Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid cells characterized by the proliferation of immature lymphocytes. It most commonly affects children and adolescents. The main symptoms include fever, bleeding, bone pain, and infections. Diagnosis involves blood and bone marrow testing to identify malignant lymphoblasts. Risk-stratified treatment typically involves chemotherapy administered in phases over 2-3 years. Prognostic factors like age, white blood cell count, chromosomal abnormalities, and early treatment response predict patient outcomes.
Management of acute lymphoblatic leukemia with light on etiology, clinical features, diagnosis and different aspects of management including chemotherapy and radiation therapy
Management of acute lymphoblatic leukemia with light on etiology, clinical features, diagnosis and different aspects of management including chemotherapy and radiation therapy
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
3. Overview
• Acute lymphoblastic leukaemia (ALL) is a
heterogeneous hematologic disease characterized by
the proliferation of immature lymphoid cells in the bone
marrow, peripheral blood, and other organs.
• Most common childhood malignancy.
• Accounts 75%–80% of acute leukemias among children
• Was first clearly described by 2 pathologists in 1845
• High complete remission rates ( 97%)and Five-Year
survival rates (89%) in children (61%) AYA
10/29/2023 3
4. ACUTE LYMPHOBLASTIC LEUKEMIA
EPIDEMIOLOGY
• Most common leukemia in children.
• Accounts for (1/3rd) of childhood Malignancies
• 60% of ALL patients are diagnosed younger than 20
years of age.
• Peak age 2-5yrs
• Boys > girls
• 2500-3500 new cases in the US annually
• 3.4 cases per 100,000
• Greatest incidence in the US among Hispanics
• Higher incidence in whites vs blacks
10/29/2023 4
5. Epidemiology contd
•Incidence is generally low in Africa and a study in
Kenya incidence of 1.2/100,000 (<15yrs)
•1 case at our oncology unit (5 yr old M died)
•ALL is 5 times commoner in children than AML
10/29/2023 5
6. Epidemiology contd
•Identical twins, the risk to the
• second twin if one twin develops leukemia is greater than
that in the general population.
•The risk is >70% if ALL is diagnosed in the first twin
during the 1st yr of life and monochorionic
• If the first twin develops ALL by 5-7 yr of age, the risk to the
second twin is at least twice that of the general
population, regardless of zygosity.
•Other siblings
10/29/2023 6
7. ALL - ETIOLOGY
•A two-step process of genetic mutation and
exposure to infection play a prominent role.
• The first step occurs in utero, when fusion gene
formation or hyperdiploidy generates a covert,
pre-leukemic clone.
•The second step is the acquisition of secondary
genetic changes that drive conversion to overt
leukemia.
•Only 1% of children born with a pre-leukemic
clone progress to leukemia.
10/29/2023 7
8. ETIOLOGY
• Children with certain genetic and immunodeficiency
syndromes are at increased risk: Down syndrome, Klinefilter
syndrome, Neurofibromatosis type 1, Bloom syndrome,
Fanconi anemia and ataxia telangiectasia.
• Radiation exposure may be associated with increased risk :
Survivors of the 1945 atomic bombings of Hiroshima and
Nagasaki have an overall relative risk of 9.1 for developing
ALL compared with an age-matched controls.
• Chemical toxins : exposure to high levels of benzene.
10/29/2023 8
9. ETIOLOGY Contd
•Secondary ALL may occur after certain
chemotherapies ( eg, cyclophosphamide, etoposide
doxorubicin)
•Viruses : Some potential associations were
identified between EBV and Burkitt-ALL ( Mature B-
Cell ALL) HTLV-1
10/29/2023 9
10. Classification of ALL
• FAB ( French-American-British) classification
• Based largely on morphology
• Little prognostic or therapeutic information to help guide treatment
decisions.
• WHO ( World Health Organization) classification
• Revised in 2008,2016
• Discarded the FAB terms since morphological classification has no
clinical or prognostic relevance.
• Changed the classification to reflect increased understanding of the
biology and molecular pathogenesis of ALL.
10/29/2023 10
11. WHO Classification of B-lymphoblastic
leukemia/lymphoma(WHO-HAEM5R)
• B-lymphoblastic leukemia/lymphoma, NOS
• B-lymphoblastic leukemia/lymphoma with recurrent genetic
abnormalities
• B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2);BCR-
ABL1(fusion)
• B-lymphoblastic leukemia/lymphoma with t(v;11q23.3); KMT2A
rearranged
• B-lymphoblastic leukemia/lymphoma with
t(12;21)(p13.2;q22.1);ETV6-RUNX1
• B-lymphoblastic leukaemia/lymphoma with ETV6::RUNX1-like
features
• B-lymphoblastic leukemia/lymphoma with hyperdiploidy
10/29/2023 11
12. WHO Classification of B-lymphoblastic
leukemia/lymphoma(5th Edition)
• B-lymphoblastic leukemia/lymphoma with hypodiploidy
• B-lymphoblastic leukemia/lymphoma with t(5;14)(q31.1;q32.3) IL3-
IGH
• B-lymphoblastic leukaemia/lymphoma with TCF3::HLF fusion
• B-lymphoblastic leukemia/lymphoma with t(1;19)(q23;p13.3);TCF3-
PBX1
• B-lymphoblastic leukemia/lymphoma, BCR-ABL1-like*
• B-lymphoblastic leukemia/lymphoma with iAMP21*
10/29/2023 12
13. WHO Classification of T-lymphoblastic
leukemia/lymphoma
• T-lymphoblastic leukaemia / lymphoma, NOS
• Early T-precursor lymphoblastic leukaemia / lymphoma
10/29/2023 13
14. Clinical Presentation
• Fever
• Signs and symptoms of anemia, such as pallor, fatigue, dizziness,
palpitations, cardiac flow murmur, and dyspnea with even mild
exertion
• Bleeding
• Disseminated intravascular coagulation (DIC) at diagnosis (about 10%
of cases)
• Blood clots
• Palpable lymphadenopathy
10/29/2023 14
15. Clinical Presentation
• Bone pain (can be severe common in lower limbs)
• Left upper quadrant fullness and early satiety due to splenomegaly
(about 10% of cases)
• Symptoms of leukostasis (eg, respiratory distress, altered mental
status)
• Kidney failure in patients with a high tumor burden
• Infections, including pneumonia
• Petechiae (particularly on lower extremities) and ecchymoses
• Rashes from skin infiltration with leukemic cells
10/29/2023 15
16. Clinical Presentation (Less Common)
• Headache is uncommon (<5 percent of cases), but leukemia involving
the central nervous system can present with
• headache, vomiting, lethargy, nuchal rigidity, and, rarely, with cranial
nerve abnormalities
• Testicular enlargement is rare (<1 percent),
• but painless unilateral testicular enlargement can be a presenting
sign of ALL/LBL.
• However, testicular involvement is present in up to 10 percent of
boys with relapsed leukemia
10/29/2023 16
17. Clinical Presentation (Less Common)
• A mediastinal mass, which is most often associated with T-ALL/LBL,
can cause superior vena cava (SVC) syndrome, which may manifest as
pain, dysphagia, dyspnea, or swelling of the neck, face, and
upper limbs due to obstruction the SVC.
• Respiratory distress may result from a mass compressing the
trachea.
10/29/2023 17
18. Diagnosis (Pre-treatment)
• Complete blood count (CBC) with peripheral smear
• Coagulation Profile (prothrombin time [PT], activated partial
thromboplastin time [aPTT], fibrinogen)
• Chemistry profile, U/E/Crs, LFTs , Uric Acids, and,LDH
• Bone marrow aspiration and biopsy – Definitive diagnostic tests
• Cultures; in particular, blood cultures
• Chest radiography
• Chest computed tomography (CT) scan, as indicated by symptoms
• Multiple-gated acquisition (MUGA) scan or echocardiogram
• Lumbar puncture
• HIV,HBSAsg, CMV,EBV
• HLA -typing
10/29/2023 18
19. Confirmatory Diagnosis
• ALL is characterized by presence of immature cells – blast cells
• of >20% in the -blood picture -bone marrow examination
• A negative myeloperoxidase (MPO) stain and a positive and terminal
deoxynucleotidyl transferase (TdT) is the hallmark of the diagnosis of
most cases of ALL
10/29/2023 19
21. Acute lymphoblastic leukemia (ALL), peripheral
blood of a child, Pappenheim stain, magnification
x100
10/29/2023 21
22. Diagnosis contd
• The polymerase chain reaction (PCR)
• Fluorescence in situ hybridization(FISH)
(to pinpoint molecular genetic abnormalities & can be used to detect small
numbers of malignant cells at diagnosis as well as during follow-up.)
• DNA microarray
( helps analyze the expression of thousands of genes in the leukemic
cell. This technique promises to further enhance the understanding of
the fundamental biology and to provide clues to the therapeutic
approach of ALL.)
• Flow cytometry helps to distinguish B-ALL from T-ALL.
10/29/2023 22
24. Phenotypically
Based on surface markers ALL derived from
• B lineage (85 percent), B-lymphoblastic leukemia
• T lineage ( 15 percent), T-lymphoblastic leukemia
• Mature B cells(1 percent) Burkitt leukemia
10/29/2023 24
26. Key Terminology in treatment
• Complete Remission : Criteria for CR include:
• Evidence of eradication of detectable leukemia cells
• ≤ 5% blasts present in the bone marrow.
• Evidence of normal Bone marrow recovery ( at least > 25% bone
marrow cellularity)
• platelet count ≥ 100 x 109/L
• neutrophil count ≥ 1 x 109/L.
• Minimal Residual Disease (MRD): Refers to residual leukemic cells
that remain following the achievement of CR, but are below the
limits of detection using conventional morphologic assessment.
10/29/2023 26
27. RELAPSE
• Reappearance of blast at any site in the body after initial remission
during chemotherapy or after completing chemo.
• Marrow relapse-poor outcome (15-20%)
• Hyper CVAD regimen
• Allogenic BM transplant
• CNS relapse –(<5%)
• Triple IT –alternate days till CSF clears, then twice weekly 6 doses. then one
dose every week 6 doses.
• cranial irradiation
• Testicular relapse
-chemotherapy plus b/l testicular radiation
10/29/2023 27
28. Risk-directed therapy
• is the standard of current ALL treatment and accounts
• for age at diagnosis, initial WBC count, immunophenotypic and
cytogenetic characteristics of blast populations, rapidity of early
treatment response and assessment of Minimal Residual Disease
MRD at the end of induction therapy.
• Pt are categorised as having
• STANDARD RISK- age 1-10 yr and a leukocyte count<50,000/µL are
used by the National Cancer Institute (NCI)
• High RISK- Children who are younger than 1 yr or older than 10 yr or
who have an
• initial leukocyte count of >50,000/µL are considered to be high risk.
10/29/2023 28
30. Prognostic Factors contd
• Characteristics that adversely affect outcome include T-cell
immunophenotype or a slow response to initial therapy.
• Chromosomal abnormalities, including
hypodiploidy, the Philadelphia chromosome, and KMT2A (MLL) gene
rearrangements, mutation in IKZF1 portend a poorer outcome.
• More favourable characteristics include a rapid response to therapy,
hyperdiploidy, trisomy of
• specific chromosomes (4, 10, and 17), and rearrangements of the
ETV6-RUNX1.
10/29/2023 30
31. ALL: TYPICAL TREATMENT
10/29/2023 31
Induction Consolidation Maintenance
Over a period
of months
2-3 years
CNS Prophylaxis (IT-MTX)
• Primary objective : to achieve and maintain a
complete remission (CR)
• Induction, consolidation, maintenance phases
• CNS prophylaxis with IT-MTX during induction and
consolidation phases
32. Remission induction
• is designed to eradicate the leukemic cells from the bone marrow.
• BFM regimen : frequently used in Pediatric ALL. Can be used in young adults
with good PS. Induction therapy consists of vincristine, daunorubicin,
prednisone, asparaginase, intrathecal cytarabine, and intrathecal
methotrexate.
• CALGB ALL : used in high-risk pediatric ALL, mostly AYA. Uses five drugs –
cyclophosphamide, daunorubicin, Vincristine, prednisone and L-
asparaginase in induction for 4 weeks.
• HyperCVAD : combination of hyperfractionated cyclophosphamide,
vincristine, Adramycin (doxorubicin) and dexamethasone alternating with
high-dose methotrexate and high-dose cytarabine – Regimen also includes a
risk-stratified schedule of CNS prophylaxis with IT methotrexate and IT
cytarabine. The dose-intensive phase spans six to seven months and is
followed by two years of maintenance therapy.
• Kasili Protocol: Vincristine, doxorubicin,prednisone, IT MTX (induction)
Cytarabine, cyclophosphamide in Consolidation
10/29/2023 32
34. Prognosis
• The outcome for patients at higher risk can be improved by
administration of more intensive therapy despite the greater toxicity
of such therapy.
• Infants with ALL, along with patients who present with specific
chromosomal abnormalities, such as t(4;11), have an even higher risk
of relapse despite intensive therapy.
• Higher levels of MRD present at the end of induction suggest a
poorer prognosis and higher risk of subsequent relapse. MRD of
>0.01% on the marrow on day 29 of induction is a significant risk
factor for shorter event-free survival for all risk categories, compared
with patients with negative MRD.
10/29/2023 34
35. Imatinib
• Imatinib is an agent specifically designed to inhibit the BCR-ABL
kinase resulting from the translocation
• The poor outcome of Philadelphia chromosome–positive ALL with
t(9;22) has been dramatically changed by the addition of imatinib to
an intensive chemotherapy backbone.
• With this approach, the event-free survival has improved from 30%
to 70%.
• For patients with CD20 positive B-lymphoblastic leukemia, rituximab
can be added
10/29/2023 35
36. Nelarabine
• Current therapies for T-cell acute lymphoblastic leukemia (ALL)
produce high responses, but approximately one half of patients will
relapse within 2 years.
• Nelarabine demonstrates antineoplastic activity in patients with
relapsed/refractory T-cell ALL. The Cancer and Leukemia Group B,
nelarabine treatment produced complete remission rates of 26%
with minimal toxicities in relapsed/refractory ALL patients.
10/29/2023 36
37. Supportive Therapy
• Cytopenias : All patients treated with traditional induction will
develop cytopenias which may require intervention.
Transfusion support : Platelets and Packed red cell transfusion when
necessary.
• Prevention of Tumor Lysis Syndrome ( Risk highest in Burkitt-ALL and
T-Cell ALL)
• Intravenous hydration
• Allopurinol
• Rasburicase
• Correction of electrolyte disturbances (Hypocalcemia,
Hyperphospahtemia)
• Antibiotic Prophylaxis while on aggressive chemotherapies :
10/29/2023 37
38. Complications following Treatment of ALL
• Late complications of therapy
• Brain tumors (cerebral irradiation)
• Secondary AML from topoisomerase inhibitors and alkylating agents
• Cardiomyopathy (anthracyclines)
• Osteoporosis/Osteonecrosis (corticosteroids)
• Growth disturbances
• Thyroid dysfunction (cranial irradiation)
• Obesity (uncertain etiology)
• Neuropsychiatric disturbances and seizures (IT MTX and cranial
irradiation)
• Emotional problems
10/29/2023 38
39. In Conclusion
• Acute lymphoblastic leukemia (ALL) is the most common cancer in
children but also occurs in adults.
• Can either B/T lymphoblastic leukemia
• WHO classification predominantly used.
• Treatment involves 3 phases can last 2-3yrs
• Central nervous system (CNS) involvement is common; most patients
receive intrathecal chemotherapy and corticosteroids and sometimes
CNS radiation therapy.
• Response to treatment is good in children, with cure possible in >
80% of children but in < 50% of adults.
• Repeat induction chemotherapy, immunotherapy, and stem cell
transplantation may be helpful for relapse.
10/29/2023 39
41. References
• Nelson’s paediatrics 21st edition
• Medscape
• Up to date
• https://www.nature.com/articles/s41375-022-01620-2
• https://www.msdmanuals.com/professional/hematology-and-
oncology/leukemias/acute-lymphoblastic-leukemia-all
• http://erepository.uonbi.ac.ke/bitstream/handle/11295/28663/Agwa
ta_
10/29/2023 41
Editor's Notes
German –Rudilf Virchow and Britsh John Bennet. The SEER database cure rates and survival outcomes for pediatric patients with ALL have improved dramatically over the past several decades. Improvements are largely due to advances in the understanding of the molecular genetics and pathogenesis of the disease, the incorporation of risk-adapted therapy, the advent of new targeted agents, and the use of allogeneic hematopoietic stem cell transplantation (HSCT). Analyses from the SEER database have shown improvements in survival for children and adolescent and young adult (AYA) patients, with 5-year overall survival (OS) rates of 89% and 61%, respectively.
The incidence varies worldwide but this may be influenced, in part, by diagnostic and reporting difference
The incidence varies worldwide but this may be influenced, in part, by diagnostic and reporting difference
Etiology is generally unknown , however genetic n environmental factors are associated with childhood leukemia .Most cases of ALL are thought to occur due to a 2 step
Trisomy 21, Males with etra x chro, mutatation in neurofibrin , mutations in the BLM gene , is a rare inherited bone marrow failure syndromes. a rare genetic condition that targets the nervous system, immune system and other systems
HTLV-1 is implicated in Adult T-cell leukemiaS
Classification of ALL depends on characterizing the malignant cells in the bone marrow to determine the morphology, phenotype as measured by cell
membrane markers, and cytogenetic and molecular genetic features.
NOS NOT OTHERWISE SPECIFIED. In addition, newly added from 4th edition in green. Those with translocation now fusion. The classification based on these groups remains largely unchanged from WHO-HAEM4R; however, the nomenclature focuses on the molecular events rather than cytogenetic alterations, to allow for the application of differing techniques for their detection
Red they have distinct genetic signatures that are associated with adverse prognosis
NK-lymphoblastic leukaemia/lymphoma has been deleted as an entity it used to be part of 4th edition classification
Typical onset of clinical symptoms of ALL is rapid. Symptoms reflect bone marrow failure or leukemic infiltration of extramedullary sites. Fever is one of the most common signs of ALL, and patients with ALL often have fever without any other evidence of infection. However, in these patients, one must assume that all fevers are from infections until proved otherwise, because a failure to treat infections promptly and aggressively can be fatal. Typical lymphadenopathy associated with ALL/LBL is nontender, firm, rubbery, and matted.
neutropropenia
Young children with bone pain may present with a limp or refusal to bear weight . Leco = >50-10x109
Infiltration of the marrow by massive numbers of leukemic cells frequently manifests as bone pain. This pain can be severe and is often atypical in distribution.
About 10-20% of ALL patients may present with left upper quadrant fullness and early satiety due to splenomegaly.
Although patients may present with symptoms of leukostasis (eg, respiratory distress, altered mental status) because of the presence of large numbers of lymphoblasts in the peripheral circulation, leukostasis is much less common in people with ALL than those with acute myelogenous leukemia (AML), and it occurs only in patients with the highest WBC counts (ie, several hundred thousand per μL).
Patients with a high tumor burden, particularly those with severe hyperuricemia, can present in renal failure.
It is important that thorough hx n examination is done n all studies necessary to confirm a diagnosis and adequately classify the type
of leukemia be performed before treatment as this would help with prognostication checking remission etc
Cardiac evaluation – Echocardiogram or cardiac scan should be performed to assess cardiac function in anticipation of treatment that includes an anthracycline.
Some experts perform HLA typing in the event that hematopoietic cell transplantation will be required for later management.
●CT of chest – For patients who are diagnosed with T-ALL/LBL, a CT scan of the chest, with contrast if possible, should be performed to evaluate the presence of a mediastinal mass.All children who are diagnosed with ALL/LBL must undergo a lumbar puncture (LP) prior to beginning therapy to evaluate potential leukemic involvement of the central nervous system (CNS) and concomitantly administer the first dose of intrathecal therapy, as described separately.
Features of blast cells very high N:C ratio ,large cells with large nucleiabsence of cytoplasmic granules presence of round or convoluted nuclei
These subclinical levels of residual leukemia are thought to be responsible for relapse after initial disease response.
Triple IT (Methotrexate/Hydrocortisone/Cytarabine)
Chimeric antigen receptor (CAR) T-cell technology will have an increasing
role in the treatment of patients who have experienced a relapse of ALL CNS HAS DECREASES TO LESS THAN 5% SINECE COMMENCEMENT OF PROPHYLACTIC CNS THERAPY
IKZF1 gene, have been shown to be associated with a poor prognosis and may
become important in treatment algorithms in the future
single most important prognostic factor in ALL is the treatment: without
effective therapy, the disease is fatal
Berlin-Frankfurt-Münster. (Cancer and leukemia group B) Hyper Cvd for highly aggressive Newer modifications of the hyper-CVAD regimen include the addition of a tyrosine kinase inhibitor in patients whose leukemia is Ph+, and of rituximab in patients whose leukemia is CD20 positive Both of these approaches have resulted in improvements in disease-free survival.
Infants younger than age 12 months with 11q23 abnormalities are at high risk of CNS relapse but because of their young age are usually treated without cranial irradiation, using intensified systemic and intrathecal chemotherapy to treat the CNS.
How ever a recent trial of 28 pediatric patients with relapsed or refractory T-ALL who were treated with single-agent nelarabine, the overall response rate was 39.3% (cited Zwaan et al. as referen state that the combination of nelarabine, cyclophosphamide, and etoposide has also been used in patients with relapsed or refractory T-ALL, with response rates comparable to single-agent nelarabine