The historical record explains why skepticism took root. Studies conducted in the 1980s and 1990s reported in-hospital mortality approaching 90 percent among patients with acute myeloid leukemia who required invasive mechanical ventilation. Against such figures, many clinicians questioned whether intensive care offered anything more than a prolonged and painful death. Yet the evidence landscape has steadily transformed. Refinements in patient selection, combined with sweeping advances in supportive care, have progressively improved outcomes, and more recent studies report in-ICU mortality rates of approximately 45 percent for critically ill patients with acute leukemia. That trajectory, from near-certain fatality to a coin-flip chance of survival, represents one of the quiet revolutions in hematology and intensive care.

A major new analysis has now brought unprecedented statistical weight to this transformation. An individual participant data meta-analysis by Chean and colleagues, published in Intensive Care Medicine, examines the outcomes of critically ill adults with acute leukemia using data from 2,003 patients treated in 55 intensive care units across 19 countries, with an inclusion period spanning more than two decades, from January 2000 to July 2023. The scale and duration of the study fill a long-standing knowledge gap created by earlier single-center investigations and limited sample-size analyses that focused mainly on patients younger than 60 years, a group that no longer reflects the real-world demographics of the disease.

What distinguishes this meta-analysis methodologically is its use of the individual participant data approach. Unlike conventional meta-analyses that rely on aggregated results extracted from published papers, an IPD meta-analysis goes back to the raw data of each contributing study and reanalyzes them. This allows researchers to improve both the quantity and quality of the evidence, to include information that was never reported in the original publications, and to standardize analyses and outcome definitions across studies. The method demands that investigators contact the corresponding author of every included trial or cohort, an arduous process that explains why such analyses remain relatively rare but carry exceptional authority when completed.

The findings confirm what many specialists hoped but could not previously prove with such rigor: ICU mortality has decreased over time among patients requiring mechanical ventilation. The authors of the accompanying editorial, Guillaume Berton and Norbert Vey of Aix-Marseille University and Institut Paoli-Calmettes in Marseille, attribute this trend to improvements on two fronts simultaneously. On the hematology side, new chemotherapy regimens have emerged, while supportive care has advanced dramatically through antimicrobial prophylaxis and improved management of febrile neutropenia, the dangerous fever that strikes patients whose infection-fighting white cells have been wiped out by both disease and treatment.

Perhaps the most striking demographic shift documented in the analysis is the changing age profile of patients reaching the ICU. The proportion of patients older than 65 years admitted to intensive care nearly doubled over the study period, rising from 18 percent before 2010 to 33 percent after 2010. This is not a coincidence of referral patterns but a direct consequence of therapeutic innovation. For decades, elderly patients with acute leukemia were often offered palliative care because intensive cytotoxic chemotherapy, the gold standard for younger patients, was considered too toxic for bodies with diminished functional reserves. That paradigm has been upended by non-intensive approaches, most notably the combination of hypomethylating agents with the BCL-2 inhibitor venetoclax, which has demonstrated a median overall survival of 14.7 months and has become the standard of care for AML patients ineligible for intensive chemotherapy.

The therapeutic revolution extends further. Although the Chean meta-analysis excluded post-transplant ICU admissions, advances in allogeneic stem-cell transplantation now allow this potentially curative procedure to be offered to increasingly older patients, with evidence supporting matched sibling, unrelated, and haploidentical donor options in those over 60. Together, these developments signal that treatment for older AML patients has moved decisively from palliative approaches to strategies with curative intent, and the resulting lengthening of survival will only reinforce the role of intensive care in this population. But with more therapeutic possibilities come new dilemmas, above all patient selection, which must rest on a careful evaluation of frailty and is tightly interwoven with the triage decisions made before ICU admission is even offered.

The meta-analysis also delivered a finding that unsettles prior assumptions: older age, defined as above 65 years, emerged as an adverse predictor of in-ICU mortality. This contrasts with earlier studies that had reported in-ICU mortality rates for elderly patients similar to those of younger cohorts. The editorial authors suggest the discrepancy may reflect variable levels of expertise among the participating centers, illustrated by differences in outcomes according to the national economic level of the countries involved. Such disparities may influence not only the quality of intensive care management but also which patients are selected for admission in the first place, raising uncomfortable questions about equity of access to critical care for older patients with leukemia.

The stakes of that triage question are amplified by what happens after patients leave the unit. A recent report highlighted in the editorial found that a significant proportion of AML patients require modifications to their antileukemic treatment following ICU discharge, altering their long-term prognosis, with older age increasing this risk. In other words, the ICU episode does not exist in isolation; it can derail the optimal cancer therapy on which survival ultimately depends. Conversely, one important limitation of the Chean analysis is that treatment response was not considered, even though response is a major determinant of survival and of the success of organ failure management. Future studies, the editorial argues, should incorporate modern response criteria, including the residual disease assessments now routinely used in hematology practice.

Finally, the editorial closes with a human dimension that data alone cannot capture: patients’ own wishes. Goals-of-care discussions are key to determining the most appropriate management strategy for critically ill patients with cancer, yet they remain relatively infrequent in practice, a gap that demands further research. Meanwhile, the treatment landscape continues to accelerate. More potent antileukemic agents are inducing deeper and longer responses, but each advance carries novel toxicities: venetoclax can trigger tumor lysis syndrome, targeted molecular therapies against FLT3, IDH, and menin can provoke differentiation syndrome causing respiratory, hemodynamic, and renal failure, and the spread of immunotherapy brings risks exemplified by cytokine release syndrome and immune cell-associated neurotoxicity seen with T-cell engagers and CAR T cells in acute lymphoblastic leukemia. As these therapies expand, the editorial concludes, more than ever a continuous close collaboration between intensivists and hematologists is paramount to ensure proper management of these increasingly complex, increasingly survivable patients.

Subject of Research: Intensive care unit access and outcomes for critically ill adults with acute leukemia

Article Title: Beyond classical boundaries: rethinking ICU access in acute leukemia

Article References: Berton, G., & Vey, N. (2026). Beyond classical boundaries: rethinking ICU access in acute leukemia. Intensive Care Medicine. https://doi.org/10.1007/s00134-026-08623-y

Image Credits: AI Generated

DOI: 10.1007/s00134-026-08623-y

Keywords: acute leukemia, intensive care unit, acute myeloid leukemia, ICU mortality, mechanical ventilation, venetoclax, hypomethylating agents, allogeneic stem-cell transplantation, tumor lysis syndrome, individual participant data meta-analysis, elderly patients, goals of care

The case began deceptively. The patient, previously healthy, arrived at the hospital in November 2019 with a one-month history of cough. He had no exposure history to toxins, dust or radiation, no family history of haematological disease, and, strikingly, no physical signs that would raise immediate alarm: no enlarged spleen or liver, no swollen lymph nodes, no skin involvement, and none of the flushing, itching or other symptoms of hyperhistaminemia that often accompany basophil-driven leukaemias. Yet his blood counts told a grimmer story. He was profoundly pancytopenic, with a white cell count of just 2.41 × 10⁹ per litre, haemoglobin of 3.7 g/dL and platelets of 12 × 10⁹ per litre, and a differential count in which a remarkable 60 percent of his circulating white cells were basophils.

A bone marrow aspirate deepened the puzzle. The marrow was hypocellular, containing 25 percent blast cells alongside 28 percent immature basophils. The blasts were medium-sized, with immature nuclei and moderate cytoplasm studded with coarse basophilic granules; no Auer rods were seen, and there was no morphological evidence of dysplasia or haemophagocytosis. When stained with toluidine blue, the blasts and immature basophils displayed metachromasia, the colour-shift reaction that is the cytological hallmark of the basophil and mast cell lineages. Electron microscopy went further, confirming round cytoplasmic granules packed with finely particulate electron-dense material inside the leukaemic cells.

Immunophenotyping by flow cytometry revealed two distinct malignant populations. The blasts expressed the stem cell and myeloid markers CD34, CD33, CD13, CD45, HLA-DR and CD117, while the immature basophils carried the basophil-associated signature CD33, CD13, CD203c, CD123, CD9, CD22, CD15 and CD11b. Critically, neither population expressed myeloperoxidase, a cytochemical negativity that is central to distinguishing basophilic leukaemia from other myeloid proliferations and, in the 2022 WHO framework, from mast cell leukaemia. Serum tryptase and histamine were normal, arguing against a mast cell disorder and helping to lock in the diagnosis of acute basophilic leukaemia.

The genetics, however, shifted the classification decisively. Conventional cytogenetics uncovered a complex karyotype and monosomal karyotype, including a der(X;1)(p11;p22), monosomy 1, t(4;20)(q31;q11), a der(7;13)(p10;q10), trisomy 8, and multiple additional structural abnormalities. Reverse transcriptase PCR was positive for WT1 and PRAME and negative for PML-RARA, DEK-NUP214 and BCR-ABL1 fusions, excluding promyelocytic and chronic myeloid leukaemia-related entities. Next-generation sequencing of a 235-gene haematological malignancy panel identified a TP53 mutation (p.I255N) with a variant allele frequency of nearly 72 percent. Under the 2022 WHO classification, these MDS-defining cytogenetic abnormalities override morphological categories, meaning the patient’s disease was formally classified as AML-MR presenting with acute basophilic leukaemia, and placed firmly in the high-risk category.

AML-MR itself is a category that has evolved considerably since its introduction in the 2008 WHO classification. It defines a clonal myeloid neoplasm with 20 percent or more blasts carrying the cytogenetic or molecular abnormalities typically seen in myelodysplastic syndromes, whether arising de novo or after known MDS or MDS/MPN. Its prognosis is among the poorest in acute myeloid leukaemia, driven largely by age, antecedent disease and karyotype. Retrospective analyses have shown that patients with MDS-defining cytogenetic abnormalities have markedly shortened overall survival, with median survival of roughly 4 to 7 months when complex or monosomal karyotypes are present, and that multiple TP53 mutations predict even worse outcomes than a single mutant allele.

Acute basophilic leukaemia, meanwhile, accounts for less than 2 percent of all haematopoietic malignancies, and most reported cases have emerged as transformation from chronic myeloid leukaemia, myelodysplastic syndromes or myeloproliferative neoplasms rather than as a de novo diagnosis. Its reported survival ranges from 2 to 16 months, reflecting a rapid clinical course and frequent resistance to therapy. Diagnostic consensus requires metachromasia on toluidine blue staining, negativity for myeloperoxidase, Sudan black B and non-specific esterase, and the absence of strong CD117 expression to exclude mast cell leukaemia, all features satisfied in this case. No characteristic marker chromosome has been described for ABL, underscoring how much remains unknown about its biology.

Treatment presented a dilemma familiar to oncologists treating elderly, high-risk patients. Because of the patient’s high ECOG performance status concerns, the team chose decitabine combined with a lower-dose CAG regimen, cytarabine, aclarubicin and G-CSF priming, a hypomethylating agent-based strategy known as D-CAG. The disease responded completely. After four consolidation courses, the patient remained in remission for ten months, a notable achievement given his constellation of adverse factors. Intriguingly, when he relapsed in September 2020, the leukaemia had shed its basophilic identity: abundant blasts were present, but no basophils were detectable by morphology or flow cytometry, while the complex karyotype and the TP53 p.I255N mutation persisted at a slightly higher variant allele frequency. The authors suggest that the hypomethylating agent may have been responsible for the unusually durable first remission, noting literature indicating that epigenetic drugs such as hypomethylating agents and histone deacetylase inhibitors can be effective against TP53-mutated AML.

The relapse proved merciless. The patient’s disease resisted multiple successive therapies, including venetoclax, dasatinib, arsenite and homoharringtonine, and he died of sepsis in February 2021. Allogeneic haematopoietic stem cell transplantation, which offers a modest survival benefit in TP53-mutated complex-karyotype AML, was declined because of age and economic constraints. The case thus illustrates both the promise and the limits of current approaches: epigenetic combination therapy can buy meaningful time even in molecularly ominous disease, but relapsed TP53-mutant AML remains one of haemato-oncology’s most stubborn challenges.

The report arrives amid a wave of investigational strategies aimed squarely at TP53-mutant myeloid neoplasms. Eprenetapopt, a first-in-class reactivator of mutant p53, combined with azacitidine produced an overall response rate of 71 percent and a median overall survival of 10.8 months in TP53-mutant MDS and AML, while the anti-CD47 antibody magrolimab plus azacitidine achieved an overall response rate of 71 percent and a median overall survival of 12.9 months in an early-phase trial. Immune checkpoint inhibitors, CD123 × CD3 bispecific antibodies and CAR-T cell therapies are all under study, though none has yet delivered breakthrough efficacy in this genetically defined subgroup. For clinicians, the message of this singular case is twofold: basophilic differentiation can be the presenting face of AML-MR, and cytogenetics must trump morphology when the two diverge; and for the growing population of patients with TP53-mutated, complex-karyotype disease, the therapeutic frontier lies in targeted and immunological approaches that do not yet exist in standard practice. As the first documented instance of AML-MR presenting as acute basophilic leukaemia at diagnosis, the case adds a rare but instructive data point to the literature on two of the most feared entities in myeloid malignancy.

Subject of Research: A rare case of acute myeloid leukaemia-myelodysplasia related presenting as acute basophilic leukaemia at diagnosis.

Article Title: Acute myeloid leukaemia-myelodysplasia related (AML-MR) presented with acute basophilic leukaemia at diagnosis

Article References: Liu, J.-X., Wang, C.-J., & Zhang, M.-X. (2026). Acute myeloid leukaemia-myelodysplasia related (AML-MR) presented with acute basophilic leukaemia at diagnosis. Holistic Integrative Oncology, 5(1), Article 68. https://doi.org/10.1007/s44178-026-00291-8

Image Credits: AI Generated

DOI: 10.1007/s44178-026-00291-8

Keywords: acute myeloid leukaemia, AML-MR, acute basophilic leukaemia, myelodysplasia, TP53 mutation, complex karyotype, decitabine, hypomethylating agents, WHO classification, flow cytometry, leukaemia relapse, targeted therapy