Graft Versus Host Disease In Cord Blood Transfusion.

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graft vs host disease

Graft versus host disease (GVHD) is a serious complication associated with allogeneic stem cell transplantation. In the course of allogeneic stem cell transplantation, a patient receives stem cells from a donated umbilical cord blood. The donor stem cells contain T-cells or T lymphocyte, a type of white blood cell that plays important role in cell-mediated immunity and protect the body via recognizing foreign invaders and obliterate them. These cells also attack cancer cells, which is how allogeneic stem cell transplantation works to treat cancer. Although, donor cells (the graft) may also attack the patient’s healthy tissues and organs (the host), which can further impair the tissue or organ’s function or may also lead it to fail altogether. This condition is known as graft-versus host disease. GVHD divided into 2 categories,

Acute GVHD (aGVHD): This is an important cause of medical complications and death resulting from allogenic stem cell transplantation. Approximately, 30 to 70 % of transplant recipients experience acute GVHD which majorly affects liver, gastrointestinal tract and skin.

Chronic GVHD (cGVHD): This condition may involve single organ or several organs. This condition last for years or even a life time and symptoms range from mild to life threatening .

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Globally, approximately 200 transplantations of cord blood (CB) from related donors and 1000 of CB transplantations from unrelated donors have been achieved . The major advantage of CB for transplantation are the absence of risk to the donor, the instant availability of cells and the chance of transmitting infectious diseases is low.  A significant advantage of CB over bone marrow is a lower risk of GVHD. The immunologic properties of lymphocytes from cord blood, experimental results  and clinical experience  demonstrated that the chances of GVHD may be reducing after CB transplantation compared to bone marrow transplantation. Because transplantation of umbilical-cord blood (UCB) has not been compared with bone marrow transplantation after adjustment for factors known to influence the risk of GVHD, the issue is controversial. GVHD after allogeneic hematopoietic stem cell transplantation is related to significant morbidity and mortality . Chances of aGVHD increase after HLA-mismatched in comparison to HLA-matched transplantations and especially attributed to mismatching at major histocompatibility antigens. On the other hand, donor–recipient mismatching for minor histocompatibility antigens may define GVHD after HLA-matched transplantation . Approximately, 35 to 50 percent of hematopoietic stem cell transplant recipients will experience aGVHD. Given the number of transplants performed, it is estimated that around 5500 patients per year will experience aGVHD .

Graft vs host disorder in cord blood transfusion

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 Treatment and management of graft vs host disease

Treatment for graft vs host disease is divided into 2 categories: First line management and second line management .

Treatment for Acute GVHD

First line management for aGVHD

  • Corticosteroids

Second line management for aGVHD

Therapy mainly used for steroid-refractory aGVHD

  • Antithymocyte globulin
  • Alemtuzumab
  • Dacluzimab
  • Infliximab

Treatment for chronic GVHD

   First line management for cGVHD

  • Corticosteroids

Second line treatment for cGVHD

Therapy mainly used for steroid-refractory aGVHD

  • Extracorporeal
  • Photophoresis
  • Mycophenolate
  • Mofetil

Related : Diseases Treatable By The Use of Stem cells.

Usage of stem cells on graft vs host disease

uses of stem cells in graft vs host disease;

Mesenchymal stem cells (MSCs) have emerged as a potential therapeutic approach in a variety of medical fields such as cancer, regenerative medicine, inflammatory diseases and autoimmune diseases due to their unique properties of major histocompatibility complex-unmatched immunosuppression and tissue repair. Additionally, both in vitro and in vivo studies indicated that MSCs own powerful immunoregulatory functions, there has been increasing interest in the potential or role of MSCs in allogeneic hematopoietic stem cell transplantation, particularly in the management and treatment of GVHD . MSCs have been used in the treatment of aGVHD because of their inhibitory effects on the proliferation and cytotoxic activity of immune system cells . The 1st trial using mesenchymal progenitor cells was conducted in 1995, in which fifteen patients benefited from administration of autologous bone marrow-derived mesenchymal stem cells . Le Blanc et al. investigated the result of haploidentical MSC infusion in a 9-year-old boy with grade IV aGVHD of the liver and gastrointestinal tract. The clinical response was significant and the patient remained well during 1-year follow-up. A study conducted by Ringdén et al, 8 patients with grade III/IV steroid-resistant aGVHD and one patient with cGVHD receives MSCs, 6 out of 8 patients with aGVHD showed complete resolution and survival rate was significantly longer compared to control group; 5 patients remained alive over a follow-up period of two months to three years post-infusion . In the 2010 meeting of the American Society of Blood and Marrow Transplantation, Kurtzberg et al. investigated the role of allogeneic MSCs for treatment of severe steroid-refractory GVHD, 64 % response rate in 59 children at 28 days after infusion was obtained which was found to correlate with 100-day survival, demonstrating that MSC therapy has an outstanding risk–benefit ratio. Prasad et al studied the use of the shelf allogeneic MSCs for the compassionate treatment of severe steroid-refractory GVHD. This study involved 12 children with treatment-resistance grade III and IV gut aGVHD. Overall, 7 patients showed complete response, 2 patients had partial response, and 3 exhibits mixed response. Nine patients indicated complete resolution of gastrointestinal symptoms. No infusional or other identifiable acute toxicity was observed in any patient. In conclusion, number of studies has confirmed the feasibility and safety of treatment with mesenchymal stem cells. Further studies are needed to support this approach as a reliable therapeutic tool for graft vs host disorder.

References:

  1. Leukemia & Lymphoma Society. Graft-versus-host disease.

https://www.lls.org/treatment/types-of-treatment/stem-cell-transplantation/graft-versus-host-disease

  1. Wagner JE, Kernan NA, Steinbuch M, et al. Allogeneic sibling umbilical-cord-blood transplantation in children with malignant and non-malignant disease. Lancet. 1995;346:214-219.
  2. Gluckman E, Rocha V, Boyer-Chammard A, et al. Outcome of cord-blood transplantation from related and unrelated donors. N Engl J Med. 1997;337:373-381.
  3. Harris DT, Shumacher MJ, Locascio J, et al. Phenotypic and functional immaturity of human umbilical cord blood T lymphocytes. Proc Natl Acad Sci U S A. 1992;89:10006-10010.
  4. Madrigal JA, Cohen SB, Gluckman E, et al. Does cord blood transplantation result in lower graft-versus-host disease? It takes more than two to tango. Hum Immunol. 1997;56:1-5.
  5. Garderet L, Dulphy N, Douay C, et al. The umbilical cord blood alphabeta T-cell repertoire: characteristics of a polyclonal and naive but completely formed repertoire. Blood 1998;91:340-346.
  6. De La Selle V, Gluckman E, Bruley-Rosset M. Graft-versus-host disease and graft-versus-leukemia effect in mice grafted with peripheral newborn blood. 1998;92:3968-3975.
  7. Horowitz MM, Bortin MM. The role of registries in evaluating the results of bone marrow transplantation. In: Treleaven JG, Barrett AJ, eds. Bone marrow transplantation in practice. London: Churchill Livingstone, 1992:367-77.
  8. Ferrara JL, Levine JE, Reddy P, et al. Graft-versus-host disease. 2009;373:1550–1561.
  9. Kuwatsuka Y, Atsuta Y, Horowitz MM, et al. Graft-versus-host disease and survival after cord blood transplantation for acute leukemia: a comparison of Japanese versus White populations. Biol Blood Marrow Transplant. 2014;20(5):662-667.
  10. Graft-versus-host disease, 2018.

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=39812

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