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2600 First @-@ line treatment of AML 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 . 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 .
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2601 = = = Induction = = =
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2602 All FAB subtypes except M3 are usually given induction chemotherapy with cytarabine ( ara @-@ C ) and an anthracycline ( most often daunorubicin ) . This induction chemotherapy regimen is known as " 7 + 3 " ( or " 3 + 7 " ) , because the cytarabine is given as a continuous IV infusion for seven consecutive days while the anthracycline is given for three consecutive days as an IV push . Up to 70 % of people with AML will achieve a remission with this protocol . Other alternative induction regimens , including high @-@ dose cytarabine alone , FLAG @-@ like regimens or investigational agents , may also be used . Because of the toxic effects of therapy , including myelosuppression and an increased risk of infection , induction chemotherapy may not be offered to the very elderly , and the options may include less intense chemotherapy or palliative care .
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2603 The M3 subtype of AML , also known as acute promyelocytic leukemia ( APL ) , is almost universally treated with the drug all @-@ trans @-@ retinoic acid ( ATRA ) in addition to induction chemotherapy , usually an anthracycline . Care must be taken to prevent disseminated intravascular coagulation ( DIC ) , complicating the treatment of APL when the promyelocytes release the contents of their granules into the peripheral circulation . APL is eminently curable , with well @-@ documented treatment protocols .
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2604 The goal of the induction phase is to reach a complete remission . Complete remission does not mean the disease has been cured ; rather , it signifies no disease can be detected with available diagnostic methods . Complete remission is obtained in about 50 % – 75 % of newly diagnosed adults , although this may vary based on the prognostic factors described above . The length of remission depends on the prognostic features of the original leukemia . In general , all remissions will fail without additional consolidation therapy .
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2605 = = = Consolidation = = =
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2606 Even after complete remission is achieved , leukemic cells likely remain in numbers too small to be detected with current diagnostic techniques . If no further postremission or consolidation therapy is given , almost all people with AML will eventually relapse . Therefore , more therapy is necessary to eliminate nondetectable disease and prevent relapse — that is , to achieve a cure .
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2607 The specific type of postremission therapy is individualized based on a person 's prognostic factors ( see above ) and general health . For good @-@ prognosis leukemias ( i.e. inv ( 16 ) , t ( 8 ; 21 ) , and t ( 15 ; 17 ) ) , people will typically undergo an additional three to five courses of intensive chemotherapy , known as consolidation chemotherapy . For people at high risk of relapse ( e.g. those with high @-@ risk cytogenetics , underlying MDS , or therapy @-@ related AML ) , allogeneic stem cell transplantation is usually recommended if the person is able to tolerate a transplant and has a suitable donor . The best postremission therapy for intermediate @-@ risk AML ( normal cytogenetics or cytogenetic changes not falling into good @-@ risk or high @-@ risk groups ) is less clear and depends on the specific situation , including the age and overall health of the person , the person 's values , and whether a suitable stem cell donor is available .
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2608 For people who are not eligible for a stem cell transplant , immunotherapy with a combination of histamine dihydrochloride ( Ceplene ) and interleukin 2 ( Proleukin ) after the completion of consolidation has been shown to reduce the absolute relapse risk by 14 % , translating to a 50 % increase in the likelihood of maintained remission .
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2609 = = = Relapsed AML = = =
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2610 For people with relapsed AML , the only proven potentially curative therapy is a hematopoietic stem cell transplant , if one has not already been performed . In 2000 , the monoclonal antibody @-@ linked cytotoxic agent gemtuzumab ozogamicin ( Mylotarg ) was approved in the United States for people aged more than 60 years with relapsed AML who are not candidates for high @-@ dose chemotherapy . This drug was voluntarily withdrawn from the market by its manufacturer , Pfizer in 2010 .
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2611 Since treatment options for relapsed AML are so limited , palliative care or enrolment in a clinical trial may be offered .
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2612 For relapsed acute promyelocytic leukemia ( APL ) , arsenic trioxide is approved by the US FDA . Like ATRA , arsenic trioxide does not work with other subtypes of AML .
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2613 = = Prognosis = =
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2614 Acute myeloid leukemia is a curable disease ; the chance of cure for a specific person depends on a number of prognostic factors .
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2615 = = = Cytogenetics = = =
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2616 The single most important prognostic factor in AML is cytogenetics , or the chromosomal structure of the leukemic cell . Certain cytogenetic abnormalities are associated with very good outcomes ( for example , the ( 15 ; 17 ) translocation in acute promyelocytic leukemia ) . About half of people with AML have " normal " cytogenetics ; they fall into an intermediate risk group . A number of other cytogenetic abnormalities are known to associate with a poor prognosis and a high risk of relapse after treatment .
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2617 The first publication to address cytogenetics and prognosis was the MRC trial of 1998 :
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2618 Later , the Southwest Oncology Group and Eastern Cooperative Oncology Group and , later still , Cancer and Leukemia Group B published other , mostly overlapping lists of cytogenetics prognostication in leukemia .
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2619 = = = Myelodysplastic syndrome = = =
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2620 AML which arises from a pre @-@ existing myelodysplastic syndrome ( MDS ) or myeloproliferative disease ( so @-@ called secondary AML ) has a worse prognosis , as does treatment @-@ related AML arising after chemotherapy for another previous malignancy . Both of these entities are associated with a high rate of unfavorable cytogenetic abnormalities .
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2621 = = = Other prognostic markers = = =
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2622 In some studies , age > 60 years and elevated lactate dehydrogenase level were also associated with poorer outcomes . As with most forms of cancer , performance status ( i.e. the general physical condition and activity level of the person ) plays a major role in prognosis as well .
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2623 = = = = Genotype = = = =
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2624 A large number of molecular alterations are under study for their prognostic impact in AML . However , only FLT3 @-@ ITD , NPM1 , CEBPA and c @-@ KIT are currently included in validated international risk stratification schema . These are expected to increase rapidly in the near future . FLT3 internal tandem duplications ( ITDs ) have been shown to confer a poorer prognosis in AML with normal cytogenetics . Several FLT3 inhibitors have undergone clinical trials , with mixed results . Two other mutations - NPM1 and biallelic CEBPA are associated with improved outcomes , especially in people with normal cytogenetics and are used in current risk stratification algorithms .
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2625 Researchers are investigating the clinical significance of c @-@ KIT mutations in AML . These are prevalent , and potentially clinically relevant because of the availability of tyrosine kinase inhibitors , such as imatinib and sunitinib that can block the activity of c @-@ KIT pharmacologically . It is expected that additional markers ( e.g. , RUNX1 , ASXL1 , and TP53 ) that have consistently been associated with an inferior outcome will soon be included in these recommendations . The prognostic importance of other mutated genes ( e.g. , DNMT3A , IDH1 , IDH2 ) is less clear .
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2626 = = = Expectation of cure = = =
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2627 Cure rates in clinical trials have ranged from 20 – 45 % ; although clinical trials often include only younger people and those able to tolerate aggressive therapies . The overall cure rate for all people with AML ( including the elderly and those unable to tolerate aggressive therapy ) is likely lower . Cure rates for promyelocytic leukemia can be as high as 98 % .
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2628 = = Epidemiology = =
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2629 Acute myeloid leukemia is a relatively rare cancer . There are approximately 10 @,@ 500 new cases each year in the United States , and the incidence rate has remained stable from 1995 through 2005 . AML accounts for 1 @.@ 2 % of all cancer deaths in the United States .
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2630 The incidence of AML increases with age ; the median age at diagnosis is 63 years . AML accounts for about 90 % of all acute leukemias in adults , but is rare in children . The rate of therapy @-@ related AML ( that is , AML caused by previous chemotherapy ) is rising ; therapy @-@ related disease currently accounts for about 10 – 20 % of all cases of AML . AML is slightly more common in men , with a male @-@ to @-@ female ratio of 1 @.@ 3 : 1 .
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2631 There is some geographic variation in the incidence of AML . In adults , the highest rates are seen in North America , Europe , and Oceania , while adult AML is rarer in Asia and Latin America . In contrast , childhood AML is less common in North America and India than in other parts of Asia . These differences may be due to population genetics , environmental factors , or a combination of the two .
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2632 = = = UK = = =
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2633 AML accounts for 34 % of all leukaemia cases in the UK , and around 2 @,@ 900 people were diagnosed with the disease in 2011 .
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2634 = = History = =
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2635 The first published description of a case of leukemia in medical literature dates to 1827 , when French physician Alfred @-@ Armand @-@ Louis @-@ Marie Velpeau described a 63 @-@ year @-@ old florist who developed an illness characterized by fever , weakness , urinary stones , and substantial enlargement of the liver and spleen . Velpeau noted the blood of this person had a consistency " like gruel " , and speculated the appearance of the blood was due to white corpuscles . In 1845 , a series of people who died with enlarged spleens and changes in the " colors and consistencies of their blood " was reported by the Edinburgh @-@ based pathologist J.H. Bennett ; he used the term " leucocythemia " to describe this pathological condition .
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2636 The term " leukemia " was coined by Rudolf Virchow , the renowned German pathologist , in 1856 . As a pioneer in the use of the light microscope in pathology , Virchow was the first to describe the abnormal excess of white blood cells in people with the clinical syndrome described by Velpeau and Bennett . As Virchow was uncertain of the etiology of the white blood cell excess , he used the purely descriptive term " leukemia " ( Greek : " white blood " ) to refer to the condition .
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2637 Further advances in the understanding of acute myeloid leukemia occurred rapidly with the development of new technology . In 1877 , Paul Ehrlich developed a technique of staining blood films which allowed him to describe in detail normal and abnormal white blood cells . Wilhelm Ebstein introduced the term " acute leukemia " in 1889 to differentiate rapidly progressive and fatal leukemias from the more indolent chronic leukemias . The term " myeloid " was coined by Franz Ernst Christian Neumann in 1869 , as he was the first to recognize white blood cells were made in the bone marrow ( Greek : µυєλός , myelos = ( bone ) marrow ) as opposed to the spleen . The technique of bone marrow examination to diagnose leukemia was first described in 1879 by Mosler . Finally , in 1900 , the myeloblast , which is the malignant cell in AML , was characterized by Otto Naegeli , who divided the leukemias into myeloid and lymphocytic .
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2638 In 2008 , AML became the first cancer genome to be fully sequenced . DNA extracted from leukemic cells were compared to unaffected skin . The leukemic cells contained acquired mutations in several genes that had not previously been associated with the disease .
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2639 = = Pregnancy = =
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2640 Leukemia is rarely associated with pregnancy , affecting only about 1 in 10 @,@ 000 pregnant women . How it is handled depends primarily on the type of leukemia . Acute leukemias normally require prompt , aggressive treatment , despite significant risks of pregnancy loss and birth defects , especially if chemotherapy is given during the developmentally sensitive first trimester .
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2641 = Love Me Like You =
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2642 " Love Me Like You " is a song recorded by British girl group Little Mix for their third studio album , Get Weird ( 2015 ) . The song was released on 25 September 2015 , as the second single from the album . Produced by Steve Mac , he co @-@ wrote the song with Iain James , Camille Purcell and James Newman . Backed by an instrumental of pianos , bells , sax and percussion , the song is a down @-@ tempo retro homage to doo @-@ wop , with lyrics about puppy love . Its composition was compared by several critics to Motown artists of the 1950s and 1960s , namely The Ronettes , The Supremes and Shadow Morton .
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2643 Critical response to " Love Me Like You " was positive : critics praised its vintage style and highlighted it as an album standout . It reached number 11 on the UK Singles Chart and has been certified gold by the BPI . The accompanying music video for the song was set at a high school dance . Unbeknownst to each member of the group , they had been invited to attend by the same date after previously meeting him in different situations . He arrives with another girl near the end of the night , and they realise that he had all been invited by the same guy , and end up dateless . Little Mix have performed the track on both the Australian and British versions of The X Factor and on Good Morning America in the United States .
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2644 = = Background and release = =
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2645 " Love Me Like You " was written by Steve Mac , Camille Purcell , Iain James and James Newman for Little Mix 's third studio album , Get Weird ( 2015 ) . It was published by Rokstone Music Ltd. under exclusive licence to BMG Rights Management ( UK ) Ltd ; Kobalt Music Group ; Sony / ATV Music Publishing ; Black Butter Music Publishing and BMG Rights Management . The song was produced by Mac and mixed by Serban Ghenea at Mixstar Studios in Virginia Beach , Virginia . It was engineered for mixing by John Hanes and engineered by Chris Laws and Dann Pursey , and mastered by Tom Coyne and Randy Merrill at Sterling Sound Studios in New York . The track was recorded at Rokstone Studios in London . Purcell also provided background vocals . The keyboards were performed by Mac , and the guitars were played by Paul Gendler . Laws and Pursey performed the drums and the percussion , respectively .
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2646 The group announced on 9 September 2015 that " Love Me Like You " would be the second single to be released from the album , and that it would be made available to pre @-@ order on 11 September , and be released on 25 September . It was released by Syco and Columbia in Ireland and the United Kingdom on 25 September 2015 . The single 's artwork was released on the same day . In their review , MTV News joked that the group were suggesting that it would be number @-@ one due to each of the band members eyeline , writing " We can 't help but get the hint they 're on the hunt for ANOTHER chart topping trophy . Leigh @-@ Anne clearly thinks she can see it in the distance , Jesy is just imagining it with her brain , Jade definitely thinks she can hear the noise of records being sold and Perrie is convinced it 's on the floor . " M magazine writer Heather Thompson described the artwork as " vibrant " . A collection of alternate versions called " Love Me Like You ( The Collection ) " was also released in Australia and New Zealand in addition to Ireland and the United Kingdom on 16 October 2015 . It consists of a Christmas mix , several remixes and an instrumental version of " Love Me Like You " and another album track called " Lightning " .
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2647 = = Composition = =
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2648 " Love Me Like You " has been described as a down @-@ tempo " ode to ' 60s doo @-@ wop " retro style pop song , which lasts for a duration of three minutes , seventeen seconds . The song is composed in the key of G major using common time and a tempo of 106 beats per minute . Instrumentation is provided by " vintage " pianos , bells and a " pumping " tenor sax . The use of percussion gives the a track a more modern style . During the track , the band members vocal range spans one octave , from the low note of D4 to the high note of E5 .
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2649 The song opens with the group harmonising " Sha la la la " over pianos . The lyrics are about puppy love , as they yearningly sing " Last night I lay in bed so blue / Cause ' I realized the truth / They can 't love me like you / I tried to find somebody new / Baby they ain 't got a clue / Can 't love me like you . " Fuse writer Jeff Benjamin described the song as being reminiscent of 1960s girl group The Ronettes but with a more modern feel for 2015 radio , highlighting the line " They try to romance me but you got that nasty and that 's what I want " as an example . Digital Spy writer Lewis Corner thought that the line " He might got the biggest ca @-@ aa @-@ ar " does not fool listeners into thinking that " they 're not actually talking about his Fiat 500 . " Several music critics compared the song to recordings from the Motown era in the 1950s and 1960s , with Andy Gill of The Independent likening it to material composed by Shadow Morton . Emilee Lindner of MTV News likened the production to material composed by Phil Spector . The Christmas mix version features added church bells and jingles .
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