Associates, RMH Regional Cancer Center

Updated: Dec 12, 2008

Introduction

Background

Anaplastic large cell lymphomas (ALCLs) are distinguished from other lymphomas by their anaplastic cytology and constant membrane expression of the CD30 antigen. Striking clinical features include frequent cutaneous and extranodal involvement, young age at presentation, and male predominance.^1,2,3

Anaplastic large cell lymphoma (ALCL) was recognized in 1985, when tumor cells consistently demonstrated labeling by the monoclonal antibody Ki-1, a marker later shown to recognize the CD30 receptor. In 1988, anaplastic large cell lymphomas (ALCL) was added as a distinct entity to the revised Kiel classification, and, in 1994, it was included in the Revised European-American Lymphoma (REAL) classification.

In the late 1980s, an unusual chromosomal translocation, t(2,5), was noted in many of these CD30-positive tumors. In 1994, the discovery of its chimeric protein product, npm-alk, served as an additional diagnostic and subclassification tool for this lymphoma. Approximately 85% of these tumors express a chimeric protein, with 70% expressing npm-alk (nucleophosmin-anaplastic lymphoma kinase), and the other 15% expressing x -alk, due to variant translocations other than t(2,5). ALK, a tyrosine kinase, is believed to be directly involved in lymphomagenesis through its interactions with the substrates in multiple signaling pathways.

Several different clinical and pathologic variants of CD30-positive large cell lymphoma and other diseases with pathologic similarities to anaplastic large cell lymphoma (ALCL) exist.^1,2,3,4,5,6 The overlap and heterogeneity have led to controversy over which diagnostic criteria should be used in anaplastic large cell lymphoma (ALCL) and whether certain subtypes should be considered as completely separate diseases.

For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education article Lymphoma.

Pathophysiology

Anaplastic large cell lymphoma (ALCL) can be divided clinically into primary and secondary subforms, with the de novo type further subclassified into systemic, cutaneous, and human immunodeficiency virus (HIV)-related forms. The primary systemic and cutaneous forms are the predominant subtypes. All types strongly express the CD30 antigen on cell membranes, and histologic review reveals the characteristic tumor cells. In addition to various clinical forms, pathologic variants exist that differ with respect to morphology, immunophenotype, and other antigen markers.

Histologically, anaplastic large cell lymphoma (ALCL) is characterized most commonly by sheets of large pleomorphic cells, abundant cytoplasm, horseshoe- or wreath-shaped nuclei, and multiple prominent nucleoli. These hallmark tumor cells may be multinucleated and can be similar to Reed-Sternberg cells in appearance. The growth pattern in lymph nodes is diffuse, and, for partially involved nodes, it shows a predilection for paracortical and sinusoidal regions.

Additional morphologic subforms distinct from the above classic type do not appear to represent separate disease entities. Morphologic anaplastic large cell lymphoma (ALCL) variants include the following:

• The monomorphic subtype demonstrates a rather nonanaplastic appearance.
• The small cell subtype contains a mixture of small and large lymphocytes, with the CD30 antigen expression mainly limited to the larger cells. This subtype is more common in children and can transform into the common type and vice versa.
• The lymphohistiocytic type has a predominance of histiocytes and a minority of hallmark cells and, therefore, can present a diagnostic challenge. Tumor cells in the giant cell–rich type are frequently multinucleated.
• The Hodgkinlike type refers to ambiguous cases in which the tumor histologically resembles both anaplastic large cell lymphoma (ALCL) and Hodgkin disease.
• Rare additional histologic types exist that include sarcomatoid, neutrophil-rich, eosinophil-rich, and signet-ring forms. In addition, as many as 15% of patients have features of more than one morphologic subtype.

Immunophenotyping in anaplastic large cell lymphoma (ALCL) exhibits consistently strong CD30 expression in all clinical and pathologic subtypes. Most tumor cells are of the null or T-cell phenotype, and the demonstration of clonally rearranged TCR genes, in most cases of both T-type and null-type ALCL, suggest that null-type ALCL is a variant of T-type ALCL.

B-cell antigenic expression is rare and is commonly observed in the HIV-related clinical form. In fact, these B-cell cases are classified separately in the Kiel classification, and, in the REAL and World Health Organization classifications, they are grouped under diffuse, large, B-cell lymphoma. Epithelial membrane antigen (EMA) expression is strongly positive in the most common morphologic types of anaplastic large cell lymphoma (ALCL), which include the classic, small cell, and lymphohistiocytic types. EMA analysis is also useful in the clinical subtype distinction, with strong expression observed in the primary systemic form and little or no expression in the other clinical forms.

Most patients with the primary systemic clinical subtype of anaplastic large cell lymphoma (ALCL) have translocation between chromosomes 2 and 5, resulting in a fusion protein that joins the N-terminus of NPM to the C-terminus of ALK. The wild-type NPM protein demonstrates ubiquitous expression and functions as a carrier of proteins from the cytoplasm into the nucleolus. The ALK wild type has its postnatal expression limited to a few cells in the nervous system and functions as a tyrosine kinase receptor. The 2;5 translocation brings the ALK gene portion encoding the tyrosine kinase on chromosome 2 under control of the NPM promoter on chromosome 5, producing permanent expression of the chimeric NPM-ALK protein (p80).

The resultant aberrant tyrosine kinase presumably triggers malignant transformation via constitutive phosphorylation of intracellular targets. The NPM/ALK rearrangements are very specific, and within the non-Hodgkin lymphoma (NHL) spectrum, they are restricted to T-cell lineage anaplastic large cell lymphoma (ALCL). Various other less common ALK fusion proteins are associated with anaplastic large cell lymphoma (ALCL), including those resulting from t(1;2), t(2;3), inv(2), and t(2;22).

All variants demonstrate linkage of the ALK tyrosine kinase domain to an alternative promoter that regulates its expression. The other clinical subtypes of anaplastic large cell lymphoma (ALCL), including the primary cutaneous form, are almost never ALK positive.

ALK– ALCLs tend to be more aggressive and are more likely to relapse. ALK+ and ALK– ALCLs have been found to have different gene-expression profiles. BCL6, PTPN12, CEBPB, and SERPINA1 genes were overexpressed preferentially in ALK+ ALCLs, whereas CCR7, CNTFR, IL22, and IL21 genes were overexpressed in ALK– ALCLs.⁶

Frequency

United States

Approximately 50,000 cases of non-Hodgkin lymphoma are diagnosed annually in the United States, which accounts for 4% of all cancers and cancer-related deaths per year.

International

Primary systemic anaplastic large cell lymphoma (ALCL) represents 2-8% of adult non-Hodgkin lymphoma cases and as many as 30% of childhood non-Hodgkin lymphoma cases.^7,8,9,10,11 Primary cutaneous anaplastic large cell lymphoma (ALCL) is demonstrated in 9% of cutaneous lymphomas.
 
Anaplastic large cell lymphoma (ALCL) constitutes approximately 2% of all lymphomas and approximately 9% of high-grade lymphomas in the Kiel registry. It represents approximately 12% of childhood lymphomas and 70% of large cell pediatric lymphomas.

Sex

A male predominance occurs in cases of primary systemic anaplastic large cell lymphoma (ALCL) that express the ALK fusion protein and in patients whose disease is limited to the skin.

Age

Primary systemic anaplastic large cell lymphoma (ALCL) demonstrates a bimodal age distribution, with the first peak representing primarily ALK-positive patients who present during the second and third decades of life. The second peak occurs in individuals older than 60 years and mainly consists of ALK-negative patients.

• Of all cases, 15-20% occur in persons younger than 20 years.
• The mean age at presentation of primary cutaneous anaplastic large cell lymphoma (ALCL) is 60 years, and it occurs only rarely in children and adolescents.

Clinical

History

• Primary systemic anaplastic large cell lymphoma (ALCL) is typically in an advanced stage at patient presentation, and the disease is rapidly progressive. These patients demonstrate an increased frequency of bone marrow involvement (30%) and extranodal involvement, including skin (21%), bone (17%), soft tissues (17%), lung (11%), liver (8%), and, rarely, the gastrointestinal tract and central nervous system. Systemic symptoms are observed in 75% of patients, with fever the most common symptom.
• Primary cutaneous anaplastic large cell lymphoma (ALCL) usually manifests as a single or localized cluster of erythematous skin nodules, some of which may demonstrate superficial ulcerations.^12,13,14 As many as 25% of patients have some degree of spontaneous regression of these lesions. Although most cases present with local involvement, patients may rarely present with disseminated cutaneous disease and are at higher risk of developing spread to other organs.
• Most cases of HIV-related anaplastic large cell lymphoma (ALCL) are actually of B-cell origin and seem instead to be related to the anaplastic variant of diffuse large B-cell lymphoma. Many patients demonstrate infection with the Epstein-Barr virus, which is absent in those with the T-cell or null-cell types of anaplastic large cell lymphoma (ALCL).
• Secondary anaplastic large cell lymphoma (ALCL) evolves from other lymphomas, most frequently from peripheral T-cell lymphomas, mycosis fungoides, Hodgkin disease, or lymphomatoid papulosis. This form of anaplastic large cell lymphoma (ALCL) tends to arise in older adults, is commonly ALK negative, and carries a poor prognosis.
• Patients with anaplastic large cell lymphoma (ALCL) present with either a primary cutaneous form or a systemic form of the illness. Patients may present with isolated lymphadenopathy or with extranodal disease at any site, including the gastrointestinal tract and bone. Patients with infiltration into musculoskeletal tissues (eg, psoas muscle) can present with backache.

Physical

The initial diagnostic evaluation of patients with any lymphoproliferative malignancy should include a careful history and physical examination, with close attention to the presence of systemic B symptoms, lymph node involvement, organomegaly, and evidence of cutaneous involvement.

Causes

The etiology of anaplastic large cell lymphoma (ALCL) is unknown. Unlike most lymphomas, a normal counterpart to this malignancy has yet to be recognized.

Differential Diagnoses

Hodgkin Disease
Lymphoma, B-Cell
Lymphoma, Diffuse Large Cell

Other Problems to Be Considered

Lymphomatoid papulosis
Malignant histiocytosis
Metastatic carcinoma
Metastatic melanoma

Workup

Laboratory Studies

• The necessary imaging and laboratory tests to appropriately evaluate a patient who may have anaplastic large cell lymphoma (ALCL) are similar to those recommended in the standard evaluation of aggressive non-Hodgkin lymphomas and are described briefly, as follows:
  • Hematology: Complete blood cell (CBC) count, peripheral smear review, and bone marrow aspiration and biopsy are standard.
  • Chemistry: Electrolyte evaluations, renal function studies, liver function tests and liver-associated enzyme tests, and uric acid evaluations are appropriate. Serum lactic dehydrogenase (LDH), beta2-microglobulin, and albumin values are useful for prognostic categorization. The LDH and beta2-microglobulin levels also serve as indirect indicators of tumor burden and proliferative activity.
  • Absolute lymphocyte count (ALC) has been reported to be an independent prognostic factor.¹⁵ ALC <1000/μ L correlates with shorter survival and lower complete remission rate.

Imaging Studies

• Chest radiographs are used to assess for lymphadenopathy, pleural effusions, and parenchymal lesions.
• Computed tomography (CT) scans of the chest, abdomen, and pelvis should be performed, with close attention to lymphadenopathy, pleural effusions, pulmonary parenchymal lesions, splenomegaly, and hepatic and splenic filling defects.
• Ultrasonography of the liver is indicated in patients who have abnormal results from laboratory liver function tests and normal hepatic imaging findings on CT scan images.
• Gallium scans, although not as useful in the initial staging workup, can be helpful for evaluating the response to treatment, because continued positive uptake in a residual mass after completion of treatment is an indicator of persistent disease.
• Magnetic resonance imaging (MRI) can be useful for detecting occult bone marrow lymphoma involvement, which is displayed as patchy distribution and, thus, will be missed on bone marrow biopsy findings. A spinal study is indicated for patients with epidural involvement and possible spinal cord compression.
• A bone scan is indicated if musculoskeletal symptoms are present or if the alkaline phosphatase level is elevated.
• Positron emission tomography (PET) scanning is gaining wider approval as a potential staging modality at both diagnosis and relapse of cases of anaplastic large cell lymphoma (ALCL).

Procedures

• Excisional biopsy of lymphadenopathy is necessary to confirm the diagnosis of anaplastic large cell lymphoma (ALCL). Critical assessments of cell morphology, lymph node architecture, immunophenotype, and molecular and cytogenetic analyses are indicated.
• Bone marrow aspiration and biopsy are performed to search for occult lymphoma involvement.
• Immunophenotyping and immunohistochemistry study of the lymphoma cells is critical in the definitive diagnosis of anaplastic large cell lymphoma (ALCL). The major features of the ALCL immunophenotype typically include CD30+, CD15 –, and CD45+. (Hodgkin lymphoma typically expresses CD30+ and CD15+.) Sixty percent of cases express one or more T-cell antigens (CD3+, CD43, or CD45RO). ALK protein may be detected in most cases (60-70%) by immunohistochemistry.

Histologic Findings

The morphology of anaplastic large cell lymphoma (ALCL) is similar within its major clinical subforms, the primary systemic and cutaneous varieties. The tumor cells are usually large, with abundant cytoplasm. They manifest prominent nucleoli, display an eccentrically located and pleomorphic nucleus that is often kidney-shaped, and tend to infiltrate lymph nodes in a sinusoidal and paracortical pattern.¹

The malignant cells stain positive for the CD30 antigen, a very sensitive but nonspecific test result that is also positive in other lymphomas, including Hodgkin disease. Most cases exhibit either T-cell or null phenotype, with frequent CD3 expression, cytotoxic protein expression, clonal T-cell receptor gene rearrangements by polymerase chain reaction (PCR), and lack of B cell – associated markers.¹⁶ The primary systemic form, unlike the primary cutaneous form, generally stains positive for EMA and usually displays the t(2;5) translocation and the chimeric p80 protein with PCR and antibody studies.

Staging

The Cotswold modification of the Ann Arbor staging system is the standard anatomic staging system for non-Hodgkin lymphoma and Hodgkin disease, and it is used to evaluate the extent of disease in patients with anaplastic large cell lymphoma (ALCL). Accurate staging allows appropriate therapeutic selection and contributes to predicting the prognosis. Staging for anaplastic large cell lymphoma (ALCL) is as follows^1,11 :

• Stage I – Involvement of a single lymph node region or lymphoid structure
• Stage II – Involvement of 2 or more lymph node regions on the same side of the diaphragm
• Stage III – Involvement of lymph node regions or structures on both sides of the diaphragm
• Stage IV – Involvement of extranodal sites beyond that designated as E (see below)
• Further staging designations include the following:
  • Suffix A – No symptoms (any disease stage)
  • Suffix B – Fever (temperature >38 º C); drenching sweats; unexplained weight loss (eg, 10% of body weight within preceding 6 mo) (any disease stage)
  • Suffix E – Involvement of a single extranodal site that is contiguous or proximal to the known nodal site (stages I-III)
• Cotswold modifications are as follows:
  • Suffix X – Denotes bulky disease (a widening of the mediastinum by more than one third or the presence of a nodal mass with a maximal dimension of >10 cm)
  • Subscripts – Used to indicate the number of anatomic regions
  • Stage III subdivisions – May be subdivided to include III(1), with or without splenic, hilar, celiac, or portal nodes, and III(2), with para-aortic, iliac, or mesenteric nodes
  • Further identification – Staging identified as clinical stage (CS) or pathologic stage (PS)

Treatment

Medical Care

• Primary systemic anaplastic large cell lymphoma (ALCL)
  • The current treatment approach for primary systemic anaplastic large cell lymphoma (ALCL) is identical to that for other types of diffuse aggressive non-Hodgkin lymphomas. Patients usually present in advanced stages, and intensive anthracycline-based chemotherapy offers a high chance of durable complete responses.
  • A combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) is the standard first-line treatment. If CD20 antigens are positive, rituximab should be added. Alternatively, substitution of mitoxantrone for doxorubicin (CNOP) or an equivalent third-generation regimen (eg, m-BACOD [ie, moderate-dose methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone], ProMACE/CytaBOM [ie, prednisone, doxorubicin, cyclophosphamide, etoposide, cytarabine, bleomycin, vincristine, methotrexate, leucovorin calcium, concomitant trimethoprim/sulfamethoxazole DS], MACOP-B [ie, methotrexate, doxorubicin, cyclophosphamide, vincristine, bleomycin], ACVB [ie, doxorubicin, cyclophosphamide, vindesine, bleomycin]) can be used.
  • Radiation therapy to bulky sites of disease may be necessary after completion of chemotherapy.
  • Compared with patients with other types of diffuse aggressive lymphomas, patients with anaplastic large cell lymphoma (ALCL) have increased and more prolonged response rates, with improved overall survival. The better prognosis holds particularly true for patients who are ALK positive, who have demonstrated significantly better survival rates than those who are ALK negative.
  • A prospective trial that used high-dose chemotherapy and autologous stem cell transplantation (ASCT) as front-line treatment revealed an excellent 5-year overall survival rate of 87%, which was significantly better than for aggressive nonanaplastic lymphomas.¹⁷ To date, no published randomized trials compare ASCT to conventional combination chemotherapy regimens.
• Secondary forms of anaplastic large cell lymphoma (ALCL): These forms are associated with a poor prognosis and also warrant treatment with a regimen containing doxorubicin.
• Primary cutaneous anaplastic large cell lymphoma (ALCL)
  • As many as one fourth of patients with primary cutaneous ALCL experience spontaneous regression of skin lesions.
  • Those with persistent localized disease can undergo surgical excision with or without radiation therapy and achieve excellent long-term survival. Those with disseminated skin involvement are more likely to experience progression to extracutaneous sites and thus may benefit from systemic combination chemotherapy.
  • The distinction of primary cutaneous ALCL from lymphomatoid papulosis, although difficult by pathologic means, should be attempted clinically, because lymphomatoid papulosis tends to run a benign clinical course despite cycles of regression followed by relapse.
• Monoclonal antibody against CD30: Monoclonal antibodies against CD30 are being tested clinically in lymphoma and Hodgkin lymphoma. HeFi-1 and SGN-30 are 2 antibodies that are being studied in preclinical and clinical models, respectively.

Medication

The goals of pharmacotherapy in patients with anaplastic large cell lymphoma (ALCL) are to induce remission, to reduce morbidity, and to prevent complications.

Antineoplastic Agents

Intensive anthracycline-based chemotherapy offers a high chance of durable, complete responses. CHOP is the standard first-line treatment. The regimen consists of (1) cyclophosphamide, doxorubicin, vincristine, and prednisone q21d, (2) restaging after first 2 cycles to document response, and (3) continuing with 2 additional cycles after complete remission is documented (not to exceed 6-8 cycles).

Cyclophosphamide (Cytoxan, Neosar)

Alkylating agent chemically related to nitrogen mustards. Active metabolites may involve cross-linking of DNA, which may interfere with the growth of normal and neoplastic cells.

Dosing

Adult

750 mg/m² IV once; repeat q21d; not to exceed 6-8 cycles

Pediatric

Not established

Interactions

Coadministration of allopurinol increases the risk of bleeding or infection and enhances myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase the half-life while decreasing the metabolite concentrations; may increase the effect of anticoagulants; coadministration with high doses of phenobarbital may increase metabolism; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity

Contraindications

Documented hypersensitivity; severely depressed bone marrow function

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Monitor for hematopoietic suppression (particularly neutrophils and platelets); regularly examine the urine for RBCs, which may precede hemorrhagic cystitis; decrease the dose in the presence of moderate renal failure

Doxorubicin (Adriamycin, Rubex)

Inhibits topoisomerase II and produces free radicals, which may destroy DNA. Combined effect inhibits neoplastic cell growth.

Dosing

Adult

50 mg/m² IV once; repeat q21d; not to exceed 6-8 cycles

Pediatric

Not established

Interactions

May decrease phenytoin and digoxin plasma levels; phenobarbital may decrease plasma levels; cyclosporine increases doxorubicin AUC (systemic clearance) and may induce coma or seizures and prolong hematologic toxicity; mercaptopurine increases toxicity; cyclophosphamide increases cardiac toxicity

Contraindications

Documented hypersensitivity; severe heart failure, cardiomyopathy, impaired cardiac function, and life-threatening arrhythmias; preexisting myelosuppression; completion of maximum cumulative dose of doxorubicin (ie, 400-550 mg/m²) or other anthracycline

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Irreversible cardiotoxicity and myelosuppression may occur; extravasation may result in severe local tissue necrosis; reduce the dose in patients with impaired hepatic function; decrease the dose in the presence of severe renal failure.

Vincristine (Oncovin)

Mechanism of action is uncertain. May involve decreased reticuloendothelial cell function or increased platelet production.

Dosing

Adult

1.4 mg/m² IV once; repeat q21d; not to exceed 2 mg/dose and 6-8 cycles

Pediatric

Not established

Interactions

CYP3A4 substrate, CYP2D6 inhibitor; acute pulmonary reaction may occur when taken concurrently with mitomycin-C

Contraindications

Documented hypersensitivity; fatal, if administered intrathecally

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in the presence of severe cardiopulmonary or hepatic impairment and in patients with preexisting neuromuscular disease; vincristine is a vesicant; avoid extravasation

Corticosteroids

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

Prednisone (Deltasone, Meticorten, Orasone, Sterapred)

Corticosteroid with antilymphocytic effects, causing lymphocyte lysis and mitosis inhibition.

Dosing

Adult

100 mg PO qd d 1-5; repeat q21d; not to exceed 6-8 cycles

Pediatric

Not established

Interactions

Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase the metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics; may decrease the effectiveness of vaccines and toxoids

Contraindications

Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI disease

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

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.

Follow-up

Further Outpatient Care

• Although late relapses can occur, patients with diffuse aggressive lymphomas usually experience recurrence within 2 years of completion of treatment. Early detection allows identification of potential candidates for high-dose therapy and stem cell transplantation. Periodic physical examinations and reimaging are recommended as follow-up care for those in remission. Long-term survivors need continued surveillance for potential treatment-associated complications.

Complications

• Tumor lysis syndrome (TLS) is a common complication of treatment for any high-grade, bulky, treatment-sensitive lymphoma and occurs after intracellular contents are released rapidly into the blood. The syndrome manifests as renal failure, hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia; these metabolic derangements may lead to sudden death if left uncorrected. Prophylactic and treatment measures include allopurinol, alkaline diuresis, and correction of potassium and phosphate abnormalities. Patients with bulky or advanced-stage anaplastic large cell lymphoma (ALCL) are at high risk of TLS and should receive prophylaxis, with close monitoring of fluid status, urine output, electrolytes, and renal function.
• Untreated or treatment-resistant systemic anaplastic large cell lymphoma (ALCL), like other aggressive systemic lymphomas, ultimately results in death, with variable earlier complications depending on the bulk and sites of disease.
• Long-term survivors of non-Hodgkin lymphoma are at increased risk of second malignancies, including all solid tumors, melanoma, Hodgkin disease, and acute myelogenous leukemia (AML).

Prognosis

• Primary systemic anaplastic large cell lymphoma (ALCL): The prognostic factors applied to other non-Hodgkin lymphomas are also relevant to ALCL and include age, LDH values, performance status, number of extranodal sites, and stage. These features are compiled in the International Prognostic Index, which provides stratification into risk groups and serves to identify patients for whom early experimental approaches may be considered. ALK status is also an important prognostic indicator because ALK-positive cases have demonstrated a significantly improved 5-year overall survival rate of 70-80%, versus 15-45% reported for those without ALK expression.
• Primary cutaneous ALCL: Localized skin presentation in those with pure cutaneous disease is associated with good long-term survival.
• Secondary ALCL: This is associated with poor prognosis.
• ALC has been reported to be an independent prognostic factor.¹⁵ ALC <1000/μ L correlates with shorter survival and lower complete remission rate.

Patient Education

References

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Keywords

malignant anaplastic lymphoma, Ki-1+ anaplastic lymphoma, anaplastic large-cell lymphoma, Ki-1 lymphoma, CD30+, ALCL, anaplastic lymphoma kinase-positive lymphoma, ALK-positive lymphoma, anaplastic Ki-1+ large cell lymphoma, lymphoma, large cell anaplastic CD30+ Ki-1 lymphoma, Ki-1 large cell lymphoma, cutaneous and nodal Ki-1 positive anaplastic large cell lymphoma, cutaneous lymphoma, skin cancer, cancer, extranodal lymphoma, extra-nodal lymphoma, systemic lymphoma, systemic cancer, anaplastic lymphoma, systemic anaplastic large-cell lymphoma

Contributor Information and Disclosures

Author

Delong Liu, MD, PhD, Associate Professor of Medicine, Division of Oncology/Hematology, New York Medical College; Chief of Hematology, Phelps Memorial Hospital Center; Director of Non-ablative Allogeneic Stem Cell Transplantation Program, Westchester Medical Center; Editor-in-Chief, Journal of Hematology and Oncology
Delong Liu, MD, PhD is a member of the following medical societies: American Society of Clinical Oncology and American Society of Hematology
Disclosure: Nothing to disclose.

Coauthor(s)

Koyamangalath Krishnan, MD, FRCP, FACP, Paul Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, Program Director, Hematology-Oncology Fellowship, James H Quillen College of Medicine at East Tennessee State University
Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, and Royal College of Physicians
Disclosure: Nothing to disclose.

Christine Urbanski, MD, Consulting Staff, Hematology/Oncology Associates, RMH Regional Cancer Center
Christine Urbanski, MD is a member of the following medical societies: American College of Physicians
Disclosure: Nothing to disclose.

Medical Editor

David Aboulafia, MD, Medical Director, Bailey-Boushay House; Clinical Professor, Department of Medicine, Division of Hematology, University of Washington
David Aboulafia, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Medical Directors Association, American Society of Hematology, Infectious Diseases Society of America, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Wendy Hu, MD, Consulting Staff, Department of Hematology/Oncology and Bone Marrow Transplantation, Huntington Memorial Medical Center
Wendy Hu, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Blood and Marrow Transplantation, American Society of Hematology, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

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