PB0608 - Transplant associated microangiopathy in children undergoing haploidentical stem cell transplant with post-transplant cyclophosphamide

Background: Haploidentical stem cell transplant (SCT) with post-transplant cyclophosphamide (PTCy) has revolutionized field of SCT making a donor available for all children needing SCT. However, this technique can lead to development of transplant-associated microangiopathy (TAMA)
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Aims: We describe here the incidence, risk factors and outcomes of TAMA in children undergoing haploidentical SCT with PTCy

Methods: We retrospectively collected data of all children developing TAMA after undergoing haploidentical SCT with PTCy. TAMA was diagnosed as per modified Jodele criteria when ≥4 of the following 7 features occur twice within 14 days: anemia, thrombocytopenia; lactate dehydrogenase (LDH) exceeding the upper limit of normal (ULN); schistocytes; hypertension; soluble C5b-9 exceeding the ULN; and proteinuria (≥1 mg/mg random urine protein-to-creatinine ratio

Results: 130 children underwent haploidentical SCT with PTCY at our center out of which 102 (78%) survived post BMT at median follow-up of 32 months. A total of 17 (13%) children developed TAMA. Out of these 10 died. Causes of TAMA were cytokine release syndrome (CRS)-2, graft vs. host disease (GVHD)-3, viral (adenovirus-3, cytomegalovirus-1, BK virus-1 Covid-2) calcineurin inhibitors-4, inotuzumab-1. TAMA proved fatal in 6 out 7 children with viral infections and only child who survived had cytomegalovirus infection. Both children with CRS died and amongst GVHD;2 out 3 died. All children with TAMA due to calcineurin inhibitor or inotuzumab recovered. In all children initially calcineurin inhibitor was stopped and methyprednisone was started 2 mg/kg . Those with no improvement were given Rituximab 100 mg/m2 weekly x 4 doses. One child with adenovirus infection and TAMA underwent plasma exchange. Eculizumab and defibrotide were unavailable. GVHD and viral infections were treated as per protocol.

Conclusion(s): TAMA is seen frequently in children undergoing haploidentical related donor SCT with PTCy. Other than calcineurin inhibitors; GVHD and viral infections are major risk factors. TAMA has high risk mortality in this setting.