======Chronic Lymphocytic Leukemia======

=====Workup=====
  * Physical Exam
  * Baseline labs
  * Imaging: CT > PET
  * Repeat peripheral flow
  * Bone marrow biopsy
  * HBV, HCV (less important now that rituxamab falling out of favor)

=====Staging=====
  * Biret
    * A: <3 lymphoid
    * B: >3 lymphoid
    * C: Hgb < 10 or platelets < 100
  * Rai
    * 0: lymphocytosis
    * I: lymphadenopathy
    * II: hepatosplenomegaly
    * III: Hgb < 11
    * IV: platelets < 100

=====Diagnosis=====
  - B cells > 5 x 10^9
  - lymphadenopathy or splenomegaly
  - cytopenia
  - CLL-related symptoms
  * if meets bottom three criteria, then small lymphocytic lymphoma

=====Treatment=====
  * first-line
    * ibutrinib (BTK inhibitor)
      * adverse effects: diarrhea, rash, bleeding, atrial fibrillation
    * venetoclax (now 1st line)
  * refractory:
    * idelalisib
    * immunotherapy
      * allo-SCT
      * CAR-T
      * lenalidomide
      * checkpoint inhibitors

=====Indications=====
  * Bone marrow failure: Hgb < 11, platelets < 100
  * Symptoms
    * weight loss >10% over 6 months
    * ECOG ≥ 2
    * T ≥ 38°C for 2 weeks
    * night sweats
  * Splenomegaly (>6 cm or symptomatic)
  * Lymphadenopathy (>10 cm or symptomatic)
  * Progression of disease
    * ALC increase >50% in 2 months
    * ALC doubling time <6 months
    
=====Complications=====
  * infection
  * autoimmune (5-10%)
    * AIHA
    * ITP
  * pure red cell aplasia
  * malignancy
    * DLBCL
    * Skin: 5-10x risk SCC/BCC


=====Poor prognostic factors=====
  * 17p13 deletion
  * 11q22.3
  * Trisomy 12
  * 13q14
  * NOTCH, SF3D1?
  * hypermutation?
  * beta-2 macroglobulin