Leukaemia is cancer of the blood or bone marrow characterized by the abnormal proliferation of white blood cells. There are four main types of leukaemia - acute myelogenous leukaemia, chronic myelogenous leukaemia, acute lymphoblastic leukaemia, and chronic lymphocytic leukaemia. Chemotherapy involves the use of drugs to treat leukaemia and is usually administered in induction, consolidation, and maintenance phases with the goal of killing cancer cells and achieving remission. Common drugs used include anthracyclines, tyrosine kinase inhibitors, corticosteroids, purine analogues, and monoclonal antibodies.

1. Chemotherapy of Leukaemia
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Swapna Chemotherapy of Leukaemia

2. Chemotherapy of Leukaemia
Leukaemia
Leukemia is a cancer of the blood or bone marrow. Bone marrow
produces blood cells. Leukemia can happen when there is a
problem with the production of blood cells. It usually affects the
leukocytes, or white blood cells.
Causes
Leukemia happens when the DNA of immature blood cells, mainly
white cells, becomes damaged. This causes the blood cells to grow
and divide continuously. Healthy blood cells die after a while and
are replaced by new cells, which are produced in the
bonemarrow.The abnormal blood cells do not die when they should.
They accumulate, occupying more space. As more cancer cells are
produced, they stop the healthy white blood cells from growing
and functioning normally, by crowding out space in the blood..
Swapna Chemotherapy of Leukaemia

3. Acute leukaemia is a clonal malignant disorder characterised by the
accumulation of immature blast cells in the BM, which replace
normal marrow tissue, including haemopoietic precursor cells. This
results in BM failure, reflected by peripheral blood cytopenias and
circulating blast cells. Infiltration of various organs is also a feature
of some forms of leukaemia.
Chronic leukemia is a disease in which clonal expasion of white
blood cells are takes place in the bone marrow.
Swapna Chemotherapy of Leukaemia

4. Classification of Leukaemia
Acute myelogenous leukemia
Chronic myelogenous leukemia
Acute lymphoblastic leukemia
Chronic lymphocytic leukemia
Acute myelogenous leukemia (AML): Acute myelogenous
leukemia represents a group of clonal hematopoietic stem cell
disorders in which both a block in differentiation and unchecked
proliferation result in the accumulation of myeloblasts at the
expense of normal hematopoietic precursors. Characterized by the
development of immature myeloblasts in the bone marrow.
Swapna Chemotherapy of Leukaemia

5. Characterized by the development of immature myeloblasts in the
bone marrow.
FAB subtype Name
M0 Undifferentiated acute myeloblastic leukemia
M1 Acute myeloblastic leukemia with minimal maturation
M2 Acute myeloblastic leukemia with maturation
M3 Acute promyelocytic leukemia (APL)
M4 Acute myelomonocytic leukemia (AML)
M4 eos Acute myelomonocytic leukemia with eosinophilia
M5 Acute monocytic leukemia
M6 Acute erythroid leukemia
M7 Acute megakaryoblastic leukemia
Swapna Chemotherapy of Leukaemia

6. Clinical Presentation:
Enlarged organs (spleen, liver), caused by increased number of
white blood cells accumulating within liver and spleen causing
tissue distension.
Increased metabolic rate with weakness and bone Bone
discomfort
Swapna Chemotherapy of Leukaemia

7. Treatment
There are 4 types of standard treatments
Chemotherapy: Systemic, intrathecal (the spinal canal, the
subarachnoid space), or regional drugs usage depends of the
AML subtype
Radiation: Different types of radiation to kill cancer cells or
keep them from growing through external and internal
approaches which depend of the AML subtype
Stem Cell Transplant: Method of administering chemo and
replacing blood forming cells
Targeted Therapy: monoclonal antibodies or other substances
to destroy specific cancer cells without harming the patient’s
normal cell
Swapna Chemotherapy of Leukaemia

8. The first Induction phase clears the blood of leukemia cells and
reduces the number of blasts in the bone marrow with the goal to
return blood counts to a normal level over time and to reach a
complete remission.
Most AML patients are treated with a combination of an
anthracycline (such as daunorubicin doxorubicin ,Adriamycin
PFS, Adriamycin or idarubicin and cytarabine.
Gemtuzumab ozogamicin is FDA approved for the treatment
of adults with newly diagnosed AML whose tumors express
the CD33 antigen (CD33-positive AML).
Swapna Chemotherapy of Leukaemia

9. Midostaurin is FDA approvd for the treatment of newly
diagnosed adult patients with AML that is FLT3 mutation
positive as detected by an FDA-approved test, in combination
with standard cytarabine and daunorubicin induction and
cytarabine consolidation. It is not indicated as a single-agent
induction therapy for the treatment of patients with AML.
Daunorubicin and cytarabine is FDA approved for the
treatment of adults with newly-diagnosed therapy-related
acute myeloid leukemia (t-AML) or AML with
myelodysplasia-related changes (AML-MRC).
Other drugs may be added or substituted for higher-risk,
refractory or relapsed patients.
Swapna Chemotherapy of Leukaemia

10. The second Consolidation phase is administered after a rest period
where the patient recovers from the first phase with the goal to kill
the leukemia cells that are still present .
Postremission therapy consists of additional intensive
chemotherapy after remission has been achieved, with or
without stem cell transplantation. If stem cell transplantation
is not used, the treatment will generally consist of four cycles
of chemotherapy. For best results, intensive chemotherapy is
given with high doses of cytarabine or other drugs.
The third Maintenance phase is necessary in only certain types of
leukemia and includes giving low doses of a chemo drug for months
or years after the consolidation phase.
Swapna Chemotherapy of Leukaemia

11. Acute lymphoblastic leukemia (ALL): Acute lymphoblastic
leukaemia is characterized by the presence in the blood and bone
marrow of large numbers of unusually immature white blood cells
destined to become lymphocytes. It arising from a single lymphoid
stem cell, with impaired maturation and accumulation of the
malignant cells in the bone marrow.
Swapna Chemotherapy of Leukaemia

12. The French-American-British (FAB) classification.
Division of ALL according to FAB criteria
L1 – cytoplasma-deficient, small blasts
L2 – more heterogenous with emphasis on cytoplasma richness and size
L3 - B-cell blasts with basophile vacuolized cytoplasma
Swapna Chemotherapy of Leukaemia

13. Clinical presentation
Frequent or unexplained fever and infection
Swollen lymph nodes
Severe generalized gingival overgrowth with localized necrosis
Swapna Chemotherapy of Leukaemia

14. Treatment Treatment can span 21
2 — 31
2 years and is broken
down into the following 4 phases
Induction therapy with the purpose to achieve remission by
killing most of the cancer cells
Consolidation (post-remission) therapy with the goal to
destroy any remaining leukemia cells in the central nervous
system (4 - 8 weeks)
Maintenance (low dose) therapy is given to prevent cancer cell
re-growth (4 weeks)
Preventive therapy to the spinal cord (chemotherapy drugs are
injected directly into the spinal cord
Swapna Chemotherapy of Leukaemia

15. There are 4 main types of the specific treatments
Chemotherapy to kill any leukemia cells that may have spread
to the brain and spinal cord) .
Targeted drug therapy to attack specific abnormalities that
cause the cancer cell growth
Radiation therapy is typically used when the cancer has spread
to the central nervous system.
Stem cell transplant may be used for patients at risk or
currently going through a relapse . Physical Therapy and
exercise are aimed at symptom management, preservation of
muscle function, pain control, and increased quality of life.
Swapna Chemotherapy of Leukaemia

16. Medications
Chemotherapy drugs: L - asparaginase, Vincristine
Steroid: Dexamethasone, Hydrocortisone
Drugs for high-risk patients: Daunorubicin, Cytarabine
Other drugs: Methotrexate, 6-mercaptopurine
Novel approaches: For some subtypes of relapsed ALL, aiming at
biological targets such as the proteasome, in combination with
chemotherapy, has given promising results in clinical trials.
Chimeric antigen receptors (CARs) have been developed as a
promising therapy for ALL.
Swapna Chemotherapy of Leukaemia

17. Chemotherapy to treat Acute Lymphocytic Leukemia (ALL)
Option 1: Chemotherapy with prednisone, vincristine sulfate, and
an anthracycline drug (e.g., daunorubicin)
Option 2: Chemotherapy with prednisone. vincristine, and
L-asparaginase or cyclophosphamide
Consolidation therapy for ALL (1-3 months in adults; 4—8 months
in children) may involve treatment with combination chemotherapy.
Chemotherapy with prednisone, vincristine , L-asparaginase and
daunorubicin, followed by Cyclophosphamide , cytarabine , and
6-thioguanine.
Option 1: Chemotherapy with prednisone, vincristine ,
L-asparaginase and daunorubicin, followed by Cyclophosphamide,
cytarabine, and 6-thioguanine
Option 2: Chemotherapy with methotrexate sodium plus
6-mercaptopurine (6-MP; Purinethol).
Swapna Chemotherapy of Leukaemia

18. Chronic myelogenous leukemia(CML): Chronic myelogenous
leukemia is the clonal hematopoietic stem cell disorder with an
abnormal increase in mature and immature granulocytes (as
neutrophils, eosinophils, and myelocytes) especially in bone marrow
and blood, that occurs especially in adults, and that is associated
with the presence of the Philadelphia chromosome CML.
Classification
Chronic phase: there are few blast cells in the blood and bone
marrow and there may be no symptoms of leukemia, this
phase may last from several months to several years
Accelerated phase: There are more blast cells in the blood
and bone marrow, and fewer normal cells
Blastic phase (the blast crisis): More than 30
Refractory CML: Leukemia cells do not decrease even though
treatment is given
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19. Clinical presentation
enlarged spleen and liver
fever and night sweats due to an elevated basal level of
metabolism
Swapna Chemotherapy of Leukaemia

20. Treatment
The only curative treatment for CML is a bone marrow
transplant or an allogeneic stem cell transplant
Other than this there are four major mainstays of treatment in
CML:
treatment with tyrosine kinase inhibitors
myelosuppressive or leukopheresis therapy (to counteract the
leucocytosis during early treatment)
splenectomy and interferon alfa-2b
Swapna Chemotherapy of Leukaemia

21. Chemotherapy to Treat Chronic Myelogenous Leukemia (CML)
Option 1: Chemotherapy with hydroxyurea (Hydrea)
Option 2: Chemotherapy with busulfan (Myleran)
Chemotherapy (chemo) is the use of anti-cancer drugs that are
injected into a vein or taken by mouth. These drugs enter the
bloodstream and reach all areas of the body, making this type of
treatment useful for cancers such as leukemia that spread
throughout the body. Any drug used to treat cancer can be
considered chemo, but here chemo is used to mean treatment with
conventional cytotoxic drugs that mainly kill cells that are growing
and dividing rapidly. Chemo was once one of the main treatments
for patients with chronic myeloid leukemia. Now, chemo may be
used to treat CML when the TKIs have stopped working. It is also
used as part of the treatment during a stem cell transplant.
Swapna Chemotherapy of Leukaemia

22. The chemo drug hydroxyurea is taken as a pill, and can help lower
very high white blood cell counts and shrink an enlarged spleen.
Other drugs sometimes used include cytarabine, busulfan,
cyclophosphamide, and vincristine. Omacetaxine is a chemo drug
that was approved to treat CML that is resistant to some of the
TKIs now in use. It can help some patients whose CML has
developed the T315I mutation that keeps most TKIs from working.
Swapna Chemotherapy of Leukaemia

23. Chronic lymphocytic leukemia(CLL) :
Chronic lymphocytic leukemia (CLL) is a monoclonal disorder
characterized by a progressive accumulation of small,
mature-appearing functionally incompetent lymphocytes in blood,
bone marrow, and organs. It is characterized by proliferation of
small, abnormal , mature B lymphocytes, often leading to
decreased synthesis of immunoglobulin and depressed antibody
response. The number of mature lymphocytes in peripheral blood
smear and bone marrow are greatly increased.
Swapna Chemotherapy of Leukaemia

24. Classification Stage division of CLL according to Rai
characterized by absolute lymphocytosis (>15,000/mm3)
without adenopathy, hepatosplenomegaly, anemia, or
thrombocytopenia.
characterized by absolute lymphocytosis with
lymphadenopathy without hepatosplenomegaly, anemia, or
thrombocytopenia.
characterized by absolute lymphocytosis with either
hepatomegaly or splenomegaly with or without
lymphadenopathy.
characterized by absolute lymphocytosis and anemia
(hemoglobin < 11 g/dL) with or without lymphadenopathy,
hepatomegaly, or splenomegaly.
characterized by absolute lymphocytosis and
thrombocytopenia (<100,000/mm3) with or without
lymphadenopathy, hepatomegaly, splenomegaly, or anemia
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25. Clinical presentation
very high numbers of circulating lymphocytes > 100 × 109/l
fatigue, night sweats, fever
thrombocytopenia
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26. Treatment
CLL is treated by chemotherapy, radiation therapy, biological
therapy, or bone marrow transplantation.
Symptoms are sometimes treated surgically (splenectomy
removal of enlarged spleen) or by radiation therapy (“de-
bulking” swollen lymph nodes).
An initial treatment regimen that contains fludarabine,
cyclophosphamide, and rituximab (known as FCR) has
demonstrated higher overall response rates and complete
response rate.
Since CLL cells must interact with the stroma in bone marrow
or lymphoid tissues to survive, these interactions need to be
explored as targets of innovative therapies, and specific
inhibition of the B-cell receptor signaling pathway, as
targeting the actively proliferating cells that maintain the CLL
clone by a cell-cycle–active agent may be an option.
Since as 20% of patients with the worst prognostic markers
have stereotypic antigen receptors, they may be valuable
points of attack.
Swapna Chemotherapy of Leukaemia

27. Chemotherapy to Treat Chronic Lymphocytic Leukemia
(CLL) Chemotherapy for CLL may be postponed if the patient has
early-stage disease and shows no related symptoms. If necessary,
induction chemotherapy may be started with an alkylating agent
such as chlorambucil or cyclophosphamide.
Option 1: Chemotherapy with chlorambucil (Leukeran) or
cyclophosphamide (Neosar) plus prednisone, if needed
A class of compounds known as purine analogs have been
developed for the treatment of CLL. Three such drugs—fludarabine
(arabinofuranosyl-2-fluoroadenine-5’-monophosphate), pentostatin
(2-deoxycoformycin), and cladribine (2-chlorodeoxyadenisine;
2-CDA)—have been tested as single-agent treatments against CLL.
These drugs usually are reserved for cases in which CLL is resistant
(unresponsive to treatment) or returns after chemotherapy with
chlorambucil or cyclophosphamid.
Swapna Chemotherapy of Leukaemia

28. Option 2: Chemotherapy with fludarabine phosphate, pentostatin
(2-deoxycoformycin; “DCF”; Nipent), or cladribine
(2-chlorodeoxyadenosine; “2-CDA”; Leustatin) . In November
2013, the FDA approved obinutuzumab (Gazyva) for use in
combination with chlorambucil to treat people with previously
untreated CLL. In February 2014, ibrutinib (Imbruvica) was
approved to treat people with CLL whose disease has progressed
inspite of previous treatment.
Swapna Chemotherapy of Leukaemia