RESULTS
From 2008 to 2018 we transplanted and followed 19 patients with PID.
Twelve of them were male (58%), and 14 survive (79%). Table 1summarizes some of their demographic and clinical features.
Their phenotypic diagnoses were: Wiskott-Aldrich Syndrome (WAS), 7
patients; Severe-combined immune deficiency (SCID), 6 patients; and,
Chediak-Higashi syndrome (CHS), Severe congenital neutropenia (SCN),
X-linked Chronic granulomatous disease (CGD), Cartilage-hair hypoplasia
(CHH), STAT1 deficiency, and Omenn syndrome (RAG1 deficiency), one
patient each. Genetic diagnosis was achieved for only 3 patients,
usually after the transplant. Eight patients (42%) were undernourished.
Mean age at HSCT was 41.9 months (range 3 to 156 months). Mean age at
diagnosis of PIDD was 10.68 months (range 1 through 40); mean diagnostic
delay (age at diagnosis – age at onset) was 7.95 months. Time elapsed
from diagnosis to transplant was, on average, 31.2 months. Only two
patients (one with SCID and one with STAT1-LOF) had a history of
inbreeding (consanguinity or endogamy), and two patients (one with CGD
and one with T-B+NK+ SCID) had adverse reactions to the BCG vaccine
(10%). Nine of the patients (47%) had a family history suggestive of
PID, or a similarly affected sibling. Regarding treatment, most patients
received monthly human intravenous gammaglobulin (IVIG) until HSCT, and
beyond (see below), as well as ambulatory prophylactic antibiotics.
Other treatments before HSCT included transfer factor (leukocyte
dialysate), prednisone, rituximab and valganciclovir.
By type, the first six grafts were obtained from umbilical cord (a total
of 7, or 37%), and the last 8 were haploidentical (a total of 12, or
63%). The donors of the latter were the patients’ parents (11 of 12),
and one sibling. Two patients had undergone a previous, unsuccessful
HSCT. The conditioning regime was myeloablative in all cases, consisting
of Busulfan, anti-thymocyte globulin (ATG), and Cyclophosphamide.
Anti-Graft-versus-host disease (GVHD) included cyclosporin, tacrolimus
(TAC), mophetil mycophenolate (MMF), cyclophosphamide, and deflazacort,
alone or in different combinations (see Table 2 ).
All patients received post-transplant cyclophosphamide, with TAC and
MMF, within the first three days. Engraftment was typically achieved
around day +14, as measured by increasing counts of neutrophils,
platelets and erythrocytes, in that order. There were seven primary
graft failures. Of these, two patients received a second rescue
transplant, one of them successful. Four patients developed GVHD, for a
prevalence of 21% (2 skin, 1 kidney, 1 lung) all of them grade I or II.
Two patients had partial or mixed chimerism (60-88%) that became
stable, and seven had a stable 100% chimerism. Immune reconstitution
was complete in 11 of 19 patients (58%). Most patients under
gammaglobulin replacement treatment were able to leave it 12 months
after HSCT (9/14); one after 24 months, and 4 still need it.
As for complications and deaths, one patient developed
post-transplantation lymphoproliferative disorder (PTLD) but recovered.
Three patients died of septic shock, one had severe pulmonary edema, and
one died of disseminated intravascular coagulation, for a total of 5
deaths, all within the first two months after transplant (days +22 to
+54, mean 34.2 days).