In Mexico, 15% of haemophilia A (HA) patients develop inhibitory alloantibodies in response to replacement therapy with factor VIII (FVIII), requiring bypass therapy such as activated prothrombin complex concentrate (APCC). Because bypass therapy has not been broadly available in Mexico even in recent years, this study aimed to evaluate the thrombin generation assay (TGA) in assessing the response to FVIII or APCC treatment in patients with severe HA positive to inhibitors. We studied 189 patients with severe HA. Clinical severity was verified by one-stage APTT-based clotting assay. Inhibitors to FVIII were investigated by the Nijmegen-Bethesda (N-B) method, and type of inhibition was assessed through serial plasma dilutions. Thrombin generation was measured with the calibrated automated thrombogram in inhibitor-positive plasmas previously spiked and incubated with FVIII or APCC. Data were analysed using anova, Student or Fisher's exact tests. We detected 47 (24.9%) subjects with high-titre (5-1700 N-B U mL(-1)) and 25 (13.2%) subjects with low-titre inhibitor antibodies (0.6-4.7 N-B U mL(-1)). We found an association between kinetic behaviour and clinical response to FVIII (P = 0.0049) or vs. FVIII response evaluated with TGA (P = 0.0007). Global concordance between clinical and in vitro response was 70%. By evaluating the capacity of thrombin formation in a plasma sample, TGA predicts the response to FVIII or APCC therapy and allows individual optimization of resources in patients with severe HA and high-titre inhibitors. The inhibition pattern of the antibodies to FVIII:C correlated with the TGA parameters and showed an association with the clinical response to FVIII.

Introduction For many patients with primary immune deficiency (PID), stem‐cell transplantation (SCT) may be life‐saving. Objective To review our experience of 11 years transplanting children with PID in Mexico. Methods Chart review of patients who underwent SCT from 2008 to 2018, to describe their diagnoses, time to transplant, conditioning regime, survival rate and outcomes. All patients received post‐transplant cyclophosphamide as graft‐versus‐host‐disease (GVHD) prophylaxis. Results 19 patients with combined, phagocytic or syndromic PID from 5 states. Twelve of them were male (58%) and 14 survive (79%). Mean age at HSCT was 41.9 months; mean time from diagnosis was 31.2 months. Seven grafts were umbilical cord and 12 haploidentical. The conditioning regime was myeloablative, with five primary graft failures. Two patients had partial and 10 full chimerism. Five patients died within 2 months after transplant. Immune reconstitution was complete in 11 of 19 patients. We found a prevalence of 21% GVHD. Discussion We describe 19 patients from Mexico with 8 PID diagnoses who underwent allogenic HSCT over a period of 11 years. Survival rate and other outcomes compare well with industrialized countries. We recommend the use of post‐transplant cyclophosphamide to prevent GVHD in scenarios of resource scarcity and a lack of HLA‐identical donors.

INTRODUCTION: For many patients with Primary immune deficiency (PID), stem-cell transplantation (SCT) may be lifesaving. OBJECTIVE: To review our experience of 11 years transplanting children with PID in Mexico. METHODS: Chart review of patients who underwent SCT from 2008 to 2018, to describe their diagnoses, time to transplant, conditioning regime, survival rate and outcomes. All patients received post-transplant cyclophosphamide as graft-versus-host-disease (GVHD) prophylaxis. RESULTS: 19 patients with combined, phagocytic or syndromic PID from 5 states. Twelve of them were male (58%) and 14 survive (79%). Mean age at HSCT was 41.9 months; mean time from diagnosis, 31.2 months. Seven grafts were umbilical cord and 12 haploidentical. The conditioning regime was myeloablative, with seven primary graft failures. Two patients had partial and 10 full chimerism. Five patients died within 2 months after transplant. Immune reconstitution was complete in 11 of 19 patients. We found a prevalence of 21% GVHD. DISCUSSION: We describe 19 patients from Mexico with 8 PID diagnoses who underwent allogenic HSCT over a period of 11 years. Survival rate and other outcomes compare well with industrialized countries. We recommend the use of post-transplant cyclophosphamide to prevent GVHD in scenarios of resource scarcity and a lack of HLA-identical donors. HIGHLIGHTSWe describe the experience of our hospital, UMAE 25 IMSS in Monterrey NL, Mexico, of 11 years performing hematopoietic stem-cell transplantation (HSCT) in pediatric patients with primary immune deficiencies.We report the clinical features, origin, diagnoses, treatment and outcome of 19 patients with 8 PID diagnoses who underwent HSCT, with a 79% survival rate, 21% GVHD prevalence, 47% stable chimerism, and 58% of complete immune reconstitution.Post-transplant cyclophosphamide has been proven effective as anti-GVHD prophylaxis. Despite all our grafts coming from umbilical cord and haploidentical donors, we were able to prevent GVHD by using post-transplant cyclophosphamide.In Mexico and Latin America, we need better local and regional donor registries. We can achieve encouraging positive results despite resource scarcity and other regional limitations.

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