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Take advantage of the testing facilities available and present early was the advice for Māori at the “Ka Mua Ka Muri” – Walking Backwards Into The Future Cancer Educational Symposium.

The symposium was organized by Cancer Society Southern to address the impact of cancer on Māori and Pasifika.

Professor Parry Guilford and Dr Scott Babington were keynote speakers at the event and, with statistics showing Māori were still lagging behind in cancer outcomes, they urged participants to present at their GP early if they had any concerns and go back or find another GP or nurse for a second opinion, if they believed their concerns had not been addressed. They said this was good advice for everyone.

“The sooner you present, the better,” Dr Babington said. “A small cancer is much easier to treat, and the treatment will provide better outcomes. Don’t be complacent. If you are concerned about anything, go to your GP straight away.

“It probably won’t be cancer, but if it is, getting it early is essential. Many cancers are treatable if they are caught early.”

Professor Guilford is developing a new non-invasive blood test to detect colorectal cancers early. Colorectal cancers are one of the most common cancers in New Zealand. The test works by identifying the DNA of cancer tumours that is circulating in the blood.

He said the test was inexpensive and could be conducted anywhere, meaning testing could be done in a community centre, the marae or in your GP’s office, which increased accessibility.

The test is still going through trials and Professor Guilford, rather than centralising the trials is bringing them to the community.

‘This is a community-based solution,’ he said. ‘In the next few months, we will be asking communities to get involved and be part of the trial. I would suggest you ask your GP and make yourselves available, especially if you have any of the symptoms or have genetic factors.

Professor Guilford said the test allowed those who were suffering from more advanced disease to be treated more quickly which was especially important with the long waiting lists for colonoscopies.

Professor Guilford also researched the genetic mutation in the CDH1 gene, which can cause stomach cancer. The mutation particularly affects Māori, and he urged people to be assessed especially if there was a family history of the cancer or they had any symptoms. He said the first step to getting tested was to approach your GP who could then refer you to the genetics company.

Toni Biddle, Tumu Whakarae (CEO) of Te Mātāpuna Hauora , opened the afternoon session. Her mission is to enhance the health and wellbeing of whānau across the community and is known for her determination to improve health outcomes for whānau.

She guided participants through steps to empower them to improve their and their families’ health journeys.

Organiser Lisia Ratima-Livesley said the aim of the symposium was to provide whānau with a comprehensive understanding of all cancers and its impact on Māori and Pasifika communities.

She also wanted to equip whānau with practical tools and strategies for supporting whanau through cancer diagnosis, treatment, and recovery.

I hope you are all well and adjusting to the fresher Southern mornings.

I am still coming down from cloud nine. The Cancer Society’s inaugural research conference In Pursuit was held at Te Pae in Christchurch earlier this month and was a resounding success. We had the honour of showcasing our best and brightest cancer experts as well as international leaders. Listening to their presentations gave an overwhelming sense of hope and confidence that our cancer landscape is changing for the better.

Some speakers had a focus on early detection and cultural and geographic equity, like Professor Parry Guilford who is focused on new technology to non-invasively detect early-stage colorectal cancers, and Jessica Fitztjohn’s vibration machine that aims to detect breast cancer out in the community for a fraction of the current cost.

We heard from Dr James McKeage who has developed a machine that allows people to administer their own treatments at home, reducing the burden on our hospitals, and impact on families when they have to travel on a regular basis.

And then there is CAR T-cell therapy which, all going well, will be available in Christchurch for Non-Hodgkins lymphoma next year. This is a huge step forward for New Zealanders and we thank John Robson and his team at BioOra for progressing with the build of a manufacturing plant in Christchurch, to be opened mid-2026.

Currently New Zealanders seeking CAR T-cell therapy need to travel to Asia or the USA for treatment at a huge personal cost. I look forward to the day this can occur here.

We were honoured to host two international speakers Dr Catherine Elliot from Cancer Research UK (CRUK) and Professor Nasir Rajpoot from Warwick University, UK.

CRUK is the largest charitable funder of research in the world. Last fiscal year it spent UK £399m (NZ$902 million) on research that has directly benefited their patients. Since the early 1980s, it has taken 170 new drugs into early clinical trials. Dr Elliot’s message was on the value of partnerships and the financial and societal gains made by investing in research.

You will read more from some of these amazing people in this newsletter and we will be sharing information from them with you over the year. The biggest out-takes must be the need to keep working together to defeat cancer. I believe it can be or at least controlled.

To do this, we need to invest in our researchers and research. The only reason these amazing advancements are not already providing good outcomes for our communities is the lack of funding. Imagine if everyone in New Zealand gave a dollar to research.

I would also like to congratulate one of our supporters, Parks Towing. This business will be celebrating their 100th year in business next week. This is a significant milestone, and we congratulate you and thank you for the many years of service to our community. It is really important to us that as a small community we all support each other where we can. This month a staff member has listed their house with Harcourts Grenadier, and another has started the process of remodeling their kitchens with Prime Kitchens, their choices were purely driven by supporting business who support us.

Let’s keep supporting each other.

Nicola Coom, Chief Executive

As New Zealand’s cancer outcomes linger behind those of other OECD countries, more and more New Zealanders are taking advantage of the US2.37 billion investment China has made in the development of CAR T-cell therapies since 2013.

Dr Lily Zhou, who travelled to Christchurch to speak at the Cancer Society’s inaugural conference, In Pursuit, works at Shanghai Sino United Hospital. She has offered free consultations to more than 10 New Zealanders who have reached out for treatment. Seven of them have been treated, and some are waiting for the right time to commence treatment.

All her consultations were with adults aged from 37 to 72. They were seeking treatment for Lymphoma, including diffuse large B cell lymphoma, Mantle cell lymphoma, Primary mediastinal lymphoma, Central nervous B cell lymphoma, and Multiple myeloma.

She firmly believes CAR T-cell therapy is a game changer in cancer treatments.

“There have been some remarkable responses in blood cancers such as myeloma, lymphoma and leukemia.

“For solid tumour, it (CAR T-cell) is still in the early stages in the trial setting, but very promising for the future.”

Dr Zhou also said CAR T-cell therapy has also shown promising outcomes in other areas such as autoimmune disease and anti-aging.

One of her success stories, New Zealander Andrew White, knows only too well the benefits of CAR T-cell therapy, and knows he’s probably still here and well because of it.

For Andrew, a sore back that wouldn’t heal in 2008 was the first step in a 16-year journey that saw him undergo two stem cell transplants in New Zealand and CAR T-cell therapy in Shanghai.

He said his lingering sore back, which turned out to be a compression fracture, was the first indication that something more serious might be going on.  Eventually, he was diagnosed with non-secretory myeloma – a rare cancer of plasma cells in the bone marrow. Only 3% of myeloma cases are non-secretory and detecting the disease is not easy. Unlike other myelomas, it doesn’t show up in your blood.

Andrew said it was a relief to know finally what was going on.

“I was living overseas at the time, in Shanghai for work, and the specialists there suggested I go down to Hong Kong to get further tests done.

“I had a compression fracture, and the specialist suspected it might be something else causing it. I had a vertebroplasty done to stabilise the fractured vertebra and a number of tests, and it was after this that they made the diagnosis. It took quite a while.”

Following this procedure, myeloma treatment followed. Opting to return to New Zealand to be close to family, he was successfully put on Velcade – a targeted drug therapy which blocks enzymes inside cancer cells, leading to the cell’s death. Unlike traditional chemotherapy, it targets only cancer cells and not healthy ones. In mid-2009, an autologous stem cell transplant followed with the outcome of complete response.

Andrew stayed in remission with no treatment until 2014, when blood tests for free-light chains indicated that the disease was making a comeback.

“I was working in Europe, so the treatment options were good. I went back on Velcade, and they added Carfilzomib (an inhibitor drug), a new treatment not available in New Zealand then. And they added Lenalidomide (drug to slow tumour growth) which may have just become available in New Zealand.”

“It was fortuitous for me to be working in different locations where different options were available. That worked well for me. At the same time, I always kept in touch with my New Zealand specialists and caught up with them when I was home. I tested my thinking on them.”

“The doctor in Germany noted during one of our conversations that it’s often good to stay busy. He was supportive of me continuing with a busy work and personal life, so long as I also “listened to my body”. While being treated, I was able to keep up a normal work schedule, which included travel. It’s a personal thing, though, and it depends on the side effects you experience. For me I had very few.

“Being busy helps to keep your mind off it. You’ve got some normality in your life, and that helped me.”

Andrew chose to follow up the treatments with another stem cell transplant and flew home for the procedure because enough cells were left over from his first treatment and were in storage in New Zealand.

“I suppose I was in a cycle of being in remission for six or seven years and then the myeloma returned. It was probably getting more aggressive each time.

Andrew was once again in China for work, and in 2022 the free light chains in his blood once again started creeping up and he suffered broken ribs which were later worsened by a bout of pneumonia.  He was put on daratumumab in combination with carfilzomib. This treatment regime was successful and part way through 2023 his myeloma was again deemed to be in remission.

Through ongoing conversations with his Shanghai specialist, he was made aware that another relapse within a shorter period of time was a real possibility. Car-T was put forward as an option while he was in biochemical remission.  Andrew decided to go ahead and undergo CAR T-cell therapy in Shanghai.

“My treatment went really well, with my specialist and the team around her conducting everything in English. All my reports also came to me in English, often on the same day.

“I was probably in the hospital for about two weeks after the Car-T infusion. Then, it was step-by-step back to work and normality. I had the willpower to do that.

“I guess CAR-T is a lot like the stem cell transplants in some ways. In my case, I felt like I had been hit by a bus for a few days. There’s no pain, but you feel lethargic, maybe have a fever, lose your appetite, and you don’t feel like doing anything.”

Andrew said it was an expensive process, but his wife and family were behind him all the way.

“It was a lot cheaper to get it done in China than in the US, I think that’s why some other Kiwis have come here. The cost and the proximity. It’s a direct flight.”

For now, everything is going well for Andrew. He had the therapy in November 2023, over a year ago, and recent bloods taken show he’s in remission and there are still Car-T cells in his blood.

What the future holds is anyone’s guess and that is why research is so necessary to improve outcomes for people and make treatments more accessible. We’ve already come a long way.

“It would be great if the therapies could be provided in New Zealand,” Andrew said. “It would make it more affordable, but there’s also the emotional support. The value of that can’t be denied.”

Dr Zhou said Andrew is the best proof of how innovative treatment helps people to improve their lives.

“He was diagnosed with myeloma in 2008 – 17years now! Previously, four different lines of treatments, including autologous stem cell transplant, had failed.

“CAR T therapy was received in 2023, with a good response of complete remission for 15 months ever since then and he has maintained a good life quality.

“I’m very happy to see him doing fantastically well now, back to normal life and diligent work. It was also my great honor to get the chance to help him.

Her wish is that telling his story will inspire more patients who have lost hope and encourage them to look at CART therapy.

Dr Zhou said CAR T-cell therapy in China has seen significant advancements, particularly since the early 2010s. Chinese researchers have developed several therapies with notable success in treating hematological cancers like lymphoma, leukemia and multiple myeloma.

The first CAR T-cell therapy was approved in 2021 in China, and five other products have been granted for clinical application since. By 2025, these innovative therapies – Yescarta / Carteyva / Fucaso /CNCT19/ Zevor-cel/ Carvykti\Chimeric antigen receptor (CAR) T-cell therapies – had achieved notable success in treating hematological malignancies in China.

“Over the past decade, the landscape has evolved significantly. CAR T-cell clinical trials were instigated in 2013, and by 2017,  China had become home to the largest number of related trials. By 2021, funding for cell therapy companies reached a cumulative US$2.37 billion, alongside a marked increase in clinical trials and basic research.”

Dr Zhou said this surge could be attributed to several factors, including strong government support, substantial capital investment, high patient demand, a distinctive healthcare system, and the dedication of Chinese physicians and scientists.

About Lily Zhou

Dr Zhou has been working as a hematologist for more than twenty years and participated in the clinical trial of BCMA CAR-T seven years ago.

Her interest in CAR-T cells was driven by a desire to provide her patients with a better outcome. She said for many years, the traditional treatments of blood cancers were chemotherapy and radiation therapy and although these methods help to improve the condition, most patients still had a poor prognosis.

“In recent years, immunotherapy has great potential in tumor treatment. Chimeric antigen receptor T-cell immunotherapy (CAR-T) uses the patient’s own T cells to better recognize and attack cancer cells, which helps to produce deeper and longer remission with remarkably good results in the treatment of hematological tumors.

“In 2017, the FDA approved the first CAR-T for the treatment of B-cell acute lymphoblastic leukemia (ALL). In October of the same year, the FDA approved CAR-T to treat B-cell lymphoma. In order to improve and enhance the therapeutic effect, CAR-T has become a research focus in recent years.

“As a hematologist, I`m very happy to help patients with leading technology and revolutionary promising treatment for blood cancers, and China has the most CAR T-cell therapy activities in research and clinical application.”

Dr Zhou has been working in the hematology area since 2004 with an MD & PhD, two- years postdoctoral scholarship in University of California in San Francisco, mainly focusing on the individualized therapy against myeloma. She explored the mechanisms of relapse and the combination of targeted/immune/cell therapy to improve treatment in the hematology area.

Currently, she is working with different centers of cell therapy with commercialised CART drugs and clinical trials.

Jen Simon is just 32-year-old and she’s already in the fight of her life battling grade 4 Anaplastic Astrocytoma, a rare form of brain cancer.

After Jen was diagnosed in 2020, she went looking for help and found the Cancer Society a great source of support. So impressed with their efforts, she wanted to help them in the work they do – supporting people diagnosed with cancer and their families.

“I am honoured to be working alongside them as their partner with Relay for Life to celebrate the lives of cancer patients and their caregivers, remember those we have lost, and continue the fight against cancer.

“If we fight together, we are stronger. And Relay for Life is such a fun event.”

Jen lived in Texas until she was 18 and then moved to New Orleans for four years of university. All up she’s lived in four countries, but New Zealand is the only place that feels like home. She lives here with her partner of seven years, Doug Barrett.

When her brain cancer was detected, it was already grade 3. Doug was with her, and her parents were waiting for a visa to come to New Zealand.

“This was during COVID so there were a lot of restrictions that caused a lot of stress for my family.”

Jen said what was great about the Cancer Society Southern, was having a place to spend time with people in similar situations. Even if they didn’t hold deep conversations, just sitting in a room with other people battling or surviving cancer made me feel less isolated.

Jen still attends the monthly group meeting, crafting, and weekly Unipol gym.

Jen said she became an ambassador for Relay for Life because she wanted to be part of a team that does everything it can to help other people.

“Reaching out to people who need support and guidance through tough times is one of the best things people can do,” she said.

New Zealand has 1200 deaths a year from colorectal cancers. That is four times the road toll and about as preventable, Professor Parry Guildford said. So why is the incident in younger age groups and in Māori and Pacific people rising?

If Otago University-based researcher Professor Guilford has his way, these statistics are about to change.

Professor Guilford was a keynote speaker at In Pursuit, the Cancer Society’s inaugural conference and his work was a major attraction.

He blames constraints, costs, and resources for the worsening statistics. He lays responsibility for the outcomes at the feet of three things:

1. Centralised diagnostic services and decision-making
2. Risk stratification and prioritisation, and
3. Willingness to accept compromised service.

Professor Guilford said people want to be empowered to look after their families. They do not want gatekeepers who decide who gets treated and who does not, impacting their families’ futures. Nor do they want waiting lists.

“What they do want is a trusted service and accessible care, both geographically and culturally.

“To provide this we need a community-driven, early detection programme that allows communities to be involved, and accessible cancer testing technology.”

Professor Guilford said these principles were the driving force behind his research, along with a desire to prevent people developing colorectal cancer by catching it before it has a chance to take hold.

His research on accessible circulating tumour DND (ctDNA), a blood test for people with symptoms, risk factors or family history of colorectal cancer, has been well documented, but Professor Guilford wants people to understand the enormous benefits of ctDNA. The test is:

• Sensitive, and highly specific – it will not clog the system with false positive results
• Scalable, flexible, and accessible – enabling organic growth with communities, and,
• A step change on the current stool (iFOBT) – it takes thirty positive iFOBT tests and subsequent colonoscopies to diagnose one cancer.

Professor Guilford said the test will lead to reduced reliance on big hospitals, better care for rural communities and, adjunct to the National Bowel Screening Programme, reduce unnecessary colonoscopies.

So why is ctDNA such a game changer? It has the ability to pick up cancer early before it causes damage and is still easily treatable. It does this by identifying the DNA of tumour cells in the blood. Testing can be conducted widely and cheaply, anywhere from the local community center, marae, or GP office, which increases access and supports people to undergo screening.

He said ctDNA detection using the Oxfords Nanopore sequencing system has low capital cost, was portable, did not need a fancy laboratory and was highly scalable. Real-time data was also provided, which could be obtained and held locally, and would be a valuable educational resource.

“The advantages of a New Zealand grown test are enormous. It means the test is owned by the community, not an overseas corporation, not driven by profit. It would have built in equity and would be developed alongside health education with no gatekeepers.

“Delays in the system will be reduced, and we will receive instant feedback and be able to make constant improvements.”

Professor Guilford said the technology would also provide a pipeline for other cancers and hopefully provide better outcomes for even more New Zealanders.

His aim is to have the test in wide use within two years.

A new facility being built in Christchurch will see CAR T-cell therapies manufactured in Christchurch for the first time. The therapy is changing the cancer landscape by using the patients’ own immune systems to fight the disease.

The Cancer Society Southern’s recently appointed mid-Canterbury and Selwyn community coordinator, Elyse Guise, says, as someone whose family has travelled overseas for the therapy, she couldn’t be happier with the move.

Elyse’s daughter, Nora, was child number two in a phase one trial for CAR T-cell therapy targeting liver cancer in children. The trial was held in Houston, Texas, in 2019 and the need to travel was one extra stress for an already stretched family.

As a five-year-old, Nora was diagnosed with a particular type of cancer which Elyse describes as a mix of child and adult liver cancer.

She had undergone the normal protocols of chemotherapy and surgeries twice, but the cancer metastasized to her lungs and even after more mop-up chemotherapy, it kept returning. A new protocol was trialed on the little girl in an effort to improve her outcomes and then a switch made to an inhibitor drug, but the cancer was stubborn.

“The inhibitor was almost like immunotherapy but in a pill form, but neither it nor the new protocol worked so she was placed in the palliative care team,” Elyse said.

“The CAR T-cell was presented to us when our oncologist went looking for what else was out there. We investigated and we wanted to give Nora every chance. She was patient number two of a phase one trial. When we signed up, I don’t think patient number one had even been treated yet.”

Elyse said they flew to Houston in October 2019. Nora’s blood was taken soon after arrival and sent to have the therapy manufactured. The therapy works by enhancing the T-cells ability to find and kill cancer cells. Each therapy needs to be targeted to the type of cancer.

“They took quite a lot of it (blood). It made Nora a little woozy, so they did it over two days.

“We flew back home six weeks later. We were at the hospital for five weeks. They gave her some mild chemotherapy for three days after (the therapy) just to knock the white blood cells out, and we had to stay there for follows-ups for the next three weeks.

“Liver cancer puts out a protein, AFP, and it helps them figure out whether the cancer is dying or growing. When we went there, Nora’s was in the mid-2000s, and they checked it again before we left, and it had gone down. It had dropped, I want to say to the 800s. It (the therapy) had definitely done something.”

Once they got home Elyse had to do blood draws, and then it was a race across town to get it into the FedEx fridges within a certain time frame. The blood was then FedExed to Houston where an AFP draw was done. Sadly, it showed the levels had gone back up.

“That’s when we knew it hadn’t worked.”

Just two weeks later, just short of her seventh birthday, Nora passed away.

Elyse said some kids probably wouldn’t have managed all the treatments, but Nora just did.

“She was a star, an absolute star. She put up with so much and when we had to tell her again that we’re going to do something else, she said that’s fine. She was absolutely brilliant.

“She had very old soul qualities.”

Elyse said when the option of the trial had come up, they were just about resigned to the fact Nora was nearing the end, and they were going to focus on spending time together and hoped they had as long as possible.

“And then we were dangled a carrot, almost like she’s going to live, and I would love to say I thought the entire time it was going to work. We were definitely hopeful, but it was a phase one trial and a limited dose. I felt a lot safer with it being a limited dose because people can go into shock. I didn’t want that to happen when you’re literally half a world away. At the same time, I absolutely wanted it to work.”

“I look back and think if we’d stay here, she’d be at school and carrying on with normal life. But over there it was just me and her mostly. I got to spend so much time with her. That was so precious.”

Elyse said it would be amazing if they could manufacture the therapies here because it’s so hard to go through it all so far away from home and home country.

“And you have to find the money. That’s (the amount) ridiculous. I had to do things I thought I’d never do to get money.

“Not in terms of illegal or anything,” she added with a laugh. “But I had to go there’s this absolutely horrible story about my child, please take it in and spread it around. We didn’t consider safety or anything.

“We just needed the money so desperately. So, I said yes to absolutely everything,

“If families had the opportunity to not have to find that money because the treatments done here not overseas, that would be incredible.

“Especially when it’s a last-ditch hope, being able to do it in your own country would be such a big financial and emotional thing.”

Elyse said it was already stressful and having to find that much money, well she didn’t sleep a lot during the six weeks of trying to find $200K.

“It was horrible. The US system is insane. I still shake my head at the amount of money we spent and what it was for.

“$200K didn’t even include manufacturing the T-cells. We only paid for the chemo and time in hospital because the therapy was part of the trial.

“I have no regrets. We tried everything including crossing the world. While it’s horrific and it’s a horrible thing to have to do, I’m also so grateful that we did it. I can’t say oh maybe if we’d gone then she’d still be here. Like, I know we did absolutely everything.

Elyse said Nora’s cancer was a solid tumour and CAR T-cell therapy for solid tumours has not proven as successful so far as for blood and other cancers. Although, the field is advancing.

What is CAR T-cell therapy? It is a therapy which uses the body’s own immune system to fight cancer. Doctors take some of your T cells (a type of white blood cell) from your blood and modify them in a lab, adding a special gene to help them recognize and attack cancer cells. The modified T cells are grown in large numbers and the supercharged cells are put back into your bloodstream. Once in your body, they find and destroy cancer cells.

The new CAR T-cell therapy manufacturing facility in Christchurch is being opened by BioOra, a collaboration between the Malaghan Institute and Bridge West.

Managing Director John Robson said the focus for the Christchurch facility is on non-Hodgkins’s lymphoma which he believes can be produced at a fraction of the cost of other countries.

John is so confident in the product and their business pathway that he’s leading the construction of the new cell therapy manufacturing facility in Christchurch.

The build is expected to start in Q2 this year, (2025) with completion scheduled for March 2026. After that comes a three-to-five-month period for commissioning of the labs and obtaining a MedSafe license to become fully operational. They have a target date of between June and August 2026 to open.

John believes this will soon become a campus for similar ventures.

John said in the first year, 400 doses would be manufactured, more than enough to provide a treatment for all New Zealanders who needed it.

Here at the Cancer Society, we simply couldn’t do what we do without the generosity of our incredible funders. Your support isn’t just about dollars, it’s about people. It means whānau facing cancer have someone to turn to. It means life-changing research happens right here in New Zealand. It means our teams can be there, on the ground, making a real difference when it matters most.

Dunedin City Council – Community Grants • Pub Charity • Happy with That Trust • Jones Foundation • New Zealand Charitable Foundation • Air Rescue Services • Foodstuff Community Trust • Buller District Council • West Coast Community Trust • Cusack Charitable Trust • Thomas Hobson Trust • John Lemon Charitable Trust • Harry J Wilson Trust • Alexander McMillan Trust • Perpetual Charitable Fund • Grassroots Trust • Lion Foundation • Southland District Council • Community Trust South • TTCF • Bowls Southland • Aoraki Foundation • Mainpower NZ • St Joans Trust • Tasman District Council • Christchurch City Council • Dunedin City Council • Aoraki Foundation • Estate of William Harold Meek Charity • William Sherriff Charitable Trust • Selwyn District Council • Chenery Memorial Trust • Music Helps • NZCT • Kiwi Gaming Foundation • Estate of George Sevicke Jones • Forest Road Trust • Oamaru Community Fund • Aotearoa Gaming Trust • McKenzie Hospice Fund • Alterno Foundation • Emma J Price Charitable Trust • George Sevicke Jones Estate • Advance Ashburton Community Foundation • Kiwi Gaming Foundation • Manchester Unity Welfare Trust • Guy Answer Waddel Charitable Trust • Alexander McMillan Trust • Otago Community Trust • A&R Edgar South Canterbury Trust • Christchurch Casino • Meridian Waiaki Power Up Fund • Central Lakes Trust • PA Blackmore Trust • Coates McKay Charitable Trust • Aotearoa Gaming Trust • Bill Torrance Charitable Trust.

We’re beyond grateful.