Leukemia and Lymphoma Lecture I

True or false: Risk factors for AML - high amounts of radiation exposure can increase the risk of AML

True

True or false: Risk factors for AML - the risk is highest about 3-5 years after chemotherapy

True

a phrase used to note that there are a high number of young, immature white blood cells present

"Left Shift"

What are the four classifications of leukemia?

1. Acute Myeloid / Granulocytic Leukemia / Acute Non-lymphocytic Leukemia 2. Acute Lymphoid / Lymphocytic Leukemia 3. Chronic Myeloid Leukemia or Chronic Granulocytic Leukemia 4. Chronic Lymphoid/lymphocytic Leukemia

What are the three basic treatment choices for post remission therapy?

1. Additional chemo 2. Stem cell transplant from a healthy donor (allogenic) 3. Stem cell transplant using the patients own stem cells (autologous)

What is the criteria for remission for Acute Leukemia?

1. Less then 5% blasts in bone marrow 2. normal peripheral blood counts/smears 3. Absence of abnormal physical findings

ALL phases of treatment:

1. Remission induction 2. CNS prophylaxis/sterilization 3. Intensification Therapy 4. Maintenance Therapy

What are the two phases of Acute leukemia treatment?

1. Remission induction 2. Post Remission

How many weeks does the BM need to recover?

2-3 weeks

How long does consolidation therapy for ALL last?

4-8 months

What is the minimum number of HLA markers that must be present for a successful match?

6

What is the median age of diagnosis for AML?

65 years old and the incidence increases w/ age

ALL Remission induction chemotherapy:

90% remission; aggressive chemo

True or false: Signs and symptoms of AML are caused by the replacement of normal blood cells w/ leukemic cells and include fever, fatigue, weight loss and FREQUENT INFECTIONS and SWELLING OF THE GUMS

True

The ASBMT considers that in patients w/ AML:

AGE <55 allogenic Hematopoietic stem cell transplant offers no survival advantage for those w/ low risk cytogenics who are in the first clinical remission. IT does offer a survival advantage vs chemo for those with high risk cytogenics

What is the most common childhood malignancy?

ALL

Auer rod on smear is pathognomonic of:

AML

Auer rods are indicative of?

AML

The 7+3 chemotherapy protocol (one drug is given as a continuous IV infusion for seven days in a row while the second drug is given for three days in a row after that) refers to which disease?

AML

What is the most common leukemia in adults?

AML

What is the most common type of acute leukemia?

AML

What leukemia has the presence of Auer rods?

AML

What is the hallmark of AML w/ labs?

Abnormal CBC is the hallmark

Proliferation of immature myeloid or lymphoid cells following transformation of the hematopoietic or lymphoid progenitor clone -ALTERATION OF DNA -ALL AND AML DIFFER IN THE NATURAL HISTORY, PROGNOSIS AND RESPONSE TO THERAPY

Acute Leukemia

Neoplasm of the myeloid line of development and causes a rapid production of precursors of the myeloid line that fail to develop into more mature cells; immature blasts occur int he bone marrow; production of these cells interferes with normal hematopoiesis, causing a decrease in the production of other cell lines such as red cells, platelets,etc.

Acute Myeloid Lymphoma

Post remission therapy:

Aimed at destroying the remaining leukemia cells and is crucial in decreasing the risk of relapse

True or false: The Philadelphia chromosome is the abnormal swap between chromosomes 9 and 22 which forms a new gene called BCR-ABL

True

Red staining, needle like bodies seen in the cytoplasm of myeloblasts; they result from abnormal fusion of the primary granules

Auer rods seen in AML

What target therapy uses the patient's immune system to fight the leukemia; the T cells are removed from the patient's blood and altered

Car T-Cell Therapy

Bone marrow Aspiration vs. Biopsy - used for cytologic assessment

BM Aspiration

Bone marrow Aspiration vs. Biopsy - evaluate the marrow for lesions, cellularity and possible infiltration by other pathologic entities

Biopsy

How is the response to induction therapy for ALL evaluated?

Bone marrow *also assess PCR for minimal residual disease

How do you CONFIRM Acute Leukemia?

Bone marrow aspiration —> BLASTS (left shift)

True or false: The intensification therapy is reduced for patients w/ a good prognosis while providing more intensive treatment for those in the high risk groups

True

How is leukemia classified?

Cell type - lymphoid vs myeloid Natural history - acute vs chronic

What is the first line treatment for AML?

Chemotherapy

What is the mainstay of treatment during the remission induction?

Chemotherapy -intense chemotherapy wipes out leukemia cells in the blood and bone marrow and produces a complete remission

What is the single most important prognostic factor in AML:

Cytogenics - certain cytogenic abnormalities are associated w/ a poor prognosis and a high risk of relapse after treatment

True or false: Trisomy 21 increases the risk for ALL by 15 fold

True

What is the treatment of tumor lysis syndrome?

IV fluids and allopurinol

Before referral for allogeneic transplantation, a suitable donor must be identified:

Ideally this person is a fully HLA - matched sibling.

Immune system has the ability to stop attacking normal cells by using checkpoints - molecules on the immune cells that need to be turned off or on to trigger an immune response. Cancer cells can use these checkpoints to avoid being attacked by the immune system; new drugs have been developed that target these checkpoint - what type of target therapy for AML is this?

Immune Checkpoint inhibitors

Leukemia Treatment Complications include:

Immunosuppression Tumor lysis syndrome

What are the two phases of therapy for AML?

Induction therapy and consolidation therapy

What is the standard of care for CNS prophylaxis?

Intrathecal chemotherapy

What is the FAB classification for ALL? (3 groups L1-L3)

L1 - kids L2-L3 - adults (L3 aggressive and poor prognosis)

Uncontrolled proliferation of hematopoietic stem cells in the bone marrow:

Leukemia

"Elevated blast count w/ decreased tissue perfusion"

Leukostasis

Very elevated blast count w/ symptoms of altered tissue perfusion -plugs of white cells block microvasculature -Dyspnea, hypoxia, visual changes, headahces

Leukostasis

What is a common sign and symptom of Acute Leukemia?

Leukostasis —> an extremely elevated blast cell count and symptoms of decreased tissue perfusion.

Common symptoms of ALL:

Malaise Fatigue Lymphadenopathy Splenomegaly

This type of targeted therapy for AML is usually given by infusion to carry drugs, toxins or radioactive material directly to targeted cancer cells; antibodies attach to the substances and kill the cancer cells

Monoclonal antibody

Intermediate risk cytogenics w/ AML - post remission therapy

Most AML is intermediate risk disease These patients have normal cytogenics or cytogenic changes not falling into good risk or high risk - this is the most difficult group to decide treatment The best treatment is not clear for this group but depends on many factors and the availability of a suitable stem cell donor

What population is ALL found in?

Mostly children

stem cell transplant uses high doses of chemotherapy and may use radiation therapy to destroy cancer cells. In this process, bone marrow/stem cells are also destroyed. Patients receive an infusion of new stem cells to rebuild blood and the immune system.

Myeloablative conditioning

Does remission mean that the disease is cured?

No - signifies that no disease can be detected with available diagnostic methods

What is the treatment for relapsed AML?

Only proven potentially curative therapy is stem cell transplant. Treatment option for relapsed AML are limited, so patients may be offered palliative care or enrollment in a clinical trial

a condition that occurs when a person has low counts for all three types of blood cells: red blood cells, white blood cells, and platelets

Pancytopenia

Good risk cytogenics for AML - post remission therapy

People w/ favorable risk disease are usually advised to continue w/ chemotherapy

Unfavorable/high risk cytogenics w/ AML - post remission therapy

People with unfavorable risk disease are usually advised to have an allogenic stem cell transplant

True or false: W/ ALL, the induction therapy given differs depending upon whether the Philadelphia chromosome is present

True

True or false: all remissions will fail w/o addition consolidation/post remission therapy

True

What is considered if induction chemotherapy fails for AML or the patient relapses?

Stem cell transplantation

Targeted therapy for ALL:

TKI's - 25% of adults w/ ALL have the Philadelphia Chromosome

Treatment that uses drugs to identify and attack specific cancer cells without harming normal cells:

Targeted therapy

Remission maintenance therapy is a standard part of ALL treatment in children and may continue for two to three years. Includes a combination of oral medications multiple times per month coupled w/ intravenous chemo.

True

True or False: With ALL, the Philadelphia chromosome is found in 1/3 of adults

True

True or false - During recovery of BM, patients may need blood and platelet transfusions A

True

a condition that occurs when a large number of cancer cells die within a short period, releasing their contents in to the blood.

Tumor lysis syndrome

True or false: ALL patients may undergo allogeneic transplantation. Prior to transplantation the patient is given high doses of chemotherapy or total body irradiation (myeloablative conditioning). Cancer cells are destroyed but all normal bone marrow cells are destroyed w/ them. The transplanted cells re-establish the blood cell production process in the bone marrow

True

True or false: Acute leukemia is related to the increased production of malignant cells coupled w/ the decreased production of mature cell lines

True

True or false: Before the use of preventative CNS therapy, up to 80% of all children w/ ALL who were in complete bone marrow remission relapsed w/ leukemic meningitis

True

True or false: End of induction and end of consolidation bone marrow MRD strongly correlate w/ survival

True

True or false: Philadelphia Chromosome translocation is uncommon in children, but if the translocation is present. TKIs (tyrosine kinase inhibitors) are added that target the protein that is always turned on

True

Induction therapy goal:

To achieve a complete remission by reducing the number of leukemic cells to an indetectable level

Consolidation therapy goal:

To eliminate any residual undetectable disease and achieve a cure

Rapid leukemic cell lysis after chemotherapy causes an over excretion of what?

Uric acid —> precipitates in the renal tubules and can lead to oliguric or anuric renal failure

Can a PCR test be useful in determining how completely the treatment has destroyed the AML cells?

Yes

Is leukostasis a medical emergency?

Yes - NEED TO REDUCE WHITE BLOOD CELL COUNTS