Make your appointment or second opinion with Dana-Farber today to meet with an onsite specialist. Explore our Online Second Opinion service to get expert advice from Dana-Farber oncologists. Adult acute myeloid leukemia AML terminal a cancer of the blood and bone marrow. This type of cancer usually gets worse quickly if it is not treated. It is the most common type of acute leukemia in adults. AML is also called acute myelogenous leukemia, acute myeloblastic leukemia, acute granulocytic leukemia, and acute nonlymphocytic leukemia. Normally, the bone marrow makes blood stem cells immature cells that become mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell. A lymphoid stem cell becomes a white blood cell. In AML, the myeloid stem terminal usually become a type of immature white blood cell called myeloblasts or myeloid blasts. The myeloblasts in AML are abnormal and do not become healthy white blood cells. Sometimes in AML, too many stem cells become abnormal red blood cells or platelets. These abnormal white blood cells, red blood cells, or platelets are also called leukemia cells or blasts. Leukemia cells can build up in the bone marrow and blood so there is less room for healthy white blood cells, red blood cells, and platelets. When this happens, infection, anemia, or easy bleeding may occur. The leukemia cells can spread outside the blood to other parts of the body, including the central nervous system brain and spinal cordskin, and gums. This summary is about adult AML. See the following PDQ summaries for information about other types of leukemia:. Most AML subtypes are based on how mature developed the cancer cells are at the time of diagnosis and how different they are from normal cells. Acute promyelocytic leukemia APL is a subtype of AML that occurs when parts of two genes stick together. APL usually occurs in middle-aged adults. Signs of APL may include both bleeding and forming blood clots. Anything that increases your risk of getting a disease is called a risk factor. Talk with your doctor if you think you may be at risk. Possible risk factors for AML include the following:. The early signs and symptoms of AML may be like those caused by the flu or other common diseases. Check with your doctor if you have any of the following:. The prognosis chance of recovery and treatment options depend on:. The extent or spread of cancer is usually described as stages. In adult acute myeloid leukemia AMLthe subtype of AML and whether the leukemia has spread outside the blood and bone marrow are used instead of the stage to plan treatment. The following tests and procedures may be used to determine if the leukemia has spread:. The disease is described as untreated, in remission, or recurrent. In untreated adult AML, the disease is newly diagnosed. It has not been treated except to relieve signs and symptoms such as fever, bleeding, or pain, and the stage are true:. In adult AML in remission, the disease has been treated and the following are true:. RecurrentAML is cancer that has recurred come back after it has been treated. The AML may come back in the blood or bone marrow. Different types of treatment are available for patients with adult acute myeloid leukemia AML. Some treatments are standard the currently used treatmentand some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who terminal not started treatment. Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy stage taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body systemic chemotherapy. When chemotherapy is placed directly into the cerebrospinal fluid intrathecal chemotherapyan organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas regional chemotherapy. Intrathecal chemotherapy may be used to treat adult AML that has spread, or may spread to the brain and spinal cord. Combination chemotherapy is treatment using more than one anticancer drug. The way the chemotherapy is given depends on the subtype of the cancer being treated and whether it has spread to the brain and spinal aml. See Drugs Approved for Acute Myeloid Leukemia for more information. Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation terminal. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated. Stem cell transplant is a method of giving chemotherapy and replacing blood-forming cells that are abnormal or destroyed by the cancer treatment. Stem cells immature blood cells are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into and restore the body's blood cells. Stem cell transplant Step 1. Blood is taken from a vein in the arm of the donor. The patient or another person may be the donor. The blood flows through a machine that removes the stem cells. Then the blood is returned to the donor through a vein in the other arm. Stem cell transplant Step 2. The patient receives chemotherapy to kill blood-forming cells. The patient may aml radiation therapy not shown. Stem cell transplant Step 3. The patient receives stem cells through a catheter placed into a blood vessel in the chest. Arsenic trioxide and all-trans retinoic acid ATRA are anticancer drugs that kill leukemia cells, stop the leukemia cells from dividing, or help the leukemia cells mature into white blood cells. These drugs are used in the treatment of a subtype of AML called acute promyelocytic leukemia. This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site. Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Monoclonal antibody therapy is one type of targeted therapy being studied stage the treatment of adult AML. Monoclonal antibody therapy is a cancer treatment that uses antibodies made in the laboratory from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells. For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment. Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment. Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help stage research forward. Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring coming back or reduce the side effects of cancer treatment. Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials. Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging. Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred come back. These tests are sometimes called follow-up tests or check-ups. Standard treatment of untreated adult acute myeloid leukemia AML during the remission induction phase depends on the subtype of AML and may include the following:. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site. Standard treatment of adult AML during the remission phase depends on the subtype of AML and may include the following:. One of the treatments being studied in clinical trials for adult AML in remission is arsenic trioxide. There is no standard treatment for recurrent adult AML. Treatment depends on the subtype of AML and may include the following:. For more information from the National Cancer Institute about adult acute myeloid leukemia, see the following:. For general cancer information and other resources from the National Cancer Institute, see the following:. Estimated new cases and deaths from acute myeloid leukemia AML in the United States in Advances in the treatment of AML also called acute myelogenous leukemia, acute nonlymphocytic leukemia [ANLL] have resulted in substantially improved complete remission CR rates. Data suggest that once attained, duration of remission may be shorter in older patients. Increased morbidity and mortality during induction appear to be directly related to age. Cytogenetic analysis provides some of the strongest prognostic information available, predicting outcome of both remission induction and postremission therapy, as seen in a trial from the Southwest Oncology Group SWOG and the Eastern Cooperative Oncology Group ECOG E Normal cytogenetics portend average-risk Stage. Patients with AML that is characterized by deletions of the long arms or monosomies of chromosomes 5 or 7; by translocations or inversions of chromosome 3, t 6; 9t 9; 22 ; or by abnormalities of chromosome 11q23 have particularly poor prognoses with chemotherapy. These cytogenetic subgroups, as seen in the trial from the Medical Research Council MRC-LEUK-AML11predict clinical outcome in older patients with AML as well as in younger patients. RT—PCR does not appear to identify significant numbers of patients with good-risk fusion genes who have normal cytogenetics. The classification of AML has been revised by a group of pathologists and clinicians under the auspices of the World Health Organization WHO. Of 31 younger-thanyears, long-term, female survivors of AML or acute lymphoblastic leukemia, 26 resumed normal menstruation following completion terminal therapy. Among 36 live offspring of survivors, 2 congenital problems occurred. The differentiation of AML from acute lymphocytic leukemia has important therapeutic implications. Histochemical stains and cell surface antigen determinations aid in discrimination. Cancer Facts and Figures American Cancer Society, Last accessed May 21, Myint H, Lucie NP: The prognostic significance of the CD34 antigen in acute myeloid leukaemia. Leuk Lymphoma 7 Geller RB, Zahurak M, Hurwitz CA, et al.: Prognostic importance of immunophenotyping in adults with acute myelocytic leukaemia: Campos L, Guyotat D, Archimbaud E, et al.: Clinical significance of multidrug resistance P-glycoprotein expression on acute nonlymphoblastic leukemia cells at diagnosis. Kottaridis PD, Gale RE, Frew ME, et al.: The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia AML adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: Yanada M, Matsuo K, Suzuki T, stage al.: Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations for acute myeloid leukemia: Slovak ML, Kopecky KJ, Cassileth PA, et al.: Karyotypic analysis predicts outcome of preremission and aml therapy in adult acute myeloid leukemia: Grimwade D, Walker H, Harrison G, et al.: The predictive value of hierarchical cytogenetic stage in older adults with acute myeloid leukemia Aml Comparison of cytogenetic and molecular genetic detection of t 8;21 and inv 16 in a prospective series of adults with de novo aml myeloid leukemia: J Clin Oncol 19 9: Brunning RD, Matutes E, Harris NL, et al.: Jaffe ES, Harris NL, Stein H, et al. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. World Health Organization Classification of Tumours, 3, pp Bennett JM, Catovsky D, Daniel MT, et al.: Proposals for the classification of the acute leukaemias. French-American-British FAB co-operative group. Stage J Haematol 33 4: Cheson BD, Cassileth PA, Head DR, et al.: Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. J Clin Oncol 8 5: Micallef IN, Rohatiner AZ, Carter M, et al.: Long-term outcome of patients surviving for more than ten years following treatment for acute leukaemia. Br J Haematol 2: The World Health Organization WHO classification of acute myeloid leukemia AML incorporates and interrelates morphology, cytogenetics, molecular genetics, and immunologic markers in an attempt to construct a classification that is universally applicable and prognostically valid. The decision to treat should be based on other factors including patient age, previous history of MDS, clinical findings, disease progression, in addition to the blast percentage, and most importantly, patient preference. Several groups have begun to investigate the use of gene expression profiling GEP using microarrays to augment current diagnostic and prognostic studies for AML. Distinct subsets can be identified using GEP that correspond to known cytogenetic and molecular abnormalities. The positive predictive value appears to be sufficiently powerful to be clinically useful only for patients with the t 8;21 and inv 16 now referred to terminal core-binding factor [CBF] leukemias and acute promyelocytic leukemia APL with the t 15; GEP identified several cases of CBF leukemias that were not diagnosed using conventional cytogenetics. In the terminal outline and discussion, the older FAB classifications are noted where appropriate. Terminal category is characterized by characteristic genetic abnormalities and frequently high rates of remission and favorable prognoses with the notable exception of those with 11q23 abnormalities. These structural chromosome rearrangements result in the formation of fusion genes that encode chimeric proteins that may contribute to the initiation or progression of leukemogenesis. Many of these translocations are detected by reverse transcriptase—polymerase chain reaction RT—PCR or fluorescence in situ hybridization FISHwhich has a higher sensitivity than cytogenetics. Other recurring cytogenetic abnormalities are less common and described below in AML not otherwise categorized. AML with maturation FAB classification M2 is the most common morphologic type correlating with t 8; The translocation t 8; 21 q22; q22 involves the AML1 gene, also known as RUNX1which encodes CBF-alpha, and the ETO eight-twenty-one gene. This type of AML is usually associated with a good response to chemotherapy and a high complete remission CR rate with long-term survival when treated with high-dose cytarabine in the postremission phase as in the Cancer and Leukemia Group B CLB and CLB trials. Expression of the neural-cell adhesion molecule CD56 appears to be an adverse prognostic indicator. Myeloid sarcomas may be present at initial diagnosis or at relapse. Most cases with this genetic abnormality have been identified as AMML Eo, but occasional cases have been reported aml lack eosinophilia. APL AML with t 15; 17 q22; q12 is an AML in which promyelocytes predominate. APL exists as two types, hypergranular or typical APL and microgranular hypogranular APL. APL has a specific sensitivity to treatment with all- trans retinoic acid ATRA, tretinoinwhich acts as a differentiating agent. Acute myeloid leukemia with 11q23 MLL abnormalities. This AML is more common in children. Two clinical subgroups of patients have a high frequency of AML with 11q23 abnormalities: AML in infants and therapy-related AML, usually occurring after treatment with DNA topoisomerase inhibitors. The MLL gene on 11q23, a developmental regulator, is involved in translocations with approximately 22 different partner chromosomes. One study from the German-Austrian Acute Myeloid Leukemia Study Group examined data on patients with cytogenetically normal AML treated with intensive induction and postremission regimens over an year period. As yet, no clear strategy exists for improving patient outcome in FLT3- mutant AML, or in patients with abnormalities other than CEBPA or the NPM1 without the FLT3-ITD, but small molecule FLT3 inhibitors are in development, and the role of allogeneic transplant is being considered. This category of AML occurs primarily in older patients. The differential diagnosis of AML with multilineage dysplasia includes acute erythroid-myeloid leukemia and acute myeloblastic leukemia with maturation FAB classifications M6a and M2. Aml cases may overlap two morphologic types. Although these therapy-related disorders are distinguished by the specific mutagenic agents involved, a recent stage suggests this distinction may be difficult to make because of the frequent overlapping use of multiple potentially mutagenic agents in treating cancer. Alkylating agent-related acute myeloid leukemia and myelodysplastic syndromes. Clinically, the disorder commonly presents initially as an MDS with evidence of bone marrow failure. The MDS phase may evolve to a higher grade MDS or AML. Although a minority of patients may present with acute leukemia, a substantial number of patients succumb to the disorder in the MDS phase. Cases may correspond morphologically to AML with maturation, acute monocytic leukemia, AMML, erythroleukemia, or acute megakaryoblastic leukemia FAB classifications M2, M5b, M4, M6a, and M7, respectively. Median survival after diagnosis of these disorders is approximately 7 to 8 months. Topoisomerase II inhibitor-related acute myeloid leukemia. This type of AML occurs in patients treated with topoisomerase II inhibitors. The agents implicated are the epipodophyllotoxins etoposide and teniposide and the anthracyclines doxorubicin and 4-epi-doxorubicin. Most cases are categorized as acute monoblastic or myelomonocytic leukemia. Other morphologies reported include APL, myelodysplastic syndromes, and acute megakaryoblastic leukemia. Cases of AML that do not fulfill the criteria for AML with recurrent genetic abnormalities, AML with multilineage dysplasia, or AML and MDS, therapy-related, fall within this category. Classification within this category is based on leukemic cell features of morphology, cytochemistry, and maturation. Acute myeloblastic leukemia, minimally differentiated FAB Classification M0. This AML shows no evidence of myeloid differentiation by morphology and light microscopy cytochemistry. Patients with this AML typically present with evidence of marrow failure, thrombocytopenia, and neutropenia. Immunophenotyping reveals blast cells that express one or more panmyeloid antigens CD13, CD33, and CD and are negative for B and T lymphoid-restricted antigens. Most cases express primitive hematopoietic-associated antigens CD34, CD38, and HLA-DR. Immunophenotyping studies are required to distinguish these disorders. This mutation appears to correlate clinically with a higher white blood cell count and greater marrow blast involvement. Acute myeloblastic leukemia without maturation FAB Classification M1. Patients usually present with anemia, thrombocytopenia, and neutropenia. Refer to the PDQ summary on Fatigue for more information on anemia. CD34 is often positive. The differential diagnosis includes ALL in cases of AML without maturation with no granules and aml low percentage of MPO positive blasts, and AML with maturation in cases of AML with maturation with a high percentage of blasts. Although no specific chromosomal abnormality has been identified for AML without maturation, mutation of the FLT3 gene has been associated with leukocytosis, a high percentage of bone marrow blast cells, and a worse prognosis. Acute myeloblastic leukemia with aml FAB Classification M2. With immunophenotyping, the blasts typically express one or more myeloid-associated antigens CD13, CD33, and CD The differential diagnosis includes: RAEB in cases with a low blast percentage, AML without maturation when the blast percentage is high, and AMML in cases with increased monocytes. Refer to the Acute myeloid leukemia with characteristic genetic abnormalities section of stage Classification section of this summary for more information. Rare cases with t 6; 9 q23; q34 are reported to have a poor prognosis. Refer to the Acute promyelocytic leukemia FAB Classification M3 section of the Acute Myeloid Leukemia With Characteristic Genetic Abnormalities section of this summary for more information. Acute myelomonocytic leukemia FAB Classification M4. Acute myelomonocytic leukemia AMML is characterized by the proliferation of neutrophil and monocyte precursors. Patients usually present with anemia and thrombocytopenia. This type of AML occurs more commonly in older individuals. Immunophenotyping generally reveals monocytic differentiation markers CD14, CD4, CD11b, CD11c, CD64, and CD36 and lysozyme. The differential diagnosis includes AML with maturation and acute monocytic leukemia. Most cases of AMML exhibit nonspecific cytogenetic abnormalities. Cases with increased abnormal eosinophils in the bone marrow associated with a chromosome 16 abnormality have a favorable prognosis. Acute monoblastic leukemia and acute monocytic leukemia FAB classifications M5a and M5b. These cells include monoblasts, promonocytes, and monocytes. These two leukemias are distinguished by the relative proportions of monoblasts and promonocytes. In acute monocytic leukemia, most of the monocytic cells are promonocytes. The extramedullary lesions of these leukemias may be predominantly monoblastic or monocytic or an admixture of the two cell types. The differential diagnosis of acute monocytic leukemia includes AMML and microgranular APL. Acute erythroid leukemias FAB classifications M6a and M6b. The two subtypes of the acute erythroid leukemias, erythroleukemia and pure erythroid leukemia, are characterized by a predominant erythroid population and, in the case of erythroleukemia, the presence of a significant myeloid component. Occasional cases of chronic myeloid leukemia CML may evolve to one of the acute erythroid leukemias. Refer to the PDQ summary on Myelodysplastic Syndromes Treatment for more information. The clinical features of these acute leukemias include profound anemia and normoblastemia. Refer to the PDQ summary on Fatigue for more information. Morphologic and cytochemical features of erythroleukemia include the following: Immunophenotyping in erythroleukemia reveals erythroblasts that react with antibodies to glycophorin A and hemoglobin A and myeloblasts that express a variety of myeloid-associated antigens CD13, CD33, CD, c-kit, and MPO. Immunophenotyping in acute erythroid leukemia reveals expression of glycophorin A and hemoglobin A in differentiated forms. Markers such as carbonic anhydrase 1, Gero antibody against the Gerbich blood group, or CD36 are usually positive. The differential diagnosis for pure erythroid leukemia includes megaloblastic anemia secondary to vitamin B 12 or folate deficiency, acute megakaryocytic leukemia, and ALL or lymphoma. No specific chromosome abnormalities are described for these AMLs. Complex karyotypes with multiple structural abnormalities are common. Chromosomes 5 and 7 appear to be affected frequently. Acute megakaryoblastic leukemia FAB Classification M7. Morphologic and cytochemical features include the following: Immunophenotyping reveals megakaryoblast expression of one or more platelet glycoproteins: Myeloid markers CD13 and CD33 may be positive; CD36 is typically positive. Blasts are aml with the anti-MPO antibody and other markers of myeloid differentiation. In bone marrow biopsies, megakaryocytes and megakaryoblasts may react positively to antibodies for Factor VIII. Refer to the PDQ summary on Chronic Myeloproliferative Neoplasms Treatment for more information on chronic myeloid leukemia or idiopathic myelofibrosis. No unique chromosomal abnormalities are associated with acute megakaryoblastic leukemia in adults. Individuals with Down syndrome trisomy 21 have an increased disposition to acute leukemia, primarily the myeloid type. In cases in which the leukemia remits spontaneously, the process is referred to as transient myeloproliferative disorder or transient leukemia. Immunophenotyping reveals markers that aml generally similar to those of other cases of childhood acute megakaryoblastic leukemia. In addition to trisomy 21, some cases may show other clonal abnormalities, particularly trisomy 8. Recurrence followed by a second spontaneous remission or persistent disease may occur. Treatment outcomes for pediatric patients with Down syndrome and persistent disease may be better than those for pediatric patients with acute aml in the absence of trisomy Acute basophilic leukemia is an AML that exhibits a aml differentiation to aml. Immunophenotypically, the blasts express the myeloid markers CD13 and CD33 and aml early hematopoietic markers CD34 and class-II HLA-DR. No consistent chromosome abnormality has been identified for acute basophilic leukemia. Acute panmyelosis with myelofibrosis also known as acute myelofibrosis, acute myelosclerosis, and acute myelodysplasia with myelofibrosis is an acute panmyeloid proliferation associated with fibrosis of the bone marrow. This disorder is very rare and occurs in all age groups. Clinical features include constitutional symptoms such as weakness and fatigue. Immunophenotypically, blasts may express one or more myeloid-associated antigens CD13, CD33, CD, and MPO. Some cells may express erythroid or megakaryocytic antigens. The major differential diagnosis includes acute megakaryoblastic leukemia, acute leukemias with associated marrow fibrosis, metastatic tumor with a desmoplastic reaction, and chronic idiopathic myelofibrosis. No specific chromosomal abnormalities are associated with acute panmyelosis with myelofibrosis. This AML is reported to respond poorly to chemotherapy and to be associated with a short survival. Immunophenotyping with antibodies to MPO, lysozyme, and chloroacetate are critical to the diagnosis of these lesions. The monoblasts in monoblastic sarcomas express acute monoblastic leukemia antigens CD14, CD, and CD11c and usually react with antibodies to lysozyme and CD Aml main differential diagnosis includes non-Hodgkin lymphoma of the lymphoblastic type, Burkitt lymphoma, large-cell lymphoma, and small, round-cell tumors, especially in children e. No unique chromosomal abnormalities are associated with myeloid sarcoma. In the case of AML, the prognosis is that of the underlying leukemia. Morphologic and immunophenotypic features of these acute leukemias include the following: The differential diagnosis includes myeloid antigen-positive ALL or lymphoid-positive AML from which biphenotypic acute leukemia should be distinguished and minimally differentiated AML from which undifferentiated acute leukemia must be distinguished. Cytogenetic abnormalities are observed in a high percentage of bilineal and biphenotypic leukemias. In general, the prognosis appears to be unfavorable, particularly in adults; the occurrence of the translocation t 4; 11 or the Philadelphia chromosome are especially unfavorable prognostic indicators. Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. Ann Intern Med 4: Brunning RD, Matute E, Harris NL, et al.: Acute myeloid leukemia with multilineage dysplasia. 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Leone G, Voso MT, Sica S, et al.: Leuk Lymphoma 41 Stage myeloid leukaemia not otherwise categorised. Venditti A, Del Poeta G, Stasi R, et al.: Minimally differentiated acute myeloid leukaemia AML-M0: Br J Haematol 88 4: Roumier C, Eclache V, Imbert M, et al.: M0 AML, clinical and biologic features of the disease, including AML1 gene mutations: Acute myeloid leukaemia M0: Br J Haematol 3: Abu-Duhier FM, Goodeve AC, Wilson GA, et al.: FLT3 internal tandem duplication mutations in adult acute myeloid leukaemia define a high-risk group. Br J Haematol 1: Alsabeh R, Brynes RK, Slovak ML, et al.: Acute myeloid leukemia with t 6;9 p23;q Am J Clin Pathol 4: Stanley M, McKenna RW, Ellinger G, et al.: Classification of cases of acute myeloid leukemia by FAB criteria: Chronic and Acute Leukemias in Adults. Martinus Nijhoff Publishers,pp Haferlach T, Schoch C, Schnittger S, et al.: Distinct genetic patterns can be identified in acute monoblastic and acute monocytic leukaemia FAB AML M5a and M5b: Panagopoulos I, Isaksson M, Stage C, et al.: Genes Chromosomes Cancer 36 1: Fenaux P, Vanhaesbroucke C, Estienne MH, et al.: Acute monocytic leukaemia in adults: Br J Haematol 75 1: Cigudosa JC, Odero MD, Calasanz MJ, et al.: De novo erythroleukemia chromosome features include multiple rearrangements, with special involvement of chromosomes 11 and Genes Chromosomes Cancer 36 4: Domingo-Claros A, Larriba I, Rozman M, et al.: Acute erythroid neoplastic proliferations. A biological study based on 62 patients. Olopade OI, Thangavelu M, Larson RA, et al.: Clinical, morphologic, and cytogenetic characteristics of 26 patients with acute erythroblastic leukemia. Bernstein J, Dastugue N, Haas OA, et al.: Nichols CR, Roth BJ, Heerema N, et al.: Hematologic neoplasia associated with primary mediastinal germ-cell tumors. Carroll A, Civin C, Schneider N, et al.: The t 1;22 p13;q13 is nonrandom and restricted to infants with acute megakaryoblastic leukemia: Cytogenetic profile of childhood and adult megakaryoblastic leukemia M7: Pagano L, Pulsoni A, Vignetti M, et al.: Athale UH, Razzouk BI, Raimondi SC, et al.: Biology and outcome of childhood acute megakaryoblastic leukemia: Zipursky A, Brown EJ, Christensen H, et al.: Transient myeloproliferative disorder transient leukemia and hematologic manifestations of Down syndrome. Clin Lab Med 19 1: Zipursky A, Thorner P, De Harven E, et al.: Myelodysplasia and acute megakaryoblastic leukemia in Down's syndrome. Leuk Res 18 3: Kounami S, Aoyagi N, Tsuno H, et al.: Additional chromosome abnormalities in transient abnormal myelopoiesis in Down's syndrome patients. Acta Haematol 98 2: Yamauchi K, Yasuda M: Comparison in treatments of nonleukemic granulocytic sarcoma: Byrd JC, Weiss RB, Arthur DC, et al.: Extramedullary leukemia adversely affects hematologic complete remission rate and overall survival in patients with t 8;21 q22;q J Clin Oncol 15 2: Hayashi T, Kimura M, Satoh S, et al.: Imrie KR, Kovacs MJ, Selby D, et al.: Ann Intern Med 5: Brunning RD, Matutes E, Borowitz M: Acute leukaemias of ambiguous lineage. Hanson CA, Abaza M, Sheldon S, et al.: Br J Haematol 84 1: Legrand O, Perrot JY, Simonin G, et al.: Adult biphenotypic acute leukaemia: Matutes E, Morilla R, Farahat N, et al.: Definition of acute biphenotypic leukemia. Sulak LE, Clare CN, Morale BA, et al.: Biphenotypic acute leukemia in adults. Am J Clin Pathol 94 1: Carbonell F, Swansbury J, Min T, et al.: Cytogenetic findings in acute biphenotypic leukaemia. Pane F, Frigeri F, Camera A, et al.: Complete phenotypic and genotypic lineage switch in a Philadelphia chromosome-positive acute lymphoblastic leukemia. Killick S, Matutes E, Powles RL, et al.: Outcome of biphenotypic acute leukemia. Untreated adult acute myeloid leukemia AML is defined as newly diagnosed leukemia with no previous treatment. The patient exhibits the following features: In addition, no signs or symptoms are evident of central nervous system leukemia or other extramedullary infiltration. Because the vast majority of AML patients meeting these criteria for remission have residual leukemia, modifications to the definition of complete remission have been suggested, including cytogenetic remission, in which a previously abnormal karyotype reverts to normal, and molecular remission, in which interphase fluorescence in situ hybridization FISH or multiparameter flow cytometry are used to detect minimal residual disease. Immunophenotyping and interphase FISH have greater prognostic significance than the conventional criteria for remission. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria. General information about clinical trials is also available from the NCI Web site. Cheson BD, Bennett JM, Kopecky KJ, et al.: Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 21 Bacher U, Kern W, Schoch C, et al.: Evaluation of complete disease remission in acute myeloid leukemia: Successful treatment of acute myeloid leukemia AML requires the control of bone marrow and systemic disease and specific treatment of central nervous system CNS disease, if present. The cornerstone of this strategy includes systemically administered combination chemotherapy. Treatment is divided into two phases: Maintenance therapy for AML was previously administered for several years but is not included in most current treatment clinical trials in the United States, other than for acute promyelocytic leukemia. Refer to the Adult Acute Myeloid Leukemia in Remission section of this summary for more information. Other studies have used more intensive postremission therapy administered for a shorter duration of time after which treatment is discontinued. Since myelosuppression is an anticipated consequence of both the leukemia and its treatment with chemotherapy, patients must be closely monitored during therapy. Facilities must be available for hematologic support with multiple blood fractions including platelet transfusions and for the treatment of related infectious complications. GM-CSF was shown to improve survival in a randomized trial of AML in patients aged 55 to 70 years median survival was In this Eastern Cooperative Oncology Stage ECOG EST trial, patients were randomly assigned to receive GM-CSF or placebo following demonstration of leukemic clearance of the bone marrow;[ 9 ] however, GM-CSF did not show benefit in a separate similar randomized trial in patients older than 60 years. In a Southwest Oncology Group NCT randomized trial of G-CSF given following induction therapy to patients older than 65 years, complete response was higher in patients who received G-CSF because of a decreased incidence of primary leukemic resistance. Growth factor administration did not impact on mortality or on survival. The administration of GM-CSF or other myeloid growth factors before and during induction therapy, to augment the effects of cytotoxic therapy through the recruitment of leukemic blasts into cell cycle growth factor priminghas been an area of active clinical research. Evidence from randomized studies of GM-CSF priming have come to opposite conclusions. A randomized study of GM-CSF priming during conventional induction and postremission therapy showed no difference in outcomes between patients who received GM-CSF and those who did not receive growth factor priming. Kebriaei P, Champlin R, deLima M, et al.: Management of acute leukemias. DeVita VT Jr, Lawrence TS, Rosenberg SA: Principles aml Practice of Oncology. Diagnosis and treatment of acute nonlymphocytic leukemia. Wiernik PH, Canellos GP, Dutcher JP, et al. Neoplastic Diseases of the Blood. Churchill Livingstone,pp Morrison FS, Kopecky KJ, Head DR, et al.: Late intensification with POMP chemotherapy prolongs survival in acute myelogenous leukemia--results of a Southwest Oncology Group study of rubidazone versus adriamycin for remission induction, prophylactic intrathecal therapy, late intensification, and levamisole maintenance. Cassileth PA, Lynch E, Hines JD, et al.: Varying intensity of postremission therapy in acute myeloid leukemia. Rebulla P, Finazzi G, Marangoni F, et al.: The threshold for prophylactic platelet transfusions in adults with acute myeloid leukemia. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto. Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. The Trial to Reduce Alloimmunization to Platelets Study Group. Use of cytokines in the treatment of acute myelocytic leukemia: J Clin Oncol 14 4: Rowe JM, Andersen JW, Mazza JJ, et al.: Stone RM, Berg DT, George SL, et al.: Granulocyte-macrophage colony-stimulating factor after initial chemotherapy for elderly patients with primary acute myelogenous leukemia. Cancer and Leukemia Group B. Dombret H, Chastang C, Fenaux P, et al.: A controlled study of recombinant human granulocyte colony-stimulating factor in elderly patients after treatment for acute myelogenous leukemia. AML Cooperative Study Group. Godwin JE, Kopecky KJ, Head DR, et al.: A double-blind placebo-controlled trial of granulocyte colony-stimulating factor in elderly patients with previously untreated acute myeloid leukemia: Buchner T, Hiddemann W, Wormann B, et al.: GM-CSF multiple course priming and long-term administration in newly diagnosed AML: Value of different modalities of granulocyte-macrophage colony-stimulating factor applied during or after induction therapy of acute myeloid leukemia. J Clin Oncol 15 Witz F, Sadoun A, Perrin MC, et al.: A placebo-controlled study of recombinant human granulocyte-macrophage colony-stimulating factor administered during and after induction treatment for de novo acute myelogenous leukemia in elderly patients. Some physicians opt to add a third drug, thioguanine, to this regimen, although little evidence is available to conclude that this three-drug regimen is better therapy. One study suggested that the addition of etoposide during induction therapy may improve response duration. Idarubicin appeared to be more effective than daunorubicin, particularly in younger adults, although the doses of idarubicin and daunorubicin may not have been equivalent. While overall survival OS was not impacted by the choice of anthracycline, the percentage of long-term disease-free survivors in a mixed-cure model did appear to be impacted hazard ratio [HR], 0. The role of high-dose cytarabine in induction therapy is controversial; randomized trials have shown prolongation of DFS [ 11 ][ 12 ] or no effect [ 13 ][ 14 ] compared with conventionally dosed cytarabine-based induction chemotherapy. AML arising from myelodysplasia or secondary to previous cytotoxic chemotherapy has a lower rate of remission aml de novo AML. These data suggest that patients with these subsets of leukemia may be treated primarily with allogeneic BMT if their overall performance status is adequate, potentially sparing patients the added toxic effect of induction chemotherapy. Older adults who decline intensive remission induction therapy or are considered unfit for intensive remission induction therapy may derive benefit from low-dose cytarabine, administered twice daily for 10 days in cycles repeated every 4 to 6 weeks. Supportive care during remission induction treatment should routinely include red blood cell and platelet transfusions when appropriate. Elaborate isolation facilities including filtered air, sterile food, and gut flora sterilization are not routinely indicated but may benefit transplant patients. The combination of ofloxacin and rifampin has proven superior to norfloxacin in decreasing the incidence of documented granulocytopenic infection. Of 31 long-term female survivors of AML or acute lymphoblastic leukemia younger than 40 years, 26 resumed normal menstruation following completion of therapy. Among 36 live offspring of survivors, two congenital problems occurred. Special consideration must be given to stage therapy for acute promyelocytic leukemia APL. ATRA is not effective in patients with AML that resembles M3 terminal but does not demonstrate the t 15;17 or typical PML-RARA gene rearrangement. Administration of ATRA leads to rapid resolution of coagulopathy in most patients, and heparin administration is not required in patients receiving ATRA. However, randomized trials have not shown a reduction in morbidity and mortality during ATRA induction when compared with chemotherapy. Administration of ATRA can lead to hyperleukocytosis and a syndrome of respiratory distress now known as the differentiation syndrome. Prompt recognition of the syndrome and aggressive administration of steroids can prevent severe respiratory distress. However, two large cooperative group trials have demonstrated a statistically significant relapse-free and OS advantage to patients with M3 AML who receive ATRA at some point during their antileukemic management. A randomized study has shown that the relapse rate was reduced in patients treated with concomitant ATRA and chemotherapy compared with ATRA induction followed by chemotherapy given in remission relative risk [RR] of relapse at 2 years, 0. The use of 6-mercaptopurine and methotrexate also produced an improvement in OS RR of relapse, 0. Two concurrent clinical trials separately conducted in Italy and Spain included ATRA plus anthracycline induction followed by three cycles of postremission and maintenance therapy. The two treatment protocols differed only in the addition of nonanthracycline drugs during postremission therapy cycles in the Italian study; doses of anthracyclines were identical between the two trials. Essentially identical relapse-free survival suggests that the nonanthracycline drugs i. The trial was stopped at an early interim analysis following randomization of patients. The cytarabine group demonstrated a superior 2-year relapse rate 4. Studies are beginning to examine the inclusion of arsenic trioxide ATO in the management of previously untreated patients. Eighty patients achieved remission with five induction deaths. Four relapses developed between 8 months and 39 months following remission attainment, all of which were in the central nervous system CNS. In another trial, investigators used an ATO-based regimen, which included gemtuzumab ozogamicin GO as the only cytotoxic drug. Patients in remission received alternating months of ATO and ATRA for a total of seven cycles; GO was substituted if either ATO or ATRA were discontinued as a result of toxicity. Eighty-two patients were treated; seven patients died during induction, the remainder achieved remission. Presence of the unique fusion transcript PML-RARA measured in bone marrow by polymerase chain reaction in patients who achieve CR may indicate those who are likely to relapse early. Coagulopathy is occasionally a problem in patients undergoing induction with ATRA plus chemotherapy. This coagulopathy can lead to catastrophic intracranial bleeding but can be well controlled with low-dose heparin infusion in the setting of clotting or with aggressive replacement of platelets and clotting factors. Aml options for remission induction therapy: Bishop JF, Lowenthal RM, Joshua D, et al.: Etoposide in acute nonlymphocytic leukemia. Australian Leukemia Study Group. Wiernik PH, Banks PL, Case DC Jr, et al.: Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult aml with acute myeloid leukemia. Vogler WR, Velez-Garcia E, Weiner RS, et al.: A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: J Clin Oncol 10 7: Berman E, Heller G, Santorsa J, et al.: Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia. Mandelli F, Petti MC, Ardia A, et al.: A randomised clinical trial comparing idarubicin and cytarabine to daunorubicin and cytarabine in the treatment of acute non-lymphoid leukaemia. A multicentric study from the Aml Co-operative Group GIMEMA. Eur J Cancer 27 6: Arlin Z, Case DC Jr, Moore J, et al.: Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia ANLL. Fernandez HF, Sun Z, Yao X, et al.: Anthracycline dose intensification in acute myeloid leukemia. Gardin C, Chevret S, Pautas C, et al.: Superior long-term outcome with idarubicin compared with high-dose daunorubicin in patients with acute myeloid leukemia age 50 years and older. J Clin Oncol 31 3: Burnett AK, Russell NH, Hills RK, et al.: Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol 30 Burnett AK, Hills RK, Hunter AE, et al.: The addition of gemtuzumab ozogamicin to low-dose Ara-C improves remission rate but does not significantly prolong survival in older patients with acute myeloid leukaemia: Bishop JF, Matthews JP, Young GA, et al.: A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Geller RB, Burke PJ, Karp JE, et al.: A two-step timed sequential treatment for acute myelocytic leukemia. Weick JK, Kopecky KJ, Appelbaum FR, et al.: A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: Double induction strategy for acute myeloid leukemia: Schoch C, Haferlach T, Haase D, et al.: Patients with de novo acute myeloid leukaemia and complex karyotype aberrations show a poor prognosis despite intensive treatment: Anderson JE, Gooley TA, Schoch G, et al.: Stem cell transplantation for secondary acute myeloid leukemia: Burnett AK, Milligan D, Prentice AG, et al.: A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and terminal myelodysplastic syndrome in patients not considered fit for intensive treatment. Controversies in platelet transfusion therapy. Annu Rev Med Murphy MF, Metcalfe P, Thomas H, et al.: Use of leucocyte-poor blood components and HLA-matched-platelet donors to prevent HLA alloimmunization. Br J Haematol 62 3: Hughes WT, Armstrong D, Bodey GP, et al.: From the Infectious Diseases Society of America. Terminal for the use of antimicrobial agents in neutropenic patients with unexplained fever. J Infect Dis 3: Rubin Stage, Hathorn JW, Pizzo PA: Controversies in the management of febrile neutropenic cancer patients. Cancer Invest 6 2: Symposium on infectious complications of neoplastic disease Part II. Protected environments are discomforting and expensive and do not offer meaningful protection. Sherertz RJ, Belani A, Terminal BS, et al.: Impact of air filtration on nosocomial Aspergillus infections. Unique risk of bone marrow transplant recipients. Wade JC, Schimpff SC, Hargadon MT, et al.: A comparison of trimethoprim-sulfamethoxazole plus nystatin with gentamicin plus nystatin in the prevention of infections in acute leukemia. Karp JE, Merz WG, Hendricksen C, et al.: Oral norfloxacin for prevention of gram-negative bacterial infections in patients with acute leukemia and granulocytopenia. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1: Prevention of bacterial infection in neutropenic patients with hematologic malignancies. A randomized, multicenter trial comparing norfloxacin with ciprofloxacin. The GIMEMA Infection Program. Bow EJ, Mandell LA, Louie TJ, et al.: Quinolone-based antibacterial chemoprophylaxis in neutropenic patients: National Cancer Institute of Canada Clinical Trials Group. Ann Intern Med 3: Huang ME, Ye YC, Chen SR, et al.: Use of all-trans retinoic acid in the treatment of acute terminal leukemia. Warrell RP Jr, Frankel SR, Miller WH Jr, et al.: Differentiation therapy of acute promyelocytic leukemia with aml all-trans-retinoic acid. Chen ZX, Xue YQ, Zhang R, et al.: A clinical and experimental study on all-trans retinoic acid-treated acute promyelocytic leukemia patients. Muindi J, Frankel SR, Miller WH Jr, et al.: Continuous treatment with all-trans retinoic acid causes a progressive reduction in plasma drug concentrations: Licht JD, Chomienne C, Goy A, et al.: Clinical and molecular characterization of a rare syndrome of acute promyelocytic leukemia associated with translocation 11; Gallagher RE, Li YP, Rao S, et al.: Frankel SR, Eardley A, Lauwers G, et al.: The "retinoic acid syndrome" in acute promyelocytic leukemia. Fenaux P, Le Deley MC, Castaigne S, et al.: Effect of all transretinoic acid in newly diagnosed acute promyelocytic leukemia. Results of a multicenter randomized trial. European Stage 91 Group. Tallman MS, Andersen J, Schiffer CA, et al.: Phase III randomized study of all-trans retinoic acid ATRA vs daunorubicin D and cytosine arabinoside A terminal induction therapy terminal ATRA vs observation as maintenance therapy for patients with previously untreated acute promyelocytic leukemia APL. Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol 24 Aml J, Liu YF, Wu CF, et al.: Proc Natl Acad Sci U S A 9: Ravandi F, Estey E, Jones D, et al.: Effective treatment of acute promyelocytic leukemia with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin. J Clin Oncol 27 4: Lo Coco F, Diverio D, Pandolfi PP, et al.: Molecular evaluation stage residual disease as a predictor of relapse in acute promyelocytic leukaemia. Head D, Kopecky KJ, Weick J, et al.: Effect of aggressive daunomycin therapy on survival in acute promyelocytic leukemia. Stone RM, Mayer RJ: The unique aspects of acute promyelocytic leukemia. J Clin Oncol 8 Yates J, Glidewell O, Wiernik P, et al.: Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: Dillman RO, Davis RB, Green MR, et al.: A comparative study of two different doses of cytarabine for acute myeloid leukemia: Mitoxantrone versus terminal in induction-consolidation chemotherapy--the value of low-dose cytarabine for maintenance of remission, and an assessment of prognostic factors in acute myeloid leukemia in the elderly: European Organization for the Research and Treatment of Cancer and the Dutch-Belgian Hemato-Oncology Cooperative Hovon Group. J Clin Oncol 16 3: Gale RP, Foon KA, Cline MJ, et al.: Intensive chemotherapy for acute myelogenous leukemia. Ann Intern Med 94 6: Although individual patients have been reported to have long disease-free survival DFS or cure with a single cycle of chemotherapy,[ 1 stage postremission therapy is always indicated in therapy that is planned with curative intent. In a small randomized study conducted by the Eastern Cooperative Oncology Group ECOGall patients who did not receive postremission therapy experienced a relapse after a aml median complete remission CR duration. While older studies have included longer-term therapy at lower doses maintenanceno convincing evidence is available with acute myeloid leukemia AML that maintenance therapy provides prolonged DFS beyond shorter-term, more dose-intensive approaches, and few current treatment clinical trials include maintenance therapy. Therefore, to address these issues, patients with AML should be included in clinical trials at institutions that treat large numbers of such patients. In a retrospective analysis of patients who received high-dose bolus cytarabine at a single institution, the most powerful predictor of cytarabine neurotoxicity was renal insufficiency. Allogeneic bone marrow transplantation BMT results in the lowest incidence of leukemic relapse, even when compared with BMT from an identical twin syngeneic BMT. This has led to aml concept of an immunologic graft-versus-leukemia effect, similar to and related to graft-versus-host disease. The improvement in freedom from relapse using allogeneic BMT as the primary postremission therapy is offset, at least in part, by the increased morbidity and mortality caused by graft-versus-host disease, veno-occlusive disease of the liver, and interstitial pneumonitis. A common clinical trial design used to evaluate the benefit of allogeneic transplant as consolidation therapy for AML in first remission is the so-called donor-no donor comparison. In this design, newly diagnosed AML patients who achieve a CR have one or more siblings, and are deemed medically eligible for allogeneic transplant, undergo HLA typing. If a sibling donor is identified, the patient is allocated to the transplantation arm. Analysis of outcome is by intention to treat; that is, patients assigned to the donor arm who do not receive a transplant are grouped in the analysis with the patients who did actually receive a transplant. Relapse-free survival RFS is the usual endpoint for this type of trial. Overall survival OS from the time of diagnosis is less frequently reported in these trials. Results of these trials have been mixed, with some trials showing a clear benefit across all cytogenetic subgroups, and others showing no benefit. Investigators attempted to address this issue with a meta-analysis using data from 18 separate prospective terminal of AML patients using the donor-no donor design, with data from an additional six trials included for sensitivity analysis. Median follow-up ranged from 42 months to months. Preparative regimens were similar among the different trials. Allogeneic transplant was compared with autologous transplant 6 trials or with a variety of consolidation chemotherapy regimens, with high-dose cytarabine being the most common. Of 18 trials reporting RFS across all cytogenetic risk groups, the combined hazard ratio HR for overall RFS benefit with allogeneic transplant was 0. Of the 15 trials reporting OS across all cytogenetic risk groups, the combined Terminal for OS was 0. In subgroup analysis according to cytogenetic risk category, there was no RFS or OS benefit of allogeneic transplant for patients with good-risk AML RFS: However, a transplant benefit was seen for patients with intermediate RFS: The conclusion from this meta-analysis was that allogeneic transplant from a sibling donor in a first CR is justified on the basis of improved RFS and OS for patients with intermediate- or poor-risk, but not good-risk, cytogenetics. An important caveat to this analysis is that induction and postremission strategies for AML among studies included in the meta-analysis were not uniform; nor were definitions of cytogenetic risk groups uniform. This may have resulted in inferior survival rates among chemotherapy-only treated patients. Autologous BMT has also cured a smaller proportion of patients in second remission. Ongoing controversies include the optimum timing of autologous stem cell transplantation, whether it should be preceded by postremission chemotherapy, and the role of ex vivo treatment of the graft with chemotherapy, such as 4-hydroperoxycyclophosphamide 4-HC [ 21 ] or mafosphamide,[ 22 ] or monoclonal antibodies, such as anti-CD In a prospective trial of patients with AML in first remission, City of Hope investigators treated patients with one course of high-dose cytarabine postremission therapy, followed by unpurged autologous BMT following preparative therapy of total-body radiation therapy, etoposide, and cyclophosphamide. A randomized trial by ECOG and the Southwest Oncology Group SWOG compared autologous BMT using 4-HC-purged bone marrow with high-dose cytarabine postremission therapy. A randomized trial has compared the use of autologous BMT in first CR with postremission chemotherapy, with the latter group eligible for autologous BMT in second CR. The two arms of the study had equivalent survival. In a retrospective analysis of patients with de novo AML treated with allogeneic or autologous BMT in first remission in whom cytogenetic analysis at diagnosis was available, patients with poor-risk cytogenetics abnormalities of chromosomes 5, 7, 11q, or hypodiploidy had less favorable outcomes following allogeneic BMT than patients with normal karyotypes or other cytogenetic abnormalities. These data were based on analysis of small subsets of patients and were not statistically significant. Poor-risk factors include deletion of 5q and 7q, trisomy 8, t 6; 9t 9; 22and a history of myelodysplasia or antecedent hematologic disorder. Patients in the good-risk group have a reasonable chance of cure with intensive postremission therapy, and it may be reasonable to defer transplantation in that group until early first relapse. The poor-risk group is unlikely to be cured with postremission chemotherapy, and allogeneic BMT in first CR is a reasonable option for patients with an HLA-identical sibling donor. Patients with normal cytogenetics are in an intermediate-risk group, and postremission management should be individualized or, ideally, managed according to a clinical trial. The rapid engraftment kinetics of peripheral blood progenitor cells demonstrated in trials of high-dose therapy for epithelial neoplasms has led to interest in the alternative use of autologous and allogeneic peripheral blood progenitor cells as rescue for myeloablative therapy for the treatment of AML. Allogeneic stem cell transplantation can be performed using stem cells obtained from a bone marrow harvest or a peripheral blood progenitor cell harvest. In a randomized trial of patients undergoing allogeneic stem cell transplantation, with either bone marrow or peripheral blood stem cells, for a variety of hematologic malignancies using methotrexate and cyclosporine to prevent graft-versus-host disease, the use of peripheral blood progenitor cells led to earlier engraftment median neutrophil engraftment, 16 vs. The relapse rate at 2 years appeared lower in patients receiving peripheral blood progenitor cells hazard ratio [HR], 0. Vaughan WP, Karp JE, Burke PJ: Long chemotherapy-free remissions after single-cycle timed-sequential chemotherapy for acute myelocytic leukemia. Cassileth PA, Harrington DP, Hines JD, et al.: Maintenance chemotherapy prolongs remission duration in adult acute nonlymphocytic leukemia. J Clin Oncol 6 4: Mayer RJ, Davis RB, Schiffer CA, et al.: Intensive postremission chemotherapy in adults with acute myeloid leukemia. Champlin R, Gajewski J, Nimer S, et al.: Postremission chemotherapy for adults with acute myelogenous leukemia: J Clin Oncol 8 7: Rohatiner AZ, Gregory WM, Bassan R, et al.: Short-term therapy for acute myelogenous leukemia. J Clin Oncol 6 2: Postremission therapy in older patients with de novo acute terminal leukemia: Goldstone AH, Burnett Terminal, Wheatley K, et al.: Attempts to improve treatment outcomes in acute myeloid leukemia AML in older patients: Baker WJ, Royer GL Jr, Weiss RB: Cytarabine and neurologic toxicity. J Clin Oncol 9 4: Haupt HM, Hutchins GM, Moore GW: Clift RA, Buckner CD, Thomas ED, et al.: The treatment of acute non-lymphoblastic leukemia by allogeneic marrow transplantation. Bone Marrow Transplant 2 3: Reiffers J, Gaspard MH, Maraninchi D, et al.: Comparison of allogeneic or autologous bone marrow transplantation and chemotherapy in patients with acute myeloid leukaemia in first remission: Br J Haematol 72 1: Bostrom B, Brunning RD, McGlave P, et al.: Bone marrow transplantation for acute nonlymphocytic leukemia in first remission: Busca A, Anasetti C, Anderson G, et al.: Unrelated donor or autologous marrow transplantation for treatment of acute leukemia. Tallman MS, Rowlings PA, Milone G, et al.: Effect of postremission chemotherapy before human leukocyte antigen-identical sibling transplantation for acute myelogenous leukemia in first complete remission. Koreth J, Schlenk R, Kopecky KJ, et al.: Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: Chao NJ, Stein AS, Stage GD, et al.: Linker CA, Ries CA, Damon LE, et al.: Autologous bone marrow transplantation for acute myeloid leukemia using busulfan plus etoposide as a preparative regimen. Sanz MA, de la Rubia J, Sanz GF, et al.: Busulfan plus cyclophosphamide followed by autologous blood stem-cell transplantation for patients with acute myeloblastic leukemia in first complete remission: J Clin Oncol 11 9: Cassileth PA, Andersen J, Lazarus HM, et al.: Autologous bone marrow transplant in acute myeloid leukemia in first remission. J Clin Stage 11 2: Jones RJ, Santos GW: Autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide purging. Proceedings of a Wyeth-Ayerst-UCLA Symposia Western Workshop Held at Lake Lanier, Georgia, November December 1, Wiley-Liss,pp Gorin NC, Aegerter P, Auvert B, et al.: Autologous bone marrow transplantation for acute myelocytic leukemia in first remission: Robertson MJ, Soiffer RJ, Freedman AS, et al.: Human bone marrow depleted of CDpositive cells mediates delayed but durable reconstitution of hematopoiesis: Stein AS, O'Donnell MR, Chai A, et al.: In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission. J Clin Oncol 14 8: Cassileth PA, Harrington DP, Appelbaum FR, et al.: Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. Zittoun RA, Mandelli F, Willemze R, et al.: Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer EORTC and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto GIMEMA Leukemia Cooperative Groups. N Engl J Med 4: Ravindranath Y, Yeager AM, Chang MN, et al.: Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood. Woods WG, Neudorf S, Gold S, et al.: Aggressive post-remission REM chemotherapy is better terminal autologous bone marrow transplantation BMT and allogeneic BMT is superior to both in children with acute myeloid leukemia AML. Harousseau JL, Cahn JY, Pignon B, et al.: Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia. Ferrant A, Labopin M, Frassoni F, et al.: Karyotype in acute myeloblastic leukemia: Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation EBMT. New clonal karyotypic abnormalities acquired following autologous bone marrow transplantation for acute myeloid leukemia do not appear to confer an adverse prognosis. Bone Marrow Transplant 21 4: Schiller GJ, Nimer SD, Territo MC, et al.: Bone marrow transplantation versus high-dose cytarabine-based consolidation chemotherapy for acute myelogenous leukemia in first remission. J Clin Oncol 10 1: Edenfield WJ, Gore SD: Stage-specific application of allogeneic and autologous marrow transplantation in the management of acute myeloid leukemia. Semin Oncol 26 1: Witherspoon RP, Deeg HJ, Storer B, et al.: Hematopoietic stem-cell transplantation for treatment-related leukemia or myelodysplasia. J Clin Oncol 19 8: Bensinger WI, Martin PJ, Storer B, et al.: Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. N Engl J Med 3: No standard regimen exists for the treatment of patients with relapsed acute myeloid leukemia AMLparticularly in patients with a first remission duration of less than 1 year. A number of agents have activity in recurrent AML. CRp refers to clearance of leukemic blasts from the marrow, with adequate myeloid and erythroid recovery but with incomplete platelet recovery although platelet transfusion independence for at least 1 week was required. Unclear is whether the inadequate platelet recovery is the result of megakaryocyte toxic effects of gemtuzumab or subclinical residual leukemia. The long-term outcomes of patients who achieve CRp following gemtuzumab are not yet stage. Gemtuzumab induces profound bone marrow aplasia similar to leukemia induction chemotherapy and also has substantial hepatic toxic effects, including hepatic venoocclusive disease. A subset of relapsed patients treated aggressively may have extended disease-free survival DFS ; however, cures in patients following a relapse are thought to be more commonly achieved using BMT. The transplantation regimens were similarly diverse. Leukemia-free survival appeared to be superior for patients receiving BMTs for two groups: Nine of 21 patients with primary refractory AML were alive and disease free at 10 years following allogeneic BMT. Autologous BMT is an option for patients in second CR, offering a DFS that may be comparable to autografting in first CR. Patients who relapse following an allogeneic BMT may undergo an infusion of lymphocytes from the donor donor lymphocyte infusion or DLIsimilar to the therapy patients with relapsing chronic myelogenous leukemia CML undergo. Refer to the Relapsing Chronic Myelogenous Leukemia section of the PDQ summary on Chronic Myelogenous Leukemia Treatment for more information. There are no published studies of any prospective trials examining the role of DLI for patients with AML who relapsed following allogeneic BMT. A retrospective study of European patients found that, out of patients who relapsed after an allogeneic BMT, patients received DLI as part of their salvage therapy. Arsenic trioxide, an agent with both differentiation-inducing and apoptosis-inducing properties against acute promyelocytic leukemia APL cells, has a high rate of successful remission induction in patients with relapsed APL. Eighty-six percent of evaluable patients tested negative for the presence of PML - RARA transcript after induction or stage therapy with arsenic trioxide. Induction with arsenic trioxide may be complicated by APL differentiation syndrome identical to ATRA syndromeprolongation of QT interval, and neuropathy. Ferrara F, Palmieri S, Mele G: Prognostic factors and therapeutic options for relapsed or refractory acute myeloid leukemia. Hiddemann W, Kreutzmann H, Straif K, et al.: High-dose cytosine arabinoside and mitoxantrone: Brown RA, Herzig RH, Wolff SN, et al.: High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy. Paciucci PA, Dutcher JP, Cuttner J, et al.: Mitoxantrone and ara-C in previously treated patients with acute myelogenous leukemia. Lambertenghi-Deliliers G, Maiolo AT, Annaloro C, et al.: Idarubicin in sequential combination with cytosine arabinoside in the treatment of relapsed and refractory patients with acute non-lymphoblastic leukemia. Eur J Cancer Clin Oncol 23 7: Harousseau JL, Reiffers J, Hurteloup P, et al.: Treatment of relapsed acute myeloid leukemia with idarubicin and intermediate-dose cytarabine. J Clin Oncol 7 1: Forman SJ, Schmidt GM, Nademanee AP, et al.: Allogeneic bone marrow transplantation as therapy for primary induction failure for patients with acute leukemia. J Clin Oncol 9 9: Spadea A, Petti MC, Fazi P, et al.: Mitoxantrone, etoposide and intermediate-dose Ara-C MEC: Greenberg PL, Lee SJ, Advani R, et al.: Mitoxantrone, etoposide, and cytarabine with or without valspodar in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome: J Clin Oncol 22 6: Estey E, Plunkett W, Gandhi V, et al.: Fludarabine and arabinosylcytosine therapy of refractory and relapsed acute myelogenous leukemia. Leuk Lymphoma 9 Sievers EL, Larson RA, Stadtmauer EA, et al.: Efficacy and safety of gemtuzumab ozogamicin in patients with CDpositive acute myeloid leukemia in first relapse. J Clin Oncol 19 Giles FJ, Kantarjian HM, Kornblau SM, et al.: Mylotarg gemtuzumab ozogamicin therapy is associated with hepatic venoocclusive disease in patients who have not received stem cell transplantation. Karp JE, Lancet JE, Kaufmann SH, et al.: Clinical and biologic activity of the farnesyltransferase inhibitor R in adults with refractory and relapsed acute leukemias: Kantarjian H, Gandhi V, Cortes J, et al.: Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia. Faderl S, Gandhi V, O'Brien S, et al.: Results of a phase study of clofarabine in combination with cytarabine ara-C in relapsed and refractory acute leukemias. Gale RP, Horowitz MM, Rees JK, et al.: Chemotherapy versus transplants for acute myelogenous leukemia in second remission. Clift RA, Buckner CD, Appelbaum FR, et al.: Allogeneic marrow transplantation during untreated first relapse of acute myeloid leukemia. J Clin Oncol 10 Meloni G, De Fabritiis P, Petti MC, et al.: BAVC regimen and autologous bone marrow transplantation in patients with acute myelogenous leukemia in second remission. Chopra R, Goldstone AH, McMillan AK, et al.: J Clin Oncol 9 Gorin NC, Labopin M, Meloni G, et al.: Autologous bone marrow transplantation for acute myeloblastic leukemia in Europe: European Co-operative Group for Bone Marrow Transplantation EBMT. Schmid C, Labopin M, Nagler A, et al.: Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: J Clin Oncol 25 Dazzi F, Szydlo RM, Craddock C, et al.: Comparison of single-dose and escalating-dose regimens of donor lymphocyte infusion for relapse stage allografting for chronic myeloid leukemia. Soignet SL, Frankel SR, Douer D, et al.: United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. Shen ZX, Chen GQ, Ni JH, et al.: Use of terminal trioxide As2O3 in the treatment of acute promyelocytic leukemia APL: Clinical efficacy and pharmacokinetics in relapsed patients. Patient Stories Breast cancer survivor offers wisdom at Faulkner satellite center. Call today to make an appointment. Make an appointment online. Our Research Clinical Trials Research Advances Featured Research Departments and Centers Integrative Research Centers Core Facilities. Appointments Make your appointment or second opinion with Dana-Farber today to meet with an onsite specialist. How to Help Discover the ways to terminal and how to get involved to support Dana-Farber. Learn More Give now. Patient Stage Poet Richard Fox gains insight — and material — through cancer treatment. Patient Story A family faces cancer in an unfamiliar city — with help. Patient Story Choosing mastectomy or not:
DIEM BROWN - Final Days and Her Peaceful Goodbye - A Tribute
DIEM BROWN - Final Days and Her Peaceful Goodbye - A Tribute
5 thoughts on “Terminal stage of aml terminal stage of aml”
If an assignment creates a new or special burden to the other original contracting party, it may also be prohibited.
When the work is done and the capital completed, they all assemble for the first great council.
Erica Ehrenberg, Retrieving Late Babylonian Art: The Seal Impressions from the Eanna Archive at Uruk.
Teachers, parents, and other adults feel disgruntled about the way they dress.
Culture is the basis that form ideas of what sex, gender, and power mean and the roles associated with in different communities.