Créditos de imagem: Sklera and chimera.

Cyclophosphamide is closely linked to the development of immunology, cancer therapy and transplantation. Immunology became the intensely active field it is nowadays in part due to understanding of diseases and in part due to animal laboratory research. Bone marrow transplantation was developed in animal research in the 1950s and 1960s.  Allogeneic transplantation of bone marrow, or more modernly of hematopoietc stem cells, as well as the understanding of graft-versus-host disease, led to many concepts directing the development of knowledge in this field. Graf versus host disease is a stepwise escalation in immune activation leading to massive cell death in target tissues.

Varying regimens of conditioning of varying intensity were developed. As modern immune suppression was developed, the practice of the use of a high dose of cyclophosphamide and regulatory T-cell reconstitution became a reality. The lack of hematopoietic stem cell toxicity and immune effects have prompted several investigators to explore the potential of cyclophosphamide for the prevention of graft-versus-host disease. Historically, haploidentical stem cell transplantation with T-cell depletion is associated with high rates of infectious complications and mortality.

A high dose of cyclophosphamide immediately after transplantation has been shown to induce immune tolerance and to effectively control graft-versus-host-disease. In haploidentical hematopoietic stem cell transplants, cyclophosphamide given as a single high dose together with standard prophylaxis reduces the incidence of graft versus host disease without the need for T cell depletion. In matched related and unrelated donors, cyclophosphamide alone has produced encouraging results. The low incidence of chronic graft versus host disease is apparent in myeloablative and nonmyeloablative conditioning regimens with survival comparable to HLA-matched transplantation.

These observations, along with the 112 cases we have of impressive results of a similar protocol for controlo f a variety of neuroimmune diseases, specially multiple sclerosis, has opened a new perspective in therapy of graft versus host disease.

Dr Paulo Bittencourt ( from the abstracts of the papers that follow)

Markey KA, MacDonald KP, Hill GR. The biology of graft-versus-host disease: experimental systems instructing clinical practice. Blood. 2014 Jul 17;124(3):354-62. doi: 10.1182/blood-2014-02-514745. Epub 2014 Jun 9.

Shabbir-Moosajee MLombardi LCiurea SO. An overview of conditioning regimens for haploidentical stem cell transplantation with post-transplantation cyclophosphamide.

Am J Hematol. 2015 Jun;90(6):541-8. doi: 10.1002/ajh.23995. Epub 2015 Apr 29.

Al-Homsi ASRoy TSCole KFeng YDuffner U. Post-transplant high-dose cyclophosphamide for the prevention of graft-versus-host disease. Biol Blood Marrow Transplant. 2015 Apr;21(4):604-11. doi: 10.1016/j.bbmt.2014.08.014. Epub 2014 Aug 23.

 

Image courtesy of Dr. Paulo Bittencourt | Dimpna
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