What is JMML and how common is it?

Dr. Kleiner: JMML is a very rare form of pediatric leukemia. It comprises less than 1 percent of infant leukemias, and it's difficult to diagnose because, unlike the common leukemias that present with a high white count, most of the children with JMML present with a low platelet count and some abnormal cells. Many times it's missed or it takes a while for it to be diagnosed

Is it ever wrongly diagnosed?

Dr. Kleiner: Sometimes it's diagnosed as something called ITP, or a low platelet count, and it takes a while for a hematologist to think of it because it's such a rare disorder. It doesn't come to the top of the list of possible diagnoses to most physicians.

What is the prognosis for children with JMML?

Dr. Kleiner: Unfortunately, the prognosis for JMML is very poor. In general, the children do not respond to standard chemotherapy that would be used for regular infant leukemia. Most of the cases are fatal by the time the child is 3 years old

What are possible complications?

Dr. Kleiner: There are many complications. Many children develop a big spleen and they have low platelets, or they are prone to bleeding in other disorders that make it difficult to treat as the disease progresses.

How long does it take for the disease to progress?

Dr. Kleiner: Most children are diagnosed, eventually, by a year and half or two years of age. If it's not picked up then, it's almost always fatal by age three.

What is the standard treatment for JMML?

Dr. Kleiner: There is a standard pediatric oncology trial in trials to treat JMML with chemotherapy and radiation. It uses very strong doses of different chemotherapy drugs in an attempt to try and cure the disease. Unfortunately, it has not been that successful, and most physicians think that a stem cell transplant is needed.

Do doctors usually outline the risks of the treatment?

Dr. Kleiner: Yes. The consent that's given to the parents does explain the chances. It also brings up the possibility of a stem cell transplant. In general, most of the children are actually referred also to a transplant center, or the physician will talk to another physician at a transplant center

One of the current trials going on to treat JMML involves using cord blood as stem cell therapy for this disease. Can parents be donors if their child develops JMML?

Dr. Kleiner: No. There are diseases and there are research protocols where you can use a parent. In leukemia in general we almost never do that

Is the blood in public blood banks from parents who donated their blood for anyone's use? In other words, the blood is not for their personal use?

Dr. Kleiner: Right. These are mothers who have relinquished their right to the cord blood in order to benefit society. The cord blood banking is considered experimental right now in the U.S., and there are very strict regulations and guidelines by the FDA in terms of what is suitable for transplant and what units could be used to be given to someone else.

If that cord blood wasn't in the bank, would Adolfo have received the chemotherapy and radiation?

Dr. Kleiner: He would have received the chemo and radiation, but he most likely would not have survived.

How did Adolfo receive the blood once you found a match?

Dr. Kleiner: Adolfo received actually 10 days of chemotherapy -- three different, very powerful drugs to destroy his leukemia cells and all of his blood forming cells -- his bone marrow -- and then he received the donated cord blood unit that came from the New York blood center as basically an IV infusion like a blood transfusion. He stayed in the pediatric bone marrow transplant unit here for approximately one month and about two weeks after he had received the infusion of the stem cells, the cord blood cells started to grow in his blood and his white count started to come up

Did Adolfo need a particular type of stem cells?

Dr. Kleiner: We have to find a match, so for cord blood we try and match six different what's called tissue types, or HLA, in order to find a particular match for the patient. One of the advantages of cord blood over a bone marrow transplant is that, particularly from minority populations, we are able to find a donor in, for minorities such as Hispanic or African Americans who do not have a donor in their regular bone marrow donor volunteer population. In Adolfo's case, he did not have a volunteer donor, so Adolfo received a five-out-of-six cord blood transplant and there was a mismatch because we could not find a perfect donor.

Are there any risks involved with the cord blood transplant?

Dr. Kleiner: The transplant itself has a lot of other risks. The drugs themselves are all very toxic, and because of your bone marrow being destroyed the transplant itself, if it's from someone else, has between a 10 and 15 percent mortality rate.

What happened to Adolfo after his transplant?

Dr. Kleiner: Basically, there was about a two-week period when Adolfo was not making any blood. After about two weeks, the new cord blood cells -- the stem cells from the cord blood -- started to grow in his own bone marrow, and his white count started to increase back to normal. He required intensive nursing and treatments as well as multiple medications to keep him from being sick -- multiple antibiotics -- and eventually, the new blood that rose from the stem cells from the cord blood started to replace his leukemia cells.

How long after the transplant did Adolfo develop complications?

Dr. Kleiner: He received drugs to prevent graft rejection disease, but about three weeks or so after his new blood started to develop he developed graft versus host disease.

How serious is that?

Dr. Kleiner: It's different in everyone. It's graded obviously on severity. In Adolfo's case, it involved his liver and his skin, and it can cause inflammation of the liver, increased liver enzymes a bad skin rash. It can involve diarrhea and bloody diarrhea.

Then Adolfo entered another trial?

Dr. Kleiner: We first tried to treat the graft versus host disease with standard drugs, which included more immune-suppressor drugs and steroids; but unfortunately for him, that didn't work, so we actually enrolled him on a trial using other forms of stem cells which are called mesenchymal stem cells.

Where do those stem cells come from?

Dr. Kleiner: Those cells are collected from an unrelated adult donor and they are cultured in the lab. There is no matching involved at all.

This was a phase 3 trial. What did that mean for Adolfo?

Dr. Kleiner: A phase III trial has a placebo arm, so we don't actually know if he received the stem cells or the placebo, but the fact that he improved immediately after receiving the thing, I'm pretty confident that he received the active arm. The trial is still ongoing to we don't now yet.

Are these trials taking place elsewhere?

Dr. Kleiner: The first use of the mesenchymal stem cells was done in Sweden. We had treated, and others around the U.S. have treated, patients with graft vs. host disease with these cells, and this is a phase III trial that's going on both in the U.S., in Canada and overseas.

How long has this study been taking place in the U.S.?

Dr. Kleiner: About a year and a half.

Is this trial only for patients with JMML?

Dr. Kleiner: No. It's for any patient that has developed usually steroid-resistant graft vs. host disease.

What happened when you gave him this second stage of stem cells?

Dr. Kleiner: He received eight infusions of stem cells, and then after two infusions, we noticed that his skin rash was basically gone and his liver enzymes improved, and we were able to taper or decrease the amount of immune-suppressor drugs that he was on.

How long did the infusions last?

Dr. Kleiner: It was over two weeks.

Was Adolfo out of the woods after overcoming his complications?

Dr. Kleiner: Well, 30 percent of the children with JMML will have a relapse of leukemia within the first year. Adolfo is now a year past his transplant and all of his blood is from the cord blood. He has no signs of any leukemia. He's pretty much off all of his immune-suppressor drugs, and basically he's now getting a one-year follow-up. He now just has to be followed for long-term effects of the chemotherapy, but essentially he's cured of his disease right now.

Does Adolfo rely completely on donated blood?

Dr. Kleiner: We measure basically with the same technology that's used to see if someone's murdered someone -- DNA technology -- to tell what percent of his DNA is from the cord blood and what percent is his, and 100 percent of his blood is from the cord blood.

Is there a chance he can go back to using his own blood?

Dr. Kleiner: There's a slight chance, but in general we don't see that in cord blood. With the type of transplant that he received, once 100 percent of your blood is converted over to the cord blood, it's rare to see a relapse of leukemia.

Is he any more likely to develop leukemia than someone who's never had it?

Dr. Kleiner: No, because the fact that he received the chemotherapy drugs may have risk 20 or 30 years down the line for other toxicities and leukemias; but his JMML should not recur.

How popular is this type of procedure?

Dr. Kleiner: Most transplant centers are using cord blood transplants. What's happening now is most centers are comparing different ways to give the cord blood safer. Different new drugs and new types of immune suppressors are being used to try and decrease the toxicity of the therapy itself.

Would parents who have a child with JMML have to come to Miami to receive this therapy?

Dr. Kleiner: No. Most pediatric transplant centers that participate can offer cord blood transplant to a child with leukemia.

Where would Adolfo be now if he had not received the cord blood?

Dr. Kleiner: Chances are, he would not be alive.

Is donation to a public cord blood bank something you would recommend to mothers?

Dr. Kleiner: I think for minority populations -- Hispanic, African American or Asian -- it's particularly effective. If a public cord blood bank is available in your area, then you should strongly consider donating to that. The mother who chose to donate Adolfo's unit obviously doesn't know Adolfo and will never know Adolfo, but basically saved his life.

For an organ transplant, there are ways that you can contact the donor. For a cord blood donor, it's illegal. The FDA has very strict rules. Every bank is a little bit different, but the New York Blood Center contacts the mother after one year. They ask her to notify them of any major medical problems in the baby (who gave the cord blood). I donated bone marrow twice to someone else who I never met. They tried to contact me, and I didn't want to know. One person died the other person is fine, but cord blood is coming from a baby. You don't know what's going to happen to that baby two years from now, so most of the banks try and contact the mother who donated the unit to try and make sure that unit in the freezer and that baby are still doing well. New York is one of the largest and oldest banks in the world, so they do that routinely; and we cannot find who that mother is. Their records are all sealed.

Are these banks in every state?

Dr. Kleiner: There are a few small public cord blood banks, but unfortunately most public banks were set up to recruit minority populations. Most large cities do have it, but Miami does not.

END OF INTERVIEW

If you would like more information, please contact:

Gary Kleiner, MD, PhD
University of Miami School of Medicine
Omar Montejo, Director of Media Relations
(305) 243-5654
omontejo@miami.edu

This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.