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Acute Myeloid Leukemias ​

AML (FAB Classification)
M0     Minimally differentiated AML
M1     AML without maturation
M2     AML with maturation
M3     Promyelocytic
M4     Myelomonocytic
M5     Monocytic
M6     Erythroleukemia
M7     Megakaryocytic leukemia
Pathology of AML
  1. AML blasts contain azurophilic granules  
  2. AML blast do not contain PAS positive material.
  3. Terminal deoxy transferase (TdT) is present in 95% cases.
    Auer rods are presents
The likelihood of entering complete remission & hence the prognosis is determined by the following factors: 
Age of Diagnosis:
  1. > 60 years has a poor prognosis
  2. Chronic intercurrent disease, acute medical problems with increasing age are associated with poor prognosis.
Chromosome findings:
  Prognosis Chromosome Findings  
  Good t (8 : 21), t (15 : 17), inv (16)  
  Moderate No cytogenetic abnormality  
  Poor Monosomy 5 and 7, Complex karyotype, Inv(3)  
Presenting Leucocyte count:
  1. A high presenting Leucocyte count is an independent prognostic factor
  2. Duration of CR is inversely related to presenting Leucocyte count
Among patients with hyperleukocytosis (>100,000mg) early central nervous system bleeding and pulmonary leukostasis and Late relapse contribute to poor outcome.
Prolonged symptomatic interval with cytopenia - Antecedent hematological disorder
  1. Poor prognosis is seen in patients with anemia, Leukopenia, thrombocytopenia for duration of more than 1 month before diagnosis.
  2. Poor prognosis is seen in patients with secondary Leukemias developing after treatment with cytotoxic agents / irradiation.
Other Prognostic features:
  1. F AB classification
  2. Characteristics of Leukemic cells: e.g. Auer Rods - poor prognosis
  3. Expression of MDRl Gene - poor prognosis
Cytogenic studies are most powerful prognostic factors
Good prognosis Moderately favorable prognosis Poor prognosis
- t (8:21)
- Inv (16) (p13, q22)
- t (15;17)
No cytogenic abnormality - Complex karyotype
- Monosomy 7 (-7)
- Monosomy 5
- Del 5q
- 3q rearrangement
- Inv.  (3)
- FLT3 internal tandem duplication
Clinical features
  1. Rarely patients may present with symptoms from a mass lesion located in the soft tissues, breast, uterus, ovary, cranial or spinal dura, gastrointestinal tract, lung, mediastinum, prostate, bone, or other organs. 
  2. The mass lesion represents a tumor of leukemic cells and is called a granulocytic sarcoma, or chloroma. 
  3. Typical AML may occur simultaneously, later, or not at all in these patients. 
  4. This rare presentation is more common in patients with t(8;21). 

CR = complete remission,  HSCT – Hemopoietic stem cell transplant
  1. Allogeneic BMT improves long – term remission to 50%
  2. Treatment of AML M3
  1. All trans retinoic acid (ATRA) is an oral drug specifically used in the treatment of AML M3. It cause retinoic acid syndrome characterized by fever, dyspnea, pulmonary infiltration, pleural and pericardial effusion.
  2. Arsenic trioxide – for refractory patients with retinoic acid.
Extra Edge: Treatment of the leukemia can result in pulmonary hemorrhage from lysis of blasts in the lung, called leukemic cell lysis pneumopathy.

Extra Edge:
Biphenotypic leukemias are leukemias that express features of more than one lineage. The patient in question has a rare leukemia that expresses both, myeloid antigens (CD 3 and CD 13) and lymphoid antigens of B cell lineage (CD 10 and C 19) and hence can be described as a Biphenotypic leukemia.

Hyperleukocytosis and Leukostasis (Independent poor prognostic factor in acute leukemia)
  1. Hyperleukocytosis is a condition in which patients with acute leukemia present with an extraordinary high leukocyte count usually greater than 100,000.
  2. The high number of circulating blasts increase the blood viscosity and predispose to the development of Leukostasis.
  3. Leukostasis refers to sludging of leukemia blasts in the microcirculation leading to obstruction of small vessels especially in the cerebral and pulmonary circulations.
  4. Once identified leukostasis requires immediate and effective treatment to lower the blast count rapidly.
  5. Immediate treatment of Hyperleukocytosis is leuko cytoreduction which is generally achieved by Leukapheresis or administration of Hydroxyurea.
  6. Immediate Administration of induction chemotherapy to a patient with hyperleukocytosis carries a high risk of Acute tumor lysis syndrome and hence induction chemotherapy is often not initiated immediately but generally follows attempts at cytoreduction.
  7. IV hydration. Allopurinol and alkalinization of urine are measures to reduce the metabolic complications of tumor lysis syndrome and are indicated as preventive measures in patients with Leukostasis and hyperleukocytosis.

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