Cord cells in clinical practice
There are currently some 80 pathologies treatable with stem cells.
Download the “Clinical indications for haematopoietic stem cell transplantation for which cord blood is suitable” table, as established by Decree of 18/11/2009 – G.U. N.303 31/12/2009
Recent studies on the use of stem cells by direct intramedullary injection have shown a faster recovery of the number of mononucleate cells (especially neutrophils) and platelets, with a smaller number of stem cells transplanted in situ. Storage of cord blood also offers the possibility of developing retroactive diagnostic investigations into hereditary and/or tumoral diseases.
Since the end of the Eighties, the use of stem cells has enabled numerous onco-haematological and immunological diseases to be effectively treated and, with the latest clinical studies on regenerative medicine, also the regeneration of tissues, such as the myocardium, muscular tissue of the heart and the pancreas.
Hematopoietic stem cells are blood-forming cells and are extensively studied and applied in clinical practice using a process that includes differentiation and transplant.
In transplants, compared with other sources of stem cells, cord blood cells have the indubitable advantage of:
- decreasing the risk of aggression from the donor’s cells on the recipient’s organism (GVHD-Graft Versus Host Disease)
- reducing the transplant time to the minimum, thanks to the immediate availability of the sample
- performing transplants even with reduced compatibility (at least 4/6 loci, the gene positions in the chromosomes)
- transplanting totally sterile cells (not contaminated by infectious agents)
Finally, for a successful transplantation it is essential to infuse a suitable number of cells. Protocols on the methods for intravenous transplantation of haematopoietic stem cells specify a minimum dose per kilogram of the recipient’s body weight, equivalent to 3 x 107 (30 million) mononuclear cells; but the more cells transplanted, the better the probability of success.
In recent years, efforts have been made to go beyond the “numeric” limit of cells obtained from cord blood units, by
- intravenous infusion of two cord blood samples (“combined transplantation”), to help the transplant take root
- ex-vivo expansion of cord cells, to replicate their number
- infusion of stem cells by direct intramedullary injection, showing a faster recovery of the number of mononucleate cells (especially neutrophils) and platelets
Other protocols currently being validated concern the expansion of stem cells in vitro, transplants after reduced chemotherapy and the infusion of selected cells.
The therapeutic use of stem cells varies according to the pathology or medical application; we speak of:
- allogeneic or heterologous transplantation (when the donor is different from the recipient of the cells)
- autologous transplantation (when the donor is also the recipient of the cells).
In allogeneic or heterologous transplantation it is essential to verify the compatibility of stem cells between donor and recipient by a tissue typing procedure, ascertaining if they are HLA compatible (Human Leukocyte Antigens). See also HLA compatibility test.
In autologous transplantation, instead, the traditional barrier of compatibility between two people no longer exists because the transplanted cord cells belong to the same individual and thus possess the same biological characteristics. This significantly reduces the risk of complications such as rejection.
Thanks to these methods and to the progress in transplant preparation techniques and GvHd prophylaxis, the number of cord blood units transplanted (for allogeneic and heterologous use) has increased exponentially (over 20,000), also compared to the usual stem cell, bone marrow and peripheral blood sources.
In 2008, during a congress in Milan, Dr Eliane Gluckman, who in 1988 performed the world’s first successful transplant with cord blood cells, stressed that the over 20,000 cord stem cell transplants were carried out for the same variety of malign and non-malign pathologies treated with bone marrow.
The data provided by international transplant centres show that pathologies obtaining the best results from haematopoietic cord stem cell treatments are:
- for both children and adults:
Acute Lymphoid Leukaemia (ALL), Acute Myeloid Leukaemia (AML), Chronic Myeloid Leukaemia (CML)
- for adults:
Myelodysplastic disorders and lymphomas following the above diseases in terms of statistic probability
Download pdf: GRAPHS OF ONCO-HAEMATOLOGICAL TRANSPLANTS IN ADULTS AND CHILDREN
(Source: Biology of Blood Marrow Transplantation – US- 2008)
(Bibliography: N.2 Ballen KK, Spitzer TR “The great debate: haploidentical or cord blood transplant” Bone Marrow Transplant 2011 Mar.)
As the graph shows, the new techniques, as well as a better selection of cord units by transplant centres, has in very recent years inverted the ratio between children and adults transplanted with haematopoietic stem cells from cord blood cells at European level.
As confirmed also by the GITMO charity (Italian Group for Bone Marrow Transplantation), the greater “recognition/acceptance” of cord cells compared to bone marrow or peripheral blood cells (after haemapheresis), means a faster recovery and a 20% greater guarantee of success as the graph on the treatment of Acute Lymphoblastic Leukaemia shows.
Download pdf: Graph of Acute Linfoblastic Leukemia Transplants
Source: Eapen M, Rubinstein P, Zhang MJ, Stevens C, Kurtzberg J, Scaradavou A, Loberiza FR, Champlin RE, Klein JP, Horowitz MM, Wagner JE. “Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study.” Lancet. 2007 Jun 9;369(9577):1947-54.
Download pdf: Graphs of Eurocord and Gitmo Transplants
Until now, there have been more allogeneic transplants of cord samples between blood relations than autologous transplants. However, regenerative medicine clinical studies show that mesenchymal or endothelial cells can also be used for autologous rather than allogeneic transplants. Read the “CLINICAL STUDIES” page.
In the future it is expected that cord blood cells will be increasingly used for autologous transplants.
In, 2009 the following transplantations were performed worldwide: (source: www.cibmtr.org)
34,000 autologous transplantations and 27,000 allogeneic transplantations from three main sources:
- haematopoietic stem cells from bone marrow
- haematopoietic stem cells from cord venous blood
- haematopoietic stem cells from peripheral blood after stimulation with haemapheresis
In the event a transplant is needed, the search for an HLA-compatible donor (if a private sample of cord stem cells is unavailable) follows this order of priority:
- among siblings (because of their greater degree of compatibility and probability of transplant success)
- among aploidentic donors (i.e. compatible father, mother or cousin)
- through international registers of donated samples (for mixed races or minors the probability of finding a compatible sample is generally low)
The search begins after a form stating the patient’s HLA typing is sent to the national register that uses a computerized system to find a donor with HLA characteristics identical to the patient’s. Once a compatible donor or cord blood cells are identified the compatibility between donor and patient has to be confirmed with further HLA typing, All the laboratories carrying out HLA typing for CSE transplants must be EFI (European Federation for Immunogenetics) or ASHI (American Society for Histocompatibility and Immunogenetics) accredited.
A compatible sample is first sought among family members since it necessarily takes longer to find it through international registers. The advantages of having a cord blood cell sample means that retroactive diagnostic tests can be carried out on hereditary and/or tumoral disease
| Leukaemia and Lymphomas Acute lymphoblastic leukaemia Acute myeloid leukaemia Acute biphenotypic leukaemia Acute undifferentiated leukaemia Adult T-cell leukaemia/lymphoma Hodgkin’s lymphoma Non-Hodgkin’s lymphomas Chronic lymphatic leukaemia Prolymphocyticleukaemia Myelodisplastic/Myeloproliferative Disorders Myelodisplastic syndromes including: Refractory anaemia (RA) Refractory anaemia with ringed sideroblasts (RARS) Refractory anaemia with excess blasts (RAEB) Refractory anaemia with excess blasts in transformation (RAEB-t) Chronic myelomonocytic leukaemia Juvenile myelomonocytic leukaemia Refractory cytopenia Philadelphia chromosome-positive myeloid leukaemia Idiopathic myelofibrosis Polycythemia vera Essential thrombocythemia Cell Plasma Disorders Multiple myeloma Cell plasma leukaemia Waldenström’s macroglobulinaemia Amyloidosis Bone-marrow disorders Acquired aplastic anaemia Fanconi anaemia Dyskeratosis congenita Paroxysmal nocturnal hemoglobinuria Blackfan-Diamond anaemia Congenital dyserythropoietic anaemia Pure red cell aplasia Congenital amegakaryocytic purpura (from mutations in the thrombopoietin receptor) Congenital platelet disorders (Bernard-Soullier’s disease, Glanzmann’s thrombasthenia ) Congenital agranulocytosis (Kostmann syndrome) Shwachman-Diamond syndrome Haemoglobinopathies Beta-type thalassemia Sickle-cell anaemia Select cases of transfusion-dependent pyruvate kinase deficit Histiocytosis Familial hemophagocytic lymphohistiocytosis Griscelli Syndrome Chediak-Higashi Syndrome Langerhans cell histiocytosis (histiocytosis X) |
Congenital disorders of the immune system Chronic granulomatous disease Leukocyte adhesion deficiency Severe combined immunodeficiency (SCID) including: Adenosine-deaminase deficiency Class I and II HLA molecule defect Zap70 defect Omenn syndrome Purine- nucleoside-phosphorilasis deficiency Reticular dysgenesis Multiple cytokine common gamma chain defect Hyper-IgM JAK3 syndrome defect Wiskott-Aldrich syndrome Lymphoproliferative disorder linked to X chromosome (Duncan syndrome or Purtillo syndrome) Cartilage-hair hypoplasia DiGeorge syndrome IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) Congenital metabolic complaints Hurler syndrome (MPS-IH) Scheie syndrome (MPS-IS) Maroteaux-Lamy syndrome (MPS-VI) Sly syndrome (MPS-VII) Adrenoleukodystrophy Fucosidosis Gaucher’s disease Krabbe’s disease Mannosidosis Metachromatic leukodystrophy Type-II mucolipidosis (I-cell disease) Batten disease (neuronal ceroid lipofuscinoses) Sandhoff disease Osteopetrosis Osteogenesis imperfecta Other hereditary disorders Congenital erythropoietic porphyria (Gunther’s disease) Other types of tumour Ewing’s sarcoma Neuroblastoma Renal cell carcinoma Rhabdomyosarcoma Other indications Evans syndrome Autoimmune lymphoproliferative syndrome (from FAS, FAS-L, Caspasi defect) Progressive systemic sclerosis |
