Leukaemia is a haematological malignancy (blood cancer) that develops in the bone marrow, blood, the lymphatic system and other tissues. The types of leukaemia are commonly divided into acute and chronic, depending on the speed of progression of the disease. 

Generally, we speak of leukaemia in the presence of biological alterations in blood cells (red cells, white cells and platelets) that cause growth and uncontrolled proliferation of the cells themselves. The name derives from the Greek word leukemia leucos = white, because the disease begins in the white blood cells responsible for fighting infections, which normally reproduce according to the needs of the body.

In patients with leukaemia, the bone marrow produces large numbers of abnormal white blood cells, which have genetic mutations in the DNA that are not working properly. The exact causes of this disease are unknown, but both genetic and environmental factors appear to be involved.

Acute leukaemia originates from the bone marrow, the place where the immature cells of blood cells reside and where these cells ripen before "exit" from the bone marrow and enter the bloodstream. The term "acute" refers to the rapid progression of the disease. When some of these immature cells undergo serious genetic damage, they begin to proliferate in an uncontrolled manner often hindering the development of normal cells. The onset of symptoms is very early, from the earliest stages of disease onset, so in some cases it can be fatal (in a few weeks or a few months) without prompt treatment and without the appropriate therapies. Nevertheless, many cases of acute leukaemia, especially in young people, can be treated and cured.

The acute forms of leukaemia are divided into two main groups: acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Acute lymphoblastic leukaemia (ALL) is the most common type in children, but it can also affect adults.


Risk factors

Some factors may increase the risk of developing acute lymphoblastic leukaemia: 


  • Cancer therapies, such as some types of radiation therapy or chemotherapy.
  • Exposure to high levels of radiation.
  • Prolonged exposure to high concentrations of chemicals used in industry, such as benzene and formaldehyde.
  • Family history of leukaemia.



Beyond avoiding exposure to radiation or cancer-causing chemicals, there is no specific way to prevent (lifestyle, eating habits) acute lymphoblastic leukaemia, since the exact causes are unclear.



Patients with acute lymphoblastic leukaemia generally report symptoms of malaise since the onset of the illness. The main symptoms are most often asthenia (fatigue), fever, and spontaneous bruising, even after minor trauma. In some cases the bleeding may be one of the first symptoms in relation to low values ​​of platelets.

For the diagnosis of acute lymphoblastic leukaemia the peripheral blood and bone marrow are always examined. Other major necessary examinations include:


  • CBC / peripheral blood smear: measures the number of white blood cells, platelets and red blood cells of the peripheral blood (PB) and details in percentage and absolute value of the five major types of white blood cells (neutrophils, eosinophils and basophils, and monocytes lymphocytes), whose rare and immature fractions (blast cells, myelocytes and pro myelocytes) may also be examined in more detail by optical microscope.
  • Bone Marrow biopsy and aspiration: both procedures are performed safely by introducing a needle into a bone at the back of the pelvis, namely the posterior superior iliac spine (links on NEJM). With the bone marrow aspiration (AM), once the needle is suitable positioned under local anaesthesia, there shall be 2-4 short repeated aspirations lasting a few seconds, in order to collect adequate samples of bone marrow. The bone marrow biopsy (BOM) is a procedure that provides the extraction of a small cylinder of bone with a special instrument. It is always performed under local anaesthesia. The execution of the BOM for framing clinical prognostic tests in suspected ALL is not always deemed necessary by onco-hematology.
  • Lumbar puncture: it is the procedure, which leads to the central nervous system (CNS) for the removal of cerebrospinal fluid (CSF) for diagnostic purposes. Through lumbar puncture you can also administer chemotherapy for CNS prophylaxis (see treatment). It is performed by placing a thin needle near the lumbar region of the spine, under local anaesthesia, to reach the cavity CSF.
  • Morphological analysis: optical microscope is to examine the morphology of bone marrow cells in samples of bone marrow aspiration and peripheral blood. It provides important information for the diagnosis and the definition of the disease stage.
  • Cytogenetic analysis: used to examine the number and structure of chromosomes of bone marrow cells in samples of bone marrow aspiration or peripheral blood. Some specific chromosomal abnormalities may be associated with a positive or unfavourable prognosis of the ALL.
  • Immunophenotypic analysis: used to examine the characteristics of the surface of leukemic cells present in samples of bone marrow aspiration and peripheral blood, facilitating the diagnosis and, in some cases, allowing to monitor the response to treatments over time.
  • Molecular analysis: it is useful to examine the presence in bone marrow cells from samples of bone marrow aspiration and / or peripheral blood of "molecular markers" of the disease that can facilitate the prognostic classification and allow you to monitor the response to treatment over time. The "molecular markers" originate from chromosomal alterations or DNA.


In most cases, the leukaemia cells affect the bone marrow and the peripheral blood. Less frequently, there may be involvement of the superficial and deep lymph nodes and increased spleen size, sometimes even the central nervous system or testicles ("sanctuaries of disease"). The latter two always require careful consideration to both the diagnosis and treatment.

There are two major subtypes of ALL: acute lymphoblastic leukaemia in B lymphocytes (ALL-B) and acute lymphoblastic leukaemia T lymphocytes (T-ALL). The distinction between B and T lymphocytes is done with the immunophenotypic analysis, which defines the characteristics of the surface of the affected lymphocytes. There are also different varieties of B-ALL and T-ALL that are set with the analysis of bone marrow and peripheral blood. ALL is very important for the study of chromosomal and molecular alterations as well as to define the risk category (high, intermediate and low) and to monitor response to treatment.

A special mention must be made to the ALL that have a specific chromosomal damage known as the Philadelphia chromosome (Ph). About 20% of adult ALL are Ph positive. This alteration is characterized by the mutual exchange of chromosomal material between chromosome 9 and chromosome 22, which results in a chromosome 22 that is smaller than normal. This chromosome damage gives a very poor prognosis. However, these patients may benefit from the recent therapy with tyrosine kinase inhibitors, in combination with traditional chemotherapy. This combination makes it possible to obtain very promising results that seem to result in a substantial change in the prognosis in a positive way.



Almost all patients with acute lymphoblastic leukaemia must be subjected to a therapy. The treatment plan depends on several factors including:


  • Age of the patient and the clinical condition
  • Subtype of ALL
  • Presence of disease in the central nervous system
  • Presence of serious infections at diagnosis
  • History of previous myelodysplasia or prior therapies (radio-chemotherapy)


In most cases the treatment of choice is chemotherapy according to patterns inserted in the context of clinical protocols shared by several centres of Haematology with experience in the field of treatment of acute forms of leukaemia. The treatment is divided into intensive and conservative.

Intensive treatment very often combines at least two chemotherapeutic agents, in order to achieve complete remission of the disease. The conservative treatment aims to implement a temporary control of disease progression without seeking complete remission, and usually involves the use of a single chemotherapy. 


Treatment of acute lymphoblastic leukaemia include:


  • Chemotherapy


Chemotherapy aims to eliminate the leukemic cells in the bone marrow and in the blood to allow the normal residual immature cells of the bone to grow and mature to produce normal blood cells. In the ICU the chemotherapeutic drugs are administered intravenously, while in the conservative therapy they can also be administered orally. 


Intensive chemotherapy is administered during hospitalization, during which the patient is subjected to close monitoring of the values ​​of very low levels of white blood cells, red blood cells and platelets (phase aplasia). The phase of aplasia may be complicated by infections that may be serious enough to require a complex antibiotic therapy. The initial phase of intensive chemotherapy is called induction chemotherapy while the subsequent stages are known as consolidation chemotherapy and/or maintenance. At the end of induction chemotherapy and in some cases consolidation/maintenance therapy, some bone marrow analyses are repeated and the peripheral blood is tested to define the response to treatment.


  • CNS prophylaxis


Leukemic cells of B-ALL and T-ALL can sometimes lurk and grow within the Central Nervous System (CNS), most often near the walls of coating called meninges. For this reason all patients with acute lymphoblastic leukaemia should receive a specific and targeted therapy (prophylaxis, specific and targeted CNS) with the use of chemotherapy or, more rarely, radiotherapy (cranio-spinal radiotherapy). The administration of chemotherapy is performed periodically during the induction therapy and consolidation therapy through lumbar puncture, allowing the right exposure of the CNS anti-leukemic drug.


  • Venous catheter


Given the need to frequently use the intravenous route of administration, especially in intensive care, a central venous catheter (CVC) is placed in a vein in the neck or under the collarbone. The catheter is usually "tunnelled" or a small portion of its runs subcutaneously before entering into the subclavian vein, in order to ensure a prolonged stay, allow easier accessibility to surgeons, and reduce the risk of infections. Thanks to the central venous catheter other exams such as blood tests, blood transfusion, and infusion chemotherapy and antibiotics can be performed or administered.


  • Transfusions


Following chemotherapy, the values ​​of blood cells often drop to very low levels before the normal blood cells start to grow again. In this phase it is very frequent that patients must resort to transfusions of red blood cells and platelets. The Haematology Unit at Humanitas has gained sufficient experience in the management of complications during aplasia post-chemotherapy in the treatment of acute forms of leukaemia.


  • Response to treatment


If the induction chemotherapy is successful, the patient achieved complete remission of the disease. The values ​​of complete recovery (or almost) also include morphological analysis of the number of leukaemia cells in the bone marrow, which is <5% and the patient is usually able to leave the hospital. The therapies of consolidation/maintenance aim to maintain complete remission for as long as possible, or until transplantation for those who may undergo such procedures. The duration of the chemotherapy and the indication to transplantation depend on the type of leukaemia, its risk category and condition of the patient.


  • Hematopoietic stem cell transplantation


Up to 65 years of age, ALL patients may be candidates for a bone marrow transplant. The autologous bone marrow transplantation (i.e. using their own hematopoietic stem cells) has a small indication in ALL.

Transplanting allogeneic cells (i.e. using hematopoietic stem cells from a healthy donor) is a full indication for all high-risk acute types of leukaemia that reach complete remission. The decision to subject a leukaemia patient to an autologous or allogeneic transplant depends on the type of leukaemia, the risk category, age of the patient, the patient’s overall health and it is always accompanied by an in-depth interview with the doctors of the Transplantation Unit regarding potential risks and benefits.

Forms of leukaemia with a positive prognosis are never candidates for transplant, unless the aim is to assist a relapse of the disease in the course of treatment or the response to treatment is deemed unsatisfactory or incomplete. Allogeneic transplantation remains the only weapon capable of offering a hope of recovery even in late-stage leukaemia or refractory to conventional treatments.

Humanitas has gained sufficient experience in stem cell transplant; it is credited for transplant from an unrelated donor, offering the possibility of transplants from alternative sources such as umbilical cord blood and haploidentical or partially compatible family donor.