基因检测的巩固将提升癌症患儿的诊疗护理

Doctors at Great Ormond Street Hospital for Children NHS Foundation Trust (GOSH) have started using a new service available as part of the North Thames Genomics Laboratory Hub (NTGLH) laboratory service to help better diagnose and manage childhood cancers.

Over the course of a few short months, more than a dozen children treated at the hospital have had results beyond what could have been achieved with standard testing, with five of them so far having their treatment or prognosis immediately improved.

Under the new NHS Genomic Medicine Service, testing is being consolidated into seven GLHs across the country to enable high throughput and more comprehensive genomic testing. At GOSH samples from children with cancer are now sent for testing using large DNA and RNA panels on the NovoSeq system in the NTGLH cancer laboratory based at the Royal Marsden. This high throughput sequencing is done in batches several times a week , and offers a more comprehensive assessment of the genome which means that it can define the underlying cause of a patient’s illness better. Doctor Jack Bartram, Consultant Paediatric Haematologist at GOSH said:

“We have been delighted with the impact this is having on patient care. The potential this testing offers ranges from improved understanding of childhood cancers and more accurate diagnosis, to changing treatment and drastically improving a child’s prognosis.”

Meet Ayaan

One of the first patients to benefit from this collaboration is 8-year-old Ayaan. In October 2020, the usually bubbly and chatty youngster became unwell with a fever, unexplained bouts of exhaustion and a lack of appetite. Her mum, Masuda, recalls: “Because we were in the midst of the COVID pandemic, I thought Ayaan could potentially be ill with the virus. But, the high temperature kept returning no matter what we did and her test came back negative.” A series of blood tests then showed Ayaan’s platelets levels were down, and within weeks she was diagnosed with acute myeloid leukaemia (AML).

Masuda said: “We were in shock, and after we had the news everything seemed to move so quickly. We were immediately transferred to GOSH, where Ayaan’s diagnosis was confirmed and she began chemotherapy. Although we felt we were in safe hands at GOSH, Ayaan’s diagnosis and treatment meant we had to stay in hospital for a month. We were away from her father and younger brother for much of that time, which was tough for us as a family. In that time, Ayaan was the quietest I’ve ever seen her.”

The experience leading up to the diagnosis had been overwhelming for Ayaan, but then came the side effects of the chemotherapy treatment. During, Ayaan’s appetite continued to wane, her hair began falling out, and she had an allergic reaction to penicillin. The family’s biggest concern, though, was that with AML Ayaan had a 60% chance of surviving.

“We all tried to be strong for Ayaan, but ultimately there was no easy way to tell her that she had a deadly cancer.”

Ayaan's mum, Masuda

A change of fortune

Three weeks after her last dose of chemotherapy, Ayaan and her family got some unexpected news. Advanced diagnostic testing made possible by the NTGLH found a variant form of the fusion gene PML-RARA that was not detectable with conventional techniques – this is associated with acute promyelocytic leukaemia (APL). Her outlook drastically changed. APL requires less intensive treatment, which meant less severe side-effects. It also meant that Ayaan could be at home with her family, instead of months of inpatient treatment. More importantly, her prognosis was also better as APL has a high-curative rate with long-term survival over 90%.

Masuda said: “Since she started on her new treatment, we’ve seen such a difference in Ayaan. She was always very popular in her class and a regular chatterbox. That stopped when she got seriously ill last year, but each day we are seeing our daughter is returning to her old self. Being on this less intense medication has definitely helped her do that.

“We have been inspired by her resilience and her determination to get back to doing the things she loves – like school. We’re now having discussions with her teachers to get her back in full-time. This isn’t something we could even imagine when we received the diagnosis the first time around.”

“Since she started on her new treatment, we’ve seen such a difference in Ayaan.”

Masuda

These outcomes show how the change in practice is benefiting our patients. Now all patients at GOSH with a new diagnosis of leukaemia have advanced genomic diagnostic performed to ensure a higher level of accuracy and best possible management of a condition. Since its roll out, clinical teams at GOSH have received answers and new insights beyond what could have been achieved with standard testing. Results are usually returned within ten days, allowing patients and their families to be told and their treatment regimens altered as soon as possible, where necessary.

Next steps

While genetic testing has been carried out for children with cancer at GOSH for a number of years, the new consolidated system established in the NTGLH means that the next-generation sequencing for genomic screening can be carried out for even more children across the region.

Professor of Genetics and Fetal Medicine at GOSH and Medical Director at North Thames GLH, Lyn Chitty, said: “These new results beautifully demonstrate the real benefit of consolidating laboratory testing, so we can offer more comprehensive testing to more children, and adults, with results available in good timescales. We would like to see are more hospitals consolidate their testing in the NTGLH, because the more users we bring into the hub, the more frequently we can run the panels and results will be available even quicker. Consolidating laboratory testing in this way means we can offer state-of-the-art techniques to the largest number of patients in London, improving their care and for some, their lives.”