Clockwork

Kezia was diagnosed with Acute Lymphoblastic Leukaemia on the 21st of May 2006.

Her treatment protocol (UKALL 2003) predicts 118 weeks of treatment. Equals 2 years and 14 weeks = 2 years 3 and a ½ months.

Two years and three and a half months will therefore come to an end on the 5th October. She will go off-treatment around 20 October.

Given a bout of chickenpox and a couple of other “minor” infections, finishing treatment only two weeks behind the protocol schedule is truly a wonder of modern science.

Maintenance Cycle 5

Starts today with a Vincristine injection and then the dreaded D for the rest of the week. One more maintenance cycle and six months to go.

I called on my Anglo-Peruvian friend Talia down in the city on Sunday to find her being visited by a silly French woman who runs a local business. When the subject turned to Kezia, she started twittering about alternative treatment, and my hackles began to rise. She insisted. Even after all her years here she hardly speaks our local language, doesn't speak English and, although I have some French, I couldn't get angry enough in French to tell her what bullshit she was spouting and ended up asking Talia to translate – which, given my increasing annoyance, she did diplomatically.

I couldn' t take any more and abruptly left.

Link, Link, Link, Link

Where are we now ?

I don´t mean geographically (I´ll leave you to work that out - maintaining blog anonymity is not easy) but in terms of Kezia´s treatment and our disjuncted, dysfunctional family life.

Time to take stock.

Today will see Kezia´s first consultation of UKALL2003 Maintenance Phase 4. Only another three 3 month maintenance cycles to go - that takes us up to November.

Is there any light at the end of the tunnel?

Maybe a pin-prick (sorry for such an apt pun).

After off-treatment (OT) in November, our consultant John wants Kezia to say in the UK for 6 weekly check-ups for at least 18 months. May 2010. Kezia will be seven years old, Jaime will be ten years old. The medical profession will only consider Kezia cured after five tears of Event Free Survival.

The pin-prick becomes smaller.

There is a slight, as yet unexplored, possibility that Jaime and Kezia could continue their education in the UK at a private, charitable and means-tested boarding school of 400 years standing and reputed academic excellence - which would certainly be advantageous to their futures. However, an initial tentative probe of Nanda was not favourably received ... but she does have a tendency to jump off at the deep-end and then, after due consideration, change her mind.

When or will we ever become a physically united family again? Ever?

So far John has not precluded Kezia, Jaime, Nanda coming back over for a holiday during those first 18 months. It would certainly help.

UKALL 2003 - the Protocol, the Regimens and Kezia's path through it

I know that Dr Crippen and Dr Rant hate checklists and flowcharts guiding them through diagnoses but in clinical trials they are necessary to obtain standardisation between participating centres and thus statistically relevant data – I am sure that Dr Crippen and Dr Rant will agree.

In the UKALL 2003 trial there is an initial diagnosis flowchart by which patients are allocated to the three treatment regimes being compared. Below I partially reproduce this up to the point where Kezia, at Day 8, was allocated to the most intense regimen.

Once our consent had been obtained to participate in the trial, the oncologists and haematologists are not obliged to follow the regimen strictly – if something is amiss, then they will, to the best of their judgement and with the parents’ consent, try non-regimen treatment. This has been the case with our friend’s teenage daughter, H., who seems to have gone through every drug side-effect in the book.

However, it was pointed out to us in the first week that there is little difference between an established protocol and the trial protocol – especially with Regime C which is a typically aggressive treatment not based on the level of Minimum Residual Disease, used partly to choose between the less-aggressive treatments of Regimens A and B (but which also take into account bloodcounts etc), but solely on the traditional clinical measurements based on bloodcounts and genetic abnormalities.

Regimens B and C during the first 28 days are the same but differ later.

Kezia’s path through the flowchart is in bold.

Under 12 months ? → yes → Interfant trial

↓ No

B-cell ALL ? → yes → Regimen C

↓ No

BCR-ABL ? → yes → Regimen C

↓ No

MLL rearrangement ? → yes → Regimen C

↓ No

Hypodiploid → yes → Regimen C

(≤ 44 chromosomes) ?

↓ No

AML1 amplification ? → yes → Regimen C

↓ No

≥ 10 years ? → yes → Regimen C

↓ No

White Blood Count → yes → Regimen B

≥ 50 x 10⁹/L

↓ No

Regimen A.

Marrow morphology at day 8/15

If on Regimen B, aged 1-15 years: → yes → Regimen C
> 25% blasts (M3) at day 8 ?

Chemotherapy Overdose

Oh dear ... something else to worry about.

Two men being treated for cancer and leukaemia at Birmingham's Heartlands Hospital died after receiving five times the correct dosage of a medication on 20 July. Apparently the drug (I wonder what) is to alleviate the side-effects of cancer treatment. A doctor and two nurses involved are apparently away from work but have not been suspended, An enquiry is taking place by both the hospital and the coroner. Press report here.

The risk is real. The UKALL 2003 protocol warns "All medical staff involved in the care of patients with leukaemia MUST be aware that the inadvertent administration of vincristine by the intrathecal route is invariably FATAL. Vincristine should NOT BE AVAILABLE when an intrathecal needle is in situ. This protocol has been written to provide separation of intrathecal methotrexate administration from intravenous vincristine administration in time. An additional precaution is that the two drugs should not be administered in the same place ...The single most crucial element in avoiding errors is the appropriate education and training of all personnel involved in the administration of chemotherapy".

Research

I promised to discuss the new research project for which Nanda had to sign a consent form and hand in yesterday.

First of all, it does not involve new or extra bone marrow or blood samples. It just involves existing bone marrow samples taken during her first four weeks of treatment.

I haven´t seen the whole consent letter but my brother summarised for me “the scientific part”. To quote:

“The aim of the study is to measure the levels of angiogenesis, MDR-1, MRP and indicators of hypoxia in the bone marrow samples taken routinely at diagnosis. These measures would then be related to the speed and extent (the level if any of minimal residual disease) of your child's response to the first four weeks of treatment. This is to help further understanding of the variations in the speed and extent to which the leukemia cells disappear from the bone marrow during the first four weeks of treatment. In many adult cancers the numbers of new blood cells (angiogenesis) and a low level of oxygen within the cancer (hypoxia) are recognised as making the tumours less responsive to treatment. It is not yet known whether the numbers of new blood vessels or low oxygen levels are important for making the treatment of childhood ALL more difficult. Also some cancers contain resistance proteins (MDR-1 and MRP) that may reduce the effectiveness of drugs such as vincristine.”

As I haven´t seen the whole consent document, I am not sure of the rest of its contents.

I am sure this consent letter has not been translated into the principal minority languages of England – Urdu, Punjabi etc – the principle ethnic minority languages of he hospital´s catchment area - let alone Nanda´s native language, an official language of the European Union. I am afraid that ethnic minorities, or many others with little literacy (whether UK or non-UK readers, writers, listeners or speakers of English) and those who don´t have a first idea about the science, are left in the dark.

A Miscellany of News

Our local general hospital is, quite obviously, not thr only one in the country under the threat of a reduction in services and beds. Yesterday the BBC reported that Scottish Health Secretary Nicola Sturgeon visited the Vale of Leven Hospital at Alexandria, West Dunbartonshire where extensive cuts are proposed.

So I visited the website of the Greater Glasgow and Clyde Trust and found a list of service reduction at the Vale of Leven Hospital.

Basically, they cannot afford to pay for locums."Continuing to provide services with locum staff is not acceptable..."

She is quoted as saying "Whatever happens will be subject to independent scrutiny and will go out to public consultation."

Back to my role as transport analyst ... it is a 45 minute bus journey between the Vale of Leven Hospital and the Royal Alexandra Hospital in Paisley where many of the services would be transferred to with buses running every two hours.

Coming south the Scarborough and North East Yorkshire Trust announced on Wednesday 600 job cuts! To make up their deficits … the trade union UNISON is not happy.

I expect (or let us say, hope that, some of) their jobs will be taken up by private companies. But, obviously with loss of salary, pensions, rights etc.

A Miss Otley has sued the Barking and Dagenham PCT in the High Court for not providing Avastin to treat her bowel cancer. After they refused to treat her with Avastin, she used 15,000 pounds of her own money and then when her own money ran out and after much improvement, the PCT refused to continue the treatment. The judge has ruled against the trust. Good news indeed.

Much closer to home … Kezia

Yesterday, a regular visit to the hospital, a blood test and picking up prescriptions. The weekly visits to the hospital seem to be based on her daily 6-mercapturine and weekly oral methotrexate treatment – according to the UKALL 2003 protocol, if her neutophil count is low, then she comes off the mercapturine and methotrexate until the neutrophil count has recovered.Yesterday everything fine.

I was hoping that hospital visits would be less frequent than weekly in this second year – but seemingly not. I will ask our consultant.

Nanda received a consent letter to sign at the hospital yesterday to authorise the use of existing bone marrow samples from Kezia for research into cancer resistance to vincristine. More details to follow.

Dr. Who

Kezia and Nanda have just got back from hospital - her counts were good enough that she can start nightly 6-mercapturine and weekly oral methotrexate.

Apparently, our consultant J. is known by Kezia as Dr Who! I wonder if he has a Tardis!

UKALL 2003 - Maintenance I

Kezia started the first maintenance phase today with Vincristine and Dexamethasone. She was also meant to start mercaptopurine and oral methotrexate but these are neutrophil and platelet count dependent and and her neutrophils had not recovered sufficiently. This was expected. Her next visit is next Tuesday, I suspect just to see if her counts have recovered enough to start these medications

Maintenance cycles run in 12 week blocks. Every 4 weeks is Vincristine (one dose) and Dexamethasone for a week, Mercapturine every day and oral MTX once a week apart from the third week of each cycle when she will receive intrathecal MTX. All the maintenance cycles follow the same pattern until the end of treatment. For girls there are six maintenance cycles, boys get more.

The Hickman Line will be removed - but there is currently a three-month waiting list for this surgery. They will not install a Portacath unless she becomes very fractious with the Vincristine injections.

UKALL 2003 - Delayed Intensification II contd

Finished!!

UKALL 2003 - Delayed Intensification II contd

Kezia had Vincristine and her last PegAsparaginase today and they are home already.

Lots of small milestones the last few weeks - the last of this drug, the last of that drug, Next week sees the first Big Milestone - the last dose of this phase (Vincristine) and then we're into the much less intensive maintenance phases! Looking forward to it! Vinvcristine once a month through the maintenance phases.

UKALL 2003 - Delayed Intensification II (again!)

Kezia's counts were good enough today to start the reconsolidation phase of DI2. Four more weeks and counting!

Chickenpox

Jaime has come down with chickenpox. Fortunately, Kezia tested positive for chickenpox antibodies at the beginning of her treatment so she shouldn't pick it up.

But as he is now off school I will be accompanying Kezia on her hospital visit tomorrow as I need to see our consultant J. and a child with chickenpox obviously cannot go the the hospital. And it is a biggie tomorrow - the start of the reconsolidation phase of Delayed Intensification II. This involves IT methotrexate followed by the lengthy administration of cyclophosphamide (our chemical warfare drug!).

UKALL 2003 - Delayed Intensification II contd

Treatment day again. Doxorubicin (her last ever - a milestone albeit a minor one!) and Vincristine. Kezia will be restarting Dexamethasone for a week. Jaime started his school holidays yesterday so went along as well. They are back from hospital as I write and Jaime got another present. At my suggestion that I will be able to look after Jaime during the next appointment, Nanda said he won't want to as he likes getting presents from the hospital!

UKALL 2003 - Young Adults II

The UKALL 2003 protocol has a Young Adult Appendix which elaborates on research into adult versus paediatric treatment regimes for young adults where it is stated that in the past "adolescents have received ALL therapy according to either paediatric or adult clinical trials, determined only by local referrals to paedatric or adult physicians". GPs decide the treatment protocol? Oh dear. Dr John - you have to decide a young adult's ALL treatment!

Fortunately, for Lucia and H., they have been put on the UKALL 2003 (paediatric) trial. Why?

Various treatment protocols in trials in several countries have found that pediatric protocols are more effective for young adults than adult protocols (the stats are on p. 128 of the protocol) . Evidence from previous UKALL trials and overseas trials is not conclusive yet but the Event Free Survival (EFS) rates and Overall Survival (OS) rates seem to be better for young adults receiving paediatric as opposed to adult treatment.

The evidence is not considered to be conclusve by the medical profession as sampling (i.e.patients) has not been sufficient, but it is strong enough to comsider further testing.

So an aim, albeit not the principle one, of the UKALL 2003 Trial is to evaluate the use of a slightly modified paediatric regime in young adults.

Differences between young adults and adults at prognosis do not seem to be important. However, there are major differences in treatment regimes.

UKALL 2003 is slightly modified for young adults. Children are first evaluated into risk groups at Day 8 when Slow Early Responders are automatically put on Regimen C. However, the USCCG 1882 trial showed no benefits to this for young adults with "normal" ALL (i.e. with no complications arising from genetic defects who automatically go onto Regime C). At Day 28 Mean Residual Disease High Risk young adults are randomised between Regimes B (with two Delayed Intensification phases) and C. Low Risk patients follow Regime B with randomisation between one and two Delayed Intensifications. No young adults follow Regime A, I assume because their age does put them at higher risk than children.

So, although the Royal Manchester Children's Hospital does not have a young adult unit as Manchester's other cancer hospital does, at RMCH you do get the advantage of following the paediatric UKALL 2003 protocol whilst at Christies you follow the adult UKALL XII protocol.

And all the more reason that the new RMCH should have a young adult unit.

And the message to the referrers is send your ALL young adult patients to a paediatric hospital.

Disclaimer: I should reiterate that this applies to T-cell ALL, not B-cell that goes on another procotol that I know nothing about, and certainly not other forms of leukeamia.

UKALL 2003 - Young Adults

Lucia draws my attention to the fact that in latest version of the UKALL 2003 (posted February 2007 - link on right) has now increased the age range eligibility to 19 + 364 days. The protocol has a Young Adult Appendix which elaborates on research into adult versus paediatric treatment regimes for young adults - next post.

UKALL 2003 - Delayed Intensification II contd

Second doses of doxorubicin and vincristine are scheduled for today. Peg Asparaginase Saturday last - Jaime went with them to the hospital and received, as Nanda described it, a "big" present. Didn't quite ascertain what ((don't think he's suffering from lack of attention, Rob!). Almost a week's worth of dexamethasone and it has kicked in. Moody. Not sure if she's got leg pains yet as happened in Delayed Intensification I.

Her Hickman Line is playing up. It is allowing medication in, but not blood out. This is probably due to a tiny bloodclot acting as a one-way gate valve. Such micro-clots are pretty common even in healthy people. J., our consultant, does not want to change the line again if not really necessary - especially as we are so near the maintenance phases and the removal of the line.

In other events ... I had quite a good weekend. Friday to Saturday we had an enormous storm. After several weeks without rain, I was grateful to have our cisterns replenished and it rained again today (Monday). However, it brought down our "izaquenteira" (Treculia africana - cannot find an English name) - this is a tree of about 10 metres height that bears medicine ball-size fruit with numerous seeds that are locally prepared into traditional dishes, one sweet, vaguely reminiscent of Indian kulfi, and one savoury with palm oil and smoked fish. The latter I adore, not having a "sweet tooth" for the former. Fortunately, it did not fall on the house but did smash into our wiremesh fencing. Probably repairable. I heard this morning that some poor guy in the city had both his cars smashed by a falling tree!

On Saturday afternoon, seven friends came round loaded with fresh bonito, saltfish, plantains and breadfruit. They cooked, I provided the beer and wine and did a pizza. Good time had by all.

UKALL 2003 - Delayed Intensification II

Just telephoned Nanda at the hospital - Kezia has started Delayed Intensification II. The last of the intensive stages - Whoopee! Eight weeks to go and we start the maintenance phases!

Next appointments tomorrow and Saturday.

Back Home

Kezia and Nanda got home Sunday afternoon. Phew!

Jaime had a good time with M. They went swimming on Saturday and he went to Sunday school at M.'s church. They then picked up Nanda and Kezia in the afternoon. He got a prize at school on Friday for progress in learning English - M. tells me he is now producing short sentences. (So maybe he can translate for Nanda and save the NHS some money!). Thanks again M.

Kezia received vincristine on Friday but her counts were too low to receive IV methotrexate - so we've now finished Escalating Capizzi II. Next up Delayed Intensification II - which Lucia assures me is the shittiest of the lot! Apparently, H. has just started it and is feeling dreadful.

UKALL 2003 - Escalating Capizzi II Update

Kezia's neutophil counts were too low on Thursday to receive IV methotrexate. As I've said before, this is not a bad thing as it means she has reached toxicity at less than the maximum dose. So she just had vincristine.

Next appointment is on 9 March - the last of Esclating Capizzi II. Then a two week rest before starting Delayed Intensification II.