Leukaemia

Notes
  • Hematopoietic stem cells (hemocytoblasts) give rise to the common myeloid progenitor cells and common lymphoid progenitor cells.
  • The common myeloid progenitor cells give rise to megakaryocytes, erythrocytes, mast calls and myeloblasts.Megakaryocytes disintegrate into thrombocyte (platelets) while myeloblasts give rise to monocytes, neutrophils, basophils and eosinophils. Monocytes give rise to macrophages.
  • The common lymphoid progenitor cells give rise to lymphoid cells that include small lymphocytes (T lymphocytes and B lymphocytes) and and large granular cells (the Natural killer cells). The B lymphocytes in turn produce plasma cells.
  • The above process of haematopoiesis occurs in the red bone marrow.
  • Leukaemia is divided into;

Acute Lymphocytic Leukaemia (ALL)

Acute Myelogenous Leukaemia (AML)

Chronic Lymphocytic Leukaemia (CLL)

Chronic Myelogenous Leukaemia (CML)

  • In acute leukemia, blasts remain immature fail to carry out their normal functions. Generally, the number of blasts increases quickly, and the disease gets worse fast.
  • In chronic leukemia, blast cells are more mature and the disease gets worse gradually.
  • ALL is the most common type of leukemia in young children.
  • AML occurs in both adults and children
  • CLL most often affects adults over the age of 55.
  • CML occurs mainly in adults.It is characterized by the Philadelphia (Ph) chromosome and/or the BCR/ABL fusion gene from translocation of the ABL gene from chromosome 9 to 22 (9;22) 9934; 911).
  • CML has 3 phases: Stable, Accelerated and Blast crisis.
  • Myeloblasts are found in AML but a special group of AML known as acute promyelocetic leukaemia (APML or ) presentsa with both myeloblasts and promyelocytes.
  •  
  • Leukemia and Lymphoma although both are the result of a malignant transformation of a cell destined to be a lymphocyte in Lymphoma the disease starts from a lymphocytic cell in a lymph node or other part of the Lymphatic System while in Leukemia the disease starts from a lymphocytic cell in Bone marrow.
  • Statistics: incidence of ALL (the most common type of leukemia) in Western nations- 42/1000 000/year.
Symptoms
  • Anemia
  • Chest pain
  • Easy bruising (purpura) and bleeding
  • Fatigue
  • Fever and night sweats
  • Granulocytopenia that often lead to recurrent infections
  • Malaise
  • Pallor
  • Tachycardia
  • Weight loss
  • Petechiae
  • Epistaxis
  • Bleeding gums
  • Menstrual irregularity
  • Joint and bone pains (advanced stage)
  • Gum hypertrophy
  • Lymphadenopathy (ALL and CLL)
  • Splenomegaly (more common in AML and CML)
  • Hepatomegaly
Diagnosis
  • Bone Marrow Aspirate
  • Trephine (with cytochemistry and immunophenotyping)
  • Full Blood Count (FBC) with differential count and peripheral blood film examination
  • Flow cytometry/ immunophenotyping and cytogenetics/molecular studies
  • Quantitative BCR-ABL assay using PCR for CML.
  • Other recommended tests:

HIV

HBV

HCV

Chest X-Ray

Abdominal ultrasound/CT Scan

ECG

LFTs

Serum creatine

Differential
  • B-Cell Lymphoma
  • High-Grade Malignant Immunoblastic Lymphoma
  • Mantle Cell Lymphoma
  • Non-Hodgkin Lymphoma
  • Anemia
  • Primary Myelofibrosis
  • Bone Marrow Failure
Management
  • ALL in children is in most cases curable if it is treated well while ALL in adults as well AML show poor prognosis.
  • Supportive treatment of leukemia include:

Transfusion of blood or their components

Antibiotic chemotherapy or prophylaxis

orrection of electrolyte imbalance

Prevention and management of tumour lysis syndrome

  • Treatment of leukemia occurs 3 phases:

 

Induction (or remission induction)

_The goal for this treatment is remmision where, although cure is not guaranteed, the tumour cells are not detectable.

_Drugs that are commonly used include: vincristine, steroids (dexamethasone or prednisone) and anthracyclines (doxorubicin or daunorubicin).

_In case of Philadelphia chromosome positive test, Bcr-Abl tyrosine-kinase inhibitors such as imatinib and nilotinib added.

_Depending on the response of the above treatment,  the following may be added: cyclophosphamide, L-asparaginase, etoposide, methotrexate or cytarabine.

_For CNS leukemia, the following drugs are used for treatment or prophylaxis: either intrathecal methotrexate or cytarabine or prednisolone and /or radiotherapy of the brain or spinal cord.

 

Consolidation (intensification)

_Continuation of treatment

_Stem cell transplant may be recommended

 

Maintenance (for about 2 years)

_Methotrexate and;

_6-mercaptopurine (6-MP)

_Vincristine and prednisone (in some cases)

_Bcr-Abl tyrosine-kinase inhibitors such as imatinib and nilotinib in case of Philadelphia chromosome positive test.

 

  • The goal of treatment is to achieve;

A complete cytogenetic response (Philadelphia negative bone marrow metaphases or more than 2 log reduction in BCR/ ABL transcripts).

A major molecular response (> 3 log reduction in BCR/ABL transcripts

  • Specific treatment include the following:

 

Type of Acute Leukemia

Treatment

AML (a part from APML)

♦Cytarabine

♦Daunorubicin (or any other anthracyclines)

♦Prednisolone

APML

♦All trans retinoic acid ♦Daunorubicin (or any other anthracyclines)

♦Arsenic trioxide (in case it relapses)

♦Prednisolone

ALL

♦Cytarabine

♦Daunorubicin (or any other anthracyclines)

♦Radiation therapy for CNS prophylaxis

♦Prednisolone

CML (a par  from blast crisis)

♦Bcr-Abl tyrosine-kinase inhibitors such as imatinib and nilotinib

♦Allogeneic bone marrow transplant

CML (withblast crisis)

As per ALL

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