Interactome based identification and validation of prefoldin 5-α for prognosing CNS leukemia in B-ALL patients.

We report here the identification and validation of prefoldin 5-alpha (PFDN5-α) for the first time as prognostic biomarker for prediction of central nervous system (CNS) leukemia of B cell acute lymphoblastic leukemia (B-ALL) origin. Since cerebrospinal fluid (CSF) cytology being the gold standard of diagnosis for CNS leukemia with poor sensitivity, mandatory prophylactic intrathecal chemotherapy is administered irrespective of patients develop CNS leukemia. Thus, using interactome studies, we identified PFDN5-α as a prognostic biomarker for predicting CNS leukemia by interacting lymphoblastic proteins and CSF from B-ALL patients using far-western clinical proteomics approach. Validation by both western and ELISA methods confirmed our results. For further clinical translation, we performed Receiver Operating Characteristic (ROC) curve analysis generated from CNS +ve (n = 25) and -ve (n = 40) CSF samples from B-ALL patients and identified PFDN5-α-CSF reactivity cut-off value as 0.456. Values below 0.456 indicate the patient is at risk of developing CNS leukemia and suggestive of having intrathecal chemotherapy. Further flow cytometry validation for CNS leukemia positivity revealed that with increasing blast cells, a decrease in PFDN5-α-CSF reactivity confirming ELISA based PFDN5α-CSF reactivity assay. Predicting CNS leukemia development risk by ELISA based PFDN5-α-CSF reactivity assay could have potential in the clinical management of CNS leukemia.

Intermediate Dose Prophylaxis in Adults with Haemophilia: A Clinical Audit from a Resource Limited Setting.

To address the scarcity of real world data on adult prophylaxis from developing world, a short term intermediate dose prophylaxis in adult haemophilia A patients was initiated. A total of eight patients aged > 18 years with moderate/severe haemophilia A were given an average dose of 23 IU/kg recombinant factor VIII (rFVIII) concentrate twice weekly for 2 months. A clinical audit was done on completion of four months. The mean age of the participants was 31.63 (± 6.98) years. The mean bleed rate during two months of episodic versus prophylactic regimen was 5.13 versus 0.63 (p = 0.01) and that of work days lost, hospital visits for hemophilia care were 30.63 (± 24.69) versus zero days, 20.63 (± 16.19) versus zero days respectively. The mean of factor VIII consumed during prophylaxis was 13,500 IU/month (i.e., 23 IU/kg/dose).The median time gap between prophylactic infusion to trough level was 67.50 h (60-74 h) and the median trough level observed was 2.50% (range 1-5%). The results of our clinical audit show that Intermediate dose prophylaxis with rFVIII concentrates in young adult patients with moderate/severe haemophilia A appears to be effective in reducing the frequency of bleeds.