This document discusses diagnosis and management of various types of leukemia. It provides information on acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML). For AML, it describes diagnostic criteria including blood tests, bone marrow examination, immunophenotyping, cytogenetics and molecular genetics. It outlines treatment including induction chemotherapy and consolidation therapy. For ALL, it similarly discusses diagnosis and treatment approaches including chemotherapy, immunotherapy and stem cell transplantation. Finally, it covers CML including the Philadelphia chromosome abnormality and treatment with tyrosine kinase inhibitors like imatinib.
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
One of my best friends (when I was a teenager) died of leukemia. Several advances have been made in the ensuing decades (see attached document). Watch this space for additional notes.
Lymphoma is the third most common cancer in children <15 years of age.The prognosis for children with newly diagnosed chemosensitive non-Hodgkin’s lymphoma (NHL) and Hodgkin’s disease (HD) has improved significantly.Despite the generally excellent prognosis of children and adolescents with Hodgkin’s lymphoma (HL), approximately 15% of patients relapse. Aggressive chemotherapy followed by autologous bone marrow transplantation has been used with some improvement in survival.
One of my best friends (when I was a teenager) died of leukemia. Several advances have been made in the ensuing decades (see attached document). Watch this space for additional notes.
Lymphoma is the third most common cancer in children <15 years of age.The prognosis for children with newly diagnosed chemosensitive non-Hodgkin’s lymphoma (NHL) and Hodgkin’s disease (HD) has improved significantly.Despite the generally excellent prognosis of children and adolescents with Hodgkin’s lymphoma (HL), approximately 15% of patients relapse. Aggressive chemotherapy followed by autologous bone marrow transplantation has been used with some improvement in survival.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
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.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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
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.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
2. Leukemia
Leukemiaare malignantdisordersof the hematopoieticstemcell
compartment, characteristicallyassociated with increased numbers of
whitecells in the bone marrowand/or peripheral blood
leukemiaare traditionallyclassified into four main groups:
• acute lymphoblastic leukemia (ALL)
• acute myeloid leukemia (AML)
• chronic lymphocytic leukemia (CLL)
• chronic myeloid leukemia (CML).
3. Risk factors for leukemia
Ionising radiation
• Afteratomic bombing of Japanese cities (myeloid leukemia)
• Radiotherapy
• Diagnostic X-rays of the fetus in pregnancy
Cytotoxic drugs
• Especiallyalkylating agents (myeloid leukemia, usually after
latent period of several years)
• Industrial exposure to benzene
4. Retroviruses
• Adult T-cell leukemia/lymphoma (ATLL) caused by human T-cell
lymphotropicvirus 1(HTLV-1, mostprevalent in Japan, the Caribbean and
someareas of Central and South America and Africa
Genetic
• Identical twin of patients with leukemia
• Down’ssyndromeand certain othergenetic disorders
Immunological
• Immunedeficiency states (e.g. hypogammaglobulinaemia A)
5. Acute leukemia
• There is a failure of cell maturation in acute leukemia.
• Proliferation of cells that do not mature leads toan accumulation of
primitivecells that take up more and more marrow spaceat the
expenseof the normal hematopoieticelements.
• Acute myeloid leukemia (AML) is about four times more common
than acute lymphoblastic leukemia (ALL) in adults.
• In children, the proportions are reversed, the lymphoblastic variety
being morecommon.
6. ACUTE MYELOID LEUKEMIA(AML)
Mostcommon leukemia in india
Morecommon in males>females, averageage >65years
>20% marrow filled with myeloblast
Lossof differentiation of myeloblast
Pancytopenia
Lymphadenopathy,hepatosplenomegaly: uncommon
Onsetwithin 2-3 months
Hyperuricemia
Skin involvementseen
7.
8.
9.
10.
11. DIAGNOSIS OF AML
MORPHOLOGICAL FEATURES
- CBC : pancytopenia
increased WBC (bad prognosis)
- Peripheral blood smear : myeloblast (Auerrods m3>m2)
12. CYTOCHEMISTRY
Positive for Myeloperoxidaseand sudan black
IMMUNOPHENOTYPING
Toconfirm the diagnosis of AML
Myeloblast – CD11b,CD13,CD15,CD33,CD117,HLA-DR
Myelomonocyte - CD11b,CD13,CD14,CD15,CD32,CD33,HLA-DR
Erythroid – spectrin,ABH ambigens, glycophonin,carbonic anhydrase 1,
HLA-DR
Promyelocytic – CD13,CD33
Monocytic – CD11b,11C,CD13,CD14,CD33,CD65,HLA-DR
Megakaryoblastic – CD34,CD41,CD42,CD61,anti-von Willibrand factor
13. CYTOGENETICS
- Translocation( 15;17) : PML –RAR alpha best prognosis
- t ( 8;21 ) : RUN –X1 – RUN X1 good prognosisexcept for m2
- t (16;16 ) : associatewith inversion 16
good prognosisexcept for m4
- any translocationsother than ( 16;16 , 8;21, 15;17 ) have bad prognosis
MOLECULAR GENETICS
- Nucleophosmin Gene mutation(M/C) : good prognosis
- CEBPA( cancerenhancer binding protein) : good prognosis
- FLT3 – ITD : bad prognosis
14. BLOOD PICTURE IN AML
Anaemia
Thrombocytopenia
Platelet <50000/microliter
TLC < 5000/ microliter in 50%
10% havecounts > 1,00,000/microliter
BONE MARROW PICTURE IN AML
3-95% leukemic blast cells
>20% is thearbitrarycut off
Mpoand Sudan black positive
Auerrods : m3>m2
Decrease in granulopoiesis,erythropoiesis,megakaryopoiesis
Marrow fibrosis is minimal
15. TREATMENT FOR AML
The first decision must be whetheror not togive specific treatment to
attempt toachieve remission.
This is generally aggressive, has numerousside-effects, and may not be
appropriate for theveryelderlyor patients with serious comorbidities In
these patients, supportive treatmentcan effectconsiderable
improvement in well-being.
Low-intensitychemotherapy, such as low-dosecytosinearabinosideor,
recently, azacitidine, is frequentlyused in elderlyand more frail patients
butonly induces remission in less than 20% of patients
16. Specific therapy
- Ideally, whenever possible, patientswith acute leukemiashould be
treated within a clinical trial.
- The aim of treatment is todestroy the leukaemiccloneof cells without
destroying the residual normal stemcell compartment from which
repopulationof the haematopoietic tissueswill occur.
- Patientshould be prepared as follows before the specific therapy
1. Existing infections identified and treated (e.g. urinary tract
infections, oral candidiasis, dental, gingival and skin infections)
2. Anaemiacorrected by red cell concentratetransfusion
17. 3. Thrombocytopenic bleeding controlled by platelet transfusions
4 . If possible, central venouscatheter (e.g. Hickman line) inserted to
facilitateaccess to the circulation fordeliveryof chemotherapy,
fluids, blood productsand othersupportivedrugs
5. Tumourlysis risk assessed and prevention started: fluidswith
allopurinol or rasburicase
6 .Therapeutic regimen carefullyexplained to the patientand informed
consentobtained
7. Consideration of entry intoclinical trial
18. Drugs commonly used in the treatmentof acute myeloid
leukemia
Induction Phase : Daunorubicin (IV)
Cytarabine (IV)
Etoposide (IV and oral)
Gentuzumabozogamicin (IV) All-
trans retinoicacid (ATRA) (oral)
Arsenic trioxide (ATO)
CONSOLIDATION PHASE : Cytarabine (IV)
Amsacrine (IV)
Mitoxantrone (IV)
19. RELAPSE PHASE : Fludarabine
Cytarabine
Arsenic trioxide (ATO)
Idarubicin
Aggressive front line chemotherapy in fit patients
- < 40yrs,withoutcomorbid condition
- 7 + 3 days regimen
7 – cytarabine ( 100-200mg /m2/day)
3 – daunorubicin (60-90mg/day)
- from day 7 : period of strictvigilant monitoring
- from day 14 : bone marrowstudy
look forremission (molecular> morphological)
20. Morphological remission
Blasts - <5%
Platelet - >100000
Absoluteeosinophilic count >100
Molecularremission : minimal residual disease is not detected
on flow cytometry
- If there is a morphological remission – Consolidate
- If tehre is no morphological remission – Repeat 7+ 3 regime
21.
22.
23.
24. ACUTE LYMPHOBLASTIC LEUKEMIA
In acute lymphoblastic leukemia (ALL), the malignantclonearises
from hematopoietic progenitors in the bone marrowor lymphatic
system resulting in an increaseof immature nonfunctioning leukemic
cells.
Infiltration of bone marrow leads toanemia, granulocytopenia, and
thrombocytopeniawith the clinical manifestationsof fatigue,
weakness, infection, and hemorrhages.
25. These symptomsare moreoften the reason a patient first seeks
medical advice rather than consequences of tumor bulk, such as
lymph nodeenlargement, hepatosplenomegalycaused by leukemic
infiltration, orsymptomsof the central nervoussystem
ALL is the most frequent neoplasticdisease in children with an
early peak at the ageof 3–4 years
26. Patientswith some rare congenital chromosomal abnormalities havea
higher risk of developmentof acute leukemia; e.g., Klinefelter’s
syndrome, Fanconi’sanemia, Bloom’ssyndrome, ataxia telangiectasia,
and neurofibromatosis.
There is a twentyfold increased incidenceof leukemia in patientswith
Down syndrome, in whom ALL is increased in childhood orAML atan
olderage.
Mostcommon typeof ALL is Pre B cell typewhich has a good
prognosis rest other like Pro B cell type, Pro T cell,Pre T cell type has
bad prognosis
27. Acute Lymphoid Leukemia - Diagnosis
Bood counts = low
Peripheral Smear = lymphoblast
Bone marrow = > 20% blastcells
if the countsare high = very bad prognosis
28. Cytological
Stains : PAS ( Periodic Acid Schiff ) positive
Acid phosphatase positive (only forT - Cell all)
Immunophenotyping
Early pre 6-Cell ALL : CD11,CD19,CD79a,TdT Positive
If associated with tumor : CO20, CD22 also present
Pro 6 - Cell ALL CD10 absent
Cytogenetics
1) Children – t(12:21) – good prognosis
2) Adults - t (9:22), t(4:11),t(1:19) has got poor prognosis and poor
response
36. • Chimeric Antigen Receptor (CAR) Tcells
- The adoptive transferof CAR-modified Tcells directed against CD19 is a
promising approach to the treatmentof CD19+ childhood oradult ALL.
• CRISPR geneeditting technique
- The CRISPER gene editing technique is used in humans to remove specfic
genes toallow the immune system to be more activated against cancer.
- Recently,this CRISPER technology has used to insert genes that allow
immunecells toattack cancer cells,potentially leaving normal cells
unharmed and increasing the effectiveness of immunotherapy
37.
CHRONIC MYELOID leukemia
Chronic myeloid leukemia (CML) is a myeloproliferativestemcell
disorderresulting in proliferation of all haematopoietic lineages but
manifesting predominantly in the granulocytic series. Maturation
of cells proceeds fairly normally.
The disease occurschiefly between the ages of 30 and 80 years, with a
peak incidenceat 55 years.
The defining characteristicof CML is the chromosomeabnormality
known as the Philadelphia (Ph) chromosome
38.
The break on chromosome 22 occurs in the breakpointclusterregion
(BCR).
The fragment from chromosome 9 that joins the BCR carries the abl
oncogene, which forms a fusion gene with the remains of the BCR.
This BCR ABL fusion gene codes for a 210 kDa protein with tyrosine
kinase activity, which playsa causative role in thedisease as an
oncogene, influencing cellularproliferation, differentiation and
survival.
In some patients in whom conventional chromosomal analysisdoes not
detecta Ph chromosome, the BCR ABL gene product is detectable by
moleculartechniques.
39. Thedisease has three phases:
• A chronic phase :
- in which the disease is responsive to treatmentand is easilycontrolled, which
used to last 3–5 years
- With the introduction of imatinib therapy, this phase has been prolonged to
encompass a normal lifeexpectancy in many patients.
• An accelerated phase (not always seen) :
- in which disease control becomes more difficult
40. Blast crises :
- In this phase the diseasewill transforms intoan acute leukemia,either
Myeloblast(70%) or Lymphoblastic (30%), which is relatively
refractory to treatment
- This is the causeof death in majorityof patients, therefore survival is
dictated by the timing of blastcrisis,which cannot be predicted.
41. Clinical features
Symptomsat presentation may include lethargy, weight loss,abdominal
discomfort, goutand sweating, butabout 25% of patientsare asymptomatic
atdiagnosis.
Splenomegaly is present in 90%; in about 10%, theenlargement is massive,
extending toover 15 cm below the costal margin.
A friction rub may be heard in cases of splenic infarction.
Hepatomegaly occurs in about 50%.
Lymphadenopathy is unusual.
42. DIAGNOSIS OF CML
Blood picture :-
- decreased hemoglobin
- mild anisopoikilocytosis
- WBC count >25000/microliter
- 50% havecount >1,00,000/microliter
- cytochemicallyabnormal WBC: LOW LAP
- Absoluteeosinophil count is increased
- Thrombocytosis : hemorrhage and thrombosisare
very rare
- Basophilia/ tryptase raised
43. - Wright geimsa stain showing bone marrow hypercellularity with
myeloid hyperplasia
Bone marrow
- marked hypercellularity
- predominantgranulopoiesis ( 30:1)
- decreased erythropoiesis
- Dwarf megakaryocytes increased
- Sea blue histiocytes/ pseudogaucher
cells
44. Moleculardiagnosis
- 95% will have philadelphiachromosome
G banding : sent in T lymphocytes
- 5% can still have BCR-ABL transcripts detectable by PCR
- FISH: is specific for ( 9:22) translocation
- Deletion of 20q, trisomy 8, del 3q, double philadelphiachromosome
has Bad prognosis
Chemical findings
uricacid - high
LDH - high
histamine - high
angiogenic factor - high
45. PHASES OF AML
ACCELERATED PHASE
- Persistant or increase in WBC count
- Persistant or increase in splenomegaly
- Persistant thrombocytopenia
- cytogenetic evaluation
- Basophilia in blood > 20%
- Blast in blood/ bone marrow 10- 19% or 5-19%
46. BLASTIC PHASE
- CML transforming into AML,myeloid sarcoma
- Blast > 20% in blood/bone marrow
- LAP increased
- myeloid > lymphoid
49. Starting with Imatinib lifelong therapy
- Chronic phase : 400mg/day
- Blast/ accelerated phase : 600-800mg/day
Side effects : Peri orbital edema,hypophosphatemia,diarrhoea
skin rashes and myelosuppression
Nilotiniband Dasatinibcan be started without imatinib also,
indicated if there is any thyrosine kinasedomain mutation
- Dasatinib : pulmonary HTN, QT prolongation
- Nilotinib: PVOD,pancreatitis
- Ponatinib : used if there is T3151 mutation
50. First 2 weeks we look forcomplete hematological response
- WBC <10,000
- Platelet < 4.5L
- Peripheral smear is normal
- Patient is asymptomatic
Complete molecular response
- By 3 months
- BCR-ABL transcripts are undetectable by PCR
Complete cytogenic response
- 6 months
- Nocells contains ph chromosome
51. Response to Imatinib :
- Full blood countsevery 2 weeks
- Bone marrowevery 6 months toassess cytogenic response -
Quantitative PCR For BCR- ABL 1 transcriptsevery 3 months
Treatment of accelerated and blast phase :
- Allogenic transplant ( when patientcomes back tochronic
phase)
- 40% response to Imatinib 600mg daily
- Imatinib pluschemotherapy : Blastic phase
52.
53.
54. CHRONIC LYMPHOCYTIC LEUKEMIA
Chronic lymphocytic leukemia (CLL) is a monoclonal proliferation of
mature B lymphocytesdefined byan absolute numberof malignant cells
in the blood (5 × 109/mL).
The presence of malignant B cells under this count in the blood without
nodal, spleen, or liver involvementand absentcytopenias is a precursorof
this disease called monoclonal B-cell lymphocytosis (MBL) with ~1–2%
chance per year of progressing to overt CLL.
55. CLL is a heterogeneousdisease in termsof natural history, with some
patients presenting asymptomaticallyand neverrequiring therapy,
• Whereas others presentwith symptomaticdisease, require multiple
lines of therapy, and eventuallydie of theirdisease
CLL is primarilya disease of olderadults, with a median age atdiagnosis
of 71 years
The male:female ratio is 2:1; however, as patients age, the ratio becomes
more even, and over the age of 80, the incidence is equal between men
and women
56. The morphology, immunophenotype, and gene expression pattern of
CLL cells are that of a mature B cell, and so it has been presumed that
the initiating cell is a mature lymphocyte, perhaps memory B
Monoclonal B cell count > 5000cells/microliter– CLL
Monoclonal B cell count < 5000cells/microliter – monoclonal B cell
Lymphocytosis
- Bone marrow not involved, perpheral blood is involved
CD markers ; CD19,CD20,CD21,CD22,CD79a,CD79b,S1gm
On mature B cell CD5,CD23 is stronglyexpressed
57. CYTOGENETIC ABNORMALITIES
The mostwell-characterized abnormalities includedel(13) (q14.3),
trisomy 12, del(11)(q22.3), and del(17)(p13.1)
The presence of soledel(13)(q14.3) isassociated with more indolent
disease, prolonged survival, and good response to traditional therapies.
58. GENE MUTATIONS
- Wholegenome and whole exome sequencing
have identified the most common mutations in
CLL to be in SF3B1, NOTCH1, MYD88, ATM,
and TP53
- Mutations of the tumorsuppressor TP53 are
found in ~5% of CLL in previously untreated
early stage disease and up to 40% in later
stages.
- TP53 mutations are associated with a poor
prognosis and expected lack of response to
DNA-damaging therapies.
64. First lineof treatment
FCR regime : Fludarabine, Cyclophosphamide,Rituximab
BR regime : Bendamustine,Rituximab
< 60 year FCR regime, >60 year BR regime
AntiapoptoticTherapies
- BCL2 is anotherpromising target in CLL.
- Venetoclax is an orally bioavailable, selective BCL2 inhibitor.
- It is currently Food and Drug Administration (FDA) approved for
marketing in patients with relapsed or refractory CLL who have the
del(17)(p13.1).
65. Immune Therapies
Current immune therapies include allogenic stem cell transplantation,
chimericantigen receptor(CAR) T-cell therapy, and oral
immunomodulatory agents such as lenalidomide
Stem cell transplantation is currently considered theonly standard curative
approach to CLL.
Because most CLL patients areolderand many havesignificant comobidity
myeloablative transplants results in extensive morbidityand mortality, making
them prohibitive in many individuals
Reduced intensityconditioning (RIC) allogeneic transplants have been
successfully incorporated into the treatmentof patients up to ~75 years in age but
still havea ≥50% frequencyof chronic graft-versus-hostdisease.
66.
67. HAIRY CELL leukemia
This is a rarechronic B-cell lymphoproliferativedisorder.
The male-to-femaleratio is 6 : 1 and the median age at diagnosis is 50 years.
Presenting symptomsare general ill health and recurrent infections.
Splenomegalyoccurs in 90% but lymph node enlargement is unusual.
Severe neutropenia, monocytopenia and the characteristic hairycells in the
blood and bone marrow are typical.
These cells usually havea B-lymphocyte immunotype but theyalso
characteristicallyexpress CD25 and CD103.
Recently, all patients with hairycell leukemia have been found to havea
mutation in the BRAF gene.