There are two internationally accepted treatment protocols, which are geographically based: * North America: the Children's Oncology Group (COG)<unk>  study * Europe: the European Working Group for Myelodysplastic Syndromes (EWOG-MDS)<unk>  study The following procedures are used in one or both of the current clinical approaches listed above: Splenectomy The theory behind splenectomy in<unk>  is that the spleen may trap leukemic cells, leading to the spleen's enlargement, by harboring dormant<unk>  cells that are not eradicated by radiation therapy or chemotherapy for the active leukemia cells, thus leading to later relapse if the spleen is not removed. However, the impact of splenectomy on post-transplant relapse, though, is unknown. The COG<unk>  study includes splenectomy as a standard component of treatment for all clinically stable patients. The EWOG-MDS<unk>  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,<unk>  patients are advised to receive vaccines against Streptococcus pneumoniae 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 often continue indefinitely. Chemotherapy The role of chemotherapy or other pharmacologic treatments against<unk>  before bone marrow transplant has not been studied completely and its importance is still unknown. Chemotherapy by itself has proven unable to bring about long-term survival in<unk> . * Low-dose conventional chemotherapy: Studies have shown no influence from low-dose conventional chemotherapy on<unk>  patients’ length of survival. Some combinations of 6-mercaptopurine with other chemotherapy drugs have produced results such as decrease in organ size and increase or normalization of platelet and leukocyte count. * Intensive chemotherapy: Complete remission with ongoing durability from<unk>  has not been possible through use of intensive chemotherapy, but it is still used at times because it has improved the condition of a small but significant number of<unk>  patients who do not display an aggressive disease. The COG<unk>  study administers 2 cycles of fludarabine and cytarabine for 5 consecutive days along with 13-cis retinoic acid during and afterwards. The EWOG-MDS<unk>  study, however, does not recommend intensive chemotherapy before bone marrow transplant. * 13-cis retinoic acid (Isotretinoin): In the lab, 13-cis-retinoic acid has inhibited the growth of<unk>  cells. The COG<unk>  study therefore includes 13-cis-retinoic acid in its treatment protocol, though its therapeutic value for<unk>  remains controversial. Radiation Radiation to the spleen does not generally result in a decrease in spleen size or reduction of platelet transfusion requirement. Stem cell transplantation The only treatment that has resulted in cures for<unk>  is stem cell transplantation, also known as 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,<unk>  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).<unk>  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<unk>  study involves 8 rounds of total-body irradiation (TBI) and doses of cyclophosphamide to prepare the<unk>  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<unk>  cells. The EWOG-MDS<unk>  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<unk>  than TBI. The EWOG-MDS study also involves cyclophosphamide and melphalan in its conditioning regimen. * Post transplant management: patients can experience relapse, causing treatment failure. It can be prevented by starting the patient with withdrawal of immunosuppressants and/or begin donor lymphocyte infusion. * Graft versus leukemia: Graft versus leukemia has been shown many times to play an important role in curing<unk> , 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<unk> . Careful management of immunosuppressant drugs for control of GVHD is essential in<unk> ; 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<unk>  back into remission.
Juvenile myelomonocytic leukemia
T-lymphoblastic leukemia/lymphoma
Acute megakaryoblastic leukemia
Acute myeloblastic leukemia with maturation
Hypodiploid acute lymphoblastic leukemia
B-cell prolymphocytic leukemia
T-cell prolymphocytic leukemia
Precursor B-cell lymphoblastic leukemia