Most children with JMML require intensive treatment, but some do not. For example, children with Noonan syndrome and those with CBL syndrome sometimes develop signs and symptoms of JMML, but the illness disappears with no treatment. Doctors will adopt a “watchful waiting” strategy if they think this is the case. Sometimes treatment is needed for these children to reduce problematic symptoms, such as an enlarged spleen or low red blood cell count. However, it is difficult to determine which children need immediate treatment and which children have this slow-growing (called indolent) form of JMML.

When my daughter Izzabella was a year old, she fell at my mother’s house, hit her head, and briefly stopped breathing. We took her to the ER where they drew some blood and did an MRI. Her platelets came back low (30,000) so her pediatrician redid the labs the next day with the same result. We were referred to a pediatric hematologist who saw her a few times. Then Izzabella started to get bruises on her legs and nosebleeds that were hard to stop. Our pediatrician sent us to the closest children’s hospital, where she was diagnosed with a blood disorder called ITP [idiopathic thrombocytopenic purpura]. She had labs drawn every three months for the next year and her platelets stayed low. At that point, they did a bone marrow aspiration (negative) and sent peripheral blood for genetic testing (showed JMML with the CBL mutation). Because this could disappear on its own, we are in a “watchful waiting” stage, and Izzabella has blood work done every three months.

Most of the time, however, children with JMML need treatment quickly. The only treatment that can cure JMML is an allogeneic stem cell transplant (SCT). This type of transplant uses cells from:

• The bone marrow of a matched or partially matched family member
• The bone marrow of a matched unrelated donor
• An umbilical cord

An allogeneic or cord blood transplant can cure about half of the children who receive it. Usually, any child with PTPN11, KRAS, or NF1-mutated JMML needs an SCT as soon as possible after diagnosis. Infants and children with CBL mutations, and few of those with NRAS mutations, may have a type of JMML that disappears without treatment. In this situation, the decision to transplant or not needs careful consideration and discussion.

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy does not cure JMML, but it may be used to (1) treat symptoms, (2) prepare for an SCT, and (3) prevent severe graft-versus-host disease after transplant. Chemotherapy drugs that are sometimes used to treat symptoms (usually while a stem cell donor is being located) are mercaptopurine, cytarabine, and 13-cis-retinoic acid. Sometimes chemotherapy is given to reduce the amount of disease prior to transplant.

All children undergoing a SCT for JMML receive high-dose chemotherapy to make room in their bone marrow for the donated stem cells. This is called “conditioning.” The chemotherapy drugs destroy cancer cells in the body and help suppress the body’s immune system to prevent rejection of donated stem cells. The drugs most often used to prepare for an SCT are some combination of busulfan, fludarabine, cyclophosphamide, and/or melphalan. No standard of care currently exists for which drugs to use for conditioning. Although total body irradiation was used in the past as part of conditioning, it is rarely used today because of the late effects it causes, especially in young children.

My 3-year-old son needed an SCT as soon as possible. His two siblings did not match, but we were able to find three exact matches on the registry. They chose a young woman in her early 20s, and the entire process went lightning fast. He was diagnosed on February 25 and had the transplant on June 11. His conditioning included cyclophosphamide, busulfan, melphalan, and a small dose of IV methotrexate. He did not get total body radiation.

Drugs are used after SCT to prevent severe graft-versus-host disease—usually tacrolimus or cyclosporine and methotrexate. However, methotrexate is usually not used in children who had umbilical cord transplants. In the past, steroids were given after transplant, but now the drug mycophenolate mofetil is more commonly used to keep the body’s immune system from attacking and rejecting the transplanted cells. This drug belongs to a class of medications called immunosuppressants. For information about the drugs discussed in this section, see Chapter 13, Chemotherapy and Other Medications.

Stem cell transplant

For children with JMML, stem cells are obtained from (1) a matched or partially matched family member, (2) matched unrelated donor, or (3) cord blood. The stem cells are given to a child through their venous catheter. Children are awake during this painless process. It generally takes two to four weeks for the stem cells to multiply and make new blood cells. After SCT, the relapse rate for children with JMML is 30 to 40%. Relapse often occurs within a few months after transplant, and the risk of relapse drops considerably one year after transplant. Children who relapse after transplant will frequently receive a second transplant. For more information, see Chapter 16, Stem Cell Transplantation.

Our son with JMML needed a transplant as soon as possible. While they searched for a donor, he was treated with 6-MP. We were lucky to find an unrelated donor who was a perfect match. We went to a major transplant center where he received nine days of conditioning with mephalan, cyclophosphamide, and busulfan. The transplant was in November 2015 and he relapsed in March 2016. We were lucky that our donor was willing to donate a second time. After a year away from home, we were able to return home. We found out just a month ago that he is in remission. His central line is finally out and he is doing all of the things little boys are supposed to do.