Stem Cell Transplants

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What is it

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Haematopoietic stem cell transplantation, also known as stem cell transplant or bone marrow transplant. Patient receives new healthy blood stem cells. Offers the chance to curing or prolonging the remission period in some of the blood cancers.

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Stem cell vs bone marrow transplant

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- bone marrow transplant - stem cells are collected from bone marrow and transplanted into a patient

- peripheral blood stem cell transplant - the transplanted cells come from the bloodstream.

They both refer to stem cell transplantation, the only difference is where the transplanted cells come from

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Types of stem cell transplant

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- autologous or autograft: use patient's own stem cells. Used in MM, lymphoma and APL. Used if there are norlt infiltration of the marrow. Less sides effect, used in older patient and/or the ones with comorbidities

- allogeneic (donor): more complex, more side effects. Synergenic - from identical twin / haploidentical - partly matched from close relative / MUD or VUD: matched unrelated donor / Fetal (cord) : stem cells from umbilical cord

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Pre-transplant

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Discussion around: type of transplant, benefits, risks, lenght of stay, fertility, tests and consent.

Tests: bone marrow aspirate and trephine (BMAT), blood tests, urine test to assess kidney function, lung function test, CXR, Echo (heart function), ECG, infection screen, scans (CT, PET, MRI), psychological evaluation, holistic needs assessment

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Stem cell mobilisation

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If having autologous transplant, the healthy cells are collected by 'mobilising' them into the blood stream through: chemo, GCSF and both. They increase the number of stem cells circulating in the peripheral blood

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Harvesting

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Harvesting or apherisis is performed using an apherisis machine. Usually done in outpatients settings, lasts 4-5 hrs. After collection, stem cells are taken to the processing stem cell lab. They froze them and stored in liquid nitrogen. They can last up to 10 years frozen

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Donor search

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The ideal donor is human leukocyte antigen (HLA) matched sibling. HLA have the ability to tell the difference from 'self' and 'not self'. Therefore, it is essential that the donor's HLA is either identical or as close as possible to the recipient to reduce GvHD or graft rejection.

The search for a donor starts early. -Once the patient is diagnosed, family are tissue typed to check if they are HLA matched (1 in 4)

-if no match, donor registries are approached.

-if no match, some patients will receive haplo-identical transplant fro a relative.

-cord blood is used if 2 fully matched cords can be found, rare in adults

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Conditioning therapy

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As part of the transplant patients must undergo conditioning therapy. These includes high dose chemo and sometimes total body irradiation (TBI). The aims are:

-to destroy the patient's stem cell in the marrow to make space for the donor cells.

-to kill any residual cancerous cells

-suppress the patient's immune system to reduce the risk of graft rejection.

For older patients there are reduced intensity conditioning where the dose of drugs and radiation are lower. This allows them to have a 'mini trasplant'.

These therapies will weakened the immune system, so patients will be more vulnerable to infections

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The transplant

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The day of the transplant is day 0, with days after is as days plus post transplant. The doner stem cells are given via one of the lumens of the CVC, and it takes 30-60 mins. In autologous, the patient is given antihistamines and hydrocortisone to prevent allergic reaction to the Dimethy sulfoxide (DMSO) - substance used to preserve cells. After infusion, flush with saline. Check obs during and after procedure. Patient might feel sore, provide analgesia

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Engraftment

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After the transplant the stem cells make their way to the bone marrow. Where they will start to mature into normal blood cells, this is called engraftment. It usually takes around 14-25 days. This is a vulnerable time for the patient as they could become unwell and they have to wait to see if the transplant was successful.

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Side effects and risks

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Similar to chemo as chemo was used in the conditioning therapy. Fatigue, diarrhoea, N&V, mucositis.

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Infections

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Infections: complication of stem cell. This may be because: aggressive chemo + TBI, the cancer, immunosuppressive drugs to prevent rejection, CVC can cause infection.Prophylactic drugs (antivirals, antifungal, antibiotics) used to prevent infections.

-viral infections: stem cell transplant can reactivate latent viruses (ie. CMV, HSV, RSV, EBV)

-fungal infections: candida can be problematic in patients undergoing stem cell transplant

- bacterial infections: PCP are a major cause of morbidity, because they can lead to lung complications.

You can recognise infections through viral signs, unusual discharge, pain in passing urine, oliguria, resp symptoms, GI symptoms, skin integrity, GCS.

Protective isolation is used to protect patients from infection (personal hygiene, clothing, visitors precautions, nutrition, oral care)

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Complications

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-liver and kidney: monitor blood tests (liver functions, urea and electrolytes), urine tests and daily weight.

-VOD (ceno-occlusive disease): daily LFT. Symptoms are yellow eyes and skin, swelling or distension abdomen and fluid accumulation. Ursodeoxycolic to prevent VOD

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Graft vs Host Disease

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GvHD: in allogeneic transplant, donor T cells recognise different HLA molecules and trigger an immunological response. Can be acute or chronic.

-acute: usually occurs up to 100 days after transplant. Symptoms grade from 1 to 4. Normally affects skin (pruritic rash) , liver (increase bilirubin and enzymes) and GI tract (diarrhoea, indigestion, anorexia, N&V)

-chronic: occurs up to 100 days. Symptoms are mild or severe can lasts moths or years. Can affect as the acute and mouth, eyes, lungs, vagina and joints.

Treatment: ciclosporin, steroids, immunosuppressive agents, exteacorporeal photospheresis (ECP) - last resource

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Other complications

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- Anaemia and thrombocytopenia (might need transfusions)

- cataracts (patients that had TBI are more prone)

-endocrine problems: hormonal problems, including infertility, reduce sexual function, early menopause, and thyroid disfunction

- secondary malignancy: new cancer that occurs as result or previous treatment.

- cardiovascular risks: coronary heart disease, stroke

Relapse: blood cancer can come back. If cancer comes back 12 months post transplant, that means there's no further curative options for them