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{{Penyangkalan-medis}}
'''Leukemia''' merujuk kepada satu kelompok penyakit [[darah]] yang ditandai dengan [[kanker]] pada jaringan-jaringan yang memproduksi darah. Leukemia adalah kanker yang paling banyak menimpa kanak-kanak di negara industri. Di [[Britania Raya]], satu dari 2000 kanak-kanak menderita penyakit ini.
{{terjemah|Inggris}}
{{Infobox Penyakit |
Name = Leukemia |
ICD10 = {{ICD10|C|91||c|81}}-{{ICD10|C|95||c|81}} |
ICD9 = {{ICD9|208.9}} |
ICDO = 9800-9940 |
Image = acute_leukemia-ALL.jpg |
Caption = Sediaan sumsum tulang dengan pewarnaan Wright. Sediaan menunjukkan leukemia limfoblastik akut prekursor sel-B.|
MedlinePlus = |
eMedicineSubj = |
eMedicineTopic = |
DiseasesDB = 7431 |
}}
'''Leukemia'''; dalam bahasa Yunani leukos ''[[wikt:λευκός|λευκός]]'', "putih"; aima ''[[wikt:αίμα|αίμα]]'', "darah"), atau lebih dikenal sebagai '''kanker darah''' merupakan penyakit dalam klasifikasi [[kanker]] (istilah medis: [[neoplasma]]) pada [[darah]] atau [[sumsum tulang]] yang ditandai oleh perbanyakan secara tak normal atau transformasi maligna dari sel-sel pembentuk darah di [[sumsum tulang]] dan [[jaringan limfoid]], umumnya terjadi pada leukosit ([[sel darah putih]]).<ref name=sumber>{{cite book
|title=Neoplasma Sistem Hematopoietik: Leukemia
|author=Simon, Sumanto, dr. Sp.PK
|publisher=Fakultas Kedokteran Unika Atma Jaya Jakarta
|year=2003}}</ref> [[Sel|Sel-sel]] normal di dalam sumsum tulang digantikan oleh sel tak normal atau abnormal. Sel abnormal ini keluar dari sumsum dan dapat ditemukan di dalam darah perifer atau darah tepi. Sel leukemia memengaruhi hematopoiesis atau proses pembentukan sel darah normal dan imunitas tubuh penderita.
 
Kata ''leukemia'' berarti [[darah putih]], karena pada penderita ditemukan banyak sel darah putih sebelum diberi terapi. Sel darah putih yang tampak banyak merupakan [[sel]] yang muda, misalnya [[promielosit]]. Jumlah yang makin meninggi ini dapat mengganggu fungsi normal dari sel lainnya.
Pada [[abad ke-19]], leukemia dilihat sebagai satu penyakit mematikan tunggal yang homogen, ditandai oleh penampakan sampel darah yang putih ('''leuko-'''). Namun dengan berkembangnya pemahaman proses patologi dan cytologi, dokter sekarang mampu mengenali penyakit berbeda yang banyak yang membutuhkan perawatan yang berbeda.
 
Pada tahun 2000, terdapat sekitar 256.000 anak dan dewasa di seluruh dunia menderita penyakit sejenis leukemia, dan 209.000 orang di antaranya meninggal karena penyakit tersebut.<ref name=Jumlah>{{cite journal
<!--
|title=Cancer incidence, mortality and survival by site for 14 regions of the world.
==Overview==
|author=Mathers, Colin D, Cynthia Boschi-Pinto, Alan D Lopez and Christopher JL Murray
Leukemia, first recognised by the [[Germany|German]] [[pathologist]] [[Rudolf Virchow]] in [[1847]], with the first case described by [[England|British]] pathologist [[John Hughes Bennett]] in [[1845]], starts when [[bone marrow]] cells multiply abnormally. This is caused by [[mutation]]s in the [[DNA]] in [[stem cell]]s. Bone marrow stem cells produce billions of [[red blood cell]]s and [[white blood cell]]s each day, respectively carrying [[oxygen]] and fighting [[infection]] throughout the body. Leukemia is characterised by an excessive production of abnormal white blood cells, overcrowding the bone marrow and often spilling out into the peripheral blood. The infiltration of the bone marrow results in decreased production and function of normal blood cells. Leukemia, dependent on the type, can spread to the [[lymph node]]s, [[spleen]], [[liver]], [[central nervous system]] and other [[organ (anatomy)|organ]]s or tissues.
|work=Global Programme on Evidence for Health Policy Discussion Paper No. 13
|publisher=World Health Organization
|year=2001
|url=http://www.who.int/entity/healthinfo/paper13.pdf}}</ref> Hampir 90% dari semua penderita yang terdiagnosis adalah dewasa.<ref name=LLS>[http://www.leukemia-lymphoma.org/all_page?item_id=9346 "Leukemia Facts & Statistics."] The Leukemia & Lymphoma Society. Retrieved 2009-07-02.</ref>
 
==Symptoms Klasifikasi ==
Leukemia dapat diklasifikasikan atas dasar:
Damage to the bone marrow results in a lack of blood [[platelet]]s, which are important in the [[coagulation|blood clotting]] process. This means people with leukemia may become [[purpura|bruised]], [[hemorrhage|bleed]] excessively, or develop pinprick bleeds ([[petechia|petechiae]]).
 
=== Perjalanan alamiah penyakit: akut dan kronis ===
White blood cells, which are involved in fighting pathogens, may be suppressed or dysfunctional, putting the patient at risk of [[infection]].
Leukemia akut ditandai dengan suatu perjalanan penyakit yang sangat cepat, mematikan, dan memburuk. Apabila tidak diobati segera, maka penderita dapat meninggal dalam hitungan minggu hingga hari. Sedangkan leukemia kronis memiliki perjalanan penyakit yang tidak begitu cepat sehingga memiliki harapan hidup yang lebih lama, hingga lebih dari 1 tahun bahkan ada yang mencapai 5 tahun.
 
=== Tipe sel predominan yang terlibat: limfoid dan mieloid ===
Finally, the red blood cell deficiency leads to [[anemia]], which may cause [[dyspnea|shortness of breath]] and [[Fatigue (physical)|fatigue]]. [[Bone]] or [[joint]] [[pain]] may occur because of cancer spreading to these areas. [[Headache]]s and [[vomiting]] are indicative of the cancer having disseminated to the [[central nervous system]].
Kemudian, penyakit diklasifikasikan dengan jenis sel yang ditemukan pada sediaan darah tepi.
* Ketika leukemia memengaruhi [[limfosit]] atau sel limfoid, maka disebut [[leukemia limfositik]].
* Ketika leukemia memengaruhi sel mieloid seperti [[neutrofil]], [[basofil]], dan [[eosinofil]], maka disebut [[leukemia mielositik]].
 
=== Jumlah leukosit dalam darah ===
Enlarged [[lymph nodes]] or [[splenomegaly]] (an enlarged [[spleen]]) may occur in some types. All [[symptoms]] may also be attributable to other diseases; for [[diagnosis]], [[blood test]]s and a [[bone marrow biopsy]] are required.
* Leukemia leukemik, bila jumlah leukosit di dalam darah lebih dari normal, terdapat sel-sel abnormal
* Leukemia subleukemik, bila jumlah leukosit di dalam darah kurang dari normal, terdapat sel-sel abnormal
* Leukemia aleukemik, bila jumlah leukosit di dalam darah kurang dari normal, tidak terdapat sel-sel abnormal
 
=== Prevalensi empat tipe utama ===
Some other related symptoms:
Dengan mengombinasikan dua klasifikasi pertama, maka leukemia dapat dibagi menjadi:
* [[Fever]], chills, and other flu-like symptoms;
* [[Leukemia limfositik akut]] (LLA) merupakan tipe leukemia paling sering terjadi pada anak-anak. Penyakit ini juga terdapat pada dewasa yang terutama telah berumur 65 tahun atau lebih
* Weakness and fatigue;
* [[Leukemia mielositik akut]] (LMA) lebih sering terjadi pada dewasa daripada anak-anak. Tipe ini dahulunya disebut leukemia nonlimfositik akut.
* Loss of [[appetite]] and/or weight;
* [[Leukemia limfositik kronis]] (LLK) sering diderita oleh orang dewasa yang berumur lebih dari 55 tahun. Kadang-kadang juga diderita oleh dewasa muda, dan hampir tidak ada pada anak-anak
* Swollen or bleeding gums;
* [[Leukemia mielositik kronis]] (LMK) sering terjadi pada orang dewasa. Dapat juga terjadi pada anak-anak, tetapi sangat sedikit
* [[Sleep hyperhidrosis|Sweating, especially at night]];
* Bone or joint pain.
* Neurological symptoms ([[headache]], [[paralysis]], [[seizure]]s) due to involvement of the brain (acute leukemias)
* Swelling of the testicle(s) and cause swelling.
* Skin symptoms
-->
== Jenis utama ==
Leukemia boleh dibahagikan secara klinikal dan patologikal kepada bentuk ''akut'' (mendadak) dan ''kronik'' (teruk):
* Leukemia akut: penghasilan pesat sel darah muda. Ini menyebabkan tulang sumsum gagal menghasilkan sel darah dewasa. Boleh terjadi pada kanak-kanak dan orang muda. Jika tidak dirawat segera, pesakit boleh meninggal dalam masa beberapa bulan ataupun minggu.
* Leukemia kronik: penghasilan banyak sel darah dewasa yamg tak normal. Biasanya mengambil masa beberapa bulan hingga tahun. Biasanya terjadi pada orang tua, tapi tidak mustahil pada orang muda. Selalunya diawasi untuk suatu tempoh sebelum dirawat untuk keberkesanan rawatan yang maksimum.
 
Tipe yang sering diderita orang dewasa adalah LMA dan LLK, sedangkan LLA sering terjadi pada anak-anak.
Leukemia juga boleh dikelaskan mengikut jenis sel tak normal yang paling banyak dijumpai dalam darah:
* Jika sel limfoid yang dijangkiti, ia dipanggil "leukemia limfosit".
* Jika sel mieloid yang dijangkiti, ia dipanggil "leukemia mielogenus".
 
== Patogenesis ==
Jika dua jenis kategori ini digabungkan, terdapat empat jenis utama leukemia:
Leukemia akut dan kronis merupakan suatu bentuk keganasan atau maligna yang muncul dari perbanyakan klonal sel-sel pembentuk [[sel]] darah yang tidak terkontrol. Mekanisme kontrol seluler normal mungkin tidak bekerja dengan baik akibat adanya perubahan pada kode [[genetika|genetik]] yang seharusnya bertanggung jawab atas pengaturan pertubuhan sel dan diferensiasi.
* [[Leukemia limfosit akut]] (ALL), paling biasa menjangkiti kanak-kanak.
* [[Leukemia mielogenus akut]] (AML), lebih biasa berlaku pada orang dewasa berbanding kanak-kanak.
* [[Leukemia limfosit kronik]] (CLL), biasanya menjangkiti orang tua > 55 tahun, boleh juga menjangkiti orang muda.
* [[Leukemia mielogenus kronik]] (CML), biasanya menjangkiti orang dewasa. Jenis paling jarang berlaku.
 
Sel-sel leukemia menjalani waktu daur ulang yang lebih lambat dibandingkan sel normal. Proses pematangan atau maturasi berjalan tidak lengkap dan lambat dan bertahan hidup lebih lama dibandingkan sel sejenis yang normal.
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==Causes==
All leukemias are due to [[mutation]]s in the [[DNA]]. [[Chromosomal translocation]]s (crossing over of parts of [[chromosome]]s to others) are common, disrupting specific [[gene]]s that mediate cell division rate. Mutations may occur spontaneously or as a result of exposure to [[radiation]] or [[carcinogen|carcinogenic]] substances. [[Cytogenetics]] and [[immunophenotyping]] are two laboratory investigations used to determine the type and aggressiveness of the leukemia and the necessity of urgent and active treatment, as well as an indication of prognosis.
 
== Etiologi ==
[[virus (biology)|Viruses]] have also been linked, with varying levels of speculation, to some forms of leukemia. Some forms of [[T-cell leukemia]] have recently been confirmed to be the result of two viruses. (See [[adult T-cell leukemia/lymphoma]]).
Penyebab leukemia belum diketahui secara pasti, tetapi diketahui beberapa faktor yang dapat memengaruhi frekuensi leukemia, seperti:
 
===Radiation Radiasi ===
[[Radiasi]] dapat meningkatkan frekuensi LMA dan LMA. Tidak ada laporan mengenai hubungan antara radiasi dengan LLK. Beberapa laporan yang mendukung:
In the early [[1990s]] concern was raised in the UK about the effect of [[nuclear power plant]]s on unborn children, when [[cancer cluster|clusters of leukemia cases]] were discovered nearby to some of these plants. The effect was speculative because clusters were also found where no nuclear plants were present, and not all plants had clusters around them. Using statistical analysis, researchers at [[Southampton University]] concluded that a link was present, deducing that radiation damage to men working at the plants had caused genetic abnormalities in their children. After this report [[British Nuclear Fuels]] initially advised workers who were being exposed to high levels of [[radiation]] not to father children, although they have since withdrawn this advice.
* Para pegawai radiologi lebih sering menderita leukemia
* Penderita dengan radioterapi lebih sering menderita leukemia
* Leukemia ditemukan pada korban hidup kejadian [[bom atom]] [[Hiroshima]] dan [[Nagasaki]], [[Jepang]]
 
===Immune systemFaktor leukemogenik ===
Terdapat beberapa zat [[kimia]] yang telah diidentifikasi dapat memengaruhi frekuensi leukemia:
In April 2005 the UK Childhood Cancer Study (UKCCS), a 15-year study tracking 11,000 children, including 1700 with leukemia, found problems relating to the immune system as a primary cause. In particular, around one in 20 children are born with slight genetic abnormalities which predispose them to leukemia, which appears to be triggered by an exaggerated immune response to infections. The study concluded that a significant factor in these exaggerated responses is children having a history of low exposure to infection - because the immune system was insufficiently trained in dealing with infection. The study found that increased levels of social activity outside the home reduced the risk of leukaemia, with the cut in risk greatest in children who attended formal daycare during their first three months of life. [http://www.newscientist.com/article.ns?id=dn7301]
* Racun lingkungan seperti [[benzena]]
* Bahan kimia industri seperti [[insektisida]]
* Obat untuk [[kemoterapi]]
 
=== Epidemiologi ===
===Electromagnetic fields===
* Di [[Afrika]], 10–20% penderita LMA memiliki kloroma di sekitar [[orbita]] [[mata]]
The UK Childhood Cancer Study (UKCCS) (see above) found no association between electromagnetic fields and the risk of childhood leukaemia [http://www.newscientist.com/article.ns?id=dn7301].
* Di [[Kenya]], [[Tiongkok]], dan [[India]], LMK mengenai penderita berumur 20–40 tahun
A large [[2005]] [[Oxford University]]
* Pada orang [[Asia Timur]] dan [[India]] Timur jarang ditemui LLK.
[http://bmj.bmjjournals.com/cgi/content/full/330/7503/1290?ehom study]
did find a statistically significant elevation of childhood leukaemia rates (relative risk 1.7) within 200 m of high-voltage [[Electric power transmission|overhead power lines]] (132 to 400 [[kilovolt|kV]]),
though the authors do not regard this as establishing a definite causal association
[http://www.hpa.org.uk/hpa/news/articles/press_releases/2005/050603_childhood_cancer_voltage.htm].
A pooled analysis of case-control studies found that children living in homes with high magnetic fields (> 0.4 [[Tesla (unit)|µT]]) had twice the risk of childhood leukaemia.
Further research is needed, but a fair current assessment would be that electromagnetic fields produced by the electric power system are "possibly carcinogenic".
-->
 
=== PerawatanHerediter ===
Penderita [[sindrom Down|sindrom down]] memiliki insidensi leukemia akut 20 kali lebih besar dari orang normal.
Perawatan umum dari leukemia adalah [[kemoterapi]], kadangkala dengan penambahan [[terapi radiasi]].
 
=== Virus ===
Bila kasusnya parah, [[transplantasi sumsum tulang]] kadangkala dibutuhkan. Tulang marrow yang sehat bila ditransplantasi di badan membantu membangun [[jaringan biologis|jaringan]] yang rusak oleh perawatan. Kesuksesan dari transplantasi sumsum tulang membutuhkan pemasangan tepat dari karakteristik darah. Hanya 20% pasien leukemia memiliki donor saudara kandung yang cocok. Dari mereka yang tidak mendapatkan yang cocok dari saudara, kurang dari sepertiga dapat menemukan pasangan yang cocok dari orang lain.
[[Virus]] dapat menyebabkan leukemia seperti [[retrovirus]], virus leukemia feline, HTLV-1 pada [[dewasa]].
 
== Penyembuhan ==
Sebuah alternatif dari transplantasi sumsum tulang adalah transplantasi [[darah tali pusat]] dengan menggunakan sel dari [[tali pusat]] untuk menggantikan sel yang rusak oleh terapi leukemia. Proses darah tali pusat mempunyai kelebihan dibandingkan dengan transplantasi sumsum tulang karena sel-sel darah tali pusat belum diprogram untuk meneyrang jaringan asing. Proses ini telah berahsil digunakan di antara anak-anak. Potensi keberhasilan di antara orang dewasa tidak begitu pasti karena sebuah tali pusat hanya mengandung sepersepuluh jumlah sel yang biasanya dipasok oleh transplantasi sumsum yang biasa.
Sebagian besar bentuk leukemia diobati dengan obat farmasi, biasanya digabungkan ke dalam sejenis kemoterapi obat-obatan multi. Bisa juga diobati dengan terapi radiasi. Dalam beberapa kasus, pencangkokan sumsum tulang juga dapat menyembuhkan leukemia. Bunga dan daun [[tapak dara]] juga berpotensi menjadi sumber obat untuk leukemia.
 
== Pengobatan kanker darah ==
Berdasarkan hasil penelitian Dr. M. Ahkam Subroto, tanaman sarang semut mengandung berbagai jenis zat aktif seperti [[flavonoid]], [[tanin]], dan zat lain yang sangat penting bagi tubuh. Kandungan zat flavonoid-nya dipercaya sebagai zat anti-kanker yang mampu melawan sel kanker terutama sel kanker darah sehingga sangat cocok dijadikan sebagai obat tradisional kanker darah.
 
Zat flavonoid sendiri memiliki kemampuan untuk menonaktifkan zat [[karsinogen]] atau zat penyebab kanker. Perkembangan zat karsinogen tersebut akan dihambat sehingga tidak akan menumbuhkan sel-sel yang abnormal. Kemudian, sel abnormal dalam tubuh dicegah supaya tidak bisa membelah diri. Dengan demikian, sel kanker tidak akan menyebar ke berbagai jaringan dan organ lain di dalam tubuh penderita. Ini merupakan obat tradisional kanker darah yang sangat ampuh untuk mengendalikan laju pembelahan sel-sel kanker di dalam tubuh.
 
Selain flavonoid, terdapat zat lain bernama tokoferol yang mirip dengan vitamin E dan sangat berguna dalam penyembuhan kanker darah. Zat ini sangat efektif untuk menangkap radikal-radikal bebas yang menjadi penyebab kanker.
 
Sarang semut sebagai obat tradisional kanker darah bisa menjadi alternatif bagi Anda yang tidak ingin menjalani pengobatan [[kemoterapi]]. Zat-zat yang terkandung dalam sarang semut secara aktif akan membunuh sel-sel kanker dalam tubuh. Para ahli juga menyarankan kepada para penderita kanker darah untuk mengonsumsi tanaman ini secara rutin. Menurut beberapa ahli, pasien yang mengonsumsi sarang semut menunjukkan kemajuan dalam proses penyembuhan dalam waktu beberapa minggu. Bahkan ada di antara mereka yang kondisinya membaik hanya dalam beberapa hari saja setelah mengonsumsi obat tersebut.
 
== Leukemia akut ==
=== Manifestasi klinik ===
Manifestasi leukemia akut merupakan akibat dari [[komplikasi]] yang terjadi pada neoplasma hematopoetik secara umum. Namun setiap leukemia akut memiliki ciri khasnya masing-masing. Secara garis besar, leukemia akut memiliki 3 tanda utama yaitu:
* Jumlah sel di perifer yang sangat tinggi, sehingga menyebabkan terjadinya infiltrasi jaringan atau [[leukostasis]]
* Penggantian elemen sumsum tulang normal yang dapat menghasilkan komplikasi sebagai akibat dari [[anemia]], [[trombositopenia]], dan [[leukopenia]]
* Pengeluaran faktor faali yang mengakibatkan [[komplikasi]] yang signifikan
 
=== Alat diagnosis ===
Leukemia akut dapat di[[diagnosis]] melalui beberapa alat, seperti:
* Pemeriksaan fisik, melihat adanya tanda anemia, pembengkakan kelenjar getah bening, dan pembesaran hati serta limpa.
* Tes darah, mengetahui kadar trombisit yang tidak normal.
* Tes sumsum tulang, mengambil sampel dari sumsum tulang untuk mendeteksi adanya sel-sel leukemia.<ref name="Informasi Kesehatan">{{Cite web|url=https://doktersehat.com/leukemia-1/|website=www.doktersehat.com|title=Leukemia: Penyebab, Gejala, Diagnosis dan Pengobatan|language=id|access-date=2020-07-15|archive-date=2020-07-15|archive-url=https://web.archive.org/web/20200715135658/https://doktersehat.com/leukemia-1/|dead-url=yes}}</ref>
 
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== Treatment options for leukemia by type ==
In addition, cord blood is slower to develop into a full complement of blood cells. However, mismatched cord transplants are less likely to trigger acute [[graft-versus-host disease]] than mismatched bone marrow would.
==='''Acute Myelogenous Leukemia (AML)'''===
It is most common for adults, but more men than women are affected.
Many different chemotherapeutic plans are available for the treatment of AML. Overall, the strategy is to control bone marrow and systemic (whole-body) disease while offering specific treatment for the central nervous system (CNS), if involved. In general, most oncologists rely on combinations of drugs for the initial, induction phase of chemotherapy. Such combination chemotherapy usually offers the benefits of early remission (lessening of the disease) and a lower risk of disease resistance. Consolidation or "maintenance" treatments may be given to prevent disease recurrence once remission has been achieved. Consolidation treatment often entails a repetition of induction chemotherapy or the intensification chemotherapy with added drugs. By contrast, maintenance treatment involves drug doses that are lower than those administered during the induction phase.
 
In addition, specific treatment plans may be used, depending on the type of leukemia that has been diagnosed. Whatever the plan, it is important for the patient to understand the treatment that is being given and the decision-making process behind the choice.
 
===='''Initial treatment of AML'''====
Initial treatment of AML usually begins with induction chemotherapy using a combination of drugs such as [[daunorubicin]] ([[DNR]]), [[cytarabine]] ([[ara-C]]), [[idarubicin]], [[thioguanine]], [[etoposide]], or [[mitoxantrone]], anabolic [[steroids]].
 
===='''Follow-up treatment'''====
Follow-up therapy for such patients may involve:
 
* supportive care, such as intravenous nutrition and treatment with oral antibiotics (e.g., ofloxacin, rifampin), especially in patients who have prolonged granulocytopenia; that is too few mature granulocytes (neutrophils), the bacteria-destroying white blood cells that contain small particles, or granules (< 100 granulocytes per cubic millimeter for 2 weeks)
* injection with colony-stimulating factors such as granulocyte colony-stimulating factor (G-CSF), which may help to shorten the period of granulocytopenia that results from induction therapy
* transfusions with red blood cells and platelets
 
Patients with newly diagnosed disease also may be considered for stem cell transplantation (SCT), either from the bone marrow or other sources. Allogeneic bone marrow transplant (alloBMT) is reserved primarily for patients under 55 years of age who have a compatible family donor. Approximately half of newly diagnosed AML patients are in this age group, with 75% achieving a complete remission (CR) after induction and consolidation therapy. Allogeneic bone marrow transplant is available for about 15% of all patients with AML. Unfortunately, it is estimated that only 7% of all AML patients will be cured using this procedure.
 
People who receive stem cell transplantation (SCT, alloBMT) require protective isolation in the hospital, including filtered air, sterile food, and sterilization of the microorganisms in the gut, until their total white blood cell (WBC) count is above 500.
 
Treatment of central nervous system leukemia, if present, may involve injection of chemotherapeutic drugs (e.g., cytarabine or ara-C, methotrexate) into the areas around the brain and spinal cord.
 
====Consolidation or maintenance therapy====
Once the patient is in remission, he or she will receive consolidation or maintenance therapy, for example, consolidation therapy with high-dose ara-C (HDAC) with/without anthracycline drugs).
 
If, however, the AML patient has resistant disease (about 15%) or relapses (about 70%), second remissions sometimes are achieved by treating them with:
 
* conventional induction chemotherapy
* high-dose ara-C (HDAC), with/without other drugs
* etoposide or other single chemotherapeutic agents
 
Elderly AML patients have special treatment concerns. They may be less able to tolerate the septicemia (blood poisoning) associated with granulocytopenia, and they often have higher rates of myelodysplastic ('preleukemia') syndrome (MDS). Individuals who are over age 75 or who have significant medical conditions can be treated effectively with low-dose ara-C. High-dose post-induction chemotherapy is unlikely to be tolerated by elderly patients.
 
Until recently, the treatment plans and responses of children with AML did not differ much from those of adults. Yet new, more intensive induction and consolidation treatments have resulted in higher remission rates and prolonged survivals. Many induction trials have produced good results using combinations of cytarabine (ara-C) plus an anthracycline (e.g., daunorubicin, doxorubicin). In children under 3 years of age, the anthracycline used for induction should be chosen with care, since doxorubicin produces more toxicity and related deaths than daunorubicin.
 
Consolidation therapy is complex, but it should include at least two courses of high-dose ara-C (HDAC). Children who have hyperleukocytosis (too many white blood cells), especially monocytic M5 leukemia, have a poor prognosis.
 
===Chronic Myelogenous Leukemia (CML)===
The challenge of treating newly diagnosed CML is to determine the best overall strategy to control the disease. General strategies for management include a variety of options:
 
'''Leukapheresis''', also known as a peripheral blood stem cell transplant, with stem cell cryopreservation (frozen storage) prior to any other treatment. The patient's blood is passed through a machine that removes the stem cells and then returns the blood to the patient. Leukapheresis usually takes 3 or 4 hours to complete. The stem cells may or may not be treated with drugs to kill any cancer cells. The stem cells then are stored until they are transplanted back into the patient.
 
'''HLA (human leukocyte antigen) typing''' of all patients under age 60, as well as typing of siblings, parents, and children, if available. This procedure will determine whether a compatible donor is available for stem cell transplantation.
 
'''Pre-treatment fertility measures''' (e.g., cryopreservation of semen prior to treatment; completion of a pregnancy prior to treatment) in young patients who have not completed their families.
 
''Interferon-alpha (INF-a) therapy'''.
 
'''Chemotherapy''' with drugs such as hydroxyurea (Hydrea®), busulfan (Myleran®) or imatinib mesylate (Gleevec(tm)).
 
In general, CML treatment options are divided into two groups: those that do not increase survival and those that do. Chemotherapeutic drugs such as hydroxyurea (Hydrea®) and busulfan (Myleran®) can normalize the blood count for a period of time, but they do not increase survival. They often are used to control blood counts in patients who cannot undergo SCT or who do not respond to interferon therapy because of age or medical considerations.
 
Gleevec, is one of a new class of cancer drugs that disables an abnormal enzyme in the cancerous cell, kills it, but leaves healthy cells virtually untouched. Other cancer therapies, such as chemotherapy, attack healthy cells as well as cancer cells, leaving patients with unpleasant and often severe side effects.
 
In June of 2006, the Food and Drug Administration (FDA) approved the oral tyrosine kinase inhibitor dasatinib (Sprycel(tm)) to treat CML that does not respond to other therapy.
 
One treatment that does impact on CML survival is allogeneic bone marrow transplantation, the use of high dose chemotherapy and radiation followed by infusion of a donor bone marrow. This procedure removes the chromosomal abnormality in a large percentage of patients and for them is curative. In addition, there is treatment with interferon (INF). About 20% to 30% of patients taking interferon show elimination of the abnormal chromosome and improved survival. Recent findings also suggest that low-dose cytarabine (ara-C), in combination with interferon, may be more beneficial than interferon alone. For patients who do not respond to interferon, autologous or allogeneic stem cell transplantation is the only alternative.
 
Patients with advanced-phase disease may be treated with cytotoxic drugs. For example, individuals showing myeloid transformation may be given drugs that are used to induce remission in AML - that is, daunorubicin and cytarabine, with or without 6-thioguanine or etoposide. Blast cell numbers will be reduced temporarily, but they will increase again within 3 to 6 weeks. Individuals showing lymphoid transformation have a slightly better outlook. They are treated with drugs used in the management of acute lymphocytic leukemia (ALL) - that is, prednisone, vincristine, and daunorubicin, with or without L-asparaginase.
 
New drugs that are being studied in clinical trials of CML include homoherringtonine with interferon-alpha (INF-a), paclitaxel (Taxol®), QS21 (a plant extract that heightens immune responses), and amifostin (a chemical that lessens some side effects of chemotherapy). In addition, clinical trials are evaluating the potential benefits of substances such as vaccines, monoclonal antibodies (immunologic substances that can direct the patient's immune system to kill cancer cells), and hormones (e.g., growth factors, interleukins).
 
===Acute Lymphocytic Leukemia (ALL)===
Proper management of ALL focuses on control of bone marrow and systemic (whole-body) disease as well as prevention of cancer at other sites, particularly the central nervous system (CNS). In general, ALL treatment is divided into several phases:
 
'''Induction chemotherapy''' to bring about remission - that is, leukemic cells are no longer found in bone marrow samples. For adult ALL, standard induction plans include prednisone, vincristine, and an anthracycline drug; other drug plans may include L-asparaginase or cyclophosphamide. For children with low-risk ALL, standard therapy usually consists of three drugs (prednisone, L-asparaginase, and vincristine) for the first month of treatment. High-risk children may receive these drugs plus an anthracycline such as daunorubicin.
 
'''Consolidation therapy''' (1-3 months in adults; 4-8 months in children) to eliminate any leukemia cells that are still "hiding" within the body. A combination of chemotherapeutic drugs is used to keep the remaining leukemia cells from developing resistance. Patients with low- to average-risk ALL receive therapy with antimetabolite drugs such as methotrexate and 6-mercaptopurine (6-MP). High-risk patients receive higher drug doses plus treatment with extra chemotherapeutic agents.
 
'''CNS prophylaxis''' (preventive therapy) to stop the cancer from spreading to the brain and nervous system. Standard prophylaxis may consist of:
# Cranial (head) irradiation plus spinal tap or intrathecal (IT) delivery (into the space around the spinal cord and brain) of the drug methotrexate.
# High-dose systemic and IT methotrexate, without cranial irradiation
# IT chemotherapy.
Only children with T-cell leukemia, a high white blood cell count, or leukemia cells in the cerebrospinal fluid (CSF) need to receive cranial irradiation as well as IT therapy.
 
'''Maintenance treatments''' with chemotherapeutic drugs (e.g., prednisone + vincristine + cyclophosphamide + doxorubicin; methotrexate + 6-MP) to prevent disease recurrence once remission has been achieved. Maintenance therapy usually involves drug doses that are lower than those administered during the induction phase. In children, an intensive 6-month treatment program is needed after induction, followed by 2 years of maintenance chemotherapy.
 
'''Follow-up therapy''' for ALL patients usually consists of:
* supportive care, such as intravenous nutrition and treatment with oral antibiotics (e.g., ofloxacin, rifampin), especially in patients with prolonged granulocytopenia; that is, too few mature granulocytes (neutrophils), the bacteria-destroying white blood cells that contain small particles, or granules (< 100 granulocytes per cubic millimeter for 2 weeks)
* transfusions with red blood cells and platelets
 
A laboratory test known as [[polymerase chain reaction]] (PCR) is advisable for ALL patients, since it may help to identify specific genetic abnormalities. Such abnormalities have a large impact upon prognosis and, consequently, treatment plans. PCR testing is especially important for patients whose disease is B-cell in type. B-cell ALL usually is not cured by standard ALL therapy. Instead, higher response rates are achieved with the aggressive, cyclophosphamide-based regimens that are used for non-Hodgkin's lymphoma.
 
Among ALL patients, 3-5% children and 25-50% of adults are positive for the Philadelphia chromosome (Ph1){{Fact|date=February 2007}}. Because these patients have a worse prognosis than other individuals with ALL, many oncologists recommend allogeneic bone marrow transplantation (alloBMT), since remission may be brief following conventional ALL chemotherapy.
 
People who receive bone marrow transplantation will require protective isolation in the hospital, including filtered air, sterile food, and sterilization of the microorganisms in the gut, until their total white blood cell (WBC) count is above 500.
 
Recurrent ALL patients usually do not benefit from additional chemotherapy alone. If possible, they should receive re-induction chemotherapy, followed by allogeneic bone marrow transplant (alloBMT).
 
Alternatively, patients with recurrent ALL may benefit from participation in new clinical trials of alloBMT, immune system agents, and chemotherapeutic agents, or low-dose radiotherapy, if the cancer recurs throughout the body or CNS.
 
===Chronic Lymphocytic Leukemia (CLL)===
The unpleasant truth is that CLL is probably "incurable" by present treatments. But, fortunately, a large group of CLL patients do not require therapy. Studies suggest that people with Stage A CLL (that is, individuals who have fewer than three areas of enlarged lymphoid tissue) do not benefit from early treatment. They may, in fact, suffer drawbacks because of it. Therefore, most oncologists base CLL treatment upon both the stage and symptoms of the patient.
 
For example, in older patients (60+ years) who have low-risk early stage disease (Rai Stage 0) a conservative "watch and wait" approach may be taken.
 
By contrast, older individuals with CLL-related complications or more advanced disease (Rai Stage III or IV) may benefit from chemotherapy and treatment with a corticosteroid (e.g., prednisone, prednisolone).
 
Corticosteroids are first-line agents for people in whom the immune systems has been altered by CLL. CLL may cause autoimmune syndromes in which the patient's immune system attacks and destroys his or her own blood cells. When the red blood cells are affected, the condition is known as immunohemolytic anemia, characterized by decreased numbers of red blood cells, which may cause fatigue, dizziness, and shortness of breath. When the blood platelets are affected, it is called immune-mediated thrombocytopenia, in which a decreased numbers of platelets may lead to bleeding.
 
For younger patients who are experiencing symptoms, the physician may consider early chemotherapy, plus allogeneic or autologous bone marrow transplantation (alloBMT; autoBMT).
 
In general, the indications for treatment are:
 
* falling hemoglobin or platelet count
* progression to a later stage of disease
* painful, disease-related overgrowth of lymph nodes or spleen
* lymphocyte doubling time (an indicator of lymphocyte reproduction) of fewer than 12 months
 
====Transformation of CLL to high-grade disease or aggressive non-Hodgkin's lymphoma====
If the patient experiences blood flow problems caused by high numbers of leukemia cells in the circulation, the physician may recommend leukapheresis, also known as apheresis, to separate out white blood cells, prior to chemotherapy.
Symptoms that are related to enlargement of the lymph nodes in one area or an overgrown spleen may be treated by localized, low-dose radiotherapy, or surgical management by splenectomy (removal of the spleen). But if leukemia has invaded the lymph nodes at many different sites, total body irradiation (TBI) may be needed.
 
====Chemotherapy for CLL====
The chemotherapeutic plans that are used most often for CLL are:
 
* combination chemotherapy with chlorambucil (Leukeran®) or cyclophosphamide (Cytoxan®) plus a corticosteroid drug such as prednisone, or
* single-agent treatments with nucleoside drugs such as fludarabine, pentostatin, or cladribine (2-chlorodeoxyadenisine; 2-CDA). However, such drugs usually are reserved for cases in which CLL is resistant (unresponsive to treatment) or returns after chemotherapy with chlorambucil or cyclophosphamide.
 
People with intermediate (Rai Stage I and II) or advanced (Rai Stage III or IV) disease may be helped by participation in a clinical trial. At the present time, clinical trials are being conducted using immunologic compounds (e.g., interferons, monoclonal antibodies) as well as new chemotherapeutic agents (e.g., bryostatin, dolastatin 10, and PSC 83 - a cyclosporine drug given with chemotherapy to overcome drug resistance).
 
===Hairy Cell Leukemia (HCL)===
[[Hairy cell leukemia]] is an incurable, indolent blood disorder in which mutated, partly matured B cells accumulate in the bone marrow. Its name is derived from the shape of the cells, which look like they are covered with short, fine, hair-shaped projections. Unlike any other leukemia, HCL is characterized by ''low'' white blood cell counts.
 
Patients with hairy cell leukemia who are symptom-free typically do not receive immediate treatment. They engage in "watchful waiting" with routine bloodwork and exams every three to six months to monitor disease progression and identify any new symptoms.
 
Treatment is generally considered necessary when the patient shows signs and symptoms such as low blood cell counts (e.g., infection-fighting neutrophil count below 1.0 K/ul), frequent infections, unexplained bruises, anemia, or fatigue that is significant enough to disrupt the patient's everyday life.
 
Patients who need treatment, which includes most newly diagnosed HCL cases, usually receive either [[cladribine]] or [[pentostatin]], which are both in a class of chemotherapeutic drugs known as [[purine]] analogs or [[nucleoside]]s. In most cases, one round of treatment will produce a prolonged remission.
 
Other treatments include [[rituximab]] infusions or self-injection with [[Interferon-alpha]]. In limited cases, the patient may benefit from [[splenectomy]] (removal of the spleen). These treatments are not typically given as the first treatment for a new patient because their success rates are lower than cladribine or pentostatin.
 
In the short term, especially when neutrophil counts are low, an immune system hormone called granulocyte colony-stimulating factor may be taken to increase white blood cell counts. This is believed to help prevent or treat an infection. Many patients also take [[antibiotics]] until their white blood cell counts have recovered to normal levels.
 
Clinical trials are being conducted with high-dose chemotherapy followed by stem cell transplantation.{{Fact|date=February 2007}}
Not every form of leukemia requires treatment. The chronic leukemias (CML and CLL) may be treated with oral medication or even with "watchful waiting".
 
== Prognosis ==
27,900 adults and 2,300 children are diagnosed each year with leukemia in the [[United States|US]]. Over the last thirty years, the chances of survival have doubled from a 22 per cent survival rate in [[1970]] to 43 per cent rate in the [[1990s]]. There is however a wide range in prognosis amongst the different types of leukemia: the outlook for an elderly patient with [[AML]] remains very poor, whilst 8 out of 10 children with [[Acute lymphocytic leukaemia|ALL]] will now be cured.
-->
 
== ReferensiLihat pula ==
* [[Metaloproteinase matriks-9]]
* {{Journal reference issue | Author=Laughlin MJ, Eapen M, Rubinstein P, Wagner JE, Zhang MJ, Champlin RE, Stevens C, Barker JN, Gale RP, Lazarus HM, Marks DI, van Rood JJ, Scaradavou A, Horowitz MM | Title=Outcomes After Transplantation of Cord Blood or Bone Marrow From Unrelated Donors in Adults With Leukemia | Journal=New England Journal of Medicine | Volume=351 | Issue=22 | Year=2004 | Pages=2265-75}} PMID 15564543
* {{Journal reference issue | Author=Rocha V, Labopin M, Sanz G, Arcese W, Schwerdtfeger R, Bosi A, Jacobsen N, Ruutu T, de Lima M, Finke J, Frassoni F, Gluckman E; Acute Leukemia Working Party of European Blood and Marrow Transplant Group; Eurocord-Netcord Registry | Title=Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia | Journal=New England Journal of Medicine | Volume=351 | Issue=22 | Year=2004 | Pages=2276-85}} PMID 15564544
* {{Journal reference issue | Author=Steinbrook R | Title=The cord-blood-bank controversies | Journal=New England Journal of Medicine | Volume=351 | Issue=22 | Year=2004 | Pages=2255-7}} PMID 15564539
 
== Pranala luar ==
* {{en}} [http://www.about-leukemia.com/html/causes.php3 The Causes of Leukemia and Potential Risk Factors] {{Webarchive|url=https://web.archive.org/web/20070521202227/http://www.about-leukemia.com/html/causes.php3 |date=2007-05-21 }}
* {{en}} [http://www.cancersource.com/zones/cancer.cfm?DiseaseID=12 FAQ on leukemia]
* {{en}} [http://www.leukemia-lymphomafaqs.org/health/Sick-V3/Leukemia.html Information andFederation advocacyof forAmerican leukemiaScientists]
* {{en}} [http://www.lrflls.org.uk/images/UKCCS_Consensus_Review_2171.pdf Unofficial summary of UKCCS,Leukemia and of UKCCSLymphoma publicationsSociety]
* {{en}} [http://leukemia.acor.org Association of Cancer Online Resources (ACOR) Leukemia Links] {{Webarchive|url=https://web.archive.org/web/20070224145506/http://leukemia.acor.org/ |date=2007-02-24 }}
* {{en}} [http://www.leukemia-research.org Leukemia Research Foundation] {{Webarchive|url=https://web.archive.org/web/20210325072740/http://www.leukemia-research.org/ |date=2021-03-25 }}
 
== Referensi ==
{{Hematologi}}
{{reflist}}
 
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