Hematologic malignancies, also called blood cancers, are cancers that affect cells of the bone marrow, the lymphatic and the immune system.

Blood cancer originates from the proliferation and the survival of the two major blood cell lineages: myeloid and lymphoid cell lines.

Leukemia (blood cancer) can be of four types: 

• Acute leukemia – Myeloblastic (AML) or Lymphoblastic (ALL)
• Chronic leukemia - Myelogenous (CML) and Lymphocytic (CLL)

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At the IEO leukemia is treated by a multidisciplinary team consisting of specialists in:

• Clinical Haemato-Oncology
• Haematopathology
• New Drugs and Early Drug Development for Innovative Therapies
• Department of Pathology and Laboratory Medicine
• Department of Medical Imaging and Radiation Sciences

High level of radiation is the main risk factor for leukemia, particularly acute myeloid leukemia (AML).

Other risk factors for leukemia are:

• Exposure to cancer-causing agents, such high doses of radiation and solvents (i.e. benzene)
• Smoking
• Bone marrow failure disorder, such as myelodysplastic syndromes
• Rare genetic syndromes

Acute Leukemia, Myeloblastic (AML) or Lymphoblastic (ALL)

Acute leukemia is a type of fast growing blood cancer that requires prompt treatment. Blood is made up of different types of cells that are produced in the interior of bones in a part called the bone marrow. When people have this type of blood cancer, their bone marrow produces abnormal blood cells that are out of control and are not effectively working according to the body needs. This type of blood cancer can cause signs and symptoms such as:

• Feeling fatigues and weak
• Bleeding
• Fever and easily catching infections

The diagnosis of acute leukemia:

Successful therapeutic plan of all blood cancers depends on the proper diagnosis at the microscopic and molecular level. This is done through comprehensive evaluation of:

• Blood tests, in particular Complete Blood Count (CBC) and blood film examination
• Bone marrow examinations, including:
  • Histological evaluation
  • Immunophenotypic analysis of blood and marrow cells
  • Cytogenetic analysis to detect chromosomal abnormalities
  • Genetic studies in order to detect disease-specific DNA abnormalities

Chronic Lymphocytic Leukemia (CLL) and Chronic Myeloid Leukemia (CML) 

Chronic leukemia is a type of blood cancer that usually grows slowly.

Main signs and symptoms are of this blood cancer are:

• Feeling of fatigue and weakness
• Ease of  catching infections
• Fevers, drenching sweats at night, and losing weight
• Lymphadenopathy and organomegaly: patients with Chronic Lymphocytic Leukemia (CLL) may have swollen lymph nodes in the neck, under the arm, or in the groin; patients with Chronic Myeloid Leukemia (CML) may present with large spleen.

The diagnosis of chronic leukemia:

• CBC (Complete Blood Count), along with blood film analysis, is the first step to suspect a Chronic Leukemia
• The diagnosis of CLL can be made by Immunophenotypic Analysis, which may show the presence of the a clonal lymphocyte population, i.e. the neoplastic CLL population
• CML diagnosis requires the detection by molecular analysis of blood or marrow DNA, revealing the presence of the distinctive bcr-abl gene, that originate by the translocation involving chromosomes 9 and 22, giving rise to the diagnostic “Philadelphia Chromosome” (Ph-1)

Treatment for Acute Leukemia, Myeloblastic (AML) Or Lymphoblastic (ALL)

Treatment is complex and depends on the type of blood cancer and other factors such as age and donor availability for bone marrow transplant.

Treatment of acute leukemia generally includes two main initial parts.

The first part of treatment is called “induction of remission” and is approximately 4 weeks. This part of treatment requires you to stay in the hospital and receive chemotherapy regimens.

Once in “remission” state, which means no abnormal blood cells are detected in the blood or bone marrow by microscopic examination, the second part starts, termed “post-remission therapy.” This part includes:

• additional chemotherapy courses for a period of 3 to 4 months and, in younger patients.
• bone marrow transplant either by using the patient’s own bone marrow cells to support the use of higher doses of chemotherapy (autologous transplant) or replacing the diseased bone marrow cells with more heathy cells from a volunteer donor (allogeneic transplant or allo-HSCT, i.e. allogeneic-Hematopoietic Stem Cell Transplantation). In fact, alloHSCT is the most effective option for patients younger than 65-70 yrs., with Acute Leukemia and unfavorable prognostic features or with refractory or relapsed of the blood cancer; the immune-mediated anti-leukemia effect, which is particular to allogeneic transplantation, makes the allo-HSCT procedure extremely effective in leukemia although much more complex compared to autologous transplantation.

Radiation therapy is sometimes used to kill remaining blood cancer cells at certain organs of the body as in cases of central nervous system involvement, usually at the end of chemotherapy courses.

The importance of blood cancer assessment following therapy

The accurate evaluation of response to therapy is crucial in Acute Leukemia (AL). In particular, molecular and immunophenotypical procedures have been developed in order to identify minimal quantities of blood cancer cells that might persist following treatment below the levels detectable by standard methods of evaluation. This is called Minimal Residual Disease (MRD). The evaluation of MRD has reached a key role in the management of AL, as well as in other blood cancers where MRD can be assessed and monitored. In particular, in AL MRD may direct the treatment strategies following induction therapy and the preferred use of additional chemotherapy versus transplant-based is often based on results of MRD. Also at our Institutions at IEO, the study of MRD both in bone marrow (BM) and peripheral blood (PB) cells is a key point in the management of AL patients. In addition, research studies are ongoing with a dual aim:  to optimize the use of MRD analysis in AL patients and to extend the population of patients with hematological malignancies that might be assessed and monitored by MRD.         

MRD is regularly assessed at given time points during treatment. Moreover, all patients undergo regular visits, with blood tests and additional clinical exams, if needed, during the various treatment steps and at long term once the whole treatment program is completed

Treatment for Chronic Lymphocytic Leukemia (CLL) and Chronic Myeloid Leukemia (CML) 

Chronic lymphocytic leukemia (CLL): Being a slowly growing and indolent blood cancer, CLL is treated when the blood cancer causes symptoms or starts growing faster than its original rate.

The main form of treatment for this blood cancer is chemotherapy combined with immunotherapy. The choice between different chemotherapy drugs is based not only on the molecular profile of the blood cancer but also on patient-related factors and comorbidities. Immunotherapy is mainly comprised of monoclonal antibodies directed against surface antigens of neoplastic lymphocytes. By far, the most extensively employed is the anti-CD20 monoclonal antibody Rituximab. Other monoclonal antibodies and novel drugs directed against molecular checkpoints that are abnormally expressed in CLL cells are under advanced development (see also: Lymphoma section, Novel targeted drugs)

Chronic myeloid leukemia (CML): CML cells harbor the abnormal bcr-abl gene, whose product is a tyrosine-kinase responsible for the over-production of myeloid blood cancers. In the last two decades, very effective drugs inhibiting the bcr-abl tyrosine-kinase product (known as Tyrosine-kinase inhibitors or TKIs) have been developed, with a of great consequence for the management and the long-term life-expectancy for patients with CML. Nowadays, most CML patients are successfully treated with TKIs, without the need for either chemotherapy or transplant procedures. TKIs are very effective in long-term control of the blood cancer and have resulted in a revolutionary success in the history of this blood cancer. Treatment requires frequent visits to evaluate the course of the blood cancer response with frequent blood and as necessary bone marrow exams.

In few cases, the blood cancer cells grow faster and becomes less controlled by the “first generation” TKI; however, newly- developed, “second or third generation”TKIs, may overcome drug-resistance.

Other treatment options, which can help to control the usually infrequent advanced stages of the blood cancer are:

• Chemotherapy: a number of regimens may be available.
• Bone marrow transplant: after intensive chemotherapy, healthy donor bone marrow cells are used to replace cells in the bone marrow of the patient.