Thursday, 28 March 2013

Treatment begins again ...

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Quite remarkably, given that Adam developed a potentially life-threatening infection on our first day in Grand Rapids, we are just finishing week one of his new treatment combination on the molecular-guided therapy trial that we've enrolled him on. Clearly we could have done without Klebsiella Pneumoniae rearing it's big, fat, ugly, head but to think we haven't lost a single day time-wise as a result is almost beyond belief.

With Craig doing his sterling work we got out of the hospital on the 15th with antibiotics and supplies to do Adam's infusions at home (or in our case Renucci House) until Tuesday night -- making a total course of 10 days IV ertapenem. His white blood cell and neutrophil counts were on the up, a good sign of his body's growing ability to fight the infection itself, though still someway short of where they ideally needed to be. And so began the daily routine; 7am antibiotics out of the fridge, 8am flush, 30-minute infusion, flush, heplock; 7pm antibiotics out the fridge, 8pm …

All went without a hitch; my first test in home nursing and I passed with flying colours. Although I must confess, after the best part of four years watching nurse after nurse pushing stuff into Adam's veins, the very first time I started applying pressure to the syringe it did feel just a little bit odd to be doing it myself.

We'd arranged to have Adam's blood counts rechecked on Monday, having given him a G-CSF shot on Saturday and skipped Sunday. As we'd hoped, his counts had continued to improve, and his neutrophils at 3,000 were now right where we wanted them to be. None of his repeat blood cultures had come back positive for infection. His sodium, potassium, albumin, and creatinine levels, which had been all over the place during the previous week as the stress of the infection took it's toll, were back within normal ranges. The whole situation was beginning to look brighter.

The last antibiotic went in on Tuesday evening and on Wednesday morning we took Adam up to clinic to have his port deaccessed -- blessed relief for the little boy who'd been accessed for 12 days straight except for a couple of hours between line changes. As Adam has a port now (as opposed to a hickman) he doesn't always have a line attached -- when he does that's referred to as being accessed. Otherwise he just has the port site on his side under the skin where the line into his vein is channeled up to. His movement is restricted when he's accessed, and he finds it difficult to sleep lying on his right side.

We saw Dr Sholler at clinic and she told us the tumour analysis was going well -- the genomics report should be available on Thursday with a view to resuming treatment on Friday.

We returned back to Renucci House, and after he'd had a couple of hours sleep during the course of Wednesday afternoon I checked Adam's temperature. He had been snuggled under the duvet -- we brought his own duvet and pillow out with us this time for added comfort -- and he felt a little hot. 38.6°. Shit. Or worse.

We don't generally panic any more, we've been doing this stuff far too long for that. But I can tell you -- this was worrisome. Having been warned that the infection Adam acquired was a particularly nasty one, having been told several times that it has a habit of coming back even after antibiotics, and having listened to the senior doctor on the ward saying he hoped Adam would recover, who wouldn't be worried? We pulled his duvet back and over the next 5 or 6 hours watched nervously as his temperature fluctuated around 38° -- 38.1°, 37.8°, 38.0°, 38.1°, 37.9°, 37.9°. Alison had packed the overnight suitcase, and we were all ready to make the call to be readmitted to the hospital. Another reading over 38.5° and that was it; back to the hospital, back on antibiotics, unable to start treatment on Friday -- and that was supposing the infection wasn't even back. If it was, if the 10 days of antibiotics and Adam's recovering immunity had failed to deal with it, what then? I decided I wasn't even going to bother going to bed. At 01:00 Adam's temperature fell to 37.4°, followed by 37.0° at 01:30, and 37.2° at 02:00. And at that point I breathed a massive sigh of relief and called it a night.

When Adam woke on Thursday his temperature was still normal, where it remained throughout the course of the morning and afternoon. The evening followed a similar pattern to the night before; temperature rising, though this time not quite as high, and for not quite as long. Whilst staying vigilant, and checking regularly, with the benefit of the previous 24 hours we weren't quite as worried this time. On Friday morning Adam's temperature was again perfectly normal, and we've not had a repeat episode since. I have no idea what the cause was, I'm just thankful it wasn't worse, and it didn't lead to anything.

On Friday we met Dr Sholler to discuss the new treatment plan. Adam needed a blood transfusion, and it turned into a long day in clinic as a hastily arranged electrocardiograph and echocardiogram were required to monitor potential side-effects of the new targeted combination therapy; thalidomide, dasatanib, and pravastatin. These drugs, amongst others, scored highly on Adam's genomics report and this particular combination was then selected by a panel of oncologists based on Adam's individual circumstances, history, etc.

Each cycle of treatment consists of 28 consecutive days of these three oral drugs, and the first cycle must be completed at the study hospital. Which means Adam will be out in Grand Rapids until mid to late April at least. We always expected this, the only variables being whether Adam was going to be well enough to even enrol on the study in the first place, and after that whether each cycle would be 21, or 28, days in duration. The big shock came when we found out the cost; thalidomide in particular is crazy expensive. The cost of a 28-day supply of the drugs is around $25,000. We are ever thankful to have the NB Alliance supporting us, and Adam's Appeal funds to give Adam the opportunity to hopefully benefit from this new trial.

Adam has tolerated everything well so far; thalidomide has a sedative effect and so is taken just before bedtime, apart from that there are no other restrictions. He's been suffering from various aches and pains, including a recurrent and persistent one in his lower back, but we are managing things reasonably well. We have to balance effective pain relief against the inevitable consequence that he will sleep and therefore be unable to eat or drink anything. Eating in particular remains an issue, but he's maintaining his weight at the moment and realistically that is our goal at this stage.

We discussed physical therapy with Dr Sholler, to try and improve Adam's muscle strength, mobility, etc. She suggested aqua therapy, and with Adam being keen we went along to a pool on Wednesday to give it a go. Alison and I came out with the same very mixed emotions. Adam, bless him, tried his absolute hardest, and he was so keen to get in the water. It's been a long time since we've seen him like that -- he even tried swimming under water to play trick on his new therapist. Unfortunately the pool was just too cold, colder than it was supposed to be; for a little boy with zero body fat and incapable of vigorous movement he was shivering within minutes and we had to get out shortly thereafter. But we've not given up. Adam's is happy to try again so we are in the process of finding a different, warmer, pool that we can go to. Providing it works out, and his immunity remains high enough, this will hopefully become a regular activity.

With the Easter holidays here, Jake and Jess are going to fly out next week to be with us. They're being escorted to Heathrow by grandparents and then flying out by themselves. Either Alison or myself will be there to meet them at Detroit airport when they land. We've rented a place by Lake Michigan, and just hope Adam stays out of the hospital and well enough that we can make the most of the time we'll all have together. They are amazing children my eldest two, getting on with their lives as they have in spite of everything that has gone on with Adam over the years. I do miss them though. Jessica was just finishing infant school when Adam was diagnosed; she'll shortly be starting her final term at junior school. It sometimes feels like her growing up has completely passed me by.

This is a photo of Adam and Jessica taken just a few weeks before he was diagnosed in 2009 …

Adam Jess

Friday, 15 March 2013

A Week In The Life: Infections, Scans, Biopsies, Home Infusions ….

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Adam is still in the hospital. This is his eighth day of incarceration, each one costing a small fortune. He has remained afebrile since last Friday, and repeat blood cultures continue to come back negative for ESBL Klebsiella Pneumoniae bacteria. This is, of course, great news, but we regard it with caution. The infection he acquired is a particularly nasty one that can return even after treatment with antibiotics, and negative blood cultures do not necessary mean there is no bacteria remaining anywhere in Adam's body.

The name Klebsiella Pneumoniae suggests Adam has pneumonia, but he does not. He has bacteremia - the bacteria found its way into his bloodstream which is what makes it so dangerous, particularly in an immunocompromised patients such as Adam. All that said, things are heading in the right direction; no fevers, negative blood cultures, and Adam's white blood cell count (a measure of his body's ability to fight infections itself) has risen steadily with each passing day. Today it's 1.5, we want it to get to around 5. However, 1.5 is a lot better than the 0.03 that it was when he was first admitted.

Looking back on the past week we actually got very lucky. Adam spiked a temperature on our first morning in Michigan, it could easily have been the day before at 30,000 ft over the middle of the Atlantic; the bacteria infection clearly responded to the broad-spectrum antibiotics which isn't always the case; and we had positive cultures and sensitivities back from the microbiology lab that allowed us to change to a targeted antibiotic within two days of admission to the hospital.

Such is the fine line that we often walk in the world of paediatric oncology …

One of the things I love about Dr Sholler is that she 'gets it' as far as what parents go through on this terrible journey. She didn't encourage us to come back to Grand Rapids, and she didn't discourage us either. She made it clear Adam would be welcomed back, but it was our decision to do what we felt was right. A few weeks ago Adam was in no position to come back out here, we wouldn't have even contemplated trying given where he was at in terms of pain and feeling generally awful. But then we managed to get on top of things, Adam became far more settled, and coming back out went from feeling like the wrong thing to being the right thing.

The plan for our visit was FDG-PET/CT on Monday, with bone marrow and lymph-node biopsy Tuesday for enrolment on the new molecular-guided therapy trial that opened here only last week. Ordinarily an infection of any sort will scupper any and all plans for therapy, but the team here got Adam prepared for Monday's scan and it went ahead as planned. He was still pretty wiped out, but apart from having to consume a contrast drink the scan doesn't require much else from Adam himself. Unsurprisingly he slept through the entirety of it.

Scan results showed progression. Of course that's horrible news, but it wasn't anything we weren't expecting. It says something when you're pleased that the scan isn't as bad as you thought it would be. There was an interval increase in intensity of the skeletal uptake, growth in the lymph nodes, all of which are now at least partially calcified, but no new areas of disease. It wasn't catastrophic, it wasn't 'get-back-on-a-plane-and-return-home-again' bad.

And so to Tuesday. If the PET/CT scan was looking shaky at one point, the prospect of bone marrow biopsies, and a long needle lymph node biopsy, on a child with an ESBL infection and zero neutrophils, might be expected to be a complete non-starter. The idea of enrolling on a clinical trial whilst getting treated as an inpatient equally so. But things are not quite the same with Dr Sholler. There are rules for sure, you cannot go on study with an active infection, period. But there is also flexibility, and a consideration of the big picture. There are competing risks, big and small, some more immediate that might warrant delay and others less immediate but that would increase with the passage of time; some lines that can't be crossed, and other boundaries that can pushed a little. How did we feel about going ahead despite the current situation, after all Adam was on strong antibiotics? Delaying biopsies beyond Tuesday/Wednesday would mean the analysis reports coming back a full week later, meaning another week before Adam could begin treatment even if he were well enough to sooner. Provided blood cultures taken Sunday morning remained negative 48-hours later on Tuesday morning (which they did) Adam would be eligible for the trial. For me it was a simple decision. The bigger question mark was whether the interventional radiologist would be prepared to perform the procedure given Adam's condition and blood counts; we left Dr Sholler to sort that one out. We had our answer when, during Monday evening, the nurse came in to say Adam would be getting platelets overnight in readiness for the following day.

Monday night was one of those horrible hospital nights. Machines beeping, interruptions, platelet transfusion, monitoring vitals, blood draw, monitoring vitals again; we didn't really get any settled sleep until 4am. And of course on the day Adam had to be nil-by-mouth he woke up complaining that he was hungry - something I'd not heard him say for weeks and weeks. From telling him he's got to eat and at times practically force feeding him, I'm now saying he can't have anything to eat until mid-afternoon! Well, I didn't actually say that, of course, I just told him he couldn't eat yet for a while. If you repeat that enough times over and over eventually you get to a point where you can say 'another half-an-hour and you can have something to eat and drink'.

Adam was as grumpy as grumpy can be on Tuesday. He just gave off this look that said 'You'd better have a very good reason for talking to me … or don't.' Not many people did. He lacked sleep. He was hungry. He was apprehensive about what was coming, he knows how it feels afterwards. If he wants to be grumpy under such circumstances I figure that's his prerogative. The anaesthetist was very approachable and listened to us explain Adam's post-anaesthetic apoplexy after getting propofol. He was more than happy to use ketamine in the first instance, and only resort to propofol if Adam started to move - clearly being totally still is rather important whilst undergoing a needle biopsy that goes in through the back, down past the kidney and into a lymph node in the pelvic region. Everything went to plan, the team got what they needed and Adam returned to the recovery area in a spaced-out ketamine-induced sleep. Only a small amount of propofol was required, and thankfully Adam woke up slowly and without adverse effects (ketamine can cause waking nightmares). As an added bonus he took longer to wake up than usual, which was also helpful as he's not allowed anything to eat or drink for another two hours after the procedure - in case he suffers an internal bleed that requires emergency surgical intervention.

Tuesday night was another rubbish night, but for a different reason. All the sleep Adam had during the day meant he wasn't able to settle down at his normal time. So on Wednesday he was grumpy as grumpy can be. Again. From lack of sleep, and a very sore back complete with three fresh new holes in it.

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Since then Adam has gradually improved; the pain in his back from the biopsy sites has receded, he's had a couple of very good night's sleep, and he's been eating and drinking alright too. We don't have anything planned now in terms of treatments or procedures until after the analysis reports on Adam's biopsies come back next week. Which hopefully means we have a full week to get clear of this infection completely. In which case, rather miraculously, we will not have lost any time as a consequence of Klebsiella Pneumoniae.

This afternoon we've been discharged back to the Renucci Hospitality House to continue Adam's antibiotic treatment as a home care patient. Tonight we have a nurse coming to us, to train me how to manage Adam's line and administer the twice daily infusions. Each dose is provided in a separate self-infusing portable pump that we will keep in a special fridge back at Renucci. We have a plan for next week in terms of going into clinic to check counts, have blood taken for repeat cultures, etc. But if this works out we're done with being an inpatient; it'll be me infusing, flushing and hep-locking for the next four days. How cool is that? Adam's pain remains under control with the fentanyl patches we're using. It's our fervent hope it remains so, and we get through to the resumption of treatment without further setbacks. We are also realistic enough to know that with this disease not only does it not always work out that way, it doesn't often work out that way …

It wouldn't be right for me to finish this update with saying something about the care Adam has received in the week that he's been inpatient here at Helen DeVos Children's Hospital. I know I speak very highly of Dr Sholler, but across the board the doctors and nurses that have been looking after our little boy have been exemplary. There are a few annoying rules, but I can hardly blame the individuals that have to abide by them can I? And even then, we've been listened to and our wishes accommodated as much as has been possible. Nobody has broken the rules for us, but they may have been bent a little once or twice for Adam's benefit. And to me that's the only consideration. Always. It's not about me, or Alison. It's about making adjustments here or there, sometimes seemingly trivial or minor, that make Adam's life just that bit more comfortable. But never anything that exposes him to additional, or unnecessary, risks. And finally, extra special thanks to Craig … without whose efforts we'd still be in room 903 in the hospital, instead of room 306 in the hospitality house.

Sunday, 10 March 2013

Not great news ...

Adam has a multi-antibiotic resistant (ESBL) form of Klebsiella Pneumoniae. We've changed to a completely different type of antibiotic that bacteria from Adam's blood culture displayed sensitivity to in the lab. Although the broad spectrum antibiotic he was on before has clearly had an immediate beneficial effect, if we continued on this path the bacteria would just up-regulate its resistance gene to overcome it.

We are now under isolation control, and had a visit from the infectious diseases team earlier this morning. All staff entering Adam's room must be gloved and gowned, whilst Alison and I are not allowed to enter the communal areas of the ward. Moreover, Adam will need to be gowned and isolated whilst in the hospital for the next six months to a year. Now we know Adam prefers to have his own room whenever possible, but as Alison told him earlier this is a rather extreme way to go about it.

Adam's immune system remains very low; he is getting daily shots of G-CSF and it will be very important to see his white blood cell count improve over the coming days in order for him to fight off this infection as quickly as possible. We are still on track for a PET/CT scan tomorrow, but beyond that we don't yet know what impact this is going to have in terms of treatment. My instinct is a lot, but we'll see. It's anticipated that antibiotics will continue for the next ten to fourteen days. At present Adam remains reasonably well and has been afebrile since Friday evening, which is something at least.

Saturday, 9 March 2013

Back in the U.S.A. ...

We are back in Grand Rapids.

Adam had a reasonable week last week, generally free of pain and ok(ish). After a lot of back-and-forth we seem to have figured out the right combination of pain meds that he requires for now to keep him comfortable. So we put together a hastily arranged plan to fly back out to see Dr Sholler, re-evaluate Adam's disease, and discuss treatment options. The support we've received from Dr Sholler these past few weeks has made such a difference; we've spoken pretty much every other day including at weekends, and in between I'll get the occasional message asking how Adam's doing if we've not spoken for a while, or he was having a difficult time when last we talked. And it's not as if she isn't a very busy person.

We've also received tremendous support from our community team - we would be lost without them, and from the symptom management team at the Royal Marsden. When we spoke to Adam's consultant at the Marsden a few weeks back she made it clear that making Adam comfortable was their primary objective, but also said she would support us in whatever it was we decided to do.

Having decided we wanted to take Adam back out to the U.S. provided he remained well enough, there were practical considerations that we needed to plan around. Adam is requiring blood once a week, and platelets twice a week at the moment. The combined effects of disease and treatment on his bone marrow. Last weekend, due to a very low platelet count, he had a slow but persistent nosebleed that blocked both nostrils with clotted blood that required us to take him up to Epsom Hospital at five in the morning. When eventually he cleared his nostrils after getting transfused the one side must have been about 8cm long; it was enormous. This episode obviously served to cause concern about the prospect of Adam spending 9 hours at 30,000 feet flying across the Atlantic.

Our plan was therefore to prepare Adam for the flight on Wednesday by giving him a blood transfusion, double platelet transfusion, a shot of G-CSF (Adam's neutrophils were now zero), 4mg of Dexamethasone (steroid), and changing his Fentanyl patches (pain relief). Our hope was we'd get all this done, and be able to settle him for a good night's sleep with a 6am start required on Thursday to catch our flight. Well, what a disaster Wednesday turned out to be.

Tara came to do Adam's bloods at 10am, which set the wheels in motion. However, it wasn't until 5pm that Epsom were ready for us to go up there; not a great start as a late finish was now already guaranteed. By the time his blood was up it was nearly an hour later, and it was around 9pm by the time they'd finished. The first pool of platelets then went up. Now the first of the bad news; they only had sub-cutaneous (injection) G-CSF. Adam demands IV when he's already accessed, and he was adamant nobody was going to stick him with a needle. From bad to worse; the first pool of platelets finished and I'm now visited by the Registrar who apologises 'but only one bag of platelets were issued.' A second bag is being issued now by St George's, the driver is still there, and it'll be with us in 1-2 hours. So, I'm faced with taking Adam home without G-CSF and only one bag of platelets, or having him stay in the hospital until very late, and then waking him at the crack of dawn for a long day of travel. The nurse then comes in to say they've found some G-CSF that they can give IV, which made my mind up as we'd give that whilst waiting for the second pool of platelets. G-CSF done, I settle down in the chair to rest whilst Adam sleeps on the bed …

I'm woken at 11:45pm by a knock on the door and a second doctor asks to speak to me outside. The one from earlier is still on the ward but I think they have decided to take it in turns to tell me things I'm not going to like hearing. She is very sorry, the platelets have arrived but they've issued the wrong ones. They are re-issuing the correct ones now but it'll be another two hours before they arrive.

I think my response was something along the lines of "What a complete and utter fuck-up." I didn't raise my voice though I hasten to add, but only because I was too drowsy from napping in the chair.

So my choices are (1) wait around to give Adam the second bag of platelets, take him home at 3am and then wake him up at 6am to go to the airport, or (2) have them de-access his port, take him home and travel on a single bag of platelets. I opted for (2); and I may not even have asked nicely for him to be de-accessed, I can't quite remember exactly. As I told them, the one time you really need things to go to plan, and for people to be on top of things ...

We get home past midnight, I put Adam straight to bed and finish my packing - eventually getting to bed myself just before 3am.

Of course, we fully expected our trip on Thursday to be a complete and utter nightmare. Adam would be tired, irritable, grumpy, uncooperative, tearful, we'd struggle to get him to eat or drink anything. As it turned out it was nothing of the sort. Adam was great company from start to finish. He didn't sleep at all on the plane, just watched his iPad; then settled down in the car on the drive from Detroit airport.

Having been unable to secure a room in either Renucci Hospitality, or Ronald MacDonald (due to the last minute nature of it all), and needing somewhere to prepare food for Adam we booked a little cottage for 4 nights in Newaygo, around 45 minutes drive North of Grand Rapids. The plan was for a clinic visit on Friday, probably with a platelet transfusion to see us through the weekend, and then to have a quiet couple of days before getting down to business next week.

So much for that idea. On Friday morning Adam spiked a fever of 39° and is currently an inpatient on the 9th floor of Helen DeVos Children's Hospital with a confirmed gram-negative blood infection. He's on IV antibiotics, and although his fever has subsided since late yesterday, he's been experiencing rigours (uncontrollable shakes) so they are keeping a close watch on him. Gram-negative bacteria are more difficult to deal with than gram-positive, so it's not the best news to start our visit with. Plans for next week will depend on his continued response to antibiotics, and how his white blood cells respond to G-CSF. That little cottage in Newaygo has long since been forgotten - I packed up our stuff this morning and we've now got a room at the Renucci Hospitality House adjoining the hospital.