Malignancy

1
Malignancy

• NHL 7.7 - mostly extranodal, all B cell type
• Others -
• Waldenstroms macroglobulinemia
• Hodgkins disease
• Adenocarcinoma - stomach, ovary, colon
• Sq cell Ca - vagina, skin, mouth, lung
• Ca - breast, prostate
• Melanoma

Cunningham-Rundes and Bodian (Clin Immunol 1999
9234-48)
2
GI Diseases (n248)

• Nodular lymphoid hyperplasia 10
• Malabsorption, no other diag. 10
• Giardiasis 8
• UC 4
• Ulc. Proctitis 3
• Crohns disease 9
• Malnutrition needing TPN 5
• Campylobacter enteritis 5

Cunningham-Rundes and Bodian (Clin Immunol 1999
9234-48)
3
Granulomatous disease

• 20 patients
• Lung, lymph nodes, skin, bone marrow, and liver
• Histology non-caseating granuloma,
  indistinguishable from sarcoidosis
• Asymptomatic/ dyspnea if lung involvement/anemia
  or thrombocytopenia if hypersplenism
• Corticosteroid effectively in some but
  increased risk of infection
• Splenectomy

4
Laboratory Abnormalities

• ? IgG, mostly with ? IgA and IgM
• Lymphopenia 20
• B cell numbers - mostly normal
• ? CD4/CD8 ratios, ? in CD4CD45 T cells
• Low or absent isohemagglutinin titers and
  specific Ab levels
• T cell in vitro proliferation subnormal in 50
  to mitogen, antigens

5
Differential diagnosis

• Primary immunodeficiency syndrome
• X-linked agammaglobulinemia
• Transient hypogammaglobulinemia of infancy
• Infectious agents
• CMV, EBV, HIV
• Malignancy
• Lymphoma, multiple myeloma, CLL
• Protein-losing states
• Nephrotic syndrome, Protein-losing enteropathy
• Drugs
• Cyclophosphamide, phenytoin, Gold,
  Penicillamine

6
XLA CVID THI
Mutation of gene Btk -- --
Family Hx X-linked -- --
Onset Late 1st year Any age 1st year
Recovery - - 2-4 y/o
Lymph node small hyperplasia --
B cell umber absence near normal normal
T cell normal subtle normal
Ig IgG ? IgA ? IgM ? IgG ? IgA ? IgM ? IgG ? IgA ? IgM ? or normal
7
Treatment

• Early and aggressive antibiotic therapy,
• Replacement with IVIG 400 mg/kg/month
• Ongoing therapy for autoimmune and inflammatory
  disorders surveillance for malignancy

8
IVIG

• Trough levels gt 350 mg/dL without infection
• Levels gt 500 mg/dL if severe infection persists
• Back or abdominal pain, nausea, vomiting, chills,
  fever, and myalgia -gt nonanaphylactic binding of
  infused Abs to microbial Ag
• True anaphylactic reactions rare flushing,
  facial swelling, dyspnea, hypotensionanti-IgA
  antibodies (IgE isotype)

9
IVIG

• Receive very low IgA product is completely IgA
  deficient
• Risk of infection
• HIV no risk
• HCV more severe course in CVID patients

10
Treatment IL-2
Clin Immunol 2001100(2) 181-90

• 15 patients received PEG-IL-2 12-18 mo / 29
  control
• ? T cell proliferative response to mitogen
• ? T cell proliferative response to antigen
  (candida and tetanus)
• ? Antibody response to immunization with
  neoantigen bacteriophage fX 174
• ? Days of bronchitis, diarrhea and joint pain

11
Treatment
Eur J Clin Invest 200030(3) 252-9

• Retinoic acidDecreased vitamin A level in CVID
  patients
• Associated with chronic bacterial infection
  and splenomegalySupplementation ? IL-10 , ?
  TNF-ain vivo ? IgA , ? mitiogen response to
  PHA
• Cimetidine ?
• IL-10 ?

12
Mortality and Survival

• 248 patients median follow-up 7 yrs (0-25)
• 57 died from 1-32 yrs after diagnosis, ages 5-90
  yrs (median age 43) - 27
• Causes -Lymphoma, cor pulmonale, hepatitis,
  malnutrition, other malignancies, vasculitis,
  etc.
• Poor prognostic signs of peripheral B cells,
  initial IgG level
• For each ? in B cell numbers, risk of death on
  follow-up ? by a factor of 0.92

Cunningham-Rundes and Bodian (Clin Immunol 1999
9234-48)