This document discusses multiple myeloma, a plasma cell disorder. It begins with an overview of plasma cell disorders and defines multiple myeloma. It then covers the epidemiology, etiology, pathophysiology, clinical features, diagnostic tests including serum protein electrophoresis and immunofixation, bone marrow examination, skeletal survey, staging, prognostic factors. It also discusses related conditions like monoclonal gammopathy of undetermined significance, smoldering myeloma, non-secretory myeloma, solitary plasmacytoma, extramedullary plasmacytoma. It concludes with discussing criteria for diagnosing multiple myeloma and initial treatment approaches.
Management of Anemia in cancer patientsAjeet Gandhi
Anemia in cancer patients are important both in terms of quality of life as well as response to therapy. Cause of anemia is multi-factorial and its management is critical in optimizing best outcomes of cancer patients
Management of Anemia in cancer patientsAjeet Gandhi
Anemia in cancer patients are important both in terms of quality of life as well as response to therapy. Cause of anemia is multi-factorial and its management is critical in optimizing best outcomes of cancer patients
According to my research, the best combined treatments for MM are botrezomib and thalidomide. Targeting the proteasome inside myeloma cells looks to be the most efficient way to fight this type of cancer
An overview of the John Theurer Cancer Center at Hackensack University Medical Center - a top-50 U.S. News & World Report Best Hospitals for Cancer – the only cancer center in New Jersey with this prestigious designation.
To request printed copies of this brochure, please contact aleahing@p4strategy.com.
Jean-Luc Harousseau, M.D., Professor of Hematology, Head, Dept. of Clinical Hematology, Director of the Cancer Center Rene Gauducheau, University of Nantes, France - Impact of Novel Therapies in the Management of Multiple Myeloma
Presented at New Frontiers in the Management of Solid and Liquid Tumors hosted by the John Theurer Cancer Center at Hackensack University Medical Center. jtcancercenter.org/CME
Plasma cell disorders is a difficult topic where most residents and students confuse with regarding to differentiating between various types of para-proteinemias or plasma cell dyscrasias. This simple presentation will highlight the key points in differentiating, diagnosing these orders. Initial management principles are discussed as well.
Multiple myeloma; Definition, clinical Features ,Laboratory Diagnosis and Tre...Nawsherwan Mohammad
Myeloma, also known as multiple myeloma, is a type of cancer that affects plasma cells in the bone marrow. These abnormal plasma cells produce an excess of antibodies, leading to weakened bones, anemia, and impaired immune function. Treatment may involve chemotherapy, targeted therapy, stem cell transplant, and supportive care to manage symptoms and improve quality of life.
Multiple myeloma
Also termed plasma cell myeloma, is a neoplastic disease characterized by plasma cell accumulation in the bone marrow, the presence of monoclonal protein in the serum or urine or both and, in symptomatic patients, related tissue damage.
Almost all cases of myeloma occur over the age of 40 years, with a peak incidence between 65 and 70 years. The disease is twice as common in individuals of African compared to those of European or Asian origin.
Smouldering myeloma The term asymptomatic or smouldering myeloma is used for cases with similar laboratory findings to multiple myeloma, but no organ or tissue damage causing clinical features.
There is about a 10% chance each year of these cases becoming symptomatic and requiring therapy.
Diagnosis
Symptomatic myeloma is diagnosed if there is:
1 Monoclonal protein in serum, urine, or both.
2 Increased clonal plasma cells in the bone marrow.
3 Disease-related organ or tissue impairment. (CRAB)
A useful acronym for myeloma-associated tissue damage is CRAB (hypercalaemia, renal impairment, anaemia, bone disease.)
Amyloidosis, serum hyperviscosity, recurrent infections, peripheral neuropathy and deep vein thrombosis are other clinical complications of myeloma, which are less frequently presenting feature
Clinical features
1 Bone pain (especially backache) resulting from vertebral collapse and pathological fractures.
2 Features of anaemia, such as lethargy or dyspnea.
3 Recurrent infections related to deficient antibody production, abnormal cell-mediated immunity and neutropenia.
4 Features of renal failure or hypercalcaemia: polydipsia, polyuria, anorexia, vomiting, constipation and mental disturbance.
5 Abnormal bleeding tendency: myeloma protein may interfere with platelet function and coagulation factors; thrombocytopenia occurs in advanced disease.
6 Amyloidosis (light chain) occurs in 5% with features such as macroglossia, carpal tunnel syndrome, heart failure, periorbital purpura and diarrhoea.
7 In approximately 2% of cases there is a hyperviscosity syndrome, with purpura, haemorrhages, visual changes, central nervous system (CNS) symptoms, neuropathies and heart failure.
Figure the pathogenesis of clinical features of MM
Laboratory diagnosis
1 Presence of a paraprotein. Serum and urine should be screened by immunoglobulin electrophoresis. The paraprotein is immunoglobulin (Ig) G in 60% of cases, IgA in 20% and light chain only in almost all the rest.
Fewer than 1% have IgD or IgE paraprotein, and a similar number are non-secretory, where neither intact immunoglobulin nor light chain can be
multiple myeloma
Pathophysiology
Malignant proliferation of plasma cells in the bone marrow.
Causes bone marrow destruction via infiltration, and bone destruction via ↑RANKL activity (causing ↑osteoclast activity).
A single clone of plasma cells produce large amounts of identical immunoglobulin (a 'paraprotein' or 'monoclonal band'), as well as free κ or λ light chains (also a 'paraprotein', or 'Bence Jones protein' if in the urine).
Classified by Ig class, with prevalence reflecting prevalence in normal blood: IgG (⅔), IgA (⅓), remainder IgM or IgD.
Immunoglobulin classes other than that of the proliferating clone are relatively low ('immunoparesis').
Epidemiology
Lifetime risk: 1/140.
Incidence steadily increases with age. Rare <55.
Slightly commoner in men.
2x commoner in blacks vs. whites.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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.
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
- 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
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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
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
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.
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.
3. Sarah Newbury, the first reported patient with multiple
myeloma.
A) Bone destruction in the sternum. (B) The patient with fractured femurs
and right humerus. (C) Bone destrucion involving femur(reported by Dr
William Macintyre in london 1845).Autopsy by dr John Dalrymple.)
IN 1873 Rutizksy coined the term multiple myeloma.
4. Epidemology
The American Cancer Society has estimated 26,850 new cancer cases of
MM in the United States in 2014, with an estimated 11,240 deaths
representing 1% of all malignancies in whites and 2% in Afarican
americans.
Among hematological malignancies it constitutes 10% (2nd in number) in
USA
The mean age of affected individuals is 62 years for men (75% >70 years of age)
and 61 years for women (79% >70 years of age).
The 5-year survival rate reported in the SEER database has increased from
25% in 1975 to 34% in 2003 due to newer and more effective treatment
options available.( survilance epidemology and end results programme).
MALES more common than females(1.6:1)
India..0.5 % of all malignancies.
KASHMIR:-76/3940(0.02%) in 2014.
5. ETIOLOGY
• Radiation
• Occupational (Ni,agricultural chemicals,benzene,petroleum,silicon )
• Mineral oil used as laxative
• Heriditary and genetic.
• HLA-cw2 over expression
• Race (2:1)
• Repeated infections(however no evident cause
associated).
• MGUS(premalignant condition).
7. Pathophysiology
Indolent phase
(MGUS , smoldering myeloma, myeloma IA )
1-3 yr or longer
Overt phase
Increase in M pr
Appearance of end organ damage
6 m0- 1 yr
Plateau phase
Aggressive terminal phase
Dependent on BM
stroma
Treat effectively
Temporarily can be controlled by
chemo
Responses short lived, survival
poor
8. Multiple Myeloma - Cytogenetics
Deletion 17p and Abnormalities associated with
chromosome 13 carry a particularly unfavorable
prognosis & respond poorly to therapy
13. Multiple myeloma
Marrow
infiltration
Release of cytokines
Bone destruction Bone pain
Hypercalcemia
IL-6
Il 1 β
Anemia
Monoclonal protein Immune deficiency
Renal failure hyperviscosity Amylodosis Infection
Neurological
symptoms
coagulopathy
EMD
14.
15. Serum Protein
Electrophoresis
Serum Protein Electrophoresis :
• Serum is placed on special paper
treated with agarose gel and exposed
to an electric current. This separates
the serum protein components into
five classifications by size and electrical
charge : serum albumin, alpha-1
globulins, alpha-2 globulins, beta
globulins, and gamma globulins.
• Immunoglobulins ( IgG, IgM, IgA)
usually migrate to gamma region but
may sometimes extend to beta region.
• SPEP should always be performed in
combination with serum
immunofixation in order to determine
clonality
17. SPEP
SPEP showing Polyclonal Gammopathy
• Shows a broad based peak in gamma
region .
• Seen in chronic infections,
inflammation, connective tissue
disease, lymphoproliferative disease.
18. Immunofixation
• More sensitive than SPEP
• Immunofixation is performed when
SPEP shows a sharp “peak” or a
plasma cell disorder is suspected
despite a normal SPEP
• Immunofixation always done to
confirm the presence of M-Protein
and to determine the type (IgM or
IgG etc and the light chain
restriction : k or λ)Unlike SPEP,
immunofixation does not give
an estimate of the size of the
M protein (ie, its serum
concentration), and thus
should be done in conjunction
with electrophoresis.
21. Skeltal survey
Skull – punched out lesions
The bone lesions - proliferation of tumor
cells, activation of osteoclasts and
suppression of osteoblasts
The bone lesions are lytic in nature and are
rarely associated with osteoblastic new
bone formation.
radioisotopic bone scanning is less useful
in diagnosis than is plain radiography.
22. MM & Skeletal Complications
~ 80% of patients with multiple
myeloma will have evidence of
skeletal involvement on
skeletal survey
• Vertebrae: 65%
• Ribs: 45%
• Skull: 40%
• Shoulders: 40%
• Pelvis: 30%
• Long bones: 25%
Dimopoulos M, et al. Leukemia. 2009:1-12.
23. .
MRI offers a sensitive means to document extent of bone marrow infiltration
and cord or root compression in patients with pain syndromes.
28. Denotes presence of an M-protein in a
patient without a plasma cell or
lymphoproliferative disorder i.e;
Undetermined Significance
Monoclonal Gammopathy of Undetermined
Significance ( MGUS)
29. • Incidence of MGUS increases with age :
• 1% of adults in US
• 3% of adults over age 70 years
• 11% of adults over age 80 years
• 14% of adults over age 90 years
• Significance : Can progress to monoclonal
Disease
IgG or IgA MGUS
IgM MGUS
Monoclonal Gammopathy of Undetermined
Significance ( MGUS)
30. • Predictors of Progression :
• Size of the M-protein at the time of recognition of MGUS -
most important predictor of progression
• IgM & IgA monoclonal proteins have a greater risk of
progression than an IgG M-protein.
• Risk of progression does not go away with time!
• Risk of progression 1% per year
• CUMULATIVE RISK
• 10% at 10 years, 25% at 25 years from diagnosis
• So, Management :
MGUS - Progression
31. • Both criteria should be met :
• Serum monoclonal protein ≥3 g/dL and/or bone marrow plasma cells ≥10
percent
• No end organ damage related to plasma cell dyscrasia (see CRAB)
• Management :
• Does not require any intervention
• Close surveillanace is necessary to ensure stability of the disease ( SPEP,
CBC, Creatinine and calcium every 3 to 4 month and Skeletal Survey
annually to pick up asymptomatic bone lesions)
Smoldering Myeloma
32. • Rare variant : About 1% of Myelomas
• May present with Bone lesions ( most common presenting
symptom bone pain)
• No serum or urine monoclonal protein ( diagnosis can be
missed if one is not aware of this entity, NSMM).
• Renal failure and hypercalcemia are generally lacking
• Anemia may be present
• Bone marrow biopsy must be performed in suspected cases:
Immunostaining for a monoclonal protein on bone marrow
sections may establish the diagnosis, Clonal plasma cell
population in marrow.
• Must rule out IgD and IgE myeloma
Non-Secretory Myeloma
33. Solitary Plasmacytoma
Localized plasma cell tumor
• Absence of a plasma cell infiltrate in random marrow biopsies
• No evidence of other bone lesions by radiographic examination
• Absence of renal failure, hypercalcemia or anemia
34. • Plasma cell tumors that arise outside the
bone marrow and no features of Multiple
Myeloma
• Most Common Primary Sites - Head and
Neck region: Upper air passages and
oropharynx (May involve draining lymph
nodes.
• Less Common Sites – Lymph nodes
(primary), salivary glands, spleen, liver, etc.
• 25% have small monoclonal spike
• Rare dissemination, rarer evolution to
myeloma
• Management :
• If completely resected during biopsy, no further
therapy
• If incompletely resected, radiation therapy locally
Extramedullary Plasmacytoma
35.
36.
37. All three criteria must be met
• Presence of a serum or urinary monoclonal
protein
• Presence of 10 percent or more clonal
plasma cells in the bone marrow or a
plasmacytoma
• Presence of end organ damage felt related to
the plasma cell dyscrasia, such as: CRAB :
Hypercalcemia (calcium > 11.5gm%), Renal
Insufficiency, Anemia (hgb < 10gm%) or Lytic
bone lesions
Multiple Myeloma
38. Multiple Myeloma
Spinal Cord Compression : oncological Emergency
Spinal cord compression occurs in 5 % of patients with multiple myeloma
( plasmacytoma or pathological fracture related)
Managed with urgent:
1. Corticosteroids
2.Neurosurgical intervention (laminectomy or
anterior decompression in pathological #) +
radiation therapy to preserve neurological function
3. Radiation therapy alone ( plasmacytoma)
39. *Thal/dex or dex are additional options
especially if immediate response is needed.
Clearly not transplantation
candidate based on age, performance
score, and comorbidity
BD/MPT, MPB, Len/dex
or clinical trial*
Potential transplantation
candidate
Nonalkylator-based
induction x 2 cycles
(BD/BDD/BTD/LD/BCD)
Stem cell harvest
Initial Approach to Treatment of MM
43. Thalidomide: Proposed Mechanism of Action
Kyle RA, et al. N Engl J Med. 2004;351:1860-1873. Rajkumar SV, et al. Leukemia.
2003;17:775-779. D’Amato RJ, et al.Proc Natl Acad Sci U S A. 1994;91:4082-4085.
44.
45.
46. Lenalidomide
Immunomodulatory derivative of thalidomide
More potent than thalidomide in preclinical models
• Dose-dependent decrease in TNF-α and interleukin-6
• Directly induces apoptosis, G1 growth arrest
• Enhances activity of dexamethasone
More favorable toxicity profile than thalidomide
Difficult to use in renal insufficiency ( dose adjust)
Richardson P, et al. Blood. 2003;100:3063. Hideshima T, et al. Blood. 2000;96:2943-2950.
47.
48.
49. Bortezomib:
A Reversible Proteasome Inhibitor
Chymo-
tryptic
Site
Post-
Glutamyl
Site
Tryptic
Site
b1 b2
b3
b4
b5
b6
b7
Cross section of b ring
Bortezomib
Adams J, et al. Invest New Drugs. 2000;18:109-121.
Adams J, et al. Bioorg Med Chem Lett. 1998;8:333-338.
H
N B
N
H
O
O
OH
N
N
OH
Interferes with intracellular pathway that
degrades proteins regulating cell cycle,
apoptosis,angiogenesis
53. Who is not a candidate for transplant ?
• Age >65 yrs
• Myeloma related organ or tissue impairment (end organ
damage) ( ROTI)
Hb 2 g /dl below the lower limit of normal
or, <10 g /dl
s. Ca - 25 mmol/l above the upper limit of
normal or, >75 mmol/ l
bone lesions- lytic lesions or osteoporosis with compression fractures
s creat - >173 µmol/ l
symptomatic hyperviscosity, amyloidosis, reccurent bac infections
(>2 episodes in 12 months)
Hence majority of
patients are not
candidates
58. Myeloablation with stem cell support
• 1.TBI (12 Gy in 8 #) and cyclophosphamide
• 2. TBI (8 Gy ) +high dose melphalan +/- Cyclo
• 3. high dose melphalan alone (140-200
mg/m2)
• High dose carboplatin /etopside /cyclo.
59. Total body irradiation
Goal – as palliation in radiation sensitive disease to eradiacte
residual cancer
Used along with stem cell support
Technique –
1. using large field size to encompass entire body – stationary beam
Extended SSD – 200-600cmStandard SSD
LINAC
60. 2. use less than whole body FS -
Moving beam / couch
61. Rigorous dosimetry
Use of compensators at head neck region
Dose variation acceptible- 10 % of prescribed dose
Supine postion , at extended SSD, using AP/PA – most
desirable
Back up must be available
Presciption – midpoint at level of umbilicus
Dose / fractionation
8- 10 Gy/ SF at dose rate
12-15 Gy @ 1-5 -2 Gy / # twice or thrice daily
Complications
Pneumonitis
fractionated regimes tolerated better
62. Role of maintenance therapy?
Why the question?
• Despite ↑remission rates, -no clear plateau in
the survival curves following conventional or HDT.
• Although the proportion of patients achieving CR
has increased, all patients eventually relapse.
• Various maintenance therapies have been
evaluated in MM in an effort to sustain remission.
63. Maintenance therapy
Depends on type , length of induction therapy
If steroids used- depends on type, dose,
schedule
No standard therapy to prolong TTP.
modest increase in only EFS not OS
Agents tried–
low dose (50 mg )alt day prednisolone
Berenson et al. Blood 2002;99:3163.
Lenalidomide(25 mg)
Br J Haematol 2013;112:1020-34
thalidomide 200 mg OD
Attal et al. Blood 2006;108:3289.
64.
65.
66.
67. Role of radiation
Mainstay of treatment prior to availability of
chemotherapy
Present day role
Definitive
solitary bone / extradural plasmacytoma
Dose – 40-50 Gy @ 2 Gy / #
Palliative
impending bone fracture- vertebra, humerus,
femur, pelvis
spinal cord compression
For irradiation hemipelvis, monitor hemogram
68. Portal
8 cm wide
Centered
on spine
Extends
one to two
vertebral
bodies
above and
below
69. • Dose- 30 Gy/ 10 #,/20 Gy/ 5 #,(30 Gy dose better than 20gy )
Radies D et al:J cli oncology:2005
• Energy- 1.25 Mv/
• Prone
• Supine- treat through table, after raising table ht to max
• Cervical spine- direct posterior field.
Thoracic spine- single post field.
• Lumbar spine/pelvis- AP – PA field / single post field
70. • Fractures of long bone - fixation - post op RT
• Symptomatic vertebral compression fractures-
vertebroplasty/ kyphoplasty - post op RT
• 50 % of nonambulatory cases regain ambulation after RT
• 67 % cases improve sphincter function
• 89 % - relief of back pain .
• Median duration of response 12 months
LECOVET ET AL:BR J HEMATOLOGY:1997
• For analgesia, however, avoid NSAID
• use lumbar corsets, braces for stabilising spine
71. Bisphosphonates
• Bisphosphonates are structural analogues of pyrophosphates that bind to
hydroxyapatite crystals in bone & inhibit osteoclast induced bone
resorption
drug IV/oral dose
pamindronate Iv 60 – 90 mg
4wkly
zoledronate iv 4 mg 4 wkly
clodronate PO 1600 mg / d
ibandronate PO 50 mg/d
Oral formulations less tolerated because of GI toxicity
Overall bisphosphonates results in 44 % relief in bone pain, 28 - 56 % decrease in
bony complications , including hypercalcemia, decrease need for EBRT.
Relatively safe & inexpensive, at least 1 yr therapy reqd for any significant
response
Zoledronic acid more
effective than pamidronate
Combining CCT well
tolerated & also improves
PFS
72. • However , these agents can cause
• Renal dysfunction –
Pamindronate – glomerular lesion , with proteinuria (nephrotic levels )
zolendronic acid – tubular dysfunction
• Ostenecrosis of jaw – before starting – all patients should have dental
examination
• Monitor s. calcium- if s. calcium reduced oral calcium 1000 mg daily and
Vitamin D (800 IU ) can be given
• Ensure adequate hydration – 2-3 l of liquids to promote excretion of
light chains, Ca , UA
73. Special clinical problems and other supportive measures
Hypercalcemia Nausea, fatigue,
confusion,
polyuria, constipation
Best approach-
admit, check
RFT,SE,Alb, Ca
IV fluids, dexam,
bisphosphonate
Renal failure Hydrate, treat hypercalcemia, reduce s
.UA,
consider hemodialysis if reasonable
evidence of good prognosis and have
not failed initial therapy
Infections Foremost cause of
death
Prophylactic use of IVIg, antibiotics not
required
Hyper viscosity Bleeding,
retinopathy,malaise,
stroke,coma
Serum M protein >
3-4 g/dl
plasmapheresis
Anemia Normocytic,
normochromic
Erythropoetin-
improves Hb by >2 g/dl
74. • ULTRA HIGH RISK MM.
• 25 % of MM patients are now are classfied in to UHRM.
• They include the following
• ISS 3 with clinical presentation as EMD OR Plasma cell
leukemia
• LDH high,FISH shows 17q deletion with PCLI >1%.
• SURVIVAL <2YRS
• POMALIDOMIDE(3rd generation im is used /currently
recommended)