Non-Oncologic Blood Disorders Patient & Family Handbook

A Family Guide to Non-Oncologic Blood Disorders

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Disclaimer The Association of Pediatric Hematology/Oncology Nurses (APHON) does not intend for any of the specific information contained in this product to be absolute or without individual patient or institutional exception. APHON takes no responsibility for the accu- racy of the material presented, which is offered here only as information that is potentially useful for readers. Furthermore, APHON in no way endorses any of the hematology or oncology treatments included in these fact sheets.

Printing Instructions

A Family Guide to Non-Oncologic Blood Disorders

Contributors

Heidi Abendroth, MSN BSN CPNP CPHON® Sameeya Ahmed-Winston, RN MSN RN CPNP CPHON® June Allison, RN CPON® Caroline Costello MBA BSN RN CPON® BMTCN Linda DelVecchio-Gilbert DNP CPNP-PC ACHPN Marika Horn, MSN RN CPNP Ellen Muir, MSN CNS Lisa Pinner, MSN RN CPON® Cheryl Reggio, RN CPON® OCN Nancy Shreve, MSN RN FNP

Contributors

Adrenoleukodystrophy

A Family Guide to Non-Oncologic Blood Disorders

Adrenoleukodystrophy

What is adrenoleukodystrophy? Adrenoleukodystrophy (ALD) is a rare inherited disease that involves a faulty gene that leads to a buildup of a long chain of fatty acids in the brain, nervous system, and adrenal glands. In ALD, there is a breakdown of the myelin sheath , the fatty covering of the nerve cells in the brain. Nerve cells are unable to send signals through the body normally, which can lead to neurological problems including movement, memory, speak- ing, and learning. In ALD, the faulty gene is found on the X chromosome. Since males have only one X chromosome, they are more adversely affected than females, who have two normal X chromosomes and are carriers of the disease. Cerebral (involving the brain) x-linked childhood ALD is the most severe form of the disease. Symptoms generally appear in males age 4 to 8. The adolescent/ adult form of the disease appears between the ages of 10 and 21 and has the same neurologically debilitating symptoms, but at a slower progression than the childhood form. The following are the most common symptoms of ALD. Howev- er each child may experience symptoms differently. Symptoms may include: • Poor attention • Confusion • Forgetfulness • Poor performance or behavior in school • Difficulty swallowing, walking, or talking • Difficulty hearing and seeing • Progressive neurolog- How is ALD diagnosed? • Blood tests to evaluate the amount of long chain fatty acids in the blood and evaluate how well the adrenal glands are working • Genetic DNA-based blood tests • Magnetic resonance imaging (MRI) of the brain to eval- uate for any changes in the brain related to destruction of the myelin sheath. Lesions on the brain caused by destruction of the myelin sheath appear prior to any symptoms of the disease. The MRI scan will produce a Loes score, which rates the severity of the damage to the brain on a scale from 0–34. Patients with low Loes scores in the early stage of the disease have a better ical symptoms that re- sult in severe disability

long-term survival rate than those with higher Loes scores. • Prenatal testing is available for those who may be affected. This can be done through amniocentesis (removing a small amount of amniotic fluid with a nee- dle inserted in the uterus) and chorionic villus sampling (removing a small amount of tissue from the placenta). What tests and procedures will my child need? • Monitoring with MRI every 6–12 months • Complete medical and family history • Physical exam • Blood tests to check adrenal function • Neuropsychological testing to evaluate different functions of the brain What are the treatment options for ALD? • Hematopoietic stem cell transplant (HSCT) is the only effective treatment for the cerebral form of ALD. The goal of HSCT is to provide your child with healthy stem cells that produce a functioning ALD protein—the protein that is lacking in patients diagnosed with ALD. Without transplant, cerebral x-linked ALD can lead to progressive debilitating disease and death within 2 years. • Treatment with adrenal hormones is indicated for adrenal dysfunction, a condition in which the adrenal glands do not produce adequate amounts of steroid hormones or other key hormones that help regulate major body functions. • Supportive treatments include physical therapy, special education, and psychological support. • Your medical team will determine the best treatment plan for your child. How successful is the treatment? Patients who undergo HSCT early in the disease have sig- nificantly improved outcomes compared to those with more advanced symptoms.

Adrenoleukodystrophy

A Family Guide to Non-Oncologic Blood Disorders

Stem Cell Transplant Indications HSCT from a related or unrelated donor is recommended for boys who have early evidence of childhood cerebral x-linked ALD. It is not recommended for patients who have already progressed with severe symptoms or who have adult onset or neonatal forms of the disease. Notes from Your Child’s Medical Team

Adrenoleukodystrophy

Cartilage-Hair Hypoplasia

A Family Guide to Non-Oncologic Blood Disorders

Cartilage-Hair Hypoplasia

What is cartilage-hair hypoplasia? Cartilage-hair hypoplasia (CHH) is an autosomal recessive disorder, meaning that each parent carries one copy of the defective gene and passes it along to their child. CHH causes short-limbed dwarfism (short stature), other associated bone abnormalities, fine sparse hair, and an abnormal immune system. The following are the most common symptoms of CHH. How- ever each child may experience symptoms differently. Symp- toms may include: • Short stature • Short fingers and toes • Bowed legs • Loose joints, especially in the hands and feet • Difficultly extending elbows • Blonde, sparse, and fine hair • Increased risk of infections, especially varicella, the virus that causes chicken pox • Severe combined immunodeficiency • Anemia (too few red blood cells) • Increased risk of cancers » » Leukemia » » Lymphomas » » Tumors of the skin, eye, and liver • Intestinal issues, including Hirschsprung disease, a disorder causing severe constipation and intestinal blockage, and celiac disease, the inability to absorb gluten from wheat or other grains • Decreased sperm count in male patients How is CHH diagnosed? Prenatal screening can be considered if there is a family history. CHH typically is diagnosed in infancy through the following steps: • Complete physical exam • Complete family history • X-rays • Blood test

What test or procedures will my child need? • Complete blood count • Immune function testing (T cell and B cell function studies) • Genetic testing to look for a mutation in the ribonucle- ase mitochondrial RNA-processing (RMRP) gene • Immunoglobulin (antibodies) level testing (IgG, IgA, and IgM) • Bone X-rays • Your child should be seen by an immunologist (immune system) and an orthopedic (bone) doctor. What are the treatment options for CHH? • Aggressive treatment of all infections. More than 50% of children with CHH have a compromised immune sys- tem and inability to protect themselves from infections. • Avoid live vaccines, including the varicella vaccination. • Prophylactic antibiotics to prevent lung infections • Surgery may be needed for severe bowing of the legs. • Your medical team will determine the best treatment plan for your child. How successful is the treatment? The life expectancy for children with CHH varies. Some chil- dren that have decreased immune systems can develop poten- tially life-threatening infections and varicella can be especially dangerous. An antiviral medication (Acyclovir) may be used to treat this infection. Growth hormone has had limited success in increasing height, and CHH patients are at greater risk of developing cancers throughout their lifetime. Stem Cell Transplant Indications Stem cell transplant is the only curative treatment for the immune system problems associated with CHH. However, stem cell transplant will not fix the other skeletal and intestinal issues that patients with CHH can experience.

Cartilage-Hair Hypoplasia

A Family Guide to Non-Oncologic Blood Disorders

Notes from Your Child’s Medical Team

Cartilage-Hair Hypoplasia

Chédiak-Higashi Syndrome

A Family Guide to Non-Oncologic Blood Disorders

Chédiak-Higashi Syndrome

What is Chédiak-Higashi syndrome? Chédiak-Higashi syndrome (CHS) is a rare inherited disease that most often is identified in infancy or early childhood. It is an autosomal recessive disorder, meaning that each parent carries one copy of the defective gene and passes it along to their child. In CHS, immune system cells are damaged and un- able to effectively fight infection. Difficulty with blood clotting also can occur, resulting in frequent bruising and a tendency to bleed easily. Among CHS patients, 50% to 80% are affected by an accelerated phase of the disease, which is triggered by viruses and infections that are not treated successfully. Rapidly dividing white blood cells are a common symptom of acceler- ated CHS. They can invade organ systems, resulting in fever, enlarged liver and spleen, life-threatening infections, bleeding, and organ shutdown. The following are the most common symptoms of CHS. However, each child may experience symptoms differently. Symptoms may include: • Frequent and life-threat- ening infections • Frequent bruising or

What tests and procedures will my child need? • Complete blood count (CBC) test to look at white blood cells, red blood cells, and platelets • Microscopic examination of a blood sample to identify distinct granules found in the cells of CHS patients • Genetic sample for mutations in a specific gene (CHS1/ LYST gene) • Neurological and IQ tests for learning disabilities • Bone marrow biopsy, if necessary What are the treatment options for CHS? • Hematopoietic stem cell treatment (HSCT) • Antibiotics and antiviral medications to prevent and treat infections • Medications to help the immune system (e.g., high dose steroids, immunoglobulin) • Interferon and occasionally chemotherapy • Your medical team will determine the best treatment options for your child. How successful is the treatment? Without HSCT, a majority of patients have a poor prognosis. HSCT can successfully treat the immune system and blood clotting dysfunctions related to the disease and prevent infec- tions and the life-threatening accelerated phase of the disease. However, the neurological manifestations of the disease are not eliminated with HSCT and patients who have under- gone HSCT continue to experience progressive neurological complications such as difficulty with walking, loss of balance, peripheral neuropathies (pain, numbness, and tingling in extremities), and learning difficulties. Stem Cell Transplant Indications HSCT is indicated for all children with CHS that have an avail- able and appropriately matched donor. Transplant has been successful using related, unrelated, and cord blood donors. The goal is to complete the HSCT prior to the accelerated phase of the disease.

• Increased sensitivity to light (photophobia) • Enlarged liver or spleen • Enlarged lymph nodes • Muscle weakness • Numbness • Difficulty walking and loss of balance • Tremors and seizures • Decreased intellectual functioning

nose bleeds due to dif- ficulties clotting blood • Light colored skin, sil- very hair, light colored eyes (oculoalbinism) • Impaired vision • Jerky eye movements (nystagmus)

How is CHS diagnosed? • Complete medical history • Physical exam

• Blood tests • Genetic testing • Prenatal testing

Chédiak-Higashi Syndrome

A Family Guide to Non-Oncologic Blood Disorders

Notes from Your Child’s Medical Team

Chédiak-Higashi Syndrome

Chronic Granulomatous Disease

A Family Guide to Non-Oncologic Blood Disorders

Chronic Granulomatous Disease

What is chronic granulomatous disease? Chronic granulomatous disease (CGD) is a genetic disorder in which neutrophilic white blood cells are unable to kill some types of bacteria and fungi. Typically, neutrophils eat bacteria and fungi and use enzymes to kill them. In children with CGD, neutrophils eat the bacteria and fungi but cannot kill them, and form granulomas (scars) from the infections. The rest of the immune system functions normally. The mutation that causes CGD affects a gene on the X chromo- some and comes from the mother. Disorders inherited on the X chromosome appear only in males. A mother with the mutated gene will not have the disease, but will be a carrier and she may pass the mutated gene on to her children. A family history of recurrent or chronic infections is one of the main risk factors for CGD. Another type of CGD, which can affect either boys or girls, is inherited through one gene from each parent (autoso- mal recessive inheritance). Children with CGD are usually healthy at birth, but develop recurrent infections in the first few months or years of life that are difficult to treat. The following are the most common symptoms of CGD. However, each child may experience symp- toms differently. Symptoms may include: • Skin infections » » Boils » » Abscess perianal (abscess around the anus) » » Impetigo, a contagious skin infection caused by staph or strep bacteria • Pneumonia caused by certain bacteria and fungi can

How is CGD diagnosed? A diagnosis of CGD usually is made during the first year of life based on the following: • Complete medical history and family history • Physical examination » » Enlarged liver » » Enlarged spleen » » Swollen lymph nodes • Specific blood tests and possible chest X-ray • Prenatal screening if there is a family history of CGD What tests and procedures will my child need? • Bone scan to look for bone infections • Chest X ray to look for infection or scarring in the lungs • Complete blood count to confirm a low number of neutrophils • Flow cytometry tests to help confirm the disease • Nitroblue tetrazolium test to help confirm the disease and detect that the mother is a carrier • Dihydrorhodamine 123 (DHR) test to test neutrophils response • Tissue biopsy What are the treatment options for CGD? • Immediate referral to a pediatric immunologist, a doctor that specializes in the treatment of the immune system • Bactrim, an antibiotic • Antifungal and antiviral medications to prevent infec- tions and treat any active infections • Interferon gamma, a protein that provides temporary immunity to protect from infections • Hematopoietic stem cell transplant (HSCT) • Some severe skin infections may require surgery. • Your medical team will determine the best treatment plan for your child.

frequently occur and is difficult to cure. • Osteomyelitis (infection of the bone) • Persistent diarrhea

• Enlarged liver or spleen • Swollen lymph nodes • Gingivitis (swelling of the gums) • Fevers • Abdominal pain • Inflammatory bowel disease

Chronic Granulomatous Disease

A Family Guide to Non-Oncologic Blood Disorders

How successful is the treatment? The severity of the disease varies and some children experi- ence more infections than others. Some doctors believe that some children with CGD have a normal life expectancy.

Stem Cell Transplant Indications HSCT provides CGD patients with functioning neutrophils that can eat and destroy the bacteria and fungi that they are exposed to. It is a cure for the disease and is highly effective in the majority of patients.

Notes from Your Child’s Medical Team

Chronic Granulomatous Disease

Congenital Amegakaryocytic Thrombocytopenia

A Family Guide to Non-Oncologic Blood Disorders

Congenital Amegakaryocytic Thrombocytopenia

What is congenital amegakaryocytic thrombocytopenia?

What tests and procedures will my child need? • Complete blood count; serum thrombopoietin levels • Bone marrow aspirate and biopsy with cytogenetics (the removal of a small amount of liquid and soft tissue from the bone marrow for more extensive analysis) What are the treatment options for CAMT? Currently, treatment for CAMT is limited. Supportive care includes the use of unrelated donor platelet transfusions to ensure that platelet levels do not fall to dangerous levels, and avoidance of medications such as aspirin and nonsteroidal antiinflammatory drugs such as Motrin. The primary treatment for CAMT is bone marrow transplanta- tion, which is the only treatment that can cure the disease. A matched sibling is the best donor, but unrelated donors can be used when a sibling donor is not available. Your medical team will determine the best treatment plan for your child. How successful is the treatment? The majority of patients do well, but bleeding complications present a challenge during transplant. Approximately 80% of patients who undergo hematopoietic stem cell transplant (HSCT) survive.

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare inherited bone marrow failure disease that manifests in early infancy, usually at birth or within the first month of life. The bone marrow does not make platelets or megakaryocytes, the cells responsible for the production of platelets, which are necessary for normal blood clotting. The bone marrow also may stop making red blood cells and neutrophils. The following are the most common symptoms of CAMT. However, each child may experience symptoms differently. Symptoms may include: • Petechiae (small, round, flat spot of bleeding in the skin or in the mucous membranes) • Purpura (red or purple discolorations of the skin) • Easy bruising • Life-threatening bleeding involving skin, mucous membranes, gastrointestinal tract, lungs, and within the brain • Reduced blood platelets and megakaryocytic deficiency, which prevents the production of adequate numbers of platelets • Skeletal abnormalities, cardiac defects, and pro- nounced delay of psychomotor development occasion- ally are reported

Stem Cell Transplant Indications HSCT currently is the only cure for this disease.

How is CAMT diagnosed? • Complete blood count

• Evaluation of the blood smear (thin layer of blood is placed on a slide and the various blood cells are exam- ined with a microscope) • Molecular and cytogenetic investigations of blood or bone marrow cells with a microscope to detect any visible changes in chromosomes that contain genetic material • Elevated serum levels of thrombopoietin

Congenital Amegakaryocytic Thrombocytopenia

A Family Guide to Non-Oncologic Blood Disorders

Notes from Your Child’s Medical Team

Congenital Amegakaryocytic Thrombocytopenia

Diamond- Blackfan Anemia

A Family Guide to Non-Oncologic Blood Disorders

Diamond-Blackfan Anemia

What is Diamond-Blackfan anemia? Diamond-Blackfan anemia (DBA) is a rare bone marrow failure syndrome, affecting the production of red blood cells. It may be inherited or be sporadic and those affected have a higher risk of cancer. The following are the most common symptoms of DBA. However, each child may experience symptoms differently. Symptoms may include: • Pale skin • Restlessness • Sleepiness • Rapid heart rate • Shortness of breath • Heart murmurs • Heart and kidney defects • Below-average height Your child may not have any other physical signs of DBA but approximately 40% of the patients, have birth defects involv- ing the face, head, hands, and especially the thumbs. How is DBA diagnosed? A bone marrow aspirate evaluates your child’s ability to make red blood cells, and a screening for specific genes will confirm the diagnosis. If these come back without an identified gene, it does not mean that your child does not have DBA. Some other blood markers also can be elevated in DBA, including: • MCV (mean corpuscular

lifelong process or done on a schedule determined by your child’s provider. Another option is a type of medication known as corticoste- roids (prednisone), which is given by mouth. It is given initially at high doses and then is tapered down to the lowest dose that keeps your child’s hemoglobin at a level above 9 gm/dl. Bone marrow (stem cell transplant) also may be considered. Your provider also may consider steroid therapy. An approxi- mate response time to therapy is 2–4 weeks once the steroids have been started. As your child gets older, he or she may no longer respond as well to therapy or go into remission where no further treatment is needed. Your medical team will determine the best treatment plan for your child. How successful is the treatment? Each of these options has complications. After approximately 2 years of blood transfusions, your child may develop iron overload and require medication daily to remove the excess iron from their body. This excess iron can be dangerous as it will build up in the liver, heart, and other organs. Long-term use of steroids can lead to osteoporosis (weak and brittle bones), pathologic fractures, diabetes, cataracts (cloud- ing of the lens of the eye), or high blood pressure. Stem Cell Transplant Indications Since DBA is a bone marrow failure syndrome, there may be a time when other blood cell lines are affected and your child cannot make white blood cells or platelets. If your child cannot tolerate steroids and has a hard time finding a suitable donor for transfusion, transplant may be considered. There also is a possibility of becoming iron overloaded due to a genetic predisposition. If this is the case, transplant may also be con- sidered. Transplant is not a first-line option due to risk of rejection, infection, and death. Donor availability (a sibling match is best option) also must be taken into consideration along with risks and benefits. Any related donor also must be evaluated for DBA; it is possi- ble to have DBA without anemia, and it may require treatment at any point in their lifetime.

deaminase (eADA) • Fetal hemoglobin (Hgb F %) • Congenital anomalies • Family history of DBA

volume) size of the red cell, which can be seen on a complete blood cell (CBC) • Erythrocyte adenosine

What tests and procedures will my child need? • Bone marrow aspirate, performed by using a needle to re- move a small amount of bone marrow from the hip bone • Blood tests, which should be performed before the first transfusion. Once a transfusion is given, the blood tested may contain that of the donor and results may be inaccurate. What are the treatment options for DBA? Red blood cell transfusion is a standard method of treatment, usually given every 3–4 weeks. Transfusion therapy can be a

Diamond Blackfan Anemia

A Family Guide to Non-Oncologic Blood Disorders

Notes from Your Child’s Medical Team

Diamond Blackfan Anemia

Dyskeratosis Congenita

A Family Guide to Non-Oncologic Blood Disorders

Dyskeratosis Congenita

What is dyskeratosis congenita? Dyskeratosis congenita is a rare bone marrow disorder. It is a genetic disease, which means it is usually inherited, or passed on in a family. Dyskeratosis congenita can affect many different parts of your child’s body. Dyskeratosis congenita is caused by a change in genes. Some- times this change happens in a child with dyskeratosis con- genita whose parents did not pass on the affected genes. Most often, though, the genes that are not working correctly are passed to children by their parents. Some parents of children with dyskeratosis congenita may have the disease, but might not show obvious signs of it. The following are the most common symptoms of dyskeratosis congenita. However, each child may experience symptoms differently. Symptoms may include: • A lacy-looking rash on the face, neck, and chest • White patches in the mouth • Abnormally shaped fingernails and toenails Patients with dyskeratosis congenita are more likely to develop other health problems, such as: • Bone marrow failure • Lung problems

How is dyskeratosis congenita diagnosed? • A complete medical history • Thorough physical exam looking for signs of dyskerato- sis congenita • Complete testing to look at how the body is functioning What tests and procedures will my child need? • Complete blood count looking at the number of each kind of blood cell • A saliva or spit test to look at the genes • A blood test that looks at the chromosomes to deter- mine if genes look short. Many times the genes in a patient with dyskeratosis congenita are shorter than normal. What are the treatment options for dyskeratosis congenita? Due to the complexity of dyskeratosis congenita, it is a chal- lenging disease to manage. Symptoms can be managed with medications as indicated for the parts of the body involved. Medicines such as steroids are given to help the body make more blood cells. Bone marrow failure associated with dys- keratosis congenita is treated with hematopoietic stem cell transplant. Your medical team will determine the best treatment plan for your child. How successful is the treatment? The only curative option for bone marrow failure is hematopoi- etic stem cell transplant.

• Low bone density • Digestive diseases

• Immunologic diseases (disorders of the immune sytem) • Cancers of the tongue, mouth, throat, stomach, colon, and rectum • Cancers of the blood and bone marrow

Stem Cell Transplant Indications • Bone marrow failure

Dyskeratosis Congenita

A Family Guide to Non-Oncologic Blood Disorders

Notes from Your Child’s Medical Team

Dyskeratosis Congenita

Fanconi Anemia

A Family Guide to Non-Oncologic Blood Disorders

Fanconi Anemia

What is fanconi anemia? Fanconi anemia (FA) is a rare inherited blood disorder and a common form of bone marrow failure. Bone marrow failure results in low blood counts when bone marrow does not pro- duce normal numbers of blood components such as red blood cells, white blood cells, and platelets. The mutation, or defect, that causes FA affects multiple genes on the X chromosome and can occur in all races and ethnicities. Affected children are born with one affected gene from each parent, and families may have more than one child affected with FA. Because of the genetic defect in DNA repair, people with FA are sensitive to drugs that treat cancer. Most children with FA are diagnosed between 6–9 years of age; however, a delay in diagnoses can occur until adulthood. A small percentage of children with FA are recognized at birth through 1 year of age. FA should be considered in children with unexplained ane- mia (low red blood cells), thrombocytopenia (low platelets), neutropenia (low white blood cells), unexplained macrocy- tosis (enlarged red blood cells), or an affected sibling. FA also may be considered in patients with cancers presenting at an unusually young age or a family history suggestive of a cancer predisposition syndrome. The following are the most common symptoms of FA. However, each child may experience symptoms differently. Symptoms may include: • Frequent nosebleeds

the palm of the hand at the base of the thumb) • Low set ears • Microcephaly (smaller than average head) • Hydrocephaly (collection of water in the head) • Smaller than average genitals • Developmental delay

How is FA diagnosed? FA may initially be misdiagnosed as another blood disorder be- cause it can take months to years to evolve in some children. Children without the common congenital malformations may initially present with an unexplained low blood count in any cell line on a routine complete blood count (CBC). If these low counts persist or progress, your child should be referred to a pediatric hematologist. What tests and procedures will my child need? • Complete medical and family history • Physical examination • CBC to look for cytopenias (low numbers of cell types) and macrocytosis (large red blood cells) • Hemoglobin profile to look for fetal hemoglobin, which is increased in FA • Serum alpha-fetoprotein to test increased levels in FA • Chromosomal breakage blood tests to rule out any other syndromes • Bone marrow evaluations including aspiration (a small sample of the liquid part in center of large bones using a special type of needle) and biopsy (a small sample of the liquid part in center of large bones using a special type of needle) What are the treatment options for FA? Your medical team will determine the best treatment plan for your child based on the severity of your child’s bone mar- row dysfunction. Initially, patients are supported with blood transfusions as indicated for cytopenias, but this does not fix the cause of the bone marrow failure. Once a diagnosis of FA is made, therapy is directed at treating the failing bone marrow.

• Fever, ulcers in the mouth, or recurrent infections due to neutropenia • Shortness of breath • Blood in urine or stool

and easy bruising due to low platelets (throm- bocytopenia)

• Tiredness • Pale coloring • Poor growth

Many children with FA are born with physical malformations that are common for the disease, including: • Short stature • Hypopigmented spots (lighter areas on skin) or café-au- lait spots (darker areas on skin) • Upper extremity abnormalities: absent or underde- veloped thumbs, absent ulnar radii, and absent or underdeveloped thenar eminence (group of muscles in

Fanconi Anemia

A Family Guide to Non-Oncologic Blood Disorders

How successful is the treatment? SCT currently is the only curative option for FA. Some doc- tors believe patients benefit from receiving SCT with the use of Fludarabine, a type of chemotherapy, as part of the SCT regimen. The severity of FA varies and requires long-term monitoring for cancer as well as other organ abnormalities. Stem Cell Transplant Indications SCT from a human leukocyte antigen-identical sibling who does not have FA or a matched unrelated donor would be indicated in your child if they have moderate to severe bone marrow failure.

Treatment options include: • Stem cell transplantation (SCT)

• Androgen therapy—androgens are artificial male hor- mones that can help your child make more blood cells for longer periods. Androgens are effective at increasing red blood cell and platelet counts, but not the white blood cells. This option is for those without a matched sibling or transplant as an option. The standard recom- mended androgen is Oxymetholone. • Hematopoietic growth factors—medications that help stimulate and raise the neutrophil count • Supportive therapy—treatment with transfusions as indicated and/or antibiotics for infections

Notes from Your Child’s Medical Team

Fanconi Anemia

Hurler Syndrome

A Family Guide to Non-Oncologic Blood Disorders

Hurler Syndrome

What is Hurler syndrome? Hurler syndrome, also known as mucopolysaccharidosis I (MPS-I), is part of a subgroup of metabolic disorders known as MPS disorders. MPS disorders are caused by a mutation in a specific gene. Genes carry an inherited code of instructions on how to create every cell and substance in the body. The mutat- ed gene in MPS disorders affects an enzyme called alpha-L- iduronidase (IDUA). This enzyme is needed to break down long chains of sugar molecules called glycosaminoglycans (GAG). The body needs GAGs to build bones and tissues. MPS disor- ders allow GAGs to build up in the body and cause damage. What are some symptoms of Hurler syndrome? Hurler syndrome symptoms appear most often in ages 3–8 when GAGs build up in the body. Infants with severe Hurler syndrome can appear normal at birth and develop physical symptoms during the first 2 years of life. The following are the most common symptoms of Hurler syndrome. However, each child may experience symptoms differently. Symptoms may include: • Developmental disabilities • Heart problems • Hearing problems and frequent ear infections • Large head size, broad forehead, thick eyebrows, coarse facial features, low nasal bridge • Cloudy corneas • Halted growth • Deformed bones and stiff joints, including the spine, hips, knees, wrists, and fingers • Breathing problems and snoring How is Hurler syndrome diagnosed? A diagnosis of Hurler syndrome is usually made based on the following: • Complete medical his-

What tests or procedures will my child need? • Blood tests or skin samples to check if the body is pro- ducing the IDUA enzyme • Genetic tests for mutations to the gene for the IDUA enzyme • Urine tests that detect for extra GAGs • X-rays to check for damage in the spine or other joints and the widening of ribs • Electrocardiogram to check heart rhythm • Echocardiogram to measure the size and function of the heart What are the treatment options for Hurler syndrome? Stem cell transplant (SCT) is the only curative treatment option. The main goal in treating Hurler syndrome is to provide the body the missing enzyme so it can break down GAGs. Com- mon treatments include: • Immediate referral to a pediatric geneticist (a doctor who studies genes and their effects) • Enzyme replacement therapy, where your child is given a drug (laronidase) that has the IDUA enzyme his or her body is missing Your medical team will determine the best treatment plan for your child. How successful is the treatment? Enzyme replacement therapy can improve breathing, growth, and problems with the bones, joints, and heart. However, there is no evidence that it has any effect on mental develop- ment problems caused by Hurler syndrome. In order to stop damage caused by the disorder before it becomes severe, SCT has the best chance of success when it is performed soon after diagnosis. Children who receive a trans- plant early enough can have normal or near-normal mental development. Further damage to the organs is prevented and hearing may improve. However, transplants for children who have developed severe organ damage may not yield as favorable results. If there is already organ damage, the risk of developing life-threatening

• Physical examination • Specific blood tests or scans • Urine tests

tory, including history of infections and family history

Hurler Syndrome

A Family Guide to Non-Oncologic Blood Disorders

Stem Cell Transplant Indications SCT replaces the abnormal cells in the bone marrow (the cells with the mutated gene) with healthy cells from a family mem- ber, an unrelated donor, or a cord blood unit. The healthy cells provide a source of the enzyme needed to break down GAGs and stop further damage to the body.

complications from transplant is higher. In addition, a trans- plant may not undo damage the disease has already done, especially to the nervous system. Your child will need to be treated for the medical issues that already exist.

Notes from Your Child’s Medical Team

Hurler Syndrome

Kostmann’s Syndrome

A Family Guide to Non-Oncologic Blood Disorders

Kostmann’s Syndrome

What is Kostmann’s syndrome? Kostmann’s syndrome, also known as severe congenital neutropenia (SCN), is a rare autosomal recessive disorder. The disorder is inherited when two copies of an abnormal gene are present. The disease results in a low number of neutro- phils, white blood cells that help fight infection. In Kostmann’s syndrome, the absolute neutrophil count (ANC) is typically less than 200/µL, resulting in increased risk of bacterial infections. Kostmann’s syndrome also predisposes patients to the devel- opment of myelodysplastic syndrome (MDS) and leukemia. The most common leukemia in SCN is acute myeloid leukemia (AML). Symptoms of Kostmann’s syndrome typically develop within the first year of life after an initial infection. The following are the most common symptoms of Kostmann’s syndrome. However, each child may experience symptoms differently. Symptoms may include: • Omphalitis (infection of umbilical cord stump) • Mouth sores, gum swelling • Sinus infection, ear infection • Urinary tract infection • Skin infections • Bone pain or fractures • Fever • Irritability • Enlarged spleen • Sepsis (infection of the blood) How is Kostmann’s syndrome diagnosed? A diagnosis of Kostmann’s syndrome is usually made during the first year of life based on the following: • Complete medical history and family history • Physical examination • Specific blood tests or scans What tests and procedures will my child need? • Bone marrow aspiration or biopsy to assess bone mar- row make-up and look for diseases or leukemia • Imaging: performed only as needed to evaluate an infection • Blood work: a complete blood count to determine the decreased number of neutrophils

How is Kostmann’s syndrome treated? • Immediate referral to a pediatric immunologist and hematologist • Basic precautions o avoid large crowds, dirty environments, and sick people o strict handwashing o antibiotics, antifungal, and antiviral medi- cations to treat any active infections • Granulocyte colony stimulating factor (GCSF), a medica- tion given to stimulate neutrophil production • Hematopoietic stem cell transplant (HSCT), the only curative option Your medical team will determine the best treatment plan for your child. How successful is the treatment? GCSF temporarily can keep children healthy, but ultimately almost all Kostmann’s syndrome patients, especially those with MDS and AML, require HSCT. Transplants done using the bone marrow of a sibling provide the best chance for success. For children who do not have fam- ily members who are suitable donors, doctors may use stem cells from an unrelated donor or cord blood. Stem Cell Transplant Indications HSCT provides Kostmann’s syndrome patients with a function- ing immune system that is capable of protecting them from infections. It is a cure for the disease and is highly effective in the majority of patients.

Kostmann’s Syndrome

A Family Guide to Non-Oncologic Blood Disorders

Notes from Your Child’s Medical Team

Kostmann’s Syndrome

Krabbe Disease

A Family Guide to Non-Oncologic Blood Disorders

Krabbe Disease

What is Krabbe disease? Krabbe disease is a rare inherited degenerative disorder of the central and peripheral nervous system. Krabbe disease is part of a group of genetic disorders called leukodystrophies that are caused by a deficiency of the enzyme Galactocerebro- sidase. When the enzyme is missing, there is a toxic buildup of abnormal fatty materials (lipids), which in turn causes destruction of the myelin sheath. The myelin sheath provides a covering around the nerves that carry signals from the brain to various parts of the body. When the myelin sheath is damaged, the brain cannot communicate with other parts of the body. Krabbe disease is inherited through a defective gene from both parents. Krabbe disease most often affects infants with onset before 6 months, but can occur in adolescence or adulthood. Krabbe disease usually is fatal before age 2, while patients with juvenile or adult onset generally live longer. What are some symptoms of Krabbe disease? The following are the most common symptoms of Krabbe dis- ease. However, each child may experience symptoms differently. Symptoms may include: • Irritability • Unexplained fever • Limb stiffness • Seizures • Feeding difficulties • Vomiting • Slowing of mental and motor development • Muscle weakness • Spasticity • Deafness • Blindness How is Krabbe disease diagnosed? • Magnetic resonance imaging (MRI), an imaging test that uses powerful magnets to create images of the organs and tissues in the body • Blood and urine tests to determine deficiency level of the missing enzyme What tests and procedures will my child need? • Imaging studies of the brain using a computed tomog- raphy (CT) scan or MRI scan, that show an unusual loss of white matter due to the loss of myelin. An MRI can

be suggestive of Krabbe disease, but is generally not accepted as a formal diagnostic tool. • Blood test is done to check for enzyme levels. • Urine test to confirm the presence of sulfatides (a major fat component of the myelin sheath) • Nerve conduction studies to measure the velocity of impulses being sent through the nervous system. When myelin is impaired, the nerve conduction is slower. • Eye examination to look for indications of visual deterioration • Newborn screen testing (only in select states) • Before birth, a mother’s amniotic fluid can be screened for Krabbe disease to look for the missing enzyme. This is not done for every family, but is used for families who have a previous child with Krabbe disease. How is Krabbe disease treated? There are no curative options for symptomatic patients who have the infantile form of the disease. Supportive care is uti- lized to manage irritability and spasticity. Stem cell transplan- tation has been utilized for patients in the presymptomatic phase with an unrelated or cord blood donor. How successful is the treatment? A stem cell transplant can help minimize permanent damage caused by this disease. The transplant provides the most effective results if performed before the onset of symptoms in patients with the infantile form or for patients with juvenile onset Krabbe disease. Children who are symptomatic at the time of transplant often do not show evidence of significant improvement after transplant. Stem Cell Transplant Indications Stem cell transplant is indicated for children who have the infantile form of Krabbe but have not started to show signifi- cant symptoms or patients with the juvenile onset form of the disease.

Krabbe Disease

A Family Guide to Non-Oncologic Blood Disorders

Notes from Your Child’s Medical Team

Krabbe Disease

Leukocyte Adhesion Deficiency

A Family Guide to Non-Oncologic Blood Disorders

Leukocyte Adhesion Deficiency

What is Leukocyte adhesion deficiency? Leukocyte Adhesion Deficiency (LAD) is an inherited disease in which white blood cells (leukocytes) and the cells that line the inside of the blood vessels do not have the ability to correctly look for and respond to infection or inflammation that may be casused by a deficiency in these cells. There are three types of LAD syndromes that have been de- fined by the unique molecule(s) that are deficient. In all three types, the white blood cell (leukocyte) cannot easily get to a site of infection or inflammation in the tissue. • LAD I: Infection fighting cells (neutrophils) cannot respond to infection because they can’t leave the blood circulation when needed • LAD II: Presence of a defect in a cell that does not allow it to go to areas of inflammation • LAD III: Similar to Type I, but also gives the body the inability to clot as it should What are some symptoms of LAD? Symptoms of LAD often develop after an initial infection within the first year of life. The following are the most common symp- toms of LAD. However each child may experience symptoms differently. Symptoms may include: • Type I » » Delayed separation of the umbilical cord » » Recurrent, often severe skin and lung infections caused by certain bacteria » » Wounds that take a long time to heal or do not heal completely • Type II » » Less severe infections » » Flattened nasal bridge, small stature, and/or severe mental impairment • Type III » » Same as Type I » » Bleeding problems

How is LAD diagnosed? A diagnosis of LAD is usually made during the first year of life based on the following: • Complete medical history and family history • Physical examination of your child • Specific blood tests as determined by your medical team • Specific diagnostic tests may be taken of certain areas of the body, including the lungs, to evaluate for infec- tion. The medical team will explain which tests may be needed. What tests or procedures will my child need? • Complete blood count test to look at white blood cells, red blood cells, and platelets • Specific genetic blood tests to look at your child’s ge- netic information. These are not always performed. • Certain types of images may be required to evaluate for the presence of an infection. How is LAD treated? Treatment of LAD depends on the type and on how severe the symptoms are. Mild to moderate disease often responds to antibiotics. Common treatments for severe disease include: • Measures to prevent infection from occurring • Management of bacterial infections with antibiotics • Granulocyte colony stimulating factor (a medication given to stimulate the production of white blood cells) • Stem cell transplant (SCT) Your medical team will determine the best treatment plan for your child. How successful is the treatment? SCT is recommended within the first year of life as a curative option for the disease. SCT is very successful for severe Type I and all Type III patients who have a matched donor. LAD Type II tends to respond well to the treatment of infections as well as measures to prevent further infection. As the immune system becomes more fully developed, the frequency of infection decreases.

Leukocyte Adhesion Deficiency

A Family Guide to Non-Oncologic Blood Disorders

Stem Cell Transplant Indications SCT is indicated for LAD I and LAD III. The goal of transplant is

to create a mature immune system that can adequately fight infections and, in the case of Type III, restore normal platelet function, which helps prevent bleeding problems.

Notes from Your Child’s Medical Team

Leukocyte Adhesion Deficiency

Metachromatic Leukodystrophy

A Family Guide to Non-Oncologic Blood Disorders

Metachromatic Leukodystrophy

What is metachromatic leukodystrophy? Metachromatic leukodystrophy (MLD) is one of a group of ge- netic disorders called the leukodystrophies. Breaking down the words reveals the definition. “Meta” means change, “chromat- ic” means color, “leuko” means white matter, and “dystrophy” means degeneration. MLD is caused by a deficiency of the enzyme arylsulfatase A. When the enzyme is missing, there is a toxic buildup of abnormal fatty materials (lipids), which causes destruction of the myelin sheath. The myelin sheath is the protective covering around the nerves that carry signals from the brain to the various parts of the body. When the myelin sheath is damaged, the brain cannot communicate with other parts of the body, such as the muscles, eyes, mouth, and other parts of the brain. MLD is a disorder that a person inherits from a defective gene from both parents. There are three forms of MLD: late infantile, juvenile, and adult. Late infantile is the most common form of MLD. What are some symptoms of MLD? The following are the most common symptoms of MLD. How- ever, each child may experience symptoms differently. Late infantile MLD symptoms typically begin around 12–20 months after birth and include: • Difficulty walking after the first year of life • Muscle wasting, weakness, and rigidity • Developmental delays • Progressive loss of vision leading to blindness • Convulsions (the muscles contract and relax rapidly and very often, which causes the body to shake uncontrollably) • Impaired swallowing • Paralysis (loss of muscle function in one or more muscles) • Memory loss • If untreated, most children with MLD do not survive past the age of 5.

Juvenile MLD symptoms begin between 3–10 years old and include: • Impaired school performance • Mental deterioration • Dementia, which leads to symptoms similar to late infantile MLD but have a slower progression • Death occurs 10 to 20 years following onset of symptoms. Adult MLD symptoms begin after age 16 and include: • Symptoms similar to depression or other types of men- tal illness • Impaired concentration • Ataxia (lack of coordination of muscles) • Seizures • Tremors • Progressive memory loss • Death occurs 6–14 years following onset of symptoms. How is MLD diagnosed? • Diagnosis is made through magnetic resonance imag- ing (MRI), an imaging test that uses powerful magnets to help create images of the organs and tissues in the body. • Blood and urine tests determine deficiency of the miss- ing enzyme. What tests and procedures will my child need? • Imaging studies of the brain using an MRI are per- formed in most cases. An MRI scan usually will show an unusual decrease in white matter due to loss of myelin. • A blood test is done to check for enzyme levels and a urine test confirms the presence of sulfatides (a major fat component of the myelin sheath).

Metachromatic Leukodystrophy

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