Acute Myelogenous Leukemia – Causes, Symptoms, Treatment

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Acute Myelogenous Leukemia /Acute myelocytic leukemia (AML) is a disorder of uncontrolled proliferation of undifferentiated myeloid precursor cells. This leads to the accumulation of immature myeloid cells, myeloblasts, in the bone marrow, and usually their presence in the peripheral blood. Acute leukemias are differentiated from chronic leukemias by the predominance of the neoplastic, clonal blast as well as by the pace with which untreated disease leads to hematopoietic failure and death within weeks to months.

Acute Myeloid Leukemia (AML) is a group of hematological diseases, phenotypic and genetically heterogeneous, characterized by abnormal accumulation of blast cells in the bone marrows and peripheral blood.

Acute myeloid leukemia/ (AML)Acute myelogenous leukemia is the most common leukemia among the adult population and accounts for about 80% of all cases. It is characterized by clonal expansion of immature “blast cells” in the peripheral blood and bone marrow resulting in ineffective erythropoiesis and bone marrow failure.

Acute myeloid leukemia (AML) is a blood and bone marrow cancer in which the bone marrow makes immature white blood cells called myeloblasts or “blasts.” This kind of cancer is called “acute” rather than “chronic” because it tends to be a fast-growing type of leukemia.

Another name

You may hear other names for acute myeloid leukemia, including:

  • Acute myelocytic leukemia
  • Acute myelogenous leukemia
  • Acute granulocytic leukemia
  • Acute non-lymphocytic leukemia

Types of Acute Myelocytic Leukemia

Classification systems of the FAB and WHO Acute Myeloid Leukemia/Acute myelogenous leukemia

A. Classification of Acute Myeloid Leukemia (FAB)

M0. Acute myeloid leukemia without differentiation
M1. Acute myeloid leukemia with minimal differentiation
M2. Acute myeloid leukemia with differentiation
M3. Acute promyelocytic leukemia hipergranular or typical
M3v. Acute promyelocytic leukemia hipogranular
M4. Acute myelomonocytic leukemia
M4v. Acute myelomonocytic leukemia with bone marrow eosinophilia
M5. Acute monocytic leukemia
M6. Acute erythroid leukemia (Erythroleukemia)
M7. Acute Megacariocytic leukemia
B. Classification of Acute Myeloid Leukemia (OMS, 2008)
AML with recurrent genetic abnormalities
Acute myeloid leukemia with t(8;21)(q22;q22); RUNX1-RUNX1T1
Acute myeloid leukemia with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
Acute promyelocytic leukemia with t(15;17)(q22;q12); PML-RARA
Acute myeloid leukemia with t(9;11)(p22;q23); MLLT3-MLL
Acute myeloid leukemia with t(6;9)(p23;q34); DEK-NUP214
Acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1
Acute myeloid leukemia (megakaryoblastic) with t(1;22)(p13;q13); RBM15-MKL1
Acute myeloid leukemia with mutated NPM1
Acute myeloid leukemia with mutated CEBPA
Acute myeloid leukemia (AML) with myelodysplasia-related changes
Therapy-related myeloid neoplasms
Acute myeloid leukemia, NOS
Acute myeloid leukemia with minimal differentiation
Acute myeloid leukemia without maturation
Acute myeloid leukemia with maturation
Acute myelomonocytic leukemia
Acute monoblastic and monocytic leukemia
Acute erythroid leukemia
Acute megakaryoblastic leukemia
Acute basophilic leukemia
Acute panmyelosis with myelofibrosis

Causes of Acute Myelocytic Leukemia

Acute myelogenous leukemias depending upon the etiology, genetics, immune-phenotype, and morphology, there are different classification systems for AML.

  • The most common risk factor for AML is a myelodysplastic syndrome. Other hematological disorders that increase the risk of AML include myelofibrosis and aplastic anemia.
  • Several congenital disorders like Down syndrome and Bloom syndrome also increase the risk of AML, which tends to present in the early 20s.
  • Environmental exposures like radiation, tobacco smoke, and benzene are also risk factors for AML Finally, previous exposure to chemotherapeutic agents is also a risk factor for AML.
  • Exposure to ionizing radiation is associated with an increased risk of multiple subtypes of leukemia.
  • Exposure to benzene is a risk factor for leukemia in adults, particularly AML.
  • Previous exposure to chemotherapy, especially alkylating agents and topoisomerase inhibitors, increases the risk for acute leukemia later in life.
  • A history of any hematologic malignancy is a risk factor for subsequently developing another subtype of leukemia.
  • Viral infections (e.g., human T-cell leukemia virus, Epstein Barr virus) are linked with subtypes of ALL.
  • Several genetic syndromes (e.g., Down syndrome, Fanconi anemia, Bloom syndrome, Li-Fraumeni syndrome) are associated with an increased risk of AML and ALL.
Factors that may increase your risk of acute myelogenous leukemia/Acute myelogenous leukemia include
  • Increasing age – The risk of acute myelogenous leukemia increases with age. Acute myelogenous leukemia is most common in adults age 65 and older.
  • Your sex – Men are more likely to develop acute myelogenous leukemia than are women.
  • Previous cancer treatment – People who’ve had certain types of chemotherapy and radiation therapy may have a greater risk of developing AML.
  • Exposure to radiation – People exposed to very high levels of radiation, such as survivors of a nuclear reactor accident, have an increased risk of developing AML.
  • Dangerous chemical exposure – Exposure to certain chemicals, such as benzene, is linked to a greater risk of AML.
  • Smoking – AML is linked to cigarette smoke, which contains benzene and other known cancer-causing chemicals.
  • Other blood disorders – People who’ve had another blood disorder, such as myelodysplasia, myelofibrosis, polycythemia vera, or thrombocythemia, are at greater risk of developing AML.
  • Genetic disorders – Certain genetic disorders, such as Down syndrome, are associated with an increased risk of AML.

Symptoms of Acute Myelogenous Leukemia

Acute myeloid leukemia/Acute myelogenous leukemia often begins with flu-like symptoms. You might have:

  • anemia due to a lack of red cells, causing persistent tiredness, dizziness, paleness, or shortness of breath when physically active
  • frequent or repeated infections and slow healing due to a lack of normal white cells, especially neutrophils
  • increased or unexplained bleeding or bruising, due to a very low platelet count
  • bone pain, swollen lymph nodes (glands), swollen gums, chest pain, and abdominal discomfort due to a swollen spleen or liver.
  • Fatigue
  • Fever
  • Weight loss or loss of appetite
  • Headaches
  • Unusual bleeding or bruising
  • Tiny red spots on your skin (petechiae)
  • Swollen gums
  • Swollen liver or spleen
  • More infections than usual
If you have fewer healthy white blood cells than normal, you may get more infections than usual. These infections may take a long time to get better. Enlargement of the spleen may occur in AML, but it is typically mild and asymptomatic. Lymph node swelling is rare in AML, in contrast to acute lymphoblastic leukemia. The skin is involved about 10% of the time in the form of leukemia cutis. Rarely, Sweet’s syndrome, a paraneoplastic inflammation of the skin, can occur with AML.[rx]
Infections can cause symptoms like these:

  • Fever
  • Weakness
  • Achy muscles
  • Fatigue
  • Diarrhea

If you have fewer platelets than usual, your blood may not clot as well as it should. You might have symptoms like these

  • Easy bruising
  • Bleeding that can be hard to stop
  • Bleeding gums
  • Small red spots under your skin caused by bleeding
  • Nosebleeds
  • Sores that don’t heal
Symptoms When AML Spreads

Leukemia cells can spread to other parts of your body and cause symptoms like these

  • Balance problems
  • Blurred vision
  • Bone or joint pain
  • Numbness in your face
  • Seizures
  • Spots or a rash on your skin
  • Swelling in your belly
  • Swollen, bleeding gums
  • Swollen glands in your neck, groin, underarms, or above your collarbone
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Diagnosis of Acute Myelogenous Leukemia

Your doctor will ask about your medical history for Acute myelocytic leukemia/Acute myelogenous leukemia. They’ll do a physical exam to look for signs of bleeding, bruising, or infection. You might have tests including:

CBC tests – A complete blood count (CBC) shows how many of each type of blood cell you have. A peripheral blood smear checks for blast cells. Specific types include tests for

  • RBC – the numbers, size, and types of RBC in the blood
  • WBC – the numbers and types of WBC in the blood
  • Platelets – the numbers and size of the platelets
  • Hemoglobin – an iron-rich protein in red blood cells that carries oxygen
  • Hematocrit – how much space red blood cells take up in your blood
  • Reticulocyte count – how many young red blood cells are in your blood
  • Mean corpuscular volume (MCV) – the average size of your red blood cells

The complete blood count (CBC) includes most or all of these. CBC is one of the most common blood tests.

  • Blood tests – Most people with acute myelogenous leukemia have too many white blood cells, not enough red blood cells, and not enough platelets. The presence of blast cells — immature cells normally found in bone marrow but not circulating in the blood — is another indicator of acute myelogenous leukemia.
  • Imaging tests – X-rays, CT scans, MRIs, and ultrasounds give a clearer picture of what’s going on inside you. They can help find infections or show when cancer has spread to other parts of your body.
  • Bone marrow tests – Your doctor uses a needle to take a sample of marrow, blood, and bone from your hip or breastbone. A specialist looks at it under a microscope for signs of leukemia.
  • Spinal tap – This is also called a lumbar puncture. Your doctor uses a needle to take some cerebrospinal fluid from around your spinal cord. A specialist checks it for leukemia cells.
  • Genetic tests – A laboratory can look at your leukemia cells for gene or chromosome changes. The results will tell your doctor more about your AML so they can help you decide on the best treatment.

Treatment of Acute Myelogenous Leukemia

The first-line treatment of AML/Acute myelogenous leukemia consists primarily of chemotherapy and is divided into two phases: induction and postremission (or consolidation) therapy. The goal of induction therapy is to achieve a complete remission by reducing the number of leukemic cells to an undetectable level; the goal of consolidation therapy is to eliminate any residual undetectable disease and achieve a cure.[rx] Hematopoietic stem cell transplantation is usually considered if induction chemotherapy fails or after a person relapses, although transplantation is also sometimes used as front-line therapy for people with high-risk disease. Efforts to use tyrosine kinase inhibitors in AML continue.[rx]

  • Remission induction therapy – The purpose of the first phase of treatment is to kill the leukemia cells in your blood and bone marrow. However, remission induction usually doesn’t wipe out all of the leukemia cells, so you need further treatment to prevent the disease from returning.
  • Consolidation therapy – Also called post-remission therapy, maintenance therapy, or intensification, this phase of treatment is aimed at destroying the remaining leukemia cells. It’s considered crucial to decreasing the risk of relapse.
  • Chemotherapy – Certain drugs can kill cancer cells or keep them from dividing. You might take these medicines by mouth, through an IV, or through a shot into another part of your body.
  • Radiation – High-energy X-rays can also stop cancer cells. Your doctor might use a large machine to send radiation toward cancer. Or they may insert a radioactive needle, seed, or wire into your body, on or near cancer.
  • Stem cell transplant – Because AML treatment can also kill healthy cells, you might get stem cells that can grow into blood cells. They might come from you or from another person.
  • Targeted therapy – This uses drugs to attack specific genes and proteins involved with the growth and spread of cancer cells.
  • Bone marrow transplant – A bone marrow transplant, also called a stem cell transplant, may be used for consolidation therapy. A bone marrow transplant helps re-establish healthy stem cells by replacing unhealthy bone marrow with leukemia-free stem cells that will regenerate healthy bone marrow. Prior to a bone marrow transplant, you receive very high doses of chemotherapy or radiation therapy to destroy your leukemia-producing bone marrow. Then you receive infusions of stem cells from a compatible donor (allogeneic transplant).

Treatment in a broad spectrum

FLT3-ITD inhibitors

Inhibition of tyrosine kinase (TK) receptors has been used successfully in various solid and hematological malignancies, including Philadelphia-chromosome positive leukemias. Given the prognostic impact and the high rate of FLT3 mutations, inhibition of this TK has long been recognized as a potential therapeutic target in AML. Tested agents include the first-generation inhibitors sorafenib and midostaurin, as well as newer second-generation agents such as quizartinib and crenolanib.

Flavopiridol

Flavopiridol (alvocidib) is a serine-threonine kinase inhibitor that inhibits cell cycle progression by targeting multiple cyclin-dependent kinases, inducing checkpoint arrest and interrupting transcriptional activity.[] This drug has been used in a group of relapsed/refractory or de novo AML patients with a combination regimen named FLAM (flavopiridol, high doses of cytarabine and mitoxantrone), with promising outcomes and low toxicity.[–]

Sorafenib

Sorafenib is a tyrosine kinase inhibitors (TKI) of RAF kinase, c-KIT, VGFR, PGFR, and FLT3-ITD, which was first used for the treatment of hepatocellular and renal cell carcinoma. As early as 2008, phase I trials of sorafenib administered as a single agent n patient with FLT3-ITD-positive relapsed or refractory (r/r) AML demonstrated significant reductions in the number of leukemic cells both in the peripheral blood and bone marrow, achieving CR in several patients., , ,  In a phase II trial of 13 patients with r/r FLT3-ITD-positive AML, single-agent sorafenib at doses of 200–400 mg twice daily established CR (including CR with insufficient hematologic recovery) in over 90% of cases.

Midostaurin

Midostaurin is another first-generation FLT3 TKI with significant but transient single-agent activity in patients with AML., As with sorafenib, its effects are limited by the rapid emergence of resistance. Combinations of midostaurin and existing chemotherapy regimens are currently under investigation: results of phase I and combined phase I/II trial of midostaurin and azacitidine have recently been published, demonstrating the tolerability and efficacy of this combination in patients with AML.

Tipifarnib

Tipifarnib is a methyl-quinolinone derivative that acts as a potent and selective nonpeptide-mimetic farnesyltransferase inhibitor (FTI) both in vitro and in vivo in hematological diseases.[] In phase I–II studies, it was demonstrated that tipifarnib (the most extensively investigated FTI) had antileukemic activity.[–] The rates of CR, partial response, and/or CR with incomplete platelet recovery (CRP) in patients with refractory/poor-risk AML were 7–14%.[–] A phase III study comparing tipifarnib (as monotherapy) with best supportive care, including hydroxyurea in patients with untreated AML ≄70 years old showed no survival benefit in the tipifarnib arm.

Lestaurtinib and Midostaurin (Selective FLT3 Inhibitors)

Lestaurtinib (CEP701) and midostaurin (PKC412) are two small orally bioavailable molecule inhibitors of FLT3 that have shown encouraging activity, both preclinically and in relapsed AML.[,,] There is an ongoing phase III clinical trial.[] Knapper et al.[] studied the effects of both molecules on 65 AML blast samples. Both agents induced concentration-dependent cytotoxicity in most cases, although responses to midostaurin required higher drug concentrations. Importantly, lestaurtinib induced cytotoxicity in a synergistic fashion with cytarabine, particularly in FLT3-mutant samples. Both lestaurtinib and midostaurin caused inhibition of FLT3 phosphorylation in all samples.[]

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Quizartinib

Second-generation inhibitors such as quizartinib have been designed to specifically target the FLT3 kinase, in order to reduce toxicity from off-target effects. In addition to this increased selectivity, quizartinib also possesses a good bioavailability and a half-life of more than 24 h, which allows for a more continuous FLT3 inhibition. A phase I study of oral quizartinib in 76 patients with relapsed/refractory AML was able to achieve a hematological response in 30% of patients, and a CR in 13% regardless of FLT3 mutational status. Among patients with FLT3-ITD, the rate of hematologic response increased to 53%, with ~23% of patients achieving CR. Patients were able to tolerate doses of up to 200 mg/day, with grade 3 QT interval prolongation as the only DLT.

Crenolanib

Crenolanib besylate is an orally available second-generation FLT3 TKI, with activity against FLT3-ITD and FLT3-TKD mutants. Unlike other FLT3 TKIs, which are subject to the emergence of resistance-conferring kinase domain mutations (such as D835Y), crenolanib appears to possess extensive ‘pan-kinase’ inhibition of secondary TKD mutations. Using concentrations far below the clinically achievable plasma levels, Smith et al. were unable to identify any single TKD mutation able to confer resistance to crenolanib. In a phase II study of 38 patients with FLT3-mutated AML (including relapsed and refractory patients), crenolanib administered at doses of 200 mg/m2 per day three times a day in 28 days cycle achieved a median EFS and OS of 8 and 19 weeks, respectively. Crenolanib is currently being studied in multiple clinical trials in AML patients, both with and without FLT3-mutated AMLs.

Lintuzumab (HuM195)

HuM195 is a recombinant humanized IgG1 monoclonal antibody anti-CD33 and is capable of mediating antibody-dependent cellular cytotoxicity.[] It has also been combined with interleukin-2 based on its ability to enhance the activation of natural killer cells and its cytotoxic activity against leukemic cells.[] HuM195 has been labeled to 111Indium and named lintuzumab. Feldman et al.[] evaluated the efficacy of lintuzumab in phase III randomized trials. They compared lintuzumab (12 mg/m2) ± mitoxantrone, etoposide and cytarabine (high doses) in 199 relapsed/refractory AML patients. Their outcome showed no difference in CR rates or OS.[]

Gemtuzumab Ozogamicin

Gemtuzumab ozogamicin was the first monoclonal antibody approved for the treatment of relapsed or refractory CD33+ AML in older patients. With gemtuzumab ozogamicin monotherapy, the overall response was 14% in relapsed/refractory AML patients.[] The gemtuzumab ozogamicin or GO ‘fever’ subsided when some groups reported on ‘sinusoidal obstructive syndrome’ (SOS) or venous-occlusive disease characterized by hyper-bilirubinaemia, painful hepatomegaly, ascites and sudden weight gain developing at a median of 10 days following gemtuzumab ozogamicin administration for patients who did not undergo an allogeneic SCT, and 13 days following a transplant for patients who had previously received gemtuzumab ozogamicin.[–]

STAT inhibitors

STAT3 tyrosine phosphorylation is upregulated in up to 50% of AML cases and confers a worse prognosis. Activation of the STAT3 signaling pathway is also stimulated by the FLT3 receptor ligand,, and may represent a key step in the development of FLT3 TKI resistance. Several small molecules of STAT3 inhibitors have been developed and are currently being investigated for the treatment of AML. showed decreased STAT3 phosphorylation and induction of apoptosis in AML cell lines treated with the STAT3 inhibitor C188-9.

IDH1/IDH2 small molecule inhibitors

The gain of function mutations in IDH-1 and IDH-2 enzymes are found in approximately 20% of cases. Recent attempts have been made to target these mutant enzymes as a potential treatment for AML. In 2013, Wang et al. published the results of AGI-6780, a small molecule inhibitor of the R140Q mutant IDH-2 enzyme. In an ex vivo model of primary human AML cells, treatment with AGI-6780 was able to overcome the differentiation block of leukemic cells. Recently, the IDH-2 inhibitor AG-221 was found to confer a dose-dependent survival benefit in a primary human IDH-2 mutant AML xenograft model. At a cellular level, AG-221 treatment was associated with an initial phase of CD45+ blast cell proliferation, followed by cellular differentiation. A phase I trial of AG-221 in IDH-2 mutant leukemia is currently underway. IDH-1 mutant enzymes are also the targets of new therapeutic inhibitors: Preliminary results of phase I trial of the small molecule inhibitor AG-120 demonstrated hematological response in 7 out of 14 IDH-1 positive patients, including 4 CR.

Clofarabine

Clofarabine is a second-generation purine nucleoside analog approved for the treatment of relapsed or refractory pediatric acute lymphocytic leukemia. In AML, it has shown activity and tolerability as a single-agent, administered intravenously at doses of 20–30 mg/m2 for 5 days, with overall response rates of ~40%., In a 2008 randomized study of 70 patients aged 60 years and older, it was reported a CR rate of 63% using the combination of clofarabine with low-dose cytarabine, compared with 31% with clofarabine alone. In a study of 320 patients over the age of 55 with relapsed/refractory AML, the combination of clofarabine and cytarabine achieved significantly higher rates of CR, CR with incomplete platelet count, and DFS when compared with cytarabine alone. Although neither of these studies was able to show an improved OS, these results suggest a synergistic action between clofarabine and cytarabine, and have spurred interest in the combination of these two agents. Recently a study was published showing the results of a phase 2 trial of clofarabine and low-dose cytarabine in older patients with newly diagnosed AML.

Monoclonal antibodies

Monoclonal antibodies exert their anti-tumor activity through direct antibody-dependent cytotoxicity or through the conjugation of cytotoxic agents, which allows for the targeted delivery of potent chemotherapy to neoplastic cells. Gemtuzumab ozogamicin (GO) is a humanized recombinant antibody directed at CD33, a transmembrane protein expressed on cells of myeloid lineage. The antibody is conjugated to the DNA-cleaving cytotoxic agent calicheamicin and is internalized by CD33-positive cells. GO received FDA approval in 2000 for the treatment of CD33-positive AML in patients 60 years or older at first relapse.

Conventional therapy

Conventional therapy is ‘traditionally’ based on an anthracycline plus cytarabine. Since 1980, daunorubicin administered in doses of 45 mg/m2 for 3 days plus cytarabine 100–200 mg/m2 by continuous infusion for 7 days is considered the ‘most common’ induction regimen (so called ‘7+3’). This regimen achieves CR in 56–76% of younger patients (<60 years old) and 38–45% of older patients (>60 years old).[,] In attempts to achieve a better outcome, other anthracyclines have been used; however, there is no consensus about which type of anthracycline is most effective.[–]

CART therapy

Chimeric antigen receptors are synthetic T-cell receptors with antibody-like specificity. They combine a single-chain variable fragment from a monoclonal antibody with the transmembrane and intracellular domains of a T-cell receptor. This allows for the creation of a host-derived population of chimeric antigen receptor-T (CART) cells, which can be directed at a pre-determined antigen. CD19-directed CART cell therapy has shown exciting efficacy in the treatment of acute lymphoblastic leukemia and B-cell lymphoma. Although this treatment does not distinguish between malignant and healthy CD19 cells, patients tolerate the depletion of CD19 lymphocytes with relatively little morbidity. In contrast to this, depletion of the normal cells of myeloid lineage is associated with unacceptable neutropenia, and attempts to apply CART cell therapy to the treatment of AML have had to focus on identifying an appropriate antigen to target malignant cells while sparing non-malignant myeloid cells.

Isocitrate Dehydrogenase (IDH) Inhibitors

The IDH1 inhibitor AG-120 and the IDH2 inhibitor AG-221 have demonstrated promising response rates in patients with AML in two separate phases I clinical trials [,]. Preliminary results were recently presented for both trials. The objective response rate (ORR) with AG-221 was 40% and 31% with AG-120 in relapsed/refractory AML patients. More interestingly the duration of the responses for AG-221 and AG-120 were more than 15 and 11 months at the analysis and remained ongoing. Overall, 76% of the responses lasted longer than six months. Based on these data, the Food and Drug Administration (FDA) has granted the medication an orphan drug designation for patients with AML.

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Nuclear Exporter Inhibitors

The anti-leukemic efficacy of reversible inhibitors of the major nuclear export receptor, chromosome region maintenance 1 (CRM1, also termed XPO1) has brought much excitement. CRM1 is a major nuclear exporter protein that mediates the export and inactivation of several tumor suppressors such as p53, p73, FOXO1, RB1, and p21 (CDKN1A) among others []. CRM1 has been shown to be upregulated in a range of solid tumors and hematological malignancies, including AML [,]. Preclinical studies indicate that the treatment of AML cell lines, patient samples, and AML xenografts with novel CRM1 inhibitors (Selinexor) induces strong anti-leukemic effects [,]. Based on these studies, Phase I/II clinical trials are currently ongoing to assess the safety, tolerability, and activity of selinexor in AML patients.

Immune Therapies

Novel antibody therapies are revolutionary in the treatment of leukemia and currently under development in AML. Monoclonal antibodies being explored include CD33 (Gemtuzumab ozogamicin) [] and bispecific antibodies such as AMG 330 (anti-CD33 and CD3) []. Chimeric antigen receptor (CAR)-transduced T cells (CARTs) are T cells engineered to express a specific antigen receptor target designed against a specific cell-surface antigen. CD123 has been found to be expressed on the majority of AML blasts but also normal hematopoietic cells. Preclinical data shows that targeting CD123 via CARTs results in rejection of human AML and myeloablation in the mouse models [].

Induction Therapy

This is a standard of care for younger patients, the elderly with low risk of treatment-related mortality (TRM), and ones with favorable and intermediate-risk factors. The induction therapy is highly toxic to bone marrow causing pancytopenias and bleeding complications, gastrointestinal system issues, kidney failure due to tumor lysis syndrome, and electrolyte disturbances. It may take up to 1 month for the cell counts to recover, and these patients need aggressive monitoring to manage any complications.

Consolidation Therapy

After achieving CR with induction therapy, consolidation therapy is initiated with high dose cytarabine, called HiDAC, and hematopoietic cell transplantation (HCT). HCT is preferred in individuals with less than 60 years of age with intermediate or unfavorable prognosis. If a donor is available, then allogeneic HCT is preferred over autologous HCT. They should be monitored for signs or symptoms of acute or chronic graft versus host disease (GVHD).

Novel Targets

Ongoing studies with Fms-like tyrosine kinase 3 (FLT3) inhibitors, IDH inhibitors, and immune therapies. All blood products must be irradiated to prevent transfusion-related graft versus host disease, which is usually fatal. IV antibiotics are given to febrile patients and prophylactic antifungal therapy is recommended.

Complications of Acute Myelogenous Leukemia

If you have acute myeloid leukemia (AML)/Acute myelogenous leukemia, you may experience complications. These can be caused by the condition itself, although they can also occur as a side effect of treatment.

  • Tumor lysis syndrome (TLS) – TLS is a complication of chemotherapy that can result when tumor cells die quickly. The widespread cellular destruction releases intracellular contents into the bloodstream overwhelming the kidneys, resulting in dangerously high serum levels of potassium, phosphorus, uric acid, and blood urea nitrogen.
  • Disseminated intravascular coagulation (DIC) – DIC is a complication of leukemia itself in which the proteins that control blood clotting become overactive, leading to both thrombosis and hemorrhage. DIC is often associated with acute promyelocytic leukemia but can be seen in other subtypes of leukemia as well.
  • Infection – Immunosuppression from chemotherapy, stem cell transplantation, or leukemia itself increases the risk of dangerous infections. Fever with neutropenia in an immunosuppressed patient should prompt an immediate evaluation for infection source and the initiation of broad-spectrum antibiotic therapy.
  • Cancer – Survivors of leukemia are at an increased risk of subsequent cancers. For example, the Childhood Cancer Survivor Study demonstrated that the 30-year cumulative incidence of any cancer after leukemia was 5.6%; the median time to occurrence of the subsequent cancer was nine years. The most common second neoplasms in childhood leukemia survivors are different subtypes of leukemia or lymphoma.

Weakened immune system

Having a weakened immune system is a common complication of AML.

Even if your blood is restored to normal working order with treatment, many of the medications that are used to treat AML can temporarily weaken your immune system.

This means you’re more vulnerable to developing an infection, and any infection you develop could be more serious than usual.

Complications arising from infection are very common in people with AML. But if treated early, nearly all infections respond to appropriate treatment.

You may be advised to:

  • take regular doses of antibiotics to prevent bacterial infections
  • maintain good personal and dental hygiene
  • avoid contact with anyone who’s known to have an infection – even if it’s a type of infection that you were previously immune to, such as chickenpox or measles
  • check with your GP to make sure your vaccinations are up-to-date – you will not be able to have any vaccine that contains “live” viruses or bacteria, such as the shingles vaccine and MMR vaccine (against measles, mumps and rubella)

Report any possible symptoms of an infection to your treatment unit immediately as prompt treatment may be needed to prevent complications.

Symptoms of an infection can include:

  • a sore throat
  • a very high temperature, and feeling hot or shivery
  • flu-like symptoms, such as headaches, aching muscles and tiredness
  • breathlessness
  • pain when peeing

Bleeding

If you have AML, you might bleed and bruise more easily because of the low levels of platelets (clot-forming cells) in your blood. Bleeding may also be excessive.

People with advanced AML are more vulnerable to excessive bleeding inside their bodies.

Serious bleeding can occur:

  • inside the skull (intracranial hemorrhage) – causing symptoms such as a severe headache, stiff neck, vomiting, and confusion
  • inside the lungs (pulmonary hemorrhage) – causing symptoms such as coughing up blood, breathing difficulties, and a bluish skin tone (cyanosis)
  • inside the stomach (gastrointestinal hemorrhage) – causing symptoms such as vomiting blood and passing poos that are very dark or tar-like in color

All these types of hemorrhage should be regarded as medical emergencies.

Infertility

Many of the treatments that are used to treat AML can cause infertility. This is often temporary, but in some cases can be permanent.

People, particularly at risk of permanent infertility, are those who have received high doses of chemotherapy and radiotherapy in preparation for bone marrow or stem cell transplant. Your treatment team can talk to you about the risk of infertility in your specific circumstances. It may be possible to do things to help keep your fertility before you begin your treatment.

For example, men can have their sperm samples stored. Women can have eggs or fertilized embryos stored, which can then be placed back into their womb following treatment.

References

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