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A. Characteristics

  1. Patients usually in the 4-5th decades with Men > Women
  2. Chronic lymphoproliferative disorder with "dry" bone marrow tap
  3. Mature low grade B cell leukemia
    1. CD19,20,22+
    2. CD11c,25, B-Ly7+
    3. CD21, CD5 Negative (found on other B cell tumors such as CLL, some lymphomas)
  4. Cells appear to have hairy projections from cytoplasm
  5. Elevated levels of annexin A1 (ANXA1) may be suitable for immunohistological diagnosis [7]

B. Presentation

  1. Incidental finding in ~25% of patients
  2. Splenomegaly
  3. Recurrent Infections
  4. Pancytopenia, anemia

C. Stages

  1. Stage I - minimal / moderate splenomegaly with normal hematocrit or mild anemia
  2. Stage II - Severe Anemia
  3. Stage III - Pancytopenia

D. Treatment [2,3]

  1. Indications
    1. Severe neutropenia (<500-1000/µL)
    2. Thrombocytopenia (<50-100K/µL)
    3. Anemia (<8-10gm/dL Hb)
    4. Recurrent infections
  2. Splenectomy
    1. Improves cell counts
    2. Systemic therapy usually required within 8 months of splenectomy
    3. Vaccination for HIB, pneumococcus, and influenza virus prior to operation
  3. Chlorodeoxyadenosine (CDA, cladribine, Leustatin®) [1]
    1. First line therapy with initial complete response ~85% with 7 day infusion (0.1mg/kg/d)
    2. Remission in >80% of patients after 1 year (~12% partial response)
    3. Less side effects with increased efficacy compared to pentostatin [4]
    4. Inhibits action of ribonucleotide reductase and DNA polymerase alpha
    5. Side effects include mild marrow suppression and thrombocytopenia and fever
  4. Pentostatin (2'-deoxycoformycin)
    1. Two week infusions with complete response rates ~65%
    2. Nausea, vomiting, rash, keratoconjunctivitis are side effects
    3. Inhibits adenosine deaminase leads to excess dATP and dADP
  5. Interferon Alpha
    1. 2MU/m2 three times per week for 12 months
    2. Partial responses occur in most patients (very few complete responses)
    3. Poorly tolerated side effects
  6. Fludarabine - some partial responses
  7. Anti-CD22 - Toxin Conjugate [5]
    1. CD22 is an adhesion molecule found only on B cells
    2. Conjugated to truncated pseudomonas exotoxin (PE38) to form BL22 molecule
    3. Predmedication with anti-TNFa Ab (infliximab) and COX2 inhibitor
    4. Induced 11 of 16 complete remissions in previously refractory patients
    5. Generally well tolerated with mild symptoms of cytokine release syndrome
    6. Two of 16 patients developed reversible hemolytic-uremic syndrome
  8. Anti-IL2 - Toxin Conjugate [6]
    1. Anti-IL2 receptor alpha chain (Anti-Tac) conjugated to PE38 to form LMB-2
    2. One complete and 3 partial remissions in 4 patients with resistant HCL
  9. Standard Chemotherapy

References

  1. Chlorodeoxyadenosine. 1992. Med Let. 34(879):87
  2. Saven A and Piro L. 1994. NEJM. 330(10):691 abstract
  3. Saven A and Piro LD. 1994. Ann Intern Med. 120(9):784 abstract
  4. Savern A and Piro LD. 1993. Ann Intern Med. 119(4):278 abstract
  5. Kreitman RJ, Wilson WH, Bergeron K, et al. 2001. NEJM. 345(4):241 abstract
  6. Kreitman RJ, Wilson WH, White JD, et al. 2000. J Clin Oncol. 18:1622 abstract
  7. Balini B, Tiacci E, Liso A, et al. 2004. Lancet. 363(9424):1869