Vymenujte urgentné stavy pri akútnych leukémiách.
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🫀 Interná medicína · 50
Akútne leukémie: akútna myeloblastová leukémia, akútna lymfoblastová leukémia
Definícia
- • Akútna myeloblastová leukémia (AML) je rýchlo progredujúca myeloidná neoplázia s klonovou expanziou nezrelých myeloidných buniek (blastov) v periférnej krvi a kostnej dreni. Akútna lymfoblastová leukémia (ALL) je malignita B- alebo T-lymfoblastov s nekontrolovanou proliferáciou abnormálnych nezrelých lymfocytov a ich prekurzorov.
Etiológia a patogenéza
- • AML: k rizikovým faktorom patrí napr. expozícia žiareniu, tabakovému dymu a benzénu.
- • AML sa môže vyvinúť z myeloproliferatívnych neoplázií (napr. myelofibróza, esenciálna trombocytémia, polycythaemia vera, CML).
- • ALL je častejšia u detí s trizómiou 21 (Downov syndróm), neurofibromatózou 1. typu, Bloomovým syndrómom a ataxiou-teleangiektáziou.
Klinický obraz
- • Príznaky AML aj ALL môžu byť prítomné len dni až týždne pred stanovením diagnózy.
- • Najčastejšie úvodné príznaky vyplývajú z poruchy krvotvorby: anémia, trombocytopénia a granulocytopénia (neutropénia).
- • ALL: častá je penetrácia do CNS a infiltrácia meningov – napr. obrny hlavových nervov, bolesti hlavy, poruchy zraku či sluchu, zmena psychického stavu.
- • APL: diseminovaná intravaskulárna koagulácia (DIK) môže byť prítomná už pri diagnóze a môže sa zhoršiť, keď rozpad leukemických buniek uvoľňuje prokoagulačné látky.
Diagnostika
- • Prvými vyšetreniami sú krvný obraz a periférny náter; pancytopénia a blasty v periférnej krvi svedčia pre akútnu leukémiu.
- • WHO 2022: pre typy AML s definujúcimi genetickými abnormalitami sa zrušila požiadavka ≥ 20 % blastov (výnimkou je AML s fúziou BCR::ABL1 a AML s mutáciou CEBPA).
- • ELN 2022 (podľa ICC): pri rekurentných genetických abnormalitách je prahom pre diagnózu AML ≥ 10 % blastov; AML s BCR::ABL1 naďalej vyžaduje ≥ 20 % blastov.
Liečba
- • AML u medicínsky zdatných pacientov: základným indukčným režimom je „7+3“ – cytarabín v kontinuálnej i. v. infúzii 7 dní a daunorubicín alebo idarubicín i. v. počas 3 dní.
- • AML u medicínsky krehkých pacientov: menej intenzívne režimy, napr. inhibítory DNA-metyltransferázy (hypometylačné látky) v kombinácii s inhibítorom BCL-2 venetoklaxom; zvážiť alogénnu transplantáciu krvotvorných buniek.
- • APL s t(15;17): pri nízkom a strednom riziku je štandardom cielená liečba kyselinou all-trans retinovou (tretinoín) a oxidom arzénu bez konvenčnej cytostatickej chemoterapie.
- • Ph+ ALL: k liečbe sa pridáva inhibítor tyrozínkinázy (napr. imatinib, dasatinib).
Komplikácie a prognóza
- • Klinický syndróm leukostázy je urgentný stav – počet leukocytov treba bez odkladu znížiť hydroxyureou alebo plánovanou indukčnou liečbou.
- • Syndróm z rozpadu nádoru: napr. hyperurikémia, hyperfosfatémia, hyperkaliémia, hypokalciémia a zvýšená LDH.
- • Granulocytopénia môže viesť k rýchlo progredujúcej, potenciálne život ohrozujúcej bakteriálnej infekcii.
Kľúčové pojmy
| akútna myeloblastová leukémia | leukaemia myeloblastica acuta |
| akútna lymfoblastová leukémia | leukaemia lymphoblastica acuta |
| akútna promyelocytová leukémia | leukaemia promyelocytica acuta |
| blast | |
| Auerove tyčinky | |
| diseminovaná intravaskulárna koagulácia | coagulatio intravasalis disseminata |
| syndróm z rozpadu nádoru | |
| leukostáza | leukostasis |
📎 Zdroje:
- Acute Myeloid Leukemia - StatPearls - NCBI Bookshelf
Acute myeloid leukemia (AML) is a rapidly progressing myeloid neoplasm characterized by the clonal expansion of immature myeloid-derived cells, known as blasts, in the peripheral blood and bone marrow.
- Acute Lymphocytic Leukemia - StatPearls - NCBI Bookshelf
Acute lymphocytic leukemia (ALL) is a malignancy of B or T lymphoblasts characterized by uncontrolled proliferation of abnormal, immature lymphocytes and their progenitors
- Acute Myeloid Leukemia - StatPearls - NCBI Bookshelf
Additional environmental exposures, including radiation, tobacco smoke, and benzene, also contribute to the risk of AML.
- Acute Myeloid Leukemia - StatPearls - NCBI Bookshelf
Patients with myeloproliferative neoplasms, which include myelofibrosis, essential thrombocythemia, polycythemia vera, and chronic myeloid leukemia, may also progress or evolve into a higher-grade myeloid neoplasm such as AML.
- Acute Lymphocytic Leukemia - StatPearls - NCBI Bookshelf
Acute Lymphocytic Leukemia is more common in children with Trisomy 21 (Down syndrome), neurofibromatosis type 1, Bloom syndrome, and ataxia telangiectasia.
- Acute Myeloid Leukemia (AML) - MSD Manual Professional Edition
Symptoms of acute myeloid leukemia may be present for only days to weeks before diagnosis.
- Acute Lymphoblastic Leukemia (ALL) - MSD Manual Professional Edition
Symptoms and signs of acute lymphoblastic leukemia (ALL) may be present for only days to weeks before diagnosis.
- Acute Myeloid Leukemia (AML) - MSD Manual Professional Edition
The most common presenting symptoms are due to disrupted hematopoiesis with ensuing: Anemia Thrombocytopenia Granulocytopenia
- Acute Lymphoblastic Leukemia (ALL) - MSD Manual Professional Edition
Central nervous system (CNS) penetration and meningeal infiltration are common and can result in cranial nerve palsies, headache, visual or auditory symptoms, altered mental status, and transient ischemic attacks/stroke.
- Acute Myeloid Leukemia (AML) - MSD Manual Professional Edition
Patients commonly present with a coagulation disorder (eg, disseminated intravascular coagulation [DIC]).
- Acute Myeloid Leukemia (AML) - MSD Manual Professional Edition
CBC and peripheral smear are the first tests performed; pancytopenia and peripheral blasts suggest acute leukemia.
- Khoury JD et al. The 5th edition of the WHO Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms (Leukemia 2022) - PMC
elimination of the 20% blast requirement for AML types with defining genetic abnormalities (with the exception of AML with BCR :: ABL1 fusion and AML with CEBPA mutation)
- Acute Myeloid Leukemia - StatPearls - NCBI Bookshelf
Perhaps a notable alteration in these guidelines is the modification to the blast threshold needed to define disease, particularly in the presence of recurrent genetic abnormalities, set at 10% or more.
- Döhner H et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN (Blood 2022) - PDF, leukemia-net.org
To avoid potential overlap with chronic myeloid leukemia in accelerated phase, AML with BCR::ABL1 still requires
- Acute Myeloid Leukemia (AML) - MSD Manual Professional Edition
The basic induction regimen (known as 7+3) includes cytarabine by continuous IV infusion for 7 days and daunorubicin or idarubicin given IV for 3 days during this time.
- Acute Myeloid Leukemia (AML) - MSD Manual Professional Edition
In medically frail patients, treat with less intensive regimens such as DNA methyltransferase inhibitors in combination with the B-cell lymphoma-2 (BCL-2) inhibitor venetoclax and consider allogeneic hematopoietic stem cell transplantation.
- Acute Lymphoblastic Leukemia (ALL) - MSD Manual Professional Edition
For patients with Philadelphia chromosome–positive (Ph+) ALL, a tyrosine kinase inhibitor (eg, imatinib , dasatinib ) can be added to the medication regimen.
- Döhner H et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN (Blood 2022) - PDF, leukemia-net.org
Clinical leukostasis syndrome is a medical emergency requiring the WBC to be promptly lowered without delay by either hydroxyurea or planned induction therapy
- Acute Lymphoblastic Leukemia (ALL) - MSD Manual Professional Edition
Other laboratory findings may include hyperuricemia, hyperphosphatemia , hyperkalemia , hypocalcemia , and elevated lactate dehydrogenase (LDH), which indicate a tumor lysis syndrome .
- Acute Myeloid Leukemia (AML) - MSD Manual Professional Edition
granulocytopenia may lead to a rapidly progressing and potentially life-threatening bacterial infection.
- MSD Manual Professional – Acute Myeloid Leukemia (Symptoms and Signs – APL a DIK)
In acute promyelocytic leukemia (APL) and some other cases of AML, disseminated intravascular coagulation (DIC) may be present when leukemia is diagnosed and may worsen as leukemic cell lysis releases procoagulant chemicals.
- MSD Manual Professional – Acute Myeloid Leukemia (Treatment – APL)
Targeted therapy with tretinoin and arsenic trioxide without conventional cytotoxic chemotherapy is very well tolerated and has become the standard of care in low- and intermediate-risk APL
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Opíšte fázy a princípy liečby ALL.
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