CML, myeloproliferative disorders and bone marrow biopsy

Myeloproliferative disorders
1. 4 types of myeloproliferative disorders
  1. Positive for Philadelphia chromosome
    1. Chronic myelogenous leukemia (CML)
      1. Clinical phases are differentiated according to the amount of blasts present in the blood
    2. Translocation between ch 9 and 22
  2. Negative for Philadelphia chromosome
    1. Polycitemia vera (PV)
    2. Essential thrombocytosis (ET)
    3. Primary Myelofibrosis (PMF)
      1. In the late phases the target is also the bone -> osteomyelosclerosis
2. The first thing to do is to reduce leukocytosis
  1. Hyperhydrating the patient and giving him hydroxyurea
CML
1. High sensitivity to the alloreactivity of the allogenase transplant
2. Response to therapy
  1. Hematologic data
  2. Cytogenetics
    1. With FISH you have greater number of cells to analyze because you don't need to have the cells replicating, so it is more sensitive than cytogenetics
    2. qRT-PCR is even more sensitive
    3. Cytogenetic response translates into a prognostic value
  3. With molecular response criteria you have an earlier chance of identifying patients who have the best response to the treatment you are giving
  4. Major molecular response
    1. 3Log reduction in the qRT-PCR
  5. Complete molecular response
    1. >4.5Log reduction from the IRIS baseline
Primary myelofibrosis
1. Risk factors associated with PMF
  1. Age >65 years
  2. Constitutional symptoms
  3. Circulating blasts (>1% in peripheral blood)
  4. Hb <10 g/L
  5. WBC > 25x10^9/L: leukocytosis
2. Prognosis after risk score calculation
  1. Low risk: median survival of 135 months
  2. Intermediate (1): median survival of 95 months
  3. Intermediate (2): median survival of 48 months
  4. High (>3): median survival of 27 months
3. Therapy
  1. Transplant
  2. Targeted therapy
    1. Inhibitors of JAK2 mutation
      1. Ruxolitinib
        Excellent patient survival and outcome compared to historical controls
  3. Other therapies
    1. Erythropoietin or Danazol stimulate erythrocyte production
    2. Hydroxyurea and splenectomy to reduce the burden of the extra medullary hematopoiesis
    3. Prednisone can be used to reduce symptoms
      1. Most of them are related to the disease-cells production of cytokines
4. Clinical features
  1. Splenomegaly
  2. Fever and some fibrosis in the bones
    1. Cytokines that induce fibrogenesis in the bone marrow
Bone marrow biopsy
1. Indications
  1. Staging of lymphoproliferative disorders
  2. Diagnosis of some lymphoproliferative disorders
    1. Only hairy cell leukemia and lymphoblastic lymphomas
  3. Suspicious metastatic involvement
  4. Chronic myeloproliferative disorders
  5. Aplastic anemia
  6. Myelodysplastic syndromes
  7. Fever of unknown origin
  8. Inadequate BM aspiration
  9. Plasma cell dyscrasia
  10. Acute leukemia
  11. Amyloidosis
  12. Bone disease
Imatinib
1. Tyrosine-kinase inhibitor
2. At 12 months from the beginning of the therapy we cannot have Philadelphia chromosome
3. Second generation TKIs
  1. Nilotinib, Dasatinib, Bosutinib, Panatinib
    1. Nilotinib is faster, more effective and gives you a greater chance of survival earlier in the treatment
  2. They would be normally used before a bone marrow transplant
4. Resistance mechanisms to Imatinib
  1. Patient compliance
  2. Absorption
  3. "Pure" resistance
    1. New mutations of the Bcr-Abl gene
  4. If patient after a year of treatment shows no progression, then the patient is a strong candidate for a BMT
Lymphomas
1. Diffuse large B-cell lymphoma
Fever of unknown origin is an indication for bone marrow biopsy
Myelodisplastic syndromes
1. Bone marrow aspiration is superior to biopsy

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CML, myeloproliferative disorders and bone marrow biopsy

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