Case Studies el pt

Arabella Gets Xcyted

Date: July 28 through November 5, 2024

by Arabella

Case Report on Xcyte Therapies T-cell Clinical Trial

Related Article:
The Story of Xcyte and Its Technology

Editor's Note: Arabella is the pen name of a patient currently going through the CTL therapy involving technology pioneered by Xcyte Therapies, Inc. She has volunteered to maintain a diary of her experiences as she goes through this cutting-edge new protocol. In these installments of her case study, she sets the stage by recounting the events leading up to her signing up for the clinical trial at CCC - a no-name identifier for a "Consortium Cancer Center" - and the events that ensue.

________

Diary of a Patient Volunteer

Arabella is a slim, active, generally healthy 66-year old recently retired corporate executive. Arabella has SLL. She's had a full life, personally and professionally, and wants it to continue. She swims, plays, hikes, paints, is involved with family and friends, and volunteers helping senior citizens. She wants more time, lots more, even dreams of ski-diving on her 85th birthday.

In the Spring of 1998, Arabella was healthy and beginning to think about retiring. Old story, the same as many - Arabella's CLL was detected by routine CBC as part of an annual physical. No symptoms, just a WBC still under 15,000. The private practice oncologist to whom she was sent called it "the good cancer" and told her she would probably live many more years and die of something else. "Come back in three months for follow-up." Familiar line?

A retrospective look at her medical records revealed a higher than normal WBC for several previous years. Not satisfied with the local oncologist's cavalier attitude, Arabella consulted with a specialist at a consortium cancer center (CCC). The decision was the same - watch and wait.

In early 2024, her symptoms became noticeable enough to interfere with Arabella's physical life style - lowered stamina, pressure in the chest and pelvis, a growing and bumpy neck, more frequent infections including a bout of pneumonia. Arabella had CT scans and got a surprise - lymph nodes of over 4 cm. in the chest and pelvis and an enlarged spleen. At about the same time, a strange thing happened to Arabella's WBC - it actually fell, going down below 10. It was in the normal range. The CCC oncologist changed the diagnosis to SLL and said it was time to treat. Fludara, he said, was the "gold standard". Doing some reading on her own later on, Arabella discovered that "SLL" stands for small lymphocytic lymphoma, a close cousin of CLL. In fact, some doctors consider CLL and SLL to be the same disease under two different names. Early stage CLL tends to be mostly in the blood and bone marrow, hence the label "leukemia". SLL patients on the other hand tend to have most of their tumor load in the lymph nodes to begin with, hence the classification of "lymphoma". Early stage SLL patients may have perfectly normal peripheral blood counts, but massive lymph nodes. CLL patients may have sky high WBC when they get their blood tests done, and in early stage of the disease may have small, almost not noticeable  lymph nodes. By the time SLL and CLL progress to late stages, it is hard to tell them apart with the disease distributed across all the compartments, blood, bone marrow and lymph nodes (including liver and spleen). The two versions of the disease may start at different points (in the lymph nodes with SLL and in the blood with CLL), but they end up at the same point when they progress to their late stages. Many of the same therapies are used for both diseases.

Reluctantly, in the Summer of 2024, Arabella started Fludara. Two rounds were all she could take. She developed a rash, probably due to the Allopurinol she was prescribed to protect her kidneys. The Allopurinol was discontinued as well as the antibiotics and antivirals. More important, the Fludara was stopped. There was talk of alternative treatment - maybe Cytoxan, maybe Leukeran. Arabella was not happy. Surprisingly, the staging CT scans showed a decrease in the size of the large lymph nodes and her spleen had shrunk. Arabella made the decision to wait.

The wait wasn’t long. In the early Winter of 2024, Arabella had more CT scans - the nodes were getting bigger again. She made the decision to go back to the CCC and undergo treatment with Rituxan. More scans in February, 2024; more Rituxan Spring 2024. Her nodes had shrunk, not to normal, but to the point where the pressure was lessened, the symptoms easier to take.

Every six months the scans were repeated and Arabella’s partial remission lasted two years. In 2024, she retired to the sunny south but kept seeing the CCC Doctor. He suggested more Rituxan; and she had two more rounds. This made a total of 16 Rituxan infusions. Follow-up scans didn’t please the consortium doc; not much improvement. He suggested adding chemo. But Arabella again wanted to wait.

In January, 2024, Arabella flew through a snowstorm to see CCC Doc. He said time to treat; and no more Rituxan – not helping. He said chemo. Arabella said no chemo. She won.

But CCC Doc had another suggestion. He told her about a clinical trial he had heard about at ASH in December, 2024, using a new technology called Xcyte. Xcyte works with the patient’s own blood, therefore, much lower incidence of allergic reactions. The patient’s blood is removed by pheresis, lymphocytes are taken out, and the rest of the blood given back to the patient. The lymphocytes are sent to Seattle to the Xcyte company, where a patented process is used, called Dynabeads, to amplify and multiply the T-cell population as well as activate them by triggering their CD3 and CD28 markers. The T-cells are then returned to the patient. The company calls them Xcellerated T-cells. Trials had been held for multiple myeloma, CLL, and kidney cancer, with fairly good results. Interestingly enough, the best response seen in CLL patients in the early trials was in the lymph nodes - the Xcellerated T-cells seem to like 'homing' in to the lymph nodes and kill the cancer cells there. Since Arabella's problem was mostly centered in the lymph nodes, this seemed a pretty good match between therapy and location of the disease in her case. The best part was the absence of any severe adverse events or reactions.

Arabella liked this! No chemo; not much gunk added to her body. Arabella decided to wait for the trial and went back to the sunny south.

The winter went by. Arabella had one infection after another -- bronchitis, diverticulitis, an abscessed tooth, a urinary tract infection. Arabella was on Levaquin or Cipro almost continually from January until the end of April. She felt fatigued, had sweats, increased peripheral neuropathy, rashes. She was convinced she needed treatment.

The trial is almost ready to be signed off says CCC Doc. Back to the CCC went Arabella. But the bureaucratic red tape took seven weeks more while Arabella got more and more tense. Just wait a little longer, CCC Doc said.

By mid-June Arabella had had it! I need treatment, she said. If not Xcyte, then more Rituxan, maybe adding Leukine or HDMP. But enough waiting! The next day the trial at CCC got signed off.

The next week, Arabella had more blood tests. Interestingly enough, all counts were in the normal range, even though during the winter’s infections, counts had been askew, either elevated or below normal. Unfortunately the lymph nodes were still there and she had not been miraculously cured. An EKG was done, and the pheresis was scheduled for the end of June. A visit to the pheresis center resulted in approval of her veins for the pheresis process.

Editor's Note: The stage is set. We await with interest Arabella's experiences as she goes through the Xcyte therapy. In the meanwhile, if you wish to learn more about Xcyte therapy and adoptive T-cell therapy in general, please read the following articles on this website: CTL Therapy; T-cell Therapy at UCSD; Combining CTL Therapy with a Biospecific Antibody.

(P. S. Unfortunately, by 2024 Xcyte Therapies itself has gone out of business and its informative corporate website and research publications are no longer available to us. As far as we can tell, its research has been abandoned by the wayside.)

Report 2: The Pheresis

Arabella's tension level rose as pheresis day approached. What had been theoretical, the Xcyte therapy, was to become an actual commitment.

Arabella and her husband Robert arrived at the pheresis center at 7 AM June 28, ready to start the procedure. She was assigned her own nurse, settled in a bed in a room where three other people were having cells drawn for autologous transplants. Her nurse started a line to draw blood for labs.

Within an hour, results were returned, and true to the nature of SLL, white counts were largely normal. Another catheter was inserted into the other arm. Blood was collected, sent to a space-age centrifuge the size of a refrigerator, which separated the blood elements. The lymphocytes rose to the top and were collected for processing. All other blood elements were returned via the first line.

An anticoagulant was administered to keep the blood from clotting. A side effect of the anticoagulant was that it bound to the calcium. Arabella's lips, toes, and fingers got twitchy. The nurse gave her Tums to chew and added calcium to the returning blood.

The CCC Doc came in, and he delivered the news that Arabella would need a second day of pheresis because one of her counts had not been high enough. One day off, and she was booked for the same bed on Wednesday, June 30.

The pheresis continued for five hours. When the outgoing line clotted, the nurses were able to clear it without needing to remove and reinsert the large needle. When Arabella's blood had been completely changed three times and 12 units of lymphocytes collected, the nurse thought Arabella had had enough. Arabella was mildly twitching, which abated when the procedure was completed. Saline was administered, and more blood work was done, and Arabella's WBC was still 6.2. Her platelets had dropped below normal, but she was assured they would rebound by Wednesday. She had to stay around awhile, and prove she could walk unassisted before she was discharged. The collected lymphocytes were sent to a special lab at CCC for processing and FedExed overnight to Seattle to the Xcyte company.

Arabella slept poorly – twitching continued and was accompanied by spasms and muscle aches. Rolaids, calcium tablets, and Tums didn’t help. In the morning, she called the nurse at the pheresis center, who called the doctor. He called, said to take Ativan, 1 mg.,  which helped, and the twitching stopped.

The next day, June 30, the second pheresis, Arabella took Ativan before leaving home. Labs were done and were good, although platelets hadn't recovered much. Good thing she had taken the Ativan because getting the lines in presented a major problem. Her veins kept clotting in one arm and rolling in the other. It took three nurses an hour to get the two lines in and required eight attempts.

She had no problem with the blood transfer. More calcium was administered and the pheresis proceeded smoothly. More than 12 units were collected. She then had saline, then labs. CCC Doc appeared and said he expected some good results and would be with Arabella during the infusion. He said at the least she will have increased T cells for infection fighters, a benefit after this past winter. The second batch of lymphocytes was sent to the special lab at CCC and FedExed overnight to Seattle to Xcyte Therapies.

The waiting begins. Four weeks for the cells to be expanded and multiplied to then be infused. Interestingly, Arabella's tension level dropped. The decision had been made, and she was on her way.

Report 3: T-Day

T-Day has arrived: July 27, 2024, the T-cell infusion, the return to Arabella of her amplified and expanded T-cells.

Arabella and Robert arrived at CCC infusion center very early. Arabella's vital signs were taken and she was put into a private room that had filtered air. Nancy, who is a transplant nurse, put a line in and drew 15 vials of blood before 7:30 a.m. CCC Doc arrived, saw how tense Arabella was, and ordered 1 mg of Ativan. Arabella was tense; Robert was tense, the doctor looked tense. Wait; eat a muffin. Don’t sugar and fat relieve anxiety?

The blood tests results arrive:

Arabella's Test Results prior to T-cell Infusion

CBC			COMP Metabolic Panel
WBC*	11.7		Alkaline Phosphatase	91
RBC	4.74		Bilirubin	0.3
Hemoglobin	13.1		Sodium	136
Hematocrit	37.9		Potassium	4.2
MCV	79.8		Chloride	99
MCH	27.5		CO2	27
MCHC	34.4		BUN	*19
Platelet	299		Creatinine	1.1
			Glucose	117
			Calcium	9.2
			Total Protein	7.5
			Ablumin	4.3
			Globulin	3.2
			SGOT	33
			SGPT	40
* Highest ever recorded for Arabella - remember she has SLL

The first bag of T-cells arrives. Nancy checks the numbers, CCC Doc checks the numbers, Arabella checks the numbers. A bag of Benadryl is infused, and the T-cell infusion is started. Nervous laughter in the room as the cells begin to enter Arabella’s body. She is okay; these are really her cells. Nancy takes vitals again and every 15 minutes during the infusion. Whew! 

By 1:00 Arabella has received two bags of her expanded and amplified T-cells. The amount -- about 50 BILLION T-cells. Who can even conceive of that  many cells - and they fit into two small bags!

Arabella has her cells back. The infusion takes only a couple of hours, then saline. She stays in the hospital room for a couple of hours more to be monitored.

Oh, the odor! Apart from the anxiety, this is the worst part of the T-cell infusion. The preservative in which the cells had been stored has a very strong odor, which is said to be like garlic. CCC Doc says that statement is an insult to garlic. Arabella was only slightly aware of it, a funny taste in her mouth. Everyone else had no doubt about the bad smell.

For the next two nights, Arabella sleeps with a towel in her pillow case and under her sheet. The odor diminishes slowly, and in about three days dissipates completely.

The first follow-up will be in one week.

Report 4: The Invasion of the T Cells

The first few days after the infusion of 50 billion T-cells, Arabella didn't notice any difference in the way she felt.

On Day 5, Arabella started having episodes of twitches. The following day, after a mild workout in an exercise group, she had an episode of shakes that lasted half an hour.

Day 7 was her first re-check with CCC Doc, who prescribed Ativan for the twitches. He said it looked like the T-cells were beginning to kick in.

Ativan helped control the twitchies. But the immune response continued to mount. CCC Doc suggested Benadryl for the punk, achy feeling, overactive bowel, sweats.

Arabella was now taking Ativan at night to help control the twitchies and Benadryl to help control the sweats.

Through the next couple of weeks, the sweats and twitching continued, accompanied by achy legs, especially on walking. Preventive Tylenol before walking helped. Certainly something was going on in Arabella's immune system.

On Day 21 Arabella saw CCC Doc again. As he walked into  the examining room, he flashed a big smile: "Your nodes are smaller, your neck is definitely smaller, axillary and inguinal smaller also. Also your spleen is smaller. Looks to me like Xcyte is  working."

Arabella wasn't as sure of the success as was CCC Doc.

As two more weeks went by, Arabella began to notice she was feeling better. Her energy level was increasing; the twitches were decreasing if not disappearing. The pressure in her abdomen and pelvis was decreasing. She stopped taking Ativan.

Arabella and Robert began to look at travel websites.

The next follow-up is scheduled for Sept. 7 and includes blood work, CT scans, and an exam and consultation.

Arabella's WBC, which had been in the normal range for the past four years even while the nodes began to blossom, was now rising. Over 13.

Week 6 was more bloods - 13 vials. WBC up to 15+

Staging scans of neck, chest, pelvis, abdomen. Wet read says "stable disease." Disappointing.

Then a visit with CCC Doc.

CCC Doc says neck nodes are not palpable. He thinks Arabella has improved. She reports feeling much better; much more energy, digestive system better than for a long time.

“Let’s proceed with the second infusion of your T-cells.”

Report 5: The Second Infusion

Mid-September, 2024.

Infusion day arrives. Arabella and Robert are not so tense today. They arrive at CCC at 9:30 AM and are put into single room with hepa filter. They had previously thought this was for Arabella's protection; actually, it was so the awful smell of the DSMO preservative wouldn't leak out and bother the other chemo patients.

Blood is drawn and pre-meds are given, including Ativan SL. About 20 minutes elapse and CCC Doc arrives with the first bag of slightly frozen cells. He warms them with his hands. Numbers are checked and rechecked. The cells are hung; the infusion starts. CCC Doc pushes the cells into the line, until every last little T-cell fighter is is back into Arabella.

The second bag of cells arrives, and again, numbers checked and rechecked, cells hung, and CCC Doc again pushes cells into tubing.

Fifty billion t-cells infused. Two hours have elapsed.

Arabella is given four hours of saline. Vitals are taken every 15 minutes. She naps. No problems.

Everyone who comes into the room says the same thing: "Oh, what a smell!" Everyone but Arabella smelled the DSMO, the preservative in which the cells had been stored. She was aware only of burning eyes and a slight scratchiness in her throat.

After six hours in the private room, Arabella's vitals are taken for the final time for the day and she is released. She feels fine.

Now we wait.

Report 6: Early Results

In the days following the second infusion of T-cells, Arabella felt tired, enough so as to need a mid-day nap. Her major symptom were sweats and hot flashes 20 or more times a day. She wore sleeveless shirts while others were wearing sweaters.

A week later, Sept. 21, Arabella visited with CCC Doc and his nurse practitioner. Here is a table of her CBC from that day.

Early Results

CBC
WBC*	15.8 H
RBC	4.89
Hemoglobin	13.2
Hematocrit	39.7
MCV	81.1
MCH	27.2
MCHC	33.5
Platelets	312
% Lymphocytes	29
% Monocytes	5
% Eosinophils	3
% Basophils	1
% Neutrophils	60
% Atypical	2
* High for Arabella - remember she has SLL

An examination showed that either seasonal allergy or low-grade infection were making her ears red. CCC Doc prescribed Levaquin for 7 days. With agreement from CCC Doc, Arabella and Robert decided to go on a two-week trip to to their winter home in Florida.

Mid-October, 2024

Five weeks after the second infusion, Arabella was feeling very well. The two weeks in Florida had been pleasant and refreshing. Her energy level had increased, and her miserable itch, which had been controlled by Naltrexone, had subsided. She had been able to decease the Naltrexone, and, just recently, eliminate it. Her neck nodes were reduced. Arabella’s SLL is characterized by enlarged retroperitoneal nodes, which cause pelvic pressure. This discomfort continued, but seemed lessened.

Arabella had her routine mammogram at the CCC. The nodes in her breast were over 2 cm., just like last year. Not so good.

Her blood work showed some changes. Her WBC had risen to 16.2. This number was double her WBC at the start of the T-cell trial. One possible explanation was that the lymph nodes were giving up their hoarded white cells, and these were now in the circulating blood. If that is correct, it is good news; peripheral blood disease is easier to treat than lymph node disease. Her percentage of lymphocytes was 56, too high, and her percentage of neutrophils was too low at 36. MCV was also too low at 80.2. However, she felt that all things considered, the CBC looked good

A visit with the CCC nurse practitioner prompted a discussion of what to do next if the CT scans and Bone Marrow Biopsy, scheduled for the following week, showed the necessity for further treatment  -  Rituxan with Leukine, maybe with HDMP. Arabella wanted to wait for further treatment, if possible.

Next week: CT scans, BMB, evaluation with CCC Doc.

Evaluation

In mid-October, four months after the pheresis, Arabella was in the final evaluative stage of the study. She appeared at the CCC to have fifteen vials of blood drawn. A busy day followed with CT scans - of the pelvis, abdomen, chest, neck. The next step was a visit with the nurse practitioner, who had had a look at the scans before the "official" reading.

The nurse practitioner thought our intrepid voyager had stable disease and didn’t see where anything happened from the T-cell infusions. Arabella, Robert and the NP talked about the likely need for treatment and about what treatment. Arabella continued to say no to chemo, but maybe Rituxan with Solumedrol, maybe with Leukine, maybe Neupogen. The next day brought a visit with the CCC hem/onc.

Evaluation CBC

CBC
Results	Current	Week Earlier
WBC*	14.5 H	16.2 H
RBC	5.08	5.22
Hemoglobin	14.1	14.2
Hematocrit	40.7	41.9
MCV	89.9 L	80.2 L
% Lymphocytes	54 H	56 H
% Monocytes	7 H	4
Platelets	272	300
* High for Arabella - remember she has SLL

The next day, back to the CCC to visit with the hem/onc. The meeting included Robert, Arabella and the nurse practitioner.

The hem/onc agreed that the jury was out. The CT results were neither good nor bad - the lymph nodes were still enlarged, but he saw some good outcomes of the study. He examined Arabella and felt that her neck nodes had decreased in size. He also thought she looked very well. He listened carefully while she told him about her increased energy level, and that she has dropped a number of drugs. He thought she might not need treatment right away; the question was when to treat. He was concerned about the rise in her counts and would continue to monitor them. If they became stable where they were, okay, she could wait. If the counts continued to rise, he would want to treat. Meantime, he was going to compare all her scans from the last four months and see if he could get a feel for which way the disease was going.

So, more waiting. Arabella was to see the hem/onc again next month. All in all, good news.

Arabella's Impression of the T-cell Study

Four months of deliberation — whether to become a study participant or not, followed by another four months of participation — pheresis, BMBs, repeated CT scans. And the net result for Arabella? Not much. But then again, there seemed to be stable disease; no real progression - some changes, but no deterioration.

If she had known the outcome in advance, would she have done Xcyte? Probably not. She needed treatment soon. Without the trial, she would have had some treatment in the spring - and might not have been any better off than she was right now.

With CLL/SLL, no treatment decision is easy. To treat now or to wait, to use chemo or rely on antibody or immunological therapy, to go with your gut feel or to accept the doctor's recommendation. We must make these decisions based on the information we have at the moment. Hindsight is always better.

The object is to hang in and have a life until a better treatment comes along to try. Arabella has managed to do that so far.