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TITULO PRINCIPAL
MARIA CAMILA RODRIGUEZ
MARIANA PATIÑO
Tercer Semestre – Medicina
UPB – Medellín
2015
INTRODUCTION
• MULTIPLE MYELOMA
Type of cancer
caused by the
uncontrolled
proliferation of
monoclonal plasma
cells
Resulting in the
production of monoclonal
immunoglobulin (Ig) and
substancial
immunosupression and
endorgan damage
INTRODUCTION
• MM is characterized by several features, including:
 Low blood counts.
 Bone and calcium problems.
 Infections.
 Kidney failure.
 Monoclonal gammopathy.
 Light chain amyloidosis.
 Solitary plasmocytomas.
INTRODUCTION
• COMPLICATIONS OF MM
RENAL DYSFUCTION
EXTRAMEDULLARY
PLASMOCYTOMA
(EMP)
INTRODUCTION
• HOW IS IT DIAGNOSED?
1. Medical history and physical examination
2. LABORATORY TESTS
 Blood counts
 Quantitative Igs
 Electrophoresis (SPEP, IFE, UPEP)
 Free light chains
 Beta-2-microglobulin
 Blood chemistry tests
3. BONE MARROW BIOPSY AND ASPIRATION
 Immunohistochemistry
 Flow citometry
 Cytogenetics
 FISH
INTRODUCTION
4. BIOPSY TESTS FOR AMYLOID
5. IMAGING TESTS
 Bone X-rays
 CAT scans
 MRI scans
 Positron emission tomography scans
 Echocardiogram
6. PROGNOSIS
INTRODUCTION
• LAMBDA CHAINS
Amino acid sequence
Light chain of immunoglobulins
Their main fuction is to
bind the antigen in the
outer part of the arm
that they conform with
the heavy chains right in
the variable region
OBJECTIVE
• The objective of the
study was to conduct a
restrospective analysis of
the clinical characteristics
of a group of patients
with multiple myeloma
who had two different
immunoglobulin Λ light
chains as determined by
immunofixation
electrophoresis (IFE).
MATERIALES Y METODOS
TRATAMIENTO
Régimen PD ± T (bortezomib y dexametasona con o sin talidomida).
Régimen PAD (bortezomib, doxorubicina y dexametasona).
Régimen VAD (vindesina, doxorubicina y dexametasona).
Régimen de TAD (talidomida, doxorrubicina y dexametasona).
Régimen TD ±CTX (talidomida, dexametasona con o sin ciclofosfamida).
ESTRATEGIAS DE
TRATAMIENTO
RADIOTERAPIA SCT TD± CTXTADVADPAD PD± T
EMP
APTOS
SIN
BORTEZOMIB
CON
BORTEZOMIB
TRATAMIENTO
Además de tratamiento antimieloma, todos los pacientes recibieron CUIDADOS DE APOYO
INTENSIVO, que incluyen:
• Hidratación intravenosa.
• Alcalinización de la orina.
• La corrección de la hipercalcemia.
• Interrupción de todos los agentes nefrotóxicos potenciales.
• Diálisis renal a los pacientes con disfunción renal grave.
PRUEBAS Y FUNDAMENTO
• IFE: Se utilizó para determinar las cadenas ligeras lambda de las inmunoglobulinas. Este
examen se emplea con mayor frecuencia para verificar los niveles de ciertos anticuerpos
asociados con MM y macroglobulinemia de Waldenstrom. Estos anticuerpos
abarcan IgG, IgM, IgA, formas de cadena ligera lambda y formas de cadena ligera kappa.
• FISH: Se utilizó para determinar que tenían anomalías t (4; 14), t (14; 16) o anomalías del 17p.
Este examen se utiliza para determinar translocaciones de los cromosomas.
RESULTADOS
DISCUSSION
NUMBER OF
REFERENCE
AUTHOR
WHAT HE SAID AGREED OR NOT
8 Yang GZ, et al
With the clinical
application of novel
strategies and agents
such as autologous
SCT and bortezomib,
this situation has
improved (about the
renal dysfunction).
9
Dimopoulus MA, et
al
The pathophysiology
of the most common
types of renal injury
observed in myeloma
is closely linked to the
renal handling of light
chains.
DISCUSSION
11 Bladé J; at al
In a study by Bladé
at al, EMP was
reported in 15-20%
of patients at
diagnosis and in an
additional 15% of
patients during
follow up.
12 Bladé J; at al
Another study
described a series
of 12 patients with
MM aged <40 years
with a high
incidence of EMP.
CONCLUTIONS
• This study is important to be the base of study in the future of MM
associated to immunoglobulin λ light chains and the next scientists could
find the cure of this pathology.
• The study couldn't find the cause of MM associated to immunoglobulin λ
light chains but this study could find relation of immunoglobulin λ light
chains and renal dysfunction and EMP.
CONCLUTIONS
• The change of the structure components of biomolecules like
immunoglobulins can cause severe problems in their function
and metabolism, that’s why molecular methods are so
important when we are looking for a diagnosis and a
treatment for some diseases like multiple myeloma.
CONCLUTIONS
• Alternating empirical treatments for different diseases that
don’t have a specific one is beneficial to understand the
effects of using certain specific drugs and methods, in order to
provide diversity of treatments to achieve the most effective
one.
Mapa conceptual: María Camila Rodríguez
Mapa conceptual: Mariana Patiño
BIBLIOGRAPHY
• Yang GZ, et al. Clinical characteristics of a gruop of patients with multiple
myeloma who had two different lambda light chains by immunofixation
electrophoresis: A retrospective study from a single center. Experimental
and therapeutic medicine. 9: 1895-1900, 2015.
• American Cancer Society. Multiple Myeloma. 2014.
• Palumbo, Antonio, M.D.; Anderson, Kenneth, M.D. Multiple Myeloma.
NEJM;364: 1046-60. 2011.
• Federal University of Agriculture, Abeokuta. Immunoglobulins: types,
functions structure and biomedical importance.
• MARTINEZ SÁNCHEZ, Lina María. Biología molecular. 8. ed. Medellín: UPB.
Fac. de Medicina, 2015.
Clinical characteristics of a group of patients with multiple myeloma who had two different λ light chains by immunofixation electrophoresis: A retrospective study from a single center

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Clinical characteristics of a group of patients with multiple myeloma who had two different λ light chains by immunofixation electrophoresis: A retrospective study from a single center

  • 1.
  • 2. TITULO PRINCIPAL MARIA CAMILA RODRIGUEZ MARIANA PATIÑO Tercer Semestre – Medicina UPB – Medellín 2015
  • 3. INTRODUCTION • MULTIPLE MYELOMA Type of cancer caused by the uncontrolled proliferation of monoclonal plasma cells Resulting in the production of monoclonal immunoglobulin (Ig) and substancial immunosupression and endorgan damage
  • 4. INTRODUCTION • MM is characterized by several features, including:  Low blood counts.  Bone and calcium problems.  Infections.  Kidney failure.  Monoclonal gammopathy.  Light chain amyloidosis.  Solitary plasmocytomas.
  • 5. INTRODUCTION • COMPLICATIONS OF MM RENAL DYSFUCTION EXTRAMEDULLARY PLASMOCYTOMA (EMP)
  • 6. INTRODUCTION • HOW IS IT DIAGNOSED? 1. Medical history and physical examination 2. LABORATORY TESTS  Blood counts  Quantitative Igs  Electrophoresis (SPEP, IFE, UPEP)  Free light chains  Beta-2-microglobulin  Blood chemistry tests 3. BONE MARROW BIOPSY AND ASPIRATION  Immunohistochemistry  Flow citometry  Cytogenetics  FISH
  • 7. INTRODUCTION 4. BIOPSY TESTS FOR AMYLOID 5. IMAGING TESTS  Bone X-rays  CAT scans  MRI scans  Positron emission tomography scans  Echocardiogram 6. PROGNOSIS
  • 8. INTRODUCTION • LAMBDA CHAINS Amino acid sequence Light chain of immunoglobulins Their main fuction is to bind the antigen in the outer part of the arm that they conform with the heavy chains right in the variable region
  • 9. OBJECTIVE • The objective of the study was to conduct a restrospective analysis of the clinical characteristics of a group of patients with multiple myeloma who had two different immunoglobulin Λ light chains as determined by immunofixation electrophoresis (IFE).
  • 11. TRATAMIENTO Régimen PD ± T (bortezomib y dexametasona con o sin talidomida). Régimen PAD (bortezomib, doxorubicina y dexametasona). Régimen VAD (vindesina, doxorubicina y dexametasona). Régimen de TAD (talidomida, doxorrubicina y dexametasona). Régimen TD ±CTX (talidomida, dexametasona con o sin ciclofosfamida). ESTRATEGIAS DE TRATAMIENTO RADIOTERAPIA SCT TD± CTXTADVADPAD PD± T EMP APTOS SIN BORTEZOMIB CON BORTEZOMIB
  • 12. TRATAMIENTO Además de tratamiento antimieloma, todos los pacientes recibieron CUIDADOS DE APOYO INTENSIVO, que incluyen: • Hidratación intravenosa. • Alcalinización de la orina. • La corrección de la hipercalcemia. • Interrupción de todos los agentes nefrotóxicos potenciales. • Diálisis renal a los pacientes con disfunción renal grave.
  • 13. PRUEBAS Y FUNDAMENTO • IFE: Se utilizó para determinar las cadenas ligeras lambda de las inmunoglobulinas. Este examen se emplea con mayor frecuencia para verificar los niveles de ciertos anticuerpos asociados con MM y macroglobulinemia de Waldenstrom. Estos anticuerpos abarcan IgG, IgM, IgA, formas de cadena ligera lambda y formas de cadena ligera kappa. • FISH: Se utilizó para determinar que tenían anomalías t (4; 14), t (14; 16) o anomalías del 17p. Este examen se utiliza para determinar translocaciones de los cromosomas.
  • 15. DISCUSSION NUMBER OF REFERENCE AUTHOR WHAT HE SAID AGREED OR NOT 8 Yang GZ, et al With the clinical application of novel strategies and agents such as autologous SCT and bortezomib, this situation has improved (about the renal dysfunction). 9 Dimopoulus MA, et al The pathophysiology of the most common types of renal injury observed in myeloma is closely linked to the renal handling of light chains.
  • 16. DISCUSSION 11 Bladé J; at al In a study by Bladé at al, EMP was reported in 15-20% of patients at diagnosis and in an additional 15% of patients during follow up. 12 Bladé J; at al Another study described a series of 12 patients with MM aged <40 years with a high incidence of EMP.
  • 17. CONCLUTIONS • This study is important to be the base of study in the future of MM associated to immunoglobulin λ light chains and the next scientists could find the cure of this pathology. • The study couldn't find the cause of MM associated to immunoglobulin λ light chains but this study could find relation of immunoglobulin λ light chains and renal dysfunction and EMP.
  • 18. CONCLUTIONS • The change of the structure components of biomolecules like immunoglobulins can cause severe problems in their function and metabolism, that’s why molecular methods are so important when we are looking for a diagnosis and a treatment for some diseases like multiple myeloma.
  • 19. CONCLUTIONS • Alternating empirical treatments for different diseases that don’t have a specific one is beneficial to understand the effects of using certain specific drugs and methods, in order to provide diversity of treatments to achieve the most effective one.
  • 20. Mapa conceptual: María Camila Rodríguez
  • 22. BIBLIOGRAPHY • Yang GZ, et al. Clinical characteristics of a gruop of patients with multiple myeloma who had two different lambda light chains by immunofixation electrophoresis: A retrospective study from a single center. Experimental and therapeutic medicine. 9: 1895-1900, 2015. • American Cancer Society. Multiple Myeloma. 2014. • Palumbo, Antonio, M.D.; Anderson, Kenneth, M.D. Multiple Myeloma. NEJM;364: 1046-60. 2011. • Federal University of Agriculture, Abeokuta. Immunoglobulins: types, functions structure and biomedical importance. • MARTINEZ SÁNCHEZ, Lina María. Biología molecular. 8. ed. Medellín: UPB. Fac. de Medicina, 2015.

Editor's Notes

  1. Los pacientes que eran adecuados para el trasplante autólogo de células madre (SCT) recibió autólogo SCT. La radioterapia local se utiliza para los pacientes con plasmocitoma extramedular (EMP) después de las terapias totales.
  2. Además de tratamiento antimieloma, todos los pacientes recibieron cuidado de apoyo intensivo incluyendo hidratación intravenosa, alcalinización de la orina, la corrección de la hipercalcemia y la interrupción de todos los agentes nefrotóxicos potenciales. Renal diálisis fue ofrecido a los pacientes con disfunción renal grave.
  3. Macroglobulinemia de Waldenstrom, macroglobulinemia primaria o linfoma linfoplasmacítico es un cáncer de los linfocitos B (un tipo de glóbulo blanco) y está asociado con sobreproducción de proteínas llamadas anticuerpos IgM. El mieloma múltiple causa anemia, lo cual hace que una persona tenga más probabilidades de contraer infecciones y presentar sangrado anormal. A medida que las células cancerosas se multiplican en la médula ósea, se puede presentar dolor en los huesos o en la espalda, sobre todo en las costillas o la espalda. Si se afectan los huesos de la columna, esto puede ejercer presión sobre los nervios, lo que provoca entumecimiento o debilidad de brazos o piernas. Otros síntomas abarcan: Problemas de sangrado Fatiga debido a la anemia Fiebres sin ninguna otra causa Dificultad respiratoria debido a la anemia Fracturas inexplicables CAUSAS DEL MIELOMA MÚLTIPLE Las células plasmáticas ayudan al cuerpo a combatir la enfermedad produciendo proteínas llamadas anticuerpos. En el mieloma múltiple, las células plasmáticas crecen fuera de control en la médula ósea y forman tumores en áreas de hueso sólido. La proliferación excesiva de estos tumores óseos hace que sea más difícil para la médula producir plaquetas y glóbulos sanguíneos saludables. El mieloma múltiple afecta principalmente a los adultos mayores. Un tratamiento pasado de radioterapia aumenta el riesgo de sufrir este tipo de cáncer.  Para detectar translocaciones recíprocas se aplica un FISH en metafase usando sondas teloméricas y centroméricas, de manera que la ausencia de una señal del telómero indica que existe una translocación, indistinguible con un FISH en interfase.