HAEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT) GUIDE FOR PATIENTS AND CAREGIVERS | J eaition, 2020Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers 157 EDITION, 2020 WELCOME AND OVERVIEW Dear parents and caregivers, The HSCT team welcomes you to our unit. We know that you and your family may feel overwhelmed dluring this difficult period. While we cannot take away your pain, we would like to help make this journey a litle easier for you and your child. This guide contains important information for your reference on what to expect of the transplant and how to provide the best care for your child. It will explain some of the side effects and challenges your child may experience over the course of the treatment and recovery. As each patient is unique, your child may or may not experience all the symptoms and treatment options listed here.Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers ACKNOWLEDGEMENT We extend our heartfelt gratitude to the following contributors who have helped make this caregiver's guidebook possible: Associate Professor Tan Ah Moy Senior Consultant Haematology /Oncology Service Department of Paediatric Subspecialties KK Women's and Children's Hospital Ms Lim Yan Yin Nurse Manager Children’s Cancer Centre, Ward 76 KK Women's and Children's Hospital Ms Chua Yi Xuan Senior Clinical Pharmacist Pharmacy Department (Oncology Pharmacy) KK Women's and Children’s Hospital Ms Jasly Koo Dietitian Department of Nutrition and Dietetics KK Women's and Children's Hospital Ms Vijayakumari K Senior Principal Transplant Coordinator Haematology /Oncology Service Department of Paediatric Subspecialties KK Women's and Children's Hospital HSCT Medical Team Haematology /Oncology Service Department of Paediatric Subspecialties KK Women's and Children’s Hospital HSCT Nursing Team Children’s Cancer Centre, Ward 76 KK Women's and Children’s Hospital ‘Oncology Pharmacist Team Pharmacy Department (Oncology Pharmacy) KK Women's and Children’s Hospital Department of Nutri KK Women's and Children's Hospital Ms Liow Hwee Hsiang Senior Certified Child Life Specialist Senior Counsellor Children's Cancer Foundation Patients and families who have contributed their stories to this guidebook. Marketing Communications Team (KK Women's and Children's Hospital) in assisting the editorial of the guidebook. Copyright © 2018 KK Women's and Children’s Hospital. All ights reserved. The material may not be reproduced or distributed, in whole or in pert, without the prior written permission of KK Women's and Children's HorpitalHaematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers FOREWORD HAEMATOPOIETIC STEM CELL TRANSPLANTATION AND CANCER IMMUNOTHERAPIES Traditionally the source of haematopoietic stem cells is the bone marrow, therefore termed “bone marrow transplant” (BMT). Peripheral blood (PB) and cord blood (CB) are the alternative sources of haematop: HSCT, the stem cells can be from @ matched family donor (usually a sibling), or matched unrelated donor. In autologous HSCT, the patient's own stem cells are used. Recent advances in stem cell transplant technology also make it possible for partially matched related donor (haploidentical HSCT) to be used when no matched donors are available. ic stem cells. In alloger HSCT is used mainly for high-risk leukaemia or relapsed leukaemia, but can be used to treat other types of cancers (e.g. high-risk neuroblastoma), as well as non-malignant conditions (e.g. certain blood disorders or immune disorders). During HSCT for cancers, high doses of chemotherapy, with or without radiotherapy, are usually given to kill cancer cells. However, the body's normal blood stem cells are alo destroyed by the intensive treatment. Healthy blood stem cells from a@ donor are then transplanted into the body, to replace the destroyed normal cells. Sometimes, the conor stem ling effect. cells can also have cancer: Cancer immunotherapy is an emerging field that involves the use of the immune system to fight cancer. Examples of cancer immunotherapies include: = Antibodies to target certain cancers (e.g. anti-GD2 antibodies for neuroblastoma) = Checkpoint inhibitors that release the callow immune killing of the cancer cells, = Cellular immunotherapies such as “CART cell therapy” that manipulate and redirect the immune cells to kill specific cancers. rakes” in the immune system and therefore Such complex therapies require a clean and safe environment to reduce the risk of serious infections, and support from our multidisciplinary medical teams to monitor and manage any complications. Therefore, @ holistic approach with medical and allied health staff working hand-in-hand with caregivers is of paramount importance to the success of HSCT. Associate Professor Tan Ah Moy Senior Consultant Director of HSCT ProgrammeHaematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers CONTENT 1 INTRODUCTION 1 2 PREPARING FOR TRANSPLANTATION 2 When will transplantation take place? Pre-trensplantation family conference Selecting a caregiver Pre-transplantation investigations and procedures Insertion of a central venous catheter Items to bring to the hospital 3 THE TRANSPLANTATION ADMISSION 5 Room setting Housekeeping Guidelines for caregivers and visitors Patient and fami General precautions Patient safety -centered care 4 ADAY INA TRANSPLANTATION ROOM 7 Atypical schedule Vital signs Blood works and lab tests Weighing your child Personal hygiene Medications Intake and output recording 5 CONDITIONING THERAPY uN Thymeglobulin® Busulfan Cydlosphosphamide Fludarabine Treosulfan Melphalan Thiotepa 6 _ INFECTION PROPHYLAXIS 14 Anti-vit Anti-fungall Anti-pneumocystis 7 TRANSPLANTATION DAY 16 Before stem cell infusionHaematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers CONTENT 9 10 W 12 13, 14 During stem cell infusion After stem cell infusion Engraftment MANAGING SIDE EFFECTS AND COMPLICATIONS 18 Transfusion of blood products Fever and neutropenia Nausea and vomiting Diarthoea ‘Mucositis and oral hygiene Sinvosoidal obstruction syndrome Fatigue Graft versus host disease DIET AND NUTRITIONAL CARE 30 Cancer treatment and nutritional needs A balanced diet Low-bacteria diet Food safety tips The use of medical supplements, traditional herbs and organic products ‘Commercial nutritional supplements Feeding by tube and parenteral nutrition COPING WITH TRANSPLANTATION AND ISOLATION 38 How can you support your child ‘Supporting siblings Preparing yourself for the transplantation Post-transplantation PLANNING FOR HOME 45 Discharge criteria Patient education and caregiver training When to call for medical help APPOINTMENT AFTER DISCHARGE 47 How does @ day in CDT look like? USEFUL TELEPHONE NUMBERS 48 PATIENT AND CAREGIVER STORIES 49 ‘An adolescents journey of undergoing allogenic HSCT ‘A mother’s journey with her child undergoing autologous HSCTHaematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers INTRODUCTION Haematopoietic Stem Cell Transplantation is also called bone marrow transplantation or stem cell transplant. WHAT IS IT ACTUALLY? “Haematopoietic” basically means blood forming. “Stem cells” are cells that can continuously replicate cells exaclly like themselves or produce different cells that make up the blood, such as red blood cells (bring oxygen to all parts of your body), white blood cells (to fight infection) and platelets (help your blood to clot when yeu bleed). The stem cell is produced in the bone marrow, a soft spongy area in the center of some of the larger bones in the body. Most of the stem cells stay in the bone marrow until they are transformed into the different blood cells, which are then released into the blood stream. This is a very active process in which millions of different cells are produced Fy hour, “Transplantation” is the process of taking the tissue or organ of one person and implanting it in another body. So, haematopoietic stem cell transplantation basically means taking blood forming cells from one person and giving it to another person. The basic idea of HSCT is to transfuse healthy stem cells into the patient after the patient's own unhealthy stem cells are eliminated by very high-dose chemotherapy and sometimes, a form of radiation therapy known as total body irradiation. The purpose of the chemotherapy and radiation therapy is to kill all cancer cells in the body, as well as any abnormal cells in the bone marrow. After the stem cells are infused into the patient, the new stem cells will start to grow in the body and make new blood cells for the body to function There are a few different types of HSCT depending on the diagnosis and goals of the HSCT. 1. Aulologous HSCT = the donor isthe patient himself/herself 2. Allogeneic HSCT — another person is donating stem cells to the patient. The person can be a sibling or an unrelated donor. The stem cells can also come from umbilical cord blood of an unrelated donor. This kind of transplantation will require a sample of blood to determine that the donor and patient have matching tissue type, also known ‘as Human Leukocyte Antigen (HLA) typing. Both the donor and patient should ideally be a 100% match, 3. Haploidentical HSCT — another person who has 50% simi stem cells to the patient, The person is ty kind of transplantation is usvally done if a fully-matched donor is not available. tissue type will donate the ally the biological parent or sibling. This Page |1Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers PREPARING FOR TRANSPLANTATION WHEN WILL TRANSPLANTATION TAKE PLACE? The timing of your transplantation is dependent on many factors, such as the status of the disease and the availability of the donor. PRE-TRANSPLANTATION FAMILY CONFERENCE Before the transplantation admission, the patient and his/her immediate family members will be invited to meet with the transplantation medical and nursing team. During this session, the transplantation doctors will discuss details such as the reason for the transplantation, the process and potential risks or side effects that the patient may experience during and after the transplantation. The patient and family members will have the opportunity to ask questions and clarify any doubts regarding the option of transplantation. Once you agree with the decision, we will need you to sign a consent form to proceed with the transplantation. SELECTING A CAREGIVER During the family conference, you will be asked to identify a main caregiver to take care of the child during the transplantation admission. Your child will be expected to stay in the hospital for approximately four to six weeks, depending on the type of transplant he/she is undergoing. The caregiver plays an important role during the admission, providing emotional support and physical care for the child. During this period, the child's immunity will be low. AS @ result, he/she will be more susceptible to catch any infection during the transplantation admission. The caregiver should ensure that the child is well before going into the tronsplantation room. PRE-TRANSPLANTATION INVESTIGATIONS AND PROCEDURES The medical team will schedule many tests and appointments before your child is admitted for haematopoietic stem cell transplantation. A schedule of the pre-transplantation evaluation will be provided for your child, The purpose of these tests is to identify any problem that exists before the transplantation and have a baseline result before the transplantation so that the medical team can compare and measure any changes during and after transplantation. Tests and appointments may include the following: = Heart studies: 2D echo (echocardiogram) + Breathing studies: Lung function test, chest X-ray + Xray bone age (left wrist) = Dental examination, mouth X-ray: © The dentist will discuss any dental problems with the transplantation doctor before filling any cavities or removing any infected teeth © Your child may need to take antibiotics before or after the dental appointment = Other blood investigations to evaluate the kidney, liver function and viral status Page |2Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers INSERTION OF A CENTRAL VENOUS CATHETER Your child will be scheduled for a central venous catheter, also known as a Hickman Line, to be inserted before the transplantation. This is a small soft tube with two lumens that is placed in the blood vessel in the chest that goes to your heart. It is used for taking blood, giving intravenous medicine, stem cell infusion and blood transfusion. The Hickman Line will be inserted by a surgeon in the operating theatre when the is placed under general anesthesia. Several centimeters of the Hickman Line can be seen remaining outside the body with the catheter stitched onto the skin to { prevent it from slipping out. A dressing will be ‘HEART placed over the Hickman Line site to prevent hickenan Ga ie = } bacteria from entering the body. mens fe woud _/ ‘akingand giving Intravenous Medicine Care of your Hickman Line If germs get into the catheter, they can go into the blood and make your child sick. It is very important to take good care of the Hickman Line so as to prevent infection. During the hospital stay, the nurses and doctors will inspect the frequently to look out for signs of infection. However, we asked for your participation in the care of your child by checking the exit site regularly as well, to lock out for the following signs of possible line infection: kman Line i The intravenous ll be changed every four days, the dressing will be changed at least once a week or whenever it is unravelled or wet. Your child may have multiple intravenous lines connected to the catheter; in which case the lines should be secured well to prevent tension as your child may feel a “pulling” sensation from the site when the line is tugged. Do inform the nurses when the infus pump alarm is activated so that our nurses can troubleshoot it promptly to prevent line blockage, which can occur if the fluid does not flow through the line continuously. Page 13Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers ITEMS TO BRING TO THE HOSPITAL You are allowed to bring some of your child's favourite toys, laptop and computer games that can keep him/her entertained during the hospital stay. Books are allowed but avoid borrowing books from common libraries because the books have been touched by many people and those may carry a lot of germs or dust. Stuffed toys and pillows/bolster are discouraged as well since these items tend to trap dust and dirt. Jackets and socks are allowed to keep the patient warm, but caregivers need to change them daily or when soiled. All items should be cleansed thoroughly and packed in a clean bag. We ask that you minimise the things that you bring to the hospital as the transplantation rooms are small. Excessive personal belongings can obstruct the space required for the doctors and nurses to examine the child or perform necessary procedures. Another reason is that these items can also gather dust over time when they are not wiped down frequently. Page | 4Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers THE TRANSPLANTATION ADMISSION ROOM SETTING Your child will be admitted to one of the transplantation rooms in ward 76. Transplantation rooms are single (isolation) rooms designed to have positive air pressure. The purpose is to let the air flow out of the room and prevent the air outside from going into the room. In this way, the patient is kept away from air-borne microorganisms. nursing or protective isolation. The rooms are also built with HEPA-filter. HEPA stands for “high- efficiency particulate air” and the filler works by removing all airborne contamination to prevent air contamination. As bacteria can thrive in a warm environment, the rooms are generally kept at a lower temperature. The temperature is centrally controlled, and you will not be able to adjust it according to your preference. However, the nurses can help by providing more blankets if you or your child feels cold. is also known as reverse barrier HOUSEKEEPING The housekeeper will start to clean the transplantation rooms from 7.00am. He/she will assist in emptying the trash bins, clean the toilet and basin, and wipe the floor surface every morning, We seek your cooperation in maintaining the hygiene of the room by cleaning up surfaces if there are spill Please keep your personal belongings so that the housekeeper can access areas such as roller tables, sofa bed, window frames and toys daily. We recommend that you use the wet wipes provided to clean these surfaces and avoid using a feather duster or dry cloths. GUIDELINES FOR CAREGIVERS AND VISITORS We understand that emotional and physical support from your loved ones can help the child to adjust to hospital stay. However, to protect the safety and health of your child and all our Patients, please follow the hospital's visiting guidelines. For allogenic and haplo-identical HSCT, only one designated caregiver can enter the room ‘and stay with the patient throughout the transplant admission. No other visitor is allowed until the patient is deemed to have adequate immunity based on blood counts For autologous HSCT, two caregivers are allowed to visit the child during daytime but only fone caregiver can stay during the night with the child. No other vi patient is deemed to have adequate immunity based on blood counts. ris allowed until the PATIENT AND FAMILY-CENTERED CARE KK Women's and Children’s Hospital practices family-centered care and consider you, the caregiver, as integral in the complete care plan of your child, especially in understanding the needs and changes in your child. The medical and nursing team’s priority is to attend to your child’s medical needs and nursing care. It is essential for parents to be closely involved in the patient’s basic care in partnership with the nursing and medical team to ensure safe and quality care is provided to the child. Every morning, the medical team will discuss your child's care and you are encouraged to ask questions or raise any concerns regarding your child's Page | 5Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers care. If you have additional questions, please let your nurses know so that the medical team can arrange to meet you. GENERAL PRECAUTIONS. You are required to wear a mask at all times to protect your child from catching any infection from you. Washing your hands and your child’s hands is the best way to prevent the spread of germs. Our hands pick up germs when we touch people or things. It would be impossible to avoid contact with germs but you can reduce the chances of infecting your child when you wash your hands or perform alcchol-based handrubs frequently. There are “5 moments of hand hygiene" that you should adhere - Before touching the patient = After touching the patient = After handling patient's body fluid (e.g. handling vomitus, diapers, assisting the child in the toilet) ~ Before aseptic procedure (more relevant for healthcare providers) = After touching patient's surroundings The antiseptic soap and alcchol-based handrubs are readily available and easily accessible in the wards. There are also handwashing guidelines placed at every sink to help you remember the ‘7 steps to handwashing! As moist environment can promote mold and fungal growth, the toilet should always be kept clean and dry. To prevent infection, the patient is not allowed to enter the bathroom at all times during the transplantation admission. The caregiver can use the toilet in the transplantation room but will need to proceed to the bathroom outside the room and located within the ward for showering, PATIENT SAFETY It is essential that your child wears the identification band at all times in the hospital. This is to ensure that the medical staff can identify him/her correctly to provide the right and safe care, The appropriate type of bed will be allocated to your child for safety reasons and to prevent falls. If your child is less than four years old, he/she will be given a cot bed. Bigger beds are nly allowed for children aged four years and above. We DO NOT allow any co-sleeping with the child on the same bed for the safety of your ¢ Ensuring your child's safety is our top priority, so we encourage you to speak up if you have any concerns pertaining to the care of your child. If you notice that our nurses, doctors or other healthcare team members have forgotten to perform hand hygiene before touching your child, please remind them. Your participation in providing safe care for your child is important. Page 16Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers A DAY IN A TRANSPLANTATION ROOM ATYPICAL SCHEDULE ‘Schedules are customised based on your child's medical needs. This is @ sample of a typical schedule for a patient undergoing transplantation 3.00am te 4.00am Vital signs monitoring 30am to 6.00am Blood drawn from the central venous catheter Intravenous (IV) medication 7B0am to 9:00am | Nurses’ assessment by morning shift nurses Morning vital signs Oral medications Weight-taking Breakfast Shower 9.00am to 11,00am | Doctor's rounds 17,00am t012.00pm __| Vital signs 12.00pmte 4.00pm | Oral and IV medication Lunch Nurses’ assessment by afternoon shift nurses ZO0pm to 6.00pm | Vitel signs IV tubing change if due Diner 7.00pm to 9.30pm | Vital signs Oral and IV medication Nurses’ assessment by night shift nurses T1.00pm to 12,00em | Vital signs Page | 7Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers VITAL SIGNS Your child’s vital signs must be checked regularly, and this can range from hourly to every four-hourly. The vital signs include the checking of your child's temperature, blood pressure, respiration and oxygen saturation. It will be recorded in the patient chart that allows us to monitor your child’s progress closely during his/her transplantation stay. If your child is asleep and it is time to take the vital signs, we may have to wake him/her. The vital signs may be taken more often such as when patients are receiving stem cell infusion, blood products, IVIG or certain medications. The nurses will let you know when we expect to take vital signs more often than every four-hourly, so you can help to prepare your child. BLOOD WORKS AND LAB TESTS Daily full blood count and renal panel will be taken from your child's central line around 4.30am to 6.00am. Lab tests may be required more often, depending on the condition of your child. The nurses will update you on the full blood count result daily because we understand that you will want to monitor your child's progress. If you need an explanation on your child's lab results, the transplant team is there to help you, © WEIGHING YOUR CHILD { \ Your child must be weighed daily, preferably early in the morning before breakfast. He/she should be weighed wearing only pajamas and after passing urine or diaper change to ensure accuracy. A weighing machine may be placed in the room for convenience to weigh your child. Your child must be weighed so that the doctor can calculate his/her medication dosage accurately and make sure the amount of fluid in your child's body is balanced. Page | 8Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers PERSONAL HYGIENE Your child will be sponged daily in the morning using packet wipes for body surface. His/her pajamas, bed linen, pillowcase and blanket should be changed daily or when soiled. It is important to moisturise your child's skin using a mild moisturiser to prevent the breakdown of dry skin that can be caused by the medications. Your child is not allowed to enter the bathroom inside the transplantation room at all times. Commode/bedpan or urinal will be provided to assist in your child’s tolleting needs. > 6 MEDICATIONS 8 ‘As nausea and vomiting can occur during your child’s treatment, we make every attempt to give your child medications intravenously through the central line. However, there are still some medications that have to be given orally. We seek your cooperation to give the oral medication at prescribed times for optimal results. A soft nasogastric feeding tube may be inserted in your child if your child refuses to take the medication orally. This is necessary to ensure all important oral medications are given. GY INTAKE AND OUTPUT RECORDING How much your child eats/drinks and the fluids received through the central line is known as intake. This helps us to check if your child has adequate nutritional requirements and fluid balance in his/her body. Output is urine, vomitus and motion that your child passes out. We want to make sure that everything that is going into your child's body is balanced by your child’s output. Therefore, it is important that you record how much your child eats, drinks and passes urine accurately. If your child has vomited or soiled a diaper, You may pass it to the nurses to weigh it. The other IV fluids and medications given will be recorded by the nurses. The doctors will use the fluid balance to make decisions about your child’s medications and treatments. Sometimes, a medication known as diuretic or commonly referred as Lasix will be given to your child to get rid of extra fluid in the body. Page | 9Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers Sample copy of an intake-output recording chart Intake Output Recording Form for Caregiver, ‘Oral take Dats and Time ‘Output ‘Sample of eeowing iniakevoutput ‘Ore intake [E 9, Water — 100m, Rice — 1 share, Nugge's —2 oes) + Ouput Eg. Unre~ 100m), Passmoton large amourt, sf, brown, Vom it-small, undigested feed) Page | 10Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers CONDITIONING THERAPY Conditioning therapy is @ high-dose chemotherapy ‘and/or radiation that each patient receives before the haematopoietic stem cell transplantation. The goals of conditioning therapy is to remove the patient's existing bone marrow cells so that new marrow cells have room to grow, and also to destroy any remaining cancerous cells in the body. If the patient is receiving cells from another person, the conditioning therapy has an additional purpose of weakening the patient's (host's) immune system so that the donor cells can be accepted by the body. Chemotherapy drugs used in conditioning therapy commonly include alkylating agents such as cyclophosphamide, busulfan, melphalan, thiotepa or nucleoside analogues such as fludarabine. These ven as intravenous infusions, and they work by interfering with the jans individualise the conditioning regimen to suit each patient's disease chemotherapy drugs are usually replication of DNA in cells. Phy: ‘and condition, Generally, common side effects of chemotherapy include hair loss, inflammation and ulceration of the oral cavity and digestive tract (mucositis), nausea and vomiting, and low blood counts. In addition to the common side effects of chemotherapy, there are some commonly used chemotherapy drugs and the potential side effects unique to each drug Page | 11Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers THYMOGLOBULIN® - Rabbit ATG contains antibodies against T-lymphocytes. it is an immunosuppressive agent used to prevent graft-versus-host disease or graft rejection. = Rabbit ATG commonly causes infusion-related reactions with symptoms such as fever, rash, rigors, for changes in blood pressure. To minimise such infusion-related reactions, rabbit ATG will be infused slowly over several hours and premedications (antihistamine and steroid) will be given as well. BUSULFAN ~ Busulfan may sometimes cause a serious liver condition known as veno-occlusive disease or sinusoidal obstruction syndrome (VOD/SOS). Doctors will monitor liver function closely with blood tests and clinical symptoms, e.g. yellowing of the skin or eyes. ~ _ Busulfan may cause fits. To prevent this potential side effect, anti-seizure medication will be given during busulfan therapy. ~ Rarely, busulfan may affect lung function months or years after treatment. Seek prompt medical attention if your child develops cough, whee: 19 oF feels breathless. CYCLOSPHOSPHAMIDE - Cyclophosphamide can form metabolites which may irritate the bladder, resulting in pain or bleeding while passing urine. To prevent this potential side effect of bladder irritation (aka haemorrhagic cystitis), patients are put on together with another medication known as Mesna. It is important to pass urine regularly during treatment to prevent accumulation of the metabolites in the bladder. + High doses of cyclophosphamide have been reported to cause cardiac side effects, including irregular heart rate, heart failure, inflammation of heart muscle, and fluid accumulation in the heart. Doctors will monitor your child's heart function closely. igorous intravenous hydration d FLUDARABINE - Fludarabine may cause fatigue, numbness and tingling of fingers and toes. - Very rarely, fludarabine may cause seizures and confusion, TREOSULFAN + Treosulfan may cause skin pigmentation. = Ensure adequate fluid intake. MELPHALAN = Melphalan can cause damage to the cells lining the mouth and gut, leading to inflammation and ulceration in the oral cavity and digestive tract. It has been found that sucking on ice chips or frozen Pedialyte during administration of melphalan infusion can reduce the severity of oral mucositis. Swish or suck the frozen Pedialyte in the mouth for approximately 30 minutes, starting from five minutes before the melphalan infusion. Page | 12Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers THIOTEPA - Thiotepa is excreted through the skin. Cutaneous reactions, e.g. hyperpigmentation, redness, blistering and itching of skin may occur during thiotepa administration. Preventive skin measures to adopt during thiotepa administration until 48 hours after the last dose of thiotop ° ° Care of Central Venous Access Catheter (CVAD) for pé ° ° The patient should have frequent sponge baths every six-hourly with warm water from sterilising filter tap. Dry the patient's skin well and pay particular attention to the folds of the skin. Dab the body gently and avoid rubbing to prevent injuries to the skin. ‘Sponge bath commences three to four hours after the initiation of the first dose of intravenous thiotepa and this is repeated for the 48 hours after completion of the last dose. The patient's clothes and linens are to be changed after every sponge bath and clothing should be loose fitting and minimal. The patient should avoid the use of any moisturiser, ointment, barrier cream, antiperspirant or deodorant during the recommended duration for skin care preventive measures. For infants and children, diapers should be avoided if possible. If this is not possible, change the diaper hourly or when soiled during the recommended duration for skin care preventive measures. Avoid using baby wipes for cleaning. Use water from the sterilising filter tap to clean the perineum thoroughly instead. Avoid tight-fitting clothes and accessories. nts on ravenous thiotepa: CVAD dressing should be changed daily or when soiled. CVAD site will be cleansed with normal saline solution and covered with gauze-type dressing with minimal tape. Avoid occlusive dressing such as tegaderm during the recommended duration for skin care preventive measures to prevent exposure of excreted thiotepa through the skin. Avoid applying any antimicrobial ointment to the CVAD site during the recommended duration for skin care preventive measures. Page | 13Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers INFECTION PROPHYLAXIS ANTLVIRAL Acyclovir © Acyclovir is given to prevent zoster virus (chicken pox, shingles). HSCT patients are vulnerable to infections as their immune systems are heavily suppressed. Doctors will monitor patients closely for signs and symptoms of infections and initiate treatment promptly. Prophylactic antimicrobial medications will also be prescribed to prevent some of these infections. These medications will usvally be continued for months after initial discharge from the hospital, _post- transplantation. ral infections from herpes simplex virus (cold sores) and varicella © Its given intravenously or orally twice or thrice a day. Intravenous acyclovir is administered over ‘at least one hour to prevent kidney impairment. It is important to ensure that the child is well- hydrated. ANTIFUNGAL HSCT patients are susceptible to infections caused by fungal organisms, e. Fungal organisms can lead to infections in the oral cavity, urinary tract, ski Fluconazole |. Candida and Aspergillus spp. blood, lungs, oF liver. © Fluconazole is given mainly to prevent Candida infections. © Fluconazole is given intravenously or orally once daily an usually well tolerated. © Fluconazole can cause drug interactions with other medications - always check with the pharmacist or doctors before taking any other medications. Page | 14Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers Micafungin © Micafungin is given intravenously once daily over one hour. © Micafungin may cause side effects such as diarrhoea. In rare cases, it may cause abnormal liver functions. Posaconazole © Posaconazole is available as a delayed-release tablet taken once daily (DO NOT crush or chew), or oral suspension taken three times daily after a full meal or liquid nutritional supplement for best absorption, © Posaconazole may cause side effects such as nausea, vomiting, diarrhea and abdominal pain. Rare but serious side effects of posaconazole include abnormal liver function and heart rhythm problems. © The level of posaconazole in the body can be monitored with blood tests, and the dose of posaconazole may be adivsted based on the levels measured. © Posaconazole can cause drug interactions with other medications - always check with the pharmacist or doctors before taking any other medications, Liposomal amphotericin B (Ambisome®) jposomal amphotericin B is given intravenously, over a minimum of two hours to prevent infusion related reactions. © Other potential side effects of amphotericin B include low potassium and magnesium levels, as well as impaired kidney function. ANTLPNEUMOCYSTIS Immunocompromised patients are susceptible to lung infection caused by pneumocystis jiroveei (formally known as pneumocystis carinii and referred to as pneumocys carinii pneumonia, or PCP). Co-trimoxazole is recommended as the first line agent for PCP prophylaxis. In patients who cannot tolerate co-trimoxazole, pentamidine is used. Co-trimoxazole (sulfamethoxazole and trimethoprim) © Cortrimoxazole for PCP prophylaxis is taken orally twice a day, on two days of the week (e.g. Mondays and Thursdays). © Cortrimoxazole should not be given to patients with G6PD deficiency and patients who are allergic to sulfonamides. ©. Side effects of co-trimoxazole include gastrointestinal discomfort, skin rashes and decrease in blood counts. Seek immediate medical attention if skin rashes appear. Pentamidine © Pentamidine is typically given as an intravenous infusion two-to four-weekly for PCP prophylaxis. ©. Te prevent the side effects of low blood pressure, the infusion is given over at least an hour, and the patient is advised to lie down during the infusion duration. Page | 15Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers TRANSPLANTATION DAY Transplantation day is commonly referred to as Day 0. It is the day your child receives his/her own stem cells or from another donor. The infusion of stem cells takes place following the completion of the pre- transplantation chemotherapy. This procedure takes place in the patient's room and is similar to a blood transfusion. The stem cells will be infused through the Hickman Line into the blood stream. Stem cells may be given to your child fresh or after they have been thawed from the frozen stem cell unit. Fresh stem cells are collected from the donor and infused immediately to your child. Frozen stem cells may include umbilical cord blood and your child’s own stem cells collected earlier through an apheresis machine, BEFORE STEM CELL INFUSION: - Your child will be given medications with/without hydration drip intravenously to prevent possible side effects. = A cardiac monitor will be used to monitor your child's heart rate, breathing rate, oxygen level and blood pressure during the infusion. DURING STEM CELL INFUSION: - The transplantation team, comprising the nurse, doctor, lab technician and the transplantation coordinator may be present in the room to observe your child closely. = The infusion time ranges from half an hour to several hours, depending on how much stem cells are required, - tis important that you understand the possible side effects your child may experience so that you can inform the medical team if such effects occur. Side effects may include: © Fever, chills, flushing, rashes and difficulty in breathing. © If the patient has any of these symptoms, the infusion will be stopped and medicine will be given to control the symptoms. The infusion is restarted when the symptoms are under control. © Your child’s urine may become darker because red blood cells break down. If this happens, the patient will receive more intravenous fluid to hydrate the kidneys. © The preservative used for stem cells that have been frozen has a “sweet corn” odor. This odor may cause nausea or headache. Anti-vomiting medications will be given to the patient to prevent this. AFTER STEM CELL INFUSION: ~ Your child will be put on a cardiac monitor for the next 24 hours after infusion is completed to monitor for any side effects that may occur after the infusion. = The transplantation team will require your assistance to record the intake and output to ensure that your child does not retain too much fluid - Inform the medical team immediately if your child is experiencing any of the side effects. Page | 16Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers ENGRAFTMENT: After the stem cells are infused into the body, they will travel through the bloodstream to the bone marrow. Engraftment occurs when the stem cells received on infusion day start to grow and make healthy blood cells in your child's body. Engraftment happens when absolute Neutrophils is > 0.5 X 3 consecutive days The time of engraftment will depend on the source of your stem cells. Source Approximate Duration Poripho ~ 2 weeks Bone Mar ~ 3 weeks Cord Blood ~ A weeks During this period, your child will be vulnerable to infection. Strict infection control precaution should be taken to prevent and minimise the risk of infection. Page | 17Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers MANAGING SIDE EFFECTS AND COMPLICATIONS TRANSFUSION OF BLOOD PRODUCTS ‘Transfusion is the administration of blood or blood products through your child's central line. It is given for many reasons. Red blood cells: Also known as Haemoglobin (Hb). They carry oxygen throughout the body and give us energy. If your child has a low Hb, called anemia, your child may receive a red blood cell transfusion. Platelets: Platelets help stop bleeding by plugging holes in blood vessels. If your child has a low platelet count, called thrombocytopenia, your child may receive a platelet transfusion. Fresh frozen plasma: Plasma is the clear liquid portion of blood that also helps stop bleeding. Intravenous Immunoglobulin (IVIG): IVIG is a part of plasma that contains antibodies that help fight infection. itis usually given once a week during the transplantation stay. Albumin: Albumin is @ blood protein that may be given to treat low blood pressure or excessive blood protein loss. The amount of blood products depends upon your child’s weight. A signed consent from you/the patient's guardian is necessary prior to a blood product transfusion. The consent will be taken by a doctor upon your child's acmission. Your child will have to be monitored closely during the transfusion and vital signs will be taken frequently. The nurse will check the temperature, pulse, respiration, blood pressure and oxygen saturation throughout the transfusion and up to one hour post transfusion. The nurse will also watch out for any side effects or reactions. A red blood cell transfusion will usvally take three to four hours to complete; platelets require 45 minutes to 60 minutes to infuse; IVIG may take three to five hours to complete or longer, depending on your child’s condition. Transfusion reactions: Common signs of reactions include fever, chills, breathing difficulty, rashes, red face, eye or lip swelling. Please inform the nurse immediately if your child experiences any of the symptoms. The nurse will stop the transfusion if these reactions occur and medication may be given to relieve the symptoms. Your child may then need these medications before each transfusion which is commonly referred as “pre-medications”. Page | 18Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers FEVER AND NEUTROPENIA, Fever and neutropenia are common complications of a transplantation treatment. Neutropenia is a decrease in the infection-fighting white blood cells called neutrophils. Your child is considered neutropenic if he/she has an absolute neutrophil count (ANC) of less than one. Fever is defined as when your child’s temperature is 38.5 degree Celsius or more than 38.0 degree Celsius measured twice within an hour. As your child has an increased risk of infection, our care team will monitor him/her for signs of infe ‘and blood will be drawn from all the central lines to check for bacteria. Stool and urine investigations may be done to rule out any infection. Your child will be prescribed with IV antibiotics which may continue even if the fever goes away. Paracetamol may also be given to lower your child’s temperature, and cooling measures such as loose light clothing, cold compress and sponging will be offered by the nurses. Page | 19Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers NAUSEA AND VOMITING Chemotherapy-induced nausea and vomiting is ¢ commen side effect which can cause fear among children. At the same time, it is one of the worrisome treatment-related symptoms for parents and caregivers. Nausea is an uncomfortable urge to vomit. Nausea can be experienced before vomiting. Some children may feel nauseous even if they have not taken anything. Vomi \9 is defined as the expulsion of food from the stomach with fluid contents through the mouth and sometimes, the nose. Frequent vomiting can cause dehydration and electrolyte imbalance. Some patients may inhale vomited feeds which can cause choking in what we term as aspiration. Fortunately, nausea and vomiting can be prevented or well-controlled with medications. These anti-vomiting medications will be given as an injection through the central venous catheter. The medical team will ensure appropriate anti-vomiting medication is given approximately 30 minutes before the commencement of chemotherapy //radiation therapy to prevent nausea and vomiting, and will continue to administer it regularly during the conditioning p iod. However, please inform your nurses if your child is experiencing any nausea so that additional anti-vomiting medications can be given. As it will be harder to control once your child starts vomiting, adequate management before the start of the distressing symptom is crucial in keeping your child as comfortable as possible during the transplantation. There are conservative measures such as giving your child his/her favourite type of food. Try to avoid unpleasant smells that can trigger nausea. Taking small frequent meals can also help manage nausee. In the event of vomiting, let your child lie on his or her side to avoid choking. Please inform the nurses immediately if your child vomited blood or vomitus resembling coffee colour. It may signal internal bleeding. If your child's frequency of vomiting is not reduced and he/she has been passing less but dark yellow urine, this may indicate dehydration. More IV fluids will be given to your child through the central line or a soft nasogastric tube may be inserted to keep him/her hydrated. Page | 20Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers DIARRHOEA Diarrhoea can be caused by one or more of the following: chemotherapy, radiation, mucositis, medications, infection, graft versus host disease and certain food or fluids (e.g. dairy and lactose-containing products). The medical team will try to decrease or change the medications or food that may be causing the diarthoea. The nurse will require your help to accurately measure and chart down the stool amount, colour and texture. If your child continues to have diarrhoea, we may send stool samples to check for infection. Your child will also be monitored closely as severe diarthoea can cause dehydration. Intravenous fluids and electrolytes will be given to replace the lost fluids. The perianal area can become sore and the skin may start to break down. If this happens, your child will be at higher risk of infection. It is very important to keep the rectum clean and dry. We recommend that you use cooled boiled water provided by the nurses to clean your child’s rectum after every time he/she passes motion or when you change his/her diaper. Protective barrier cream is recommended to prevent further breakdown and to help the skin heal. You can check with your nurses on the appropriate product to use. Your child may be offered pain medications or gels to relieve any pain or soreness in the p Hond hygiene is important in preventing the spread of infection. We ask that all caregivers wash your hands with soap and water before and after touching the patient and upon entering or exiting the inner room. Page | 21Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers MUCOSITIS AND ORAL HYGIENE ‘Mucositis is the inflammation and ulceration of the lining of the mouth, throat and the rest of the digestive tract commonly developed in most transplantation patients. This is caused by the conditioning chemotherapy /radiotherapy that damage the cell lining. Mucositis usually occurs a few days later after starting the conditioning therapy. The symptoms can persist for seven to 14 days or longer before healing begins. During this period, your child is also more prone to oral fungal and viral infections. Thus, effective oral hygiene is extremely important. Teeth brushing Use a small, soft bristle toothbrush with fluoridated toothpaste. Brush at least two to three times a day. Rinse toothbrush well after every use and allow to air dry. Replace toothbrush every three months or when bristles are worn out to ensure effective brushing ‘and to minimise infection. Toothbrush should be changed following an oral infection. © Foam cleaning sponges (moistened with water or diluted chlorhexidine) may be used when your child is unable to tolerate tooth brushing (e.g. when your child has no teeth or has severe mucositis e000 ° oral ulcers). Mouthwash © Helps keep mouth moist and clean by removing debris. © Use mouthwash after every meal or brushing, and avoi ‘an hour after rinsing © Either 0.9% sodium chloride or salt-water is recommended. © Mouthwash containing xylitol or fluoride is recommended if your child can tolerate the taste and is able to spit it out. © Short-term chlorhexidine mouthwash may be recommended. However, prolonged use may result in brown stains on the teeth. eating and drinking during the first half Page | 22Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers Lip balm © Oral cryotherapy is a treatment using ice chips or popsicles placed in the mouth to prevent the development of oral mucositis if you received a type of chemotherapy called melphalan. © Your child will be advised to suck the ice chips or popsicles five minutes before the infusion and to continue doing so for the next 30 minutes. Important Note: If your child complains of sore gums or pain during brushing, please refrain from brushing his/her teeth to prevent gum bleed. Frequent mouthwash will be adequate. Page | 23Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers SINUSOIDAL OBSTRUCTION SYNDROME This is also known as veno-occlusive disease. It is a condition in which the tiny vessels inside the liver are damaged by chemotherapy /radiation, causing blockage and obstruction inside these liver vessels. This leads to enlarging of the liver, causing pain over the right upper quadrant of the abdominal, fluid retention causing weight gain, and yellowing of the skin and eyes. If these symptoms occur, your child may require frequent platelet transfusion. A preventive medication called ursodeoxycholic acid will be given to your child to reduce this risk. Sometimes, a drug called defibrotide may be given to your child for treatment depending on your child's condition. Supportive care will be provided, such as taking out or reducing the dose of the medications that will further harm the liver, reducing fluid intake or giving medication to pass out excess fluid. Blood tests to check I's progress. iver function will be taken more frequently to monitor your Page | 24Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers FATIGUE Fatigue can be described as feeling more tired than usual. The fatigue that comes with the transplantation treatment is different from the fatigue of daily life because it may last longer, and rest does not always help. Fatigue can be caused by: tion or other medications ‘Treatment such as chemotherapy, ra ‘Physical factors such as change of routines in sleeping and daily activities * Mental or emotional factors such as stress, anxiety, worry, sadness or fear ‘Some of the strategies that may be useful to you in helping your child cope better with fatigue during the treatment period includ © Frequent short rest periods during the day © Regular light exercise (e.g. light stretches, changing of position in bed or a daily walk within the transplantation room) © Develop @ normal sleep routine Discuss your concerns with the transplantation team * Discuss with your nurse to develop a routine that may suit your child to minimise disturbance during the stay Page | 25Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers GRAFT VERSUS HOST DISEASE (GVHD) GVHD is a potential complication of allogeneic and haploidentical HSCT. The conditioning therapy suppresses your immune system to stop your body from rejecting the donor stem cells. Once the donor stem cells begin to engraft and function as your new immune system, the donor T-lymphocytes (a type of white blood cell) of your new immune system (graft) may see your child's body (host) as foreign and react by trying to destroy your child’s tissues and organs. However, having mild GVHD can be a good thing if your child has a cancerous disease. The donor T cells, aside from attacking your body cells, will also destroy any residual or remaining cancer cells. Doctors call this the graft versus host disease or tumour effect. This will help to prevent the disease from coming back. Acute GVHD which usually starts within 100 days of transplantation, typically affects three main organs: skin, gastrointestinal tract and liver. Signs and symptoms may include: 1. Skin © Rashes: usually happens on the palms, soles of the feet and behind the ears. Rashes can also appear in other places. It vsvally causes itchiness and occasionally, pain. If severe, the skin may develop blisters. 2. Gastrointestinal tract * Diarrhoea * Nausea/vomiting * Stomach pain or cramping Little or no interest in eating ‘* Abnormal liver function (Raised bilirubin level) © Yellowish skin and eyes (Jaundice) ic GVHD typically starts after day +100 and may have similar symptoms. Page | 26Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers Certain medications are given to prevent GVHD and they are known as immunosuppressants (e.g. ciclosporin, tacrolimus, methotrexate, mycophenolate, sirolimus). Immunosuppressants are given to reduce the risk of GVHD, by reducing the ability of the donor T-lymphocytes from attacking the host's organs and tissues. These medications will be continued for a few months to a year after HSCT, depending on the condition of your child. If your child develops GVHD, doctors may consider the use of corticosteroids for the treatment of GVHD. Tacrolimus + Tacrolimus is given as an intravenous infusion during the initial period of HSCT. It is also available in oral suspension and oral capsules (0.5mg, Img), and is to be taken twice daily. Oral tacrolimus is best absorbed when taken on empty stomach (i.e. one hour before food or two hours after food). if your child experiences stomach discomfort, it may be taken with food. Take consistently with or without food. - Different brands of Tacrolimus are not interchangeable - it is advisable to only obtain supply from the hospital pharmacy. = Tacrolimus dose is titrated according to the level of tacrolimus in the blood. Tacrolimus levels will be monitored once or twice weekly. Blood samples are drawn right before the next dose (trough). To ensure accuracy of the blood test results: © Always take the medication at the same time each day (about 12 hours apart), and consistently with or without food. © On the day of blood test, remember to give the morning dose only after the nurse has drawn the blood sample. (Do bring along the medication to the hospital on the day of CDT visit, so that the dose may be given once the nurse has drawn the blood sample.) - Tacrolimus is subjected to many potential drug interactions, which can result in higher or lower levels of tacrolimus. © A-commonly encountered drug-to-drug interaction is that between antifungal medications (e.g. fluconazole, posaconazole, itraconazole, voriconazole) and tacrolimus. Antifungal drugs can cause higher levels of tacrolimus in the blood. Pharmacists and doctors will ensure close monitoring and titration of tacrolimus whenever antifungal drugs are started or stopped. ~ Always check with the pharmacist or doctors before taking any medications or supplements. DO NOT take pomelo or grapefruit while on tacrolimus. ~ Side effects of tacrolimus include: increased blood pressure, impaired kidney function, deranged electrolytes (magnesium, potassium), increased triglycerides, increased blood sugar, insomnia, headaches and tremors. itis important to maintain good fluid intake to reduce the risk of kidney problems. - Always wear gloves when handling immunosuppressant drugs. DO NOT handle with bare hands. Methotrexate ~ Methotrexate is usvally given intravenously on days +1, 3, 6 and 11. ~ Side effects of methotrexate include: bone marrow suppression, oral ulcers, impaired liver function. Page | 27Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers Mycophenolate - Mycophenolate is given twice or thrice a day. Oral suspension and capsules should be taken on ‘empty stomach, either one hour before or two hours after food. However, it may be taken with food if your child experiences stomach discomfort. = Side effects of mycophenolate include: diarrhoea, stomach discomfort, low electrolytes (magnesium, potassium), headache, anxiety, tremor. - Always wear gloves when handling immunosuppressant drugs. DO NOT handle with bare hands. Ciclosporin - Ciclosporin is given as intravenous infusion twice a day during the initial period of HSCT. itis also available in oral solution and oral capsules (10mg, 25mg, 100mg}. - Different brands of ciclosporin are not interchangeable - it is advisable to only obtain supply from the hospital pharmacy. - Ciclosporin dose is titrated according to the level of ciclosporin in the blood. Ciclosporin levels will be monitored once or twice weekly. Blood samples are drawn right before the next dose (trough). To ensure accuracy of the blood test results: © Always take the medication at the same time each day (about 12 hours apart), and consistently with or without food. © On the day of the blood test, remember to give the morning dose only affer the nurse has drawn the blood sample. (Do bring along the medication to the hospital on the day of Children's Day Therapy (CDT) visit so that the dose may be given once the nurse has drawn the blood sample.) - Ciclosporin is subjected to many potential drug interactions, which can result in higher or lower levels of ciclosporin. © A commonly encountered drug-to-drug interaction may occur between antifungal medications (e.g. fluconazole, posaconazole, itraconazole, voriconazole) and ciclosporin. Antifungal drugs can cause higher levels of ciclosporin in the blood. Pharmacists and doctors will ensure close monitoring and titration of ciclosporin whenever antifungal drugs are started or stopped. - Always check with the pharmacist or doctors before taking any medications or supplements. DO NOT take pomelo or grapefruit while on ciclosporin, = Side effects of ciclosporin include: increased blood pressure, impaired kidney function, low electrolytes (magnesium, potassium), increased hair growth, swollen gums, increased triglycerides, headache and tremor. It is important to maintain sufficient fluid intake to reduce the risk of kidney problems. - Always wear gloves when handling immunosuppressant drugs. DO NOT handle with bare hands. Page | 28Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers = Sirolimus is available as oral tablets and is given once daily. May be taken with or without food. Take consistently with meals to minimise absorption variability. - Sirolimus dose is titrated according to the level of sirolimus in the blood. Sirolimus levels will be monitored approximately once every week. Blood samples are drawn right before the next dose {trough). - To ensure accuracy of the blood test results: © Always take the medication at the same time each day, and consistently with or without food. © On the day of the blood test, remember to give the morning dose only after the nurse has drawn the blood sample. (Do bring along the medication to the hospital on the day of CDT visit, so that the dose may be given once the nurse has drawn the blood sample.) ~ Sirolimus is subjected to many potential drug interactions, which can result in higher or lower levels of sirolimus. © Acommonly encountered drug-to-drug interaction is that of antifungal medications. (e.g. fluconazole, posaconazole, itraconazole, voriconazole) and sirolimus. Antifungal drugs can cause higher levels of sirolimus in the blood. Pharmacists and doctors will ensure close monitoring and titration of sirolimus whenever antifungal drugs are started or stopped. = Always check with the pharmacist or doctor before taking any medications or supplements. DO NOT take pomelo or grapefruit while on sirolimus. - Side effects of sirolimus include: stomach discomfort, increased lipid levels, headache, swelling of hands and feet, and joint pain. - Always wear gloves when handling immunosuppressant drugs. DO NOT handle with bare hands. Page | 29Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers DIET AND NUTRITIONAL CARE CANCER TREATMENT AND NUTRITIONAL NEEDS A child with cancer can have predisposing factors affecting food intake and metabolism. Cancer treatments which include surgery, radiotherapy, and chemotherapy, could complicate @ child's nutritional needs. The child’s body has to work hard to repair damaged cells, excrete waste products, and at the same time, build new cells to support normal growth and development. Although parents know that children need to obtain adequate energy and nutrients, children who are ill often do not eat well. Some side effects arising from the treatment may compromise the child's nut Goals of nutritional car Achieve normal growth and development. © Prevent significant weight loss, Le. 5% to 10% of usual body weight, to optimise treatment outcomes. to continue with normal activiti (© Improve quality of life. (© Prevent problems or delays in treatment. Page | 30A BALANCED DIET Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers Children undergoing cancer treatment can benefit from a well-balanced diet by consuming food from each of the following food groups. It is important that you do not omit any food groups to ensure overall nutrition adequacy (e.g. include at least one food item from each food group per meal). we ALTHY Py sw $90 an eh O iran os US “My Healthy Plate” is a friendly visual tool on healthy eating habits designed for Singaporeans by the Health Promotion Board (HPB). Notrients provided Examples Rice and alternatives Provides energy, vitamins (especially B Vitamins — thiamine, riboflavin, and niacin), magnesium, and fibre (if wholegrain products are chosen). Rice, noodles, bread, biscuit cereal, oats, chapatti, thosai, pasta and potatoes. ‘Meat and alternatives Essential for growth, healing and a strong immune system. Meat, fish, poultry, eggs, milk and dairy products, tofu, dried beans, and nuts. Froits and vegetables Provides phytochemicals which act as antioxidants to protect cells from damage. (Note: fruit/vegetable juices should not replace a meal) Eat a colourful variety of fruits and vegetables (e.g. red, green, yellow, orange), including fresh, frozen and canned froits, juices. Dietary fats Good source of energy and essential for many body functions. Use healthier unsaturated off e.g. canola oil, soybean oll or olive oil, margarine (trans fat free), seeds and nuts. Page | 31Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers LOW-BACTERIA DIET Children who undergo chemotherapy, radiotherapy or bone marrow transplant may have lower immune functions and are at risk of developing food-related infections. The purpose of a low-bacteria diet is to avoid food that are more likely to contain infection-causing microorganisms. The appropriate diet will be advised by your doctor and should be stricly adhered to when your child is undergoing intensive treatment. The table below provides a list of safe food choices. If your child has other symptoms such as loss of appetite, loss of weight, diarrhoea, abdominall bloating, taste changes and severe sore mouth, you may ‘ask for a referral to see a dietitian for further advice. Food Categories Recommended Food Food to Avoid Rice and alternatives Cooked rice, porridge, noodles, pasta, oats, chapati, thosaii, idl All types of bread, e.g. dinner rolls, sweet rolls, plain buns, muffins, plain waffles, pancakes, French toast Boiled, baked or fried potato All cereals, cooked and ready-to-eat except those containing probiotics Breakfast cereals, e.g. coco pops, honey stars and commercially packaged baked cereal/muesl bars! Reheated rice Raw grain products e.g. raw oats Creamefilled buns Infant cereal with probiotics (Check the ing probiotics is added) nt list to se ‘Meat and alternatives Thoroughly cooked or canned beef, pork, lamb, mutton, chicken, fish and other seafood such as prawn, crab cand squid Well-cooked egg (firm egg white ‘and yolk) Cooked tofu (cut into one inch cubes ‘and boiled for at least five minutes) Well-cooked processed meat (c.g. hotdog, sausage, ham, nugget, crabstick, meat ball and fishball) Raw or undercooked beef, pork, lamb, mutton, chicken, fish (e.g. sashimi, sushi, fish roe}, seafood, egg, tofu Meat and cold cut from delicatessens (e.g. ham, smoked salmon, salami, meat paté) Tempeh products or fermented soy products (e.g, nattd, fermented beancurd) Page | 32Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers Food Catego Recommended Food Food to Avoid Milk and dairy © All pasteurised or UHT milk ‘© Unpasteurised or raw milk, cheese, products ‘© Formula milk powder for infants or yoghurt and other milk products growing children ‘* Yoghurt and cultured milk beverages * Medical nutritional supplements (e.g. yoghurt drinks, kefir) without probiotics ‘* Commercial formulas with probiotics © Nutritionally complete © Yoghurt Melts (use as advised by dietitian) «Homemade eggnog (Check the ingredient list for probiotics as manufacturers have the tendency to reformulate their products) Ice cream allowed include: Ice cream NOT allowed include: + Pre-packaged ice cream! sherbet!, | * Soft serve ice cream and frozen fresh homemade milkshake using yoghurt dispensed from machines pasteurised or UHT milk © Dry, refrigerated or frozen pasteurised whipped cream toppings Cheeses allowed include: Cheeses NOT allowed include: '* Those made from pasteurised milk | ¢ Mold-ripened e.g. Blue, Roquefort, including processed cheese slices feta and soft cheeses (c.g. cheese spreads, cream cheese, (c.g. Brie, Camembert, goat cheese) cottage cheese and ricotta cheese) | Cheese made from unpasteurised © Commercially packaged hard milk (e.g. paneer) and semi-soft cheeses * Cheese from food kiosks or fast (e.g. milk cheddar, mozzarella, food outlets parmesan, swiss) © Cheese containing chilli peppers or uncooked vegetables Vegetables ‘© Well-cooked fresh, frozen or canned | * Unwashed raw vegetables or fresh vegetables ‘* Fresh or dried herbs added during cooking herbs ‘¢ Fresh herbs for garni ing © All raw vegetable sprouts {e.g. bean sprouts, alfalfa sprouts) ‘* Salads from delicatessens, salad bars and fast food restaurants ‘* Fermented vegetables (e.g. kimchi, pickles, saverkraut) Page | 33Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers Food Categories Recommended Food Food to Avoid Fruits and nuts ‘When in hospital: All berries © Apple or canned fruits are provided When at home: © Well-washed, peeled fruits (to consume immediately once fruits are cut) * All cooked, canned or frozen fruits © Commercially packaged fruit * Dried fruit in baked products (e.g. raisin bread/muffin, fruit cake) © Shelled, roasted nuts from a can bottle or packet, and nuts in baked products (e.g. peanut cookies) Bananas Unwashed fruits with edible skin All pre-cut fruits sold at shops or supermarkets Unroasted raw nuts and unshelled roasted nuts All nuts and dried fruits that are sold in bulk and exposed Fats and oils ‘© Margarine, butter, peanut butter © Cooking © Commercial, shelf-stable? mayonnaise and salad dressing (refrigerate after opening) Fresh salad dressings conta cheese with mold (e.g. Blue, Roquefort or raw eggs e.g. caesar salad dressing, homemade mayonnaise, hollandaise sauce) Desserts and snacks + Freshly baked commercial and homemade cakes, pies and pastries without cream ‘+ Homemade and commercial packaged puddings’ and jelly’ + Homemade and commercial packaged cookies! and biscuits! * Potato chips!, corn chips!, pretzels’ © Homemade popcorn * Candy Cream-filled cakes and pastry products Homemade ice cream, mousse, eggnog, soufflé, meringue ‘Mass-produced snacks from common serving containers (e.g. popcorn, candy floss) Page | 34Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers Food Cate; Recommended Food Food to Avoid Beverages Boiled water Home-made ice using boiled water All canned, bottled and powdered beverages Pasteurised soya milk! Instant and brewed coffee and tea Herbal teas brewed from commercially packaged tea bags Home-brewed drinks (e.g. chrysanthemum tea - waish chrysanthemum flowers thoroughly and boil together with water, barley water) Homemade smoothies Non-carbonated bottled, mineral, spring and natural water Unboiled water taken directly from the tap Water from water coolers and dispensers Ice from ice machines in public places ce-blended drinks or slushies from bulk machines Tea made from loose leaves Opened drinks left at room temperature for one hour or more Miscellaneous Salt, granulated sugar and brown sugar Spreads! (e.g. jam and jelly, Kaya - coconut jam, chocolate or hazelnut spread) - refrigerate after opening Cooked spices Commercial pasteurised Grade A honey Tomato ketchup, chilli sauce, mustard, soy sauce, BBQ sauce, oyster sauce - refrigerate after opening Cooked gravy and sauces Cream and non-cream-based soups (canned or home-made) Pepper Spices added after cooking Raw or unpasteurised honey® Herbs and herbal supplements? Miso products e.g. miso soup ‘Use individvally packaged or wrapped portions whenever possible 7 Only allowed for children above 3 years. Avoid opening the packaging in front ofthe child 2Shelf-stable refers to unopened conned, bottled, or packaged food products that can be stored before opening at room temperature; may require refrigeration after opening, “Wash the top of the can with water before opening. SPasteurived honey products are allowed for children over one year of age and after more than nine months post transplantation. ‘Herbs and herbal supplements are not regulated for purity or for effect on health, and may also contain harmful ingredients. Important Note: Avoid purchasing food from food courts, food retail outlets etc. Food purchased from such places can carry a potential risk for foodborne illness as food safety can be compromised due to inappropriate food handling and food storage temperatures. Page | 35Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers FOOD SAFETY TIPS Food preparation and cooking © Wash your hands before preparing and eating food. © Avoid cross-contamination by using separate cutting boards for cooked food and raw food. © Wash fruits and vegetables thoroughly under running water before peeling, cutting or cooking. © Thaw meat, fish or poultry in the refrigerator or microwave. Do not thaw food by leaving them on the table or countertop at room temperature. © Cook defrosted meat right away ond do not refreeze. © Cook food thoroughly at high temperatures of 75°C or higher. Food storage and reheating © Store cold food at a safe temperature of 4°C or colder. © Cooked food should be served and consumed promptly or kept in the refrigerator/freezer within ‘one hour after cooking. Avoid leaving food at room temperature for more than one hour. © Consume leftover food within 24 hours of cooking, © Microwave cooking or reheating can leave cold spots in food where bacteria can survive. If there is no turntable appliance, rotate the dish a quarter turn once or twice during cool © No reheating of rice. Avoid reheating all other food more than once. ‘Adapted from the Academy of Nutrition and Dietetics, Fred Hutchinson Cancer Research Centre and Memorial Sloan-Kettering Conler affer discussion with Paeds Onco consults Guidelines from Agri-Food & Veterinary Authority of Singapore, Tho British Dietetic Association 2016 Neviropenie Dietary Advice for Heematology Patients Policy and United Stotes Department of Agricullure Food Safely and Inspection Service Food Safely Information. Page | 36Haematopoietic Stem Cell Transplantation (HSCT) Guide for Patients and Caregivers THE USE OF MEDICAL SUPPLEMENTS, TRADITIONAL HERBS AND ORGANIC PRODUCTS Many parents believe that organic products have ad no strong scientific evidence to support this. If you intend to use organic products, you may wish to consider other factors such as cost, availability and convenience. Giving your child traditional herbs is strongly discouraged as there may be some interaction between traditional herbs and cancer treatment. Please seek advice from your child’s oncologist if you have any concerns. ional benefits for their children. However, there is Certain multivitamins supplements may interfere with the chemotherapy drugs. Do not give any multivitamins supplements unless prescribed by the oncologist. ‘COMMERCIAL NUTRITIONAL SUPPLEMENTS Nutritional supplements may be useful in ensuring your child gets adequate energy, protein and nutrients, particularly when he/she is unable to eat well. It can be used to supplement in-between meals or replace @ meal, You may consult your child's oncologist, nurse or dietitian on the age-appropriate nutritional supplements to use. FEEDING BY TUBE AND PARENTERAL NUTRITION If your child is unable to eat or drink in adequate amount, your medical team will discuss alternative ways of meeting his/her nutritional needs. This may include tube feeding or parenteral nutrition (PN). The most common is a nasogastric tube (NG tube), which is inserted via the nose to the stomach. ‘A complete nutritional supplement will be given through the tube to maintain the normal function of the gastrointestinal tract. PN bypasses the normal digestion process in the stomach and bowel. It is « special liquid food, which contains complete nutrition, given into the blood. PN will be given through the intravenous line, mostly via central line, to provide nutrients if the gastrointestinal tract is not working properly. Page | 37