EBMT NEWSLETTER | July 2015 | Volume 47 - Issue 2

Important dates
Rafael F. Duarte is the Chair of the EBMT Transplant-related complications and Quality of Life Working Party and the Vice-Chair of the Society’s Scientific Council.

He has recently reported in The Lancet HIV an important proof-of-concept case showing that allogeneic cord blood hematopoietic cell transplantation (HCT) is a potential platform to cure HIV infection. A previous report in 2009 showed Timothy Ray Brown, also known as the "Berlin patient", to be cured of HIV infection following allogeneic HCT from a matched unrelated donor with a rare homozygous natural variant of the CCR5 chemokine receptor gene (CCR5-Δ32/Δ32) that confers resistance to HIV cell entry.

Dr. Duarte is answering our questions about this research, the potential advantages of cord blood as a cell source in this setting and the role of allogeneic HCT in patients with HIV infection.
  1. What are the key new findings coming from your recent study in The Lancet HIV?
The Berlin Patient provided years ago seminal proof that allogeneic HCT with CCR5-Δ32/Δ32 hematopoietic cells can eradicate HIV and lead to a functional cure of HIV infection. However, the low prevalence of the CCR5-Δ32/Δ32 genotype (<1% in Caucasians and lower in other ethnic groups) and the stringent HLA-matching criteria for conventional donors made it very unlikely to identify potential donors to develop this therapeutic strategy further. Our case builds on this evidence to show that CCR5-Δ32/Δ32 cord blood cells can successfully eliminate HIV-1 and render the recipient’s immune system resistant to HIV infection. Given their more permissive HLA-compatibility criteria, our data support the use of cord blood transplantation as a platform for broader application of this therapeutic strategy to patients with HIV infection.
  1. How would the use of cord blood transplantation increase the chances of finding an appropriate CCR5-Δ32/Δ32 donor for HIV infected patients?
In our case we used a dual transplant protocol originally developed at Hospital Puerta de Hierro in Madrid, which combines cord blood with haploidentical donor hematopoietic cells. This protocol achieves faster neutrophil engraftment and comparable outcomes to other cord blood HCT protocols while allowing the use of cord blood units with somewhat lower cellular content. This lower cellular requirement would facilitate the identification of suitable units from a repository of approximately 300 CCR5-Δ32/Δ32 cord blood units for approximately 80% of potential transplant candidates, and thus, provides a major advantage in this setting of HIV infection.
  1. Would you say that allogeneic HSCT is a curative strategy for individuals with HIV?
I’d be very cautious with such statements. Allogeneic HCT is a complex procedure with well-established indications, and HIV-infected individuals should at present be considered for allogeneic HCT only if they have a standard indication, normally a hematological malignancy. The role of using CCR5-Δ32/Δ32 cells in HIV-patients in need of an allogeneic HCT is very promising, but remains experimental and should be developed further before broader recommendations can be made. 
  1. Then, what other studies and projects are in the pipeline to help developing this strategy further?
A number of partners and colleagues are making efforts towards the development of readily available inventories of CCR5-Δ32/Δ32 cord blood units. In particular, I would like to highlight the commitment in this particular area from the Spanish Organización Nacional de Trasplante and our National Cord Blood Program. We hope to start a first clinical trial in this area in the next few months. At an international level, EBMT has led on clinical research in HCT for HIV-infected individuals, both on autologous HCT for patients with lymphoma and more recently on the outcome of allogeneic HCT in these patients, and will surely play a central role to catalyze international collaboration in this field.
  1. Given the importance of the topic, and the potential role of our Society that you just mentioned, do you plan to launch new educational activities in this area?
Of course. In fact, during the next EBMT Annual Meeting in Valencia, and in close collaboration between the Society and the Local Organizing Committee, we have planned to hold a workshop focused on HCT and Cellular Therapy for HIV. You’re all invited to meet us in Valencia for an update on this topic and many other exciting scientific and educational activities. 
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