Sister runs off with sweetheart (5)
I believe the answer is:
nurse
'sister' is the definition.
(I've seen this before)
'runs off with sweetheart' is the wordplay.
'off with' is an anagram indicator.
'sweetheart' becomes 'e' (the heart/centre of 'sweet').
'runs' anagrammed with 'e' can make 'NURSE'.
(Other definitions for nurse that I've seen before include "Patient tender" , "Tend - care for" , "Nanny" , "dogfish or > worker bee" , "Nourish" .)