Myelodysplastic syndrome (MDS) is a group of bone marrow disorders where the bone marrow fails to produce mature and healthy blood cells. This leads to low blood cell counts and a risk of developing acute myeloid leukemia. MDS is characterized by dysplasia in one or more cell lines and subgroups are defined by specific percentages of blasts in the bone marrow and blood. Common subgroups include refractory anemia, refractory anemia with ringed sideroblasts, and refractory anemia with excess blasts. Chromosomal abnormalities are present in many cases of MDS and help define prognosis.
Myelodesplastic syndrome by haider zamanHaider zaman
Myelodesplastic syndrome presentation may easy for Medical student to know about Myelodesplastic syndrome & its classification and Sign and Symptoms,Genetically Abnormalities in MDS,Diagnosing,Morphological abnormalities in MDSs
AML:ACUTE MYELOID LEUKAEMIA
for medical colleges teaching faculty and students as well. it includes AML causes , histopathological slides of subclasses of Acute myeloid leukemia, classification , diagnosis, management modalities, complications .Acute leukemias are stem cell disorders characterized by malignant neoplastic proliferation and accumulation of immature and non functional hematopoietic cells in the bone marrow.
The neoplastic cells show increased proliferation and/or decreased apoptosis.
If the defect primarily affects the common myeloid progenitor (CMP) then it is called Acute myeloid leukemia.
Acute myeloid leukemia (AML) is a neoplastic disease characterized by infiltration of the blood, bone marrow, and other tissues by proliferative, clonal undifferentiated cells of the hematopoietic system.
AML is the result of a sequence of somatic mutations in a multipotential primitive hematopoietic cell or, in some cases, a more differentiated progenitor cell.
It can be slow growing or rapidly fatal.
AML is the predominant form of leukemia during the neonatal period
Incidence : 1.5/100,000/year in infants decreases to approximately 0.4 per 100,000 children ages 5 to 9 years, increases gradually to 1.0 persons per 100,000 until age 25 years, and thereafter increases exponentially until the rate reaches approximately 25/100,000 persons.
AML accounts for 15 to 20 percent of the acute leukemias in children and 80 percent of the acute leukemias in adults.
Men > Women (4.5 : 3)
HEREDITY
1) Chromosomal aneuploidy like Trisomy 21 noted in Down syndrome
2) Defective DNA repair, e.g., Fanconi anemia, Bloom syndrome, and Ataxia telangiectasia
3) Congenital neutropenia ie Kostmann syndrome
4) Germline mutations of CCAAT/enhancer-binding protein α (CEBPA), runt-related transcription factor 1 (RUNX1), and tumor protein p53 (TP53) have also been associated with a higher predisposition to AML
RADIATION
Peaks after 5 to 7 yrs of exposure.
Therapeutic radiation alone seems to add little risk of AML but can increase the risk in people also exposed to alkylating agents.
CHEMICAL AND OTHER EXPOSURES
Exposure to benzene, plastic, rubber, petroleum products, paint, ethylene oxide, herbicides and pesticides can increase the risk.
Smoking can also increase the risk
DRUGS
Anticancer drugs are the leading cause of therapy-associated AML.
Alkylating agent–associated leukemias occur on average 4–6 years after exposure, and affected individuals have aberrations in chromosomes 5 and 7.
Topoisomerase II inhibitor–associated leukemias occur 1–3 years after exposure, and affected individuals often have aberrations involving chromosome 11q23.
Other agents like Chloramphenicol, phenylbutazone, and, less commonly, chloroquine and methoxypsoralen.
SYMPTOMS :
Present with nonspecific symptoms initially.
Fatigue is the first symptom
Fever with or without infection will be present in approximately 10% patients
Bleeding, easy bruising
occasional
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
How to Split Bills in the Odoo 17 POS ModuleCeline George
Bills have a main role in point of sale procedure. It will help to track sales, handling payments and giving receipts to customers. Bill splitting also has an important role in POS. For example, If some friends come together for dinner and if they want to divide the bill then it is possible by POS bill splitting. This slide will show how to split bills in odoo 17 POS.
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
Palestine last event orientationfvgnh .pptxRaedMohamed3
An EFL lesson about the current events in Palestine. It is intended to be for intermediate students who wish to increase their listening skills through a short lesson in power point.
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
The Art Pastor's Guide to Sabbath | Steve ThomasonSteve Thomason
What is the purpose of the Sabbath Law in the Torah. It is interesting to compare how the context of the law shifts from Exodus to Deuteronomy. Who gets to rest, and why?
1. MODERATOR – Prof. DR. - ANIL KAPOORMODERATOR – Prof. DR. - ANIL KAPOOR
2. What Is Myelodysplastic Syndrome?
The myelodysplastic syndromes are a group of disorders
characterized by one or more peripheral blood cytopenias
secondary to bone marrow dysfunction.
In MDS the bone marrow cannot produce blood cells
effectively, and many of the blood cells formed are
defective.
These abnormal blood cells are usually destroyed before
they leave the bone marrow or shortly after entering the
bloodstream.
As a result, patients have shortages of blood cells, which
are reflected in their low blood
3. Characteristics
Varying degree of tri-lineage cytopenia ( red blood
cells, white blood cells and platelets).
Dysplasia
Normocellular or hypercellular B.M.
May progress to acute leukaemia
4. Incidence
1- Disease of elderly.
2- Median age is 65 years.
3- <10% are younger than 50 years.
4- Incidence rates 1/100,000 pop./ years.
5- Incidence rise to 1/1000 / years in > 60 years old.
6- Male slightly higher than female
21. Chromosomal abnormalities and MDS
Chromosomal abnormalities are present in up to
50%of de novo cases of MDS and in virtually all
cases of secondary MDS. The most common are:
Abnormality - 7 +7 +8 5q- 7q- 11q- 12q- 13q- 20q- inv3 i(17q) t(1;3) t(1;7) t(3;3)
Frequency(%) 15 5 19 27 4 7 5 2 5 1 5 1 2 1
22. Deletion of the long arm of chromosome 5
(5q- syndrome )
Strongly associated with RA.
5q- accounts for up to 70% of cytogenetic abnormalities in
this subtype.
The q arm of chromosome 5 is particularly rich in genes,
which encoded haemopoietic growth factors and their
receptors. For example , IL-3 , IL-4 , IL-5 , GM-CSF and the
M-CSF receptor are located in this region.
The potential for the loss of any or all of these genes
contribute to the disruption of ordered haemopoiesis.
23. Monosmy 7 and 7q-
Most strongly associated with secondary MDS.
Associated with the loss of a major surface
glycoprotein (gp 130) in neutrophile and susceptibility
to bacterial infection secondary to impaired
granulocyte monocyte chemotatic activity.
24. Deletion of the q arm of chromosome 11
(11q-)
Account for 20% of the chromosomal abnormalities
in RAS.
This abnormality is associated with raised iron stores
and high ring sidroblast counts.
The presence of the gene , which encoded the H-
subunit of ferritin at chromosome 11 , may explain
this
25. Abnormalities of chromosome 17 (i17q)
It involves the loss or disruption of the Р53 tumor
suppressor gene are seen in CML in association with
transformation to the blastic phase and in up to 5%
of cases of primary MDS.
This predisposes to certain dysplastic features and
neutrophil vaculation.
26. Abnormalities of chromosome 3
Dysmegakaryopiesis and thombocytosis appear to be
associated with Abnormalities of chromosome 3
27. The importance of indication of chromosomal
abnormalities
To confirm diagnoses .
To know the stage of disease.
To know the direction of progression of disease.
Multiple genetic abnormalities indicate late events in
MDS.
28. Abnormal localization of immature
precursors
Presence of 3 or more small clusters of myeloblasts
and promyelocytes (5 – 8 cells) in marrow trephine
biopsy in the central portion of the marrow away
from the vascular structure and the endosteal
surface of the bone trabeculae
30. Signs and Symptoms
Excessive tiredness, shortness of breath, and pale skin can
be caused by anemia (shortage of red blood cells).
Serious infections with high fevers can be caused by
leukopenia (not having enough normal white blood cells)
and, in particular, by having neutropenia or
granulocytopenia (too few mature granulocytes).
Excessive bruising and bleeding, for example, frequent or
severe nosebleeds and/or bleeding from the gums, can be
due to thrombocytopenia (not having enough of the blood
platelets needed for plugging holes in damaged blood
vessels).
34. Refractory Anemia
RA Definition:
Dyplasia of the erythroid series only.
Clinically, anemia is refractory to hematinic
therapy
Myeloblasts < 1% blood and < 5% marrow
<15% ringed sideroblasts in marrow
No Auer rods
Other etiologies of erythroid abnormalities must
be excluded. These include:
drug/toxin exposure -vitamin deficiency
viral infection -congenital disease
35. Refractory Anemia
Epidemiology:
5-10% of MDS cases.
Older patients
Morphology:
Anisopoikilocytosis on peripheral smears
Dyserythropoiesis with nuclear abnormalities
(megaloblastoid change)
< 15% ringed sideroblasts
36. Refractory Anemia
Genetics:
25% may have genetic abnormalities
Prognosis:
Median survival is 66 months
6% rate of progression to acute leukemia
39. Refractory Anemia with Ringed Sideroblasts
RARS definition:
Dyplasia of the erythroid series only.
Clinically, anemia is refractory to hematinic
therapy
Myeloblasts < 5% in marrow, absent in blood
>15% ringed sideroblasts in marrow
No Auer rods
Other etiologies of ringed sideroblasts must be
excluded. These include:
Anti- tuberculosis drugs
Alcoholism
40. Refractory Anemia with Ringed Sideroblasts
Epidemiology:
10-12% of MDS cases.
Older patients
Males > females
Morphology:
Dimorphic pattern on peripheral smears
Majority RBC’s normochromic, 2nd
population
hypochromic
Dyserythropoiesis with nuclear abnormalities
(megaloblastoid change)
41. Refractory Anemia with Ringed Sideroblasts
Genetics:
Clonal chromosomal abnormalities in
<10%; in fact, development of such an
abnormality should prompt reassessment of
diagnosis.
Prognosis:
Median survival 6 years (72 months)
1-2% rate of progression to acute leukemia
46. Refractory Anemia with Excess Blasts
RAEB definition:
Refractory anemia with 5-19% myeloblasts in the
bone marrow.
RAEB-1:
5-9% blasts in bone marrow and <5% blasts in blood.
RAEB-2:
10-19% blasts in the bone marrow
Auer rods present
47. Refractory Anemia with Excess Blasts
Epidemiology: 40% of MDS cases.
Older patients (over 50 years)
Morphology:
Dysplasia of all three cell lines often present
Neutrophil abnormalities may include:
Hypogranulation
Pseudo-Pelger-huet (hyposegmentation/barbells)
Megkaryocyte abnormalities may include
Hypolobation -Micromegakaryocytes
48. Refractory Anemia with Excess Blasts
Morphology (con’t.)
Erythroid precursor abnormalities may include:
Abnormal lobulation -megaloblastoid change
Multinucleation
0-19% myeloblasts in the blood
5-19% in the marrow
Bone marrow:
Usually hypercellular (10-15% hypocellular)
Abnormal localization of immature precursors (ALIP) may be
present
Immunophenotype:
Blasts express CD 13, CD33 or CD117
49. Refractory Anemia with Excess Blasts
Genetics:
Clonal chromosomal abnormalities found in 30% - 50% of
RAEB cases. The abnormalities include:
+8 – -5 – del(5q)
– -7 – del(7q) – Complex karyotypes
Prognosis:
Median survival, RAEB-1 = 18 months
Median survival, RAEB-2 = 10 months
RAEB-1 = 25% rate of progression to acute leukemia
RAEB-2 = 33% rate of progression to acute leukemia
52. Refractory Anemia with Excess Blasts in
Transformation (RAEB-t)
•
21-30 percent blasts in the marrow; more than
5 percent in the bloodstream
•
normal or hypercellular (filled with cells)
marrow
•
accounts for about 25 percent of cases
53. Chronic Myelomonocytic Leukemia
(CMML)
•
5-20 percent blasts in the marrow; less than 5
percent in the bloodstream
•
cytopenia of at least two cell lines
•
normal or hypercellular (filled with cells)
marrow
•
accounts for 15 to 20 percent of cases.
55. WHO
Refractory anemia
Refractory anemia e ringed siderblast
Refractory cytopenia e multilineage dysplasia
Refractory cytopenia e multilineage dysplasia &
ringed sideroblasts
Refractory anemia e excess blast-1
Refractory anemia e excess blast-2
Myelodysplastic syndrome unclassified
MDS associated e isolated del (5q)
56. WHO
Subtype Blood Bone Marrow
RA Anemia Erythroid
dysplasia only
RARS Anemia Erythroid dys
>15% ringed
RCMD Bi- pancytopenia >10%Dysp in 2
or more cell
lineage
RCMD-RS Bi-pancytopenia >10%Dys 2 or
more cell lineage
>15% ringed
57. WHO
subtype Blood Bone Marrow
RAEB-1 Cytopenia
<5% blast
Uni-multilineage
dys, 5-9%blast
RAEB-2 Cytopenia,
5-19%blast or Auer
rods
Uni-multi dys
10-19%blast
Or Auer rods
MDS-U cytopenia Myeloid or
megakaryocte dys
MDS with 5q Anemia,nor or
increased PLT
Mega e hypolobated
nuclei, <5%blast
58. Prognostic Groups
Two groups based on survival and evolution to acute
leukemia
1.) “Good” group
Refractory anemia (RA)
Refractory anemia with ringed sideroblasts (RARS)
5q - syndrome
2.) “Bad” group
Refractory anemia with excess blasts (RAEB)
Refractory anemia with excess blasts in transformation (RAEB-t)
CMML
MDS unclassified can be either
59. International Prognostic Scoring System
(IPSS) Factors
(1) the percentage of blasts in the bone
marrow.
(2)whether chromosome abnormalities are
present and, if so, which ones.
(3)how low the patient's blood counts are. These
are given a score; the lowest scores have the
best outlook for survival.
60. Prognostic Scoring
The International Myelodysplastic Syndrome Working
Group developed a scoring system based on 3 variables:
00 0.50.5 1.01.0 1.51.5 2.02.0
% Blasts% Blasts
<5<5 5-105-10 ---- 11-2011-20 20-3020-30
KaryotypKaryotyp
ee
Normal, -Y,Normal, -Y,
del(5q),del(5q),
del(20q)del(20q)
SingleSingle
karyotypickaryotypic
anomaly,anomaly,
DoubleDouble
abnormaliyabnormaliy
≥≥ 33
abnormalities,abnormalities,
chr 7chr 7
abnormalitiesabnormalities
Chr 3 abn.Chr 3 abn.
CytopeniCytopeni
aa
0-10-1 2-32-3
66. Prevention & Treatment
of Infections
Prevention
Prophylactic antibiotics no role
Patient education know your nadir
report a fever
recognize signs of infection
avoid illness, crowds
update vaccinations
Treatment Febrile neutropenia guidelines
www.nccn.org/MDS v1..2008
67. Iron Chelation Options
Deferoxamine (Desferal®)
Route: SQ
t ½: 0.5 hours
Dosing: Infused over 8-12 hrs
5-7 nights/week
Deferasirox (Exjade®)
Route: PO
t ½: 12-16 hours
Dosing: Dissolved in solution, taken daily
72. Differential Diagnosis
Non-neoplastic simulators
Other myelodysplastic disorders
eoplastic disorders may simulate myelodysplasia
Vitamin/micronutrient deficiencies
B12/folate
Copper
Ring sideroblasts present
Cytoplasmic vacuoles
May be due to
Zinc excess
Gastrectomy
Total parenteral nutrition
Infections
HIV
Parvovirus
HHV-6 in children
Toxins
Ethanol
Heavy metals
Growth factors
-macrophage colony-stimulating factor (GMCSF
Erythropoietin
Drugs (numerous)
