ALL

ACUTE LYMPHOBLASTIC
LEUKEMIA
Alyssa Mellott

LEUKEMIA

Systemic disease

Diagnosed based on type of white blood cell

affected & speed at which it progresses
Acute

vs. Chronic
Myelogenous vs. Lymphocytic

ALL

ALL

Forms in bone marrow

B

& T lymphocytes: a mature form of lymphoblasts that are

critical to the immune system

3 subtypes
1.

Adults

2.

Mature B cell

Genetic changes

3.

Precursor B cell

Precursor T cell*

Pediatric*

Invades blood & spreads to lymph nodes & lymphoid

organs

EPIDEMIOLOGY

Most common subtype of leukemia

Most common cancer diagnosed in children

More prominent in:

2-10

year olds
White people
Males

ETIOLOGY

Family history

Chromosome instability disorders

Ex.

Viral infections
Ex.

Downs Syndrome

Epstein Barr

Radiation exposure
Previous

radiation or prenatal x-rays

Environmental factors

PRESENTATION

Neutropenia

Hemorrhage

Fever

Fatigue

Malaise

Bone/joint pain

Petechiae

Pallor

Lymphadenopathy

Enlarged spleen

PHYSIOLOGY & LYMPHATICS

PHYSIOLOGY & LYMPHATICS

Bone marrow produces lymphocytes

ALL: too many lymphocytes & they dont function

properly

Cant fight infection & overcrowding = less RBCs &

platelets

This causes
Bleeding

(lack of platelets)
Fatigue (lack of RBCs)
Build up of WBCs in spleen, lymph nodes, & liver =
swelling & discomfort

ALL VS. LYMPHOMA

Both can develop from lymphocytes

ALL starts in the bone marrow & can spread

to other parts of the body

Lymphoma starts in lymph nodes & other

organs & can spread to the bone marrow

TREATMENT

Radiation, chemotherapy, & bone marrow

transplant
Combination

or alone
Chemo alone is most common

CHEMOTHERAPY

Chemo alone 3 steps

1.

Agents: doxorubicin, methotrexate, vincristine, ect.

2.

Induction: intense 2-3 weeks, goal is remission

Consolidation: goal to kill remaining cells

Agents: same + cytarbine & etoposide

3.

Maintenance: goal to reduce risk of leukemia

coming back

Agents: mercaptopurine & methotrexate tablets +

vincristine injection

RADIATION THERAPY

TBI

Conditioning

for

bone marrow
transplant
1200 cGy
6 fractions

German Helmet
1800-2400

cGy

Cranial Spinal +
German helmet
Helmet

to 2400 cGy
Spine to 1500 cGy

Treatment of testis
2000-2400

cGy
Relapse due to
methotrexate
Can be prophylactic

BONE MARROW TRANSPLANT

For patients in fair

health
Can

do lower dose TBI for

weaker patients

Chemotherapy can
severely damage normal
bone marrow cells
Restore

bone marrows
ability to make blood

Autogeneic vs.
Autologous
Severe side effects

TBI: PATIENT EXAMPLE

7 year old male

Presented with
lymphadenopathy &
petechiae in 2011 ALL

Relapse in 2014

Testes

= sanctuary site
Methotrexate

= sanctuary site
Remission

Started 3 cycles of chemo

again
Reinduction

Had chemotherapy &

prophylactic cranial
radiation to 1200 cGy in
2011
CNS

Orchiectomy in June 2014

due to relapsed testicular
disease

Vincristine
Steroids
Doxorubicin
Asparaginase

TBI and testicular boost at

MXE in September to
prepare for BMT

TBI: PATIENT EXAMPLE

TBI
1200

cGy total
6 fractions/BID
6 mV

Boost to testes
1200

cGy total
6 fractions/BID
12 meV

TBI: PATIENT EXAMPLE

OPTION 1:
ANTIBODY THERAPY

Antibody therapy
A

form of targeted therapy

Radiation

and chemotherapy side effects can

limit quality of life

Focus

on pediatric relapse cases

Usually a poor prognosis (~30% in 5 years)

OPTION 1:
ANTIBODY THERAPY

1. Monoclonal antibodies
In

phase III trial for pediatric ALL

Leukemic

blasts express antigens on their surface that

can be selectively targeted by monoclonal antibodies

This

allows directed delivery of highly potent drugs

Advantages

over chemo:

Longer circulating half-lives

Greater accumulation in tumor cells
Fewer systemic side effects

OPTION 1:
ANTIBODY THERAPY

2. Antibody-Drug Conjugates (ADCs)

Next

generation of antibodies
Being tested for ALL & AML
A highly potent cytotoxic agent is bound to an
antibody by a linker, resulting in selective
targeting of leukemia cells

3. Bispecific T-Cell Engager (BiTE)

Each antibody contains two binding sites

One designed to engage the patients own immune

system and the other to target malignant cells

OPTION 1:
CONCLUSIONS

Less severe side effects

More

targeted

Minimal changes over last 50 years in drugs to induce &

maintain remission in pediatric leukemia

Could change routine management of this disease

Cannot not penetrate blood-brain barrier

Still

a challenge to get these drugs to sanctuary sites

CNS & testes

Still in trials

OPTION 2:
PRE-BMT BUSULFAN

Busulfan (BU)
Alkylating

agent
One of most potent anti-leukemia drugs
Very toxic to normal bone marrow cells but not
immunosuppressive

Need fludarabine to get new stem cells to engraft

Limited

toxicity to organs
Most common alternative to TBI

Study: childhood leukemia survivors

Best

conditioning treatment for BMT?

TBI 174 patients vs. Busulfan 66 patients

Health status & quality of life?

Median follow up = 10.1 years

OPTION 2:
CONCLUSIONS

Patients that
developed more
than three late
complications
59.2%

of TBI
patients
44% of BU patients

OPTION 2:
SIDE EFFECTS
Side Effects

BU

TBI

Height growth
failure

27.3%

49.4%

Overweight*

22.7%

13.8%

Hypothyroidism

15.2%

28.2%

Secondary Tumors 4.5%

11.5%

Gonadal
Dysfunction

48.1%

53.9%

Alopecia*

25.8%

2.9%

Cataract

4.5%

51.7%

OPTION 2:
CONCLUSIONS

Seems to be equally effective

BU

replace TBI?
Children & TBI

More damaging to physical and mental development

(lower IQ)
Higher risk for secondary cancers

Patients considered were all long-term

survivors
TBI

seems to have more serious side effects in

children

MY OPINION

Antibody therapy vs. common chemotherapy

agents
Side

effects
Relapse/ALL

Better prognosis?

BU vs. TBI as conditioning for BMT

Side

effects
Long term quality of life
Pediatric development

REFERENCES

Bernard F, Auquier P, Michel G, et al. Health status of childhood leukemia survivors

who received hematopoietic cell transplantation after BU or TBI: an LEA study. Bone
Marrow Transplantation [serial online]. May 2014;49(5):709-716. Available from:
Academic Search Complete, Ipswich, MA. Accessed October 23, 2014.

Childhood Lymphoblastic Leukemia Treatment. Cancer.gov. National Cancer

Institute, n.d. Web. 30 Oct. 2014.
<http://www.cancer.gov/cancertopics/pdq/treatment/childALL/HealthProfessional>.

Hackworth, Ruth. "Pediatric Tumors." Applied Technical Oncology. Lecture. 2014.

"Intravenous Busulfan Before Stem Cell Transplant." MD Anderson Cancer Center.

University of
Anderson Texas MD Anderson, n.d. Web. 30 Oct. 2014.
<http://www2.mdanderson.org/cancerwise/2010/05/qa-intravenous-busulfanbefore-stem-cell-transplant.html>.

"Stem cell transplant for acute lymphocytic leukemia." American Cancer Society.
American Cancer Society, n.d. Web. 30 Oct. 2014.
<http://www.cancer.org/cancer/leukemiaacutelymphocyticallinadults/overviewguide/leukemia-all-overview-treating-bonemarrow-stem-cell>.

Vedi A, Ziegler D. Antibody therapy for pediatric leukemia. Frontiers In Oncology

[serial online]. April 2014;4:1-10. Available from: Academic Search Complete, Ipswich,
MA. Accessed October 27, 2014.