Acute leukemia tends to become severe quickly and therefore needs to be treated as soon as possible. If left untreated, the disease is fatal.
The therapeutic goal is to achieve regression of leukemic cells (remission) and normalization of blood values. Achieving these conditions is not always possible.
The therapy lasts several months and requires hospitalization of the patient, as well as intensive hygiene measures to reduce the possibility of infections arising.
Acute myeloid leukemia (AML)
The therapy of acute myeloid leukemia is mainly based on the use of chemotherapy cytotoxic at high doses and, if conditions permit, on stem cell or bone marrow transplant. The goal of treatment is to eradicate the disease (complete remission), after the patient has overcome the period of aplasia (marrow failure), allowing healthy stem cells to repopulate the marrow.
The therapy can be summarized with the following protocol:
- First phase ofinduction of remission: is based on the use of two drugs, the cytosine arabinoside (ARA-C, antiblastic) and the daunomycin (intercalating agent), with the aim of rapidly destroying resistant leukemia cells and preventing early relapses.
- Subsequent post-remission therapy: once complete remission is achieved, the patient is subjected to treatment Consolidation and of maintenance. They can also be used for some forms of AML growth factors to increase the formation of blood cells.
In promyelocytic leukemia, a subgroup of AML, therapy with all-trans-retinoic acid (ATRA, acid derivatives of vitamin A) combined with chemotherapy.
Results of AML therapy and survival
in general, complete remission can be achieved in approximately 70% of AML patients. Better response rates to therapy (up to 85%) are achieved in patients under 60 years of age and without a history of myelodysplasia.
Chemotherapy treatment failures for acute myeloid leukemia are attributed mainly to two factors: resistant leukemia and death from infection or hemorrhage. These consequences are more controllable than in the past, following the improvement of transfusion support therapy and antibacterial and antifungal treatment. The mortality rate is closely related to age, with a 5-year survival of approximately 50% of children and approximately 20% of adults under the age of 60.
Acute lymphocytic leukemia (ALL)
For patients, therapies modeled on prognostic criteria identified based on immunological and cytogenetic characterization are proposed. Generally speaking, as regards the specific control of leukemic proliferation, patients are treated according to different phases.
First phase of ALL treatment
- Induction therapy: cortisone therapy is carried out, followed by intensive chemotherapy with cytostatics (combination of a triad of drugs that includes vincristine, prednisone and anthracyclines, commonly associated with L-asparaginase).
- Consolidation/intensification therapy: the aim is to exercise minimal residual disease control and prevent relapses with ARA-C and methotrexate. Induction and consolidation therapy lasts for several months, during which the patient is hospitalized. Often, to prevent and treat meningeal localizations of leukemic cells, local chemotherapy or irradiation of the skull and/or affected lymph nodes is also necessary. In forms of ALL positive for the Philadelphia chromosome, patients can also be treated with inhibitors of tyrosine kinase activity (example: Imatinib, Dasatinib…).
Second phase of ALL treatment
- Maintenance therapy: a conventional treatment with cytostatics, 6-mercaptopurine (6-MP) and methotrexate is undertaken, which lasts approximately a year and a half and which in the majority of cases can be performed on an outpatient basis. In other cases, high-dose chemotherapy or total body irradiation followed by stem cell or bone marrow transplant is considered.
- Marrow transplant: the procedure is aimed above all for the treatment of patients at risk, in first complete remission. Patients with low-risk ALL can use this therapy in second remission. Generally, allogeneic marrow transplant is preferred, since the autologous form does not demonstrate significant differences compared to chemotherapy alone.
Results of ALL therapy and survival
In children it is possible to achieve complete remission in 90-95% of cases and, probably, a cure in about two thirds of these. In adults the results are relatively lower (70% complete remissions).
Generally, the treatment of chronic leukemia is less intensive and radical than the treatment of acute leukemia, but lasts longer. Most therapies can be administered on an outpatient basis (orally or intravenously).
It is not possible to completely prevent the disease from progressing, but treatment can help control the disease and significantly lengthen the chronic phase.
Cure of chronic leukemia is possible in rare cases and only if high-dose chemotherapy with subsequent stem cell or bone marrow transplant is used.
Chronic myelogenous leukemia (CML)
Treatment of chronic myelogenous leukemia must begin relatively early.
Depending on the situation and clinical picture, patients are treated, for several years, with:
- Tyrosine kinase inhibitors (example: Imatinib, Nilotinib or Dasatinib): they act specifically on leukemic cells. They inhibit the tyrosine kinase activity of the BCR/ABL fusion protein by blocking the ATP-binding site, resulting in proliferative arrest and induction of apoptosis in leukemic cells. The introduction of these drugs and the demonstration of their effectiveness have modified the therapeutic algorithm of patients, inducing complete and persistent cytogenetic and molecular responses over time (80-90% of cases).
- Interferon (IFN)in association or not with cytosine arabinoside: protocols involving the use of IFN allow, in some patients, a lengthening of the chronic phase and the induction of complete responses in 10-30% of cases, but it is not tolerated by 20% of patients and is ineffective in accelerated or blastic phase.
- Chemotherapy with cytostatics or traditional antiblastic drugs (example: busulfan): uses chemotherapeutic agents, such as hydroxyurea, 6-mercaptopurine and 6-thioguanine, specific for the cell cycle (or a particular phase thereof) to reduce the neoplastic mass quite quickly.
- High-dose chemotherapysimilar to that used for acute leukemia, proposed in an attempt to eradicate tumor cells.
- Stem cell (or bone marrow) transplant: it is undoubtedly the only therapeutic procedure capable of eradicating the Ph+ clone, but it is still burdened by high toxicity and therefore recommended only to patients with CML resistant to tyrosine kinase inhibitors and/or in an advanced stage of the disease.
Chronic lymphocytic leukemia (CLL)
Treatment of CLL must take into account the risk factors present at the time of diagnosis.
The aim of the therapy is in most cases containment and not eradication.
Chemotherapeutic therapeutic strategies include, among the most active molecules, gli alkylating agents which cyclophosphamide And chlorambucil. Alkylation therapy has proven effective in determining partial or complete remission of the disease in 45-86% of cases.
Another class of drugs is made up of purine analoguesincluding the fludarabine it has proven to be the most effective molecule, with a remission ranging from 70-80%, of which approximately 30% is complete. Fludarabine is myelo- and immunosuppressive and is considered the first-line drug in the treatment of patients under 65 years of age and in good general condition. If the patient is elderly or in poor general condition, the use of alkylating agents is considered, since these drugs cause fewer side effects.
In younger patients, especially when standard treatments do not promise a good prognosis, more aggressive therapeutic alternatives such as autologous transplant or allogeneic. Allogeneic transplantation appears to be potentially curative, especially if treatment occurs before patients have registered chemoresistance.
Finally, an important treatment modality consists of monoclonal antibodies directed against antigens expressed on the membrane of lymphocytes of chronic lymphocytic leukemia. These monoclonal antibodies act by inducing, after specific interaction with the antigen, complement-mediated cell lysis, antibody-dependent cytotoxicity and apoptosis.
Some examples are represented by the following monoclonal antibodies:
First-line therapy of CLL
- Initial stage: Patients should be monitored without any treatment until the initial signs of progression appear (enlargement of the lymph nodes or spleen, worsening of blood values, etc.). Early treatment has proven incapable of prolonging the survival of these leukemic subjects. If risk factors are present, pharmacological therapy involves the association of: fludarabine ± cyclophosphamide ± rituximab. In younger patients, under certain circumstances, a stem cell or bone marrow transplant may be considered following high-dose chemotherapy or total body irradiation.
- Intermediate stage: If they do not present significant clinical signs, patients should be observed for 4-6 months or longer. If signs of progression occur, an appropriate treatment should be chosen taking into account the patient’s age, status and life expectancy. For example, if the patient is age 65: chlorambucil/cyclophosphamide ± rituximab.
- Advanced stage: Must undergo aggressive chemotherapy treatment and, in selected cases, leukapheresis or whole body radiation therapy.
SECOND line therapy of CLL
There second line therapyintended for patients who present disease relapseis partly different and its success depends on factors such as the clinical stage, the negative prognosis, the number of previous treatments and the refractoriness of the last treatment.
Results of therapy
The prognosis of patients with CLL is very variable: survival varies from a few months to a few decades. Some leukemic subjects present an aggressive clinical course and an evolution that is difficult to control, while others remain asymptomatic and do not require any therapeutic intervention for several years.
Other articles on ‘Therapies for the various Types of Leukemia’
- Leukemia – Stem Cell Transplant and Bone Marrow Transplant
- Leukemia – Causes, Symptoms, Epidemiology
- Leukemia: Diagnosis
- Leukemia: Cure and Treatment
- Side Effects of Leukemia Treatments