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