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"HSCT" redirects here. For the supersonic aircraft, see High Speed Civil Transport. The High Speed Civil Transport (HSCT was a NASA project to design a Supersonic transport.



Hematopoietic stem cell transplantation (HSCT) is the transplantation of blood stem cells derived from the bone marrow (that is, bone marrow transplantation) or blood. Hematopoietic stem cells (HSCs are Stem cells that give rise to all the blood cell types including Myeloid ( Monocytes and Macrophages, Neutrophils Bone marrow is the flexible tissue found in the hollow interior of Bones In adults marrow in large bones produces new Blood cells It constitutes 4% of Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells such as nutrients and oxygen—and transports Waste products Stem cell transplantation is a medical procedure in the fields of hematology and oncology, most often performed for people with diseases of the blood, bone marrow, or certain types of cancer. Hematology ( American English) or haematology ( British English) is the branch of biology (physiology Pathology, Clinical laboratory Oncology is the branch of medicine that studies Tumors ( Cancer) and seeks to understand their development diagnosis treatment and prevention Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells such as nutrients and oxygen—and transports Waste products Bone marrow is the flexible tissue found in the hollow interior of Bones In adults marrow in large bones produces new Blood cells It constitutes 4% of Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled

Stem cell transplantation was pioneered using bone-marrow-derived stem cells by a team at the Fred Hutchinson Cancer Research Center from the 1950s through the 1970s led by E. Donnall Thomas, whose work was later recognized with a Nobel Prize in Physiology and Medicine. Nobel Prize Recipients The Hutchinson Center is home to three recipients of the Nobel Prize in physiology or medicine. Dr Edward Donnall (Don Thomas (born March 15, 1920) is an American Physician, professor emeritus at the University of Washington The Nobel Prize (Nobelpriset (Nobelprisen is a Swedish prize established in the 1895 will of Swedish chemist Alfred Nobel; it was first awarded in Peace, Literature Thomas' work showed that bone marrow cells infused intravenously could repopulate the bone marrow and produce new blood cells. A blood cell (also called blood corpuscle) is any cell of any type normally found in Blood. His work also reduced the likelihood of developing a life-threatening complication called graft-versus-host disease. Graft-versus-host disease (GVHD is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize [1]

The first physician to perform a successful human bone marrow transplant was Robert A. Good. Robert Alan Good ( May 21 1922 – June 13 2003) was an American Physician who performed the first successful human

With the availability of the stem cell growth factors GM-CSF and G-CSF, most hematopoietic stem cell transplantation procedures are now performed using stem cells collected from the peripheral blood, rather than from the bone marrow. Granulocyte-macrophage colony-stimulating factor, often abbreviated to GM-CSF, is a Protein secreted by Macrophages T cells Mast Granulocyte colony-stimulating factor ( G-CSF or GCSF) is a Colony-stimulating factor hormone In the Circulatory system, venous blood is Blood returning to the Heart (in Veins. Collecting peripheral blood stem cells[2] provides a bigger graft, does not require that the donor be subjected to general anesthesia to collect the graft, results in a shorter time to engraftment, and may provide for a lower long-term relapse rate. In modern medical practice general anaesthesia ( AmE: anesthesia) is a state of total unconsciousness resulting from General anaesthetic drugs

Hematopoietic stem cell transplantation remains a risky procedure with many possible complications; it has traditionally been reserved for patients with life-threatening diseases. While occasionally used experimentally in nonmalignant and nonhematologic indications such as severe disabling auto-immune disease and cardiovascular disease, the risk of fatal complications appears too high to gain wider acceptance[3][4]. Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which results in an immune response against its own cells and tissues Cardiovascular disease or cardiovascular diseases refers to the class of diseases that involve the Heart or Blood vessels ( arteries and

Contents

Indications for stem cell transplantation

Many recipients of HSCTs are multiple myeloma[5] and leukemia patients [6] who would not benefit from prolonged treatment with, or are already resistant to, chemotherapy or total body irradiation. Multiple myeloma (also known as MM, myeloma, plasma cell myeloma, or as Kahler's disease after Otto Kahler) is a type of Leukemia or leukaemia (Greek leukos λευκός, "white" aima αίμα, "blood" is a Cancer of the Blood Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer. Total body irradiation (TBI is a form of Radiotherapy used primarily as part of the preparative regimen for haematopoietic stem cell (or bone marrow transplantation Candidates for HSCTs include pediatric cases where the patient has an inborn defect such as severe combined immunodeficiency or congenital neutropenia with defective stem cells, and also children or adults with aplastic anemia[7] who have lost their stem cells after birth. Pediatrics (also spelled paediatrics) is the branch of Medicine that deals with the medical care of Infants Children and Adolescents Severe combined immunodeficiency ( SCID) or Boy in the Bubble Syndrome is a genetic disorder in which both "arms" ( B cells and T cells Neutropenia (adjective neutropenic) from Latin Prefix neutro- and Greek Suffix -πενία (deficiency is Other conditions[8] treated with stem cell transplants include sickle-cell disease, myelodysplastic syndrome, neuroblastoma, lymphoma, Ewing's Sarcoma, Desmoplastic small round cell tumor and Hodgkin's disease. Sickle-cell disease or sickle-cell anaemia (or anemia) is a Blood disorder characterized by Red blood cells that assume an abnormal rigid The myelodysplastic syndromes (MDS formerly known as "preleukemia" are a diverse collection of hematological conditions united by ineffective production (or Neuroblastoma is the most common extracranial solid Cancer in childhood and the most common cancer in infancy with an annual incidence of about 650 new cases per year in the Lymphoma a type of Neoplasm that originates in Lymphocytes (a type of White blood cell in the vertebrate Immune system) Ewing sarcoma is a malignant round-cell tumor It is a rare disease in which Cancer cells are found in the Bone or in soft tissue. Dsrct2jpg|thumb|right||Cell exhibiting blue oval and round shapes of desmoplastic small round blue cell tumor]] Desmoplastic small round cell tumor is classified as a Hodgkin's lymphoma, also known as Hodgkin's disease is a type of Lymphoma first described by Thomas Hodgkin in 1832 More recently non-myeloablative, or so-called "mini transplant," procedures have been developed that require smaller doses of preparative chemo and radiation. This has allowed HSCT to be conducted in the elderly and other patients who would otherwise be considered too weak to withstand a conventional treatment regimen.

Graft types

Autologous

Autologous HSCT involves isolation of haematopoietic stems cells (HSC) from the patient and storage of the harvested cells in a freezer. The patient is then treated with high-dose chemotherapy with or without radiotherapy in the form of total body irradiation to eradicate the patient's malignant cell population at the cost of also eliminating the patient's bone marrow stem cells, then return of the patient's own stored stem cells to their body. Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer. Bone marrow is the flexible tissue found in the hollow interior of Bones In adults marrow in large bones produces new Blood cells It constitutes 4% of Autologous transplants have the advantage of a lower risk of graft rejection and infection, since the recovery of immune function is rapid. Also, the incidence of a patient experiencing graft-versus-host disease is close to none as the donor and recipient are the same individual. Graft-versus-host disease (GVHD is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize However, in malignant disease the likelihood of cancer relapse and related mortality is high relative to allogeneic HCST[9].

Allogeneic

Allogeneic HSCT involves two people: the (healthy) donor and the (patient) recipient. Allogeneic HSC donors must have a tissue (HLA) type that matches the recipient. The human leukocyte antigen system ( HLA) is the name of the Major histocompatibility complex (MHC in humans Matching is performed on the basis of variability at three or more loci of the (HLA) gene, and a perfect match at these loci is preferred. The human leukocyte antigen system ( HLA) is the name of the Major histocompatibility complex (MHC in humans Even if there is a good match at these critical alleles, the recipient will require immunosuppressive medications to mitigate graft-versus-host disease. Immunosuppression involves an act that reduces the activation or Efficacy of the Immune system. Graft-versus-host disease (GVHD is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize Allogeneic transplant donors may be related (usually a closely HLA matched sibling) or unrelated (donor who is not related and found to have very close degree of HLA matching ). Allogeneic transplants are also performed using umbilical cord blood as the source of stem cells. Umbilical cord blood up to 180mL of Blood from a newborn baby that is returned to the neonatal circulation if the Umbilical cord is not prematurely clamped In general, by transplanting healthy stem cells to the recipient's immune system, allogeneic HCSTs appear to improve chances for cure or long-term remission once the immediate transplant-related complications are resolved[10][11][12].

HSC sources and storage

To limit the risks of transplanted stem cell rejection or of severe graft-versus-host disease in allogeneic HSCT, the donor should preferably have the same human leukocyte antigens (HLA) as the recipient. Transplant rejection occurs when a transplanted organ or tissue fails to be accepted by the body of the transplant recipient Graft-versus-host disease (GVHD is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize The human leukocyte antigen system ( HLA) is the name of the Major histocompatibility complex (MHC in humans About 25 to 30 percent of allogeneic HSCT recipients have an HLA-identical sibling. Even so-called "perfect matches" may have mismatched minor alleles that contribute to graft-versus-host disease.

Peripheral blood stem cells

Peripheral blood stem cells[13] are now the most common source of stem cells for allogeneic HSCT. They are collected from the blood through a process known as apheresis. The donor's blood is withdrawn through a sterile needle in one arm and passed through a machine that removes white blood cells. The red blood cells are returned to the donor. Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood The peripheral stem cell yield is boosted with daily subcutaneous injections of Granulocyte-colony stimulating factor, serving to mobilize stem cells from the donor's bone marrow into the peripheral circulation. Granulocyte colony-stimulating factor ( G-CSF or GCSF) is a Colony-stimulating factor hormone

Umbilical cord blood

Umbilical cord blood is obtained when parents elect to harvest and store the blood from a newborn's umbilical cord and placenta after birth. In placental Mammals the umbilical cord (also called the birth cord or funiculus umbilicalis) is the connecting cord from the developing Embryo The placenta is an Ephemeral organ present in placental Vertebrates, such as Eutherial Mammals and Sharks during Gestation Cord blood has a higher concentration of HSC than is normally found in adult blood. Umbilical cord blood up to 180mL of Blood from a newborn baby that is returned to the neonatal circulation if the Umbilical cord is not prematurely clamped

Storage of HSC

Unlike other organs, bone marrow cells can be frozen for prolonged time periods (cryopreserved) without damaging too many cells. This is necessary for autologous HSC because the cells must be harvested months in advance of the transplant treatment. In the case of allogeneic transplants fresh HSC are preferred in order to avoid cell loss that might occur during the freezing and thawing process. Allogeneic cord blood is stored frozen at a cord blood bank because it is only obtainable at the time of childbirth. Umbilical cord blood up to 180mL of Blood from a newborn baby that is returned to the neonatal circulation if the Umbilical cord is not prematurely clamped A cord blood bank is a facility which stores umbilical Cord blood for future use Childbirth (also called labour, birth, partus or parturition) is the culmination of a Human Pregnancy or To cryopreserve HSC a preservative, DMSO, must be added and the cells must be cooled very slowly in a control rate freezer to prevent osmotic cellular injury during ice crystal formation. Dimethyl sulfoxide (DMSO is the Chemical compound with the formula (CH32SO Osmosis is the Diffusion of a solvent (frequently water through a semi-permeable membrane, from a solution of low solute concentration (high water potential HSC may be stored for years in a cryofreezer which typically utilizes liquid nitrogen because it is non-toxic and it is very cold (boiling point -196°C. Liquid nitrogen (liquid density at the Triple point is 0707 g/mL is the liquid produced industrially in large quantities by Fractional distillation of )

Conditioning regimens

Myeloablative transplants

The chemotherapy or irradiation given immediately prior to a transplant is called the conditioning or preparative regimen, the purpose of which is to help eradicate the patient's disease prior to the infusion of HSC and to suppress immune reactions. Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer. Irradiation is the process by which an item is exposed to Radiation. The bone marrow can be ablated with dose-levels that cause minimal injury to other tissues. In allogeneic transplants a combination of cyclophosphamide with busulfan or total body irradiation is commonly employed. Cyclophosphamide (the generic name for Cytoxan Neosar Revimmune also known as cytophosphane is a Nitrogen mustard alkylating agent, from the oxazophorines group Busulfan is a Chemotherapy drug that is a cell cycle non-specific alkylating agent (slows the growth of cancer cells Total body irradiation (TBI is a form of Radiotherapy used primarily as part of the preparative regimen for haematopoietic stem cell (or bone marrow transplantation This treatment also has an immunosuppressive effect which prevents rejection of the HSC by the recipient's immune system. Immunosuppression involves an act that reduces the activation or Efficacy of the Immune system. An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor The post-transplant prognosis often includes acute and chronic graft-versus-host disease which may be life-threatening; however in certain leukamias this can coincide with protection against cancer relapse owing to the graft versus tumor effect[14]. Graft-versus-host disease (GVHD is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize Autologous transplants may also use similar conditioning regimens, but many other chemotherapy combinations can be used depending on the type of disease.

Non-myeloablative (or "mini") allogeneic transplants

This is a newer treatment approach using lower doses of chemotherapy and radiation which are too low to eradicate all of the bone marrow cells of a recipient. Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer. Radiation, as in Physics, is Energy in the form of waves or moving Subatomic particles emitted by an atom or other body as it changes from a higher energy Bone marrow is the flexible tissue found in the hollow interior of Bones In adults marrow in large bones produces new Blood cells It constitutes 4% of Instead, non-myeloablative transplants run lower risks of serious infections and transplant-related mortality while relying upon the graft versus tumor effect to resist the inherent increased risk of cancer relpase[15][16]. Also significantly, while requiring high doses of immunosuppressive agents in the early stages of treatment, these doses are less than for conventional transplants[17]. Immunosuppressive agents are a class of drugs which act to suppress the normal activity of the Immune system. This leads to a state of mixed chimerism early after transplant where both recipient and donor HSC coexist in the bone marrow space. In Zoology, a chimera is an animal that has two or more different populations of genetically distinct cells that originated in different Zygotes if the Decreasing doses of immunosuppressive therapy then allows donor T-cells to eradicate the remaining recipient HSC and to induce the graft versus tumor effect. T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity. This effect is often accompanied by mild graft-versus-host disease, the appearance of which is often a surrogate for the emergence of the desirable graft versus tumor effect, and also serves as a signal to establish an appropriate dosage level for sustained treatment with low levels of immunosuppressive agents. Graft-versus-host disease (GVHD is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize Immunosuppressive agents are a class of drugs which act to suppress the normal activity of the Immune system. Because of their gentler conditioning regimens, these transplants are associated with a lower risk of transplant-related mortality and therefore allow patients who are considered too high-risk for conventional allogeneic HSCT to undergo potentially curative therapy for their disease. These new transplant strategies are still somewhat experimental, but are being used more widely on elderly patients unfit for myeloablative regimens and for whom the higher risk of cancer relapse may be acceptable[18].

Engraftment

After several weeks of growth in the bone marrow, expansion of HSC and their progeny is sufficient to normalize the blood cell counts and reinitiate the immune system. An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor The offspring of donor-derived hematopoietic stem cells have been documented to populate many different organs of the recipient, including the heart, liver, and muscle, and these cells were have been suggested to have the abilities of regenerating injured tissue in these organs, however recent research have shown that such lineage infidelities does not occur as a normal phenomenon. Hematopoietic stem cells (HSCs are Stem cells that give rise to all the blood cell types including Myeloid ( Monocytes and Macrophages, Neutrophils The heart is a muscular organ in all Vertebrates responsible for pumping Blood through the Blood vessels by repeated rhythmic The liver is a vital organ in the human body and is present in Vertebrates and some other animals Muscle (from Latin musculus, diminutive of mus "mouse" is contractile tissue of the body and is derived from the

Complications and side effects

HSCT is associated with a high treatment-related mortality in the recipient (10% or higher), which limits its use to conditions that are themselves life-threatening. Major complications are veno-occlusive disease, mucositis, infections (sepsis) and graft-versus-host disease. Mucositis is the painful Inflammation and Ulceration of the Mucous membranes lining the Digestive tract, usually as an adverse effect of Sepsis is a serious medical condition characterized by a whole-body inflammatory state (called a Systemic inflammatory response syndrome or SIRS caused Graft-versus-host disease (GVHD is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize

Infection

Bone marrow transplantation usually requires that the recipient's own bone marrow is destroyed ("myeloablation"). Prior to "engraftment" patients may go for several weeks without appreciable numbers of white blood cells to help fight infection. This puts a patient at high risk of infections, sepsis and septic shock, despite prophylactic antibiotics, and accounts for a large share of treatment-related mortality. An infection is the detrimental Colonization of a host Organism by a foreign Species. Sepsis is a serious medical condition characterized by a whole-body inflammatory state (called a Systemic inflammatory response syndrome or SIRS caused Septic shock is a very serious medical condition caused by decreased tissue perfusion and oxygen delivery as a result of Infection and Sepsis, though the Prophylaxis ( Greek "προφυλάσσω" to guard or prevent beforehand) is any medical or Public health procedure whose purpose In modern usage an antibiotic is a Chemotherapeutic agent with activity against Microorganisms such as Bacteria, fungi or Protozoa The immunosuppressive agents employed in allogeneic transplants for the prevention or treatment of graft-versus-host disease further increase the risk of opportunistic infection. Immunosuppressive agents are a class of drugs which act to suppress the normal activity of the Immune system. An opportunistic infection is an infection caused by Pathogens that usually do not cause disease in a healthy Immune system. Immunosuppressive drugs are given for a minimum of 6-months after a transplantation, or much longer if required for the treatment of graft-versus-host disease. Transplant patients lose their acquired immunity, for example immunity to childhood diseases such as measles or polio. An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor Measles (rubeola is a Disease caused by a virus specifically a Paramyxovirus of the genus Morbillivirus. Poliomyelitis, often called polio or infantile paralysis, is an acute viral Infectious disease spread from person to person primarily via For this reason transplant patients must be re-vaccinated with childhood vaccines once they are off of immunosuppressive medications. A vaccine is a biological preparation which is used to establish or improve immunity to a particular disease

Veno-occlusive disease

Severe liver injury is termed hepatic veno-occlusive disease (VOD). Elevated levels of bilirubin, hepatomegaly and fluid retention are clinical hallmarks of this condition. Bilirubin (formerly referred to as hematoidin) is the yellow breakdown product of normal Heme Catabolism. Hepatomegaly is the condition of having an enlarged Liver. It is a nonspecific medical sign having many causes which can broadly be broken down into Infection There is now a greater appreciation of the generalized cellular injury and obstruction in hepatic vein sinuses, and it has thus been referred to as sinusoidal obstruction syndrome (SOS). Severe cases are associated with a high mortality. Anticoagulants or defibrotide may be effective in reducing the severity of VOD but may also increase bleeding complications. An anticoagulant is a substance that prevents coagulation; that is it stops Blood from clotting Defibrotide is a Deoxyribonucleic acid derivative (single stranded derived from cow Lung or porcine Mucosa. Ursodiol has been shown to help prevent VOD, presumably by helping the flow of bile. Ursodiol, also known as ursodeoxycholic acid and the Abbreviation UDCA, is one of the secondary Bile acids which are metabolic byproducts Bile or gall is a bitter yellow or green Alkaline fluid secreted by Hepatocytes from the Liver of most Vertebrates In many species

Mucositis

The injury of the mucosal lining of the mouth and throat and is a common regimen-related toxicity following ablative HSCT regimens. It is usually not life-threatening but is very painful, and prevents eating and drinking. Mucositis is treated with pain medications plus intravenous infusions to prevent dehydration and malnutrition.

Graft-versus-host disease (GVHD)

GVHD is an inflammatory disease that is unique to allogeneic transplantation. It is an attack of the "new" bone marrow's immune cells against the recipient's tissues. This can occur even if the donor and recipient are HLA-identical because the immune system can still recognize other differences between their tissues. It is aptly named graft-versus-host disease because bone marrow transplantation is the only transplant procedure in which the transplanted cells must accept the body rather than the body accepting the new cells. Acute graft-versus-host disease typically occurs in the first 3 months after transplantation and may involve the skin, intestine, or the liver, and is often fatal. The skin is the outer covering of living tissue of an animal (or plant In Anatomy, the intestine is the segment of the alimentary canal extending from the Stomach to the Anus and in humans and other mammals consists The liver is a vital organ in the human body and is present in Vertebrates and some other animals High-dose corticosteroids such as prednisone are a standard treatment; however this immuno-suppressive treatment often leads to deadly infections. Corticosteroids are a class of Steroid hormones that are produced in the Adrenal cortex. Prednisone is a synthetic Corticosteroid drug that is usually taken orally but can be delivered by Intramuscular injection and can be used for a great number Chronic graft-versus-host disease may also develop after allogeneic transplant. It is the major source of late treatment-related complications, although it less often results in death. In addition to inflammation, chronic graft-versus-host disease may lead to the development of fibrosis, or scar tissue, similar to scleroderma; it may cause functional disablity and require prolonged immunosuppressive therapy. Scleroderma is a chronic Autoimmune disease characterized by a hardening or Sclerosis in the Skin or other organs Graft-versus-host disease is usually mediated by T cells when they react to foreign peptides presented on the MHC of the host. T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity.

Graft versus tumor effect

The beneficial aspect of the Graft-versus-Host phenomenon is known as the "graft versus tumor" or "graft versus leukemia" effect. For example, HCST patients with either acute and in particular chronic graft-versus-host disease after an allogeneic transplant tend to have a lower risk of cancer relapse[19][20]. This is due to a therapeutic immune reaction of the grafted donor lymphocytes, more specifically, the Natural Killer cells, against the diseased bone marrow of the recipient. A lymphocyte is a type of White blood cell in the Vertebrate Immune system. Bone marrow is the flexible tissue found in the hollow interior of Bones In adults marrow in large bones produces new Blood cells It constitutes 4% of This lower rate of relapse accounts for the increased success rate of allogeneic transplants compared to transplants from identical twins, and indicates that allogeneic HSCT is a form of immunotherapy. GVT is the major benefit of transplants which do not employ the highest immuno-suppressive regimens.

General prognosis

Prognosis in HCST varies widely dependent upon disease type, stage, stem cell source, HLA-matched status (for allogeneic HCST) and conditioning regimen. A transplant offers a chance for cure or long-term remission if the inherent complications of graft versus host disease, immuno-suppressive treatments and the spectrum of opportunistic infections can be survived[21][22]. In recent years, survival rates have being gradually improving across almost all populations and sub-populations receiving transplants[23].

Conditions treated with bone marrow or HSC transplantation

Acquired

Congenital

See also

References

  1. ^ Thomas ED, Lochte HL, Lu WC et al. Acquired pure red cell aplasia (or PRCA refers to a type of Anemia affecting the precursors to Red blood cells but not to White blood cells. Acute lymphoblastic leukemia ( ALL) is a form of Leukemia, or cancer of the white blood cells. Acute myeloid leukemia ( AML) also known as acute myelogenous leukemia, is a Cancer of the Myeloid line of White blood cells characterized In Medicine, amyloidosis refers to a variety of conditions in which Amyloid Proteins are abnormally deposited in organs and/or tissues Choriocarcinoma is a malignant and aggressive Cancer, usually of the Placenta. Chronic lymphocytic leukemia (also known as "chronic lymphoid leukemia" or "CLL" is a type of Leukemia, or cancer of the white blood cells ( Lymphocytes Chronic myelogenous (or myeloid leukemia ( CML) is a form of Leukemia characterized by the increased and unregulated growth of predominantly Myeloid cells Dsrct2jpg|thumb|right||Cell exhibiting blue oval and round shapes of desmoplastic small round blue cell tumor]] Desmoplastic small round cell tumor is classified as a Essential thrombocytosis (ET also known as essential thrombocythemia is a rare chronic blood disorder characterized by the overproduction of Platelets by Megakaryocytes Ewing sarcoma is a malignant round-cell tumor It is a rare disease in which Cancer cells are found in the Bone or in soft tissue. Hodgkin's lymphoma, also known as Hodgkin's disease is a type of Lymphoma first described by Thomas Hodgkin in 1832 Multiple myeloma (also known as MM, myeloma, plasma cell myeloma, or as Kahler's disease after Otto Kahler) is a type of The myelodysplastic syndromes (MDS formerly known as "preleukemia" are a diverse collection of hematological conditions united by ineffective production (or The non-Hodgkin lymphomas are a diverse group of hematologic cancers which encompass any Lymphoma other than Hodgkin lymphoma. Paroxysmal nocturnal hemoglobinuria (PNH sometimes referred to as Marchiafava-Micheli syndrome, is a rare acquired potentially life-threatening disease of the blood characterised Primary Polycythemia, often called Polycythemia vera (PCV polycythemia rubra vera (PRV or erythremia occurs when excess red blood cells are produced Radiation poisoning, also called " radiation sickness " or a " creeping dose " is a form of damage to organ tissue due to excessive exposure to Adrenoleukodystrophy (ALD (also known as Addison-Schilder Disease or Siemerling-Creutzfeldt Disease) is a rare (1 in 20000 boys inherited disorder that leads to Thrombocytopenia (or -paenia, or thrombopenia in short is the presence of relatively few Platelets in Blood. Griscelli syndrome is a rare Autosomal recessive disorder characterized by Albinism (hypopigmentation with Immunodeficiency, that usually causes death Hemophagocytic lymphohistiocytosis (HLH is an unusual syndrome characterized by Fever, Splenomegaly, Jaundice, and the pathologic finding of Hemophagocytosis Hurler syndrome, also known as Mucopolysaccharidosis type I ( MPS I) Hurler's disease or gargoylism, is a Genetic disorder Inborn errors of metabolism comprise a large class of genetic Diseases involving disorders of Metabolism. Kostmann syndrome also known as Severe Congenital Neutropenia (SCN is a rare inherited form of Severe Chronic Neutropenia usually detected soon after birth Krabbe disease (also known as globoid cell leukodystrophy or galactosylceramide lipidosis) is a rare often fatal degenerative disorder that affects the Metachromatic leukodystrophy ( MLD, also called Arylsulfatase A deficiency) is the most common form of a family of genetic diseases known as the Leukodystrophies Neuroblastoma is the most common extracranial solid Cancer in childhood and the most common cancer in infancy with an annual incidence of about 650 new cases per year in the Sickle-cell disease or sickle-cell anaemia (or anemia) is a Blood disorder characterized by Red blood cells that assume an abnormal rigid Thalassemia (from Greek θαλασσα thalassa sea + αίμα haima blood British spelling "thalassaemia" is an inherited Autosomal recessive Wiskott-Aldrich syndrome (WAS is a rare X-linked recessive disease characterized by Eczema, Thrombocytopenia (low Platelet count John Raymond Hobbs BSc Hons MD, BS, MRCS, DObst RCOG, FRCP, FRCPath (1957). "Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy". New England Journal of Medicine 157: 491–496. PMID 13464965.  
  2. ^ Cutler C, Antin JH (2001). "Peripheral blood stem cells for allogeneic transplantation: a review". Stem Cells 19 (2): 108–17. Stem cells are cells found in most if not all multi-cellular Organisms. PMID 11239165.  
  3. ^ Tyndall A, Fassas A, Passweg J, et al (1999). "Autologous haematopoietic stem cell transplants for autoimmune disease--feasibility and transplant-related mortality. Autoimmune Disease and Lymphoma Working Parties of the European Group for Blood and Marrow Transplantation, the European League Against Rheumatism and the International Stem Cell Project for Autoimmune Disease". Bone Marrow Transplant. 24 (7): 729-34. doi:10.1038/sj.bmt.1701987. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 10516675.  
  4. ^ Burt RK, Loh Y, Pearce W, et al (2008). "Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases". JAMA 299 (8): 925-36. doi:10.1001/jama.299.8.925. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 18314435.  
  5. ^ Bladé J, Samson D, Reece D, et al (1998). "Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant". Br. J. Haematol. 102 (5): 1115–23. Blackwell Publishing Ltd was a Learned society publishing company based in Oxford, England. PMID 9753033.  
  6. ^ Pavletic SZ, Khouri IF, Haagenson M, et al (2005). "Unrelated donor marrow transplantation for B-cell chronic lymphocytic leukemia after using myeloablative conditioning: results from the Center for International Blood and Marrow Transplant research". J. Clin. Oncol. 23 (24): 5788-94. doi:10.1200/JCO.2005.03.962. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16043827.  
  7. ^ Locasciulli A, Oneto R, Bacigalupo A, et al (2007). "Outcome of patients with acquired aplastic anemia given first line bone marrow transplantation or immunosuppressive treatment in the last decade: a report from the European Group for Blood and Marrow Transplantation (EBMT)". Haematologica 92 (1): 11–8. PMID 17229630.  
  8. ^ CIBMTR Summary Slides I.
  9. ^ Bruno B, Rotta M, Patriarca F, et al (2007). "A comparison of allografting with autografting for newly diagnosed myeloma". N. Engl. J. Med. 356 (11): 1110-20. doi:10.1056/NEJMoa065464. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17360989.  
  10. ^ Russell N, Bessell E, Stainer C, Haynes A, Das-Gupta E, Byrne J (2000). "Allogeneic haemopoietic stem cell transplantation for multiple myeloma or plasma cell leukaemia using fractionated total body radiation and high-dose melphalan conditioning". Acta Oncol 39 (7): 837–41. Acta Oncologica is the official journal of the five Nordic oncological societies PMID 11145442.  
  11. ^ Nivison-Smith I, Bradstock KF, Dodds AJ, Hawkins PA, Szer J (2005). "Haemopoietic stem cell transplantation in Australia and New Zealand, 1992-2001: progress report from the Australasian Bone Marrow Transplant Recipient Registry". Intern Med J 35 (1): 18–27. Blackwell Publishing Ltd was a Learned society publishing company based in Oxford, England. doi:10.1111/j.1445-5994.2004.00704.x. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15667464.  
  12. ^ [http://clltopics.org/BMT/OnlyRealCure.htm CLL article}
  13. ^ Cutler C, Antin JH (2001). "Peripheral blood stem cells for allogeneic transplantation: a review". Stem Cells 19 (2): 108–17. Stem cells are cells found in most if not all multi-cellular Organisms. PMID 11239165.  
  14. ^ Toze CL, Galal A, Barnett MJ, et al (2005). "Myeloablative allografting for chronic lymphocytic leukemia: evidence for a potent graft-versus-leukemia effect associated with graft-versus-host disease". Bone Marrow Transplant. 36 (9): 825-30. doi:10.1038/sj.bmt.1705130. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16151430.  
  15. ^ Alyea EP, Kim HT, Ho V, et al (2006). "Impact of conditioning regimen intensity on outcome of allogeneic hematopoietic cell transplantation for advanced acute myelogenous leukemia and myelodysplastic syndrome". Biol. Blood Marrow Transplant. 12 (10): 1047-55. doi:10.1016/j.bbmt.2006.06.003. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17067911.  
  16. ^ Alyea EP, Kim HT, Ho V, et al (2005). "Comparative outcome of nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients older than 50 years of age". Blood 105 (4): 1810-4. doi:10.1182/blood-2004-05-1947. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15459007.  
  17. ^ Mielcarek M, Martin PJ, Leisenring W, et al (2003). "Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation". Blood 102 (2): 756-62. doi:10.1182/blood-2002-08-2628. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12663454.  
  18. ^ Alyea EP, Kim HT, Ho V, et al (2005). "Comparative outcome of nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients older than 50 years of age". Blood 105 (4): 1810-4. doi:10.1182/blood-2004-05-1947. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15459007.  
  19. ^ Baron F, Maris MB, Sandmaier BM, et al (2005). "Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning". J. Clin. Oncol. 23 (9): 1993-2003. doi:10.1200/JCO.2005.08.136. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15774790.  
  20. ^ Toze CL, Galal A, Barnett MJ, et al (2005). "Myeloablative allografting for chronic lymphocytic leukemia: evidence for a potent graft-versus-leukemia effect associated with graft-versus-host disease". Bone Marrow Transplant. 36 (9): 825-30. doi:10.1038/sj.bmt.1705130. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16151430.  
  21. ^ Russell N, Bessell E, Stainer C, Haynes A, Das-Gupta E, Byrne J (2000). "Allogeneic haemopoietic stem cell transplantation for multiple myeloma or plasma cell leukaemia using fractionated total body radiation and high-dose melphalan conditioning". Acta Oncol 39 (7): 837–41. Acta Oncologica is the official journal of the five Nordic oncological societies PMID 11145442.  
  22. ^ Nivison-Smith I, Bradstock KF, Dodds AJ, Hawkins PA, Szer J (2005). "Haemopoietic stem cell transplantation in Australia and New Zealand, 1992-2001: progress report from the Australasian Bone Marrow Transplant Recipient Registry". Intern Med J 35 (1): 18–27. Blackwell Publishing Ltd was a Learned society publishing company based in Oxford, England. doi:10.1111/j.1445-5994.2004.00704.x. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15667464.  
  23. ^ Data analysis slides by Center for International Blood and Marrow Transplant Research

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