CPI-0610

                      Well, not a memorable name, that, but hopefully a memorable and successful clinical trial. The study protocol just changed and the dosage increased. Funny thing: the drug is so new the manufacturers haven’t started making higher dose capsules (25 mg is the higest), so David will be taking 12 capsules of unusual size every morning.

            A not-so-funny thing: here’s the warning in the description: “In case of contact with the powder: wash skin immediately with soap and copious amounts of water for at least 15 minutes. If in eyes, rinse with copious amounts of water for at least 15 minutes.”

Here’s the study description of the drug:

CPI-0610 is a small molecule inhibitor of a group of proteins called BET proteins. By blocking BET proteins from binding to certain cancer-causing genes, CPI-0610 may result in these genes being deactivated (switched off). CPI-0610 has shown anti-tumor activity in previous laboratory studies.

(By the way, technically, individual leukemic blood cells are ‘tumors’. The name isn’t exclusive to solid masses.)

            The cycles are 21 days long. He takes the capsules for two weeks, then has a week off (of pill taking; he’ll still visit clinic twice a week). In this first cycle, he’ll have his blood drawn on Day 15 through 19. (Actually, he gets Sunday off.)

Today, Day One, we’ve spent the whole day at the clinic, from 7:30 a.m. to 5 p.m. There have been blood draws, after the first daily dose, at ½, 1, 1 ½, 2, 3, 4, 6, and 8 hours and EKGs (electrocardiogram, which measures electrical activity of the heart) at 1, 2, 4, and 6 hours. The portable EKG machine comes right to the room, so we’ve stayed in room 138 all day. Actually, midday I took the T to Harvard station and walked to the Cambridge Public Library to pick up a score of the Brahms’ German Requiem. We’re attending a concert on April 11^th and I want to learn the music better. I then walked down Broadway from the library to Kendall (the MIT stop). I was going to walk across the Longfellow Bridge, but it started to rain, so I bailed and took the T across the Charles River.

Tomorrow, Day Two, we’ll come in the morning for a blood draw at the 24 hour mark (plus or minus 3 hours, a comfortable window).

            From MGH we’ll drive to Logan airport and pick up Annie at noon. We’ll spend the day with her. Saturday Jim and I fly to Chicago and Annie and David drive to New York City to visit R’el, Peter, Xiomara, and Andrew. David gets a reprieve and doesn’t have to come back to clinic until Tuesday.

No More Decitabine

                   Our optimism about the decitabine took a nosedive today. Although David went through the fourth round without hydroxyurea, today the white blood cell counts are up again: from 8.93 last Thursday to 18.39 on Monday and a whopping 46.07 today. Yes, we’re back to doubling in 3 days. He’ll take 2 gram/day of hydroxyurea again and discuss clinical trial options on Monday. The hydroxyurea can keep the white blood counts low in the short term, but since it doesn’t attack the leukemia factory in the bone marrow, it can’t cure the leukemia.

He had another echocardiogram today: his heart’s poor ejection fraction barred him from certain clinical trials back in August. We hope he has recovered sufficiently to be eligible for a trial now, since the conventional treatments have not been effective in achieving remission.

He also had a bone marrow biopsy today. It was originally scheduled to assess the effect of the decitabine, but based on the blood draws we can see it isn’t working at this point. The clinical trials require biopsies to assess eligibility, so Judy took extra samples for those. We’ll get the preliminary results on Monday, as well as the echocardiogram results.

Jim and I are planning a trip to the Midwest starting 28 March. Originally we envisioned a road trip so that David could come, but he can’t be away from MGH for more than 5 days, so we’ll fly, see Annie in Madison, and Matt and Charlotte in Chicago. If Matt can arrange his schedule, we’ll drive to Wabash College in Crawfordsville, northwest of Indianapolis, where Matt is an admissions officer.

Date of Blood Draw (CBC)	White Blood Cell Count	% Blasts in circulation	Absolute Neutrophils	Hematocrit (red blood cells)
13-Feb-15	3.53	31.0%	0.39	19.40
19-Feb-15	5.89	30.0%	0.47	22.40
23-Feb-15	10.02	25.5%	1.60	21.20
26-Feb-15	9.97	53.0%	1.20	18.20
2-Mar-15	5.48	32.4%	0.51	24.40
5-Mar-15	4.09	28.6%	0.97	22.90
9-Mar-15	5.40	30.3%	1.14	20.40
12-Mar-15	8.93	60.0%	0.54	26.10
16-Mar-15	18.39	56.0%	1.84	23.60
19-Mar-15	46.07	67.0%	4.15	21.20

Decitabine: Hypomethylating Agent

            We saw Dr. Fathi yesterday. David asked him: since the decitabine seems to be effective, would he have chosen it as the initial treatment. He said no: the 7-3 cytarabine/daunorubicin regimen that David started nearly a year ago at Walter Reed is the standard first-line treatment for someone of David’s age with AML (acute myeloid leukemia). Over the whole population it has a remission rate of about 70%. And David did achieve remission from it, it just relapsed. Decitabine therapy has a remission rate of 40% or less. So, based on statistics, which is all we have to go on, the treatment choice was reasonable. Of course, for each individual patient, the remission rate is either zero or 100 percent.

            The current decitabine infusion therapy isn’t technically chemotherapy. At high doses, decitabine can be used as chemotherapy, with the goal of killing leukemic cells (and healthy blood, hair, and gut cells as collateral damage). But at this lower dose, it’s a “hypomethylating agent”. The theory is that the decitabine can reactivate tumor suppression genes in individual cells (cool, huh?) and thus allow the leukemic blasts to mature into healthy cells.

For five days, February 23 through 27, we went to Cox 1 each day for the fourth round of decitabine infusion therapy. The next bone marrow biopsy, probably in about three weeks, will indicate how well the decitabine is working. It will also show the status of the various mutations involved. The bone marrow has its own ecology, like a garden. David has multiple mutations of his white blood cells, like a garden with a variety of weeds. If you pull out one type of weed, there’s the danger that another, existing weed will invade the newly cleared area. Unfortunately, we don’t know how to pull out all the weeds at the same time or speed the spread of beneficial plants.

And speaking of gardens, today we had a thaw: 40 degree weather and puddles in our driveway. Still plenty of snow, but in March there’s always hope of spring.

Last week we had some excitement. My idyllic afternoon dishwashing was interrupted by a sudden crash and breaking glass. My first thought was that a giant icicle (we have several) had hit our bay window. But the staircase landing was full of glass and snow, no ice. Looking through the shattered window, we saw a 12 foot piece of our gutter forming an upside-down V in a snowbank. Roof snow had melted and refrozen into a heavy ice dam on top of the gutter. The ice was probably a few hundred pounds. The weight had broken the gutter in two and sent one piece careening to the ground, bashing the window on its descent. The remaining partial gutter, also full of heavy ice, hung directly over the power line to our house. A contractor friend came to the rescue and successfully removed the gutter. He also gave us some insulating foam board to cover the window until we can get it repaired. Was someone talking about gardens?

Icicyles and Snowdrifts

            The snow has stopped here in Lexington. Our acre lot is a dramatic landscape of huge icicles, peaked, windswept drifts, low-lying tree trunks deep in snow, and circular wells carved out around other trees. The red of Sam’s Ford is completely gone on three sides; the North Wind has blown away some of the snow on the garden side.

            David continues to look good. He’s got a beard worthy of a mountain man and was able to visit Manhattan last weekend.

            His counts look good: the white blood cell count has stayed below 4 for 9 days, down from 9.13. The blast percentage is 42%, not great: normal is below 5%. He had a transfusion of red blood cells Friday, but doesn’t have to return to Cox 1 until Wednesday this week.

            For an hour a day, from 28 January to 1 February, David had his third course of five decitabine infusions. We hope the low WBC counts are at least partially caused by the decitabine. (The hydroxyurea certainly accounts for at least some of the dip.)

At the end of this 28 day cycle (5 days of decitabine, 23 days off), the nurse practitioner will do yet another bone marrow biopsy, to see whether the decitabine is attacking the leukemic blasts in the bone marrow itself. The marrow is the leukemia factory; we’re hoping the decitabine is scoring direct hits there. We’ll know in about two weeks if it’s making any headway.

Date of Blood Draw (CBC)	White Blood Cell Count	% Blasts in circu-lation	Hematocrit (red blood cells)	Platelets	Absolute Neutro- phils
5-Jan-15	2.16	6.0%	25.60	39.00	0.17
8-Jan-15	1.58	4.0%	22.10	39.00	0.16
12-Jan-15	1.04	4.7%	22.40	40.00	0.12
15-Jan-15	1.40	16.0%	22.40	38.00	0.03
19-Jan-15	2.29	22.0%	23.70	29.00	0.05
23-Jan-15	3.42	23.0%	23.80	36.00	0.34
28-Jan-15	9.46	49.0%	22.90	58.00	1.51
30-Jan-15	11.80	30.8%	20.90	78.00	1.30
1-Feb-15	9.13		23.60	66.00
4-Feb-15	3.39	42.0%	23.10	39.00	0.41
13-Feb-15	3.53	pending	19.40	49.00	Pending

Quiet As Falling Snow

            I haven’t posted for nearly a month, because there’s been no news: no blood transfusions, no sudden rise in white blood cell counts. A blessed, quiet month.

            We’ve had a lot of snow. Jim and I actually got out of Boston one Sunday evening, just ahead of one of the storms, and came back during another. We spent that first week of February in temperate San Francisco, staying with our niece Carla and her husband Daniel and visiting Ted and Kathy Perry. They are famous in our family history, cheerfully lending Jim their car so he could drive 33 miles from Princeton to Westfield for a first date with Mary Hazen.

            We visited the giant redwoods in Muir Woods in Marin County, and spent five days touring San Francisco: the obligatory cable car ride and a fun morning tooling around in a little go car (a glorified three wheeled motorcycle with GPS-triggered commentary), Dungeness crab on Fisherman’s Wharf, and even the Walt Disney Family Museum. Matt gave us the special edition boxed set of Mary Poppins and Saving Mr. Banks, so I’m on a Walt Disney kick.

            Matt visited David while we were gone and they had a whirlwind trip to Manhattan to see R’el. The trip ended with the three of them stuck in the snow of our driveway, after a harrowing drive home. They got the car unstuck and picked us up early Sunday morning. By Monday night my arm ached so from shoveling that I couldn’t sleep.

            I’m writing this from 205 Water St., Perth Amboy, NJ, my parents’ home since 1985. The Salvation Army truck drivers came today and nearly emptied the house: 3 recliners, futon, cabinets, tables, desks, and chairs. I said goodbye to the dining room set that’s older than me, and the loveseats I lay on as a baby. Mom had them upholstered 40 years ago, but they look brand-new, crisp and spotless. Luckily the driver couldn’t take the old metal student’s desk or the white resin porch chair (with the notice on the back written in Sharpie: “Stolen from 205 Water St.” Perhaps it did deter a would-be thief.) So, here I sit, at an old grammar school desk as dusk falls, watching Staten Island fade beyond the Arthur Kill and the rather lurid yellow Barge Restaurant sign glowing, half hidden by a sycamore tree. The white and pink Christmas cacti are blooming in the front bay window; the orchid is way past its prime. Mom and Dad loved this view for 29 years. I’ll miss it too.

The Ordinariness of One Pretty Good Day after Another

              The outpatient clinic on Cox 1 was closed for MLK Day, so we went to Lunder 10 for the requisite semi-weekly labs. The counts continue to look good; no need for a transfusion today. David stopped taking hydroxyurea several days ago, so it appears that the decitabine is effectively lowering the white blood cell count.

            Here are the numbers:

Date of Blood Draw (CBC)	White Blood Cell Count	Percentage Blasts in circulation	Absolute Neutrophils	Hematocrit (red blood cells	Platelets
5-Jan-15	2.16	6.0%	0.17	25.60	39.00
8-Jan-15	1.58	4.0%	0.16	22.10	39.00
12-Jan-15	1.04	4.7%	0.12	22.40	40.00
15-Jan-15	1.40	16.0%	0.03	22.40	38.00
19-Jan-15	2.29	pending	pending	23.70	29.00

            So, we continue trying to remember to appreciate each uneventful day. As Jim wrote in his summary of the past year: “Except for a few days of severe intestinal pain just before Christmas, the past five weeks have been the best since March. Mary, David, and I each seek in our own way to deal with the prospect of imminent death mixed with the ordinariness of one pretty good day after another.”

Happy Little Christmas

            6 January 2015: Epiphany, the day to celebrate the wise men from the east finding the young child, Jesus, and presenting him with gold, and frankincense, and myrrh.

            December was rough. After watching David’s white blood counts rise, to 90, 91, and 95 (very bad news) in the first week of December, he was admitted to Lunder 10, inpatient, on December 19^th, with severe abdominal pain: enteritis, or inflammation of the intestine. He was discharged on Wednesday, 24 December, in time for Christmas. And for 27 hours on December 27-28, all of our progeny were together in Lexington.

            New Year’s Eve, Matt drove David down to Manhattan to spend the holiday with all their siblings at R’els Manhattan apartment. Some went to Central Park for the midnight 4-mile run.

            On Friday, 2 January, David began the second round of decitabine chemotherapy. It’s caused some nausea and fatigue. His hematocrit (red blood cells) and platelet counts are relatively stable; the white blood cell count is low, which is great news. He finished his fifth and final infusion today and will take 3 weeks off while his blood counts recover.

            Here are the blood counts. For now, the goal is very low WBC.

Date of Blood Draw (CBC)	White Blood Cell Count	Percentage Blasts in circulation	Absolute Neutrophils
19-Dec-14	35.24	68.0%	1.40
20-Dec-14	27.57	55.8%	0.96
23-Dec-14	12.83	55.0%	0.38
24-Dec-14	7.99	23.4%	0.36
28-Dec-14	2.91	32.4%	0.10
31-Dec-14	2.56	7.6%	0.00
2-Jan-15	2.56	18.0%	0.13
5-Jan-15	2.16	6.0%	0.17