CM III - Acute & Chronic Leukemia

What is the supportive therapy initiated prior to tx for ALL?

tumor lysis prophylaxis •IVF's •Allopurinol Tumor lysis prophylaxis •Phoslo Neutropenic abx, antiviral, PCP, antifungal +/- transfusion during tx •Hgb < 7 •PLT < 10,000

Describe the pathophys of CLL?

•Acquired mutation of lymphoid precursor stem cell. --> over proliferation of impaired B -cells stuck in maturation sequence between pre-B cells and mature B-cells in the bone marrow. Results in: suppression of normal blood cell production and infiltration of lymph nodes, spleen and liver

What is a unique s.s of APL?

•Coagulopathy- BLEEDING and CLOTTING --> DIC due to hyperfibrinolysis and depletion of clotting factors

What additional test are done on bone marrow sample to assist w/ risk stratification and prognosis of AML?

•Cytogenetic analysis: blood or bone marrow done to look for certain changes in the chromosomes. •Immunophenotyping / Flow cytometry: A process used to identify cells, based on the types of antigens on the surface of the cell •Molecular Diagnostics: Testing for specific mutations at the DNA level through polymerase chain reaction testing( PCR)

Prior to starting tx for ALL what is required?

•ECHO-> assess EF prior to chemotherapy •Placement of a central venous catheter

What are the s.s of CML?

•Fatigue- most common •Fever •Weight loss •Night sweats Abdominal fullness & early satiety --> splenomegaly (MPF also has splenomegaly/early satiety as hallmark)

What is a neutropenic fever? Is it an oncologic emergency?

•Fever > 38.0*C ( 100.4 *F) > 1*hr. or fever x1 38.3 ( 101.0 *F) or greater •ANC < 1500/mcl broad spec abx + pancultures --MUST

In HIGH risk or certain Intermediate risk situations when tx'ing CLL what is the gold standard?

•Fludarabine or Bendamustine based chemotherapy

What are the typical transfusion parameters?

•Hgb < 7 •PLT < 10,000

What AML classification system is broken down into 8 subtypes?

•Historical classification FAB ( French American British) classification M0-M7 (used more commonly in practice still)

What lab elevations/decreases will be seen in tumor lysis syndrome?

•Hyperphosphatemia •Hyperuricemia •Hypocalcemia •Hyperkalemia PUCK

Prior to initiation of chemo for AML, what supportive therapies should be onboard?

•IVF's •Allopurinol Tumor lysis prophylaxis •Phoslo - dec phosphate levels prophylactic abx if neutropenic +/- transfusion (during chemo)

Describe the CNS prophylaxis that occurs in ALL therapy?

•If CNS is positive at diagnosis, then twice weekly lumbar punctures with intrathecal chemotherapy until spinal fluid is negative x2; then resume prophylaxis schedule received each chemo cycle

What additional labs should be conducted on the BM sample to assist in classification/tx plans/prognosis ?

•Immunophenotyping •Cytogenetics •Molecular studies

When is immunosuppression necessary following stem cell transplant?

•Immunosuppression therapy is required following a CORD or allogenic SCT to help prevent graft versus host disease (GVHD)

why would you order a BMP in a w.u for ALL?

•Including LDH, Uric Acid, Phosphate level-> Tumor lysis labs ( PUCK) •Hyperphosphatemia •Hyperuricemia •Hypocalcemia •Hyperkalemia

What intrathecal chemo is used to prophylaxis for CNS sx assoc with ALL?

•Methotrexate or Cytarabine +/- hydrocortisone for headache/N/V prevention

ALL s/s of BM dysfunction

•Neutropenia --> fever, recurrent infections •Anemia --> fatigue, weakness, DOE •Thrombocytopenia --> bleeding, petechial rashes •Bone pain --> marrow expansion •*Headache-CNS involvement

General principles of a stem cell transplant

•Pt must be in remission or have minimal residue disease prior to transplant •Pt will receive preparative chemotherapy prior to transplant; then "rescue" with infusion of stem cells •Stem cells can be collected from the donor or patient through peripheral blood collection or Bone Marrow Harvest •Immunosuppression therapy is required following a CORD or allogenic SCT to help prevent graft versus host disease (GVHD)

What is seen on PE in someone w. CML?

•Splenomegaly- most common •Hepatomegaly •Bruising •Lymphadenopathy- not as common in CML

What is the prognosis for APL?

•Survival and Cure rates are high >90% 5 yr survival

What is tumor lysis syndrome? Is it an oncologic emergency?

•The rapid destruction of tumor cells leads to a massive release of intracellular components, which subsequently damage the kidneys and may cause potentially life-threatening renal failure Yes

What is a common finding on CBC in CLL?

•Total WBC > 20K- differential demonstrates an isolated lymphocytosis anemia/thrombocytopenia in late stages

What is the best initial test for suspected AML and what would you see?

•WBC total maybe normal, elevated or decreased. •BLASTS in peripheral blood --> BLASTS stain positive for Myeloperoxidase (+) •Thrombocytopenia varying degrees •Anemia varying degrees

Stem cell transplant in AML is based on?

•risk group at time of dx • age < 60yr, •performance status •cytogenetic risks

What is the goal of consolidation or intensification therapy in ALL? How long does it last?

4-8 months --> Goal to maintain remission & eradicate residual disease combo of drugs used from induction

After remission does not occur after the initial induction tx for AML, what is the pt at risk for?

increases likelihood of prognostic factors affecting disease resistance and or higher relapse rates

Remission rates of AML decline with ______ age

increasing

What are the components of ALL tx?

induction - attain remission consolidation - 4-8 months, maintain remission maintenance - prevent relapse CNS prophylaxis - intrathecal chemo

What is the only known risk factor for CML?

ionizing radiation

•Neoplastic disease of the bone marrow characterized by UNREGULATED proliferation of a cell line describes?

leukemia

What will be seen on CBC in CML?

leukocytosis- WBC Mean -100,000 with a mild left shift from myeloblasts-> to mature granulocytes --> neutrophilia --> basophilia --> eosinophilia

What is the only proven cure for CML?

Allogenic stem cell transplant

What will be seen on peripheral blood smear in AML?

Blast with Auer Rods pathognomonic of AML (seen in M3 frequently) - not in ALL

What is the confirmatory test used for an AML workup? What will be seen?

Bone marrow aspirate and bone marrow biopsy > 20 % myeloid blasts in the bone marrow to make diagnosis --> BX will also look at other aspects of BM to further stratify risk/come up with tx plan

Besides sx of pancytopenia d/t bone marrow dysfunction, what is another bone marrow sx that is seen in AML? Why?

Bone pain Due to bone marrow expansion

APL has s/s of bleeding or clotting?

Both •Increased expression of a receptor for plasminogen and on the surface of leukemic promyelocytes= increased fibrinolysis

What is the best initial test for w/u of ALL?

CBC w/ peripheral smear

Cytogenetic analysis of a BM BX in someone w/ CML will show?

+ BCR/ABL gene-> translocation (9;22) --> AKA Philadelphia chromosome Burkitt's Lymphoma: 8;14 Follicular Lymphoma: 14;18 ALL Poor Risk- T(4:11) CML- 9;22- philly APL- 15;17 - M3

"What three things do i need you to know about APL (M3)?

1) ATRA + Chemo in 3 phases (ATRA in all of them) 2) They have high risk of bleeding (DIC) 3) best acute leukemia to have as cure rates are 90% and d/n require stem cell transplant

What are the two phases of tx for AML?

1. Induction chemotherapy-goal to achieve remission •Cytarabine + Anthracycline (standard " 7+3" ) •3-4 week hospital course --> pts will become neutropenic (abx) thrombocytopenic and anemic d/t treatment 2. Consolidation Chemotherapy- maintain remission & eradication micro disease •HIDAC-> high dose cytarabine

What is the goal of the maintenance phase of ALL tx? How long does it last?

2-3 years prevent relapse

Tx for APL is broken down into?

3 phases of tx induction, consolidation, maintenance

What drug therapies are used for ALL maintenance phasE?

6-mercaptopurine PO QD + methotrexate weekly + intrathecal chemotherapy

What WBC value at time of dx w/ AML increases prognostic risk factors?

> 100K

Meningeal infiltration, teste enlargement, splenomegaly and lymphadenopathy are all extramedullary sx of?

ALL

What is the MC type of cancer in children?

ALL

A thymic mass (mediastinal mass) is an extramedullary sx of?

ALL --> Tcell version

Headache/CNS involvement is more common in ALL or AML?

ALL --> able to pass BBB

PCP prophylaxis is used in ALL or AML? Why?

ALL --> because steroid use with intrathecal chemo reduces immune system and can result in PCP infection (bactrim)

what stain is used to see immature lymphoblasts in ALL? What about AML?

ALL: (TdT) Terminal deoxynucleotidyl transferase (+) AML: Myeloperoxidase

Blast with Auer Rods are pathognomonic for?

AML

What is the MC acute leukemia in adults?

AML

Standard 7+3 tx is common in what leukemia?

AML 1. Induction chemotherapy-goal to achieve remission •Cytarabine + Anthracycline (standard " 7+3" ) •3-4 week hospital course 2. Consolidation Chemotherapy- maintain remission & eradication micro disease •HIDAC-> high dose cytarabine

Gingival hyperplasia is a s/s of what leukemia?

AML --> in particular, the M5 subtype may also see as general extramedullary sx --> leukemia cutis, granulocytic sarcoma

are people with ALL or AML more at risk for leukostasis? (AMS, headache, SOB/dyspnea, micro occlusions, papriasm)

AML > ALL

ACUTE PROMYELOCYTIC LEUKEMIA ( M3) is treated how compared to other AML?

ATRA

In general, what is the tx for APL (M3) ?

ATRA + chemo in 3 phases ---> "i don't really need you to know all the info on this slide just know ATRA + Chemo in 3 phases"

Stage 0 CLL = ?

Abs lymphocyte > 5K

Stage 1 CLL = ?

Abs lymphocyte > 5K swollen lymph nodes

Stage 3 CLL = ?

Abs lymphocyte > 5K swollen lymph nodes splenomegaly anemia

Stage 4 CLL = ?

Abs lymphocyte > 5K swollen lymph nodes splenomegaly anemia thrombocytopenia

Stage 2 CLL = ?

Abs lymphocyte > 5K swollen lymph nodes splenomegaly/hepatomegaly

What are 4 basic types of leukemia?

Acute Myelocytic Leukemia ( AML) Chronic Myelocytic Leukemia ( CML) Acute Lymphocytic Leukemia ( ALL) Chronic Lymphocytic Leukemia ( CLL)

Which of the following is an appropriate treatment option for a patient diagnosed with CML ? •A. Fludarabine based chemotherapy •B. Induction chemotherapy with 7+3 •C. Imatinib •D. Atra + arsenic

Answer C Treatment for CML is a tyrosine kinase inhibitor the first developed was Imatinib ( Gleevec) since that time other tyrosine kinase inhibitors are also available such as Dasatinib ( Sprycel) which can also be utilized.

Clicker q What baseline test should be performed prior to starting chemotherapy particular with an Anthracyclines? A.ECHO B.CXR C.CT chest D.Brain MRI

Answer Is A: ECHO Anthracyclines can cause long term affects on the heart muscle resulting in cardiomyopathy

Clicker Q What steps should be taken to help to prevent Tumor lysis syndrome? A. Antibiotics, Antifungals and antivirals B. Aggressive IV fluids, allopurinol and phoslo C. Induction Chemotherapy D. Dexamethasone initiation

Answer is B Remember TLS typical most often occurs with induction chemotherapy as many of the blasts cells are destroyed and electrolytes and uric acid are spilling into circulation. P.U.C.K Hyperphosphatemia Hyperuricemia Hypocalcemia( due to binding with Phos) Hyperkalemia

A 66 y/o M presents to the clinic for his annual exam. He has no complaints other then some increased fatigue which he contributes to old age. His PMH consists of HTN, and hyperlipidemia, both are currently well controlled on his current regimens. His PE is unremarkable except for palpable cervical lymphadenopathy. Pt routine cbc demonstrates Hgb 11 HCT 33 WBC 36K and PLT 324. Peripheral smear demonstrate 96% small normal appearing lymphocytes. What is the most likely diagnosis? A. CML B. CLL C. AML D.ALL

Answer is B. Elderly male asymptomatic other then lymphadenopathy which was palpable in exam. Remember painless lyohadenopthy is common in CLL size may wax and wane but does not fully resolve. Another big clue here is the lab elevated WBC and peripheral smear is demonstrated an isolated lymphocytosis of small appearing lymphocytes. Based upon pt labs he has RAI stage 3 due to the development of his anemia

59-year-old healthy male complains of no symptoms, but on a routine CBC has a markedly increased white blood cell count of 50,000/mcl. A peripheral blood smear demonstrates leukocytosis with myeloid cells present at various stages of differentiation, with more mature cells present at a greater percentage than less mature cells. The cytogenetic analysis is positive for the Philadelphia chromosome. Based upon the information provided what is the most likely diagnosis? A.AML B.ALL C.CLL D.CML

Answer is D The clues: older male, asymptomatic with elevated WBC which demonstrates varying stages of mature myeloid cells, with more mature forms then immature forms. So we know ALL and CLL can not be the answer because we would see lymphocytes. It is also unlikely to have AML be the answer based upon more mature cells in circulation then immature blasts. What should seal the deal here is the Philadelphia chromosome abnormality which is seen in CML.

A 66y/o M presents to the clinic for his annual exam. He has no complaints other then some increased fatigue which he contributes to old age. His PMH consists of HTN, and hyperlipidemia, both are currently well controlled on his current regimens. His PE is unremarkable except for palpable cervical lymphadenopathy. Pt routine cbc demonstrates Hgb 11 HCT 33 WBC 36K and PLT 324. Peripheral smear demonstrate 96% small normal appearing lymphocytes. Based upon your suspected dx his current stage what is the best treatment option for this pt? A. 7+3 induction chemotherapy B. Atra + anthracycline C. Observation D. Fludarabine based chemotherapy

Answer is D. He likely has CLL Based upon pt labs he has Rai stage 3 due to the development of his anemia Treatment options include fludarabine or bendamustine based chemotherapy regimens If he was elderly with a poor performance status you could consider chlorambucil chemotherapy single agent it has less side effects. Another option would be tyrosine kinase inhibitor ibrutinib if they wanted to avoid chemotherapy.

52 year-old male is diagnosed with chronic myeloid leukemia (CML). Which of the following would you most commonly expect to find on the physical examination of this patient? A. Lymphadenopathy B. Spooning of the nail beds C. Jaundice D. Splenomegaly

Answer is D. In CML the most common PE exam finding is splenomegaly Spooning of the nail beds ( koilonychia is seen in sever iron def anemia) Jaundice can be seen in hemolytic anemias along with other liver pathologies and obstructive issue within the biliary system. Painless Lymphadenopathy can be seen in CML however it is much more common and often the 1st clinical exam finding in CLL.

Clicker Q The induction phase of treatment in Acute Promyelocytic leukemia is the standard "7+3" regimen. A.True B.False

Answer: B False APL treatment differs from standard 7+3 induction. APL treatment utilizes ATRA ( all trans- retinoic acid) 7+3 induction= 7 days of cytarabine and 3 days of an anthracycline

Clicker Q These spindle shaped particles in the Blast cell are commonly found in ALL A.True B.False

Answer: False theses are auer rods which are found in AML

What are the two general sub-types of ALL? What is more common?

B-Cell Acute Lymphoblastic Leukemia: • MORE COMMON T-Cell Acute Lymphoblastic Leukemia: •More common in teenagers •Overall poorer prognosis

What is the confirmatory test for ALL? What is seen?

BMBX •Demonstration of > 20 % bone marrow lymphoblasts

In addition to a CBC w. peripheral smear, what other labs should be ordered in a w.u of AML?

BMP, Uric Acid, Phos, LDH --> tumor lysis syndrome --> occurs w/ tx but also can occur due to the simple overproduction of cells Coagulation labs- INR, PT/PTT Fibrinogen --> DIC (APL in particular, aka M3)

Which leukemia D/N require BM BX for confirmation?

CLL

isolated lymphocytosis on CBC is common in what type of leukemia?

CLL

smudge cells are seen in?

CLL

What is the MC form of leukemia in adults? What adults specifically?

CLL (AML is MC form of acute leukemia and is thought of as an adult leukemia whereas CLL avg age dx is 70 and its more accurate to say older adults) •More common in Caucasian males - dx at 71 years

•Philadelphia chromosome ( T 9;22), forming the abnormal gene BCR/ABL describes?

CML Burkitt's Lymphoma: 8;14 Follicular Lymphoma: 14;18 ALL Poor Risk- T(4:11) CML- 9;22- philly APL- 15;17 - M3

What is CLL?

Chronic lymphocytic leukemia is a Clonal proliferation of incompetent maturing B lymphocytes

What occurs during the chronic phase of CML?

Chronic phase: mature cells proliferate along with mutated clone; normal bone marrow function intact. Pt may have nonspecific symptoms night sweats, fever and wt loss.

what are the two groups leukemias are classified into? How are they further classified?

Chronic: insidious onset, usually less aggressive cells are more mature forms. Acute: rapid onset, aggressive disease cells are poorly differentiated with immature BLASTS forms By the cell lineage --> Myelocytic or Lymphocytic

After a dx of AML has been made, what needs to occur prior to tx?

ECHO --> assess baseline EF prior to chemotherapy ---> Particularly anthracycline = cardiomyopathy •Central line Placement - PICC

Describe the pathophys of Acute Promyelocytic Leukemia (APL M3)?

Gene Mutation: Translocation (15;17) PML- RARA gene --> Arrest of leukocyte differentiation at the Promyelocyte stage --> excess promyelocytes

What are the extramedullary sx assoc w. AML?

Granulocytic sarcoma: Masses formed from immature blasts infiltration anywhere in body- such as the spleen (splenomegaly) Leukemia Cutis: blasts invading skin Gingival Hyperplasia: Common in M5 ( monocytic leukemia) Vs ALL: CNS- Meningeal infiltration Gonads-> testicular enlargement Spleen-> enlargement Lymphadenopathy

What is the now historical classification system used for AML? What was it based on? (although it's used more in practice)

Historical classification FAB ( French American British) classification M0-M7 (used more commonly in practice still) Based on: Morphology & basic staining

For those high risk/certain intermediate situation CLL pts who wish to avoid chemo, what is a potential therapy option?

Ibrutinib --> targeted tyrosine kinase inhibitor

What is the goal of induction in AML tx? What is the goal of consolidation tx in AML?

Induction: first remission --> if stop tx here it will come back consolidation: maintain remission/eradicate micro disease

What is the MC risk assoc w/ AML?

MDS -> most common risk another would be: Myeloproliferative disorder

ALL pts with ALL require? why is this done?

lumbar puncture ØHigh risk of CNS involvement esp. with relapse disease require prophylactic treatment of CNS

Blast that are myelo in nature stain + w/ what?

Myeloperoxidase

Why is AMS a rare (meaning it's not seen really) sx of AML and when could it possibly occur?

NOT a common presentation in AML as usually does NOT cross BBB --> may be more likely in a leukocytosis resulting in leukostasis in AML

What are potential complications assoc w. an acute leukemia?

Neutropenic fever= oncological emergency Leukostasis= oncological emergency (AML>ALL) Tumor Lysis Syndrome= oncological emergency

Most people w/ AML present w/ what risk factors?

No identifiable risk factors "de-novo"

Most pt w/ ALL present w. what risk factor?

None --> de novo (also AML)

What are the more generic sx assoc w. AML?

Pancytopenia •Pallor, tachycardia •Fever •Bleeding •Altered mental status, headache, cranial nerve palsies -RARE

What can confirm the dx of CLL? What are you looking for?

Peripheral blood flow cytometry •Looking for specific antigens on the B lymphocytes in peripheral circulation

Describe the pathophys of acute leukemia?

Precursor cell (can be myeloid or lymphoid lineage) stuck in stage of maturation --> produces lots of immature BLASTs in BM --> spill into peripheral blood Clonal proliferations --> dec in other cell lines ØAnemia ØThrombocytopenia ØNeutropenia

What may be the first presentation of AML

Signs of oncological emergencies Neutropenic fever Leukostasis

What are environmental exposure risk factors assoc w. AML?

Smoking 1.5% increased risk Ionizing radiation Benzene, soot, coal dust & creosote exposure

what subtype of ALL is MC in teens and has a worse prognosis?

T-Cell Acute Lymphoblastic Leukemia - worse prognosis

Current classification system for AML is and is based on?

The WHO Based on: morphology, immunophenotyping, genetic markers and association with previous chemo/radiation

CML is the uncontrolled clonal proliferation of _____ differentiated WBCs

mature the chronic part indicates more mature cells that are released whereas in acute blast/immature cells are released

what is the tx for leukostasis?

Treatment: emergent leukapheresis and/or chemotherapy

What is the protocol for prophylaxis for tumor lysis syndrome?

•Aggressive IVF's and strict I/O monitoring •Allopurinol 300mg po daily or rasburicase 6mg po x1 dose •Phoslo 1334mg po TID •Replace Calcium as needed-> Calcium gluconate

What occurs during the induction phase of APL tx? " i do not need you to know everything on this slide"

•All-trans-retinoic acid (ATRA) plus Chemo OR •ATRA + arsenic trioxide (ATO)

What is the only curative tx for CLL?

•Allogeneic stem cell transplant

What age is AML MC in?

•Average age of onset 65; however effects ALL age groups

What is the general tx for neutropenic fever?

broad spec abx + pancultures

What are the granulocytes?

neutrophils, eosinophils, basophils --> CML

what is the tx for stage 0-1 CLL? (elevated WBC +/- lymphadenopathy)

observation

Can ALL occur in adults?

Yes --> worse prognosis than children

Describe the pathophys of CML?

single, specific genetic mutation known as the Philadelphia chromosome --> (T 9;22), forming the abnormal gene BCR/ABL Burkitt's Lymphoma: 8;14 Follicular Lymphoma: 14;18 ALL Poor Risk- T(4:11) CML- 9;22- philly APL- 15;17 - M3

What is the goal of induction in ALL and AML

achieve remission - massive reduction in tumor cell numbers

As a result of tumor cell breakdown and elevations/decreases in critical lab values (PUCK), what can occur?

acute kidney injury (AKI), cardiac arrhythmias seizures, and even death

What drug is commonly used in the initiation phase of AML and requires an echo priror to initiation?

anthracycline ECHO --> assess baseline EF prior to chemotherapy ---> Particularly anthracycline = cardiomyopathy

How does CLL commonly first present?

asymptomatic - slow course Painless lymphadenopathy commonly the 1st sign

The majority of children w/ ALL are cured w/ ______

chemo alone

What will be seen on CBC in someone w. ALL?

circulating BLASTS anemia, thrombocytopenia & neutropenia (TdT) Terminal deoxynucleotidyl transferase (+) in immature lymphoblasts

What is a genetic disorder assoc w/ AML?

down syndrome

BM BX will show what in CML?

granulocytic hyperplasia

What are blast cells?

immature neutrophils, monocytes, lymphocytes and erythrocytes

You are managing a AML patient who presents w. hematuria, an atrial arrhythmia and seizures w. the following labs Cr: elevated BUN: elevated K+: elevated Phos: elevated Ca+: low Uric acid: high What is the dx? what is the tx?

tumor lysis syndrome tx w. •Aggressive IVFs and strict I/O monitoring •Allopurinol 300mg po daily or rasburicase 6mg po x1 dose •Phoslo 1334mg po TID •Replace Calcium as needed-> Calcium gluconate

What drugs are used during the induction phase of ALL tx?

vincristine, prednisone, anthracycline, and asparaginase

Pts w. CLL may develop what type of hemolytic anemia? What are the labs seen from this ?

warm autoimmune hemolytic anemia •Coombs: + •MCHC- elevated •Reticulocyte, LDH, Bilirubin -> elevated •Haptoglobin-> decreased •Smear in warm autoimmune hemolytic anemia: spherocytes •Treatment: steroids + folate

What are the sx of leukostasis ? (think thick blood)

Ø*Dyspnea ØChest pain Ø*Headache Ø*Altered mental status ØRetinal thrombus ØPriapism ØDecreased urine output

Who are the higher risk groups for ALL and AML?

ØDown Syndrome( trisomy 21) ØPrevious malignancy/previous chemotherapy

How will coag labs present if a pt w/ APL is experiencing issue w. DIC?

ØFibrinogen -> decreased Ø PT & PTT-> prolonged

What is the tx for CML?

ØImatinib --> targets Philadelphia chromosome t( 9;22) specifically

What are the high risk factors (bad) assoc w/ BM transplant in ALL?

ØIncreasing age >35yr ØT-CELL lymphoblastic leukemia-poor prognosis ØPoor( high risk) cytogenetics : severe hypodiploid ALL (less than 46 chromosomes) or T(4:11) ØNo remission after 1st induction cycle

What cytogenetic mutations result in low risk (favorable) prognostic factors in AML? (you should know at least one of them)

ØLow Risk( favorable) : T( 15;17) M3 APL <-- know this one (DIC/ATRA) inversion 16 ; T( 8;21) Ø High Risk ( unfavorable) : FLT-3; monosomy 5 or 7, complex cytogenetics with multiple deletions

As CLL progresses, what sx will be present?

ØLymphadenopathy ØFatigue, low grade fever, petechiae and weakness ØSplenomegaly & Hepatomegaly ØRecurrent infections

what is the peak age of onset for ALL? is it MC in boys or girls?

ØPeak age of onset 2-5 yrs. Boy > Girls

Leukostasis is MC in which acute leukemia?

• AML > ALL

What occurs during the accelerated phase of CML?

• Accelerated phase: cytogenetic abnormalities occur at a faster rate; acquired new mutations pt. become symptomatic due to suppression of other cell lines

What are the three types of stem cell tx?

• Autologous- Patients own stem cells • Allogenic- Stem cell from a sibling or a matched unrelated donor( MUD) • CORD ( umbilical cord blood)

What occurs during the blast phase of CML?

• Blast phase/ Terminal phase: immature cells rapidly proliferation "Blast Crisis"-> mimics Acute leukemia ≥ 20 % blasts within the bone marrow

What are the three phases of CML?

• Chronic phase: mature cells proliferate along with mutated clone; normal bone marrow function intact. Pt may have nonspecific symptoms night sweats, fever and wt loss. • Accelerated phase: cytogenetic abnormalities occur at a faster rate; acquired new mutations pt. become symptomatic due to suppression of other cell lines • Blast phase/ Terminal phase: immature cells rapidly proliferation "Blast Crisis"-> mimics Acute leukemia ≥ 20 % blasts within the bone marrow --> leukostasis, TLS etc

What is the gene mutation assoc w. Acute Promyelocytic Leukemia (APL) M3? What is the prognosis?

• Gene Mutation: Translocation (15:17) PML- RARA gene low risk = favorable

Apart from the bone marrow dysfunction assoc w/ ALL, what extramedullary sx can occur?

•*CNS- Meningeal infiltration •Gonads-> testicular enlargement •*Spleen-> enlargement •*Lymphadenopathy •Mediastinal Mass(thymus) -> 15% of those with T- cell ALL

CML epidemiology

•8450, new cases are estimated in 2020 •1,130 pt will die 2020 •Myeloproliferative Disorder Age 64 mean dx, MC in males

What occurs during the maintenance phase of APL tx? "i do not need you to know everything on this slide"

•ATRA + Methotrexate + 6 mercaptopurine •ATRA alone

What occurs during the consolidation phase of APL tx? "i do not need you to know everything on this slide"

•ATRA + chemotherapy OR •ATRA + arsenic

What is indicative of CLL on peripheral blood smear?

•Absolute lymphocytosis small mature lymphocytes •Smudge cells

What occurs during leukostasis? Is it an oncological emergency?

•Accumulation of Blasts in the circulation leads to impaired tissue perfusion due to increased blood viscosity Yes

why is a BM BX done in CLL?

•BM done to confirm progression NOT NEEDED FOR CONFIRMATION