Payment by Result

I'm slowly clearing up the dining table, covered in shit (sorry, papers) in anticipation of the family's arrival on 31 July.

As I clear up all these papers, more accumulate. On top of the latest pile is the British Society of Haematology/Royal College of Pathologists' January 2008 report Haematology Consultation Workforcr: The Next 10 Years. Table 1 is entitled Initiatives since the previous workforce document (2001) and is divided into "Rgulatory Initiatives" and "Influential Initiatives".

One of the latter is "Payment by Results". How the hell are they going to evaluate and pay Kezia's consultant on whether she survives leukaemia when he is following an approved protocol for the treatment of T-cell ALL?

Is the doctor reponsible for me drinking like a chimney and smoking like a fish?

The Haematology Lab

Leeds Teaching Hospitals' Haematological Malignancy Diagnostic Service have an excellent, but very technical, website on the diagnosis of a whole range of blood disorders (lymphomas, leukaemias etc) and diagnostic techniques.

UKALL 2003 - Regimens A, B and C

The UKALL 2003 trial initially chooses your child's treatment regimen based on a series of diagnostic tools - prognosis factors based on previous experience and lab tests. Thus ... I will try to reinvent the wheel as I promised not to do previously.

If your child is under one year old, s/he will go onto another protocol trial.

If your child's ALL is effecting the White Blood B-cells (see the post on Haematology), s/he will follow a different protocol developed by the UK Childhood Cancer Study Group (sorry – I don't know any details right now). UKALL 2003 is only involved with T-cell ALL.

If the child has any of various genetic abnormalities which have been shown to put the child at a higher risk of later relapse, then s/he will automatically be put on Regimen C.

If your child is older than 10 years old, then s/he will automatically be put on Regimen B.

If your child has an initial White Blood Count (i.e. mostly malformed T-cells) greater then 50 (x 10⁹ per litre), then s/he will go on Regimen B.

Kezia “passed” all the above (phew!) except the last one. So she went on Regimen B. I was confused at first between Regimens B and C – don't worry, in the first stage of treatment Regimens B and C are the same. They differ in later stages of treatment.

They then look at the number of lymphoblasts in your child's bone marrow at Days 8, 15 and 28 of the initial treatment.

If at Day 8 and the child is on Regimen B and the blood-producing cells of the bone marrow show more than 25% lymphoblasts, then s/he is automatically transferred to Regimen C. S/he is also thus classified a Slow Early Responder (SER). This was the case with Kezia (and by the way H.).

If your child is on Regimen A and there are more than 25% lynmphoblasts at Day 15, then s/he will go onto Regimen C.

If your child is on Regimens A or B and has less than 25% lymphoblasts at Days 8 or 15, then s/he will stay on the same Regimen (course of treatment).

If your child is older than 16 years, s/he will continue on Regimen B regardless of the Bone Marrow results.

The next bone marrow test is at Day 28 – the end of the Induction phase. If your child has already been assigned to Regimen C, this will not make any difference.

However, if your child is on either Regimens A or B, then the 28 day count can decide the future course of treatment. If your child still has between 5% and 25%, s/he will go onto the Regimen C treatment. More than 25% s/he will stop being part of the UKALL2003 trial and will be treated under another protocol.

Less than 5% of lymphoblasts, your child will be allocated randomly to Regimens A or B.

This is really one of the objectives of the trial. As I said before, Regimen A is the least intensive/aggressive and Regimen C is the most intensive/aggressive. The drugs for killing the leukaemia attack both good and bad cells. They want to see if a low-level of leukaemia, needs less amounts of drugs to kill the disease. They cannot take too many risks with our treatment, so only children with less than 25% at days 8/15 and less than 5% at Day 28 will really go on to experiment between Regimens A (less aggressive) and B (more aggressive).

I'll about the differences between the regimens in a later post.

Medical Stuff - Part 1: Haematology

Ok, I'll take the plunge and try to explain a bit about what Acute Lymphoblastic Leukaemia is and how Kezia is being treated. If I get anything wrong, and any of our readers are in the medical profession, please correct me through the Comments or by email.

First we need to take a look at blood. The study of blood is haematology. Haematologists are doctors who know a lot about blood. If you don't understand a bit about blood, you won't understand much about leukaemia.

Blood cells can be divided into three types: red (RBC), white (WBC and also known as leucocytes) and platelets (PLT). You'll see these abbreviations on lab reports so I'll start using them now.

When you whizz blood around at very high speed in a centrifuge, it separates out into these three types: white cells are white, red cells are red and platelets are a kind of bilious yellow.

Red cells are important for carrying oxygen and other nutritious things round your body. White cells defend your body against all the millions of things that would like to attack and eat you. Platelets are there to clot your blood if you cut yourself – those nasty scabs form because of platelets – if you didn't have them, you'd bleed until there was no blood left at all - which means you're dead.

The important ones as far as leukaemia goes are the white cells, and, sod's law, there's a bunch of different types which we need to get to grips with.

• Neutrophils (MNEUT): these constitute around 65% of the WBCs. They defend you against bacterial infections and are the first ones to respond to an attack. Kind of like suicide bombers in that they die during the attack and turn into pus.
• Eosinophils (MEOS): these constitute around 4% of the WBCs and defend against parasitic infections.
• Basophils (MBASO): less than 1% of the WBCs. These are responsible for responses to allergies and release histamines causing inflammation.
• Lymphocytes (MLYMPH): around 25% of WBCs. Divided into further sub-types.
• B-cells - these make antibodies that bind to the attackers enabling their destruction. The arms factories.
• T-cells - CD4+ (helper) cells coordinate the immune response – the generals telling the different troops where to go. CD8+ (cytotoxic) cells are the SAS of WBCs that kill virus infected cells. Natural Killers are the MI6 of WBCs. They can kill infected cells that are displaying a signal to the other troops not to kill them (hello I'm friendly! e.g. cancer cells).
• Monocytes (MMONO): 6% of WBCs. These are similar to our MNEUTs but get to live a bit longer.

All of these are produced in the bone marrow. And they all derive from Hemopoietic Stem Cells (HSCs), also known as Hemocytoblasts. These cells split and form precursors of all of the above as well as the precursors of RBCs and platelets. The immediate precursors are known as blasts which then develop into the -cytes above before being thrown out into the blood to do their work.

In Acute Lymphoblastic Leukaemia something goes wrong with the HSCs. They start producing more and more lymphoblasts which never grow up into lymphocytes. The lymphoblasts take over all the space in the bone marrow allocated to the the other types of blasts – red, white and platelets. This gives rise to low RBC levels (anaemia) and low platelet counts (danger of bleeding).

They also head out into the blood. As they have not matured into lymphocytes, they can't fight the attackers as they should. Hence people with ALL are prone to infections.

Initial diagnosis is by a blood test - positive results show a large number of lymphoblasts. This is then confirmed by a bone marrow sample which, if positive, will also show a large number of lymphoblasts.

Other clinical signs are an enlarged spleen (WBCs accumulate here), anaemia (lack of RBCs) and a reduced platelet count.