lymphatic system

this is a great medical illustration of the lymphatic system. I'm posting it because it shows the parts that were spicifically irradiated as part of the preparation for my bone marrow transplant.

preparing for my transplant

I think no matter what sort of transplant you are getting -stem cell - bone marrow- autologous - allogenic, the weeks right before the transplant are busy and somewhat unnerving!
For my transplant i have had to have many tests, a bone marrow biopsy to check on my cancer, and Echo cardiogram to check my heart muscle, a pulmonary function test to check my lungs, many many blood tests, an EKG (electrical activity of my heart), a chest ex ray, and more blood tests.
I also meet with many people. I met with a social worker about our family's strengths and needs, another social worker who guided us through all the consents i had to sign, a class all about BMTs, and a class about my catheter care. I also have an appointment to have the catheter put in (a tube in your chest for infusions and blood draws not, thank goodness, one for peeing!) another with radiology to get measured for the radiation treatments i will get and of course a meeting with my transplant doctor. All this in the next couple of weeks before i'm admitted for conditioning.

Because i will be having the TLI /ATG nonmyleoblative conditioning for my unrelated donor cells i will be doing alot while out patient. I will be admitted for only a week, five nights and six days if everything goes according to plan. The reason i'm admitted is that the ATG could make me very sick if i have a bad reaction to it, and it will make me quite sick, like a bad case of the flu, if things go well. I ill start off each day with radiation treatments then come back to the room where my mom will help me put on lots of lotion. then later in the afternoon i will get my ATG, which is either a shot or an infusion. Then i'm discharged to go home and commute to the ITA (infusion treatment area i think) everyday for all my meds and more of the radiation.

At the end of the second week of conditioning the will give me my donors stem cells! this will be alot like a platelet or red blood cell infusion. they will hook everything up to my catheter and hang a bag of cells that look alot like red cells on the IV poll, set the pump to the proper rate and stand back while the cells go into my veins. They will swim around in there for awhile till they finally settle into my bone marrow and engraph.

I will be given two forms of immune suppression drugs: Cyclosporine and Mycophenolate Mofetil. go ahead and google them, i'm sure they ave more side effects than you can shake a stick at! i will take the Cyclosporine fir 6 months and the Mycophenolate Mofetil (MMF) for about 3 months.

the effect of ATG & TLI

I asked my main contact at Stanford, the nurse who coordinates the search for an unrelated match, Paige Hafer, about the personal experience of the ATG / TLI (antithymocyte globulin and fractionated total lymphoid irradiation).

She replied: The ATG/TLI prep for transplant is much lower in toxicity than a chemo/total body irradiation preparative regimen. The ATG infusion is difficult during the first several days....that's why we have patients receive it in the hospital.  The TLI is very well tolerated.

The chemo/total body irradiation is has many toxicities including significant nausea, mouth sores & very low blood counts requiring frequent blood and platelet transfusions.

The ATG/TLI may cause a small drop in your counts, but not as much as the other preparative regimen.  You may need some transfusions.

Either way, the diet and activity restrictions we ask you to follow are
the same.

Qualifying for the New Tretment

I saw my regular oncologist, Dr. Breeden, last week and he told me that Stanford will want another Bone Marrow Biopsy before the decision about which treatment protocol will be used can be made. this is because previous test are not clear as to the number of blasts i have in my bone marrow. So they will be checking that one last time and hopefully every one will agree on how many blast there are and they will be less than 10%.

They doctors have had trouble agreeing on the number in the past as the counting of blasts is a subjective thing, it's based on visually distinguishing the look of the cell from a normal immature cell. Breeden says this can be highly subjective, but that when it's done by machines the cells re damaged and the count can be artificially low.

the reason they need the blasts to be below 10% is because that is a sign of how fast the disease is progressing. the risk with the hyperfractionated Total Lymphoid Irradiation and Anti-Thymocyte Globulin (ATG) is that it leaves the elimination of the cancer cells to the new stem cells. if the new cells takes too long to notice the cancer and go after it, the cancer could take over. so the regime is only used when the MDS in not progressing toward AML.

I believe i am fine because i feel so different than i did when i was sick from the AML. I'm fatigued and i have various symptoms, such as breathlessness but i don't have that deep bone pain or the deep chills that left me shivering and teeth chattering under every blanket in the house! nor is my breathlessness anything like it was back in 2002 when i once had to lay down on the trail waiting for my breathing and heart to slow enough to go on.

I'm really beginning to hope for the TLI + ATG. i told myself i was going to stay neutral on which one was chosen, but it sounds so exciting to be part if this trial and looking at much less organ involvement of risk of mortality from the preparatory treatment. I know there is more of a concern about long term effects which re as yet unknown, and that's why i will be fine with which ever way it goes, but sometime the immediacy of living takes precedence over the possibility of GVHD or reoccurrence down the road.

What's So Special about Stanford's Approach?

Allogeneic stem cell transplants can be performed using Reduced-Intensity Stem Cell Transplants (RI-SCT) treatment regimens resulting in a lower treatment-related mortality rate and relying on a Graft-Versus-Tumor (GVT) effect of the donor stem cells for the anti-cancer effect.

The most recent efforts have been directed at administering RI-SCT in the hopes of decreasing regimen-related toxicities, leaving patients strong enough to survive a later onset of GVHD. These strategies have met with some success, but acute GVHD has continued to be a major problem.

In addition, there has been concern about the long-term effectiveness of this approach. Most reduced-intensity treatment regimens delay Graft Versus Host Disease (GVHD) and infectious complications and do not prevent them.

Some research for RI-SCT regimens is in the direction of increasing dose intensity to determine regimen-related morbidity and mortality with doses of drugs or irradiation that are somewhat reduced from truly myeloablative doses. They administer increased doses of Total Body Irradiation (TBI) and chemotherapy. The question in these studies is how much more needs to be added to get better results.
 
One of the major goals of Stanford's research has been to separate GVHD reaction (bad) from the GVT effect (good). Researchers seek to control GVHD while preserving GVL. Most studies have shown that a GVT effect can not be detected in the absence of GVHD.

But Stanford is finding Total Lymphoid Irradiation (TLI) {NOT TBI} and ATG effective in preparing patients for an allogeneic stem cell transplant. They found that the regimen of results in a low incidence of acute GVHD while maintaining anti-tumor activity of the graft and a good survival in patients.

In this model, regulatory natural killer (NK) cells become the predominant T cell subset. Secretion of high levels of IL-4 by the host NK cells protects against GVHD following hematopoietic stem cell transplant. However, CD8+T cells remain intact.

They are also reducing the damage to health tissues by fractionating the radiation. Fractionation refers to a method radiation therapy. The total dose of radiation is divided into several, smaller doses over a period of several days.This results in fewer toxic effects on healthy cells. This maximizes the effect of radiation on cancer and minimizes the negative side effects.

Immune Therapy Conditioning

This is a brief explanation of the therapy that Stanford has developed for some bone marrow diseases which involves manipulating the immune system before infusing the new stems cells.

One advantage is that the procedure is much easier on the body so you are more likely to survive the treatment. Instead of massive doses of chemotherapy designed to eliminate all you cancerous stem cells which then also damages other cells, they manipulate your immune system so as to create graft vs cancer effect while eliminating graft vs host disease. The graft - the new stem cells, must be encouraged to hunt down all the remaining cancer while not attacking you body.

So Stanford uses Fractionated Total Lymphoid Irradiation (TLI). With their hi tech machines, they zap the lymph system to control the lymphocytes. It's fractionated in that it's given a little bit over time. This destroys the T cells that would go to war with the donor cells and keeps the T cells that would regulate and teach the donor cells.

Stanford also gives Anti Thymocyte Globulin (ATG): An immunosuppressive agent that selectively destroys T lymphocytes. This Immunosuppressive protein (?) has been used for a while for organ transplants. Stanford is using it successfully with the bone marrow transplants since 2005. The brand name is call Thymoglobulin.

Dr Miklos explained to me that this treatment leaves my  own "regulatory" T cells which then control the donor cells, tells them not to attack me!

I will add more details as i am able to get my hands on full articles and not just abstracts.

hla EXAMPLE

I'm reposting the comment cuz it' lost all it's formating and is hard to follow:
Kayla, I'm going to illustrate an exaggerated case of parental contributions to children's HLA types to support the idea that one of the parental contributions could matter more than another in some cases. Here goes:

The c and r for this exercise label alleles that are either common or rare in the population.

Hypothetical mother's chromosomes:
1Ac 2Zc 3Pr 1Br 2Yr 3Pr

She is heterozygous at two loci, 1 and 2,
homozygous at the third, 3, for the P allele.

The father's chromosomes in this example:
1Cc 2Wc 3Qc 1Dr 2Vr 3Pr

The possible children will be all four combinations, if there is no recombination. Possibility 1:
1Ac 2Zc 3Pr 1Cc 2Wc 3Qc

Possibility 2:
1Ac 2Zc 3Pr 1Dr 2Vr 3Pr

Possibility 3:
1Br 2Yr 3Pr 1Cc 2Wc 3Qc

Possibility 4:
1Br 2Yr 3Pr 1Dr 2Vr 3Pr

In terms of having common alleles that are found most often in the population, possibility 1 is the best and possibility 4 is the worst.

Now if there was something called gene conversion in locus 3 such that the mother's 3Pr is converted to 3Qc, then possibility 5, similar to possibility 1, would have all common alleles:

1Ac 2Zc 3Qc 1Cc 2Wc 3Qc

Of course if both parents are average in their alleles, many alleles will be commonly occuring in all progeny. Also, if the parents are similar in HLA's, half-siblings would be possible matches.

comments encouraged.

HLA Matches

I am sorry that there has been such a delay in writing this article. I think I am so scared of not being ale to find a match for my own BMT that I've been incoherent every time I try to write about it. Nonetheless, writing helps my brain be more orderly, so i will push through and write this so i can go onto the next thing. My apologies if it's unclear or too personal.

When you are not using you own bone marrow and must use the bone marrow of another person, you must find someone with a match. The thing that needs to match is called HLA, Human Leukocyte Antigen. These antigens are on each person's Leukocytes - your white blood cells. They are proteins on the surface of the white blood cells that help them distinguish self from non-self in the never ending effort to defend against invaders. When someone gets some other form of transplant, kidney or heart for instance, the patient's white blood cells might recognize the cells of the heart or kidney as invaders because the cells don't have the proper identification and the resulting attack would be a rejection of the transplanted organ. That's why they need to match the HLA for those transplants.

Moreso for a bone marrow transplants. In preparing for the BMT (in all it's varieties) your own white blood cells with their antigens are wiped out along with the other cells in your bone marrow. The donor's stem cells take their place and begin to create new blood cells including new white blood cells with the donor's antigens. So those white blood cells get to work defending the body, using the old information from the donor. If the cells of the patient are too different the new cells decide that their new environment is the enemy and attach the patient. This is Graft Vs Host Disease, the graft of cells is attacking it's host - the patient.

So it's important that the antigens have the same patterns so that the new cells will feel at home and won't attack.  It's also important that they match so that the patient's remaining immune system doesn't attach the new cells - this is transplant rejection.

A perfect match is yourself or your identical twin,

The next best chance is a full sibling because the pattern of HLA that each person has is inherited. We all have 6 major antigens,  2 sets, 3 per set.  One set of three is inherited from each parent. The sets do not change or rearrange so that there only 4 possible combinations for each offspring. This is why a sibling has a 25% chance of matching  (1 in 4).  My full sibling Adam is not a match - he's been tested.

A half sibling like my sister Cecile has a 50% chance of having inherited the same three antigens from our dad as i did, but her other 3 antigens are no more likely to match than an stranger's (say one in a million -  i really don't know). I'd have to ask my statistics loving husband what the chances are, but obviously they are hardly any better than a stranger because there are so many possibilities for the other set of three.  

This same dynamic is true of my children - who will have inherited one of my sets for sure, 100% for the first three, but the second set will have come from my husband, and it's really unlikely that his antigens are anything like mine because we are ethnically different. His ancestors are Eastern European Jews; mine are pretty mixed up but basically Northern European. However, there have been some experiments with these close family mismatches because there are other factors that can improve the transplant having to  do with my offspring sharing my immune system at a critical time in their development.

My son is already registered with  bone marrow bank so we can check his patterns. My daughter is too young and too small and my mom is too old and has too many health issues. So i'm pretty much looking at the computers to find a match though all the bone marrow banks. For some reason this takes months. I think it's because not only do the 6 antigens have to match, but the various expression of the antigen, like flavors or something, also have to match.
Ok, that's done!

About BMTs

In this new column i will explain the various aspects of Bone Marrow Transplants. I'm going to work at making material I've read a bit more understandable. In gong for simple language i might make things a bit less accurate but we'll see how that goes.

So here goes!

BMT is short for Bone Marrow Transplant but may be used to mean many sorts of transplant procedures.

There are three major distinguishing characteristics of transplants: from where the stems cells are collected; the relationship of the donor of the cells to the patient; and the type of preparatory regime before the transplant.

Where stems cells come from:
The material that is transplanted is always stem cells. They are called Hematopoietic Stem Cells (HSC) because they are the precursors to making blood. The cells can come from Bone Marrow (that fleshy stuff in the middle of the bone), or from the peripheral  blood vessels or from umbilical cord blood after a live birth. (I'm reading now that more than stem cells are transplanted but that's the important part).

Bone marrow must be gathered from inside the bone. Doctors have to poke a hole like they do for a biopsy and aspirate. About 1 in every 100,000 cells in the marrow is a long-term, blood-forming stem cell; other cells present include stromal cells (supporting framework), stromal stem cells, blood progenitor cells, and mature and maturing white and red blood cells. Donors are anaesthetized for the repeated puncture and removal with a syringe.

Stem Cells also circulate throughout the body and are out side the bone marrow, in our veins and arteries. The cells are gathered from the peripheral blood (blood that circulated in our veins and arteries) of an adult. In order to gather enough cells the donor will be given granulocyte-colony stimulating factor (GCSF) a few days before the "harvest" to increase the circulating stem cells. Doctors insert an tube into the donor's vein and pass the blood through a filtering system that pulls out the cells and returns the red blood cells to the donor. Of the cells collected, just 5 to 20 percent will be true HSCs.

Another source of HSCs is the stem cells from an umbilical cord. After the cord is cut from a live birth there remains precious blood in it that has unique qualities. These stem cells are the most basic, they can produce any sort of cell given the correct signals. They are so basic that the matches which are so important in transplants from mature people are not such a problem. I believe most of these transplants are still experimental and one of the challenges is that there may not be enough cells for a full sized person.

Currently there are experiments testing the use of enriched stem cells or highly purified stem cells.

The next distinction of types of transplants  from whom the cells came.
There are three major sources: the self (Autologous), an identical twin (Syngeneic), any other person who's not a twin (Allogeneic).

Autologous; Used when the bone marrow is not cancerous or when there are sufficient non cancerous cells to return to the body after the patient has received aggressive chemo that depletes the bone marrow.

Allogeneic:  Allogeneic transplants may be from a sibling, other relative, or someone unrelated to the patient (as is always the case when it's from umbilical cord blood - well maybe you could have frozen your own stems cells 50 years ago - i wonder if they could last that long!)

Syngeneic: Even though cells that come from an identical twin of the patient, come from someone else, it's much more like a transplant from the self, because the cells are identical to the patients.

There's yet another form of transplant that mixes these sources stating with an autologous followed by an allogeneic. It also has mixed preparation regime.

Another distinction of types of transplant is based on the approach of the conditioning regimen. The conditioning, or preparatory regimen is the way in which the bone marrow is removed from the body in order to receive the new bone marrow.

This is called ablation - the "removal of a body part or the destruction of its function, as by a surgery, disease, or noxious substance." The American Heritage Stedman's Medical Dictionary. Bone marrow ablation is a process whereby the human bone marrow cells are eliminated in preparation for a bone marrow transplant. This is performed using high-intensity chemotherapy and total body irradiation.

The regime can be either myeloablative or non-myeloablative. The purpose is two fold: 1) to help eradicate the patient's disease prior to the infusion of new cells and 2) to suppress immune reactions.

Non-myeloablative allogeneic transplants use lower doses of chemotherapy and radiation. Doses that are not intended to eradicate all of the bone marrow cells. Rather non-myeloablative transplants rely on the action of the graft versus tumor effect. The new cells battle the remaining cancerous cells.

Non-myeloablative transplants require high doses of immunosuppressive agents in the early stages of treatment. This leads to a state of mixed chimerism (composed of two genetically distinct types of cells) early after transplant where both recipient and donor HSC coexist in the bone marrow space. Decreasing doses of immunosuppressive therapy then allows donor T-cells to eradicate the remaining recipient HSC and to induce the graft versus tumor effect.

There are many different protocols, probably as many as there are transplant centers! which chemo, how much radiation, how much immune suppression etc.

(the citation for this article is everything i've been reading so check out any of the links in the side bar.)

I hope this version is clearer! - kayla

cost of prescription drugs

I fell so blessed to be insured by Kaiser. they give me such great coverage. today i picked up about a months worth of drugs i will need for my home recovery of my stem cell transplant. it cost me 100.00 which is not cheap until you look at what i would have paid: $1568.90 and that does not cover the heprin for keeping my line clear which the pharmacy decided i'm supposed to have at no cost because of my outpatient status! we still have to go back next week for one of the anti nausea medicines which they did not have in stock, and it was a drag that i had to walk up to the hospital pharmacy to get the heprin, I was also lamenting that the whole thing took about 3 hours and i was leaving at the same time as a ton of health care workers. but then the gate was up and no attendant in sight so i parked for free! another $6.00 blessing!
The whole transplant involves so many uninsured costs, like the cost of my mom's housing near the hospital, the cost of daily house cleaning (we need to sanitize and sterilize like crazy!), getting the heater ducts and rugs professionally cleaned, the gas of commuting to the hospital, the costs associated with boiling and storing strile water, oh and a ton of hand sanitizer and antibacterial germicidal household cleaners, and a mountain of skin lotion for my radiation treatments. Stanford is particular strict when it comes to avoiding infection and GVHD so there is much to do, and alot of it requires pulling out your wallet.
So i'm thankfully that the treatment is so well covered and that i have family pitching in to make all this possible, my step grandmother paying for daily house cleaning, my mother in law assisting with things to make us comfortable (first thing i got was a flece blankie for the car!) and my husband's father's cousin's surviving wife contributing to the extra expenses. I was thinking we would need to fund raise but things are looking pretty good after all.

the pulmonary function test

This test was much longer. but still under an hour. for this a stayed in my street clothes. the technician was great and took his time explaining everything to me before we did it and then explaining again as we did each step.

I got my own mouthpiece which i held between my lips, being sure to keep my tongue below the tube and to press my skinny lips with my fingers to hold them against the tube so no air would escape.

he then put a plastic padded clip on my nose and put me in a booth with the door shut. the mouth piece was attached to some hoses that were attached to the computer. I was told  to take deep breaths in and out, to hold it to pant and to pretend to pant when the air was cut off. (this was weird!)

each combination of breathing and holding had to be done three times so that he could compare them and use two that were withing 10% of each other.

he had me rest in between each one to allow the dizzies to go away. then in part two he gave me four dose of albuteral - the broncial dilator that asthmatics use. When i take it, i take two doses and it makes me shaky, 4 made me really shaky! Then we worked with the door open on the booth and did more deep breathing and breathing out against pressure in the tube. again we did each test three times.

because i really was getting dizzy we slowed down  and chatted about old jobs we used to have and what the test machine was like before the computer became part of the process. He was a very interesting tech and he made this test so much more fun than it was when i had it done back in 2002.

That fellow made everything hard and seemed very cross with me. the booth was outrageously hot that time. i was sweating so hard i couldn't keep the tube in my mouth! so it was a much nicer test this time.

what the echo was like

If you have ever had a sonogram then you know alot about what the echo cardiogram  is like. they gave me a robe for my top and had me lay on a table on my side. she then put gel on the end of the hand held sonogram wand and pressed it against my chest to "look" at my heart.

I could see the monitor she used and there was a moving picture  of one of my heart's chambers beating away. she measured and clicked on the computer screen and then doubled the picture so that one of the representations of my heart had a brightly colored overlay that showed the direction of the blood flow, and if any blood was not moving along.
 very cool.

she did this several times looking at different chambers and valves from different angles. it took a little over 20 minutes.

All the tests in Preparation

I now have i list of almost all the tests that need to be done before my transplant. i'm sure there are variations between various hospitals, but i'm sure they all do alot. So there's a 24 hour urine test with a blood draw when i bring in the sample, both testing for creatine, which tells them how my kidneys re functioning. Then there's a bone marrow biopsy to keep track of the course of my disease and to see if i still qualify for the study. I'll have an Electrocardiogram, which takes a picture of my heart and can tell if my heart is emptying fully, the strength of it. this is particularly important in my case where i've had chemo in the parst which can damage your heart. and a respatory/ pulmonary function test which sees how well my lungs are doing. There will be an EKG, which tests the electrical impulses of my heart and tells the doctors that it's ticking right along. There will be many blood tests which i don't even know wht those are for. they will look for signs that previous infections are still lurking so they can be prepared, like CMV which is usually just  cold but is dangerous in a transplant as it lives on and flares up later. I(i don't think i've hd that.) And the fungal pneumonia i had 5 years ago is likely to come back. Chicken pox can come back as shingles and so on. so the days before a transplant are filled with many doctor appointments.

Disappointing Caregivers Class at Stanford

My mom has gone to the caregivers class that Stanford gives a couple of times and found it to be much more informal than the write up they give us on it. Last week my husband spent over an hour and a half traveling in each direction to attend the class at my urging. But it isn't really a class, despite the information from Stanford that shows some five different classes, some about caregivers' self care, another about resources, relaxation and meditation ... that sort of thing.

The reality is that there's a woman there who will answer any questions you have. So having questions answered in nice but it's neither a group nor a class. Morey was the only one there last week, the previous meeting were attended by my mom and one other caregiver. not what i wanted for my caregivers at all! I wanted them to be doing things, meditating or relaxation techniques, tips on boiling 5 liters of water a day, how to organize and delegate tasks, what the hospital and clinic are like ... so on. So now i'm sorry i urged them to go.

We have to attend a class called teaching for transplant that they give. it's required for me and my caregivers. but i've gotten the inside dope that i could teach this class better than it's currently taught. so we will endure it. I think that for me the most informative experience is reading first person narratives. i keep looking for someone who's undergone the new conditioning at Stanford. but in the end we each have our own experiences.

I should make a list of things to do

Since i got the news that there were 12 potential donors number of things to do has gone bezerk! there's the continued dentist issue, the car maintenance, the home cleaning, the desire to take off and spend time with nature, my family and my camera. i know once they doctors find a match there will be a whirlwind of tests to insure i'm healthy enough for the transplant and then packing for the hospital.

About a month back i started buying personal care items for the hospital and stashing them in a bag in the closet. this has the advantage of spreading out the expense of all the wonderful lotions and bath sponges and so on that i got to treat myself nicely with. Being super clean is an important part of Stanford's approach to avoiding GVHD, and taking very good care of your skin is a big part of that. If my preparation involves radiation therapy then i need to go into with the healthiest skin possible. so i've started really paying attention to the kind of skin care my daughter does and following her example, but with all natural organic products.

likewise, the car needs to be in tip top shape to be commuting between Stanford and SF everyday, and we have postponed the much needed new tires. I can't even seem to find time to get the car washed and inside vacuumed out, but that will move closer to the top of the list. But we need to renew the registration , get tune up and check the breaks and clutch too.

I planned a little family vacation with both kids (my son's coming home from college on break) and hopefully Morey can join us for some of it.

i have the name of a couple of companies that clean household heating ducts, shampoo carpets, that sort of thing, so i need to find out about the expense of that and schedule that for before i go in the hospital - cuz otherwise someone will have to stay home for that when they also need to be with me at the hospital. i learned from my SJ friends that getting things done once you are in the hospital is near impossible!

It would clearly help if i made a list!!