Acute Leukaemia

The answer first

Acute leukaemia is a clonal expansion of immature haematopoietic precursor cells (blasts) that arrests normal marrow function. The patient presents over weeks with the consequences of marrow failure — infection (neutropenia), bleeding (thrombocytopenia, and disseminated intravascular coagulation in acute promyelocytic leukaemia), and fatigue (anaemia). The diagnosis rests on demonstrating 20 per cent or more blasts in the marrow or blood, with subtyping by immunophenotype and genetics ^[2].

Two bedside rules that change outcome: ^[1]

1. Suspect APL? Start ATRA now. Acute promyelocytic leukaemia (APL, formerly M3) is the form of AML defined by the t(15;17) PML-RARA fusion. It presents with a bleeding emergency driven by DIC. All-trans retinoic acid (ATRA) reverses the coagulopathy and is started on suspicion — not on cytogenetic confirmation — because the principal danger is early death from cerebral or pulmonary haemorrhage ^[3].
2. New leukaemia plus fever? Treat as neutropenic sepsis within one hour. Cultures then a broad-spectrum antipseudomonal beta-lactam (piperacillin-tazobactam or ceftazidime). The door-to-antibiotic time is a measurable survival determinant.

For fit adults with non-APL AML the backbone is 7+3 induction (7 days of cytarabine infusion plus 3 days of an anthracycline, daunorubicin 60 to 90 mg/m2), with midostaurin added for FLT3-mutated disease and the decision to consolidate with chemotherapy or allogeneic stem cell transplant driven by the 2022 European LeukemiaNet (ELN) risk group ^[1][4][6]. For the older or unfit patient the standard is azacitidine plus venetoclax ^[5].

For acute lymphoblastic leukaemia (ALL), the adult paradigm has shifted to paediatric-inspired regimens for younger adults (up to about 40 to 45 years), with a tyrosine kinase inhibitor added for Philadelphia-chromosome-positive disease and intrathecal CNS prophylaxis throughout ^[10][11].

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References11ShowHide

1. [1]Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN Blood, 2022.PMID 35797463
2. [2]Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia Blood, 2016.PMID 27069254
3. [3]Lo-Coco F, Avvisati G, Vignetti M, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia N Engl J Med, 2013.PMID 23841729
4. [4]Stone RM, Mandrekar SJ, Sanford BL, et al. Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation N Engl J Med, 2017.PMID 28644114
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7. [7]Castaigne S, Pautas C, Terré C, et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study Lancet, 2012.PMID 22482940
8. [8]Sanz MA, Lo Coco F, Martín G, et al. Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups Blood, 2000.PMID 10942364
9. [9]Sanz MA, Montesinos P How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia Blood, 2014.PMID 24627526
10. [10]Huguet F, Leguay T, Raffoux E, et al. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study J Clin Oncol, 2009.PMID 19124805
11. [11]Foà R, Bassan R, Vitale A, et al. Dasatinib-Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults N Engl J Med, 2020.PMID 33085860