Haploidentical HSCT: a 15-year experience at San Raffaele

Area of Science:

• Hematology
• Immunology
• Transplant Medicine

Background:

• Hematopoietic stem cell transplantation (HSCT) is crucial for high-risk hematological malignancies.
• HLA haploidentical family donors offer a viable HSCT source.
• San Raffaele Scientific Institute has 15 years of experience in HSCT platforms and cellular interventions.

Purpose of the Study:

• To review HSCT strategies for hematological malignancies.
• To present findings on T cell-depleted haploidentical HSCT with genetically modified T cells.
• To discuss novel GvHD prophylaxis for unmanipulated PBSC transplants.

Main Methods:

• Investigated T cell-depleted haploidentical HSCT with genetically modified donor T cells (TK007 study).
• Conducted a phase III multicenter randomized trial (TK008 study) for this approach.
• Employed sirolimus-based, calcineurin inhibitor-free GvHD prophylaxis for unmanipulated PBSC transplants (TrRaMM study).

Main Results:

• T cell-depleted haploidentical HSCT with modified T cells promotes rapid immune reconstitution.
• This approach effectively controls GvHD.
• Sirolimus-based prophylaxis enables safe infusion of unmanipulated PBSCs from haploidentical donors.

Conclusions:

• Haploidentical HSCT is a promising therapy for high-risk hematological malignancies.
• Genetically modified T cells enhance immune recovery and GvHD control post-transplant.
• Novel GvHD prophylaxis strategies expand transplant options using haploidentical donors.