After Doris' transplant and prior to her relapse, I did quite a bit of research on Donor Leukocyte Infusions (DLI). Basically, DLI involves boosting the original donor's white blood cells with a growth factor called G-CSF. Through a pheresis procedure, the white cells are separated from the blood and then transfused into the recipient--in this case the relapsed patient. The idea is to induce a graft-versus-leukemia (GVL)effect, which kills leukemia cells.

In preliminary reports, DLI appears to be effective in inducing a significant number of antileukemic responses with a low incidence of GVHD. However, DLI in its present form is no magic bullet. It appears to be a feasible approach for persons with relapsed Chronic Myeloid Leukemia that has not progressed to the blast phase. With acute leukemias, however, DLI does not seem to work unless the patient has attained remission first. On the other hand, it may be worthwhile to undergo DLI prior to a post-transplant relapse if PCR tests revealed residual leukemia cells.

When I have told people about Doris' relapse 85 days after her allogenic Bone Marrow Transplant (BMT), many have asked, "Why doesn't she just have a second transplant?" The answer is, it isn't that simple. Here are some things to consider (Bear in mind I am not a physician):

1) Second transplants have a very high mortality rate, even among patients who are in remission. Hence, it is much better to be in remission before going for another BMT.

2) For a 2^nd transplant to be viable, the patient should be able to pass the proscribed medical tests. BMT is tough on all the major organs and systems of the body.

3) Time to relapse following BMT is an important prognostic factor. With a relapse at less than six months post-transplant, the odds of re-inducing a remission with acute leukemia are probably less than 15%. Doris relapsed at approximately 3 months following her BMT.

4) Aggressiveness of the disease. All I know here is that Doris' WBC went from 3,000 to 47,000 in only 5 days and over 90 percent of her marrow was packed with leukemia blasts. Had the numbers been much smaller, I'm sure we would have had more options--and more time to apply them.

The recommended strategy to re-induce another remission for Doris was High Dose Ara-C. The thought of high dose anything for Doris was awful. The first six months following a BMT is a fragile period where the body is slowly re-acquiring its immunity.

Given Doris' extreme circumstances, we opted for something new and different. After my article on Doris' transplant appeared in our local newspaper, a mother wrote to me describing her young daughter's post-transplant relapse (ALL) and treatment with B43-PAP. The young girl had been on it for almost two years and was doing fine. This was a real world example of the promise of this new drug.

I immediately searched the medical journals for information about this new drug. I learned that B43-PAP is a two-part concoction. B43 is a mouse protein that binds to the CD-19 antigen on the leukemia cell. PAP is a pokeweed toxin. The B43 carries the weapon--the PAP--to the leukemia cells. It has been touted as a smart weapon.

In one study using mice, B43-PAP along with Vincristine, Prednisone, and L-Asparginase was 100% effective in wiping out CD-19+ ALL. In another study using monkeys, B43-PAP along with Ara-C was quite effective. (Clinical Cancer Research 2, 1533-1542, September 1996)

On the National Cancer Institute's Physicians Data Query I found a phase I clinical trial, an induction protocol using B43-PAP and VPL. Our oncologist inquired into the protocol and found that 15 out of 18 children who had participated had attained remission. That was all I needed to say, "Let's do this."

Once we decided to sign Doris up for this phase I clinical trial, Doris underwent an array of cardiac and pulmonary tests in order to meet eligibility requirements. She passed all tests with flying colors. This took several days during which Doris was not receiving any treatment for the relapsed leukemia. She was receiving IV fluids and her face was getting puffy. I was terrified that her white count would skyrocket each day. I had read that leukemia cells divide every 12 hours. But her WBC held steady at 47,000 for 4 days until she began the new treatment.

Doris received the regular induction chemo drugs as described above in the Dalton Cancer Clinic at MCV Hospital in Richmond. In addition, she received two rounds (One round=30 min. Infusion on 5 consecutive days) of B43-PAP at Children's National Medical Center in Washington, DC.

A day 7 bone marrow aspiration showed 17% blasts--a big reduction from the 97% blasts in her marrow at relapse. It was not clear at this early stage of induction that the B43-PAP had anything to do with the reduction of blasts. By Day 14, she was down to 3% blasts. This was good news but only half of the coin. The other half involved a good marrow recovery with no blasts.

Meanwhile, Doris began having severe problems with increased heart rate, low blood pressure, low albumin levels, water retention, and extreme fatigue. After each administration of B43-PAP Doris wound up in the Pediatric Intensive Care Unit (PICU) at MCV. She became so weak that we had to get her a wheelchair. Her resting pulse rate was 140 and when she would get up to walk from one room to the next it would jump up to 160. Her condition was pure torture. She described it as twice as bad as going through the bone marrow transplant" She'd say, "It's like a bone marrow transplant but without the transplant."

We learned during the treatment with B43-PAP that Doris was receiving the highest dose in the study. The study called for administration of B43-PAP in three increasing doses. Maybe the higher dose explains a lot of the side effects she experienced. There is a question that hasn't been answered regarding this new drug. Is the PAP, the pokeweed toxin, effective in killing chemo resistant leukemia cells? Can it be demonstrated that drug resistant leukemia cells do not simply pump the PAP out?

Also, B43-PAP is being used in consolidation regimens prior to BMT. I think this is the best use of this new drug. Hopefully, its use prior to BMT will help better eliminate residual leukemia cells, which has been associated with successful outcomes following BMT.