RESULTS
Between January 2015 and July 2020, 40 patients received a
haploidentical transplant at The Hospital for Sick Children. Indications
for transplant included: AML (n=11), ALL (n=9), immunodeficiency (n=4),
marrow failure (n=4), lymphoma (n=3), chronic myeloid leukemia (n=3),
mixed phenotypic acute leukemia (n=2), myelodysplastic syndrome (n=2),
and other (n=2). From this cohort, five patients received a
haploidentical transplant with a non PTCy approach. We excluded one of
the five patients because that patient also received a non PTCy
prophylaxis with etanercept.
Patient demographics and transplantation details are summarized in Table
1. A total of four patients (2-12 years) received a haploidentical HCT
with a PBSC graft and Aba-based GVHD prophylaxis. Our cohort included
one patient with a prior liver transplant for erythropoietic porphyria,
two patients who have had a previous haplo-HCT with PTCy for
hematological malignancy (CML and AML) complicated by secondary graft
failure and one patient with a primary immunodeficiency (interferon
gamma receptor 1 [IGR1] deficiency) who had concurrent mycobacterial
avian complex infection.
All our cohort had significant concerns for the use of PTCy GVHD
prophylaxis either due to recent prior high dose cyclophosphamide,
concern of alkylating therapy exposure or organ dysfunction and
therefore required an alternative regimen. Our GVHD prophylaxis included
Aba (10mg/kg) on day -1 & +5 in four patients, methotrexate
(5mg/m2) on day +1, 3, & 6 in three patients,
tacrolimus starting on day +1, in four patients and mycophenolate
mofetil starting on day +1, in four patients. Two patients received two
additional doses of abatacept (four total) on day +32 and day +56 for
acute skin GVHD. There were no infusion reactions or adverse effects
noted with Aba infusion. Rituximab (375mg/m2) was
given on day +1 as EBV prophylaxis in two patients with EBV
seropositivity.
The median number of CD34+ cells dose was 6.75
x106 cells/kg.
The median time to neutrophil and platelet
(>20 ×109/L) engraftment was 23 days
(range, 20-26 days) and 51 days (range, 17-91 days), respectively. Three
patients had viral re-activations seen on routine monitoring but no
signs of clinical disease. Specifically, two patients had asymptomatic
CMV reactivation and one patient had adenovirus, all treated
successfully with pre-emptive anti-viral therapy. One patient developed
transplant associated thrombotic microangiopathy (TA-TMA) on Day + 16
and resolved with medical management. The TA-TMA was likely secondary to
the calcineurin inhibitor.
One patient had stage 3 skin acute GVHD (overall grade II), 46 days
post-transplant, which quickly responded to methylprednisone and then an
oral prednisone taper. One patient had both stage 3 skin and stage 1
gastrointestinal (GI) acute GVHD (overall grade II) 40 days
post-transplant which responded to methylprednisone and restarting
tacrolimus which were subsequently weaned. Two patients had mild chronic
skin GVHD.
At a median follow up of 1.1 years (range: 214 days- 1.7 years), all
four patients are alive with stable engraftment and full donor
chimerism. They have had no evidence of disease and a performance score
of 100 at last follow up. Three patients are off immunosuppressive
therapy (patient 1 at 18 months, Patient 2 at 130 days, Patient 4 at 247
days), one patient is on gradual wean of immunosuppression for mild
chronic skin GVHD.