The differential diagnosis list includes infectious diseases like Epstein–Barr virus, cytomegalovirus, human herpesvirus 6, histoplasma, mycobacteria, and toxoplasma, which can produce similar symptoms.

[16] The COG JMML study includes splenectomy as a standard component of treatment for all clinically stable patients.

The EWOG-MDS JMML study allows each child's physician to determine whether or not a splenectomy should be done, and large spleens are commonly removed prior to bone marrow transplant.

When a splenectomy is scheduled, JMML patients are advised to receive vaccines against Streptococcus pneumoniae and Haemophilus influenza at least two weeks prior to the procedure.

[17] The role of chemotherapy or other pharmacologic treatments against JMML before bone marrow transplant has not undergone final clinical testing, and its importance is still unknown.

Generally, JMML clinical researchers recommend that a patient have a bone marrow transplant scheduled as soon as possible after diagnosis.

[19] Prognosis refers to how well a patient is expected to respond to treatment based on their individual characteristics at time of diagnosis.

A significant number of JMML patients do achieve complete remission and long-term cure after a second bone marrow transplant, so this additional therapy should always be considered for children who relapse.