DISCUSSION:
We describe a series of 19 patients from Mexico with 8 PID diagnoses who underwent allogenic HSCT at a single center in Monterrey, NL over a period of 11 years. 58% of them were male, and 79% survived. Their age at transplantation ranged from 3 months to 13 years old. The mean time from diagnosis was 31.2 months. Only 21% developed GVHD, and one patient suffered from PTLD.
To our knowledge, this is the first report of its kind in our country. Although the sample size is small, we want to share our experience to encourage other hospitals to perform HSCT in their patients with severe PID. Our figures in survival and GVHD prevalence compare well to what has been reported with centers in industrialized countries, which is no small feat when we consider that all our stem cells came from umbilical cord or haploidentical donors, in a country with limited therapeutic options and a very small donor registry.
Patiroglu et al in Turkey 2017 (8), reported the outcomes of 20 transplanted PID patients (of which 6 were also SCID), with a median age at transplant of 21 months, 11 related HLA-matched, 6 haploidentical; they found a 65% survival rate, and a prevalence of 30% for GVHD. In Seoul, Yi et al . described in 2018 their experience of 26 patients in 11 years (9), most of which had WAS, CGD, or SCID; they found a 73.1% survival rate, and 85% of patients with complete chimerism after 1 year. In India, Uppuluri et al (10) transplanted 16 children with PID, and used post-transplant cyclophosphamide on days 3-4; they found a 50% prevalence for GVHD.
The Paris group at Necker Hospital recently reported their experience with post-transplant cyclophosphamide to reduce the risk of graft failure and GVHD in children with PID or osteopetrosis without an HLA-identical donor (11). They found a 77.7% survival rate after two years, with a cumulative incidence of 45.8% and 24.2% for acute and chronic GVHD. In the rest of North America and Europe, nearly four decades of experience and research have allowed for excellent survival rates. From their large cohorts we have learned that the outcome is largely dependent on active infection-free status at the moment of transplant (5,6).
HSCT remains the only curative treatment for many children with PIDD. The guidelines for HSCT in children with PID are accepted and known internationally; they are considered standard practice pretty much everywhere in the world (3). The determinants of the differences in outcomes are therefore fourfold: 1) early diagnosis, 2) the availability of HLA-matched donors, 3) the availability of effective therapeutic agents, and 4) each center’s learning curve. Mexico and Latin America are lagging in all those four determinants, and yet we need to respond to our newly diagnosed PID patients with the best care and ingenuity that we can summon. The need for local and regional donor registries is especially felt, as the chances of finding an unrelated HLA-matched donor are lower for patients from under-represented ethnic groups, and also because having to import cells or donors from abroad prolongs waiting times and makes the final cost far more expensive.
In Mexico and Latin America, we need multicenter collaboration and regional donor registries. We have found that we can achieve encouraging results in the outcome of our patients despite resource scarcity and other limitations we share with developing countries and small centers elsewhere.
We would like to repeat this analysis when we reach 100 patients transplanted for PID. In the meantime, the best we can do is to keep learning from other centers’ experiences, continue teaming up with other specialists, and collaborate with researchers in other hospitals and countries. The British Cycling Olympic team famously focused their efforts on making small improvements in every aspect of their craft (12). As we deal with scarcity, unpredictability and the many obstacles of transplanting children with PID in our country, we subscribe to this philosophy of “marginal gains” in every aspect that can be improved, in order to better the chances of survival for our next patient.
To conclude, after 11 years performing allogeneic HSCT in 19 children with PID, we can recommend the use of post-transplant cyclophosphamide to prevent GVHD. A courageous attitude, stoic patience, and a philosophy of “marginal gains” for improvement cannot hurt, and these may all be learned from our patients as they journey through their illnesses enduring frightening procedures.