David Meng found it strangely difficult to believe he was dying.
He knew he was sick – a barely-functioning immune system; two months of constant fevers and coughing from an intractable fungal lung infection; so much muscle-loss that he couldn’t sit on a chair without a cushion to pad his sitting bones. But death? It just didn’t seem possible.
Yet his doctor was clear – if they didn’t act soon, he was in very serious trouble.
The dilemma was this: the transplant David had received two months earlier using bone-marrow cells donated by his father had failed, meaning he needed a repeat transplant. But having a second transplant while he was still fighting a lung infection was considered an unacceptably high risk, which was why for eight long weeks the doctors had been holding off.
Yet with every passing day, Meng was losing more strength, and now he was being told that if the doctors waited until the lung infection was completely beaten, he might be too weak to survive the transplant process.
“I was,” says Meng with characteristic understatement, “a little surprised at the seriousness of the situation.”
“Either wait for a kind of eventual death, or take a gamble and seek death out. “
Meng, 33-year-old business consultant who lives on Auckland’s North Shore, remembers how his mother – herself a doctor – broke down as the clinical haematologist explained the situation. Yet for Meng the decision seemed an easy one: he was really tired of the vomiting, diarrhoea, rashes and constipation; of the coughing and the three-hour cycle of fevers; of the blood tests and injections and drips that had turned his arms into pincushions.
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“I’d been lying in bed for two months. I didn’t even flinch. I just said yeah, let’s do it.”
Meng didn’t realise it yet, but he was about to be the beneficiary of a remarkable act of community spirit. The high-risk transplant did in fact take him to the brink of death, but then 21 strangers, none of whom he’d ever met, agreed to endanger their own health in order to create a complex supply chain of life-saving medicine tailormade just for him.
Twenty-one times, a network of nurses, doctors, technicians and administrators prepared a concoction made of specialised white blood cells called granulocytes, which were then shuttled to Meng’s hospital bedside and poured into his bloodstream so they could disseminate through his body and attack the bacteria and fungi Meng’s own immune system was unable to combat.
It’s a rare, complex and expensive therapy, used just a handful of times each year in New Zealand. It is only used on patients who are in a grave condition, and it doesn’t always work: a recent study by NZ Blood Service found that around 77% of recipients were still alive 30 days after receiving their transfusions. David Meng is one of those who made it.
In New Zealand, granulocyte donations are collected only at NZ Blood Service’s donor centre in Epsom, Auckland. The same centre also distributes whole blood, blood plasma and platelets, and whisks up a dozen or so other products used to treat conditions including shock, liver failure and haemophilia. Perhaps their creepiest product is the bottle of eyedrops they can make for you out of your own blood serum.
But even by these standards, granulocyte transfusion therapy is something out of the ordinary – a treatment that’s wheeled out only for a specific type of patient in a specific kind of peril.
Transfusion medicine specialist Dr Richard Charlewood says the typical granulocyte transfusion therapy patient is either someone with leukaemia whose chemotherapy has wiped out the bone marrow cells along with the cancer cells, or someone with the rare condition aplastic anaemia (where the bone marrow fails to make enough blood cells) who has received similar treatment as a prelude to a bone-marrow transplant.
In either case, the treatment temporarily obliterates the patient’s immune system, and until their immunity has rebooted they need to be isolated in a special hospital ward with plenty of high-powered antibiotics and anti-fungals close to hand. But if an infection still takes hold, and the usual medicines don’t work, that’s when the call goes out to the Blood Service.
“We have a policy on who can get the granulocytes,” says Charlewood.
The patient needs to have an extremely low white blood cell count, and they need to have tried at least two different combinations of antibiotics already without success.
Unsurprisingly, the typical granulocyte patient won’t be looking good.
“They’ll be feverish and feeling sick. They’ll often have low blood pressure, a fast pulse, and various organ systems taking strain – the kidney, the liver, the lungs. They may be on a ventilator. They’re not at all well.”
Yet the policy also dictates that, apart from their acute, life-threatening infection, the patient must have a reasonable prognosis.
“This is not just a last-ditch attempt for someone who’s not going to make it.”
Meng has aplastic anaemia rather than leukaemia. When he was diagnosed in his mid-20s during a routine blood test he was told that his levels of white blood cells, red blood cells and platelets were all so low it was a miracle he was standing up. Since then he’s lived a more-or-less ordinary life with the help of blood tranfusions and some powerful immunosuppressive drugs. But over time the effectiveness of those treatments waned.
So early this year, Meng received his first transplant. First, his own failing bone-marrow was nuked with a brutal combination of chemotherapy and radiation. Then cells from his father’s marrow were sucked out directly from the bone before being infused into Meng’s bloodstream.
Once in Meng’s body, they were meant to find their way to where the old bone-marrow used to live, take up residence and restart the production of blood cells. And at first, things seemed to go well. He went home after just a few weeks. But then he started getting fevers and was rushed back to hospital, where tests showed the transplant had failed.
Two months later he was still in hospital, enduring infections that just wouldn’t quit, and waiting for the repeat transplant that could cure him – or kill him.
When the decision to go ahead with the second transplant was finally made, the Blood Service was put on notice that Meng might need some extra help during the post-transplant period. Sure enough, he did.
When a patient needs a batch of granulocytes, apheresis coordinator Charlotte Carroll logs into the Blood Service donor database then gets on the phone.
The database helps her find donors whose blood-type matches the patient, but she also needs to talk to them in person, because her request is a little out of the ordinary. What amazes Carroll is that just about everybody says yes.
Donors are asked if they’re willing to receive an injection of a “granulocyte colony-stimulating factor” (GCSF) the day before they donate, and also to swallow two steroid pills (which also help boost white-cell production). There are potential side-effects, including trouble sleeping, restlessness, bone pain and – in extremely rare cases – serious reactions such as a spleen rupture. For this reason, the donations are one-offs: someone who gives a granulocyte donation this way will not usually ever be asked to do it a second time and never again after that.
Handing over your granulocytes is also rather less convenient than donating a unit of whole blood. The donor lies in a hospital-style bed in a special room at the Epsom donor centre. Blood is drawn from a vein and pumped though a computerised centrifuge that extracts the desired granulocyte cells (along with some plasma and tiny quantities of all the other cell types). Then the remainder of the blood is redirected back to the donor via a second vein. The whole process takes two-and-a-half to four hours.
The soup of granulocytes and plasma is then analysed (to be medically useful there need to be a minimum of 10 billion granulocytes in a unit), safety-tested for diseases, irradiated, insulated against excessive heat or cold, packaged, labelled and couriered – all within the tight 24-hour window before the cells became unusable. If the granulocytes need to be flown somewhere outside Auckland, the timeline gets even tighter.
All that for a single 200ml dose. So for a patient like Meng, who needed 21 doses, Carroll had to book in 21 donors, only locking in each appointment a few days ahead, based on the latest update from his clinicians.
The final step of the journey starts at the hospital bedside, when the bag of the granulocytes is transfused directly into the patient’s bloodstream over the course of an hour or two.
Once installed, the visitors can get to work. The bulk of the granulocytes are “neutrophils”, a sub-type that’s hard-wired to attack any bacteria and fungus it encounters, without needing to learn about specific threats. Neutrophils, says Charlewood, “are the Pacmen of the immune system: they just go around eating things.” They dash about, do their chomping, then die. You’ve seen a collection of dead neutrophils before: they’re the main constituent of pus.
Transfused granulocytes work pretty fast, says Charlewood, but it’s not a Hollywood-style instant cure.
“It normally takes a couple of days for infections to start settling, because the white cells have to get in there, find the bacteria or fungus, and start killing them.”
Eventually, the patient should start making their own white cells, and the granulocyte transfusions can stop.
Charlewood has seen some remarkable recoveries. There was one patient in intensive care who was so sick that his consultant haematologist, who was taking a fortnight’s leave, “basically said his farewells to the patient. But when he came back, not only was the patient not dead, he was at home, doing just fine.”
Curiously, the effectiveness of granulocyte transfusion therapy hasn’t been confirmed with a randomised controlled trial – the gold standard of medical proof. Charlewood says that’s simply because the therapy is currently used so seldom, and in such specific situations.
“There’s been an attempt to do an international randomised control trial, but they struggled to get the numbers necessary to draw any conclusions.”
As a result, some clinicians believe granulocyte transfusion therapy works and others aren’t so sure.
Charlewood doesn’t like the word “believer” – “but my reading and my experience with the cases we’ve been involved in would suggest that it does work, and that we’ve been able to turn around patients that would not otherwise be expected to survive.”
I’d hoped to talk to one of the granulocyte donors whose cells had ended up in David Meng specifically, but the Blood Service has tight privacy rules forbidding them from connecting donor with recipient (though they do have a rather cute smartphone app which alerts you whenever a unit of your donated blood has been used somewhere).
I did, however, get on the phone to a granulocyte donor whose cells ended up in someone other than Meng.
Aucklander Brett Maitland, 58, has been donating blood for 25 years. Every three weeks he pops into the Epsom centre for a couple of hours to donate platelets. He happens to be blood type O, and he always tests negative for the common virus CMV, meaning his blood is perfect for use in babies. One time he learnt that a single donation had been split into 50 tiny portions, each the right size for use by a premmie in intensive care.
Maitland was in his car when he got the phone call asking if he’d donate some granulocytes, and he said yes right away. He had no qualms about the injection and the steroid. They talked him through all the risks and side-effects but really, says Maitland, it was no big deal. He knows nothing about the patient who got the benefit of his granulocytes, “but you know you’re doing something good”.
David Meng wasn’t especially aware that he was receiving a miracle drug gifted to him by 21 strangers. He was pretty crook at the time, and was being pumped full of a huge variety of substances. He also didn’t know that at 21 units, his was one of the longest courses of granulocytes ever used in New Zealand.
But once the fevers had stopped, and it was confirmed that the second bone-marrow transplant had taken and he was producing his own white blood cells again, and once he’d gone home to his parents’ place and begun the incredibly slow process of regaining his strength and weight and muscle-tone, he did learn a little more about how granulocytes had helped him out of danger.
It hasn’t been easy going since then. There’s been more vomiting and diahorrea and fevers and shakes; there were viral infections, and a skin rash caused by his own immune system clashing with his father’s transplanted bone-marrow cells. Chemo left his feet slightly numb. He still takes a small handful of drugs every day, though far fewer than he used to. His immune system is still compromised, so for now he has to avoid sick people, salads and raw foods.
“I’m missing my sushi.”
When we talk, its been 100 days since the second transplant, “and it’s only the last couple of weeks that I’ve been really good. I can drive. I can walk. I’ve had the mental capacity to read a book, and things like that.”
Without the granulocyte transfusions, says Meng, “we don’t know what would have happened. But from the doctors’ perspective I was in a pretty dire situation, and that was the only option they had”.
He’s amazed that so many strangers were willing to give up their time, and even take a risk with their own health, to help him out like this. He feels pretty lucky to live in a country where he’s been looked after so well. He’s impressed that there are scientists and doctors smart enough to figure this stuff out.
“Modern medicine is amazing, isn’t it.”
* For more information on the NZ Blood Service, or how to donate blood yourself, see www.nzblood.co.nz.
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