Haplo-Identical Bone Marrow Transplant Protocol using Reduced Intensity Conditioning for Fundeni Clinical Institute

Purpose:

Even if the romanian population is ethnically compact caucasian-type population, many of the patients referred for bone marrow transplantation lack a suitable donor. In order to expand the donor pool and the accesibility to transplant for those who have indications it is necessary to perform haplo-identical bone marrow transplant procedure in Fundeni Clinical Institute. Since 2009 Romania established a National Volunteer Stem Cell Donor Registry (RNDVCSH), the goal was to enlarge the possibility to find HLA-matched unrelated donors (MUD) for patients. This approach offered transplant for only up to 60%patients referred for transplantation in 2014, even we chose one HLA-mismatch donors.

The haploidentical transplant protocol proposed for our institution is based on Sidney Kimmel Comprehensive Cancer Center protocol from Johns Hopkins University School of Medicine. The major milestones of this protocol include: patient eligibility, donor selection criterias, evaluation of the haplo donor, the conditioning regimen plan and additional supportive care, the bone marrow harvest, prophylaxis of graft versus host disease, assessment during and after the transplant.

Donor must be HLA-haploidentical first-degree relatives of the patient with signed consent.

The patient, parents and children are typed at the allelic level for HLA-A, -B,-C,-DRB1 and -DQB1. They will perform also de HLA-antibody search using cross-match test in complement-dependent cytotoxicity.

The conditioning regimen is composed by Fludarabine 30 mg/m2/day (from day -6 to day -2) combined with Cyclophosphamide 14,5 mg/kgIBW/day (from day -6 to day-5) and TBI at 2 Gyîn day -1. In case of lacking TBI procedure at 2 Gy dose in day -1, it could be replaced by two dose of Busulfan iv in day -3 and day-2 (dose=3,2 mg/kgIBW/day) for those with acute and chronic leukemias.

The donor will have general anesthesia,the target yield of marrow is 4 x 10^8 total nucleated cells/kg recipient using his IBW.

The GVHD prophylaxis consisted of post-transplant Cyclophosphamide (PTCy) of 50mg/kgIBW/day in IV administration in day +3 and +4, followed by tacrolimus and mycophenolatemofetil (MMF) beginning day +5. The MMF will be stopped at day+35, the tacrolimus will continue till 6 months after the transplantation.

Conclusion:

One of the most important factors affecting transplantation outcome is proper timing.Therefore, donor availability is an crucial issue. Haploidentical related donors are available for almost all patients, so the use of those donors is a viable alternative.