ImpactU Versión 3.11.2 Última actualización: Interfaz de Usuario: 16/10/2025 Base de Datos: 29/08/2025 Hecho en Colombia
Starting Cyclosporine on Day Zero and Mycophenolate on Day + 1 in Unmanipulated Peripheral Blood Haplo Transplant with Cyclophosphamide Post-Transplantation Is Feasible, Abrogate the Severity of Cytokine Release Syndrome and Achieves a Very Low Rate of aGVHD
IntroductionThe use of unmanipulated peripheral blood from haploidentical donors (UPB Haplo) with post transplantation cyclophosphamide (PT-Cy) is often associated with a higher incidence and severity of cytokine release syndrome (CRS) and aGVHD when it is compared with bone marrow source (BM haplo). Recently it has been published (1Biol Blood Marrow Transplant. 2018; 24: 1243-1249Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar) a modification of PT-Cy protocol moving the day of administration of cyclosporine (CsA) and mycophenolate (MMF) from day +5 to zero and + 1 and using BM haplo with encouraging results. With the aim to reduce the incidence of CRS and aGVHD we did the same but keeping UPB haplo as a cellular source.Methods and patientsThe conditioning used was fludarabine 150 mg/m2, melphalan 100-120 mg/m2, and TBI 200-400 cGy or the same but with busulfan 4 mg/kg instead of melphalan, the CsA began on day zero and continuous until d+180, MMF was administered from d+ 1 to d+ 60 and PT-Cy 50 mg/kg on days +3 and +4 (fig 1).After a signed informed consent, 22 patients were transplanted; median age was 31 y (range 18-64), the diagnoseswere: acute lymphoid leukemia 11, acute myeloid leukemia 7, two had lymphoma, 1 myelodysplasia, and another, chronic myeloid leukemia. 50 % were in first remission, 36% in second, and 14% in third or with active disease.ResultsAll of the donors shared 4 out of 8 alleles with the recipient; their median age was 27 y (range 10-52) in 77% of the cases was a sibling, in 18% a child and in 5% a parent, 4 males received cells from female donors. A median of 7.2 × 10(6)/kg (range 3.9-12) of CD34 and 3 × 10(8)/kg of CD3 were infused.The engraftment rate of 21 patients alive at day +30 was 100%, the median time to achieve 500 neutrophil and self-sustained platelets was 15 and 16 days respectively (range 13-22 and 15-29), one patient with mix chimerism had secondary graft failure. The only manifestation of CRS was fever in 8 out of 22 (36%), range of temperature 38.2 to 39 ¼ C, median duration of 2.5 days.With a median follow-up for surviving patients of 9.5 months (range 3- 18) the incidence of aGVHD (GII-IV) was 5 %. Regarding cGVHD, the follow-up is still short, but only 2 out of 17 evaluable cases had extensive disease.Event was defined as death for any cause or relapse; 3 patients died due to an infection and 2 relapsed, the event-free survival at day 100 was 90% and at one year (Kaplan-Meier) 71.8% (fig 2).ConclusionIn this series of 22 patients, the administration of CsA on day zero and MMF on day + 1 in the UPB haplo transplant with PT-Cy was feasible and it decreased the severity and incidence of CRS and of aGVHD, even achieving a rate similar to that which has been reported using BMT haplo. The follow-up is still short to draw conclusions regarding the incidence of cGVHD and relapses, but they also seem encouraging. This strategy deserves further assessment with a bigger number of patients and longer follow-up.