eMedicine Specialties > Hematology > Stem Cells and Disorders
Lymphoma, Malignant Anaplastic (Ki 1+): Treatment & Medication
Updated: Dec 12, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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.
Adult
750 mg/m2 IV once; repeat q21d; not to exceed 6-8 cycles
Pediatric
Not established
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
Documented hypersensitivity; severely depressed bone marrow function
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.
Adult
50 mg/m2 IV once; repeat q21d; not to exceed 6-8 cycles
Pediatric
Not established
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
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
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.
Adult
1.4 mg/m2 IV once; repeat q21d; not to exceed 2 mg/dose and 6-8 cycles
Pediatric
Not established
CYP3A4 substrate, CYP2D6 inhibitor; acute pulmonary reaction may occur when taken concurrently with mitomycin-C
Documented hypersensitivity; fatal, if administered intrathecally
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.
Adult
100 mg PO qd d 1-5; repeat q21d; not to exceed 6-8 cycles
Pediatric
Not established
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
Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI disease
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.
More on Lymphoma, Malignant Anaplastic (Ki 1+) |
| Overview: Lymphoma, Malignant Anaplastic (Ki 1+) |
| Differential Diagnoses & Workup: Lymphoma, Malignant Anaplastic (Ki 1+) |
 Treatment & Medication: Lymphoma, Malignant Anaplastic (Ki 1+) |
| Follow-up: Lymphoma, Malignant Anaplastic (Ki 1+) |
| References |
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Further Reading
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
