A Patient Story: CAR-T Cells

Posted on January 26th 2021

NHS Blood & Transplant has been involved in the collection, processing and
storage of cells as part of the process to treat NHS patients with Chimeric
Antigen Receptor (CAR) T cells for several of the first wave of NHS treatment
centres commissioned at the end of last year. CAR-T cells are genetically
engineered to target CD19, a protein on the surface of lymphocytes that is
present in some forms of leukaemia and lymphoma.

Nitya Raghava was diagnosed with Acute Lymphoblastic Leukaemia at the
age of 16 and received standard chemotherapy at Bristol Royal Hospital for
Children, achieving a good initial response. 23 months into treatment she
relapsed (her leukaemia came back). Following further chemotherapy, during
which she completed her A levels achieving grades to be accepted by
University College London (UCL), she achieved complete remission and was
referred for Allogeneic Stem Cell transplant. Following Human Leucocyte
Antigen (HLA) typing (“tissue typing”) by The Histocompatibility and
Immunogenetics (H&I) laboratory in NHSBT Filton, she was found to be a full
match with her sister.

Her sister donated stem cells at the Therapeutic Apheresis Services (TAS)
unit in Bristol, which were processed and some stored at the Cellular and
Molecular Therapies (CMT) laboratory, Filton. The initial transplant proceeded
without too many problems but she relapsed by day 64.

Until CAR-T cells became available, there were no curative treatment options
for a patient in this position and she would have entered palliative care at this
point. The Eliana trial of CAR-T cells shows an approximate 50% cure rate.
She was referred to the national panel and accepted as one of the first NHS
commissioned patients to receive this treatment. This provided a tight timeline
for NHSBT to complete the necessary regulatory and practical agreements
with the hospital and the pharmaceutical company, Novartis, to proceed.
Nitya had cells collected by TAS Bristol on 20th December 2018, they were
cryopreserved at CMT Filton before shipping to USA on 27th December for
manufacture. They were shipped back to Filton at the end of January and
stored under our Genetically Modified Organism (GMO) licence. The patient
was given preparatory chemotherapy and the cells were transferred to
University Hospitals Bristol for infusion on 6th February. She developed a very
common early complication of CAR-T cells called cytokine release syndrome,
but this was low grade and easily managed allowing her discharge from
hospital as planned after 14 days. The CAR-T cell therapy appears to have
cured her leukaemia with no detectable disease in her bone marrow within a
month and this remains the case on most recent testing 4 months after cell

Unfortunately, she developed graft versus host disease (GvHD) from the
CAR-T, which while predicted as a possible complication had not been
reported anywhere previously. The cells have unintentionally attacked her
skin, liver and gut as well as intentionally attacking the targeted leukaemia
cells. She is now receiving extracorporeal phototherapy at TAS Bristol
alongside 3 other treatments to control the GvHD. While skin and bowel
symptoms have resolved, she has persistent liver impairment resulting in
referral for potential liver transplantation.

Despite all of this she is planning to go to university in the autumn. She would
not be alive today without the services she has received from NHSBT. In total
she has received 18 units of red blood cells and 28 doses of platelets since
her leukaemia diagnosis. She has used diagnostic services (H&I) with TAS
and CMT providing therapeutic interventions. It is possible that she may also
require the services of Organ Donation and Transplantation (ODT) in the near
future. She was the first NHS CAR-T patient that NHSBT were involved with
but many more have and continue to follow.

Source: NHSBT


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