acute leukemia
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acute leukemia
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UAEU - CMHS - Hematology-Oncology Course - MMH 302 - HONC 320. Education material for medical students - It cover basic principles of hematology and oncology, including CAR-T and gene editing. It can be used for study and review. It illustrates main principles of hematology and oncology.
chronic myeloid leukemia, CML, epidemiology, BCR ABL1 gene, philadelphia chromosome, t(9;22), CML incidence, etiology of CML, pathophysiology of CML, phases of CML, treatment of CML, Allogenic stem cell transplant, TKI therapy for CML, Sokal index for CML,
UAEU - CMHS - Hematology-Oncology Course - MMH 302 - HONC 320. Education material for medical students - It cover basic principles of hematology and oncology, including CAR-T and gene editing. It can be used for study and review. It illustrates main principles of hematology and oncology.
chronic myeloid leukemia, CML, epidemiology, BCR ABL1 gene, philadelphia chromosome, t(9;22), CML incidence, etiology of CML, pathophysiology of CML, phases of CML, treatment of CML, Allogenic stem cell transplant, TKI therapy for CML, Sokal index for CML,
BIBLIOGRAPHY:
Datta Parul, Textbook of Pediatric Nursing, edition 4, The medical sciences publishers, 4838/24 Ansari road, Daryaganj, New Delhi, 110002, India
INTRODUCTION
Leukemia is the most common type of childhood malignancy.
It is characterized by persistent and uncontrolled production immature and abnormal WBCs.
It is a disease of abnormal proliferation and maturation of bone marrow which interferes with the production of normal RBCs, WBCs and platelets.
Leukemia is defined as uncontrolled neoplastic proliferation of leukocyte precursors.
According to National Cancer Institute,
Leukemia is defined as a cancer that starts in blood-forming tissue, such as the bone marrow, and causes large number of abnormal cells to be produced and enter the bloodstream.
95-98% of childhood leukemia are acute type.
70-75% of acute lymphocytic leukemia.
common malignancy of children less than 15 years.
peak incidence is four years of age.
males are more affected than females.
twice more common in white then black in children.
The exact cause is unknown.
viruses like HPV ,Epstein Barr virus ,human T cell lymphoma leukemia virus (HTLV).
Radiations
exposure to chemicals and drugs like benzene and Dilantin
familial predisposition
chromosomal abnormalities like Down syndrome
Genetic like Fanconi's anemia ,bloom syndrome
ACUTE LYMPHOCYTIC LEUKEMIA
Primary disorder of bone marrow in which normal bone marrow elements are replaced by immature or undifferentiated blast cells.
develop when lymphoid cell line is affected.
characterized by anemia, thrombocytopenia, neutropenia, especially granulocytopenia.
the incidence rate is one in 2000 live birth.
the peak age of onset is 3 to 7 years and males are more affected than females
According to French American British classification on the basis of cell morphology it is classified as
L1
L2
L3
According to type of cell it is classified as
T cell
B cell
Pre-B cell
Null cell
T cell
10 to 15% ,high risk ,seen in older children especially males ,featured as mediastinal mass ,hepatosplenomegaly ,high WBC count ,CNS involvement and has poor prognosis.
B cell
1 to 2% children ,aggressive form ,poor prognosis and high-risk type.
Pre-B cell
Good prognosis and respond well to therapy.
Null cell
No cellular surface markers (80% ).
Great imitator, with vague and varied signs and symptoms, resembling almost any disease.
Peripheral blood examination which shows decrease hemoglobin, RBC, hematocrit and platelet count
bone marrow analysis in which large number of lymphoblasts and lymphocytes with hypercellular visible.
chest X-ray
CSF
Chemotherapy
radiation therapy
bone marrow transplantation
supportive and symptomatic management
Chemotherapy
Remission induction chemotherapy
Vincristine, Prednisolone, Asparaginase and Adriamycin are given for 4-6 weeks.
maintenance therapy or systemic continuation
6 MP (Mercaptopurine) and MTX (Methotrexate) are given for 2.5-3 years.
late intensification or THERAPY
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!
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
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Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
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
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.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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
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.
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
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
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.
5. The most common malignant neoplasms of
childhood are………………
INTRODUCTION
6. The most common malignant neoplasms of
childhood are Leukemias.
INTRODUCTION
7. The most common malignant neoplasms of
childhood are Leukemias.
Which one is the commonest type of
childhood Leukemias?
AML
ALL
CML
JCML
INTRODUCTION
8. The most common malignant neoplasms of
childhood are Leukemias
Which one is the commonest type of
childhood Leukemias?
AML …………….%
ALL …………….%
CML .……………%
JCML …………….%
INTRODUCTION
9. The most common malignant neoplasms of
childhood are Leukemias
Which one is the commonest type of
childhood Leukemias?
AML …………….%
ALL 80%
CML .……………%
JCML …………….%
INTRODUCTION
10. The most common malignant neoplasms of
childhood are Leukemias
Which one is the commonest type of
childhood Leukemias?
AML 10%
ALL 80%
CML 2-3%
JCML 1-2%
INTRODUCTION
15. 1- Acute lymphoblastic leukemia/lymphoma
Synonyms: Former Fab L1/L2
• Precursor B acute lymphoblastic
leukemia/lymphoma. Cytogenetic subtypes:
t(12;21)(p12,q22) TEL/AML-1
t(1;19)(q23;p13) PBX/E2A
t(9;22)(q34;q11) ABL/BCR
T(V,11)(V;q23) V/MLL
• Precursor T acute lymphoblastic
leukemia/lymphoma
2-Burkitt's leukemia/lymphoma Synonyms:
Former FAB L3
3-Biphenotypic acute leukemia
CLASSIFICATION
EITIOLOGY
16. B-cell ALL
• Early pre-B ALL (pro-B ALL) - 10%
• common ALL - 50%
• pre-B ALL - 10%
• mature B-cell ALL (Burkitt leukemia) - 4%
T-cell ALL
• pre-T ALL - 5% to 10%
• mature T-cell ALL - 15% to 20%
CLASSIFICATION
EITIOLOGY
38. B Lineage T Lineage
CD19/CD79a/CD22 CD3 (surface/cytoplasmic)
Pre-pre-B ALL — Precursor T ALL CD1a, CD2,
CD5, CD7,
CD8, cCD3
Common ALL CD10 (CALLA) Mature T ALL Surface CD3
(plus any other
T-cell markers)
Pre-B ALL Cytoplasmic
IgM
Mature B-cell
ALL
Cytoplasmic or
surface Ig
56. Outcomes of treatment
A remission (complete remission)
Minimal residual disease
Active disease
57. Prognosis
Sex
Ethnicity
Age at diagnosis
Whether the cancer has spread to the brain or
spinal cord
Initial white blood cell count
Response of patient to initial treatment
Genetic disorders such as Down's Syndrome
ALL subtype
Cytogenetics
Chromosome translocations
Editor's Notes
bimodal age distribution: an early peak at around 4 to 5 years where the incidence may be as high as 4 to 5 per 100,000 population, followed by a second gradual increase at around age 50 where it reaches up to 2 per 100,000 population
Blasts"The immature blood cells of an acute leukemia are generally called blasts. One has to be aware, that in bone marrow a small number of blasts is absolutely normal.
A malignant blast population may be detected because of
Increase of immature cells
Abnormal marker expression of immature cells
based on morphologic criteria (cell size, cytoplasm, nucleoli, basophilia, and vacuolation)
Whereas the morphologic distinction between L1 and L2 has lost its prognostic significance, L3 morphology is associated with mature B-cell ALL (Burkitt's lymphoma) and is characterized by a high rate of cell turnover giving rise to the "starry sky" pattern on marrow biopsies
the morphologic distinction of L1, L2, and L3 morphologies is abandoned as no longer relevant. Both FAB and WHO classification systems continue to rely heavily on morphological assessment
L1 ALL - uniform small blasts, scanty cytoplasm, high nuclear cytoplasmic ratio
L2 ALL - blast cells are larger, heterogeneous, lower nuclear cytoplasmic ratio, prominent nucleoli
L3 ALL – blasts are large with prominent nucleoli, strongly basophilic cytoplasm, and cytoplasmic vacuoles
The recent WHO International panel on ALL recommends that the FAB classification be abandoned, since the morphological classification has no clinical or prognostic relevance. It instead advocates the use of the immunophenotypic classification mentioned below.
Genetic predisposition
Trisomy 21, Klinefelter's syndrome,
Inherited diseases with excessive chromosomal fragility such as Fanconi's anemia, Bloom's syndrome, and ataxia-telangiectasia
Infectious etiologies:
HTLV-1 as the etiologic agent of adult T-cell leukemia/lymphoma (ATLL)
Epstein-Barr virus (EBV) with mature B-cell ALL
HIV-related lymphoproliferative disorders
Varicella and influenza viruses
Radiation
Benzene and other chemicals
A genetic predisposition to ALL can be deduced from a higher incidence of ALL among mono- and dizygotic twins of ALL patients
trisomy 21, Klinefelter's syndrome, and inherited diseases with excessive chromosomal fragility such as Fanconi's anemia, Bloom's syndrome, and ataxia-telangiectasia have a higher risk of developing ALL (10–14). Recent studies have implicated a protective effect of a polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene in infant and adult ALL, pointing toward genetic susceptibility genes as part of ALL etiology
Infectious etiologies are implicated in the pathogenesis of ALL (17,18). Associations have been described with HTLV-1 as the etiologic agent of adult T-cell leukemia/lymphoma (ATLL) (19), and Epstein-Barr virus (EBV) with mature B-cell ALL and HIV-related lymphoproliferative disorders (20). Associations have further been suggested with varicella and influenza viruses
headache, nausea and vomiting, lethargy, irritability, nuchal rigidity, papilledema.
are pallor, petechiae, and ecchymosis in the skin and mucous membranes and bone tenderness
Liver, spleen, and lymph nodes are the most common sites of extramedullary involvement
An anterior mediastinal (thymic) mass is present in 7 to 10 percent of childhood cases
A bulky, anterior mediastinal mass can compress the great vessels and trachea and possibly lead to the superior vena cava syndrome or the superior mediastinal syndrome. 68 Patients with this syndrome present with cough, dyspnea, orthopnea, dysphagia, stridor, cyanosis, facial edema, increased intracranial pressure, and sometimes syncope
Painless enlargement of the scrotum can be a sign of a testicular leukemia or hydrocele,
ocular involvement (leukemic infiltration of the orbit, optic nerve, retina, iris, cornea, or conjunctiva), subcutaneous nodules (leukemia cutis), enlarged salivary glands (Mikulicz syndrome), cranial nerve palsy, and priapism (resulting from leukostasis of the corpora cavernosa and dorsal veins or sacral nerve involvement). Epidural spinal cord compression at presentation is a rare but serious finding that requires immediate treatment to prevent permanent paraparesis or paraplegia. In some pediatric patients, infiltration of tonsils, adenoids, appendix, or mesenteric lymph nodes leads to surgical intervention before leukemia is diagnosed.
ALL is associated with exposure to radiation and chemicals in animals and humans. The association of radiation and leukemia in humans has been clearly established in studies of victims of the Chernobyl nuclear reactor and atom bombs in Hiroshima and Nagasaki. In animals, exposure to benzene and other chemicals can cause leukemia. Epidemiological studies have associated leukemia with workplace exposure to chemicals, but these studies are not as conclusive. Patients who are treated for other cancers with radiation and chemotherapy often develop leukemias as a result of that treatment
he needs further information about what he sees?
E.g., a patient shows an increase of lymphocytes in his blood. The reason for this may be a leukemia or it may just be a reaction to a viral infection. With flow cytometry this important discrimination is rather easy.
Another example: in the microscope you definitely spot blasts, you are sure that the patient has an acute leukemia. But what kind. It may be an acute lymphocytic leukemia or an acute myeloid leukemia. This distinction is important for therapy and for prognosis. Flow cytometry usually can give the answer.
Sometimes flow cytometry helps to define the leukemia subgroup. For example the so called M7, the megakaryoblastic leukemia. Flow cytometry also helps to define lymphoma subgroups, for example the distinction between CLL, hairy cell leukemia or other subgroups.
large platelets in blood films, normal hemoglobin concentration, and absence of leukocyte abnormalities in blood or marrow
Patients with ALL or aplastic anemia can present with pancytopenia and complications associated with marrow failure. However, in aplastic anemia, hepatosplenomegaly and lymphadenopathy are rare, and the skeletal changes associated with leukemia are absent. The results of bone marrow aspiration or biopsy usually distinguish between the two diseases, although the diagnosis can be difficult in a patient who has hypocellular marrow that is later replaced by lymphoblasts. In one study, transient pancytopenia preceded ALL in 2 percent of all pediatric cases. 75 During the preleukemic phase in these patients, PCR analysis demonstrated monoclonality.
ALL should be considered in the differential diagnosis of patients with hypereosinophilia, which can be a presenting feature of leukemia or can precede its diagnosis by several months
Infectious mononucleosis and other viral infections, especially those associated with thrombocytopenia or hemolytic anemia, can be confused with leukemia.
Patients with acute infectious lymphocytosis, pertussis or parapertussis can have marked lymphocytosis However, even when leukocyte counts are as high as 50 x 109/liter, the affected cells are mature lymphocytes rather than lymphoblasts. Bone pain, arthralgia, and occasionally arthritis mimic juvenile rheumatoid arthritis, rheumatic fever, other collagen diseases, or osteomyelitis. Bone marrow should be examined if glucocorticoid treatment is planned for presumed rheumatoid diseases.
WBC Normal, Reduced 0.1 thou, increased 10-12 tho, Hyperleukocytosis 1 million 500 thousand
Most patients have circulating leukemic blast cells. Hypereosinophilia, generally reactive, may precede the diagnosis of ALL by several months. 70 Some patients, principally male, have ALL with the t(5;14)(q31;q32) chromosomal abnormality and a hypereosinophilic syndrome (pulmonary infiltration, cardiomegaly, and congestive heart failure). These patients often do not have circulating leukemic blasts or other cytopenias and have a relatively low percentage of blasts in the bone marrow
CBC (Anemia, neutropenia, and thrombocytopenia)
leukocyte counts range widely, from 0.1 to 1500 x 109/liter (median 10–12 x 109/liter). Hyperleukocytosis (>100 x 109/liter) is seen in 10 to 16 percent of patients.
Profound neutropenia (<0.5 x 109/liter) is found in 20 to 40 percent of patients, rendering them at high risk for infection
Most patients have circulating leukemic blast cells.
Hypereosinophilia,
hypereosinophilic syndrome (pulmonary infiltration, cardiomegaly, and congestive heart failure). These patients often do not have circulating leukemic blasts or other cytopenias and have a relatively low percentage of blasts in the bone marrow
Occasionally, a child with ALL has a hemoglobin level as low as 1 g/dl.
Decreased platelet counts often are seen at diagnosis (median, 48–52 x 109/liter).
Occasional patients, principally male, present with thrombocytosis (>400 x 109/liter).
Decreased platelet counts often are seen at diagnosis (median, 48–52 x 109/liter). This finding differs from immune thrombocytopenia because the decreased platelet counts almost always are accompanied by anemia, leukocyte abnormalities, or both.
WBC Normal, Reduced 0.1 thou, increased 10-12 tho, Hyperleukocytosis 1 million 500 thousand
Most patients have circulating leukemic blast cells. Hypereosinophilia, generally reactive, may precede the diagnosis of ALL by several months. 70 Some patients, principally male, have ALL with the t(5;14)(q31;q32) chromosomal abnormality and a hypereosinophilic syndrome (pulmonary infiltration, cardiomegaly, and congestive heart failure). These patients often do not have circulating leukemic blasts or other cytopenias and have a relatively low percentage of blasts in the bone marrow
CBC (Anemia, neutropenia, and thrombocytopenia)
leukocyte counts range widely, from 0.1 to 1500 x 109/liter (median 10–12 x 109/liter). Hyperleukocytosis (>100 x 109/liter) is seen in 10 to 16 percent of patients.
Profound neutropenia (<0.5 x 109/liter) is found in 20 to 40 percent of patients, rendering them at high risk for infection
Most patients have circulating leukemic blast cells.
Hypereosinophilia,
hypereosinophilic syndrome (pulmonary infiltration, cardiomegaly, and congestive heart failure). These patients often do not have circulating leukemic blasts or other cytopenias and have a relatively low percentage of blasts in the bone marrow
Occasionally, a child with ALL has a hemoglobin level as low as 1 g/dl.
Decreased platelet counts often are seen at diagnosis (median, 48–52 x 109/liter).
Occasional patients, principally male, present with thrombocytosis (>400 x 109/liter).
Decreased platelet counts often are seen at diagnosis (median, 48–52 x 109/liter). This finding differs from immune thrombocytopenia because the decreased platelet counts almost always are accompanied by anemia, leukocyte abnormalities, or both.
Coagulopathy, usually mild, can be seen in 3 to 5 percent of patients, most of whom have T cell ALL
The level of serum lactate dehydrogenase is increased in most patients with ALL and is well correlated with the size of the leukemic infiltrate. 77 Increased levels of serum uric acid are common in patients with a large leukemic cell burden, a finding that reflects an increased rate of purine catabolism. Patients with massive renal involvement can have increased levels of creatinine, urea nitrogen, uric acid, and phosphorus. Occasionally, patients with T cell ALL present with acute renal failure, despite a relatively small leukemic infiltrate. 78 Rarely, patients present with hypercalcemia resulting from release of parathyroid hormone-like protein from lymphoblasts and leukemic infiltration of bone. 79 Liver dysfunction as a result of leukemic infiltration occurs in 10 to 20 percent of patients, usually is mild, and has no important clinical or prognostic consequences. 59 Serum immunoglobulin levels (mostly IgA and IgM classes) are modestly decreased in approximately one third of children with ALL. The reduction reflects the decreased number and impaired function of normal lymphocytes. 80 Urinalysis may show microscopic hematuria and the presence of uric acid crystals.
Chest radiography: Evaluate for a mediastinal mass. In general, no other imaging studies are required. However, if the physical examination reveals enlarged testes, perform ultrasonography to evaluate for testicular infiltration.
Testicular ultrasonography: Perform testicular ultrasonography if the testes are enlarged on physical examination.
Renal ultrasonography: Some clinicians prefer to evaluate for leukemic kidney involvement to assess the risk of tumor lysis syndrome.
Echocardiography and ECG: Obtain an echocardiogram and an ECG before anthracyclines are administered.
potassium, phosphorus
Chest radiography is needed to detect enlargement of the thymus or mediastinal nodes, with or without pleural effusion (see Fig. 91-3). Although bony abnormalities, such as metaphyseal banding, periosteal reactions, osteolysis, osteosclerosis, and osteopenia, can be found in 50 percent of patients, especially children with low leukocyte counts at presentation, 81 skeletal roentgenography is not necessary for case management. Spinal roentgenography is useful in patients with suspected vertebral collapse.
Testicular ultrasonography
Renal ultrasonography
Echocardiography and ECG
Flow cytometry can answer this question quickly and reliably. Some antigens are typical for AML others for ALL. Some antigens are typical for B-ALL others for T-ALL. How reliably a marker defines a lineage can be estimated from a table published by the European group for the immunophenotyping of leukemias (EGIL).
Precursor T-cell acute lymphoblastic leukemia/lymphoma. Flow cytometry. Staining pattern seen in a marrow cells from a patient with acute lymphoblastic leukemia/lymphoma, precursor T-cell type. The upper left panel shows the pattern of leukocyte common antigen (CD45) versus side-scatter analysis. Lymphoblasts have slightly dimmer CD45 staining than mature lymphocytes but merges with the normal lymphocyte population. The upper middle and upper right panels show that the bright CD45+ population (indicated by R1 and shown in red on gated graphs) contains a subpopulation of cells that are negative for surface CD3 and surface CD19 but co-express CD4 and CD8 (a common thymocyte phenotype). In this case, the CD4+/CD8+ population accounts for approximately 26% of all cells in the marrow. The lower row of dot plots indicates that this population is surface CD3 negative, surface CD5 positive, surface CD7 positive, and co-expresses cytoplasmic CD3 and terminal deoxynucleotidyl transferase (TdT). TdT is a nuclear antigen, but can be assessed by flow cytometry using permeabilization methods that are also used for assessing cytoplasmic marker staining (cellular fixation in formalin, followed by incubation of antibody with cells in a very weak detergent solution).
Precursor B ALL blasts are positive for TdT, HLA-DR, CD19, and CD79a. Different stages of maturation have been defined as pre-pre-B ALL (pro-B-ALL), common ALL, and pre-B ALL. Whereas pre-pre-B ALL blasts are positive for CD19, CD79a, or CD22, but no other B-cell differentiation antigens, common ALL (cALL, early pre-B-ALL) is characterized by expression of CD10 (common ALL antigen, CALLA), and pre-B-ALL by expression of cytoplasmic immunoglobulins with or without CD10. Mature B-cell ALL (Burkitt's lymphoma) blasts are positive for surface immunoglobulins (sIg, usually IgM), are clonal for or light chains, and are negative for TdT. Similarly to B-lineage ALL, T ALL can be further stratified into subtypes based on different stages of intrathymic differentiation (37,38). Surface CD3 (sCD3) is the most lineage-specific marker for T-cell differentiation and is typically positive in mature T ALL. Mature T ALL is also positive for either CD4 or CD8 but not both. Blasts in pre-T-ALL are negative for sCD3, but may still express cytoplasmic CD3 (39). Pre-T-ALL is negative for both CD4 and CD8. CD52 is expressed in about 30 to 50% of cases of T ALL. It is not lineage-specific, but may have therapeutic significance when using the anti-CD52 monoclonal antibody alemtuzumab.
Coexpression of markers from more than one lineage can be demonstrated in 15 to 50% in adult ALL and 5 to 35% in children (40–44). Using flow cytometry, lineage can be assigned in more than 95% of cases and truly biphenotypic leukemias are rare (45,46).
T(1;19)(Q23;P13.3)
oligonucleotide or cDNA microarray technologies are being investigated to identify previously unrecognized molecular ALL subtypes
TRISOMY 8 (+8), G-BANDING
DUP(1)(Q12-21) G-BANDING
del(6)(q15-q22) G-banding. Arrow indicates deletion on long arm of chromosome 6.
A: ALL, less nucleoli, condensed nuclear chromatin, and cytoplasmic granules are absent.
B: AML, delicate nuclear chromatin, prominent nucleoli, and fine azurophilic cytoplasmic granules..
A & B are AML while C & D are ALL
The combination of vincristine, corticosteroids, and anthracyclines achieves complete remission (CR) rates of 72 to 92% with a median remission duration of around 18 months and has been the backbone of ALL induction regimens (102). Dexamethasone is often substituted for prednisone because of better in vitro antileukemic activity and achievement of higher drug levels in the cerebrospinal fluid (CSF) (103,104). Intensification of induction by use of additional agents has positively influenced outcome in some ALL subsets [e.g., T-lineage ALL (cytarabine and cyclophosphamide) and mature B ALL (fractionated doses of cyclophosphamide and high-dose methotrexate)] (90,91,95,105–107). Hematopoietic growth factors
high-dose methotrexate in standard risk B-lineage ALL; cyclophosphamide and cytarabine in T-lineage ALL; and high-dose methotrexate and high-dose cytarabine in high-risk B-lineage ALL.
No maintenance therapy is given in mature B-cell ALL
Philadelphia chromosome (Ph)-positive ALL remains disputed, but requires reconsideration in view of the emergence of effective BCR-ABL tyrosine kinase inhibitors such as imatinib
A remission (complete remission) is usually defined as having no evidence of disease after treatment. This means the bone marrow contains fewer than 5% blast cells, the blood cell counts are within normal limits, and there are no signs or symptoms of the disease. A molecular complete remission means there is no evidence of leukemia cells in the bone marrow, even when using very sensitive tests, such as PCR.
Minimal residual disease is a term used after treatment when leukemia cells can't be found in the bone marrow using standard tests (such as looking at cells under a microscope), but more sensitive tests (such as flow cytometry or polymerase chain reaction) find evidence that leukemia cells remain in the bone marrow.
Active disease means that either there is evidence that the leukemia is still present during treatment or that the disease has relapsed (come back) after treatment. For a patient to be in relapse, they must have more than 5% blast cells present in the bone marrow.
Age: Younger patients tend to have a better prognosis than older patients. There is no set cutoff for this, but generally those younger than 50 do better than those in their 50s, while people in their 50s do better than those in their 60s or older.
Initial white blood cell count: People with a lower WBC count (less than 50,000) at the time of diagnosis tend to have a better prognosis.
ALL subtype: In general, T-cell ALL has a better prognosis, while mature B-cell ALL (Burkitt leukemia) has a poorer prognosis. Other subtypes of B-cell ALL fall somewhere in between. It's important to note that these rules aren't absolute. For instance, some subtypes of T-cell ALL have a better outlook than others.
Chromosome translocations: The presence of Philadelphia chromosome (a translocation between chromosomes 9 and 22), which is found in 20% to 25% of ALL cases, predicts a poorer prognosis. The same is true of a translocation between chromosomes 4 and 11, which is found in about 5% of cases.
Response to chemotherapy: Patients who achieve a complete remission (no evidence of leukemia remaining) within 4 to 5 weeks of starting therapy tend to have a better prognosis than those in whom this takes longer. Patients who don't achieve a complete remission at all have a poorer outlook. The prognostic value of minimal residual disease (described below) is still being studied.
Sex: females tend to fare better than males.
Ethnicity: Caucasians are more likely to develop acute leukemia than African-Americans, Asians and Hispanics and tend to have a better prognosis than non-Caucasians.
Age at diagnosis: children between 1-10 years of age are most likely to develop ALL and to be cured of it. Cases in older patients are more likely to result from chromosomal abnormalities (e.g. the Philadelphia chromosome) that make treatment more difficult and prognoses poorer.
White blood cell count at diagnosis of less than 50,000/µl
Whether the cancer has spread to the brain or spinal cord
Morphological, immunological, and genetic subtypes
Response of patient to initial treatment
Genetic disorders such as Down's Syndrome
Cytogenetics, the study of characteristic large changes in the chromosomes of cancer cells, has been increasingly recognized as an important predictor of outcome in ALL.[12]
Some cytogenetic subtypes have a worse prognosis than others. These include:
A translocation between chromosomes 9 and 22, known as the Philadelphia chromosome, occurs in about 20% of adult and 5% in pediatric cases of ALL.
A translocation between chromosomes 4 and 11 occurs in about 4% of cases and is most common in infants under 12 months.
Not all translocations of chromosomes carry a poorer prognosis. Some translocations are relatively favorable. For example, Hyperdiploidy (>50 chromosomes) is a good prognostic factor.