Lymphopenia

Muronomab-CD3 is a murine monoclonal antibody directed against the CD3 complex of the T-lymphocyte antigen receptor. This drug selectively diminishes the T-lymphocyte pool resulting in a strong lymphopenia. Similar to other nonhuman antibodies the generation of human antimurine antibodies (HAMA) limits its long-term use. 

Lymphocyte 20-40% T cells (cell-mediated immunity) B cells (humoral antibody response) Lymphocytosis Viral infections (e.g., mononucleosis) Tuberculosis Fungal infections Lymphopenia human immunodeficiency virus... 

Hematological Effects. Persistent clinical lymphopenia and thrombocytopenia were observed in a 64-year-old man exposed to 241 Am when an ion-exchange column containing about 100 g of241 Am exploded in his face (Filipy et al. 1995). The explosion resulted in contact exposure through the intact and lacerated skin and presumed inhalation exposure (see Sections 3.2.3.1 and 3.2.3.2 for additional information regarding this accident). 

Low levels or absence of adenosine deaminase (ADA) is associated with one form of severe combined immunodeficiency disease (SCID) characterized by B-andT-lymphocyte dysfunction due to toxic effects of deoxyadenosine (HI9). Most patients present as infants with failure to thrive, repeated infections, severe lymphopenia, and defective cellular and humoral immunity. Disease severity is correlated with the degree of deoxyadenosine nucleotide pool expansion and inactivation of S-adenosylhomocysteine hydrolase in red blood cells. Up to now, more than 40 mutations have been identified (A4, H20, S5, S6). The majority of the basic molecular defects underlying ADA deficiency of all clinical phenotypes are missense mutations. Nonsense mutations, deletions ranging from very large to single nucleotides, and splicing mutations have also been reported. It is likely that severe... 

Purine nucleoside phosphorylase (PNP) deficiency engenders a combined immunodeficiency and neurologic abnormalities and is usually fatal in childhood (G4). Patients with PNP deficiency have profound lymphopenia and a small thymus with poorly formed Hassall corpuscles. Lymphocyte enumeration shows markedly decreased numbers of T cells and T-cell subsets, with normal percentages of B cells. Point mutations and a splicing mutation have been identified in some PNP-deficient patients (H4). 

Cladribine (2-CdA) -purine analogue antimetabolite -bone marrow suppression -fever in 50% (probably due to tumor lysis) -rash in 50% -immunosuppression (with profound T-cell lymphopenia)... 

Pentostatin -purine analogue antimetabolite inhibits adenosine deaminase -nephrotoxicity (including acute renal failure) -bone marrow suppression -neurotoxicity—lethargy, fatigue, seizures, coma -immunosuppression (lymphopenia) -nausea and vomiting -fever -anorexia -hepatotoxicity... 

Except for lymphopenia, which was observed at all dose levels, no other effects were measured in the 100 and 300 mg/kg groups. At 900 mg/kg, significant decreases occurred in body weight, food intake, blood lymphocytes, and thymus weight, and significant increases occurred in thyroid weight, mesenteric lymph nodes, and histopathology (Vos etal. 1983)... 

The oral LD50 of diepoxybutane in rats is 78mg/kg body weight, whereas the inhalation LCso is 371 mg/m for a 4-hour exposure. Rats exposed via inhalation experienced lacrimation, clouding of the cornea, labored breathing, and lung congestion. Leukopenia and lymphopenia were produced in rabbits after six intramuscular injections of 25 mg/kg. ... 

Adverse reactions occurring in 3% or more of patients receiving rifapentine combination therapy include the following Rash pyuria proteinuria hematuria urinary casts neutropenia lymphopenia hyperuricemia and an increase in ALT and AST. 

Tablet combination therapy Adverse reactions occurring in at least 3% of patients include the following Abdominal pain alopecia anemia anorexia anxiety arthralgia back pain bacterial infection blurred vision concentration impairment cough depression dermatitis diarrhea dizziness dry mouth/skin dyspepsia dyspnea eczema fatigue/asthenia headache hypothyroidism increased sweating injection site reaction insomnia irhtability/anxiety/nervousness lymphopenia memory impairment mood alteration myalgia nausea neutropenia pain pruritus pyrexia rash resistance mechanism disorders rigors thrombocytopenia vomiting weight decrease.

Lab test abnormalities Elevations of liver enzymes and CPK, lymphopenia, and neutropenia occurred. These were reported in similar proportions of zanamivir and lactose-vehicle placebo recipients with acute influenza-like illness. 

Lab test abnormalities Liver function test abnormalities, CPK or creatinine elevations, lymphopenia, triglyceride elevations occurred in at least 3% of patients. 

Other adverse events may include pancytopenia, aplastic anemia, neutropenia, leukopenia, thrombocytopenia, lymphopenia, leukocytosis, lymphadenopathy, coagulation disturbances, hypotension/shock, heart failure, angina/MI, tachycardia, bradycardia, tachypnea/hyperventilation, abnormal chest sounds, pneumonia/pneumonitis, rash, urticaria, pruritus, erythema, flushing, diaphoresis, diarrhea, bowel infarction, arthralgia, arthritis, blindness, blurred vision, diplopia, hearing loss, otitis media, tinnitus, vertigo, photophobia, conjunctivitis, nasal/ear stuffiness, and anuria/oliguria. 

Bone marrow toxicity Peginterferon alfa-2a suppresses bone marrow function and may result in severe cytopenias. Ribavirin may potentiate the neutropenia and lymphopenia induced by alpha interferons including peginterferon alfa-2a. Alpha interferons may be associated with aplastic anemia very rarely. 

Finally, in this brief overview of lymphocyte defects, mention should be made of mutations affecting major histocompatibility-complex (MHC) Class II molecules. These mutations affect a multiprotein transcription factor complex that regulates the expression of MHC Class II molecules (121). Affected patients have undetectable levels of MHC Class II antigens HLA-DP, DQ, and DR on the surface of monocytes and B cells. Lack of these antigen-presenting molecules leads to impaired immune response. Affected individuals have moderate lymphopenia with a severely reduced number of CD4+ T cells and normal or increased numbers of CD8+ T cells. Since MHC molecules in the thymic epithelium play a key role in positive and negative selection of primitive T cells, selection of competent T cells is also affected in the absence of MHC Class II antigens. 

Leukocytosis Lymphopenia Eosinopenia Altered inflammatory response Gastrointestinal Peptic ulceration Fatty liver Pancreatitis Nausea, vomiting Metabolic... 

Rare reactions include hypersensitivity reactions, lymphopenia, malignancies, and serious infections requiring hospitalization (such as abscess, pneumonia, and postoperative wound infection),... 

Drug interactions No formal drug interaction studies have been conducted with Rebif. Monitoring patients for neutropenia and lymphopenia is required if Rebif is given in combination with myelo-suppressive agents. 

Pentostatin is an adenosine deaminase inhibitor primarily used as an antineoplastic agent for lymphoid malignancies, and produces a profound lymphopenia. It is now frequently used for steroid-resistant graft-versus-host disease after allogeneic stem cell transplantation, as well as in preparative regimens prior to those transplants to provide severe immunosuppression to prevent allograft rejection. 

Diepoxybutane is highly toxic to rats (oral LC50 78 mg/kg bw), mice and rabbits. Among surviving animals, there was eye, skin and respiratory tract damage. Intramuscular injection of rabbits with 25 mg/kg bw produced leukopenia and lymphopenia. However, once weekly gavage dosing of rats for one year with 5 mg D,L-diepoxybutane was not toxic (lARC, 1976). 

A deficiency of the vitamin can result in lymphopenia, convulsions, dermatitis, irritability, and nervous disorders in humans. A defidency in monkeys may cause arteriosclerosis, while in rats, acrodynia. Research indicates that all animals require vitamin Bg, Bacteria in intestines generate some of this vitamin, but relatively little is available to humans in this form. Endogenous sources are available to plants, fungi, and some bacteria. 

---