Treatments

Treatment for Sickle Cell Disease and Thalassemia

Sickle cell disease (SCD) and Thalassemia are both genetic blood disorders that affect the form and function of hemoglobin, leading to a range of health issues, including anemia, repeated infections, and episodes of chronic pain . Although these conditions share some similarities in their manifestations and impact on the body, their underlying genetic causes and treatments can differ significantly.

Sickle Cell Disease (SCD): SCD is characterized by the production of abnormal, rigid, sickle-shaped red blood cells (RBCs) that can block blood flow and can cause pain episodes, medically called vaso-occlusive crises. While treating a patient with SCD, our aim is  to manage pain and prevent complications.

Hydroxyurea: It is the only approved medicine that is effective in reducing the pain in Sickle Cell Disease. So, basically it makes the red blood cells bigger and helps them stay rounder and more flexible — and makes them less likely to turn into a sickle shape. The medicine does this by increasing a special kind of hemoglobin called hemoglobin F. Hemoglobin F is also called fetal hemoglobin because newborn babies have it. By reducing the sickling of red blood cells, it decrease the frequency of pain crises and the need for blood transfusions.

Pain Management: During vaso-occlusive episodes, effective pain management is crucial. This often requires a combination of medications, including NSAIDs, opioids, and adjuvant pain relievers.

Blood Transfusions: Regular blood transfusions can reduce the risk of stroke in children with SCD and manage complications such as acute chest syndrome. However, long-term transfusion therapy carries risks, including iron overload, which must be managed with chelation therapy.

Stem Cell Transplantation: Currently, the only potential cure for SCD is hematopoietic stem cell transplantation (HSCT). A hematopoietic stem cell transplantation (HSCT) is a procedure that involves replacing a patient's bone marrow with healthy stem cells from a donor. The donor can be a sibling, unrelated donor, or an identical twin.

Gene Therapy: Genome editing with techniques such as CRISPR/Cas9 we can now correct the genetic defect that causes the disease. We can also increase fetal hemoglobin production. However, most of these treatments are still largely in the experimental phase.

Treatment for Thalassemia

In Thalassemia, due to mutations in the DNA of red blood cells that make haemoglobin, the production of hemoglobin is low. This leads to anemia. Treatment involves management of symptoms to improve patient's quality of life.

Blood Transfusions: Regular transfusions can help maintain hemoglobin at a healthy level but can lead to iron overload, and thus require iron chelation therapy to prevent damage to vital organs.

Bone Marrow or Stem Cell Transplantation: This offers a potential cure for some patients with thalassemia, especially if done early in life. However, it comes with the risks associated with any stem cell or bone marrow transplant, including graft-versus-host disease.

Gene Therapy: For Thalassemia, gene therapy aims to introduce functional genes into the patient’s bone marrow to correct the deficit in hemoglobin production. Several clinical trials have shown promising results, offering hope for a future cure.

Treatment for Pediatric Cancers

Pediatric cancers are not as common as adult cancers. The treatment of paediatric cancers may involve a combination of surgery, chemotherapy, and radiation therapy. Now, we also have immunotherapies which can be tailored to effectively eliminate specific type and stage of cancer.

Surgery is the most common and effective in the treatment for pediatric cancers, especially for solid tumors such as Wilms tumor (a type of kidney cancer) or certain brain tumors. The goal is to remove as much of the cancerous mass as possible. However, the surgery should be meticulously planned to avoid any sort of damage or long-term impact to the child.

Chemotherapy, the use of drugs to kill cancer cells, is effective in removing the residual cancer cells post-surgery, and also in cancers that are more diffuse, like leukemia (blood cancer).

Children can tolerate higher doses of chemotherapy than adult. However, if not performed by an expert, the side effects can be severe, impacting growth, organ function, and potentially leading to the development of secondary cancers later in life. Therefore, it is crucial for pediatric oncologists to carefully plan and precisely calibrate the doses.

Radiation therapy uses high-energy particles or waves, such as X-rays, gamma rays, electron beams, or protons, to destroy or damage cancer cells. In children, there's a significant concern about the long-term effects of radiation, including the risk of secondary cancers and impacts on growth and development. Nowadays, we apply it with precision techniques such as proton therapy, which can target tumors and minimize exposure to surrounding healthy tissues.

Targeted therapies are designed to target specific genes, proteins, or the tissue environment that contributes to cancer growth and survival, offering the promise of more effective and less toxic treatments. Immunotherapies harness the power of the patient's immune system to attack cancer cells, with treatments such as CAR T-cell therapy showing remarkable success in treating certain paediatric leukaemia’s.

The treatment of paediatric cancers is interdisciplinary, involving paediatric oncologists, surgeons, radiation oncologists, trained nurses, psychologists to support the child and its family through treatment. This care includes management of side effects, both acute and long-term, and also addressing the psychological and emotional impact of cancer treatment on children and their families.

The most important aspect of treatment is early diagnosis. Most childhood cancers are curable if treated on time by a paediatric oncologist. Over the last three to four decades the success rate has increased to 90 % from 10-20 %. 

Cell and Gene therapy

CAR T-cell therapy and gene therapy represent a revolutionary shift in the treatment of cancers and blood disorders. These are precision medicines which target the diseased cells without harming the surrounding cells. These innovative therapies use genetic engineering to treat diseases at the molecular level.

CAR T-Cell Therapy:

Chimeric Antigen Receptor (CAR) T-cell therapy is a ground-breaking approach that reprograms a patient's T cells to seek out and destroy cancer cells. This process involves collecting T cells from the patient's blood and genetically modifying them in the laboratory to express CARs on their surface. These CARs are designed to recognize and bind to specific proteins (antigens) on the surface of cancer cells. Once the modified T cells are infused back into the patient, they multiply and launch a targeted attack against the cancer cells.

CAR T-cell therapy has shown remarkable success in treating certain types of blood cancers, such as acute lymphoblastic leukemia (ALL) in children and young adults, and certain types of lymphomas in adults.For patients with these types of cancers who have relapsed or not responded to conventional treatments, CAR T-cell therapy offers a powerful and potentially life-saving option. The success of CAR T-cell therapy has led to extensive research and clinical trials aimed at expanding its use to treat other forms types cancer, including solid tumors.

Gene therapy represents another facet of genetic medicine, aiming to treat or prevent disease by modifying the genetic material of a patient's cells. This can involve replacing a mutated gene that causes disease with a healthy copy of the gene, inactivating a mutated gene that is functioning improperly, or introducing a new or modified gene into the body to help treat a disease.

Significant progress has been made in the treatment of blood disorders, such as hemophilia, through the use of gene therapy. Hemophilia is a condition where the blood is unable to clot correctly.By introducing a functional copy of the faulty gene into the patient's cells, gene therapy can potentially provide a long-lasting solution to this life-threatening disorder, reducing or eliminating the need for frequent and costly blood transfusions or clotting factor replacements.

Sickle cell disease (SCD) is an area where gene therapy has shown promise. This disease is caused by a mutation in the gene responsible for coding hemoglobin. As a result, the red blood cells become abnormally shaped, which can lead to pain, organ damage, and even death. Gene therapy aims to correct this mutation or introduce a new gene that can produce healthy hemoglobin, offering hope for a cure to patients suffering from this debilitating condition.

Challenges and Future Directions

Both CAR T-cell therapy and gene therapy face challenges such as the complexity and cost of treatment, as well as the potential for side effects. As research progresses, there is hope that these therapies will become more accessible, affordable, and applicable to a wider range of diseases. Ongoing advancements in genetic engineering, coupled with a deeper understanding of the molecular underpinnings of cancer and blood disorders, hold the promise of transforming these once futuristic therapies into standard care. This offers new hope to patients around the world.