Juvenile myelomonocytic leukemia surgery

Splenectomy
The theory behind splenectomy is that in JMML, the spleen acts as a trap for leukemic cells, which leads to their enlarged size. The fear is that since radiation and chemotherapy attack active leukemia cells rather than dormant ones, if the spleen is not removed it may harbor JMML cells that can later lead to relapse. The impact of splenectomy for post-transplant relapse, though, is unknown. The COG JMML Study includes splenectomy as a standard treatment for all clinically stable patients. The EWOG-MDS JMML Study allows each child’s physician to determine whether or not a spleenectomy 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 pneumoneae and Haemophilus influenza at least 2 weeks prior to the procedure. Following splenectomy, penicillin may be administered daily in order to protect the patient against bacterial infections that the spleen would otherwise have protected against; this daily preventative regimen will usually continue until the patient is an adult.

Stem cell transplantation (a.k.a. bone marrow transplant)
The only treatment that has resulted in cures for JMML is a bone marrow transplant, with about a 50% survival rate. The risk of relapsing after transplant is high, and has been recorded as high as 50%. Generally, JMML clinical researchers recommend that a patient have a bone marrow transplant scheduled as soon as possible after diagnosis. A younger age at bone marrow transplant appears to predict a better outcome.

Donor
Transplants from a matched family donor (MFD), matched unrelated donor (MUD), and matched unrelated umbilical cord blood donors have all shown similar relapse rates, though transplant-related deaths are higher with MUDs and mostly due to infectious causes. Extra medicinal protection, therefore, is usually given to recipients of MUD transplants to protect the child from Graft Versus Host Disease (GVHD). JMML patients are justified for MUD transplants if no MFD is available due to the low rate of survival without a bone marrow transplant.

Conditioning regimen
The COG JMML Study involves 8 rounds of total-body irradiation (TBI) and doses of cyclophosphamide to prepare the JMML child’s body for bone marrow transplant. Use of TBI is controversial, though, because of the possibility of late side-effects such as slower growth, sterility, learning disabilities, and secondary cancers, and the fact that radiation can have devastating effects on very young children. It is used in this study, however, due to the concern that chemotherapy alone might not be enough to kill dormant JMML cells. The EWOG-MDS JMML Study includes busulfan in place of TBI due to its own research findings that appeared to show that busulfan was more effective against leukemia in JMML than TBI. The EWOG-MDS study also involves cyclophosphamide and melphalan in its conditioning regimen.

Graft versus leukemia
Graft versus leukemia has been shown many times to play an important role in curing JMML, and it is usually evidenced in a child after bone marrow transplant through some amount of acute or chronic Graft Versus Host Disease (GVHD). Evidence of either acute or chronic GVHD is linked to a lower relapse rate in JMML. Careful management of immunosuppressant drugs for control of GVHD is essential in JMML; importantly, children who receive less of this prophylaxis have a lower relapse rate. After bone marrow transplant, reducing ongoing immunosuppressive therapy has worked successfully to reverse the course of a bone marrow with a dropping donor percentage and to prevent a relapse. Donor lymphocyte infusion (DLI), on the other hand, does not frequently work to bring children with JMML back into remission.