Haploidentical stem cell transplantation is now a well accepted transplant platform for an increasing proportion of patients without matched sibling or unrelated donors. Initial studies in the 1980s were associated with unacceptably high rates of graft rejection and acute graft-versus-host disease.rr However in recent years, the development of newer platforms for haploidentical transplantation incorporating alternative conditioning regimens, in-vivo and ex-vivo T-cell depletion, KIR ligand mismatching, intensified immunosuppression and post-transplantation cyclophosphamide have revolutionised its utility.rrrrr
Post-transplant cyclophosphamide is the most widely used platform, first developed by the Johns Hopkins group.r Cyclophosphamide is not toxic to primitive haematopoietic stem cells, induces tolerance to minor histocompatibility antigens, selectively targets proliferating alloreactive T-cells, and permits immune reconstitution.rr Initial studies used conditioning comprised of fludarabine, cyclophosphamide and 2Gy TBI in association with Day +3 (+/-Day +4) dose of post-transplant cyclophosphamide (50mg/kg), tacrolimus and mycophenolate. T-replete bone marrow was infused in all patients.r Further studies have shown its utility and encouraging results as the sole GVHD prophylaxis in matched sibling BMT cohort.r
Current evidence for this reduced intensity protocol is based on the recently updated patient cohort from Johns Hopkins using bone marrow.r Two separate groups including a multicentre collaboration including UK, US & Australia have shown equivalent results using PBSCs as a stem cell source.rr Further refinements by multiple groups with altered conditioning and/or immunosuppressive combinations are being trialled whilst maintaining the post-transplant cyclophosphamide backbone in attempts to further improve results.
There have been 2 retrospective single centre studies comparing haploidentical transplant to other donor sources showing similar outcomes measures.rr In addition, a recent CIBMTR registry study has also demonstrated comparable results between haploidentical transplants and unrelated donors using both myeloablative & reduced intensity regimens.r Of note, the most recent EBMT registry update published demonstrated that haploidentical transplants have surpassed cord blood transplant numbers. There are no published randomised studies that compare different donor sources. There is an ongoing randomised trial between double cord blood transplant and post-transplant cyclophosphamide by the BMT CTN group.
The following table outlines major efficacy results using this protocol with bone marrow or PBSCs graft source.rrr
This figure shows overall survival in the CIBMTR retrospective cohorts by donor type and adjusted for age and DRI for: (A) Myeloablative or (B) Reduced intensity regimens.r
© Blood 2015
Overall graft rejection rates are <10% with rates of severe Grade 3-4 acute GVHD also <10% regardless of graft source. Chronic GVHD remain also at acceptable levels of <20%.
Note is made of no increased infective complications, and in particular no CMV disease although CMV reactivation is reported in up to 50%.