Hsct.docx
This document was uploaded by user and they confirmed that they have the permission to share it. If you are author or own the copyright of this book, please report to us by using this DMCA report form. Report DMCA
Overview
Download & View Hsct.docx as PDF for free.
More details
- Words: 1,295
- Pages: 7
Hematopoietic stem cell transplantation •
Hematopoietic growth factors
•
Hematopoietic growth factors are used to support cancer patients through the treatment of disease
•
Colony stimulating factors are a family of glyco proteins produced by various cells and stimulate production maturation regulation and activation of cells in hematologic system
•
The name of the CSF is based on various cell line it affects
•
Granulocyte macrophage CSF
•
Granulocyte CSF
•
Erythropoietin
•
Interluekin-11( platelet GF)
•
HSC: Key Definition
•
Haematopoietic Stem Cell –
•
Cell produced in bone marrow that gives rise to all other blood cells (white cells, red cells, and platelets) •
Replenishes itself
•
Relatively resistant to injury
•
But, that can be eliminated with high doses of chemotherapy or radiation therapy
•
Key Vocabulary
Bone marrow
tissue found predominately in spaces of the bones of the hips, legs, arms and spines. •
Stem Cells
produced in the bone marrow and found in circulating blood. •
Hematopoietic stem cell transplantation
•
Bone marrow transplantation and peripheral stem cell transplantation are life saving procedures for malignant and nonmalignant diseases
•
The therapeutic approach was previously known as bone marrow transplantation as bone marrow was the original source of cells
•
but since stem cell can be collected from peripheral blood the procedure is referred to as hematopoietic stem cell transplantation
•
HSCT - definition
•
Definition
any procedure where hematopoietic stem cells of any donor and any source are given to a recipient with intention of repopulating/replacing the hematopoietic system in total or in part •
Indication for HSCT
•
Neoplastic disorders –
– •
Hematological malignancies •
Lymphomas (Hodgkin and non-Hodgkin)
•
Leukemias (acute and chronic)
•
Multiple myeloma
•
MDS
Solid tumors
Non-neoplastic disorders –
Aplastic anemia
–
Autoimmune diseases
–
Immunodeficiency
–
Inborn errors of metabolism
•
Sources of stem cells
•
Bone marrow
•
Peripheral blood
•
Umbilical cord blood
•
Fetus liver
•
Cell Types for Transplantation
•
BM is harvested from the posterior iliac crests under epidural or general anesthesia.
•
The anterior iliac crest or sternum can be used if larger quantities of marrow are required
•
The BM is collected with heparinized syringes and large-bore needlesand is stored in culture medium. The marrow can be infusedimmediately after harvesting but can be stored at 4°C for24 hours without loss of stem cell viability, allowing
•
The cell dose required for stable long-term engraftment is not clearly defined.
•
A nucleated cell dose of 2 × 108/kg is generally considered adequate,
•
This requires between 700 and 1,500 mL of BM from an adult donor.
•
National Marrow Donor Program guidelines limit BM removal to 15 mL/kg of donor weight.
•
As only a small percentage of total body BM is removed, peripheral blood leukocyte counts are notaffected.
•
After harvesting, the marrow is filtered to remove small particles or clots before intravenous transfusion into the recipient.
•
Red blood cells and plasma can be depleted if the recipient has high anti-A or anti-B antibody titers and major or minor ABO mismatches
•
(2) Peripheral Blood Stem Cells
•
Collected by apheresis following hematopoietic growth factor “mobilization” and/or chemotherapy
•
approved hematopoietic growth factors: Granulocyte colony stimulating factor (G-CSF), Granulocyte/macrophage stimulating factor (GM-CSF), Erythropoietin (Ep), Interleukin-11 (IL-11)
•
Advantages:
Easy to collect large numbers of stem cells Multiple collections possible •
Disadvantages:
Pre-treatment with HGF risk to normal donors? ↑ tumor cell proliferation ↑ circulating tumor cells → ↑ graft contamination with tumor cells
Bone pain May require central venous access •
(3) Cord Blood Stem Cells
Advantages: •
Collection has no risks for mother or infant
•
Readily available, anonymous banks, family donation
Disadvantages: •
Low cell dosages may limit to small recipients
•
Availability of HLA-matched donor
•
Multiple collections impossible Types of HSCT
•
Allogenic
•
Stem cells are acquired from a donor who is HLA matched to recipient
•
Advantages
•
Eradication of tumor cells with high dose therapy
•
Stimulation of graft vs tumor effect in which donor WBC identify and attak tumor cells in the host
•
Indicated in leukaemias, lymphomas and multile myeloma
•
HLA Typing Human Leukocyte Antigen
•
HLA are proteins found on short arm of chromosome 6
•
3-antigens important in HSCT, –
HLA-A
–
HLA-B
–
HLA-DR
one set of 3 from each parent
•
Brings to a total of six antigens to match
•
A full match is “6/6” or “perfect” match
•
Syngenic transplantation
•
A typeof allogenic transplantation which involves obtaining stem cells from one identical twin and infusing to the oter
•
Therefore no GVHD /graft vs tumor effect occurs
•
Autologous transplantation
•
Patients receive their own stem cells back following myeloablative chemotherapy
•
The aim of the therapy is purely rescue
•
Enables the patient to receive intense chemotherapy/radiation therapy by supporting them with previously harvested stem cells till their bone marrow regenerates on its own
•
Restoration takes 4 to 6weeks
•
Used to treat hematologic malignancies
•
Procedure
•
Harvest procedure
•
Hematopoietic stem or from recipient according to type of procedure using two different methods
•
The process of developing stem ells from the bone marrow was developed originally as a procedure in OR under general anesthesia , multiple bone marrow aspirations from bone marrow from iliac crest or sternum is taken
•
Takes 1 to2 hrs
•
Post procedure donor may experience pain at donor site
•
The body will replenish the removed bone marrow in one week
•
In the other procedure peripheral stem cells are obtained for blood
•
Done using cell separator average time is 2 to 4hrs but can take longer
•
Requires multiple collections as peripheral blood has less no of stem cells
•
mobilization of stem cells to peripheral blood can be achieved by chemotherapy/ using hematopoietic growth factors
•
Chemotherapy with cyclophosphamide is useful
•
Harvested marrow is processed to remove bone fragments ( not required for peripheral blood)
•
Stem cells are bagged with cryo preservative and either stored / used immediately
•
For autologous transplant since it comes from patient stem cells are treated / purged to remove any undetected cancer cells
•
Umbilical cord blood can also be cryopreserved after HLA typing but can produce only less no of stem cells
•
Preparative regimen & stem cell infusions
•
For malignant diseases patients receive myeloablative therapy with high dose chemotherapy or total body irradiation to treat underlying disease
•
this is called as conditioning regimen
•
The timing of stem cell harvest and reinfusion is critical for autologous transplantation
•
The conditioning regimen is commenced ony after the stem cells are harvested & the stem cells are reinfused only afeter the effects of conditioning regimen is over (24-48 hrs)
•
Stem cell infusions can be given IV or given as bolus
•
the infused stem cells reconstitute the bone marrow elements rescuing the recipients hematopoietic system
•
it takes 2 to 4 weeks for the marrow to restart the hematopoietic stem cell production
•
during pancytopenic period the patient to be protected from infection
•
Complications
•
Graft Versus Host Disease
•
Condition where donor T-Cells recognize recipient as foreign and attacks the patient skin, bowel, liver, and other tissues
•
This graft-versus-host reaction leads to GVHD signs and symptoms
•
HLA or Tissue Typing
•
Rate of GVHD
Donor 6/6
Incidence 40%
5/6
50%
4/6
80%
3/6
90% •
Graft vs. Host Disease GVHD
•
Acute
Up to Day +100 •
Skin
•
Liver
•
Gut
•
Chronic
After Day +100 •
Skin
•
Mucous Membranes
•
Gut
•
Liver
•
Scleroderma
•
Acute GVHD Grading
•
Acute and Chronic GVHD Therapy
•
Steroids and Cyclosporine / Tacrolimus
•
Other modalities of immunosupression
Hematopoietic growth factors
•
Hematopoietic growth factors are used to support cancer patients through the treatment of disease
•
Colony stimulating factors are a family of glyco proteins produced by various cells and stimulate production maturation regulation and activation of cells in hematologic system
•
The name of the CSF is based on various cell line it affects
•
Granulocyte macrophage CSF
•
Granulocyte CSF
•
Erythropoietin
•
Interluekin-11( platelet GF)
•
HSC: Key Definition
•
Haematopoietic Stem Cell –
•
Cell produced in bone marrow that gives rise to all other blood cells (white cells, red cells, and platelets) •
Replenishes itself
•
Relatively resistant to injury
•
But, that can be eliminated with high doses of chemotherapy or radiation therapy
•
Key Vocabulary
Bone marrow
tissue found predominately in spaces of the bones of the hips, legs, arms and spines. •
Stem Cells
produced in the bone marrow and found in circulating blood. •
Hematopoietic stem cell transplantation
•
Bone marrow transplantation and peripheral stem cell transplantation are life saving procedures for malignant and nonmalignant diseases
•
The therapeutic approach was previously known as bone marrow transplantation as bone marrow was the original source of cells
•
but since stem cell can be collected from peripheral blood the procedure is referred to as hematopoietic stem cell transplantation
•
HSCT - definition
•
Definition
any procedure where hematopoietic stem cells of any donor and any source are given to a recipient with intention of repopulating/replacing the hematopoietic system in total or in part •
Indication for HSCT
•
Neoplastic disorders –
– •
Hematological malignancies •
Lymphomas (Hodgkin and non-Hodgkin)
•
Leukemias (acute and chronic)
•
Multiple myeloma
•
MDS
Solid tumors
Non-neoplastic disorders –
Aplastic anemia
–
Autoimmune diseases
–
Immunodeficiency
–
Inborn errors of metabolism
•
Sources of stem cells
•
Bone marrow
•
Peripheral blood
•
Umbilical cord blood
•
Fetus liver
•
Cell Types for Transplantation
•
BM is harvested from the posterior iliac crests under epidural or general anesthesia.
•
The anterior iliac crest or sternum can be used if larger quantities of marrow are required
•
The BM is collected with heparinized syringes and large-bore needlesand is stored in culture medium. The marrow can be infusedimmediately after harvesting but can be stored at 4°C for24 hours without loss of stem cell viability, allowing
•
The cell dose required for stable long-term engraftment is not clearly defined.
•
A nucleated cell dose of 2 × 108/kg is generally considered adequate,
•
This requires between 700 and 1,500 mL of BM from an adult donor.
•
National Marrow Donor Program guidelines limit BM removal to 15 mL/kg of donor weight.
•
As only a small percentage of total body BM is removed, peripheral blood leukocyte counts are notaffected.
•
After harvesting, the marrow is filtered to remove small particles or clots before intravenous transfusion into the recipient.
•
Red blood cells and plasma can be depleted if the recipient has high anti-A or anti-B antibody titers and major or minor ABO mismatches
•
(2) Peripheral Blood Stem Cells
•
Collected by apheresis following hematopoietic growth factor “mobilization” and/or chemotherapy
•
approved hematopoietic growth factors: Granulocyte colony stimulating factor (G-CSF), Granulocyte/macrophage stimulating factor (GM-CSF), Erythropoietin (Ep), Interleukin-11 (IL-11)
•
Advantages:
Easy to collect large numbers of stem cells Multiple collections possible •
Disadvantages:
Pre-treatment with HGF risk to normal donors? ↑ tumor cell proliferation ↑ circulating tumor cells → ↑ graft contamination with tumor cells
Bone pain May require central venous access •
(3) Cord Blood Stem Cells
Advantages: •
Collection has no risks for mother or infant
•
Readily available, anonymous banks, family donation
Disadvantages: •
Low cell dosages may limit to small recipients
•
Availability of HLA-matched donor
•
Multiple collections impossible Types of HSCT
•
Allogenic
•
Stem cells are acquired from a donor who is HLA matched to recipient
•
Advantages
•
Eradication of tumor cells with high dose therapy
•
Stimulation of graft vs tumor effect in which donor WBC identify and attak tumor cells in the host
•
Indicated in leukaemias, lymphomas and multile myeloma
•
HLA Typing Human Leukocyte Antigen
•
HLA are proteins found on short arm of chromosome 6
•
3-antigens important in HSCT, –
HLA-A
–
HLA-B
–
HLA-DR
one set of 3 from each parent
•
Brings to a total of six antigens to match
•
A full match is “6/6” or “perfect” match
•
Syngenic transplantation
•
A typeof allogenic transplantation which involves obtaining stem cells from one identical twin and infusing to the oter
•
Therefore no GVHD /graft vs tumor effect occurs
•
Autologous transplantation
•
Patients receive their own stem cells back following myeloablative chemotherapy
•
The aim of the therapy is purely rescue
•
Enables the patient to receive intense chemotherapy/radiation therapy by supporting them with previously harvested stem cells till their bone marrow regenerates on its own
•
Restoration takes 4 to 6weeks
•
Used to treat hematologic malignancies
•
Procedure
•
Harvest procedure
•
Hematopoietic stem or from recipient according to type of procedure using two different methods
•
The process of developing stem ells from the bone marrow was developed originally as a procedure in OR under general anesthesia , multiple bone marrow aspirations from bone marrow from iliac crest or sternum is taken
•
Takes 1 to2 hrs
•
Post procedure donor may experience pain at donor site
•
The body will replenish the removed bone marrow in one week
•
In the other procedure peripheral stem cells are obtained for blood
•
Done using cell separator average time is 2 to 4hrs but can take longer
•
Requires multiple collections as peripheral blood has less no of stem cells
•
mobilization of stem cells to peripheral blood can be achieved by chemotherapy/ using hematopoietic growth factors
•
Chemotherapy with cyclophosphamide is useful
•
Harvested marrow is processed to remove bone fragments ( not required for peripheral blood)
•
Stem cells are bagged with cryo preservative and either stored / used immediately
•
For autologous transplant since it comes from patient stem cells are treated / purged to remove any undetected cancer cells
•
Umbilical cord blood can also be cryopreserved after HLA typing but can produce only less no of stem cells
•
Preparative regimen & stem cell infusions
•
For malignant diseases patients receive myeloablative therapy with high dose chemotherapy or total body irradiation to treat underlying disease
•
this is called as conditioning regimen
•
The timing of stem cell harvest and reinfusion is critical for autologous transplantation
•
The conditioning regimen is commenced ony after the stem cells are harvested & the stem cells are reinfused only afeter the effects of conditioning regimen is over (24-48 hrs)
•
Stem cell infusions can be given IV or given as bolus
•
the infused stem cells reconstitute the bone marrow elements rescuing the recipients hematopoietic system
•
it takes 2 to 4 weeks for the marrow to restart the hematopoietic stem cell production
•
during pancytopenic period the patient to be protected from infection
•
Complications
•
Graft Versus Host Disease
•
Condition where donor T-Cells recognize recipient as foreign and attacks the patient skin, bowel, liver, and other tissues
•
This graft-versus-host reaction leads to GVHD signs and symptoms
•
HLA or Tissue Typing
•
Rate of GVHD
Donor 6/6
Incidence 40%
5/6
50%
4/6
80%
3/6
90% •
Graft vs. Host Disease GVHD
•
Acute
Up to Day +100 •
Skin
•
Liver
•
Gut
•
Chronic
After Day +100 •
Skin
•
Mucous Membranes
•
Gut
•
Liver
•
Scleroderma
•
Acute GVHD Grading
•
Acute and Chronic GVHD Therapy
•
Steroids and Cyclosporine / Tacrolimus
•
Other modalities of immunosupression
More Documents from "lakshmi"
Hsct.docx
April 2020 33
Big Data Ieee.docx
April 2020 28
02-unit-2.pptx
April 2020 26
Ieee Si.docx
April 2020 32
Time Table.docx
April 2020 24