The Road to Day 0: Barriers from HLA Typing to Infusion in the Era of Haploidentical Transplantation in Mexico

Abstract

<h3>Introduction</h3> In the era of haploidentical (haplo) transplantation (alloHSCT) donor availability has been greatly improved and is no longer the biggest barrier for grafting. This fact is particularly important in low and middle-income countries, (LMIC) where access to alternative donors is scarce. On the other hand, most outcomes-based publications in the field are focused on the transplanted and not in an "intent-to-transplant" basis. Contributing causes for not reaching transplantation have yet to be reported in this context. Therefore, as early adopters of haplo alloHSCT we aimed to evaluate the characteristics and outcomes of patients starting at the time of HLA typing, regardless of the event of transplantation. <h3>Methods</h3> Adults who were HLA-typed and considered potentially eligible for transplantation in our center were included. Since 2015 haplo donors have become the immediate next best option when a matched sibling donor is unavailable due to a lack of access and/or increased costs of alternative donors. Related allogeneic transplantation has been subsidized by our government, reducing costs to a minimum for the uninsured. We performed a retrospective review of patient records from January 2016-December 2018, regardless of diagnosis, donor source and conditioning regimen planned. The reasons for not performing alloHCT were assessed. A landmark survival analysis from the time of HLA typing was performed, as well as logistic regression analyses to evaluate covariates associated to not reaching transplantation. <h3>Results</h3> 135 patients were HLA-typed and considered eligible to proceed to alloHCT. Forty-seven (34.8%) were not transplanted. In N=6, alloHSCT was considered unnecessary. The proportion of patients who received alloHSCT was similar regardless of the availability of a matched sibling vs haplo donor (68.2 vs 66.7%, p=0.53). Transplanted patients had a significantly lower disease risk index (DRI) and more frequently had private healthcare. The reasons for not proceeding with alloHSCT were disease status (refractory/relapsed disease prior to conditioning) in 15 patients (36.6%), followed by procedure rejection by patient/family and/or treatment abandonment in 12 (29.2%), 5 (12.2%) did not have a suitable donor, 4 (9.7%) due to economic difficulties, and 4 (9.7%) developed comorbidities. A high DRI and lack of insurance were associated with a higher risk for not getting a transplant in both univariate and multivariate analyses. The outcome of patients that were not transplanted was dismal, particularly for high/very high DRI patients (Figure 1, Panels A-D). <h3>Conclusion</h3> In the era of haplo transplantation, the biggest barrier in our context is disease activity/relapse, followed by patient rejection or abandonment, and not the availability of a donor. We must avoid delays and increase patients and family education in order to overcome these limitations.