eMedicine Specialties > Pediatrics: General Medicine > Oncology
Lymphoproliferative Disorders: Treatment & Medication
Updated: Nov 24, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- Children with inherited immunodeficiency syndromes
- Truly malignant neoplasms are sometimes difficult to differentiate from nonmalignant lymphoproliferative disorders (LPDs) with aggressive features. When the underlying immunodeficiency manifested to only a minor degree and when the histologic features are marked nuclear atypia and other features of a high-grade neoplasm, standard chemotherapeutic regimens are usually recommended. These regimens include cyclophosphamide, prednisone, vincristine, and doxorubicin.
- In other cases, local control of the lymphoproliferative disorder by using surgical resection or irradiation with adjunctive interleukin-2 or monoclonal antibody therapy may prove beneficial.
- Boys with X-linked immunodeficiency syndrome appear to benefit from immunoglobulin therapy.
- If cytotoxic therapy is chosen in child with an underlying immunodeficiency syndrome, myelosuppressive therapy may worsen their immunocompromise beyond what is ordinarily expected. Therefore, care should be taken to begin support for febrile neutropenia and other infections in a timely fashion. As described above, bone marrow reconstitution with an immunocompetent donor appears to be the best method to prevent lymphoproliferative disorders in children with severe inherited immunodeficiency syndromes.
- Patients with posttransplant lymphoproliferative disorder (PTLD)
- PTLDs are varied and somewhat depend on the nature of the allograft and on the immunosuppressive agents used to prevent graft (or host) rejection. The histologic grades of lymphoproliferative disorders can vary widely in this setting and range from a benign oligoclonal expansion of lymphoid cells to a high-grade neoplastic process. Low-grade tumors usually respond favorably to a reduction in immunosuppression, whereas high-grade tumors may require chemotherapy, irradiation, and/or surgery.
- Cyclosporin A and antithymocyte globulin are associated with the development of lymphoproliferative disorders within months of transplantation, often in the GI tract. In many instances, Epstein-Barr virus (EBV) DNA transcripts can be identified with Southern blotting, anti-EBV-encoded RNA (EBER) staining, or polymerase chain reaction (PCR), but results of serologic tests are frequently nonreactive. The lymphocytic infiltration into transplanted organs can often mimic organ rejection.
- In contrast to the lymphoproliferative disorders observed in primary immunodeficiency syndromes, the most successful means of control after transplantation are diminishing or discontinuing immunosuppressive drug therapy.
Surgical Care
- Surgical resection plays a role in managing lymphoproliferative disorders.
- Circumstances are limited to obtaining enough tissue to make a diagnosis and to debulking large tumors that compromise surrounding vital structures. However, in most cases, the primary means to control lymphoproliferative disorders is medical management.
Consultations
- In children with a suspected lymphoproliferative disorders, consultation with a physician familiar with the underlying immunodeficiency syndrome is indicated, in addition to consultation with a pediatric oncologist.
- Consider an infectious process with appropriate consultation with a pediatric infectious disease specialist.
Diet
- In children, diet does not appear to play a role in the pathogenesis or treatment of lymphoproliferative disorders.
Activity
- Activity does not appear to play a role in the treatment or pathogenesis of lymphoproliferative disorders.
Medication
Antineoplastic agents
Prescribe chemotherapeutic agents only to children with the help of clinicians who are experienced with the doses and toxicities of these drugs. The drugs detailed below are those used in standard CHOP regimen and include cyclophosphamide, hydroxydaunomycin (doxorubicin), vincristine (Oncovin), and prednisone.
Doxorubicin (Adriamycin)
Alkylating agent with several mechanisms of action (eg, DNA intercalation, topoisomerase-mediated DNA strand breaks, oxidative damage by producing free radicals).
Adult
40 mg/m2 IV days 1 and 22
Pediatric
Administer as in adults
Increased risk of cardiotoxicity when combined with chest irradiation; 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
Documented hypersensitivity; severe heart failure, cardiomyopathy, impaired cardiac function (cumulative anthracycline dose >450 mg/m2 is relative contraindication); preexisting myelosuppression
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Irreversible cardiac toxicity and myelosuppression may occur; extravasation may result in severe local tissue necrosis; reduce dose in impaired hepatic function; may cause nausea, diarrhea, or alopecia
Cyclophosphamide (Cytoxan)
Exerts cytotoxic effect by alkylation of DNA, leading to interstrand and intrastrand DNA crosslinks, DNA-protein crosslinks and inhibition of DNA replication.
Adult
750 mg/m2 IV on days 1 and 22
Administer with mesna, 400 mg/m2 IV with first dose; repeat after 3 h and after each dose of cyclophosphamide
Pediatric
Administer as in adults
Coadministration of phenobarbital may enhance metabolic activation of cyclophosphamide (prodrug); inhibits cholinesterase, potentiating effect of succinylcholine; 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 toxicity; may increase effect of anticoagulants; thiazide diuretics may prolong cyclophosphamide-induced leukopenia
Documented hypersensitivity; nephropathy, hemorrhagic cystitis, and myelosuppression
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in bone marrow suppression and impaired renal or hepatic function; may need to modify dosage; may cause myelosuppression (ie, leukopenia, hemolytic anemia, thrombocytopenia), alopecia, hemorrhagic cystitis (monitor for hematuria), cardiotoxicity (at high doses), impaired fertility, headache, darkening of skin and fingernails; moderate-to-high emetogenic potential (based on the dose) causes anorexia, diarrhea, stomatitis, and mucositis
Vincristine (Oncovin)
Plant-derived vinca alkaloid. Inhibits mitosis by binding tubulin. Inhibits microtubule formation in mitotic spindle, arresting metaphase.
Adult
1.5 mg/m2 IV; not to exceed 2 mg/dose and not > 1 time/wk
Pediatric
Administer as in adults
Acute pulmonary reaction may occur when taken concurrently with mitomycin-C; asparaginase, cytochrome P450 (CYP) 3A4 inhibitors (eg, itraconazole, quinupristin-dalfopristin, sertraline, ritonavir), granulocyte-macrophage colony-stimulating factor (GM-CSF, eg, sargramostim, filgrastim), or nifedipine increase toxicity; CYP3A inducers (eg, carbamazepine, phenytoin, phenobarbital, rifampin) may decrease effects
Documented hypersensitivity; patients with demyelinating form of Charcot-Marie-Tooth syndrome; universally fatal if delivered intrathecally
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Dosage modification required in patients with impaired hepatic function, patients receiving other neurotoxic drugs, or patients with preexisting neuromuscular disease; avoid extravasation (can cause tissue damage); severe constipation and/or peripheral neuropathy are relative contraindications
Prednisone (Deltasone, Meticorten, Orasone, Sterapred)
Combines ubiquitous uses and likely to downregulate inflammatory proteins by directly signaling with intrachromosomal binding sites.
Adult
40 mg/m2/d PO qd for 30 d; not to exceed 60 mg/d
Pediatric
Administer as in adults
Barbiturates, phenytoin, rifampin may decrease effectiveness; coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; serious infections (excluding meningitis and septic shock) and fungal or varicella infections
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Administer with meals to decrease GI upset; abrupt discontinuation of glucocorticoids may cause adrenal crisis
Early-onset adverse effects include glucose intolerance, hypertension, agitation and indigestion
Late-onset adverse effects include immune suppression and increased susceptibility to sepsis, adrenal suppression, hypertension, urinary calcium loss and osteopenia, gastric irritation, and bleeding
Antiemetic agents
Antineoplastic-induced vomiting is stimulated through the chemoreceptor trigger zone, which then stimulates the vomiting center in the brain. Increased activity of central neurotransmitters, dopamine in the chemoreceptor trigger zone or acetylcholine in the vomiting center appears to be major mediators for inducing vomiting. After the administration of antineoplastic agents, serotonin (5-HT) is released from enterochromaffin cells in the GI tract. With release of 5-HT and its subsequent binding to 5-HT3-receptors, vagal neurons are stimulated and transmit signals to the vomiting center, resulting in nausea and vomiting.
Antineoplastic agents may cause nausea and vomiting so intolerable that patients may refuse further treatment. Some antineoplastic agents are more emetogenic than others. Prophylaxis with antiemetic agents before and after cancer treatment is often essential to ensure administration of the entire chemotherapy regimen.
Ondansetron (Zofran)
Selective 5-HT3–receptor antagonist that blocks 5-HT peripherally and centrally. Ameliorates chemotherapy-induced nausea and vomiting.
Adult
0.3 mg/kg/d IV; not to exceed 24 mg/d
Pediatric
Administer as in adults
Although CYP inducers (eg, barbiturates, rifampin, carbamazepine, phenytoin) change half-life and clearance, dosage adjustment usually not required
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Headache (common adverse drug reaction)
Uroprotective antidote
Mesna is a prophylactic detoxifying agent used to inhibit hemorrhagic cystitis caused by ifosfamide and cyclophosphamide.
In the kidney, mesna disulfide is reduced to free mesna. Free mesna has thiol groups that react with acrolein, which is the ifosfamide and cyclophosphamide metabolite considered responsible for urotoxicity.
Mesna (Mesnex)
Inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity.
Adult
Dose depends on ifosfamide or cyclophosphamide, typically 60-100% of antineoplastic agent used; may be administered as initial bolus, followed by continuous or intermittent IV infusions before and after chemotherapy regimen
Pediatric
Administer as in adults
May increase warfarin affect, adjust dose according to international normalized ratio (INR) target
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Monitor morning urine for hematuria before ifosfamide or cyclophosphamide dose; common adverse effects include hypotension, headache, GI toxicity, and limb pain
More on Lymphoproliferative Disorders |
| Overview: Lymphoproliferative Disorders |
| Differential Diagnoses & Workup: Lymphoproliferative Disorders |
 Treatment & Medication: Lymphoproliferative Disorders |
| Follow-up: Lymphoproliferative Disorders |
| Multimedia: Lymphoproliferative Disorders |
| References |
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Further Reading
Keywords
lymphoproliferative disorders, LPD, immune dysfunction in children, immune deficiency disorders, immune disorder, X-linked immunodeficiency, agammaglobulinemia, autoimmune lymphoproliferative syndrome, severe combined immunodeficiency, common variable immunodeficiency
