Anaphylaxis Following Human Prothrombin Complex Concentrate in a Child with Lupus Anticoagulant Hypoprothrombinemia Syndrome: A Cautionary Tale.

A previously healthy 3-year-old girl presented with a short history of mucocutaneous bleeding and a spontaneous left knee hemarthrosis following a nonspecific viral gastroenteritis. Initial investigations for a bleeding disorder revealed a normal platelet count; however, coagulation studies revealed a prothrombin time (PT) of 25 seconds and an activated partial thromboplastin time (APTT) of 66 seconds (both prolonged). The APTT did not correct on mixing with normal plasma, and further testing confirmed the presence of a strong lupus anticoagulant (LA). One-stage assays of factor VIII, VII, and X were normal, but factor II was markedly reduced. Based on this distinct clinicopathological picture, a diagnosis of lupus anticoagulant hypoprothrombinemia syndrome (LAHS) was made. Due to the presence of a hemarthrosis, the patient was treated with clotting factor concentrate. Human prothrombin complex concentrate (PROTHROMBINEX-VF) was used as a source of factor II replacement; however, during the infusion the patient developed anaphylaxis necessitating resuscitation. The patient was observed without further factor replacement, and the bleeding symptoms resolved over several days. Within 3 weeks her PT and factor II had normalized but the APTT remained prolonged. After 6 months the coagulation profile had completely normalized and the LA was negative. It is unusual to require replacement of factor II in paediatric LAHS because bleeding is typically minor and self-limited. Anaphylaxis to clotting factor concentrates has not been previously reported in the context of LAHS, but is well described in patients with congenital factor IX deficiency (hemophilia B). Whilst the potential mechanism for anaphylaxis in our patient is unknown, it is recommended that human prothrombin complex concentrates should be used cautiously in paediatric LAHS.

Use of brentuximab vedotin as salvage therapy pre-allogeneic stem cell transplantation in relapsed/refractory CD30 positive lympho-proliferative disorders: a single centre experience.

BACKGROUND: The role of brentuximab peri-allogeneic transplantation in patients with relapsed and/or refractory CD30 positive lymphomas remains poorly defined. AIM: To assess the outcome of use of brentuximab as a bridge to allogeneic stem cell transplantation (SCT) in patient with relapsed/refractory CD30+ classic Hodgkin lymphoma cHL and anaplastic large cell lymphoma (ALCL). METHODS: Outcomes of consecutive patients with relapsed/refractory cHL/ALCL treated with brentuximab as a bridge to SCT were determined by retrospective review of individual medical records. Survival analysis was measured from start of brentuximab treatment. RESULTS: A total of 12 patients (10 cHL, 2 ALCL) had received brentuximab as a planned bridge to allogeneic SCT. Median age was 27 years (range 20-54 years); median prior lines of therapy was 4 (range 3-6) and all except one patient had undergone prior autologous SCT (92%). Patients received at median of 3 brentuximab doses pre-allogeneic SCT (range 1-4), with an overall response rate of 66.7%. At a median follow up of 30 months (range 6-52 months), 2 years progression free survival and overall survival post-allogeneic SCT is 58 and 92% respectively. Incidence of non-relapse mortality, grade 3-4 acute graft versus host disease and extensive stage chronic graft versus host disease is 8, 17 and 18% respectively. Of five patients who subsequently relapsed post-SCT, four remain alive with disease control post manipulation of immune-suppression. CONCLUSION: Our experience suggests that brentuximab use pre-allogeneic SCT is not associated with any significant post-transplant toxicity, and is associated with a rapid response in a majority of patients with relapsed/refractory CD30 positive lymphomas. Brentuximab may thus provide a non-toxic bridge to allogeneic SCT for patients with relapsed/refractory CD30 positive cHL or ALCL.