Acute leukemia - Biology, clinical features and therapy- Goorha Flashcards Preview

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Flashcards in Acute leukemia - Biology, clinical features and therapy- Goorha Deck (41):

Chronic infection or inflammation (growth factor dependent), paraneoplastic syndromes (eg Hodgkin lymphoma; growth factor dependent), myeloproliferative disorders (eg chronic myeloid leukemia; growth factor independent) would cause what mechanism of leukocytosis?

Increased production of WBCs in the bone marrow


Endotoxemia, infection, and hypoxia would cause what mechanism of leukocytosis?

Increased release from the marrow stores


Exercise and catecholamines would cause what mechanism of leukocytosis?

Decreased margination (more cells to pick up in peripheral blood draw)


Clucocorticoids would cause what mechanism of leukocytosis?

decreased extravasation into tissues


Follicular hyperplasia is caused by stimuli that activate:

humoral immune responses.


What cells are found in the mantle zone of 2ndary lymphoid follicles?

Mantle cells (small, resting naive B cells)


What are centroblasts?

darker staining cells within the germinal center that are blastlike, proliferating B cells.


What are centrocytes?

make up a lighter zone of the germinal center. Composed of B cells with irregular or cleaved nuclei contours.


What causes paracortical hyperplasia?

stimuli that trigger T cell mediated immune responses, such as acute viral infections.


What is sinus histiocytosis?

refers to an increase in the number and size of the cells that line lymphatic sinusoids. Although non-specific, this form of hyperplasia may be particularly prominent in lymph nodes draining cancers such as carcinoma of the breast. The lining lymphatic endothelial cells are markedly hypertrophied and macrophages are greatly increased in numbers, resulting in the expansion and distention of the sinuses.


These causes would lead to leukocytosis of this mature cell type:
Acute bact'l infections, especially those caused by pyogenic orgs.; sterile inflammation caused by, for ex: tissue necrosis (MI, burns)

neutrophilic leukocytosis (neutrophilia)


These causes would lead to leukocytosis of this mature cell type:
Allergic disorders such as asthma, hay fever, parasitic infestations; drug rxns; certain malignancies (eg: Hodgkin lyph, and some NH lymphomas); autoimmune disorders (eg: pemphigus vulgaris, dermatitis herpetiformis) and some vasculitides; atheroembolic disease (transient)

Eosinophilic leukocytosis (eosinophilia)


These causes would lead to leukocytosis of this mature cell type:
Rare, often indicative of a myeloproliferative disease (eg: CML)

Basophilic leukocytosis (basophilia)


These causes would lead to leukocytosis of this mature cell type:
Chronic infections (eg: TB), bacterial endocarditis, rickettsiosis, and malaria; autoimmune disorders (eg: SLE); inflammatory bowel diseases (eg: ulcerative colitis)



These causes would lead to leukocytosis of this mature cell type:
Accompanies monocytosis in many disorders associated with chronic immunologic stimulation (eg: TB, brucellosis); viral infections (eg: Hep A, CMV, EBV); Bordetella pertussis infection



Which is NOT a common symptom of acute leukemia?
Nose bleeding
Hearing loss

Hearing loss is NOT a symptom of leukemia unless cancer invades the ear drum. (uncommon)

Fever- leukemia may directly stimulate fever or immunosuppression can lead to infection.
Nose bleeding- anemia
Rash- cutaneous involvement of leukemia


T/F: acute myeloid leukemia and acute lymphoid leukemia can be easily differentiated by review of the peripheral blood smear.

False. Although auer rods are a hallmark of myeloid leukemia blasts, they are not seen in nearly all the blasts present in a smear and thus are not ideal for differentiating the two leukemias. Peripheral blood flow cytometry studies (immunophenotyping) will differentiate the two definitively.


Why do leukemias cause morbidity and mortality?

Bone marrow failure, neutropenia, thrombocytopenia
Infiltration of orgens: liver, spleen, lymph nodes, meninges, brain, skin, or testes.


Which carries greater risk of CNS involvement:



Which is more difficult to treat, primary AML (de novo) or secondary AML (develops from MDS or other hematological malignancies) [more common as people age]?



Which of the following are major causes of acute myeloid leukemia?
1- Smoking
2- Chemotherapy
3- Pre-existing hematological disorder such as myelodysplastic syndrome
All of the above
2 & 3

2 & 3


What comprises the vast majority of etiologies of acute leukemia?



Are acute leukemias usually considered medical emergencies requiring immediate treatment? Why or why not?

Yes. They are very rapidly proliferating and the sooner you catch them, the better the chances of survival.


Malignant transformation of acute leukemia occurs in these cells (stage of maturation):

hematopoietic stem cells or early progenitors


List the immunological markers (antigens) present on AML and ALL cells that are used in their differentiation.

Myeloid: MPO, CD33, CD13, HLA-DR
Lymphoid: TdT, CD10, CD19, CD20


Acute promyelocytic leukemia (APL M3) is associated with what cytogenetic finding?



Explain how PML-RAR causes cancer.

PML-RAR homodimerization acts as a corepressor binding and repressing genes that signal for differentiation of immature myeloid line cells (no differentiation = bad)
They also activate a self-renewal program that results in uncontrolled proliferation.


Explain how all-trans retinoic acid and arsenic help fight cancer caused by a PML-RAR translocation. Why is this better then cytotoxic chemotherapy as a treatment?

Both remove the abnormal protein product of PML-RAR fuson from the DNA, allowing for differentiation.
Also results in reduction in leukemia initiating stem cells.
Cytotoxic chemo kills all rapidly proliferating cells. ATRA and arsenic can specifically target the genetic mutation product of PML and only alter the PML cells.


Pt's immunophenotyping of suspected leukemia cell is positive for CD13, CD33, CD34, CD7, CD117 and myeloperoxidase and is
Negative for CD2, CD3, CD19, CD10, TdT.
DO you suspect myeloid or lymohoid involvement?



Pt has AML FAB M2 on morphology with t(8;21) and missing Y chr. Molecular analysis showed no evidence of c. kit mutation. What risk group is this pt's AML?

Better risk.


c kit mutation in AML. Good, intermediate, bad prognosis?



FLT3 mutation in AML. Good, intermediate, bad prognosis?

Bad prognosis


Generally, in pts with better risk subtypes of AML, is chemotherapy alone sufficient treatment?

Yes, pts with better risk category AML tend to respond well to chemo alone. Higher risk procedures such as stem cell transplantation are reserved for pts with higher risk category AMLs such as those with FLT3 mutations.


What is remission induction therapy?

1 to 2 courses of intensive therapy to achieve complete response (absence of detectible leukemia cells)


What is post-remission therapy? Is it always done, regardless of whether we can "see" cancer in the body?

consolidation therapy: 3 to 4 courses of intensive short-course therapy to further reduce the subclinical body burden of tumor.
Always done. Just because you cannot find the cancer, does not mean it is not there.


What is maintenance chemotherapy with regards to treating AML?

months to years of less intensive therapy to further prevent recurrence


Which ALL pt has the worst prognosis?
A) An 8 yo with ALL with E2a-PBX t(1;19)
B) A 21yo with T-ALL and normal cytogenetics
C) A 16yo with TEL-AML1 t(12;21)
D) A 50 yo with BCR-ABL1 t(9;22)

D) for two reasons. Age is the 1st reason. The older you get, the worse you will do with cancer. Catch it young, and catch it fast. The second reason is that the t(9;22) adn BCR-ABL1 are associated with poor prognosis.
T-cell ALL and TEL-AML1 are good risk


In both adult and childhood ALL, the genetic abnormalities MLL-AF4 and BCR-ABL translocations are associated with poor/intermediate/good outcomes?



In childhood ALL, the genetic abnormalities of hyperdiploidy, E2A-PBX and TEL-AML are associated with a poor/intermediate/good outcome? In adults these abnormalities are rare.



How do you counter hyperuricemia from tumor cell breakdown?



What study gives you the best understanding of prognostic variables and thus better risk stratification?

Cytogenetics to see what genes are mutated/translocated