for
chemotherapy Treatment aims to induce a lasting
remission, defined as the absence of detectable cancer cells in the body (usually less than 5% blast cells in the bone marrow) or the absence of
minimal residual disease. Over the past several decades, there have been strides to increase the efficacy of treatment regimens, resulting in increased survival rates. Possible treatments for acute leukemia include
chemotherapy,
steroids,
radiation therapy, intensive combined treatments (including
bone marrow or
stem cell transplants), targeted therapy, and/or growth factors.
Chemotherapy Chemotherapy is the initial treatment of choice, and most people with ALL receive a combination of medications. There are no surgical options because of the body-wide distribution of the
malignant cells. In general, cytotoxic chemotherapy for ALL combines multiple antileukemic drugs tailored to each person. Chemotherapy for ALL consists of three phases: remission induction, intensification, and maintenance therapy. Adult chemotherapy regimens mimic those of childhood ALL; however, they are linked with a higher risk of disease relapse with chemotherapy alone. Two subtypes of ALL (B-cell ALL and T-cell ALL) require special considerations when it comes to selecting an appropriate treatment regimen in adults with ALL. B-cell ALL is often associated with cytogenetic abnormalities (specifically, t(8;14), t (2;8), and t(8;22)), which require aggressive therapy consisting of brief, high-intensity regimens. T-cell ALL responds the most to cyclophosphamide-containing agents. Recent updates on the treatment of adult acute lymphoblastic leukemia (ALL) include advancements in immunotherapy, particularly the use of monoclonal antibodies like blinatumomab and inotuzumab ozogamicin, which target specific cancer cells and are used alongside stem cell transplantation. Additionally, tyrosine kinase inhibitors (TKIs) such as imatinib and dasatinib are incorporated for Philadelphia chromosome-positive ALL, improving treatment outcomes.
Radiation therapy Radiation therapy (or radiotherapy) is used on painful bony areas, in high disease burdens, or as part of the preparations for a
bone marrow transplant (total body irradiation). In the past, physicians commonly utilized radiation in the form of whole-brain radiation for central nervous system prophylaxis, to prevent the occurrence and/or recurrence of leukemia in the brain. Recent studies showed that CNS chemotherapy provided results as favorable, but with fewer developmental side effects. As a result, the use of whole-brain radiation has been more limited. Most specialists in adult leukemia have abandoned the use of radiation therapy for CNS prophylaxis, instead using intrathecal chemotherapy.
Tyrosine-kinase inhibitors (TKIs), such as
imatinib, are often incorporated into the treatment plan for people with
Bcr-Abl1+ (Ph+) ALL. However, this subtype of ALL is frequently resistant to the combination of chemotherapy and TKIs, and allogeneic stem cell transplantation is often recommended upon relapse. it is also a promising standalone therapy in children.
Immunotherapy Chimeric antigen receptors (CARs) have been developed as a promising
immunotherapy for ALL. This technology uses a
single chain variable fragment (scFv) designed to recognize the cell-surface marker
CD19 as a method of treating ALL. CD19 is a molecule on all B-cells and can be used to distinguish the potentially malignant B-cell population. In this therapy, mice are immunized with the CD19 antigen and produce anti-CD19 antibodies.
Hybridomas developed from mouse spleen cells fused to a myeloma cell line can be developed as a source for the cDNA encoding the CD19-specific antibody. The cDNA is sequenced and the sequence encoding the variable heavy and variable light chains of these antibodies are cloned together using a small
peptide linker. This resulting sequence encodes the scFv. This can be cloned into a
transgene, encoding the precursor to the CAR endodomain. Varying arrangements of subunits serve as the endodomain. They generally consist of the hinge region that attaches to the scFv, a transmembrane region, the intracellular region of a costimulatory molecule such as
CD28, and the intracellular domain of
CD3-zeta containing
ITAM repeats. Other sequences frequently included are:
4-1bb and
OX40. The final transgene sequence, containing the scFv and endodomain sequences is then inserted into immune effector cells that are obtained from the person and expanded
in vitro. In trials these have been a type of
T-cell capable of
cytotoxicity. Inserting the DNA into the effector cell can be accomplished by several methods. Most commonly, this is done using a
lentivirus that encodes the transgene. Pseudotyped, self-inactivating lentiviruses are an effective method for the stable insertion of a desired transgene into the target cell. Other methods include
electroporation and
transfection, but these are limited in their efficacy as transgene expression diminishes over time. The gene-modified effector cells are then transplanted back into the person. Typically, this process is done in conjunction with a conditioning regimen such as
cyclophosphamide, which has been shown to potentiate the effects of infused T-cells. This effect has been attributed to making an immunologic space within which the cells populate. In a 22-day process, the "drug" is customized for each person. T cells purified from each person are modified by a virus that inserts genes that encode a chimaeric antigen receptor into their DNA, one that recognizes leukemia cells.
Obecabtagene autoleucel (Aucatzyl) was approved for medical use in the United States in November 2024.
Relapsed ALL Typically, people who experience a relapse in their ALL after initial treatment have a poorer prognosis than those who remain in complete remission after induction therapy. It is unlikely that recurrent leukemia will respond favorably to the standard chemotherapy regimen that was initially implemented. Instead, these people should be trialed on reinduction chemotherapy followed by
allogeneic bone marrow transplantation. These people in relapse may also receive
blinatumomab, as it has been shown to increase remission rates and overall survival rates, without increased toxic effects. Low-dose
palliative radiation may also help reduce the burden of tumors inside or outside the central nervous system and alleviate some symptoms. There has also been evidence and approval of use for
dasatinib, a
tyrosine kinase inhibitor. It has shown efficacy in cases of people with Ph1-positive and
imatinib-resistant ALL, but more research needs to be done on long-term survival and time to relapse. Moreover, patients undergoing a stem cell transplantation can develop a
graft-versus-host disease (GvHD). It was evaluated whether mesenchymal stromal cells can be used to prevent GvHD. The evidence is very uncertain about the therapeutic effect of mesenchymal stromal cells in treating graft-versus-host disease after stem cell transplantation on all-cause mortality and the complete disappearance of chronic acute graft-versus-host disease. Mesenchymal stromal cells may result in little to no difference in the all-cause mortality, relapse of malignant disease, and incidence of acute and chronic graft-versus-host diseases if they are used for prophylactic reasons.
Supportive therapy Adding physical exercises to the standard treatment for adult patients with haematological malignancies like ALL may result in little to no difference in mortality, quality of life, and physical functioning. These exercises may result in a slight reduction in depression. Furthermore, aerobic physical exercises probably reduce fatigue. The evidence is very uncertain about the effect on anxiety and serious adverse events.
Cell therapy Brexucabtagene autoleucel (Tecartus) was approved by the FDA in October 2021 for the treatment of adults with relapsed or refractory B-cell precursor ALL, and later by the EMA in December 2021. Each dose of brexucabtagene autoleucel is a customized treatment created using the recipient's immune system to help fight the leukemia. The recipient's
T cells, a type of white blood cell, are collected and genetically modified to include a new gene that facilitates the targeting and killing of the lymphoma cells. These modified T cells are then infused back into the recipient. == Prognosis ==