The default 5-tuple (Source IP, Destination IP, IP Protocol, Source Port, and Destination Port) stickiness provides the most optimal traffic distribution to targets, and is suitable for most TCP and UDP based applications, with some exceptions. The default 5-tuple stickiness is not suitable for TCP or UDP based applications that use separate streams or port numbers for control and data, such as FTP, Microsoft RDP, Windows RPC and SSL VPN. Control and data flows of such applications can land on different target appliances and can cause traffic disruption. If you want to support such protocols, you should enable GWLB flow stickiness using 3-tuple (source IP, destination IP, IP protocol) or 2-tuple (source IP, destination IP).
Some applications do not use TCP or UDP transport at all, but instead use IP protocols such as SCTP and GRE. With the default 5-tuple stickiness of GWLB, traffic flows from these protocols can land on different target appliances and can cause disruption. If you want to support such protocols, you should enable GWLB flow stickiness using 3-tuple (source IP, destination IP, IP protocol) or 2-tuple (source IP, destination IP).
Please see flow stickiness documentation for how to change flow stickiness type.