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July 11, 2003
It is Friday and I am sitting in an apartment in the Pete Gross House with a view over Lake Union toward north Seattle in one direction and over the Space Needle to the Olympic Mountains in another, with the buildings of downtown Seattle slightly to my left. I am preparing for a stem cell transplant, and the Pete Gross House is a six-story apartment building that houses only transplant patients and their families. I was diagnosed with low-grade lymphoma (small cleaved-cell) in 1995, and at least one lymph node in my right cheek near my parotid gland has transformed into an aggressive lymphoma (diffuse large B-cell) within the last year. I was told I needed to have an allogeneic transplant (my own bone marrow would be destroyed and a donors stems cells substituted in its place) to survive, and I found I had a match in my younger brother. In part because of insurance problems, I am now preparing to undergo treatment with high doses of a new drug, a targeted radio-labeled antibody called Bexxar, and chemotherapy, followed by an autologous transplant (some of my own stem cells will be saved and re-infused after my bone marrow is destroyed).
I had a high dose of Cytoxin on Monday and VP-16 (Etoposide) on Monday, Tuesday and Wednesday as mobilization therapy for the stem cell transplant. I currently have hives on my legs and some on my ankles and torso from the VP-16 and am taking Benydryl to control it, which makes me somewhat sleepy. My wife and my two boys (ages 10 and 12) are here in the apartment with me. My wife is my “caregiver” and the boys attend a “summer camp” downstairs in the Pete Gross House school every weekday from 9:00 to 2:00.
I am preparing for the transplant at the Seattle Cancer Care Alliance (SCCA), a relatively new outpatient/day-hospital facility located near the exit from I-5 onto Mercer Street in Seattle which is about a ten minute walk from the Pete Gross House. SCCA requires me to have a “caregiver” who can drive, change the dressing on my chest port or central catheter (a tube entering my chest and extending though a vein to a point near my heart), and attend to other tasks. Sometimes it seems like I could do these tasks myself, but as groggy as I have been during the early part of this week from Benydryl, Ativan and the chemotherapy medication, I understand why a caregiver is necessary.
The “summer camp” downstairs for the boys is in a school that is part of the Seattle Public School system, but caters to children and siblings of patients (and to patients) of SCCA. The SCCA is an alliance between the Fred Hutchinson Cancer Research Center, Children’s Hospital and the University of Washington.
I am receiving daily shots of G-CSF (Neupogen) while waiting for my white counts to drop and rise again so that my stem cells can be “harvested” (a word that always makes me think of cutting wheat, or shooting a certain number of deer in an area) in preparation for the autologous transplant. The central catheter in my chest is a Cook catheter, put in at Stanford Hospital during my last round of chemotherapy there.
By way of background, I was diagnosed with low grade non-Hodgkins lymphoma (NHL) in February 1995 in my groin and near my vena cava major. It was slow growing, and I was on watch and wait until 1999, when I was treated with Cholorambucil and Prednisone because a tumor threatened to block the uretor from my left kidney and cause an infection. The treatment was effective, but lumps appeared on my left neck just above my tonsil and in my right parotid gland three or four months after the therapy ended. I tried a variety of treatments for them, including
Rituxan, a vaccine sponsored by Favrille, Inc., an anti-CD22 monoclonal antibody (Lymphocide), and
Rituxan + CPG. The Rituxan was initially partially effective, but by the Spring of 2002 it was becoming clear that none of the treatments were really working on the lump in my parotid gland, and that lump was beginning to grow more quickly than in the past.
In the Summer of 2002, I started again on Chlorambucil. All the lumps seem to disappear except the one in my parotid gland, which responded only in part. At the third round, Prednisone was added and the parotid lump finally responded. I thought I would go into another remission, and we proceeded to purchase a condominium in Palo Alto where my job is located and where we had been renting for a year. Unfortunately, the lump came back and I was moved to a stronger treatement: Cytoxin, Vincristine and Prednisone (CVP). A needle aspiration taken resulted in a verdict that the lump in my cheek was still low grade. However, two rounds of CVP in November and December failed to eradicate it. It would shrink each time but quickly grow back. I was told this is called “kinetic failure”.
After five weeks without treatment in December, the lump was very prominent, and the doctors at Stanford Medical Center in Palo Alto, California near my home did a core biopsy of it, after giving me warnings about possible damage to the facial nerves. Important nerves controlling much of the face apparently come out of the jaw and run under or through the parotid gland.
The biopsy has handled without a hitch except that the specimen was preserved in a fluid like formaldehyde in stead of being preserved live, which seemed to make some difference. It showed that the NHL had transformed to an histology consistent with large diffuse B-cell NHL, a more aggressive type of lymphoma than my original diagnosis. The low grade NHL also remained present, so that in effect I have two diseases. I was told that the more aggressive treatment was required and the doctor prescribed CVP and Adriamycin (CHOP). The latter can potentially be damage the heart, but CHOP is the standard therapy for large diffuse B-cell NHL.
I was aware that the prognosis following transformation is worse than for low-grade NHL, or even for NHL that presents initially as intermediate grade (such as large B-cell). However, some transformed patients had responded well to CHOP and I was hopeful.
In the fall of 2002 I had consulted a naturopath who recommended a regimen for me that included avoidance of certain foods to which tests had shown I was mildly allergic, and taking very high doses of anti-oxidants (AO). The AO included high doses of vitamins C and E, co-enzyme Q-10, quercitin, selenium, green tea and melatonin. The diet also included carrot juice for vitamin A and blueberries, as well as high does of folic acid, niacinol and other B vitamins. I also took Salmon oil, and followed this regime during the CVP and first Chop treatment, experiencing few side effects from the chemo.
Unfortunately, I also continued to experience kinetic failure, as evidenced on a chart I kept every other day showing the decrease and increase of the length and width of the lump in my parotid gland. As I knew that Andrew Weil (the author and doctor) suggested that AO may protect cancer cells from chemotherapy, and as my doctors generally recommended no more than a “one-a-day” multiple while taking chemo, I stopped the AO before the second round of CHOP and continued only on a multiple (without iron or copper) and Salmon oil.
The results of stopping AO were noticeable from the chart I was keeping. The lump only regained about ¾ of its size in three weeks, instead of its full size, as it had been doing. I told the doctors what I had done. However, they focused on the failure of the CHOP to overcome kinetic failure, which substantially disturbed them and was considered a sign of a poor prognosis. They started talking seriously to me about a bone marrow transplant. . My LDH had risen to around 400 after originally being in the neighborhood of 150.
The doctors recommended a treatment using Etoposide, Cis-Platinum, Ara-C and Prednisone (or a related drug) (ESHAP), a therapy requiring me to enter the hospital at Stanford for a continuous drip over four ½ days to ensure adequate hydration. ESHAP can be very hard on the kidneys. I believe it is a “salvage” therapy (a term I am not fond of—it sounds like dragging an old hulk of a ship out of the sea and repairing it enough to sell off to someone before it sinks again).
I started the first round of ESHAP in late February and early March.
August 6, 2003
On July 7, I received cyclophosphamide and, on July 7, 8 and 9, etoposide, as mobilization therapy. The purpose was to mobilize my stem cells in preparation for an autologous transplant. A minimum of 5 million units of stem cells are required for the transplant, and the attending doctor said that he would like to collect a total of 10 million, if possible. Unfortunately, I proved difficult to collect, and spent 4 days on the apheresis machine, receiving escalating doses of G-CSF each day, and finally collected a total of 7 million units.
The first and last days were extended sessions of almost 5 hours and the other days were regular sessions of just over 2 hours. The apheresis process removes calcium from the blood, and I had a lot of calcium-containing foods and drink prior to the sessions. The short sessions were no problem, but by the end of the long sessions I felt fidgety and a little nauseous.
The bag with the collected cells did not appear substantially different from day to day, but I understand the cells were passed through or over molecules that pulled out +CD34 cells, and not enough +CD34 cells were collected until the last day. (This understanding was apparently incorrect as Dr. Gopal later told me that the non CD34+ conditioning would be applied—see below.)
On Friday, August 1, I had a CAT scan to determine if I still had any measurable disease, a requirement to qualify for the high-dose radio-labeled antibody (HDRA or high dose Bexxar) protocol. On August 6, 2003, I had a bilateral bone-marrow biopsy and aspiration, which was the most difficult one during the 8 or 9 years that I have had NHL. Later that afternoon, I had an opportunity to speak with the HDRA protocol research nurse.
In response to my questions, she stated that I should receive a test for HAMA (human anti-mouse antigens or something like that—these antigens may be present in patients previously exposed to mice or to Bexxar or other drugs containing molecular sequences derived from mice) followed on August 13 by a test dose of HDRA. The test dose consists of cold (non-radioactive) antibody equal to the full therapeutic dose of HDRA, with a small amount of hot (radioactive) antibody mixed in. The purpose of the cold antibody is to ensure that I do not have any HAMA reaction. Most people do not, but the technician told me one child who kept pet mice was disqualified. The purpose of the hot antibody is to permit gamma scans on August 15, 18 and 19. The research nurse said that HDRA tends to accumulate in certain organs, such as the liver or kidneys. The particular organs are different for each individual, and the gamma scans are used to determine which organs are receiving the highest dosage. The therapeutic dosage is then adjusted to give that organ the maximum safe dosage of HDRA.
If I qualify, I will receive HDRA on August 22. After receiving HDRA, a patient must remain isolated for 8 to 12 days, until he is no longer hot. During that time, no one may come into his hospital room, and all food containers and any uneaten food must remain in the room. The HDRA is excreted through the skin and the patient must wear gloves if he handles anything that he wishes to get back immediately after isolation ends. Otherwise, the items must be set aside until they are “cold”. The door of the room remains open, but a lead-lined screen is placed across it. People can visit by sitting on the other side of the screen and talking (it only screens the middle part of the body), and hydration bags and other items are passed over the screen.
The main side effects during this period are reportedly mild nausea and boredom. When radiation from the HDRA drops to 7 units (millirems), the patient can come out of isolation and receive conditioning chemotherapy. I will receive cyclophosphomide and VP-16 (etoposide), the same drugs that I received during mobilization, but in stronger (“conditioning”) doses. The nurse said I would probably develop mucocitis (inflamation and sores in my mouth) from the combination of the HDRA and chemo, and would remain in the hospital approximately two weeks following the transplant. The transplant is given after receiving the chemo and when radiation from the HDRA drops to two units or lower.
Although patients receiving Bexxar (which has I 131, or radioactive Iodine) also receive Lugol’s solution (a high-iodine solution), approximately 75% develop hypothyroidism over a period of three years and have to take synthetic hormone. About 5% of patients develop secondary cancers over time, and, like the chemo, HDRA affects fertility.
August 9, 2003
No appointments for the last few days. The bone marrow aspirations and biopsies seem to have been well done, and there is only a small black and blue spot on the right side. They are not very sore and I have been able to resume most of my yoga exercises. I have made a point of doing yoga, climbing stairs and riding my bicycle for an hour or two each day to stay physically fit for the ordeal of the transplant.
I have been sneezing and my nose has been running some, but it is not consistent and hopefully is not a cold. A cold could delay the transplant.
We went on a yacht trip for 2 or 3 hours as part of a program sponsored by Beams and Dreams today. Beams and Dreams sponsors the trips free to cancer patients, and it was a very welcome break. Monday, I will receive information on the HDRA treatment.
August 13, 2003
On Monday, we had an informational meeting with Dr. Gopal, who is one of the lead investigators in the HDRA study that I will be participating in.
I was first informed of the results of my recent tests: A total of about 6 cubic cm of lymphoma remain at the two internal sites that also appeared on prior CAT scans, but there were no signs of lymphoma in my bone marrow biopsies or blood samples.
I asked Dr. Gopal about treating or cleaning the stem cells that were removed during mobilization in preparation for the transplant. He stated that it is possible to extract only cells marked with +CD34 which should eliminate any mature B and T cells (and thus presumably any lymphoma cells) from the stems cells. He said that this was not done in my case because my blood showed no signs of lymphoma, and because eliminating T cells slowed the recovery process and would leave me more susceptible to infection for a longer period of time while awaiting engraftment (the re-establishment of stem cells in my bone marrow to generate white and red blood cells and platelets). Query, however, whether the G-CSF during the mobilization (with especially large doses during the last two days) might also have stimulated growth of the lymphoma and caused it to re-enter my blood stream. Such possibility was included in one of the waivers I signed.
Dr. Gopal indicated that there were 52 patients in a completed phase I (or possibly phase I/II) HDRA study with several kinds of lymphoma. Two year disease-free survival for such patients is about 70%. However, this figure is somewhat misleading because 1) some patients had low-grade lymphomas, others transformed lymphoma, and still other high-grade lymphoma—the statistics are not broken down by kind or grade of lymphoma, and 2) dosages were being tested in the study, so that some patients received less (and some more?) than what is now considered to be the optimum dose.
The earliest patients who received HDRA are out 12 or 13 years. However, statistically significant numbers of patients are available only for about eight years. Within that period, about 1% per year (7% at eight years) have developed secondary malignancies, including leukemia, skin cancer and colon cancer. On Tuesday I saw my attending physician, and asked how a transplant patient could develop myelodysplasia (a precursor to leukemia), since all blood cells exposed to the radiation and chemo are destroyed and the stem cells that are reinfused have not been exposed. He indicated that 99.9% of blood cells are destroyed, leaving some small number that are exposed to the radiation and chemo and can develop abnormalities leading to dysplasia. Query, if not all blood cells are destroyed, are all lymphoma cells destroyed?
The current HDRA study is phase II and aims to treat approximately 100 patients. About 45 have already received treatment. One patient has died from complications to his/her lungs caused by the HDRA.
With regard to dosing, the goal is to deliver no more than 25 Gys (pronounced “Grays”) to the most susceptible organ in the body, which, according to Dr. Gopal, is usually the lungs (90% of time—about 10% of time it’s the liver and a small amount some other organ). Such dose is believed to deliver about 50Gys to the lymphoma.
Today, Wednesday, I received the test dose of HDRA with the full amount of CD-20 antibody, and as noted above a small amount of radiation. The nurse, the technician and my wife were all in the room while I received it. The procedure took about one hour and involved a much smaller amount of fluid then Rituxin infusions. Prior to and after receiving the infusion, I underwent a Gamma scan, which involved lying on a table with my hands in my pockets while a machine somewhat like the one used for a Mugga Scan or CAT Scan measured gamma radiation from the infusion. I also had to stand at one end of the room while a machine at the other measure some type of radiation—it registered almost 40,000 units or hits within one minute, but I am not sure what it was measuring.
I asked the radiation technician about Gys. He said they are a measure of radiation commonly used in Europe. One Gy is equal to 100 rads. A rem is apparently equal to one rad. As mentioned above, I will only be able to leave the isolation room when I am giving off no more than 7 millirems per hour.
Dr. Gopal indicated that TBI (total body irridation) delivers a maximum of about 12 Gys. However, it is delivered in a series of short bursts over several days. The 25 Gys delivered by the HDRA (or 50 Gys to the lymphoma) are delivered over eight to twelve days.
The radioactive iodine in the HDRA has a half-life of eight days. It is apparently produced in Canada, shipped to Maine or another northeastern state where it is processed, and then shipped to Seattle and the antibody is attached. The dosage is adjusted according to the amount of radiation the iodine is giving off at the time of the infusion.
Any personal belongings in the room that I touch will be quarantined for approximately 60 days after I leave, and then can be released. If I use gloves and do not come in physical contact with an item, it can leave the room when I do.
I asked Dr. Gopal whether receiving a full dose of the antibody in the test dose would saturate the CD-20 sites and prevent the therapeutic infusion of Bexxar 10 days later from binding to same sites. He said that while this was a concern in early days of using HDRA, binding to CD-20 sites is apparently a dynamic process and earlier doses do not prevent later doses from binding.
I will receive a much higher dose of VP-16 (etoposide) than delivered in any chemo regimes (ESHAP and mobilization) I have already undergone. It is dissolved in alcohol. The dose of cytoxin will be approximately the same as used for mobilization. My stem cells will only be reinfused when I am giving off no more than 2 millirems per hour and no earlier than 48 hours after I complete the infusion of cytoxin.
Last night at the Pete Gross House I met the wife of a patient who has undergone HDRA therapy and chemo, and is now waiting for reinfusion of his stem cells. His principal problem seems to mucositis; Dr. Gopal also warned that this is a significant problem lasting a week or two. I mentioned that there is a 1% per year possibility of developing a secondary cancer and was met with some surprise by the woman who apparently was unaware of the problem. However, I know the issue is included in the waivers we all signed and I assume she didn’t understand when it was explained to her. I live in two worlds, one where I try to shut out the negative possibilities and get back to the troubles and pleasures of ordinary life, and another where I calculate (without emotion or with unbearable anxiety, depending on the stage of acceptance I happen to be in at the time—a matter largely outside my control) the severity of side effects and likelihood of death to try to make the best treatment (or life) choices. . I hope I have not added to her anxiety.
Tomorrow is free, but I have to undergo Gamma Scans on Friday, Monday and Tuesday in preparation for treatment to begin on Friday of next week.
August 18, 2003
I had gamma scans on Friday and Monday. The original count on Wednesday for my total body (where I stand against a wall with a counter about 10 to 15 feet away that measures all gamma rays it receives) was about 39,000 for one side (one minute facing the counter—I also do one minute facing away). On Friday it was about 24,000 and today about 11,000.
I bought a lot of throw-away clothes at Wall-Mart. The radiation technician said while the half-life of the isotope is 7 or 8 days, its half-life in the body is much shorter because it is excreted through the urine and skin. For the first 12 hours, some free iodine is being excreted, but otherwise, it is only excreted as fast as the B cells are metabolized.
August 19, 2003
During the gamma scan today, Larry, the technician, told me that the restrictions against exposure to radiation are very strict in Washington. While I have to wait 10 days here in order to get down to 7 millirems/hour, if I were in a state with less strict standards, such as New York, I could probably leave the room in 4 days, subject to observing certain precautions about getting too close to my wife, kids and other people. He also told me that the initial (test) dose I received last Wednesday was giving off about 1 millirem/hour when I first received it.
I have been feeling kind of depressed today and didn’t get around to doing my yoga. I keep wondering whether it is worth it to expose my body to high radiation.
My assistant at my office told me today that my computer seemed to have a virus, and I purchased and downloaded some brand-name anti-virus software. At the same time, I also purchased some web-protection software from the same company. It completely cut me off from any connection to the internet. A neighbor at the Pete Gross House happened to stop by whose job is maintaining computer systems at a University in Oregon and he tried to delete the internet software. He spent an hour or two and got nowhere, so we no longer have an internet connection, unless perhaps through David’s (my son’s) iBook.
August 20, 2003
Did yoga this morning, as almost every morning but yesterday. My blood counts and neutrafils (a class of white cells that acts like front line soldiers protecting my body from bacteria and other micro-organisms) as of Monday are down—perhaps an effect of the antibody last Wednesday?
August 21, 2003
Last day before entering the hospital. Had a blood draw this morning to test for HAMA. Have been getting clothes, books, etc. ready for entering the hospital. Larry, the radiation technician, said that I can’t get rid of the antibody any faster than the B-cells are metabolized, so I figure there should be no harm in trying to get rid of as much as possible of the free iodine, which is water soluble. I plan to drink a lot, use laxatives and exercise and wipe off the sweat. I also plan to change clothes two or more times a day, especially for the first couple of days when radiation levels are highest.
I asked the nurse about taking higher doses of Lugol’s solution (iodine) than prescribed, since my neighbor’s wife was told to take 15 drops each time when she went through a similar (but lower dosage) protocol. The nurse said unofficially that there shouldn’t be any problem taking 8 or 9 drops. I took 10 as my most recent dose.
I am a little nervous and wonder if I should be writing a last note to everyone.
August 22, 2003
I entered the hospital at the University of Washington today to receive the HDRA infusion and start isolation. The nurse wheeled in a big lead cube, about 2 ½ feet on a side with a lead cover and an IV pump attached. She hooked the IV up, but continued to carry out tasks in the room as the IV began to pump HDRA into my catheter. The infusion took an hour and the nurse came back in at the end, disconnected the IV pump and wheeled the lead container out of the room. Larry (the radiation technician) came in and checked me with a radiation (gamma?) counter.
My door is open, with a curtain I can pull across. This is a lead guard about waist high across the door. It’s only about 1½ feet wide—apparently the height to protect reproductive organs. People can and do stand outside the door and talk to me with the curtain open.
I did yoga twice today, once about 3:00 p.m. and once about 10:00 p.m. I was given Zofran before the infusion and felt fine most of the day. I started getting nauseous about 8:00 p.m. and finally asked for more anti-nausea medication at 11:00 p.m.
To protect my thyroid as much as possible, I was given Lugol’s solution and instructed to take it for 14 or 15 days. David said it was boring without me around when I spoke with him by telephone.
August 26, 2003
In isolation, just going along. I have been doing at least one round of Kundalini yoga each day—it is somewhat like yoga calisthenics and not like the Hatha yoga that I did for a while as an undergraduate. My brother taught me the routine. The first days I did two rounds followed by sponge baths to remove sweat, because regular baths are not allowed for the first two days. I change clothes regularly and throw the used ones away. The biggest problem has been ongoing nausea and vomiting a couple of times a day. I have been taking the highest dose of Lugol’s Dolution that anyone recommended, but the nausea seems more likely to be caused by the HDRA.
August 27, 2003
The nausea continues. I try to control it with various medications, but I still vomit from time-to-time. The radiation count is down to 16 (I am not certain of the units referenced).
August 29, 2003
September 4, 2003
I got out of isolation on Sunday, August 31, and received an infusion of VP-16 (Etoposide) the same day, followed by Cytoxin on Tuesday, September 2. Slight nausea continues and I vomit once or twice a day.
My mouth and other epithelial tissue have been getting worse. Today is the first day I really feel I can’t eat. All foods hurt or are scratchy, and make me feel like I have heartburn as they go down, and also make me want to vomit. I vomited after drinking carrot juice this morning. I feel enervated—no energy at all. I received a red blood cell transfusion yesterday and will receive platelets today. Continuing diarrhea over the last few days? Difficile? (a kind of bacteria) or the lining of my colon sloughing off. Probably the latter.
My wife and boys come and spend some time everyday.
September 5, 2003 (day 0 of the transplant—my rebirth-day)
I got seven packets of my stem cells infused today. They came out of the cryo-box looking like small skinned and boned fillets of chicken breast. They are dissolved in DMSO, which feels like an attack on my body as it is being infused. I vomited part way through the procedure (I seem to have a hair-trigger gag reflex these days).
September 6, 2003 (day 1)
Last night was very difficult. Everything in my mouth and throat is raw and globs of mucous gradually build up in the back of my throat causing me to gag. I was connected to a PSA (which injects morphine into my catheter when I push a button), and it provides some relief.
September 8, 2003 (day 3)
I have been having neutropenic fevers every night, but I felt good in the morning when my temperature comes down after taking Tylenol. Large folds of skin are gradually coming loose in my mouth.
September 10, 2003 (day 5)
I am receiving various high doses of medication, including antibiotics, anti-emetics, anti-fungals and anti-virals. The most noticeable symptom is not from these drugs but from the radiation and chemo. The skin in my mouth, throat and sinuses is inflamed and gradually sloughing off. It’s very painful, almost unbearable during the first few days post-transplant. At one point, the nurse told me not to apply the aspirator (suction tube) directly to the tissue over and over again as I was in danger of pulling off the uvula in the back of mouth.
Each day the condition changes a little, and I learn how to control certain symptoms better. The doctors say that healing only begins to kick in about 10 to 14 days post transplant. They also say that all patients on the HDRA and VP-16 (Etopocide) therapy suffer severe mucocitis. The question is not whether any part of the mucocitis can be avoided (it can’t), but rather how to control the pain to make it bearable until engraftment occurs.
Today I am supposed to get a chest X-ray and I was started on Flagel, an anti-biotic. The doctors keep tinkering with the mix of drugs, because I tend to run a mild neutropenic fever. I am receiving all my food and hydration by TPN (total parenteral nutrition) because I can’t eat or drink anything.
My counts today are:
Polys 0 (same as neutrophils)
Platelets 13,000/32,000 (before and after transfusion of same)
I keep drifting through morphine dreams, each serious and vivid. Some seem to provide insight, but overall I don’t like the sensation.
Despite the pain, everything seems to be going the way it’s supposed to, for which I am very thankful.
September 14, 2003 (day 9)
I am still in the hospital room in the transplant unit, getting a mixture of antibiotics, anti-fungals, etc. Each day the doctors seem to adjust or change them slightly. This is in part because I started running neutropenic fevers toward the end of last week. Such fevers are typically controlled with Tylenol. The doctor (Anaceti) said they would give me Imipenem as a last resort to control resistant bacteria, but I didn’t receive it immediately. They gave it to me a few days later after explaining what they were doing to my brother and my wife (see below). I kept having neutropenic fevers, but only once a day, and I recently broke out in a rash from the Imipenem. The doctors seemed to decide the fevers were caused by the antibiotics and other drugs, although I later learned that such fevers often happen for no identifiable cause during the post-transplant period before engraftment..
I rinsed out and coughed up a lot of blood and dead tissue, but my mouth and jaw areas are still quite sore. A lot of my time here is spent rinsing my mouth. For pain and to control nausea, I have been receiving Ativan, Benedryl, and self-administered infusions of morphine as needed. My thoughts and words easily get off topic. On Friday, my brother, came to visit. He and my wife were both present to listen to the doctors’ explanation of treatment and other issues. It was a relief to have two people close to me with coherent minds to listen and ask questions of the doctors.
My wife comes every day, sometimes bringing the kids. She stayed overnight sleeping in a fold-down chair several nights last week during the worst of the mucocitis. Part of the effect of the morphine and Ativan is that things around me seem to take on other shapes and meanings. For example, looking at the medication pole, pumps and hanging medication bags out of the corner of my eye, I thought I saw a waitress with her order book in hand waiting to make my order. When I looked directly, the illusion disappeared. I also thought the same objects were a gas station attendant wanting a different credit card from me. When I turned to ask him about it, I realized I was sitting on the toilet with my elbow on my knee and my arm supporting my head. Another time, I sat up on the edge of the bed without thinking and disconnected my IV tube, but realized what I was doing in time to pinch the leaking tubes and call a nurse.
October 5, 2003
I am day 30 post-transplant and have been out of the hospital since Tuesday, September 23. I am now being followed on an outpatient basis at SCCA. I had entered the hospital on August 22 and I received HDRA on that day. After spending 9 days in isolation, I received VP-16 (Etoposide) on August 31 and Cytoxin on September 2. My transplant took place on September 5, day 0. A lot happened over the last month, and in some ways I have a different body now.
Mucocitis – Very severe. I spent days doing little more than rinsing my month with saline solution and using Lidocaine to control the pain. I had a suction device to drain saliva which became quite stringy and later foamy. I looked in the mirror once and could see all this tissue coming off and surrounding my tongue and uvula. Almost the whole time, however, I could still swallow pills (with substantial effort).
Morphine – I had a morphine drip. I could push a button to inject morphine into my catheter every six minutes or longer, as needed. During the night I woke up a few times and tried to write down the thoughts in my head. They are short and incoherent when I read them now, although they seemed insightful at the time.
TPN – I was on total parenteral nutrition for two weeks or longer. The lining in my throat started to come apart when I was eating a tuna sandwich. While I was on TPN, I didn’t eat or drink. I only put saline solution in my mouth to rinse with; water didn’t feel good, although I could get a little down as necessary to take pills. Swallowing saline was less painful but the nurse said it would make me sick. Living without eating and without drinking was a special sensation. Eating came to seem to me like a gross physical connection to the world, an animal thing. The act of eating, digesting and defecating seemed unnecessary, another world.
Eating – I had to relearn how to eat again after the TPN, and at first could only handle things like chicken broth and lactaid milk. I tried eating eggs, a fortified milkshake and a few other things, but usually vomited. If I didn’t mark my menu sheet, the kitchen would send up full trays of food which were very nauseating to me. I tried baked potatoes, but they were disgusting. Someone had dug them out of the ground and put them on my plate. Ugh! I am eating many things now, but have had to relearn the tastes of certain foods. For a while, most vegetables tasted unpleasant to me, like eating leaves in the woods that were somehow foreign or alien. Maybe it’s the traces of poisons and bitter chemicals many vegetables have. A few days ago, we went to Ivar’s Salmon House and I had crab. The crab was enjoyable, as were the slivered beans and carrots on my plate, but I could not eat the rice pilaf. I tried the salmon but didn’t like it, and the cornbread was too gritty. I had a high quality chocolate candy, and it hardly tasted sweet or chocolate-like. I could barely taste a hint of chocolate if I breathed through my nose while holding it in my mouth. Coffee tastes like burnt bark. I have been building up my calorie intake by drinking, and finally got off permission last Tuesday, September 30, to discontinue a portable hydration pump that I had been required to use for hours everyday.
Exercise – I did a Kundalini yoga routine and walked a few miles or more everyday to build myself up before entering the hospital. I did the yoga routine while in isolation, but gave it up when the chemo started. However, I had a few hours off the TPN each day, and forced myself to walk up and down the two or three hallways open to immuno-compromised patients, usually at least 2000 steps (I had a pedometer). After I got out, I started walking up the 96 steps from the basement parking garage in our apartment at the Pete Gross House (80 from the 1st floor). After one flight my heart would start racing and I would sweat. I had to stop for 4 or 5 minutes before going on. The doctors and nurses seem to think I am doing well, and I think the exercise is a substantial part of it.
Neutropenia – Neutrophils are white cells that are the front line soldiers of the body, and release from the hospital is based in part on achieving a neurtophil count of at least .5 (also referred to as 500). I worked very hard to get out of the hospital and there was some difference of opinion among the doctors as to whether I should be released on September 23.
Platelets – Platelets assist with blood clotting, and normal platelet range is 150,000 or more. While in the hospital my platelets dropped as low as 10,000 to 12,000 where ordinary acts such as blowing one’s nose can cause bleeding. The radiation from the Bexxar seems to have been particularly had on the stem cells that produce platelets and my platelet count has stayed low.
Pic Line – A few days before I left the hospital, my catheter developed a leak and had to be removed. The cuff that held it in place remained in my chest, a small part of it visible in the incision where the catheter had been inserted. A Pic Line was inside my left arm a few inches above the elbow bend. Like the catheter, it also extends through my vein to a point near my heart to allow medications to be injected without injections of damage to my blood vessels.
Rashes – I got a fairly severe rash on my lower legs, apparently from the VP-16 (Etopocide). Fortunately, it didn’t itch. I also got a rash from an anti-bacterial drug, Imipenum, that eventually spread over my whole body. It did itch, but not severely. The doctors were quite concerned about the rashes, but fortunately they disappeared. The VP-16 rash caused some skin peeling. The other rash just disappeared some days after the medicine was stopped, although the doctor had told me that he thought it might blister or peel like a severe sunburn.
Smells – My nose became very sensitive to certain smells while I was on TPN. When my wife and sons leaned close to me I could smell their hair and another similar smell that differed slightly for each of them. The health care workers usually didn’t get close enough to me to smell, and they were constantly putting alcohol solution and cleansing compounds on their hands that hid other smells. The doctors gave me anti-bacterials, anti-fungals, etc., through my catheter. They gave me one drug, Ceftaz, that smelled terrible and made my urine me smell terrible. I could smell it on my lumen (the blue ends of the catheter in my chest), but fortunately not on all of my body. It smelled like the bottom of a hamster cage that hadn’t been cleaned for weeks, and it made it almost unbearable to go into the bathroom at times.
Transplant – The cells came in little plastic bags in a cooler, and the bags had to be warmed before they were infused. The cells looked like little skinless chicken breast fillets in vacuum-packed pastic. The cells were in a substance called DMSO, which caused a kind of shock to my body and made me shake while the cells were being infused, but otherwise it was not bad. The DMSO caused a taste in my mouth like canned corn. I sat cross-legged on the bed and watched the whole procedure to take place.
Memory – I definitely suffered memory loss. I watched a movie, Heartburn, during the mobilization, and almost completely forgot both that I had watched it and the contents of the movie. I watched it again this Wednesday night and the scenes seemed familiar, but I could not remember the way they were connected or did not have a clear recollection of the movie. I have forgotten a lot of other events as well, but if I am reminded of them, I can almost always recall parts or all of the event. I simply can’t recall it spontaneously. Also, if I start out to do two things at once, I usually forget one of them, and I don’t remember if I have completed repetitive events (like taking tablets every day) for the day. However, as of day 46 post-transplant, my memory is getting better. It was also affected by the CHOP and ESHAP, but seemed to return almost to normal by the end of the 2 ½ months that I went without chemo prior to mobilization.
October 16, 2003
I was supposed to have had an “exit” interview to be released from SCCA on Friday, October 10, which was subsequently changed to Monday, October 13. However, my neutrophil counts have been bouncing around. From over 1.0, they fell to .56 last Friday (almost neutropenic), but bounced back up to .95 a day or two later. My platelet count has been steadily declining to 12,000 on Friday, but it bounced up to 20,000 a day later and then started falling again. Dr. Holmberg consequently indicated I should stay in Seattle and be monitored at SCCA another couple of weeks to October 24. She prescribed G-CSF yesterday, which brought my neutrophil and white count up to the normal range today. I also received a red blood cell transfusion today because my hematocrit had dropped to 26%. Although, it was up to 27% today before the transfusion, it has slowly but consistently trended downward. I also received today an IL-11 (Neumega) shot to encourage platelet growth. The dosage was based on body weight, and I apparently received a dose that is a new standard. It is much smaller than the standard dose previously used, as the drug appears to be relatively new and undergoing continuing adjustment as to the proper dose. It is a cytokine that stimulates the production of platelets in many patients. I had muscle aches and felt very tired after receiving it, as well as having heartburn for a while and some mild digestive irritation. Some places, like the right side of my tongue, that have almost healed, began to ache for a while following the injection.
Last Sunday we went to my hometown of Leavenworth in Eastern Washington State and stayed two nights. My wife drove.
The clear plastic adhesive covering at the point where my Pic Line enters my arm kept coming loose, and the doctor advised me against yoga, which I had just begun to do again.
November 20, 2003
I continued the IL-11 shots for 20 days. They had unpleasant side effects, such as making me grouchy, reddish skin, bone aches, and edema in my hands and feet, which made the neuropathy in my feet (from the CHOP and ESHAP) irritating, even when I was lying down. Some symptoms continue, even after stopping the IL-11. My platelets have finally started to trend upward, however, climbing to 21,000. I received a G-CSF (Neupogen) and Epogen (Procrit) shot last Friday, but all of my counts have been trending down recently. I received a red blood cell transfusion on Tuesday, which helped a lot as I was feeling tired, short of breath with mild exertion and dizzy when I stood up from a squatting position. I also felt depressed, and the transfusion seemed to improve my mood also.
Today, I noticed that I seem to have completely lost that part of my sense of taste that is located in my nose. I can still taste sweet, salty, etc., but food has no other flavors. I ate a meal of sardines, raw onion, tomato and sweet, hot mustard, and couldn’t taste anything but the sweetness of the mustard and a slight sourness and slight burning/numbness from the onion. This is a recent development, but I have been noticing over the past several days that food seems different.
Also, over several weeks, I have developed more neuropathy in my hands. Although relatively slight, it seems to cover my whole palm now.
October 3, 2004
It has been ten months since my last entry and much has occurred. I continued on G-CSF for several months, gradually decreasing the number shots to a few a week and then discontinuing them. I returned to work in December, but am still not yet on a full-time schedule. The Pic Line was removed and in February or March, I had the cuff that remained in my chest from the central catheter removed. The evening following the cuff removal, I developed fevers and chills and spent the night in the hospital on intravenous antibiotics. I have not received any more infusions. My red blood counts have been very slowly recovering. My platelet count remains quite low and in August it suddenly took a dive from around 50,000 to around 15,000, and now hovers around 25,000. My white counts remain about half of normal, but will rise in response to drug like G-CSF. My taste has returned about 80%, I no longer have neuropathy in my hands, and the neuropathy in my feet has improved somewhat. Some side effects continue and others come and go. The most notable side effect is that my memory and ability to grasp and analyze facts have definitely been impaired. However, I continually am required to memorize material for my work and notice my mental abilities gradually improving.
The good news, the fantastic news, is that so far there has been no sign of recurrence of the disease! My first annual checkup has been delayed to mid-October, and I am hoping for the best. However, I have already had a year that I might not have had without all the effort of the doctors, nurses and researchers and the prayers and support of family, friends and church groups. I would like to thank them all.
May 2007 update:
A lot has happened to me during the last few weeks. I mentioned that there seemed to be a mass growing in my upper left femur. The oncologists finally did a biopsy of it early in the month and it turned out to be a recurrence of the aggressive component of the lymphoma I had before the transplant. Fortunately, all other tests, including a biopsy of my pelvis, were negative, suggesting that the lymphoma had not recurrred anywhere else in my body.
Dr. Levy ordered radiotherapy which started about a week later. I had radiation from above and below my left leg every day for seven days, not including the weekend. Then, on Saturday, May 19th, as I was getting ready for bed, I was standing and shifted slightly to the left. My left femur fractured just below the knob at the top of the bone. It turned out to be a complete break crossing the site of the biopsy hole. They operated on Sunday, reset the bone and put a pin in it.
The fracture was more shocking then anything I went through during the transplant, because it was so unexpected and painful. Fortunately, I fell back on our bed which is rather high, and the bone did not damage the surrounding tissue or poke through the skin.
I spoke to the orthopedic doctor a few days after the operation, and he was as surprised as I was by the fracture. Clearly the lymphoma, radiation and biopsy had each played a role, but they should not have been enough to cause the fracture. The doctor indicated he could have banded the bone around the biopsy site if he had expected any problem, but he did not.
What he apparently did not realize was that the area had been exposed to intense radiation from the high dose radio-labeled antibody ("HDRA") (I-131) during the transplant in 2003. When I explained that the femur was exposed to 25 to 50 Grays (which I believe is 2,500 to 5000 rems) of radiation over 8 or 9 days prior to the transplant, he was surprised, and said that might explain the problem. Apparently bone is only able to withstand so much radiation over an individual's lifetime. If the radiation exceeds such amount, the bone simply will not heal any longer. Radiation under a certain amount (38 of some unit) does not affect the bone, which almost always heals; exposures between can result in healing going either way.
Points worth noting are that HDRA can cause potential problems later because it involves an exposure to a large amount of radiation, and that doctors do not have any experience with it and may not see it. My doctor, who is an expert in the field of cancer orthopedics and comes across as a brilliant physician, simply did not realize that I had been exposed to such prior radiation. I suspect that if there had been a record in my chart saying that my femur had been irradiated with so many rems over so many days by a machine, he would have seen it and made judgements accordingly. Since few people have had HDRA, I think he either did not notice or wrote off the HDRA as a standard dose of Bexxar (HDRA is many times stronger than Bexxar and causes all the epithelial tissue in one's body to slough off after a week or two - a very painful experience).
In my case, this oversight has had practical consequences. If the doctor had realized the situation, he said he would have leaned more toward replacing the upper half of my femur with an artificial prosthesis. That would have eliminated the observable cancer as well as resolving the bone problem. As it is, they put a pin in my femur and I will have to go through more radiation treatments, starting tomorrow. The radiation works well, but since the area is already so vulnerable, it is possible that the healing will stop and the orthopedic doctors will have to go in to replace the upper femur with a prosthesis in any case. Also, in the meantime, the cancer is still there. Although it has not been spreading, as you know lymphoma is unpredictable. It could spread and I would much rather be rid of it sooner rather than later.
I think it would be worthwhile to warn others who have been exposed to HDRA about this problem. Do you have any suggestions for where it would be useful to post it? I am sorry to admit being so technologically challenged, but I am not even quite clear if my notes to you at lymphomation are posted to the entire group or only to you.
Late September 2007 Update
It is late September. I had a second operation on my leg in June and am moving to a non-myeloablative allo transplant with a related donor and addition radiation conditioning. There have been complications that may be related to my HDRA transplant in 2003, and comments are set out below from my experience during these last several months that may be useful to other post-HDRA transplant patients.
Despite my femur fracturing at the biopsy and radiation site on May 20, the full course of radiation was carried out in late May and June delivering 43 Grays ("Gys") to my upper femur and surrounding area. The fracture was reset with "pins" on May 20, but showed no sign of calcification (healing) at 5 weeks post-operation. In view of the aggressive nature of the recurrent lymphoma, the orthopedic doctor agreed to my request to do another operation as soon as possible. As a result, I had the upper 1/2 of my left femur "resected" or replaced with a metal prosthesis on June 28, removing the bone affected by lymphoma.
Prior to the second operation, a transplant doctor had suggested beginning an allo transplant without further treatment as soon as my leg recovered. However, because I had experienced the aggressive nature of the disease in the past, I requested a PET / CAT scan before the June 28 operation. It showed a mass in the head of my left humorus (arm). As a result, after the operation, I had two rounds of RICE chemotherapy, each requiring a three or four day hospital stay, and additional radiation to the humorus head (about 20 Gys).
A week after the first round of chemo, I developed a neutropenic fever with a white count of 0.2. In the hospital emergency room, an MRI showed a fluid mass along the prosthesis, penetrating into the surrounding muscles that the infectious disease doctors believe was caused by an infection. I was started on infusions of antibiotics every 6 hours. Although a later biopsy did not confirm any infection, I have been on the antibiotics ever since (about 6 or 7 weeks). Despite the antibiotics, the thigh around my upper femur has remained swollen even while my leg function has improved.
The chemo rounds put the lymphoma into remission for the time being. The prospects for the non-myeloablative transplant appear good, although the lymphoma doctor indicated they have had few transplant patients with transformed lymphoma. The potential infection in the swollen thigh and attendant antibiotic infusions complicate the procedure.
I am very thankful to still be here four years after my auto transplant, and to be preparing for the allo with a good shot at yet more years. None of this would be possible but for the skill, support, hard work (and prayers) of my doctors, caregivers and friends. However, I have also learned several lessons that may be useful to those traveling the post-HDRA road:
1. My orthopedic and radiation doctors made decisions without being aware of the HDRA exposure, and possible risks of cumulative radiation to bone and lymph system. While I have not confirmed, information on the internet indicates that bones stop calcifying (i.e., healing) at cumulative radiation exposures greater than about 50Gys. If correct, then exposure to HDRA followed by a fractionated dose of 43Gys of radiation (the treatment dose to my femur) means the femur failed to heal because it was exposed to excessive radiation. Also, the continued swelling in my thigh could be a result of damage to the lymph system valves in my upper leg or pelvis. No doctor will make a commitment on this point, but information on the internet indicates that high doses of radiation can cause "lymphdema" or swelling. Such damage, if it occurred, may explain the continued swelling in my upper thigh.
I recommend obtaining copies of your HDRA records and carrying them with you. In particular, the dosiometry or gamma ray study done before the transplant is the only document that can assist in identifying how much radiation each part of your body received. Unfortunately, the chart is not very precisely correlated to parts of the body, and I have received estimates of exposures to my upper femur ranging from 2Gys to 20 Gys or more. A U of W doctor simply said it is difficult to determine the amount of radiation. However, having the chart and/or related records will signal your doctors that you have indeed been exposed to high doses of radiation. Because HDRA transplants are not yet common, it is easy for doctors to discount them, or identify them with ordinary Bexxar treatment (an agent exposing tissues to much lower doses or radiation). HDRA was identified as "Bexxar" in some physicians’ reports in my records. It is import that your physicians’ consider exposures your tissues might have received from HDRA before applying more radiation.
2. A doctor in one department may not be familiar with the details of your medical history with another department, especially if the file is thick. Always be prepared to tell any doctor in advance of getting an operation or other procedure about your prior transplant and exposure to HDRA. I was not prepared or I would have insisted on resection when my leg first broke to avoid the additional factionated doses of radiation to the area.
3. The doctors in one hospital may not be familiar with your records at another hospital. Until I requested the SCCA / U of W to send the dosiometry / gamma ray chart to the doctors at Stanford, none of them appear to have seen it.
4. Always know the details of any biopsy procedures your doctor orders and tell the technician performing them the names of each procedure. In 2003 and again this year, doctors have ordered biopsies with more than one procedure and the second was not performed.
5. Always pay attention to any mass that appears in your body after the transplant. A small mass first showed up in my femur in October 2006, and it grew to appear as a large white spot on an MRI in December. Prior to the transplant, I had transformed lymphoma with both low grade small cell and aggressive large diffuse cell elements. It is apparently unusual for an aggressive lymphoma to return after several years, and the lymphoma doctors reviewing my scans in December told me to return in a few months, perhaps assuming the mass was a recurrence of low grade lymphoma. I did not want to deal with the disease again, and did not push the matter. In fact, the mass turned out to be a recurrence of the aggressive lymphoma. If I had insisted on a biopsy in December, I could have moved to radiation and transplant without a broken leg and second recurrence in my arm.
6. When the mass was first diagnosed as large diffuse cell, I asked about amputating my leg. Each doctor asked that question has winced, and one doctor (with kind intent) warned me about being perceived as being "off the reservation". As background, I do not wish to give up my leg, but on the other hand I could perform 90% of my current life functions without it if amputation gave me a better shot at a successful transplant. If the fluid around the prosthesis mentioned above turns into an infection during the transplant, then in fact I may have had a better shot with an amputation. Doctors do not travel the road patients travel, and sometimes they don't understand the stakes involved.
In summary, an HDRA worked well for me. However, post-transplant keep key HDRA records with you as well as key records from other hospitals or departments, aggressively investigate any masses that appear, inform your doctors of your history in detail in advance of any procedures, and review with technicians any procedures ordered by a doctor.