3. INTRODUCTION
Acute lymphoblastic leukemia
malignant (clonal) disease of the bone marrow
early lymphoid (B or T) precursors proliferate and replace the
normal hematopoietic cells of the marrow
loss of production of normal red blood cells, white blood cells, and
platelets
4. Eventually, the leukemic cells
escape from the marrow into the bloodstream and
accumulate in lymph nodes, the spleen, and normal organs.
INTRODUCTION
5. • If untreated, acute leukemia is usually fatal within a few months.
• However, with modern therapies, survival after diagnosis can be
markedly prolonged, and many patients can be cured.
INTRODUCTION
7. Epidemiology
• Most common Cancer in Children
• Incidence of leukemia in Indian pediatric population is reported as
34%, of which 25% is ALL
• Represents approx. 20% of all leukemias among adults
• Incidence is ~ 3- 4 cases per 100,000 children under the age of 15
years.
8. • Overall, males experience a slightly higher leukemia risk than females.
• Adolescents, and young adults are also at a higher risk.
• Bimodal peak
• 2 to 4 years
• sixth decade
• The chance of survival in ALL decreases with increasing age.
Epidemiology
9. OUTCOME IN THE INDIAN
POPULATION IS POOR
Reasons include:
• Lack of treatment compliance
• Belief in alternate medicine
• Lack of knowledge
• Cultural and social factors
• High infection rates, and financial difficulties.
• High sepsis-related mortality.
10. Pathophysiology
• ALL occurs due to the
malignant transformation of
hematopoietic stem cells
• It can also involve a more
committed stem cell that has a
limited self-renewal capacity
11. • In ALL, these malignant cells are
generally immature, poorly
differentiated, abnormal leukocytes
(blasts) that are lymphoblasts.
• These blasts can undergo –
clonal expansion and
proliferation,
leading to replacement and
interference of the development and
the function of normal blood
products with malignant cells,
leading to clinical symptoms.
12. ETIOLOGY
LARGELY UNKNOWN
Factors associated with increased risk include:
• Genetic
• Syndromes of impaired DNA repair
• Ataxia telengectasia
• Bloom’s syndrome
• Down syndrome
15. CLINICAL FEATURES
Due to marrow failure:
- Proliferation and accumulation of blast cells → suppression of hematopoiesis
• Anemia (Fatigue, SOB during normal physical activities, Dizziness, Pale
complexion)
• Thrombocytopenia (Easy Bruising, Prolonged bleeding from minor cuts,
appearance of petechiae, Frequent or severe nosebleeds, Bleeding gums, Blood in
the urine)
• Neutropenia (Frequent infections, Fever)
16. CLINICAL FEATURES
Nonspecific (common)
• Fever
• Bleeding
• Bone pain
• Presence of Petechiae
Musculoskeletal pain - 43 %
• Limp/Refusal to bear weight
• Bone pain
Lymphadenopathy (~50% on
presentation)
Organomegaly
Hepatomegaly (64 %) and/or
splenomegaly (61 %) and lymph
nodes are the most common sites
of extramedullary involvement
17. CLINICAL FEATURES
CNS symptoms (5 %)
Increased ICP
o Headache (uncommon < 5 %)
o Vomiting
o Lethargy
o Papilledema
o Nuchal rigidity
o Cranial nerve abnormalities
• Testicular involvement (<1 %)
Painless enlargement of the scrotum
• Mediastinal mass (10 %)
Tracheal compression
Associated pleural effusions
Superior vena cava syndrome
Pain
Dysphagia
Dyspnea
Swelling of the neck, face, and
upper limbs.
18. CLASSIFICATION OF ALL
• The older, traditional classification of ALL is based on the –
Morphologic and Cytochemical features is the FAB classification
• Now been replaced by the newer WHO classification based on the
Immunological features
• Genetic
19. FAB system
L1 –
• Small cells with homogeneous
chromatin,
• regular nuclear shape,
• small or absent nucleolus, and
• scanty cytoplasm;
• subtype represents 25-30% of
adult cases
20. L2 –
• Large and heterogeneous cells,
• Heterogeneous chromatin,
• Irregular nuclear shape, and
• Nucleolus often large;
• subtype represents 70% of cases
(most common)
FAB system
21. L3 -
• Large and homogeneous cells
• with multiple nucleoli,
• moderate deep blue cytoplasm, and
cytoplasmic vacuolization that
often overlies the nucleus (most
prominent feature)
• subtype represents 1-2% of adult
cases
FAB system
22. WHO CLASSIFICATION
• WHO classifies L1 and L2 subtypes of ALL as either precursor B / T
lymphoblastic leukemia/lymphoblastic lymphoma.
• The L3 subtype of ALL is included in the group of mature B-cell
neoplasms.
23. • In 2016 WHO published a revised classification of ALL which
included 2 new provisional entities for B-ALL.
• The first, B-lymphoblastic leukemia/lymphoma, BCR-ABL1-like,
was originally reported as a subtype of poor-prognosis childhood ALL
with a gene expression profile similar to Philadelphia chromosome–
positive ALL.
• Some cases of this subtype of ALL respond to therapy with tyrosine
kinase inhibitors.
WHO CLASSIFICATION
24. • The second, B-ALL with intrachromosomal amplification of
chromosome 21, is characteristically detected by FISH with a probe
for RUNX1 that reveals 5 or more copies of that gene.
• This subtype occurs in older children and is associated with a poor
prognosis.
WHO CLASSIFICATION
25. B CELLALL
• Mature B-cell ALL is the leukemic equivalent of
Burkitt’s lymphoma
Have poor prognosis
• CR remission rates : 40%
• Remission duration :11 months
Treatment for mature B-cell ALL differs from that for other types of ALL
• Short cycles at frequent intervals over a period of 6 months.
26. • Currently there is no subdivision of T-ALL, with the exception of two
new provisional subtypes.
• Early T-cell precursor lymphoblastic leukemia is a subtype with only
limited early T-cell differentiation with retention of some myeloid and
stem cell characteristics.
• Natural killer cell lymphoblastic leukemia/lymphoma is another newly
described subtype.
WHO CLASSIFICATION
33. BONE MARROW ASPIRATION AND
BIOPSY
• Definitive diagnostic test
• Immunophenotyping helps to elucidate the subtype
• Diagnosis of ALL is made when at least –
30% lymphoblasts (FAB classification) or
20% lymphoblasts (WHO classification) are present in the bone
marrow and/or peripheral blood.
34. • In addition, slides should be stained with MPO (or Sudan black) and
TdT (Terminal deoxynucleotidyl transferase),
unless another method is used, such as flow cytometry.
BONE MARROW ASPIRATION AND
BIOPSY
35. • Bone marrow samples should also be sent for flow cytometry and
cytogenetics
• ~ 15% of patients with ALL have a t(9;22) translocation (ie, Ph
chromosome), but other chromosomal abnormalities may also occur,
such as –
• t(4;11),
• t(2;8), and
• t(8;14).
BONE MARROW ASPIRATION AND
BIOPSY
36. IMMUNOHISTOCHEMISTRY
• A negative MPO stain and a positive TdT (Terminal
deoxynucleotidyl transferase) is the hallmark of the diagnosis of
most cases of ALL.
37. • Positive confirmation of lymphoid (and not myeloid) lineage should
be performed by flow cytometric demonstration of lymphoid antigens,
such as –
• CD3 (T-lineage ALL) or
• CD19 (B-lineage ALL).
IMMUNOHISTOCHEMISTRY
39. FLOW CYTOMETRY AND
CYTOGENETICS
• Although > 95% of cases of the L1 or
L2 subtype of ALL are positive for TdT
(Terminal deoxynucleotidyl
transferase),
TdT is not specific for ALL;
TdT is absent in L3 (mature B-cell)
ALL.
However, TdT helps to distinguish ALL
from malignancies of more mature
lymphocytes (ie, NHL).
40. • Flow cytometry helps to distinguish B-ALL from T-ALL
• Flow cytometry can also identify whether patients are eligible for
certain therapies, e.g. CD20 (rituximab).
FLOW CYTOMETRY AND
CYTOGENETICS
41. • Flow cytometry shows if the cells are positive for –
• CD10,
• CD19,
• CD 20
• CD22,
• CD34, and
• TdT.
FLOW CYTOMETRY AND
CYTOGENETICS
42. CYTOGENETICS
• Cytogenetic abnormalities occur in ~ 70% of cases of ALL in adults
• Abnormalities of chromosome number –
• Hypodiploidy,
• Hyperdiploidy
are more common in ALL than in AML.
43. Immunophenotyping of ALL
Cells – ALL of B-Cell Lineage
(85% of cases of adult ALL)
Immunophenotyping of ALL
Cells – ALL of T-Cell Lineage
(15% of cases of adult ALL)
44. PCR
• Studies for BCR-ABL analysis by PCR or cytogenetics help
distinguish patients with Ph+ ALL from those with the lymphoid
blastic phase of CML.
• Most patients with Ph+ ALL have the p190 type of BCR-ABL,
whereas patients with lymphoid blastic CML have the p210 type
of BCR-ABL
45. CSF EXAMINATION
CNS leukemia is:
• Presence of at least five leukocytes per microliter of CSF
and the detection of leukemic blast cells.
• Presence of cranial nerve palsy.
46. • LP is used to evaluate CNS involvement.
• In pediatric patients, LP is typically included in the diagnostic workup.
• NCCN guidelines advise that timing of LP should be consistent with
the chosen treatment regimen, and recommend performing LP
concurrently with initial intrathecal therapy.
CSF EXAMINATION
47. CNS status is classified as follows, on the basis of CSF findings-
• CNS-1: No lymphoblasts in CSF, regardless of WBC count
• CNS-2: WBC < 5/mcL in CSF with presence of lymphoblasts
• CNS-3: WBC ≥5/mcL in CSF with presence of lymphoblasts
CSF EXAMINATION
48. NCCN GUIDELINES
Diagnosis of ALL generally requires the following :
• Demonstration of ≥20% bone marrow lymphoblasts
• Morphologic assessment of Wright/Giemsa–stained bone marrow aspirate
smears
• H&E–stained bone marrow core biopsy and clot sections
• Comprehensive flow cytometric immunophenotyping
53. • Considerable progress has been made in understanding the biology of
ALL, which has led to treatment strategies tailored to specific disease
subgroups.
• This has resulted in dramatic improvements in the outcomes of
children with ALL, with cure rates up to 80%.
• The therapeutic approach for adult ALL is modeled on pediatric
regimens, and although initial remission rates range between 80% to
90%, only 25% to 50% of adults achieve long-term DFS.
TREATMENT OF ALL
54. • This stark difference in outcome for adults as compared to children
has been variously attributed to the greater incidence of adverse
cytogenetic subgroups found in adults and possibly poorer tolerance
and compliance of adults with intensive therapies required for the
successful treatment of ALL.
TREATMENT OF ALL
55. TREATMENT OF ALL
• Over last 5 decades, there is dramatic improvement in the prognosis.
56. The four components of specific ALL therapy are
(a) induction of remission,
(b) intensification and/or consolidation,
(c) maintenance therapy, and
(d) CNS prophylaxis
TREATMENT OF ALL
57. TREATMENT OF ALL
• Single agent chemotherapy in 1950’s
• Combination agents in 1960’s
• Leukemia in CNS as initial site of relapse became progressively more evident.
• Rationale : Leukemic cells, even if subclinical, were present in CNS of all patients. Protected from
systemic chemotherapy by BBB.
• Radiation to CNS in 1970’s
• Pivotal step boosting long term DFS to > 50%
• Intensive therapy since 1980’s with good supportive care
• Complete remission > 95%
• Long term EFS > 80%
58. COMPLETE REMISSION RATES % with Different
chemotherapy agents
SINGLE AGENTS
METHOTREXATE (MTX)
• 20 – 40 %
• 12 mgs IT
MERCAPTOPURNE (MP)
• 25 %
• 75 mg/m2 IV
PREDNISONE (PRED)
• 40 – 60 %
• 40mg/m2 PO
VINCRISTINE (VCR)
• 60 – 80 %
• 1.4 mg/m2 IV
DAUNORUBICIN (DNR)
• 5 – 40 %
• 30 mg/m2 IV
L –ASPARAGINASE (ASP)
• 45 – 70 %
• 6000 u/m2 IM
DRUG COMBINATIONS
VCR / PRED
• 85 %
VCR / PRED/ ASP
• 90 – 95 %
PRED / VCR / MTX / MP
• 90 %
59. Phases
(a) induction of remission,
(b) intensification and/or
consolidation,
(c) maintenance therapy, and
(d) CNS prophylaxis
61. REMISSION INDUCTION (4 – 6 WEEKS)
• Aim : To rapidly kill most tumor cells and get the patient into
remission
Clinical Remission:
Presence of < 5% leukemic blasts in the bone marrow, Normal blood
counts, absence of tumor cells from blood, absence of other signs and
symptoms of the disease.
• CNS prophylaxis should begin during this phase of treatment with
MTX – 12 mg IT on days - 1, 8, 15, 22 and continue during the
consolidation/intensification period.
62. REMISSION INDUCTION
Combination of:
• Prednisolone (1mg/kg p.o days 1-28 days) or dexamethasone
• Vincristine - 1.5mg/m2 i.v weekly one dose x 4 weeks
• Asparaginase (better tolerance in pediatric patients) - 1,00,000
u/m2(total dose) in divided doses of 10,000 u daily for 10 days
• and
• Daunorubicin (used in Adult ALL) 30mg/m2 i.v weekly one dose x 4
weeks
• CR rates of 80% - 90% have been achieved.
63. REASSESS
After 4 weeks of phase 1 induction assess marrow for remission.
• If there is remission - taper prednisolone and after 1 week - restart
phase 2 induction
• If there is no remission - give 2 more weekly doses of vincristine and
doxorubicin - and then assess - if still no remission - go for alternate
regimen.
64. Alternate regimens
• Cyclophosphamide 650mg/m2 i.v days 1 and 15
• Cytosine arabinoside 75mg/m2 i.v x 4 days a weeks for 4 week i.e
day
1-4,8-11,15-18,22-25
• Methotrexate 12mg/m2 IT days 1,8,15,22
65. INTENSIFICATION (CONSOLIDATION)
THERAPY (6 – 8 MONTHS)
• Aim: To further reduce tumor burden
• When normal hematopoiesis is restored, patients in remission become
candidates for intensification therapy
• High doses of multiple agents not used during the induction phase or
readministration of the induction regimen.
66. • Vincristine, cyclophosphamide, cytarabine, daunorubicin, etoposide,
thioguanine or mercaptopurine in different combinations.
• CNS protection
Intrathecal methotrexate or cytarabine is usually used combined
with or without cranial irradiation
INTENSIFICATION (CONSOLIDATION)
THERAPY (6 – 8 MONTHS)
67. CONTINUATION THERAPY (2 TO 3 YEARS
FROM THE TIME OF DIAGNOSIS)
• Aim: To kill any residual cells that were not killed by remission
induction, and intensification regimens
• Long-term drug exposure or the host immune system is needed to kill
residual, slowly dividing leukemic cells or to suppress their growth
and thus allow programmed cell death to occur.
68. • Daily oral mercaptopurine,
• once weekly oral methotrexate,
• once monthly 5-day course of intravenous vincristine and
• oral corticosteroids are usually used.
CONTINUATION THERAPY (2 TO 3 YEARS
FROM THE TIME OF DIAGNOSIS)
69. VARIOUS REGIMENS
• Berlin-Frankfurt-Munster regimen
(BFM)
• Larson Regimen
(Cancer and leukemia Group B :CALGB)
• Hyper CVAD and MTX/HIDAC REGIMEN:
MD Anderson Cancer Center
70.
71.
72. Standard-intensity regimens (older adults)
HYPER-CVAD / METHOTREXATE -CYTARABINE
Cycles 1, 3, 5, and 7
(3-4 wk between cycles):
• CYCLOPHOSPHAMIDE 300 mg/m2 IV over
2h every 12 h for six doses starting on day
1 plus mesna 600 mg/m2/day continuous
IV infusion on days 1-3, starting 1 h
before plus
• VINCRISTINE 2 mg IV on days 4 and
11 plus doxorubicin 50 mg/m2 IV on day
4 plus dexamethasone 40 mg PO on days
1-4 and 11-14
Cycles 2, 4, 6, and 8 (3-4 wk
between cycles):
• METHOTREXATE 200 mg/m2 IV over 2 h followed by 800
mg/m2 IV over 22 h on day 1 plus
• CYTARABINE 3 g/m2 (1 g/m2 for patients older than 60 y)
IV over 2 h every 12 h for four doses starting on day
2 plus
• Leucovorin 15 mg every 6 h for eight doses beginning 12
h after the completion of methotrexate infusion,
• Methylprednisolone 50 mg IV every 12 h on days 1-3
73. MAINTENANCE CHEMOTHERAPY (FOR UP TO 2 Y):
• 6-MERCAPTOPURINE 50 mg PO 3 times daily plus
• METHOTREXATE 20 mg/m2 PO weekly plus
• VINCRISTINE 2 mg IV monthly plus
• PREDNISONE 200 mg PO daily for 5 d monthly (with vincristine)
Standard-intensity regimens (older adults)
HYPER-CVAD / METHOTREXATE -CYTARABINE
74. CALGB 8811 ALL REGIMEN
COURSE I – INDUCTION (4 WK):
• Cyclophosphamide 1200 mg/m2 (800
mg/m2 if patients older than 60 y) IV on day
1 plus
• daunorubicin 45 mg/m2/day (30 mg/m2/day
if patients older than 60 y) IV on days 1-
3 plus
• vincristine 2 mg IV on days 1, 8, 15, and
22 plus
• prednisone 60 mg/m2/day PO on days 1-21
(days 1-7 if patients older than 60 y)
• Also includes L-asparaginase 6000 U/m2 SC
on days 5, 8, 11, 15, 18, and 22; however, L-
asparaginase is no longer commercially
available
COURSE II – EARLY INTENSIFICATION (4
WK/CYCLE, FOR TWO CYCLES):
• Intrathecal methotrexate 15 mg on day
1 plus cyclophosphamide 1000 mg/m2 IV on
day 1 plus
• 6-mercaptopurine 60 mg/m2/day PO on days
1-14 plus
• cytarabine 75 mg/m2/day SC on days 1-4 and
8-11 plus
• vincristine 2 mg IV on days 15 and 22 plus
• L-asparaginase 6000 IU/m2 SC on days 15, 18,
22, and 25 (no longer commercially available)
75. CALGB 8811 ALL REGIMEN
COURSE III – CNS PROPHYLAXIS AND
INTERIM MAINTENANCE (12 WK):
• Cranial radiation 1800-2400 cGy on days
1-12 plus
• intrathecal methotrexate 15 mg on days
1, 8, 15, 22, and 29 plus
• 6-mercaptopurine 60 mg/m2/day PO on
days 1-70 plus
• methotrexate 20 mg/m2 PO on days 36,
43, 50, 57, and 64
COURSE IV – LATE INTENSIFICATION
(8 WK):
• Daunorubicin 30 mg/m2 IV on days 1, 8,
and 15 plus
• vincristine 2 mg IV on days 1, 8, and
15 plus
• dexamethasone 10 mg/m2/day PO on
days 1-14 plus
• cyclophosphamide 1000 mg/m2 IV on day
29 plus
• 6-thioguanine 60 mg/m2/day PO on days
29-42 plus
• cytarabine 75 mg/m2/day SC on days 29-
32 and 36-39
76. CALGB 8811 ALL REGIMEN
COURSE V – PROLONGED MAINTENANCE
(UNTIL 24 MO FROM DIAGNOSIS):
• Vincristine 2 mg IV on day 1 plus
• prednisone 60 mg/m2/day PO on days 1-5 plus
• methotrexate 20 mg/m2 PO on days 1, 8, 15, and 22 plus
• 6-mercaptopurine 80 mg/m2/day PO on days 1-28;
repeat all every 4wk
79. Blinatumomab
• Blinatumomab, sold under the brand name Blincyto, is used as
a Category 1 – 1st line treatment for Philadelphia chromosome-
negative ALL
• It belongs to a class of constructed monoclonal antibodies, bi-specific
T-cell engagers (BiTEs), that exert action selectively and direct the
human immune system to act against tumor cells.
80. • Blinatumomab specifically targets the CD19 antigen present on B cells.
• In December 2014, it was approved by the US FDA on the outcome of
clinical trials that were ongoing at the time of approval.
• Blinatumomab is given as a continuous IV infusion for 28 consecutive days
per cycle - start therapy at 9 mcg/day; escalate to 28 mcg/day after 7 days if
the toxicity does not recur. If the toxicities occurred at 9 mcg/day, or if the
toxicity takes more than 7 days to resolve, discontinue therapy permanently
Blinatumomab
81. • When blinatumomab was approved, Amgen announced that the price
for the drug would be US $178,000 per year, which made it the most
expensive cancer drug in the market beating -
Merck's pembrolizumab which was priced at US$150,000 per year
when it launched (in September 2014).
Blinatumomab
82. ROLE OF RADIATION IN ALL
• CNS prophylaxis
• CNS Therapy (active disease)
• TBI
• Testis prophylaxis(sanctuary sites)
• Palliation
83. CNS PROPHYLAXIS
Indications:
• Overt CNS involvement at time of diagnosis
• High risk disease
• <1 yo, >10 yo
• WBC > 50,000
• T-cell ALL
• Philadelphia chromosome (BCR-ABL translocation)
84. CNS PROPHYLAXIS
• PCI for CNS prophylaxis as frontline treatment for patients with ALL
led to an increase in survival in the 1970s.
• However, toxicity from PCI is significant, particularly with early trials
using 24 Gy
• Dose can be reduced to 12-18 Gy to reduce toxicity
85. Dana-Farber Cancer Institute (DFCI)/Acute Lymphoblastic
Leukemia (ALL) Consortium
• DFCI Consortium protocol: cranial RT 12 Gy
• Indications:
T-cell phenotype,
CNS-3 status at diagnosis, or
residual disease after induction
86. COG AALL0232 protocol (High risk B-precursor ALL)
• Prophylactic 12 Gy cranial RT
• Slow early responders (day 15 BMBx shows L2/L3 disease)
• Patients pre-treated with steroids (e.g. for bronchiolitis symptoms)
• Therapeutic 18 Gy cranial RT
• CNS 3 disease
• Therapeutic 24 Gy testicular RT
• Initial testicular involvement, and continued evidence of testicular
involvement at the end of Induction
87. Dose varies on protocol
• 24 Gy in past, rarely used due to toxicity.
• 18 Gy (standard dose) associated with decreased risk of CNS complications
• 12 Gy has been used more recently in European trials
• Fraction size
• Usually 180 cGy
• Sometimes 160 cGy (thought to be lower neurocognitive effects)
• Volume
• Cranial radiation only (no spinal irradiation)
• Areas to watch
• Cribiform plate (reported site of failure for medulloblastoma)
• Temporal lobes
88. CRANIAL IRRADIATION
• Include the subarachnoid space
within the cranial vault.
• Inferior margin : cribriform plate,
middle cranial fossa, lower border
C2 .
• The posterior globe of the eye is
included.
• SHIELD: anterior half eye
89.
90. NEURAXIS IRRADIATION
INDICATIONS
• OVERT CNS LEUKEMIA IN ADULTS: Unsuitable for chemotherapy,
isolated CNS relapse.
DOSAGE:
• TO THE CRANIUM - 24 TO 30 Gy.
• TO THE SPINE - 15 to 18Gy.
• 1.5 TO 1.8 Gy /#
91. ALLOGENIC STEM CELL TRANSPLANTATION
• Usually done in second
remission.
Can be done in first remission in
high risk patients:
• WBC>25000
• Poor initial response to remission
Long-term event-free survival
rates range from
• 30 to 40 % with chemotherapy
alone
• 40 to 60 % with allogeneic
transplantation
96. METABOLIC COMPLICATIONS
• Tumor lysis syndrome
• Hyperuricemia , hyperphosphatemia, hypocalcemia , hyperkalemia
• Especially with B cell or T cell ALL or B cell precursor leukemia with High-risk factors such as –
• elevated WBC count, especially > 50,000/mm3;
• marked elevation of LDH, especially >1000 U/L;
• baseline hyperuricemia; and
• baseline renal dysfunction
97. • Management:
• Hyperuricemia :
• Aggressive hydration
• Allopurinol or rasburicase (recombinant urate oxidase)
• Hyperphosphatemia :
• Phosphate binder, such as aluminum hydroxide
• Calcium carbonate (if the serum calcium concentration is low)
METABOLIC COMPLICATIONS
98. LEUKOSTASIS
• Occurs with elevated blast count (WBC > 100000/mm3 )
• Symptoms -
Dyspnea,
headache,
confusion and
hypoxia
99. Management :
• Leukapheresis and aggressive
hydration is repeated daily in
conjunction with chemotherapy
until blast count is < 50000
LEUKOSTASIS
100. INFECTION CONTROL
Infection can be
• Due to Neutropenia
Management:
• Broad-spectrum antibiotic until fever is controlled.
• Suggested regimens include a third- or fourth-generation cephalosporin or
carbapenem with or without vancomycin.
• Antibiotics can be modified based on response to therapy; additional antibiotics might
be needed for resistant organisms
101. Afebrile patients should receive prophylactic antibiotics, such as –
• ciprofloxacin (or levofloxacin) and
• acyclovir (or valacyclovir), and
• an azole antifungal (posaconazole, voriconazole, itraconazole, or fluconazole)
during induction therapy
INFECTION CONTROL
102. CARE DURING REMISSION INDUCTION
THERAPY
1. Reverse protective isolation and air filtration
2. Elimination of contact with people with infections
3. Refraining from eating certain food products, such as raw cheese,
uncooked vegetables, or unpeeled fruits
4. Use of antiseptic mouthwash, especially for patients with mucositis.
5. Administration of granulocyte colony stimulating factor can quicken
recovery .
103. HEMATOLOGIC SUPPORT
• ALL or its treatment can lead to thrombocytopenia, anemia and marrow
suppression
Hemorrhagic manifestations are common
Management:
Platelet transfusion
Packed red cells transfusion
104. FOLLOW UP
• If the patient completes chemotherapy for 2 years without
relapse -stop chemotherapy and follow up is suggested then.
• No relapse within 5 years can be declared as cured.
105. LATE EFFECTS OF TREATMENT
• Cranial irradiation - Cognitive and intellectual impairment, CNS neoplasms
• Chemotherapeutic drugs - Secondary AML
• Endocrine dysfunctions - Short stature, obesity, growth retardation
• Anthracycline - Cardiotoxicity
• Steroid - Avascular necrosis of bone
106. RELAPSE
• Reappearance of blast at any site in the body after initial remisson during chemotherapy or after
completing chemotherapy.
• MARROW RELAPSE
• Poor outcome
• Hyper CVAD regimen can be tried
• Allogenic BM transplant
• CNS RELAPSE
• Cranial irradiation
• Intrathecal therapy
• TESTICULAR RELAPSE
Chemotherapy plus b/l testicular radiation (Dose: 24 to 26 Gy in 1.5- to 2.0-Gy fractions)
107. CONCLUSION
• Chemotherapy cures more children than adults; adolescents benefit
from intensive regimens
• Children: Multiagent chemotherapy plus CNS chemotherapy; 2/3rd
patients are cured
• Adults: Poorer prognosis as compared to children; Choice of
chemotherapy may depend on institutional policies
