Mucosa-Associated Lymphoid Tissue Medication
- Author: Sara J Grethlein, MD; Chief Editor: Emmanuel C Besa, MD more...
In patients who have Helicobacter pylori infection in association with a mucosa-associated lymphoid tissue (MALT) lymphoma (MALToma), especially if it is a gastric MALToma, the first line of therapy is treatment of the H pylori infection. In asymptomatic patients with low-grade MALTomas who are not infected with H pylori or whose MALToma does not respond to H pylori treatment, options include observation as opposed to active intervention.
If treatment is required, treatments similar to those used for other low-grade non-Hodgkin lymphomas (NHLs) are used. Monotherapy with agents such as chlorambucil, cyclophosphamide, fludarabine, or rituximab may be employed. Combinations of chemotherapy agents, with or without rituximab, may also be used. Patients with large-cell MALTomas are treated with combination chemotherapy (usually CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone]), with or without rituximab.
Antineoplastics interrupt proliferative activity and induce programmed cell death in proliferating B cells of MALTomas.
Cyclophosphamide is transformed primarily in the liver to active alkylating metabolites. These metabolites interfere with the growth of susceptible rapidly proliferating malignant cells. The mechanism of action is thought to involve cross-linking of tumor cell DNA.
Doxorubicin results in a conformational change of DNA and interferes with RNA polymerase, causing inhibition of protein synthesis.
Vincristine is a vinca alkaloid extracted from the plant Catharanthus rosea. It is cell cycle specific (M phase). The mitotic apparatus is arrested in metaphase via disruption of the microtubules. Absorption of vincristine through the GI tract is variable; therefore, administer the drug intravenously. It is metabolized extensively in the liver and excreted primarily via bile. Neurotoxicity is the limiting factor during therapy. Peripheral neuropathy is vincristine's most common adverse effect at usual doses.
Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. These agents modify the body's immune response to diverse stimuli.
Prednisone is metabolized by the liver to the active metabolite prednisolone. This binds extensively to albumin and transcortin. The unbound portion crosses cell membranes and binds to specific cytoplasmic receptors, inducing a response by modifying transcription and, ultimately, protein synthesis. Prednisolone is further metabolized to inactive compounds. It is used as a component of the CHOP combination chemotherapy regimen.
These agents inhibit cell growth and proliferation. Some agents may also suppress immune cells involved in MALTomas.
Fludarabine is a nucleotide analogue of vidarabine that is converted to 2-fluoro-ara-A, which enters the cell and is phosphorylated to form the active metabolite 2-fluoro-ara-ATP, which inhibits DNA synthesis.
Etoposide inhibits topoisomerase II and causes DNA strand breakage, causing cell proliferation to arrest in the late S or early G2 portion of the cell cycle.
Mitoxantrone inhibits cell proliferation by intercalating DNA and inhibiting topoisomerase II.
Bleomycin is a glycopeptide antibiotic that inhibits DNA synthesis. It is used for palliative purposes in the management of several neoplasms.
Chlorambucil alkylates and cross-links strands of DNA, inhibiting DNA replication and RNA transcription.
Monoclonal antibodies are genetically engineered chimeric murine-human immunoglobulins directed against proteins involved in cell cycle initiation.
Rituximab is a genetically engineered chimeric murine-human monoclonal antibody that is directed against the CD20 antigen found on the surface of normal and malignant B cells. The antibody is an immunoglobulin G1 (IgG1)-kappa containing murine light- and heavy-chain variable region sequences and human constant region sequences.
Antibiotics are the mainstay of therapy aimed at eradicating H pylori, the major etiologic agent of gastric MALToma.
Clarithromycin inhibits bacterial growth, possibly by blocking the dissociation of peptidyl transfer RNA (tRNA) from ribosomes, causing RNA-dependent protein synthesis to arrest.
Metronidazole is an imidazole ring-based antibiotic that is active against various anaerobic bacteria and protozoa. It is used in combination with other antimicrobial agents (except for Clostridium difficile enterocolitis).
Amoxicillin is an acid-stable semisynthetic penicillin. Its antimicrobial activity is pH-dependent, with the minimal inhibitory concentration (MIC) decreasing as the pH increases.
Proton Pump Inhibitors
Proton pump inhibitors (PPIs) are used in combination with antibiotics for eradication of H pylori.
Omeprazole decreases gastric acid secretion by inhibiting the parietal cell proton pump (hydrogen/potassium adenosine triphosphatase [H+/K+ ATPase]).
Lansoprazole suppresses gastric acid secretion by specific inhibition of the H+/K+-adenosine triphosphatase (ATPase) enzyme system (ie, proton pump) at the secretory surface of the gastric parietal cell. The drug blocks the final step of acid production, inhibiting basal and stimulated gastric acid secretion and therefore increasing gastric pH. Lansoprazole's effect is dose related. The drug is easy to administer to children because it is available as a capsule or an oral disintegrating tablet or in granular form for use in an oral suspension.
Esomeprazole is an (S)-isomer of omeprazole. It inhibits gastric acid secretion by inhibiting the H+/K+-ATPase enzyme system at the secretory surface of the gastric parietal cells.
Dexlansoprazole suppresses gastric acid secretion by specifically inhibiting the H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells.
Rabeprazole sodium suppresses gastric acid secretion by specifically inhibiting the H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells.
Pantoprazole suppresses gastric acid secretion by specifically inhibiting the H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells.
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