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.