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.