Leukemia is a type of cancer characterized by the uncontrolled growth of hematopoietic precursor cells, with various types including acute and chronic forms affecting both children and adults. Treatment options consist of chemotherapy regimens like the '7 + 3' induction therapy for AML, stem cell transplants, and novel therapies such as inotuzumab ozogamicin for B-cell ALL, each having distinct side effects and goals. Effective treatment aims to induce remission and reduce symptoms, with ongoing clinical research exploring advanced therapeutic approaches.

1. • What is leukemia?
It is the neoplastic (malignant) proliferative (out of proportion) growth of hematopoetic
precursor cells that diffuses out of the bone marrow.
• Types of leukemia:
1) Acute lymphocytic leukemia (ALL)- Common in young children can also occur in adults.
2) Acute myelogenous leukemia (AML)- Occurs in adults and childrens most common in
adults.
3) Chronic lymphocytic leukemia (CLL)- The most common chronic adult leukemia, may feel
well for years without needing treatment.
4) Chronic myelogenous leukemia (CML)- This type of leukemia mainly affects adults, may
have few or no symptoms for months or years before entering a phase in which the
leukemia cells grow more quickly.
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2. Cell lineage
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3. Types of Treatment:
1)Chemotherapy or other drug therapies-
a) Induction therapy- First phase of treatment. The goal is to destroy as many
cancer cells as possible in order to achieve (induce) a complete remission
(reduction or disappearance of the signs and symptoms of a disease).
b) Consolidation (Post-remission) therapy-The goal of consolidation therapy is
to lower the number of residual leukemia cells in the body, or eliminate them
entirely to help prevent the leukemia from returning.
2)Stem cell transplantation- After the chemotherapy, the patient receives an
infusion of stem cells to replace the stem cells destroyed by the intensive
therapy.
3)Clinical trials- Taking part in a clinical trial may be the best treatment choice
for some.
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4. The most common induction regimen for AML includes Cytarabine
(antimetabolite) and an anthracycline drug, such as Daunorubicin ore
Idarubicin (intercalating agent).
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5. Lets talk about the Treatment.
• 7 + 3 (Cytarabine + Idarubicin) is a Chemotherapy Regimen.
• “7” – refers to Cytarabine given daily for 7 days and
• “3” – refers to Idarubicin given daily for 3 days.
• Combination designed to rapidly kill cancer cells in the blood stream and bone
marrow.
• Goals of therapy: 7 + 3 chemotherapy is given to eliminate leukemia cells from
the body and to decrease symptoms from AML, such as bleeding, bruising, and
recurrent infections. 7 + 3 induction is commonly given with the goal of cure.
• Idarubicin is an intravenous infusion given over 10 to 15 minutes once daily on
Days 1, 2, and 3
• Cytarabine is given as a 24-hour continuous intravenous infusion on Days 1, 2,
3, 4, 5, 6, and 7 that is 168 h continuously
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6. • "7 + 3" requires a 19- to 28-day stay in a hospital (or sometimes longer). If no
leukemia is detected on 14th day then, patients usually go home once their
white blood cell count returns to the normal range.
• Patients go on to get consolidation chemotherapy with HiDAC (High-Dose Ara-
C) or IDAC (Intermediate-Dose Ara-C). If the bone marrow biopsy on Day 14
shows leukemia, another induction cycle of chemotherapy is usually
recommended. This is then referred to as re-induction. Re-induction
chemotherapy may be different than 7+3 induction therapy and have different
side effects.
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7. • Idarubicin side-effects:
• Increases your risk of bleeding. It is normal to receive red blood cell & platelet
transfusions if receiving idarubicin
• May cause nausea, vomiting, diarrhea, and mouth sores (stomatitis)
• Leakage into skin or surrounding muscle may cause severe irritation
(extravasation)
• May temporarily turn urine orange
• Causes hair loss, This is usually temporary and reversible
• May increase the risk of infection due to decrease white blood cell count
(neutropenia). It is normal to receive I.V. antibiotics after idarubicin is infused
• Has been linked to the development of other cancers in a small number of
people (1.5% chance at 10 years)
• May cause a series of symptoms known as Cytarabine (Ara-C) Syndrome
(manageable with corticosteroids) within 6 to 12 hours after administration.
Symptoms may include fever, rash, chest pain, muscle aches, bone pain,
tiredness, and inflammation and redness of the eye
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8. Hyper-CVAD, Chemotherapy Regimen for Acute Lymphoid
Leukemia (ALL).
• Hyper-CVAD A & Hyper CVAD B
Part A
• C - Cyclophosphamide (Cytoxan)
• V - Vincristine
• A - Adriamycin (doxorubicin)
• D - Dexamethasone
• Commonly given with the goal of cure of ALL.
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9. • Cyclophosphamide (alkylating agent) intravenous (I.V.) infusion, usually given
over three hours, every 12 hours (twice daily) on Days 1,2,3 (six doses total)
• Mesna (inactivates toxic metabolite, acrolein) I.V. infusion, usually given over
24 hours on Days 1,2,3, ending on Day 4
• Vincristine (mitotic inhibitor) I.V. infusion, usually given over 15 minutes on
Days 4 and 11
• Doxorubicin(antibody active against solid tumor) I.V. infusion, given over 2 - 24
hours (infusion time depends upon hospital guidelines) on Day 4
• Dexamethasone (immunosuppressants) 40 mg (ten 4 mg oral tablets) by
mouth on Days 1,2,3,4 and 11,12,13,14
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10. • Side effects:
• Nerve pain in hands or feet may increase after each dose. It is usually reversible
if treatment is stopped or dose is adjusted
• May cause constipation; preventative medicines may help decrease or avoid
constipation
• Leakage into skin or surrounding muscle may cause severe irritation
(extravasation)
• Nausea, vomiting, diarrhoea, mouth sores
• May cause high blood sugar, weight gain, irritability, high blood pressure,
difficulty sleeping, stomach ulcers, bone loss, muscle weakness
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11. • Part B
• Methotrexate (folate antagonist) intravenous (I.V.) infusion, usually given over
24 hours on Day 1
• Cytarabine (pyrimidine antagonist) I.V infusion, usually given over two hours,
every 12 hours on Days 2 and 3 (four doses per Cycle)
• Leucovorin (for toxic effects of MTX) I.V. infusion or 15 mg to 50 mg oral
tablet, starts 12 hours after the end of methotrexate infusion and continues
every six hours until the level of methotrexate in the blood decreases to a safe
level
• Prednisolone eye drops. 2 drops in each eye every six hours, started before
the first dose of cytarabine
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12. • MTX side effects:
• The risk of experiencing these side effects is much higher if methotrexate is not cleared from
the body appropriately:
• 1. Low red blood cells, white blood cells, and platelets, Kidney injury, Liver injury, Severe
diarrhea, Mouth ulcers, Stomach ulcers
• May interact with non-steroidal inflammatory drugs (NSAIDs), aspirin, proton-pump
inhibitors, phenytoin, and sulfa or penicillin antibiotics. These drugs should NOT be used the
day before or the day of therapy with methotrexate.
• Cytarabine Side effects:
• FDA Black-Box Warnings for low white blood cells, low platelets, low red blood cells, nausea,
vomiting, diarrhea, mouth sores, liver damage, and abdominal pain
• May cause a series of symptoms known as Cytarabine (Ara-C) Syndrome within 6 to 12 hours
after administration. Symptoms may include fever, rash, chest pain, muscle aches, bone pain,
tiredness, and inflammation and redness of the eye
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13. -Antibody Drug Conjugates-
• In its simplest form, ADCs are comprised of an
antibody to which is attached a cytotoxic agent
through a linker. The antibodies are generally fully
humanized monoclonal antibodies (mAbs) which
have high selectivity for tumor-associated antigens,
long circulating half-lives, and little to no
immunogenicity. Thus, mAbs provide an ideal
delivery platform for selective targeting of tumor
cells. If combined with cytotoxic agents that can be
released within the tumor cells once they have
been delivered by the selective antibodies, then
the eradication of the tumor cell can be realized
while sparing normal cells which have not been
targeted by the antibody—thus providing a magic
bullet. However, the realization of this theory has
taken decades to implement and is still a work in
progress.
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15. Aspect of design
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16. About the drug
• Inotuzumab ozogamicin (InO) is a calicheamicin-conjugated antibody targeting
CD22 on B-cell ALL cells.
• It then binds to the leukemia cell surface, it then enters the inside of the
cancer cell. Once inside the cell, the antibody releases drug, calicheamicin
which damages the DNA of the leukemia cell and causes the cell to die.
• Inotuzumab ozogamicin is given to kill leukemia cells and restore normal bone
marrow activity. It is given with the goal of achieving disease remission, and
possibly a cure, in patients who have relapsed or who are refractory after at
least one prior treatment for ALL.
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17. About the therapy
• Up to 2 hours for Days 1, 8, and 15 of each cycle (one hour infusion followed
by one hour observation period)
• Infusion times are based on clinical studies, but may vary depending on
doctor preference or patient tolerability. Pre-medications and intravenous
(I.V.) fluids, such as hydration, may add more time
• Inotuzumab ozogamicin is usually given in an outpatient infusion center,
allowing the person to go home afterwards. On occasion, it may be given in
the hospital if someone is too sick.
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18. Side effects
• Serious side effects included increased risk of severe liver damage in patients
who receive Besponsa after certain kinds of stem cell transplant, infusion-
related reactions, and heart problems. Women who are pregnant or
breastfeeding should not take Besponsa because it may cause harm to a
developing fetus or a newborn baby.
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19. You should
• Find Cancer Early
• Stay Away From Tobacco
• Eat Healthy & Get Active
• Be Safe in the Sun
• Protect Against HPV
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20. Refrence books
5. Wilson and Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry.pdf
1. Graham L. Patrick - An Introduction to Medicinal Chemistry.pdf
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21. Refrence articles
1. https://link.springer.com/article/10.1007%2Fs11095-015-1657-7
2. https://www.chemoexperts.com/
3. https://www.nature.com/articles/s41408-020-00345-8
4. https://www.ncbi.nlm.nih.gov/books/NBK557680/
5. https://clinicaltrials.gov/ct2/show/NCT00422591
6. https://www.lls.org/
7. https://njbio.com/antibody-drug-conjugates/
8. https://www.cancer.org/latest-news/fda-approves-besponsa-
inotuzumab-ozogamicin-for-all.html
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22. Thank you for listening patiently.....
By Disha jain.
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