Information Pathway. Intensive treatment autologous stem cell transplant. The principle behind stem cell transplantation. What are stem cells?

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1 Information Pathway Myeloma UK Broughton House 31 Dunedin Street Edinburgh EH7 4JG Tel: + 44 (0) Fax: + 44 (0) Myeloma Infoline Charity No. SC Myeloma Awareness Week June Intensive treatment autologous stem cell transplant Initial treatment for the majority of newly diagnosed myeloma patients involves combinations of chemotherapy and chemotherapy-like drugs. These combinations, which are given in relatively low doses, provide an effective way of treating myeloma. However, it is clear that some patients benefit from increasing the dose of chemotherapy and the higher the dose, the more effective the treatment is likely to be. However, high doses of chemotherapy (high-dose therapy (HDT)) are toxic to the blood-forming stem cells in your bone marrow and would result in your blood cell production being severely affected, potentially causing lifethreatening problems. It is possible to get round this by using your own bone marrow stem cells. These can be used following high-dose chemotherapy to allow the bone marrow to recover and restart blood cell production. This is called an autologous stem cell transplant (SCT) The principle behind stem cell transplantation Intensive chemotherapy, called conditioning treatment, is normally used after induction treatment. Induction treatment aims to get the myeloma under control and to kill as many myeloma cells as possible. It has been shown that following this up with high doses of chemotherapy (conditioning) can kill even more myeloma cells and this can result in better control of the myeloma, better quality of life and longer survival. The use of your own stem cells effectively rescues your bone marrow, allowing blood cell production to continue, protecting the normal marrow from the effects of the chemotherapy. The various stages of HDT and SCT are described in detail in this information sheet. What are stem cells? Your body has various types of stem cell, but, when talking about transplantation in myeloma, we are talking about blood stem cells. Blood stem cells exist in your bone marrow and have the ability to divide and develop into three main types of cell found in your blood; each of these cells performs an essential function in your body: Red blood cells carry oxygen from your lungs to the rest of your body White blood cells combat bacteria and viruses to fight infection Platelets form clots and help to control bleeding from injuries

2 What types of transplant are available? There are two types of SCT. The first is when the stem cells collected are your own. These are normally collected after induction treatment. Using these stem cells after high-dose chemotherapy is known as an autologous SCT. The second is when the stem cells are donated from another person, usually a sibling (known as an allogeneic SCT). This information sheet describes the process of an autologous SCT. The allogeneic SCT is described in detail in the Intensive treatment allogeneic stem cell transplant information sheet. You can get a copy of this information sheet from your doctor or nurse. The autologous stem cell transplantation process The information from this point on outlines the autologous SCT process. Induction treatment The purpose of induction treatment is to reduce the number of myeloma cells in your bone marrow before stem cells are collected. Courses of induction treatment usually last for several months (typically four six months) and are given in cycles. The number of cycles given will depend on your individual myeloma-related factors. The current induction treatment of choice in the UK is cyclophosphamide, Thalidomide Celgene TM and dexamethasone (CTD). CTD is described in detail in the Cyclophosphamide, thalidomide and dexamethasone (CTD) information sheet. You can get a copy of this information sheet from your doctor or nurse. It is important that you experience a good response to your induction treatment in order to progress to the stem cell collection stage of the process. If you do not have a good response, you may be switched to an alternative induction treatment. Potential induction treatment side-effects The chemotherapy used for induction treatment can cause side-effects such as: Fatigue Sore mouth Sickness Increased risk of infection Hair loss Damage to nerves in the hands and feet Constipation These side-effects can vary greatly between individuals, but are almost always short-term and usually resolve once treatment has finished. Detailed information about chemotherapy can be found in the Chemotherapy information sheet. You can get a copy of this information sheet from your doctor or nurse. Once you have reached the desired response to induction treatment you can move onto the next stage of the process. Information Pathway Intensive Treatment autologous stem cell transplant 2

3 Pre-transplant tests and investigations It is likely you will need some tests and investigations to check that you have responded well enough to your induction treatment and to ensure that you are fit enough to undergo the HDT and SCT. You may have some or all of the following tests and investigations before receiving HDT and SCT: Blood tests Chest X-ray Bone marrow biopsy Tests of heart, lung and kidney function Serum Free Light Chain Assay (SFLCA) Each of these tests is described in detail in the Myeloma tests and investigations information sheet. You can get a copy of this information sheet from your doctor or nurse. In addition, you may also have an ECG (electrocardiogram). This is a trace of your heart rhythm and it involves a number of wires being placed on your chest, ankles and wrists. This test is to check that your heart is healthy. The procedure is not painful but you will have to lie still for 5 10 minutes. Central venous catheter insertion During your transplant you will need a number of intravenous drugs and regular blood tests. The easiest way to administer these is to have a central line put in. The central venous catheter is a flexible, hollow tube, which is inserted into a large vein in your chest. The catheter is inserted under the skin, so that while it exits the skin around five ten cm below the collarbone: the tip of the catheter actually sits in one of the large veins that lead into your heart. You may hear the line being called a Hickman catheter / line, a Groshong catheter / line or simply a central line. If you have a central line put in your nurse will show you how to care for it. If you do not have a central line put in you will receive your high-dose chemotherapy directly into a vein, normally in the arm or hand, via a small tube (cannula). Mobilisation of stem cells In preparation for SCT, you will have treatment to stimulate your stem cells to multiply and move from your bone marrow into your peripheral blood stream so that enough cells are available to be collected. This process is known as stem cell mobilisation. Mobilisation is achieved by giving a special type of drug called a growth factor. Growth factors increase the number of stem cells in the bone marrow, causing them to spill over into the blood, where they can be collected more easily. A common growth factor is called G-CSF (granulocyte-colony stimulating factor) and is given as an injection under the skin for several days prior to collection of the stem cells. Although it is possible to mobilise stem cells using G-CSF alone, a cycle of chemotherapy is often given before the G-CSF injections. Chemotherapy will temporarily reduce the number of stem cells in your bone marrow. When your bone marrow recovers, it goes into stem cell production over-drive and, with the addition of G-CSF, it is usually much easier to collect the desired number of stem cells. The type of chemotherapy most often used for mobilisation is cyclophosphamide. This may require an overnight stay in hospital. Cyclophosphamide is described in the Chemotherapy information sheet. You can get a copy of this information sheet from your doctor or nurse. Information Pathway Intensive Treatment autologous stem cell transplant 3

4 G-CSF is given consecutively over about five to seven days when used alone, or about 10 days when used after cyclophosphamide. Potential side-effects of G-CSF G-CSF injections can cause side-effects for some patients. The most common side-effect is flu-like symptoms. These symptoms are temporary and should disappear when the injections stop. More information about growth factors and their side-effects can be found in the Growth factors information sheet. You can get a copy of this information sheet from your doctor or nurse. Collecting stem cells Collecting stem cells from the peripheral blood can be done as an outpatient, so an overnight stay in hospital is not normally needed, and no anaesthetic is involved. To make sure that there are enough stem cells in your blood for collection to take place, a blood test may be taken. If your cell count is high enough, collection will take place using a special machine known as a cell separator or apheresis machine. Collecting the stem cells usually takes about three to four hours. A line will be inserted into a vein in each arm. If you have a central line already in place this may be used. Blood is taken from one arm and goes through the line, into the apheresis machine. Your stem cells are separated from the rest of your blood and are retained. Your remaining blood is returned to you through the line into your other arm. Sometimes enough cells will be collected in just one session. However, you may require two or three sessions over consecutive days to achieve the number of cells required. If you have difficulty mobilising enough stem cells your doctor will talk to you about your options. There is an alternative drug (Mozobil ) to G-CSF that can be used to mobilise stem cells and this may be an option. Potential side-effects of stem cell collection During stem cell collection the most common side-effect is a cramp-like or tingling sensation in the hands, feet or around the mouth. This happens because your blood is mixed with an anti-coagulant drug that stops it from clotting in the machine; when the blood is returned to you, it can cause a drop in your body s calcium levels. This is usually easily corrected by drinking some milk. Once your stem cells have been collected, they will be mixed with a chemical called DMSO and then frozen. DMSO prevents water in the cells from forming ice crystals, which would permanently damage the cells during the freezing process. Receiving the high-dose therapy After the stem cells have been frozen and stored, the next step is to receive your high-dose therapy followed by the transplant of your stem cells. Although it can vary from patient to patient, it is likely you will be in hospital for approximately three to four weeks. The high-dose therapy is a chemotherapy drug called melphalan which is given intravenously, usually via your central line. Immediately before starting this high-dose therapy, you will be given extra fluid via a drip, which aims to prevent any dehydration and kidney damage caused by the toxicity of the chemotherapy. If your kidney function is poor, the dose of chemotherapy may be adjusted. Information Pathway Intensive Treatment autologous stem cell transplant 4

5 Potential side-effects of high-dose therapy The most common side-effects of high-dose therapy are: Nausea and vomiting: when you begin your high-dose therapy you will be given an anti-sickness drug to help prevent and minimise the nausea and vomiting Diarrhoea: this is a common side-effect of the high-dose therapy. You will need to drink extra fluids to keep hydrated; alternatively, intravenous fluids can be given. You may by prescribed a drug to help stop the diarrhoea Sore mouth: it is common to have a sore mouth after receiving high-dose therapy. Your nurse will show you how to care for your mouth Altered taste and smell: the high-dose therapy can alter your sense of taste and sense of smell. This is quite normal and your sense of taste and sense of smell will return to normal, although this may take some time Fatigue: you may feel very tired and lethargic and find you are unable to concentrate, or that you are sleeping more than usual. This is quite common and it may be some time before your energy levels return to normal. Fatigue may persist longer than the other side-effects noted above Hair loss: you may lose your hair, or it may not fall out but become thinner than it was before treatment Having your stem cells returned the transplant Within a day of so of receiving the high-dose therapy your bone marrow will be ready for your stem cells to be returned to you. At this point the frozen bags of stem cells are brought to the ward, thawed in a warm water bath and given back as an intravenous infusion. This process, which takes on average about an hour, is relatively straightforward. Potential side-effects of the transplant The most common temporary side-effect of this step is caused by the DMSO and may include: Nausea Feeling chilled Vomiting Experiencing unusual odour and taste of garlic or sweetcorn In rare cases, the infusion may cause low blood pressure, a fast heart rate and shortness of breath. Medications are given before the infusion process to prevent or lessen some of the expected effects of DMSO infusion. Engraftment Once the stem cells are put back into the bloodstream, they migrate to the bone morrow, where they settle and develop into new blood cells a vital process known as engraftment. The engraftment process signals the beginning of the recovery period but you will remain immunocompromised for a few weeks. This means you will need to stay in a clean environment such as a single room, or special bay for an average of days. This is often referred to as the period of isolation. Rarely, stem cells do not engraft well. In the event of this happening, treatment can be carried out with injections of growth factors to stimulate the stem cells, and in some cases a top-up of stem cells may be given if they are available. Information Pathway Intensive Treatment autologous stem cell transplant 5

6 There are a number of reasons for stem cells not engrafting well, including certain viral infection and sideeffects caused by drugs used to treat particular types of infection. Supportive care whilst in isolation The period of time waiting for the stem cells to engraft and start producing new blood cells is, for many patients, the toughest part of the transplant process. Until the new blood cells are produced and show up in your bloodstream, you will be at risk from infection and anaemia. Special precautions and supportive measures are necessary during this time and your nurse will discuss these with you. You can also find more information about the risks of infection in the The symptoms and complications of myeloma information sheet. You can get a copy of this information sheet from your doctor or nurse. Advantages and disadvantages of HDT and SCT The potential advantages and disadvantages of HDT and autologous SCT include: Advantages HDT and SCT are relatively safe for patients up to the age of years as long as they are fit enough The potential for improvement in quality of life after the transplant may mean fewer ongoing and future complications, such as myeloma bone disease There is evidence to suggest that duration, quality of response and overall survival are better when HDT and SCT are performed rather than standard-dose treatment alone Disadvantages HDT is more toxic than standard doses of treatment and therefore the risk of side-effects is higher HDT and SCT may affect fertility The success of this or any other treatment cannot be guaranteed; not all patients will achieve the desired response It is possible that the re-infused stem cells may be contaminated with myeloma cells, although there is no definitive evidence from clinical studies that this causes patients to relapse any sooner Table 1: Potential advantages and disadvantages of HDT and SCT How do I know if my treatment has worked? The aim of treatment is to destroy the myeloma cells in order to control your symptoms and complications. In order to find out how you are responding to treatment, several tests will be carried out on a regular basis. These tests may vary from patient to patient, but would generally include regular blood and urine testing, bone marrow biopsies and occasional X-rays or scans. Response to HDT and SCT is often categorised using the response criteria in Table 2. Information Pathway Intensive Treatment autologous stem cell transplant 6

7 Treatment outcome Stringent Complete Response Complete Response (CR) Very Good Partial Response (VGPR) Partial Response (PR) Stable Disease (SD) Definition CR as defined below plus normal free light chain ratio and absence of myeloma cells in the bone marrow Less than 5% plasma cells in the bone marrow, no detectable paraprotein 90% or greater reduction in blood and urine paraprotein Reduction of paraprotein in blood by more than 50% and reduction in 24-hour urinary paraprotein by more than 90% Not meeting criteria for CR, VGPR, PR or progressive disease Table 2: International Myeloma Working Group uniform response criteria 2009 Further treatment after HDT and ASCT Depending on your response to HDT and SCT, further treatment may be recommended. This further treatment falls into two categories: Treatment which aims to prolong the response to HDT and SCT Treatment for myeloma that has returned (relapsed) more quickly than expected Treatment to prolong response There is some evidence to suggest that, in certain patient groups, maintenance treatment can help to prolong the period of response after HDT and SCT. Not every patient will benefit from maintenance treatment and the potential benefits must be balanced against any side-effect that occurs. Maintenance treatment is described in the Maintenance treatment information sheet. You can get a copy of this information sheet from your doctor or nurse. Treatment for myeloma that has relapsed Despite the potential for an excellent response to HDT and SCT, like all myeloma treatment it is not curative and relapse almost always occurs. The duration of your response and previous responses to other drugs and drug combinations are factors which are taken into account when deciding on further treatment options. Treatment for relapsed myeloma is described in the Treatment options for relapsed myeloma information sheet. You can get a copy of this information sheet from your doctor or nurse. Information Pathway Intensive Treatment autologous stem cell transplant 7

8 The future Autologous SCT is routinely used as part of the treatment for myeloma patients. Improvements in induction, consolidation and maintenance drugs may improve response to SCT in the future. The role of SCT in myeloma treatment may change in the future. As novel drugs and drug combinations with better efficacy are developed, and provide better responses, HDT and SCT may no longer be required. Other information available from Myeloma UK Myeloma UK has a range of Essential Guides, Infoguides and Infosheets available covering many areas of myeloma, its treatment and management. To order your free copies call our Myeloma Infoline on This information is also available on our website at To talk to someone about any aspect of myeloma, call our Myeloma Infoline on The Myeloma Infoline is open from Monday to Friday, 9am to 5pm and is free to phone from anywhere in the UK. From outside the UK, call +44 (0) (charged at normal rate). About Myeloma UK Myeloma UK is the only organisation dealing exclusively with myeloma and its related disorders in the UK. Our broad and innovative range of services cover every aspect of myeloma from information and support to improving standards of treatment and care through research, education, campaigning and raising awareness. Our strategy is to take an integrated approach to systematically address the barriers and challenges that are slowing down myeloma research and the development of, and access to, new treatments, optimal care, information and support. We receive no government funding and rely almost entirely on voluntary donations and fundraising activities. With Myeloma UK you can Call our Myeloma Infoline on for information, practical advice, emotional support and a listening ear Get free Infopacks, Infoguides and Infosheets about myeloma Learn about myeloma from experts and meet others affected by myeloma by attending Patient and Family Myeloma Infodays Subscribe to our newsletter Myeloma Matters Visit our website Join a Myeloma Support Group Author: Anne-Marie Haughey Research and Clinical Information Writer, Myeloma UK Issue date: August 2010 Myeloma UK Broughton House, 31 Dunedin Street, Edinburgh EH7 5JG Tel: + 44 (0) Fax: + 44 (0) myelomauk@myeloma.org.uk Charity no. SC Information Pathway Intensive Treatment autologous stem cell transplant 8