Thalassemia is an inherited blood disorder characterised by low haemoglobin (Haemoglobin is an iron rich protein present within the Red Blood Cells of the body. Haemoglobin is responsible for carrying oxygen to all parts of the body). Normal haemoglobin binds iron with alfa and beta globin (protein) chains. Due to genetic mutations in both the genes inherited from the parents, either alfa or beta chains are absent or reduced. This results in precipitation of other globin chains inside the red blood cells, leading to deformity of the red cells. These deformed red cells get destroyed either within the bone marrow (spongy material within the bones) or spleen resulting in anemia (Pallor). This is called Thalassemia Major.

When an individual inherits only one abnormal gene, the manifestations are very mild. This is called Thalassemia Minor or Thalassemia Trait.

The commonest form of Thalassemia in India is Beta-Thalassemia, where Beta-globin chains are deficient. When instead of absolute absence of one type of globin chain, there is reduction only; the condition is called Thalassemia Intermedia.

Other Thalassemia like Syndromes such as HbE, HbD etc. when co-inherited with Beta-thalassemia gene give rise to Thalassemia Intermedia.

Symptoms of Thalassemia Major

The symptoms appear between 3-7 years age. The child starts becoming listless, irritable and pale. The parents often visit the doctor several times before this is detected. The spleen enlarges in size and the eyes turn yellow from jaundice. The child is unable to grow and play like other children of his age.

Symptoms of Thalassemia Intermedia

This depends on the severity of the affection of globin gene production. In more severe form, the symptoms are same as Thalassemia major, but they start later in life. Often they don't need regular blood transfusion.

Symptoms of Thalassemia Trait

This does not produce any symptom and is often detected on routine blood tests. The red cell morphology is abnormal but the Hb is usually near normal.

Complete Blood Count

An astute haematologist easily picks up the diagnosis on routine blood tests.

Hemoglobin Electrophoresis

This is needed to confirm the diagnosis. HbF is the major component with very little of normal haemoglobin (HbA).

Genetic Tests

Genetic tests are done to test for the mutations of Thalassemia. This is needed in the following situations:

• When the child is already transfused and the diagnosis cannot be confirmed by electrophoresis.
• When a couple wants to confirm the status of the foetus i.e. antenatal testing.

There are two approaches to the treatment of Thalassemia major:

1. Transfusion and Chelation (Removal of iron from body)

This involves regular red cell transfusion to maintain the Hb above 12 gm% and not let it drop below 9.5 gm%. This enables normal growth and development.

However, such regular transfusion loads our body with excess iron which affects the heart, liver and other organs. There are medicines, both Intravenous and Oral, to remove excess iron from our body. Effective iron chelation helps in maintaining organ function in regularly transfused patients.

Other side effects of transfusion include:

• Transmission of viral infections
• Transfusion reactions
• Development of antibodies against red cells.

During chelation, the effect on eyes and ears has to be monitored. Odd infections with bacteria like Yersinia can also occur.

2. Bone Marrow Transplantation (BMT)

ALLOGENEIC Bone Marrow Transplantation (BMT) is the only curative treatment for this condition. This works by replacement of diseased stem cells with healthy donor stem cells. Once healthy stem cells start producing normal red cells with normal Hb, the patient is cured.

This doesn't change the genetic composition of the patient, it only changes the genetic composition of the bone marrow.

What is the best age for patients with Thalassemia to undergo Bone Marrow Transplantation?

Best age is between 2 to 5 years. However, successful BMT has been carried out in older children and young adults.

Who can be the donor?

• Matched Family donor is the best option.
• A person who has Thalassemia trait can be a donor for a patient with Thalassemia major.
• Results with Matched Unrelated Donor are improving.
• Recent studies have shown that HAPLOIDENTICAL (Half Matched) FAMILY DONOR might be a viable option for patients with Thalassemia major.

How do we predict the success or failure of BMT in a particular patient?

Prof. Lucarelli from Pessaro, Italy had proposed a scoring system for patients undergoing BMT for Thalassemia. This takes into account the effectiveness of transfusion, chelation and degree of iron overload. The patients are classified as Class I, Class II, Class III.

Outcome based on Pessaro Classification: Thalassemia free Survival

• Class I: 90%
• Class II: 80%
• Class III: 60%

Do patients with Thalassemia Intermedia need BMT?

Following categories of patients need Bone Marrow Transplantation:

• Those with severe symptoms
• Those who are transfusion dependent
• Those who choose to be cured knowing the risks and benefits

Sickle Cell Anaemia is the most common form of sickle cell disease (SCD). SCD is a serious disorder in which the body makes sickle-shaped red blood cells. "Sickle-shaped" means that the red blood cells are shaped like a crescent.

Normal red blood cells are disc-shaped and look like doughnuts without holes in the centre. They move easily through the blood vessels. Red blood cells contain an iron-rich protein called haemoglobin. This protein carries oxygen from the lungs to the rest of the body.

Sickle cells contain abnormal haemoglobin called sickle hemoglobin or hemoglobin S. Sickle hemoglobin causes the cells to develop a sickle, or crescent shape.

Sickle cells are stiff and sticky. They tend to block blood flow in the blood vessels of the limbs and organs. Blocked blood flow can cause pain and organ damage. It can also raise the risk for infection.

When both parents have a normal gene and an abnormal gene, each child has a 25 percent chance of inheriting two normal genes; a 50 percent chance of inheriting one normal gene and one abnormal gene; and a 25 percent chance of inheriting two abnormal genes.

People who inherit a sickle hemoglobin gene from one parent and a normal gene from the other parent have sickle cell trait. Their bodies make both sickle hemoglobin and normal hemoglobin. People who have sickle cell trait usually have few, if any, symptoms and lead normal lives. However, they can pass the sickle hemoglobin gene to their children.

People who inherit both sickle hemoglobin genes from both parents develop Sickle Cell Disease. Their bodies make mostly sickle hemoglobin.

Sickle cell anemia is most common in people whose families come from Africa, South or Central America (especially Panama), Caribbean islands, Mediterranean countries (such as Turkey, Greece, and Italy), India, and Saudi Arabia.

The signs and symptoms of sickle cell anemia vary. Some people have mild symptoms. Others have very severe symptoms and are often hospitalized for treatment. Sickle cell anemia is present at birth, but many infants don't show any signs until after 4 months of age.

The most common signs and symptoms are linked to anemia and pain. Symptoms may include:

• Severe pain in arms, back, abdomen and legs
• Fever
• Strokes — one-sided weakness or paralysis in arms, face or legs; or finding difficulty in talking, walking or seeing
• Shortness of breath or difficulty in breathing
• Chest pain
• Severe infections
• Blood flow blockage in liver or spleen
• Anemia
• Delayed growth
• Hand & foot syndrome i.e. swelling in the feet and hands
• Pale skin
• Vision problems
• Kidney failure
• Pulmonary Hypertension

Complete Blood Count and PERIPHERAL Blood Smear

The characteristic finding of SCD is circulating sickle shaped red cells. Routine examination of the blood count reveals anemia. Reticulocytosis i.e. increase in young red blood cells is almost always seen.

Hemoglobin Electrophoresis

This is the cornerstone of diagnosis and is used to detect Hemoglobin S. HbA2 and often HbF are increased in SCD.

Prenatal Diagnosis

May also be detected by examining the DNA from the chorionic villus biopsy or from the cells of amniotic fluid.

Supportive Treatment

• Folic acid
• Penicillin prophylaxis
• Pneumococcal vaccine.
• All the infections should be identified and should be treated early.
• Treatment of painful crisis or other complications.

Specific Treatment

• Hydroxyurea: Data have shown that it decreases the painful crisis episodes. This drug decreases Neutrophil concentration and stickiness of red cells and increases fetal hemoglobin (HbF).
• Red cell Transfusion: Used frequently in Sickle Cell Disease to increase Hb concentration and decrease the concentration of sickle red cells.
• Exchange red cell transfusions: This is done to reduce the concentration of sickle cells without increasing the concentration of red cells too much.

ALLOGENEIC BMT was first carried out in 1980 in a patient with Acute Leukemia who also had Sickle Cell Disease. Since then several centers in the Europe and North America have successfully performed BMT for Sickle Cell Disease.

This shows that 90% of the most severely affected patients with Sickle Cell Disease are cured with BMT if they have a matched family donor.

However, very few patients with Sickle Cell Disease have a Matched Family Donor. The Unrelated Donor Transplants are often complicated by severe Graft Versus Host Disease (GVHD).

BMT in Sickle Cell Disease has produced the best results one can expect in any severe inherited disease.

Recent studies have shown that Haploidentical BMT can cure the majority of patients with Sickle Cell Disease with nearly 100% chance of finding a donor.

How is Conditioning for BMT done in Sickle Cell Disease?

Primarily Reduced Intensity conditioning is used in adults and conventional high dose chemotherapy or radiation is the preferred option in children.

Who can be a donor for BMT?

Although we prefer a matched family donor, a Half matched (Haploidentical) family donor or an unrelated donor provide excellent survival.

The blood cells have a limited lifespan. Red blood cells survive 3 months, white cells survive for 24 hours and platelets survive for 5 days. The bone marrow is an amazing organ which produces billions of blood cells every day to keep up with the requirements of our body. When the bone marrow fails, the cell production slows down and often stops. This is called aplastic anemia.

The incidence of Aplastic anemia in Asian countries is 5 times higher than in Europe or USA.

Aplastic anemia results from damage to the mother cells or stem cells which are no longer able to produce normal blood cells. This can happen due to the following causes:

• Chemicals and toxins such as benzene and pesticides
• Infections such as hepatitis
• Drugs such as arsenic, gold, painkillers and some antibiotics
• Inherited conditions such as Fanconi's Anemia
• Most commonly, the cause is not known and thought to be due to an immune mediated attack by the body on its own stem cells.

The diagnosis of aplastic anemia needs awareness of the condition and a strong index of suspicion. The patient can present with fever due to infection, bleeding and bruising due to low platelet count and fatigue due to anemia.

A routine blood test shall show at least two of the three cell lines of red cells, white cells and platelets being low. A marrow biopsy is mandatory to confirm the diagnosis and rule out other causes of marrow failure like leukemia.

It is important to look for a causative factor and stop any drug or exposure to chemical that might have caused it.

The investigations include blood tests to look for infections, autoimmune diseases like lupus and chromosomal breakage study to rule out Fanconi's anemia.

Classification

• Severe: neutrophil count less than 500 cells/microliter (normal 1500-6000/microliter)
• Very Severe: neutrophil count less than 200 cells/microliter
• Nonsevere: none of the above

Supportive Therapy

We cannot survive without functioning blood cells. Immediate treatment involves transfusion of red cells and platelets and treatment of infections. However, the patient must be referred to a center where curative treatment can be given as soon as possible. Repeated blood transfusions reduce the success rate of BMT.

Immunosuppressive Treatment

Antithymocyte globulin, a drug produced from horse or rabbit by injecting human lymphocytes in them, is the main drug. It suppresses the immune system and allows the marrow to recover. This drug is given with another oral medicine called Cyclosporine. About 60-70% of the patients improve with this treatment. However, it takes 3-6 months for the marrow to recover and many patients may relapse or develop other marrow disorders in the future.

Blood and Marrow Transplantation (BMT)

BMT cures 90% of the patients with aplastic anemia if carried out early and from a matched family donor. BMT is the treatment of choice for young patients with a matched sibling donor.

For patients without a matched family donor, HAPLOIDENTICAL DONOR TRANSPLANTATION is now giving results as good as a matched family donor. At BLOODSRUS, we offer the best survival for patients with aplastic anemia through BMT.

Acute Lymphoblastic leukemia (ALL), is a cancer that starts from white blood cells called lymphocytes in the bone marrow (the soft inner part of the bones, where new blood cells are generated).

The term "acute" means that the leukemia can progress quickly, and if not treated, would probably be fatal within a few months. 'Lymphoblastic' means it develops from early (immature) forms of lymphocytes, a type of white blood cell.

Acute Lymphoblastic Leukemia is the commonest childhood cancer. This arises from abnormalities in the precursors of normal lymphocytes which are otherwise a normal part of our immune system necessary to fight infections. These abnormal cells rapidly fill up the bone marrow space suppressing the normal cells.

In most cases, the disease is characterised by certain abnormalities in the chromosomes which promote abnormal growth of certain lymphoid cells rather than maturation to normal lymphocytes.

This is not known in most cases. However, exposure to radiation, exposure to high voltage electric wires and chemical exposures are few known risk factors.

Symptoms

• General weakness
• Fatigue
• High temperature (fever)
• Weight loss
• Frequent infections
• Bruising easily or with no obvious cause
• Bleeding from the gums or nose
• A fine rash of dark red spots (called purpura)
• Blood in urine or stools
• Pain in the bones or joints
• Breathlessness
• Swollen lymph glands
• Enlarged liver or spleen

Complete Blood Count

The characteristic finding of Acute Lymphoblastic Leukemia is high white blood cell count with low haemoglobin and platelets. Routine examination of the blood under the microscope may confirm the presence of abnormal cells (blasts).

Bone Marrow Examination

This is necessary for confirmation of the diagnosis. There must be more than 30% of abnormal cells (blasts) in the marrow for it to be called Acute Lymphoblastic Leukemia.

Flow Cytometry

ALL has two broad subtypes- B cell Acute Lymphoblastic Leukemia and T cell Acute Lymphoblastic Leukemia. There are further subtypes in the individual categories. This has got implications on the choice of treatment and the likely outcome.

Cytogenetics

This is testing for abnormalities in the chromosomes. Certain genes are brought next to each other by a process called 'translocation' leading to uninterrupted growth and proliferation of white blood cell precursors in the bone marrow (e.g., Philadelphia Chromosome). Both are normal genes, but when they interact they produce an abnormal protein which drives the cancer. The absolute increase (Hyperdiploid) or decrease (Hypodiploid) in the number of chromosomes in the cancer cells are also features of ALL. Certain changes in sequence of the genes called mutations are also seen which have an impact on outcome of treatment.

Classification

Unlike cancers of solid organs, Acute Lymphoblastic Leukemia and other blood cancers are not staged by the extent of involvement. Certain features related to the patient and the disease help in classifying the patients as: Standard-Risk or Good-Risk, Intermediate-Risk and High-Risk.

• Age: if the patient is 2–10 years old, it is considered favourable
• Cytogenetics: Certain chromosomal abnormalities such as increase in number of chromosomes (Hyperploidy) and translocation are features of a favourable outcome.
• Response to Treatment: Response to steroids after 7 days is probably a very good indicator of how the disease is going to respond to further treatment.

Minimal Residual Disease (MRD)

Minimal Residual Disease (MRD) means patient still has a minimum disease and has not fully recovered. Response to treatment is conventionally checked with a bone marrow morphology which establishes COMPLETE REMISSION (CR). However, CR means that the number of leukemia cells in the body are less than 10⁹ or 1000 million cells. At this level, they cannot be seen under the microscope.

MRD is the detection of cells below 1%, which can range from 1 in 1000 to 1 in a million cells. This enables us to check for response to treatment with a much higher sensitivity than possible under the microscope.

Treatment Phases

• Induction Therapy: The first phase of treatment to kill most of the leukemia cells in the blood and bone marrow and restore normal blood cell production.
• Consolidation Therapy: Also known as post-remission therapy. Aimed at destroying any remaining leukemia cells in the body.
• Maintenance Therapy: Helps in preventing leukemia cells from regrowing. Treatments used in this stage are often given at lower doses over a long period of time.
• Preventive treatment to the spinal cord: Patients suffering from acute lymphocytic leukemia may also receive treatment to kill leukemia cells located in the central nervous system. In this treatment, chemotherapy drugs are injected directly into the fluid that surrounds the spinal cord.
• Radiation Therapy: Radiation therapy uses high-powered beams, such as X-rays, to kill cancer cells. If the cancer cells have spread to the central nervous system, your doctor may recommend radiation therapy.

Depending on patient's evaluation, the phases of treatment for acute lymphocytic leukemia can span up to 2-3 years.

Role of Chemotherapy

• 90% of the children with Standard Risk Acute Lymphoblastic Leukemia are cured with Chemotherapy alone.
• 60-70% of children with Intermediate Risk Acute Lymphoblastic Leukemia are cured with Chemotherapy alone.
• 40% of children with High Risk Acute Lymphoblastic Leukemia are cured with Chemotherapy alone.

ALL has a tendency to spread to the brain. Hence, the treatment involves giving intrathecal chemotherapy periodically through a Lumbar Puncture. Intravenous chemotherapy is also given over 6 months, followed by oral drugs for 18-30 months. Boys are treated for a longer duration than girls.

Adolescents and Young Adults (AYA)

Patients between ages 16 and 25 are called Adolescents and Young Adults (AYA). The results in this age group are slightly inferior than in younger children.

When is BMT needed?

• Most children with Standard or Intermediate Risk Acute Lymphoblastic Leukemia are cured with chemotherapy and do not need a BMT.
• Most children with High Risk Acute Lymphoblastic Leukemia might need a BMT.
• Most Children with a positive MRD after intensive chemotherapy would benefit from a BMT.

Conditioning

Total Body Radiation is an important component of conditioning for BMT.

Who can be a donor?

Although we prefer a matched family donor, a Half matched (Haploidentical) family donor or an unrelated donor can also be used.

Results of BMT

• BMT reduces the risk of relapse i.e. recurrence of disease by 50% compared to chemotherapy.
• If the child is MRD negative before BMT, the risk of relapse is negligible.
• BMT is the only cure for patients who relapse early after chemotherapy.

A slowly progressing disease in which too many white blood cells (not lymphocytes) are made in the bone marrow. Chronic Myeloid Leukemia was the first disease where the molecular abnormality leading to cancer was deciphered. A unique translocation between chromosomes 9 and 22 leads to the formation of BCR-ABL fusion protein which results in uncontrolled proliferation of white blood cells.

Phases of Chronic Myeloid Leukemia

• Chronic phase: elevated blood counts with enlarged spleen. Patients are asymptomatic or mildly symptomatic.
• Accelerated Phase: The disease starts getting out of hand. The spleen gets bigger despite treatment. The blasts in the blood and marrow start to increase (10 to 19%).
• Blast Crisis: This is when the disease develops to a full blown leukaemia with marrow blasts more than 20%.

What Causes Chronic Myeloid Leukaemia?

This is largely unknown as in most cases of leukaemia. Risk factors: More common in males; More common in the elderly with a median age at diagnosis of 65 years; Exposure to ionising radiation; Low Immunity; Inflammatory bowel conditions, such as ulcerative colitis or Crohn's disease; Using pesticides at work.

How is CML in Children different from that in Adults?

• CML is less common in children
• Long term outcome of TKI therapy is not known in children. We are not talking of 10 or 20 years of treatment but for 50 to 60 years or more.
• BMT should still be considered in children as first line therapy if the right donor is identified.

In most patients there are no symptoms, 25% of the patients are detected when the disease has progressed to accelerated or blast phase. Common symptoms include: Frequent Infections; Weight loss; Tiredness and looking pale; Swollen lymph glands; Abnormal bruising or bleeding; Abdominal discomfort due to an enlarged spleen; Poor appetite; Sweating at night; Headaches; Bone pain.

Diagnosis

Complete Blood Count: high white blood cell count with low haemoglobin and high platelet count. Bone Marrow Examination: necessary for confirmation; in chronic phase, blast count is less than 5%. Flow Cytometry: to confirm type of transformation. Cytogenetics: essential for confirmation of diagnosis. Karyotyping: establishes classic translocation between chromosomes 9 and 22. PCR: a test done on the DNA and establishes the amount of BCR/ABL product.

Treatment

Targeted therapy; Chemotherapy; Biologic therapy; High-dose chemotherapy with Bone Marrow Transplant.

BMT was the treatment of choice for Chronic Myeloid Leukemia until Tyrosine Kinase Inhibitors (TKI) were developed.

When is BMT needed?

• When patients stop responding to Tyrosine Kinase Inhibitors (TKI)
• When Chronic Myeloid Leukemia is in Accelerated Phase or Blast Crisis.

Conditioning

High to Moderate dose of chemotherapy is generally used in conditioning for BMT in younger patients.

Who can be a donor?

Although, a matched family donor is preferred, a Half matched (Haploidentical) family donor or an unrelated donor can also be used. However a Haploidentical (Half Matched) Donor who has Natural Killer Cell mismatch with the patient is an ideal donor for CML as it reduces the risk of relapse.

Results of BMT in CML

BMT remains the only curative treatment for Chronic Myeloid Leukemia.

• Chronic Phase: 90% are cured
• Accelerated Phase: 40-60% are cured
• Blast Crisis: 20-40% are cured

Hodgkin's lymphoma is a distinct cancer of lymphoid tissue derived from germinal B cells of lymph glands, defined by the presence of very characteristic cells called REED-STERNBERG cells or its variants with characteristic immunophenotype in a background of different types of cells.

Types of Hodgkin's Lymphoma

• Nodular sclerosing HL
• Mixed-cellularity subtype
• Lymphocyte-rich or Lymphocytic predominance
• Lymphocyte depleted
• Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL)

What Causes Hodgkin's Lymphoma?

The exact cause of Hodgkin disease is not known. Most Hodgkin's lymphomas occur when an infection-fighting cell called a B cell develops a mutation in its DNA. The mutation tells the cells to divide rapidly and to continue living when a healthy cell would die.

Risk Factors

• Age: Generally Age group 15-35 and 55 years and above are diagnosed with Hodgkin's lymphoma.
• Sex: Mostly Male are suspected to be on higher risk of Hodgkin's lymphoma.
• Previously exposed to the Epstein-Barr virus (EBV), a common virus that causes glandular fever.
• Medical condition that weaken immune system, such as HIV.
• Previous treatment with chemotherapy or radiotherapy for Non-Hodgkin's Lymphoma.

• Painless swelling of the lymph nodes in neck, armpits, groin (swollen glands)
• Fatigue
• Fever and chills that come and go (38°C / 100.4 F)
• Unexplained Itching all over the body
• Loss of appetite
• Soaking night sweats
• Unexplained Weight loss

Other symptoms that may occur

• Coughing, chest pains, or breathing problems if there are swollen lymph nodes in the chest
• Excessive sweating
• Pain or feeling of fullness below the ribs due to swollen spleen or liver
• Pain in lymph nodes after drinking alcohol
• Skin blushing or flushing

Lymph Node Biopsy

Hodgkin's lymphoma is diagnosed from Biopsy of lymph gland or other involved tissues. Histopathology reveals five subtypes: Nodular Sclerosis and Mixed cellularity are more common. Detection of cell surface antigens by Immunohistochemistry (IHC) is confirmatory. Expression of CD30 and CD15 are seen in the RS cells, except in NLPHL, where CD20 is expressed.

Blood tests; Imaging tests (X-rays, CT scan, PET); Bone Marrow Biopsy; Additional Tests: Serum LDH, ECG, Echocardiogram and Lung Function Test before starting treatment.

Staging

• Stage I: Hodgkin disease is found in only 1 lymph node area or lymphoid organ such as the thymus. The cancer has not spread to other areas of the body.
• Stage II: Hodgkin disease is found in 2 or more lymph node areas on the same side of (above or below) the diaphragm.
• Stage III: Hodgkin disease is found in lymph node areas on both sides of (above and below) the diaphragm. It may also have spread to an area or organ near the lymph node areas or to the spleen.
• Stage IV: Hodgkin disease has spread widely through 1 or more organs outside of the lymph system.

Treatment Options

• Chemotherapy
• Radiation therapy
• High-dose chemotherapy and Bone Marrow transplant

Favourable, Limited Stage Disease: Treated with short course chemotherapy and involved field radiotherapy; >95% cure rate.

Unfavourable, Limited Stage Disease: Similar treatment but more intensive; > 90% cure rate.

Advanced Disease: ABVD/BEACOPP >60%-80% cure rates.

However, use of radiotherapy is not favoured in small children unless absolutely necessary.

BMT for Hodgkin's Lymphoma

About 30% patients with advanced disease and 10% patients with Limited disease relapse. Once Hodgkin's lymphoma relapses, the treatment is well-defined:

1. Salvage Chemotherapy
2. Autologous Peripheral Blood Stem Cell Collection
3. High Dose Chemotherapy and Autologous BMT

If the patient is PET negative before BMT, 80% of the patients are cured. If the patient is PET positive, the cure rate is only 20%.

If a patient achieves a complete remission, even in advanced disease, there is no need to perform a BMT upfront.

When is Allogeneic BMT needed?

• When the disease recurs after Autologous BMT
• When PBSC cannot be mobilised for Autologous BMT

There is a strong Graft versus Tumour effect against HL in the setting of Allogeneic BMT. In the setting of High Risk and Relapsed Hodgkin's lymphoma, best results are obtained with HAPLOIDENTICAL DONOR and REDUCED INTENSITY CONDITIONING. 70% patients are cured with this procedure.

Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders that can occur when the blood-forming cells in the bone marrow are damaged. This damage leads to low numbers of one or more type of blood cells. They represent 5–10% of all myeloid malignancies in children. MDS is characterized by ineffective haematopoiesis and increased cell death.

MDS can affect children as well, although the incidence is less than 5%. Anemia is the commonest manifestation of MDS in adults, but low white cell or platelet count is commoner in children.

The bone marrow is more often less cellular like Aplastic anemia and this entity is called Refractory Cytopenia of Childhood (RCC). This condition has to be differentiated from Aplastic Anemia.

Symptoms

• Shortness of breath
• Weakness or feeling tired.
• Having skin that is paler than usual
• Easy bruising or bleeding
• Petechiae (flat, pinpoint spots under the skin caused by bleeding)
• Fever or frequent infections

Classification

This is based on number of cell lines affected (i.e. 1, 2 or 3) and the number of blasts in the bone marrow.

• Refractory Anemia
• Refractory Cytopenia with Multilineage Dysplasia
• Refractory Anemia with Ring Sideroblasts
• Refractory Anemia with Excess Blasts

The three most important parameters determining the outcome: 1. Number of Cytopenias, 2. %age of blasts in bone marrow, 3. Abnormalities in the chromosomes. Based on these three parameters, an International Prognostic Scoring System has been developed.

The diagnosis is made by careful and diligent examination of Blood and Bone Marrow samples by an experienced Hematologist. Along with that study of chromosomes from the bone marrow cells (Cytogenetics) is needed.

The abnormalities of chromosomes are divided as GOOD or BAD: Good: normal, -Y, del5q, del20q. Bad: Monosomy i.e. deletion of one of the pair of chromosomes, mostly chromosomes 5 and 7 and other complex abnormalities.

Treatment

The Only Curative Treatment of MYELODYSPLASTIC SYNDROME (MDS) Is an Allogeneic BMT.

As the disease is mostly seen in older patients, a Reduced Intensity Conditioning is preferred.

The BMT should be done early, before the onset of life threatening infections or multiple transfusions which may lead to iron overload. Some of the patients with higher blast count or abnormal chromosomes might benefit from a short course of chemotherapy before the BMT.

Who can be a donor?

Although we prefer a matched family donor, a Half matched (Haploidentical) family donor or an unrelated donor provide excellent survival. However a HAPLOIDENTICAL DONOR, who has Natural Killer Cell mismatch with the patient, provides the best survival through its graft versus leukemia effect.

Other Treatments (for older patients not fit for BMT)

• Red Cell and Platelet Transfusions as needed
• Erythropoetin injections to reduce blood transfusion requirements
• Hypomethylating agents such as Azacytidine or Decitabine which are milder forms of chemotherapy.