Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The disease that we will be learning about today is:

Acute Promyelocytic Leukemia

What is Acute Promyelocytic Leukemia?

• Acute promyelocytic leukemia is a rare subtype of acute myeloid leukemia (AML)
  • These are cancers that affect the white blood cells
• Acute promyelocytic leukemia (abbreviated as either APL or APML) is distinguished by two different factors:
  • The presence of a chromosomal translocation affecting retinoic acid receptor alpha (RARα or RARA)
  • Its responsiveness to all-trans retinoic acid (tretinoin) therapy
• In this leukemia, immature granulocytes, called promyelocytes, accumulate in abnormal numbers
• First described by Norwegian and French physicians in 1957, it was identified as a hyperacute illness with median survival time of under a week.
  • Today, survival rates are much better

How Do You Get It?

• The chromosomal translocation is a key factor in the origins of acute promyelocytic leukemia
• Involvement of the RARA gene on chromosome 17 in a reciprocal translocation with the promyelocytic leukemia (PML) gene on chromosome 15 is found in 95 percent of cases.
• There are also eight other much rarer gene arrangements that have been linked to APL
  • These sometimes involve the fusion of RARA and PML, which results in the expression of a hybrid protein with abnormal functions

What Are The Symptoms?

• In general, the symptoms of acute promyelocytic leukemia are similar to standard acute myeloid leukemia and can include:
  • Anemia
  • Coagulopathy
  • Chills
  • Breathing problems
  • Neutropenia
    • This greatly increases the risk of infection
  • Fatigue
  • Bicytopenia
  • Weakness
  • Elevated white blood cell count
  • Low platelets
    • This results in increased risk of bleeding
    • Bleeding from the brain, nose, gums is common
    • Patients often bruise easily
    • Menstrual bleeding also increases

How Is It Treated?

• A critical characteristic of acute promyelocytic leukemia is that it is sensitive to all-trans retinoic acid (ATRA), or tretinoin. This is the acid form of vitamin A.
  • This treatment is administered as a form of chemotherapy, but unlike other chemotherapies, the cancer cells are not killed directly.
  • Instead, this treatment causes the cancerous promyelocytes to terminally differentiate
  • While this treatment can induce a brief remission on its own, long term benefits requires the use of another, more traditional chemotherapy in combination.
• Arsenic trioxide has become the chemo of choice to use alongside ATRA.
• Around 90 percent of patients see remission with this treatment.
  • This therapy is associated with a unique set of side effects called differentiation syndrome. Symptoms include:
    • Peripheral edema
    • Shortness of breath
    • Weight gain
    • Fever
    • These side effects can be treated with dexamethasone
• Another treatment that has been used successfully in acute promyelocytic leukemia is the monoclonal antibody gemtuzumab ozogamicin.
• After patients see a successful remission with these treatments, two years of maintenance therapy is often used with a combination of mercaptopurine, methotrexate, and ATRA.
• In cases of relapse, arsenic trioxide is being investigated and has shown some effectiveness in induced remission.
• Other investigational approaches include histone deacetylase inhibitors
• Prognosis for patients is generally good; one study suggests a ten year survival rate of 80-90 percent.

Where Can I Learn More???

• Check out our cornerstone on this disease here.
• Learn more about this condition from the Leukemia & Lymphoma Society.