Meeting
Patient #3
When I was in Washington, D.C. at the
Leukemia & Lymphoma Conference, I sat at a table for a small group
discussion. I was honored to be in the presence of Dr. Carl June’s “Patient #3”
– Doug Olson. He was cured of the same 17p deleted leukemia that I have.
Doug Olson, a scientist involved with
blood testing, had been a patient of Dr. David Porter at the Abramson Cancer
Center at the University of Pennsylvania since he was diagnosed at the age of
49 in 1996.
Doug
Olson’s Prior Cancer Treatments:
Doug Olson was initially diagnosed in
stage I CLL/SLL. In 2002 he received his first treatment of two cycles of
rituximab plus fludarabine to combat his progressive leukocytosis (elevated white blood cell count greater than 11,000
per mm3) and adenopathy
(enlarged lymph nodes). His blood count normalized and he had a partial
resolution of enlarged lymph nodes.
In 2006 Olson was treated with four
cycles of rituximab and fludarabine, since the cancer was progressing. Again
his response was normalization of blood counts and a partial regression of enlarged
lymph nodes. Olson’s cancer did not progress for 20 months, and he was not
treated for another two years.
A bone marrow biopsy indicated his bone
marrow was infiltrated with leukemia cells February 2009. Three out of 15 cells
contained 17p deletion and a FISH (fluorescence in
situ hybridization) test showed that 170 of 200 cells had a deletion of TP53 on
chromosome 17p. He was treated with rituximab with bendamustine for one cycle
and bendamustine without rituximab for three additional cycles. He had a severe
allergic reaction to rituximab. This cancer treatment resulted in only a slight
improvement in lymphocytosis (an
abnormal increase in the number of lymphocytes, which can be B-cells, T-cells
or NK-natural killer cells). Olson had a CT (computed tomography) scan and he
was found to have progressive enlarged
lymph nodes.
Re-engineered
Serial Killers
Olson was running out of options. His
physician Dr. David Porter was working on an experimental cancer treatment
process with Dr. Carl June training a person’s own immune system to kill cancer
cells. Olson decided that he wanted to be a participant in that clinical trial
(ClinicalTrials.gov number NCT01029366) to assess the safety and feasibility of
infusing autologous CART19 T-cells in patients with relapsed or refractory
B-cell neoplasms.
In December 2009 the researchers at U of Penn collected
Olson’s T-cells by leukapheresis
(passing his blood through a machine that removed the cells and returned the
other blood components back into the patient’s veins). The T-cells were then frozen while Olson was treated
with chemotherapy to get rid of any remaining T-cells in his body. Olson
received alemtuzumab (an anti-CD52, mature-lymphocyte, cell-surface antigen)
for 11 weeks. Olson had stable disease for six months and was officially
enrolled in the Phase I clinical trial July 2010.
Olson’s T-cells were re-engineered by a bold approach –
by being injected with a disabled H.I.V.-1 that turned into “serial killers.”
The reprogrammed T-cells produce chimeric antigen receptors (CARs) that target
a protein called CD19 and attack the B-cell carrying that protein. Dr. June’s
team was the first to use the H.I.V.-1 as the vector in gene therapy for cancer
patients. Three patients were enrolled. All three participants in the study had
advanced p53-deficient CLL.
The new T-cells were then introduced back
into his body. Olson said after two weeks he thought he had the worst case of
the flu he had ever had. The researchers were concerned that he was dying.
Apparently the serial killers were doing their job. All his B-cells were
destroyed (both healthy and leukemic). It took Olson two weeks to recover. When
the researchers found that there was no evidence of leukemia in his body, they
were as surprised and elated as Olson.
The re-engineered T-cells remain in his
body to keep the cancer in check. The problem of no B-cells results in
vulnerability to infection. Every three to four weeks Olson has to go in for an
infusion of intravenous
gammaglobulin (IVIG) -- a blood product containing antibodies from plasma
donors.
The Leukemia & Lymphoma Society is funding Dr. Carl
June’s team CARs research. The next milestone is to target only leukemic
B-cells. This blood cancer procedure will soon be developed to apply to other
cancers (i.e. pancreatic, colon, mesothelioma and ovarian).
I hope to hang in there long enough (with the help of ibrutinib)
to also reap the benefits of this cancer treatment. And to think … I was looking
in the face of a man that could be the forerunner of my cure. It was a good
day. J
The scientific articles can be read in
full in:
New England Journal of Medicine
Science Translational Medicine: Integrating Medicine and
Science
