Leukemia: Diagnosis Patient case - PowerPoint Presentation

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Leukemia: Diagnosis

Patient case:

3yo, PH/fully immunized male p/w daily fevers for 10-12 days, with intermittent

b/l

anterior thigh

pain

Saw PMD day prior to admission who ordered labs and then called family today with results saying “all cell counts were abnormal” and told parents to bring child to CHOC

ED

Where do you start?

HISTORY!

Keep a rough differential in mind from the chief complaint in order to tailor your questions

Ask a thorough infectious history

Possible

DDx

:

Viral

infections (

esp

EBV, CMV), TB, PNA, strep throat, UTI, otitis media, osteomyelitis, Kawasaki disease/vasculitis, leukemia, lymphoma, etc.

What questions should you ask if concerned about oncologic process?

Fever/chills/ night sweats/weight loss/ fatigue (

B-symptoms

)

SOB, cough (

possible mediastinal mass

)

Frequent infections (

immunocompromised

)

Bruising/rashes/bleeding (

low platelets

)

Bone pain (

issues with bone marrow

)

History:

Fever/chills for the past 10-12 days (forehead sensor measuring 104-105 F daily), then stopped measuring because they knew when he was having fevers

B/l

proximal leg pain started 2 weeks ago, no injury/trauma, was not bearing weight initially but has been improving recently

Night sweats ~5 times in the last 2 weeks

Abdominal pain when picking

pt

up from under his arms/sides of abdomen

No weight loss, but decreased appetite

No URI symptoms, no recent travel, no TB risk factors, no new animal exposures, no rash, no sick contacts

He is normally very active, but taking more naps

Has bruising on his shins but he is active and always bumps into stuff, bruising is normal for him on his legs

Ancillary hx:

Unremarkable

, he is UTD on vaccines

Next?

Physical Exam!

Gen:

Tired-appearing

, fussy, but not-toxic appearing

HEENT:

No

abnormal findings-no tonsillar hypertrophy/exudates, no pallor

CV: RRR, no murmurs, pulses equal

b/l

Resp: CTAB, no increased WOB

GI: NT, ND, soft,

some fullness on the right upper quadrant

, otherwise no masses

GU:

Circumcised

, testes descended,

right testicle seems slightly larger than left

but

is not firm

Extrem

: WWP, no swelling

Lymph:

N

o

cervical/clavicular/axillary/inguinal lymphadenopathy

Neuro:

Normal

tone, moving all extremities, no gross focal deficits, CNs intact

Skin:

No

rashes anywhere,

bruises noted on shins

b/l

What labs are important to get when thinking of oncologic processes?

CBC w/ diff, CMP

Remember other Tumor Lysis Labs! (LDH, uric acid, phosphorous level are

not

part of CMP!)

Blood culture!

DIC panel (don’t forget this!)

Consider

CRP/

ESR

Infectious work-up as indicated (UA, urine culture,

resp

panel, viral titers,

Quantiferon

, etc.)

Results:

What is your differential now?

Hopefully an oncologic process by now!

ALL (most common childhood cancer) & AML

AML and ALL are caused by sporadic mutations, it is not

hereditary

This is important when counseling the parents

There is nothing that parents could have done to have prevented it

Other siblings and future children are not at higher risk and do not need to “get tested”

What do you need to consider at this point?

Very elevated WBC

(191.8)

Need to immediately consider:

1. Has great potential for Tumor Lysis Syndrome

2.

Vaso

-occlusive crisis

Get Chest XR:

T cell ALL can have mediastinal mass

Lymphoma can have a mediastinal mass

Tumor Lysis:

Is he in Tumor

Lysis

now?

Electrolytes seem stable, but he is at a very high risk

Be careful! Even giving fluids can cause cells to lyse!

Monitor labs frequently!

Tumor Lysis:

The organs we typically worry about during Tumor Lysis:

1. Kidneys:

Uric

acid deposits in the kidney and cause injury

2. Liver:

Uric

acid deposits and can cause liver injury

3. Heart:

Elevated

K+ can cause arrhythmia/V fib or V tach

Treatment:

Hyperkalemia

: Stabilize

cardiac membrane if evidence of heart involvement with

C

alcium Gluconate, Lasix and Kayexalate, Insulin, AlbuterolElevated uric acid: Allopurinol or rasburicase

Hyperphosphatemia: AlternaGel (binds to phosphorous)Allopurinol is usually started as TID medication, rasburicase is usually once daily, AlternaGel is usually started as q 4 hrs.Sometimes these kids need to be monitored very closely in the PICU with frequent lab draws

Vaso-occlusive

issues:

Immature blasts are “sticky” can cause similar issues seen in patients with Sickle Cell disease

Priapism, stroke, kidney injury, etc.

Need to monitor

patient very closely

With this patient, be careful with RBC transfusion because it can

worsen

or induce

vaso

-occlusive issues

May be worth holding off on transfusion if

pt

is not symptomatic and if you do, can

give

pRBCs

aliquots and infuse very slowly

If you have a chance, go to the pathologist (in the basement of CHOC), and you can see the peripheral smear. This is similar to what we saw:

Diagnosis:

Bone marrow is Gold Standard

To diagnose leukemia, you need >20

%

blasts in the bone marrow

Can also send

peripheral

blood for Flow Cytometry

Lower CD numbers (CD4, CD8) are typically T cells

Higher CD numbers (CD19, CD20) are typically B cells

High risk leukemia:

Criteria that makes you high risk:

1. Initial WBC at presentation: >50 K

2. Age: <1 year or >10years

3. Testicular involvement (usually unilateral, large, and firm)

4. CNS involvement

Also high risk

if:

Unfavorable genetics (such as Philadelphia chromosome)

N

ot

under

remission

at the end of Induction (Day 29)

Treatment:

Many clinical trials out there and depending on the cancer, treatment regimen differs

For ALL however,

induction

(first month of treatment) is mostly the same:

Day 1:

Lumbar puncture

(to look for CNS involvement)

Intrathecal cytarabine: Day 1

Vincristine: Day 1, 8,15, 22

Dexamethasone: Days 1-28

Pegasparagase

: Day 4

Intrathecal Methotrexate: Day 8 and 29

Day 29:

Bone marrow biopsy is done again on Day 29 and we look for

Minimal Residual Disease (MRD)

:

The hope is that the blast cells are <0.01 % (down from >20% on initial

bone

marrow biopsy)

If >0.01%, they are classified under high risk and will need more intense chemotherapy going forward

Our kid:

Flow cytometry showed:

AML

(usually get ~10 new diagnoses of AML a year at CHOC). Most new diagnoses are ALL (again the most common childhood cancer). This was also confirmed on

bone

marrow

biopsy

Started on a new clinical trial (St.

Judes

AML

Study), consisting

of intrathecal

(Methotrexate

+

Hydrocortisone

+

Cytarabine), Azacitadine, Cytarabine, Dauorubicin, and EtoposideHe had no CNS involvement or testicular involvement, but because of his WBC >50 K, he is considered high riskInitially, we gave 6cc/kg

pRBC transfusion, CXR showed no mass, gave platelet transfusion as he needed procedures to get a central line in, LP, and bone marrowWhen starting chemo, we monitored WBC with daily CBC, tumor lysis labs every 6 hrs, gave Rasburicase, Allopurinol TID, and Alternagel every 4

hoursHe is currently Day 7 of treatment and doing well and stable. WBC is still 151

Important to remember:

US has one of the better survival rates for childhood cancers than other countries. Not because we have better chemotherapy regimens, it is because of the supportive

care

Nutrition (optimizing diet and even TPN if needed),

Psychology

, empiric Abx if needed, family and patient support/well-being

,

access to the hospital, controlling nausea and constipation, acting fast on side-effects when they

arise,

all play a huge role in the survivorship of our

Onc

patients