Therapy of blood diseases
As a patient of Dr Pavlu, you will have access to the most effective treatment available. He believes in personalised therapy and takes every possible step to choose the most appropriate treatment. This page provides an overview of principles of treatment of haematological disorders. It explains some terms used when explaining treatment options.
- Watchful waiting (watch and wait)
- Supportive care
- Transfusion therapy
- Antimicrobial treatment
- Antimicrobial prophylaxis
- Systemic anti-cancer therapy
- Targeted therapy
- All-trans-retinoic acid (tretinoin)
- Monoclonal antibodies
- Tyrosine kinase inhibitors
- Azacitidine and decitabine
- Bone marrow or stem cell transplantation?
Some haematological diseases and disorders do not require any treatment at the time of diagnosis but warrant monitoring a patient’s symptoms and blood results, so treatment starts when it is beneficial. This strategy applies even to some malignant haematological disorders (blood cancer), particularly if they are slow growing, for example in some cases of early chronic lymphocytic leukaemia. However, watchful waiting cannot be used when early treatment is beneficial or when delay in starting treatment would make treatment more difficult in future.
Supportive care is extremely important in haematology and in many diseases, itself prolongs or saves lives. In some diseases, it is the only treatment available. Supportive care includes:
Transfusion therapy: In the UK blood obtained from blood donors is filtered and divided into red cells, platelets and plasma for separate use. Red cells are used in many cases of anaemia and platelets in some cases of low platelet count. Some patients need regular red cell transfusion support every month, or more frequently, depending on the severity and nature of their disease. Platelets are sometimes also required regularly but more frequently as they do not survive long after transfusion – usually just one or two days.
Growth factors: Some patients with anaemia may benefit from treatment with erythropoietin also known as Epo, a growth factor normally produced by the kidney. Erythropoietin stimulates the bone marrow to make more red cells and can be given as injections under the skin. Similarly growth factors to promote white cells (granulocyte-colony stimulating factor, abbreviated as G-CSF) and platelets can be sometimes used.
Antimicrobial treatment: some haematological disorders make patients more prone to infections. Some treatments given to patients with blood disorders weaken the immune system, making infection more likely. This includes chemotherapy which very often causes low white cell counts, particularly of neutrophils – white cells responsible for fighting bacterial and fungal infections.
The medical term for low neutrophil count is neutropenia and patients with neutropenia are known as being neutropenic. Severe neutropenia is a neutrophil count below 0.5 x 109/L and patients with this form of neutropenia are at very high risk of developing bacterial infections, which can make people extremely unwell rapidly. Prompt administration of antibiotics can be life saving. Patients with severe neutropenia or those expected to develop it are usually given an emergency telephone number to call 24 hours a day or they are told to attend a rapid emergency admission unit, or accident and emergency should they become unwell in any way or develop fever. They are advised to monitor their body temperature regularly for fever (temperature 38oC or above) and this is considered an emergency even if they feel well.
Antimicrobial prophylaxis: antimicrobial drugs including antibiotics, antiviral drugs, and antifungal drugs can be given not only to treat infections but also to reduce the chance of developing them – this is known as prophylaxis. Although useful, prophylaxis can never prevent all infections, so prompt antimicrobial treatment is still essential.
Immunosuppression is a term that refers to a state when people are prone to infections because their defence against infections – immunity – is low (suppressed). This can be due to diseases affecting the immune system or due to drugs that alter its functions. Most malignant haematological disorders (blood cancer) can cause immunosuppression, and so can many benign diseases of white cells and aplastic anaemia.
The term immunosuppression is also used for therapy given for autoimmune disorders in which the immune system attacks its own body. Haematologists treat a whole range of autoimmune diseases including autoimmune anaemias, immune thrombocytopenia (ITP) and aplastic anaemia. Immunosuppression is also used prior to and following bone marrow transplantation.
The most common immunosuppressive treatments used in haematology are:
Corticosteroids:These potent immunosuppresses are used for wide range of disorders, can be applied externally or systemically both into the vein or by mouth. Examples include prednisolonone, methylprednisolone, dexamethasone, but many others are used. Side effects include difficulty sleeping, heartburn, and with prolonged use, muscle wasting and thinning of bones. Long term systemic corticosteroid therapy must not be interrupted or suddenly stopped as this may lead to serious medical problems (Addisonian crisis).
Monoclonal antibodies: Antibodies against lymphocytes, for example rituximab, are often used for a whole range of autoimmune diseases, for example for immune thrombocytopenic purpura. They are also used for the treatment of lymphoma.
Ciclosporin and mycophenolate mofetil (MMF): These drugs are used for the treatment of many autoimmune disorders including autoimmune anaemia often together with corticosteroids or when corticosteroid dose reduces. They can be also combined together. They can both have side-effects and ciclosporin (also spelled cyclosporine) blood levels usually require monitoring.
Anti-thymocyte globulin: Anti-thymocyte globulin is used for treatment of aplastic anaemia and sometimes before bone marrow transplantation.
Chemotherapy: Many chemotherapy agents are also used as immunosuppressants, for their ability to reduce immune system function, particularly lymphocytes. Commonly used are; cyclophosphamide, methotrexate, or etoposide.
Systemic Anti-Cancer Therapy
Systemic anti-cancer therapy (SACT) is a term used for all medications given into veins, under the skin or by mouth as a treatment of cancer. It includes traditional cytotoxic drugs (chemotherapy) that affect all dividing cells of the body as well as drugs that more or less more precisely target the cancer cells (targeted therapy). These treatments are normally alongside the supportive care. All these drugs may cause side effects, some more likely than others. Dose and intensity of treatment also determines how the treatment is tolerated. Anti-emetics and other drugs that reduce side effects are routinely prescribed.
Classical cytotoxic chemotherapy is most effective on cells that are actively growing and dividing cells. It affects normal as well as cancer cells, but often normal cell recover faster from chemotherapy. Chemotherapy drugs are sometimes used alone, but more often drugs with different mechanism of action are combined together. This should increase their effects and help to reduce the side effects.
Chemotherapy drugs are given in cycles. So, after a drug or drug combination is given – over the time of one or more days – there is a break during which the body has time to recover. As soon as this happens next course (cycle) of treatment is given. The number of courses administered depends on a response to treatment. This is assessed by different ways in different types of cancer. In lymphoma CT scan or CT-PET is used, in leukaemia bone marrow needs to be examined, in myeloma paraprotein level can usually be measured.
The first cycle of chemotherapy (or sometimes first two cycles) in treatment of acute leukaemia is called induction. If no leukaemia can be detected by examining bone marrow under microscope, this is called complete remission. Achieving complete remission after induction is a good sign, but it does not mean cure, more treatment is necessary after this. Induction is followed by intensification cycle or by consolidation chemotherapy.
Different chemotherapy drugs have different side effects, but they are some side effects common to most of chemotherapy used in haematology. These include:
Neutropenia – medical term for low neutrophil count. Neutrophils are white cells responsible for fighting bacteria, so prompt antibiotic treatment of infections is required during neutropenia (see supportive care).
Anorexia – medical term for loss of appetite. This is very common with chemotherapy.
Nausea – feeling sick is common whereas vomiting is experienced rarely due to modern anti-emetics (anti-sickness medications).
Fatigue – feeling of tiredness and low in energy is common, particularly with high dose chemotherapy.
Alopecia – loss of hair is common with chemotherapy. After recovery, the hair grows back. Many patients choose to wear wig for the duration of chemotherapy.
Teratogenicity – this means a potential to disturb development of the embryo or fetus. Teratogenic drugs can therefore cause birth defect. It is very important to use effective contraception while on chemotherapy. This applies to both men and women.
Extravasation – is a serious complication of some chemotherapy drugs that can only be given into veins, but leak under the skin and cause damage to the tissue. Examples of these drugs, also known as vesicants are doxorubicine, idarubicine or vincristine. Some chemotherapy is only given into big veins – known as central veins – via bigger cannulas known as central lines or catheters.
Targeted therapy is a newer anti-cancer therapy that takes advantage of differences between normal cells and cancer cells. It can be sometimes used alone and sometimes in combination with traditional chemotherapy. These drugs also have side effects, although different to traditional chemotherapy. Many can also harm the foetus, so effective contraception is mandatory. These are some examples of targeted therapy used in haematology.
All-trans-retinoic acid, abbreviated ATRA, with the generic name tretinoin, is a very potent form of vitamin A used for acute pro-myelocytic leukaemia. This drug very significantly improved the outcome of patients with this rare subtype of acute myeloid leukaemia. Currently it is used in combination with chemotherapy or/and arsenic.
Azacitidine and decitabine work as standand chemotherapy when given in standard doses. However, when used in low doses, they can reverse some DNA changes induced by cancer. Both drugs are currently in use for treatment of myelodysplastic syndrome and a subset of acute myeloid leukaemia. They are very well tolerated and can control myelodysplastic syndrome or leukaemia for many months.
Lenalidomide and thalidomide modify the patient’s own immune system to help it to control some myeloma. It is also effective in a rare type of myelodysplastic syndrome. Side effects include effects on the foetus and predisposition to thrombosis.
Monoclonal antibodies, for example rituximab, are used to help boost the immune system response against lymphoma and chronic lymphocytic leukaemia. It is usually used in combination with chemotherapy.
Proteasome inhibitors work by stopping complexes of enzymes called proteasomes from breaking down regulatory proteins that control cell division. They are used mainly to treat multiple myeloma, but can be helpful in treating some types of lymphoma.
Tyrosine kinase inhibitors are drugs that work by stopping tyrosine kinases – enzymes which can become abnormal in cancer cells. The first use of these drugs was to treat chronic myeloid leukaemia with imatinib – a drug that inhibits bcr-abl1 tyrosine kinase. Many tyrosine kinases are currently used in haematology and even more are in development.
Bone marrow or haematopoietic stem cell transplantation is discussed here.