Assignment #1: Types, Staging, and treatment of  Acute lymphoblastic leukemia 

sub-Types:

• • B-cell acute lymphoblastic leukemia/lymphoma: This subtype begins in immature cells that would normally develop into B-cell lymphocytes. This is the most common ALL subtype. Among children, B-cell lineage ALL constitutes approximately 88 percent of cases. Among adults, B-cell lineage represents 75 percent of cases.
  • T-cell acute lymphoblastic leukemia: This subtype of ALL originates in immature cells that would normally develop into T-cell lymphocytes. This subtype is less common, and it occurs more often in adults than in children. Among adults, T-cell lineage represents about 25 percent of cases. Among children, T-cell lineage represents approximately 12 percent of cases.

  • Mature B-Cell Acute Lymphoblastic Leukemia (Burkitt-Type)

  • Philadelphia chromosome positive (BCR-ABL fusion) ALL[ chromosomes 9 and 22]

 

 

Staging 

ALL will likely spread to other organs before it is detected, therefore it does not use the traditional staging method based on the spread.  Physicians often factor in the subtype of ALL and the patient’s age to determine the stage. 

Different stage of the disease 

Untreated: Untreated ALL means that the leukemia is newly diagnosed. more than 25% of the cells in the bone marrow are immature white blood cells 

Remission 

• Partial Remission: less than 25% of the cells in the bone marrow are blast cells.
• Complete Remission: less than 5% of the cells in the bone marrow are blast cells.there are no general signs or symptoms of ALL. RBC is normal 

Relapsed: leukemia has come back after treatment and reaching remission.25% of the cells in the bone marrow are blast cells.

Refractory: leukemia did not respond to treatment

 

Treatment:

 First Stabilize the patient:

Most patients with B-cell and T-cell ALL are diagnosed with Hyperuricemia and hyperphosphatemia with secondary hypocalcemia  before even initiating chemotherapy so first it is necessary to stabilize the patient. 

• Hyperuricemia= allopurinol or rasburicase 
• Hyperphosphatemia= aluminum hydroxide, calcium carbonate
• Thrombocytopenia- platelet transfusion
• Fever and granulocytopenia- blood culture and broad spectrum antibiotics
• extreme leukocytosis (leukocyte count >400 × 109/L)- Leukapheresis or exchange transfusion (in small children) can be used to reduce the burden of leukemic cells

 

Precursor B-Cell and T-Cell Acute Lymphoblastic Leukemia Treatment 

Chemotherapy: is the primary induction treatment for ALL

• [first line to cure] Induction= prednisone + vincristine + daunorubicin
• [once remission is achived]Consolidation= high dose Methotrexate
• Maintenance= low dose Methotrexate [Some subtypes of ALL, such as T-cell ALL and Burkitt type leukemia (mature B-cell ALL), may not need maintenance treatment]
• Prophylaxis for CNS = Intrathecal Methotrexate or cranial radiation
• Prophylaxis for Testes= radiation or Chemotherapy
• Bone marrow transplant is the last resort

 Mature B-Cell Acute Lymphoblastic Leukemia (Burkitt-Type)

The most effective treatment regimens for mature B-cell (Burkitt-type) ALL are drug combinations that include cyclophosphamide and/or ifosfamide given over a relatively short time (3 to 6 months).high-dose cyclophosphamide, high-dose methotrexate, vincristine, doxorubicin, and conventional doses of cytarabine. 

Philadelphia chromosome positive (BCR-ABL fusion) ALL

Tyrosine Kinase Inhibitor = Imatinib

 A stem cell transplant may be offered to people with ALL while they are in remission. It is also used following relapse if a complete or partial remission can be reached.

 

Side Effects  

Chemotherapy can lead to Tumor lysis syndrome= elevated potassium, uric acid (acute kidney injury) and phosphate. 

• Prevent tumor lysis syndrome: hydrate and allopurinol
• Direct Testicular Radiation leads to permanently low testosterone so infertility
• Intrathecal methotrexate= acute leukoencephalopathy
• Cranial radiation= neurocognitive dysfunction
• All the chemotherapy agents cause Liver toxicity

Supportive Therapy 

• antibiotics, antivirals or antifungals to prevent or fight infections
•  indwelling catheters
• amelioration of nausea and vomiting, pain control
• continuous psychosocial support for the patient and family

 

Sources:

Candian Cancer Society 

Leukemia and Lymphoma Society 

American Society of Clinical Oncology