Day 5: Bone marrow transplant

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In cases where leukaemia has not responded to treatment, or when the patient relapses, then a bone marrow transplant is a common course of treatment.

Bone marrow transplants are used with the aim of completely resetting the patients immunity.

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What are the other indications for a bone marrow transplant?

BMTs are usually done for:

  • Malignancies – ALL, CML, neurblastoma, non-Hodgkin’s lymphoma, Wilm’s tumour, rhabdomyosarcoma
  • Bone marrow disease – aplastic anaemia, thalassaemia, sickle cell disease, Wiskott-Aldrich syndrome, chronic granulomatous disease, severe combined immunodeficiency, Diamond-Blackfan syndrome
  • Metabolic disease – mucopolysaccharoidoses, adreneleukodystrophy, glycogen storage disorders

Where do the cells come from?

BMTs can be allogenic or autogenic.

Allogenic transplants can be from a sibling, an unrelated donor, or from cord blood (related or unrelated). Any full sibling has a 1 in 4 chance that they will be a match.

Matching is done via tissue typing and mainly checks the HLA match – aiming for  6 out of 6 alleles matched in a sibling donor, or 5 out of 6 in a cord transplant (as this is a more naive immune system).

Stem cells with be collected from the donor via a bone marrow aspirate, from the cord of a newborn, or via apheresis (peripheral blood stem cell collection).

Autologous transplants are more commonly used in children with brain tumours – these are often given as mini-transplants. As these patients often have intense chemotherapy, the stem cells are collected from the patient prior to starting chemo and then give back to them at the end of each cycle to help build them up before the next cycle.

What are the stages of a bone marrow transplant?

The key stages are:

Pre-transplant evaluation – this will include the decision to proceed to transplant, donor selection and tissue typing, and also an assessment of pre-transplant organ function.

Conditioning therapy – this usually lasts 5-10 days and consists of high dose chemotherapy and radiation. These will be termed minus days i.e. the first day of conditioning might be D -7.

Infusion of the stem cells – this is known as D0. Stem cells are infused over minutes to hours (depending on the volume). Isolation commences from the time of infusion. Note that patients can have toxicity from DMSO (dimethyl sulfoxide) which is used to preserve the stem cells – this can cause nausea/vomiting, haematuria, an unpleasant odour. It is mainly excreted via the lungs over 48 hours.

Engraftment – this is when a neutrophil count of 0.5 is achieved on two consecutive days.

Post-transplant – this is usually split into early (0-3 months) and late (3-12 months)

What are the complications?

Some patients will experience early problems that are not directly related to the stem cells, but rather are side effects from the high dose chemotherapy.

Complications from the actual BMT include:

  • Nausea/vomiting
  • Mucositis
  • Pancytopenia – bleeding and life-threatening infections
  • Veno-occlusive disease
  • Graft versus host disease
  • Opportunistic infections – CMV, PCP

What are the mortality rates?

Treatment-related mortality in matched sibling donors is 5-10%. In unrelated donors it is 20-25%.

There are huge psychosocial implications for families during the transplant. There will be fear that the child will die during treatment, or relapse after the treatment. There will be the distress of watching their child endure complications of the treatment we are giving. Also, being stuck in a room for months can lead to loneliness and isolation. Parents can often second guess their decision to proceed to transplant. Overall is it a highly stressful time, and it’s important to be mindful of this when dealing with these families.

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About 

Tessa Davis is a paediatric emergency registrar from Glasgow and Sydney, but currently living in London. Tessa tries to spend time with her 3 kids in between shifts. @tessardavis | + Tessa Davis | Tessa's DFTB posts