Haploidentical Transplant: New Hope for Treatment of Blood Diseases and Cancers in Children

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Every parent wants to see their children’s bright future with good health. However, blood diseases and certain types of cancer are among the most common diseases in children. Particularly, the incidence of leukemia is as high as 1,200 cases per year in Thailand. Children under the age of 5 years old diagnosed with acute leukemia have a 94% of 5-year survival rate, whereas the rate is reduced to 92% in children between 5 and 15 years old. Another common blood disease found in children is thalassemia. If the symptoms are severe, the children often suffer from anemia with an enlarged liver and spleen, requiring regular blood transfusions. With innovative haploidentical transplants, stem cells from parents or donors who have matched only half the patient’s HLA type can be used to treat blood diseases and hematologic malignancies. Considered an advanced stem cell transplantation technique, this approach gives these young patients a higher chance for a cure and improved quality of life, enabling them to grow happily.

What is hematopoietic stem cell transplantation (HSCT)?

HSCT replaces abnormal cells in the bone marrow to treat several kinds of diseases. Hematopoietic stem cells can be derived from bone marrow, peripheral blood, or umbilical cord blood. There are two major types of transplantation, depending on the donors of the stem cells:

Autologous hematopoietic stem cell transplantation uses stem cells collected from the bone marrow or peripheral blood of the patient.
Allogeneic hematopoietic stem cell transplantation uses stem cells collected from donors. Donors can be either related or unrelated donors with 100% Human Leukocyte Antigen (HLA matching) as the patient. Nonetheless, searching for such entirely matching donors, whether from donors with or without blood relations, is quite difficult and takes a long time. This makes the progression of the disease more severe, and the patient loses the opportunity to receive effective and timely treatment.

Medical advancement allows for the use of stem cells from donors whose HLA type matches only 50%, a technique known as haploidentical hematopoietic stem cell transplantation. The haploidentical donor can be half-matched, either parent or siblings. Given that, it becomes faster and easier to find a suitable donor. The patient can receive effective treatment conducted in a timely manner with an increased chance of a cure.

Haploidentical transplantation for blood diseases and hematologic malignancies in children

Haploidentical transplantation can be used as a treatment option in children with the following diseases:

Thalassemia
Leukemia
Severe Aplastic Anemia
Primary Immunodeficiency

Whether hematopoietic stem cell transplantation is an effective treatment for each patient, the doctor’s consideration will be made upon the type and severity or condition of the disease, as well as the type of stem cells that will be transplanted, the source of a donor, and other factors or underlying conditions of each individual.

How is haploidentical transplantation performed?

Health checks for patients and stem cell donors. Patients require a series of tests, such as blood tests for infections, heart conditions, chest x-rays, liver, and kidney function tests, hearing and vision screening, and bone marrow and cerebrospinal fluid examination, ensure that they are ready for transplantation. In some cases, additional growth development tests are needed. Donors must undergo blood tests, infection screening, chest x-rays, and liver and kidney function tests.

Preparation before the transplant. Before transplantation, patients will be given high-dose chemotherapy, called conditioning or preparative regimen, via central venous catheter on the chest (it may be administered along with radiation to destroy the patient’s bone marrow). This normally takes 8-10 days, depending on treating conditions. This conditioning regimen using high-dose chemotherapy aims to suppress the immune system and destroy cancerous or abnormal cells as much as possible. Moreover, it helps make room in the patient’s bone marrow for new blood stem cells to grow. The conditioning regimen given to the patients before implantation also helps prevent the patient’s body from rejecting the transplanted stem cells.

Stem cell donors receive injections to stimulate white blood cells for approximately 4 – 5 days. Their stem cells will then be collected by a hematopoietic stem cell machine.

Haploidentical stem cell transplantation begins with the infusion of the donor cells into the patient’s veins through a central venous catheter, just like a blood transfusion. However, the patient’s vital signs and conditions will be closely monitored during the transplant. The donated stem cells will enter the patient’s bloodstream and bone marrow, where they can grow into various types of healthy, fully functional blood cells. The engraftment usually takes about 2 –3 weeks.

During the transplant, the patient needs to recover in a sterile transplantation room in the hospital. The room is positive-pressure ventilation with a high-efficiency filter to remove germs and air contaminations. The patient will be closely monitored and treated if any possible complications develop during treatment. Medications will be administered through the central venous catheter, such as antibiotics, specially prepared blood components, lymphocyte stimulatory drugs, and immunosuppressants to prevent Graft Versus Host Disease (GVHD). On average, patients need to stay in a sterile environment for 6 – 8 weeks, depending on the outcome of each patient.

After being discharged, follow-up appointments will be made regularly with blood tests, especially during the first 100 days, to monitor treatment outcomes and assess the possibility of complications, e.g., infections, low blood cell count, and oral sores.

Caring for children after haploidentical transplantation

After the transplantation, patients need special care from a multidisciplinary team of doctors, such as a pediatric hematologist, pediatric oncologist, critical care pediatrician (pediatric intensivist), and nurse and clinical pharmacist who are specialized in Haploidentical Transplantation.

In addition, hematopoietic stem cell transplants must be performed in a positive-pressure HEPA room in a special ward for transplantation in order to reduce the risk of infections. Most importantly, the unit must be ready to treat GVHD, a possible complication in which the donated stem cells (graft) view the recipient’s cells (host) as an unfamiliar threat. As a result, the donated cells attack the recipient’s cells, causing a wide range of symptoms affecting the skin, gastrointestinal (GI) tract, or liver. To manage GVHD by using photopheresis, the white blood cells, called lymphocytes, are removed and radiated using UVS light to stop them from reacting to the transplanted cells, resulting in less reaction between the graft and host cells. Furthermore, integrative care from a multidisciplinary team of doctors, including a nutritional therapist, nutritionist, psychologist, psychiatrist, and various other specialists, takes the physical and mental health of the patient into account.

Possible complications of haploidentical transplantation

Although haploidentical transplantation can treat various conditions leading to a possible cure, there may be some relevant complications, such as:

Complications during chemotherapy and radiation therapy. Patients may experience nausea, vomiting, fever, fatigue, loss of appetite, watery stool, bloody urine, etc. Nevertheless, these symptoms can be treated or prevented.

Considerable complications after initial transplantation

Infections. During the first 2 – 3 weeks, there is a high risk of infections from bacteria, viruses, and fungi, especially when the white blood cell counts are low. Although the number of white blood cells may have returned to normal levels and the patient can be discharged, they are more susceptible to infections than normal, particularly during the first year. This is because the patient will be put on immunosuppressants, causing them to have a less immune response to transplanted cells. Their immune system will return to normal within 1 – 2 years. Patients usually experience fever after stem cell transplantation. If fever arises, doctors perform differential diagnostics to find the root cause and administer antibiotics that cover the most common infections (empirical treatment) until the pathogenic results are conclusive. Treatment using antibiotics and other medications may be adjusted as necessary.
Low blood cell counts. Patients may have anemia and red spots on their bodies. There might be some bleeding in the gums or other tissues due to low red blood cell and platelet counts. While waiting for the donated stem cells to become fully functional, patients normally periodically receive red blood cells and platelets.
Ulcers in the oral and digestive tract. As a result of chemotherapy and radiation therapy, patients may develop these ulcers, causing oral pain, painful swallowing, and inability to eat. This usually occurs in the first two weeks after stem cell transplantation. If the condition is too severe, it may be necessary to receive nutrients intravenously. Unfortunately, digestive tract ulcers can lead to the spread of infection, including bacteria, viruses, and fungi.
GVHD. GVHD can be classified into two types; acute and chronic GVHD. Acute GVHD can occur within the first 100 days after stem cell transplantation. Patients may develop redness on their skin, diarrhea, or abnormal liver function. Chronic GVHD can develop later than acute GVHD, where patients may experience skin rashes or subcutaneous skin changes, abnormal liver function, dry eyes, dry mouth and sores, stomach aches, weight loss, joint pain, and abnormal lungs function.
Veno-occlusive disease. As a result of high-dose chemotherapy and radiation therapy during the patient preparation prior to stem cell transplantation, veno-occlusive disease happens when the small blood vessels inside the liver become occluded. Patients often have weight gain, jaundice, enlarged liver, pain, or the development of ascites fluid. This usually occurs around 2 weeks to 1 month after stem cell transplantation.

Treatment outcomes of haploidentical transplantation: New hope for children with blood diseases

As haploidentical transplantation replaces cancer or abnormal cells in the bone marrow, this approach can cure thalassemia, leukemia, and other diseases in children. Rather than using a 100% matched donor, haploidentical transplantation requires only 50% matching of HLA hematopoietic stem cells from donors such as parents. Therefore, it is easier to find suitable donors, allowing timely and effective treatment. However, whether or not haploidentical transplantation is an appropriate option in children depends on the type and severity of the disease, including the physical readiness of each patient.

Haploidentical transplantation helps increase the survival rate of children after one year of transplantation compared to other treatment options. In addition, the mortality rate after 100 days is very low. More importantly, transplantation helps increase the chances of a complete cure for children. It poses a very low rate of recurrence. Hence, it ensures a good quality of life for the patients, enabling them to grow up happily.

Haploidentical Transplantation at Bangkok Hospital

Child’s Health Center at Bangkok Hospital, and Hematology Center at Bangkok Cancer Hospital Wattanosoth provide the following services:

Consultation and treatment from a team of pediatricians specialized in hematology and oncology, including pediatric oncologists, pediatricians, and a multidisciplinary team for children aged 1-15 with hematologic diseases, such as thalassemia and leukemia, as well as other hematologic related diseases.
Consultation and HLA typing test to be used for haploidentical transplantation.
Administration of chemotherapy for hematologic malignancies prepared by specialized and qualified pharmacists under close supervision of doctors and nurses who closely follow up on the efficacy and safety of the patient during treatment.
Stem cell transplantation procedure that meets international standards, including a positive pressure room equipped with HEPA filter to prevent infection in immunocompromised patients. This leads to a reduction in the risk of acquiring infections for both transplant patients as well as patients who received high-dose chemotherapy.

“Haploidentical stem cell transplantation is a medical advancement that enables children with blood disorders to have a higher chance of a cure and good quality of life again. This treatment requires comprehensive knowledge, medical expertise, a special sterile hospital room, as well as hospital readiness to ensure that patients receive the best possible treatment and gain a better quality of life.”

Prof.Dr. Suradej Hongeng (Pediatric Hematology and Oncology) Bangkok Hospital
Dr. Pongpak Pongpitcha (Pediatric Hematology and Oncology) Bangkok Hospital

Reference:

Anurathapan U, Tim-Aroon T, Zhang W, Sanpote W, Wongrungsri S, Khunin N, Chutipongtanate S, Chirdkiatgumchai V, Ngiwsara L, Jaovisidha S, Khongkraparn A, Pakakasama S, Svasti J, Setchell KDR, Wattanasirichaigoon D, Hongeng S. Comprehensive and long-term outcomes of enzyme replacement therapy followed by stem cell transplantation in children with Gaucher disease type 1 and 3. Pediatr Blood Cancer. 2023;70:e30149.

Anurathapan U, Hongeng S, Pakakasama S, Songdej D, Sirachainan N, Pongphitcha P, Chuansumrit A, Charoenkwan P, Jetsrisuparb A, Sanpakit K, Rujkijyanont P, Meekaewkunchorn A, Lektrakul Y, Iamsirirak P, Surapolchai P, Sirireung S, Sruamsiri R, Wahidiyat PA, Andersson BS. Hematopoietic Stem Cell Transplantation for Severe Thalassemia Patients from Haploidentical Donors Using Novel Conditioning Regimen. Biol Blood Marrow Transplant. 2020:26:1106.

Anurathapan U, Hongeng S, Pakakasama S, Sirachainan N, Songdej D, Chuansumrit A, Charoenkwan P, Jetsrisuparb A, Sanpakit K, Rujkijyanont P, Meekaewkunchorn A, Lektrakul Y, Iamsirirak P, Surapolchai P, Satayasai W, Sirireung S, Sruamsiri R, Wahidiyat PA, Ungkanont A, Issaragrisil S, Andersson BS. Hematopoietic stem cell transplantation for homozygous β-thalassemia and β-thalassemia/hemoglobin E patients from haploidentical donors. Bone Marrow Transplant. 2016;51:813.

Anurathapan U, Pakakasama S, Mekjaruskul P, Sirachainan N, Songdej D, Chuansumrit A, Charoenkwan P, Jetsrisuparb A, Sanpakit K, Pongtanakul B, Rujkijyanont P, Meekaewkunchorn A, Sruamsiri R, Ungkanont A, Issaragrisil S, Andersson BS, Hongeng S. Outcomes of thalassemia patients undergoing hematopoietic stem cell transplantation by using a standard myeloablative versus a novel reduced-toxicity conditioning regimen according to a new risk stratification. Biol Blood Marrow Transplant. 2014;20:2066.

Anurathapan U, Pakakasama S, Rujkijyanont P, Sirachainan N, Songdej D, Chuansumrit A, Sirireung S, Charoenkwan P, Jetsrisuparb A, Issaragrisil S, Ungkanont A, Sruamsiri R, Srisala S, Andersson BS, Hongeng S. Pretransplant immunosuppression followed by reduced-toxicity conditioning and stem cell transplantation in high-risk thalassemia: a safe approach to disease control. Biol Blood Marrow Transplant. 2013;19:1259.

Tannumsaeung S, Anurathapan U, Pakakasama S, Pongpitcha P, Songdej D, Sirachainan N, Andersson BS, Hongeng S. Effective T-cell Replete Haploidentical Stem Cell Transplantation for Pediatric Patients with High-risk Hematologic disorders. Eur J Haematol. 2023;110:305-312.