Information on what's happening now
Ok, so I think everybody's now got the idea that there's been a change of sorts, as in, Leukemia cells in the last biopsy, so
the treatment is being detoured to include something else, to get Margie back into remission.
I found an overview to further make your eyeballs roll back into your head. It's important to keep in mind a couple of things as you're reading this:
1. So far, there is no cure for Leukemia, so a person being treated by "traditional means" ie; by an oncologist that is using the treatments available to them may only have access to traditionally used treatment: chemotherapy being an example.
2. Margie is at a research hospital. Not only are the treatments being used way ahead of the "traditional" but also, treatments for the benefit of not only Margie, but those Leukemia patients that come after her as well as the top notch transplant team members who not only administer treatment but also are there to research and figure out how to beat this crappy disease.
So, the level of care and medical direction is far ahead of what we are typically used to and used to hearing about.
So, I'm (kathleen) am writing some information further explaining Margie's type of transplant but also the treatment that will begin soon so as to put her back into remission. (so that she can have a transplant)
Stay with me: this is equally profound, exciting and cool (mixed with some freaky) all with the goal of getting Margie past Leukemia!
Acute myeloid leukemia (aml) is a malignant disease of the bone marrow. This disease is usually treated with aggressive chemotherapy if patients are fit enough for this treatment. Unfortunately, this chemotherapy cures only a minority of patients. The results are poorer in older patients because the disease might be more resistant to treatment, and pateints are less able to tolerate the aggressive treatment. Bone marrow or stem cell transplants have been performed to try to increase the number of cures by reducing the relapse risk. This procedure has been mainly used in patients undeer the age of 50 because the risks involved in the treatment increase with age. Part of this risk relates to the high doses of chemotherapy and/ or total body irradiation, which are given to the entire body to attempt to kill the cancer cells and prevent rejection of the donor cells.
We (transplant team members) have performed an initial study to test whether stem cell transplants can be done with lower dose treatments in older patients. The aim of this treatment is to eliminate cancer cells by an immune reaction of donor cells against the cancer. We have experiencein more ethan 100 patients treated this way, mainly between the agesof 50 and 72, with a variety of different blood cancers and treated at three collaborating centers. Used by itself, this new appproach appears safer than standard transplants and has often been done mostly in the outpatient department. In most patients engraftment (growth of donor cells) was achieved, and in those followed for more than 2 months rejection of donor cells occurred in only one patient. The main side effect of these transplants has been graft-versus-host disease (GVHD), an immune reaction of the donor cells against the patients body. This experience has encouraged us to further test the effectiveness of this transplant in older patients with AML.
It is known that immune reactions of the donor cells against cancer contribute significantly to the ability to achieve cure after transplantation. One element of this research study will be to test whether immune cells, specifically lymphocytes, from the donor can be used to treat AML. The main reason for using this treatment is the evidence that strong immune responses can occur from donor lymphocytes and remissions from cancer have been reported in patients whose cancer came back after a bone marrow transplant. This type of treatment is called a donor lymphocyte infusion (DLI). It has been shown that it is possible to get complete remissions of the cancer by using DLI. This type of immune response against cancer cells is usually called a graft -versus-leukemia (GVL) effect. Thus one aspect of this treatment will be to establish growth of donor cells in your body in hopes of obtaining a GVL effect. This is achieved by giving treatment to suppress your immune system at the time the stem cell transplant is given. Unfortunately, the same immune responses that lead to a GVL effect can also cause graft-versus-host disease (GVHD), which can manifest itself as skin rashes, nausea, diarrhea and abnormal liver function. It is not possible to clinically measure the amount of GVL that is occurring following a transplant, but evience of GVHD is readily apparent and can be used to establish the presence or absence of GVL. If you do not develop GVHD by 56 to 84 days after the transpnat and have had successful growth of donor cells, we will give you another boost of donor cells in an attempt to maximize the GVL effect. If t here is still no GVHD by 65 days after the first boost of donor cells, we will give you a second, higher dose boost of donor cells.
However, for patients with advanced disease, the GVL effect may not be enough to control the disease. Thus a second aspect of this treatment will be to use a new approach designed to deliver more radiation to your bone marrow ans pleen where leukemia cells live while delivering less radiation to non-leukemic tissue. This is done by attaching ("labeling") radioactive iodine (a molecule which produces radiation) to monoclonal antibodies and injectivng theminto the body using your Hickman catheter. Monoclonal antibodies are special proteins made by mouse cells grown in sterile broth, and are attracted to target molecules on the surface of the leukemic cells as well as normal cells in the bone marrow and spleen. By attaching the radioactive isotope to the antibodies, we hope that hte antibody will carry the radiation to leukemic cells and kill them. We have treated over 70 patients with this technique on other research studies for younger patients, combining the radiolabeled antibody with conventional transplant treatments. In this study, we will combine the radiolabeled antibody with the low -dose immunosuppressive therapy in an attempt to kill many of your leukemia cells so that the GVL effect has a chance to kill cells remaining after treatment.
Still with me?
That's an overview of treatment for AML. It reads a little backwards, as mom will be given the antibody therapy first, then onto transplant. Needless to say, your positive thoughts and prayers are appreciated- I personally visualize an aura around her that represents her success and eventual transcendence over Leukemia.
Susie D, thank you for your beautiful thoughts- my parents love for eachother is so apparent as seeing them hold eachother up through this is inspiring as it would be no other way.
Love, K
p.s. , I would like to take just a moment to encourage anyone that has been reading but not commenting to take the next step... click your mouse on that comment link right below here...it's easy. I recently highlighted it in red. ( need extra motivation? you'll be published!)
really, just click it...now... do it. I promise, your computer will not blow up. if you need help with it, email me!
artgirl62@earthlink.net
Thanks Kathleen for all your overwhelming support to your family. You are truly a rock like your mother.
ReplyDeleteI am going home today I so wanted to be at the appointment with the "mouse Dr." but I'm getting a little cold so off I go on back to the ferry" any cherry pie? where is that receipe anyway?
Suzy, Thanks for that beautiful writting it touches everyones heart I know.
Margie and Bob,
Its amazing watching you the days i'm here getting up and going to infusion appointments and then in the evening, so much for retirement and sleeping in, I know you both enjoyed that. Today will be the last day of the infusin and you get to go home for two days! How exciting life can be! Margie and Bob are looking forward to this.
Now about this mouse thing, I'm not talking the scientific one but the computer one. Call on Kathleen she's a very good computer instructor. Love to all, cathy
P.S. I just wanted to add Richard Keeps calling me from wherever he is and always asking about you Margie, He said to tell you He loves you, He's calling again tonight.
Mom:
ReplyDeleteIn the spirit of trying to keep YOUR spirits up through the use of humor, I must ask: once the mouse antibodies enter your bloodstream, will you suddenly have a profound craving for cheese and in addition, will you have an unexplained need to sing," Here I come to Save the Day"??
Love,
Randy
Good one Randy! I needed a laugh after reading about the latest treatment plan. Thanks.
ReplyDeleteAlso, Kathleen, thank you for boiling down the information describing this newest procedure for everyone on the blog. It helps to see it in a form that covers the potential benefits only. I read the entire protocol last night and I can just imagine what Margie must be thinking about it. Yikes!... doesn't even begin to cover it. To read her humorous comments concerning it helped ME to feel better. To take some of this (awful) stuff in stride with your funny bone in tact shows a great strength of spirit. Love, Susie
Hi Margie, I am new to blogs so I don't even know if this is going to get to you! I just wanted to let you know that I am praying for you as you travel this path. May God give you strength and His peace and may he give your Drs wisdom. Blessings, Alice (Cathy's sister-in-law)
ReplyDeleteIs this Dr.Mouse himself ?! Thought you might like to read this if you haven't read it before. This is an article that I just found. Hope you and Dad are enjoying your time at home on the island. Love, Susie (There was a picture of him too, but I couldn't get it to copy onto this site. He looks young.)
ReplyDeleteTriple-threat academic on board
John Pagel steps up to the challenge of developing and improving antibody therapies for lymphoma, leukemia patients
John Pagel
Dr. John Pagel leads leukemia studies of radioimmunotherapy at the Center as the principal investigator of several human clinical trials. With his colleagues, Pagel is working to increase the usefulness of antibody therapy by "pretargeting" radiation directly to the cells. He is also researching nonradioactive chemical partners to antibodies.
Photo by Todd McNaught
By CHRISTINE LOFTUS
The age-old challenge faced by every cancer researcher is one of simple precision: how to selectively target and kill cancerous cells, while causing the minimal amount of collateral damage to healthy cells, the innocent bystanders in this cellular battle.
Several years ago, scientists at the Hutchinson Center helped to pioneer one elegant approach to the problem. In radioimmunotherapy, antibodies, a natural component of the immune system with the ability to recognize and attack cancer cells, are loaded with radioactive molecules. The antibody transports the source of radiation to the tumor sites, where the targeted cells are confronted with a molecular one-two punch: Antibody binding initiates the process of cell death, while the radioactive atom delivers deadly radiation to the cancerous cells.
The pioneering work of Drs. Fred Appelbaum and Oliver Press, among others, established the Center as an international leader in this field. As it evolves, the next generation of medical researchers, including Dr. John Pagel, step up to the task of making radiolabel therapy safer and more effective for leukemia and lymphoma patients.
Recently awarded a faculty position in the Clinical Research Division, Pagel began his research career at the Center under Press' supervision.
"John joined my laboratory in July 2000 and since that time has impressed everyone in our group with his tremendous energy, determination, unparalleled industry, superlative laboratory skills, intelligence and his dedicated approach to translational research," Press said.
Pagel now leads the leukemia studies of radioimmunotherapy at the Center as the principal investigator of several human clinical trials. Last year, he was the recipient of prestigious Career Development awards from the Lymphoma Research Foundation and Damon Runyon Cancer Research Foundation, which will fund his research to develop and improve various types of antibody therapy in the treatment of non-Hodgkin's lymphomas and acute leukemias.
Pretargeting reduces 'friendly fire'
The success of radioimmunotherapy as a cure for bloodborne cancers like leukemia and certain lymphomas is limited by one main problem. After the radioactive antibody is injected into the patient's bloodstream, it can take many hours for the protein to achieve maximal localization at targeted cancer sites. Up until that point, the radioactive antibody meanders throughout the body, emitting radiation in an indiscriminate way. Healthy tissues and organs are exposed to lethal beta particles intended for the tumor cells, and this sort of "friendly fire" causes grave side effects. To overcome this problem, Pagel and collaborators have developed a method called "pretargeting." Using animals for preliminary tests, Pagel has separated the delivery of the antibody from the delivery of the radiation with a multi-stage approach. First, the cold antibody, without its radioactive label, is injected into the animal, where it gradually localizes to the specific sites of cancer. The radioactive molecules are introduced later and, through a molecular engineering trick, are able to specifically bind to the antibodies.
In preclinical animal studies, Pagel and his group have demonstrated a level of radiolabel selectivity for tumor sites that is at least 10- to 50-fold higher than existing radioimmunotherapy procedures. "We hope, in the relatively near future, to translate that success directly into human clinical trials," Pagel said.
If that works, the therapeutic benefit of radioimmunotherapy might be radically increased. "The idea is that if we can improve the targeting specificity of the absorbed radiation delivered directly to the tumor sites, we will be able to allow for the safe escalation of the therapeutic dose since we are not increasing nonspecific toxicities," he said. Higher levels of radiation should reduce relapse rates, a frequent and tragic occurrence in non-Hodgkin's lymphomas and acute leukemias.
Antibody therapy without radioactivity
There are ways to enhance the usefulness of antibody therapy without resorting to the extremes of radioactivity, which can be expensive, time-consuming and inconvenient for the patient. For example, Pagel is pursuing research with nonradioactive chemical partners to antibodies.
In the past, researchers have combined antibody therapy with classical chemotherapy agents to achieve a synergistic effect in tumor killing. While this supplemental chemotherapy can markedly improve survival rates, it also burdens a patient with the infamous side effects associated with chemotherapy, as healthy tissues and cells are poisoned as well.
Pagel is exploring the idea that certain nontoxic substances may augment the anti-cancer actions of antibodies in the same way. In close collaboration with Center scientists Dr. Ajay Gopal, Press and others, Pagel has recently published two studies of low-toxicity, synergistic partners for antibody therapy, using both human and mouse cells to model non-Hodgkin's lymphomas. For example, Pagel and Gopal found that a synthetic derivative of vitamin A, fenretinide, amplifies the therapeutic actions of rituximab, the first FDA-approved antibody treatment and a very common treatment for B-cell lymphomas.
In mice with established lymphoma tumors, the fenretinide-rituximab combination proved significantly more powerful than rituximab alone, and human trials are to begin in the near future. Pagel points out that the most exciting aspect of this variety of antibody therapy is its lack of toxicity, thereby making it suitable for long-term, maintenance treatment of patients in danger of relapsing, such as patients with indolent lymphomas or older lymphoma patients who may not be able to tolerate traditional chemotherapy.
Following their footsteps
Pagel says he chose to come to the Center specifically with the goal of conducting translational research in the tradition of his mentors, Appelbaum and Press. Translational medicine, or "bench-to-bedside" research, is the direct application of basic laboratory sciences to the clinical practice of treating individual patients. The gap, between molecular models and test tube experiments all the way to treatment options presented to cancer patient, is tremendous.
According to frequent collaborator Gopal, Pagel certainly has the ability to bridge these distances. "John is the one of the few young 'triple threat' academicians," Gopal said. "He is an expert clinician, a skilled bench and clinical investigator and a superb teacher."
In turn, Pagel relies on support of the entire Center research community, past and present. "The Center is one of the very few places in the country, quite possibly in the world, where such multidisciplinary and collaborative research could be done."
While the laboratory research constitutes most of his work, Pagel's role as a physician, on the stem-cell transplant team and in his own lymphoma and leukemia clinic at the Seattle Cancer Care Alliance, provides the rewards of patient contact. He describes the intimacy of patient-clinician relations with reverence.
"Working with leukemia and lymphoma patients, I have the unique opportunity to help every single person, patient and family member, whom I come in contact with, to improve or impact their life in some way, however small."
It's an honor and a privilege, he says, to be allowed so close to patients as they and their families navigate such a delicate stage of life. In this way, Pagel can witness the translation of all his laboratory studies — mouse models, response rates, apoptosis induction, radioisotope distributions — into the health and well-being of each individual patient.
Center News Table of Contents
Fred Hutchinson Cancer Research Center
1100 Fairview Ave. N. PO Box 19024 Seattle, WA 98109
©2007 Fred Hutchinson Cancer Research Center, a non-profit organization.
Terms of Use & Privacy Policy.