The Aplasia-Leukaemia Syndrome

Mufti, Ghulam J.; Hamblin, Terry J.; Lee-Potter, Jeremy P.

doi:10.1159/000206918

Cited by 11 publications

(3 citation statements)

References 3 publications

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“…However, disease phenotypes can transform between AHF and MNs. The natural transformation of AA to MNs has been widely investigated ( 11 – 14 ) and is generally ascribed to the acquisition and accumulation of oncogenic mutations due to selective pressure and immune exhaustion in the setting of a chronic inflammatory milieu ( 15 – 18 ). It is well known that antithymocyte globulin (ATG) plus cyclosporine-based immunosuppressive therapy (IST) promotes leukemic transformation.…”

Section: Reciprocal Transformations Between Aa and Mnsmentioning

confidence: 99%

“…While hMDS is an unequivocal MN, AA has a high frequency of transformation to MNs. The natural evolution from AA to MNs is usually a long-term process ( 11 – 14 ) and is frequently attributed to genetic damage or immune exhaustion due to an inflamed BME ( 15 – 18 ). However, leukemic transformation can occur during or shortly after IST ( 19 – 23 ).…”

Section: Decreased Inflammatory Strength Facilitates Leukemic Transfo...mentioning

confidence: 99%

“…During infectious episodes, patients demonstrate positive immune responses and frequently experience an aplastic crisis. After successful treatment of underlying infections, dampened inflammatory stress-powered antileukemic immunity leads to the expansion of previously suppressed leukemic clones and facilitates the appearance of symptomatic MNs, which is distinct from the naturally occurring clonal evolution in AA ( 11 – 14 ) due to the acquisition of novel somatic mutations and immune exhaustion in the chronic inflammatory milieu ( 16 , 17 , 321 , 323 ).…”

Section: Decreased Inflammatory Strength Facilitates Leukemic Transfo...mentioning

confidence: 99%

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When inflammatory stressors dramatically change, disease phenotypes may transform between autoimmune hematopoietic failure and myeloid neoplasms

Zhao,

Ju,

Xiu

et al. 2024

Front. Immunol.

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Aplastic anemia (AA) and hypoplastic myelodysplastic syndrome are paradigms of autoimmune hematopoietic failure (AHF). Myelodysplastic syndrome and acute myeloid leukemia are unequivocal myeloid neoplasms (MNs). Currently, AA is also known to be a clonal hematological disease. Genetic aberrations typically observed in MNs are detected in approximately one-third of AA patients. In AA patients harboring MN-related genetic aberrations, a poor response to immunosuppressive therapy (IST) and an increased risk of transformation to MNs occurring either naturally or after IST are predicted. Approximately 10%–15% of patients with severe AA transform the disease phenotype to MNs following IST, and in some patients, leukemic transformation emerges during or shortly after IST. Phenotypic transformations between AHF and MNs can occur reciprocally. A fraction of advanced MN patients experience an aplastic crisis during which leukemic blasts are repressed. The switch that shapes the disease phenotype is a change in the strength of extramedullary inflammation. Both AHF and MNs have an immune-active bone marrow (BM) environment (BME). In AHF patients, an inflamed BME can be evoked by infiltrated immune cells targeting neoplastic molecules, which contributes to the BM-specific autoimmune impairment. Autoimmune responses in AHF may represent an antileukemic mechanism, and inflammatory stressors strengthen antileukemic immunity, at least in a significant proportion of patients who have MN-related genetic aberrations. During active inflammatory episodes, normal and leukemic hematopoieses are suppressed, which leads to the occurrence of aplastic cytopenia and leukemic cell regression. The successful treatment of underlying infections mitigates inflammatory stress-related antileukemic activities and promotes the penetration of leukemic hematopoiesis. The effect of IST is similar to that of treating underlying infections. Investigating inflammatory stress-powered antileukemic immunity is highly important in theoretical studies and clinical practice, especially given the wide application of immune-activating agents and immune checkpoint inhibitors in the treatment of hematological neoplasms.

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Section: Reciprocal Transformations Between Aa and Mnsmentioning

confidence: 99%

Section: Decreased Inflammatory Strength Facilitates Leukemic Transfo...mentioning

confidence: 99%

Section: Decreased Inflammatory Strength Facilitates Leukemic Transfo...mentioning

confidence: 99%

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When inflammatory stressors dramatically change, disease phenotypes may transform between autoimmune hematopoietic failure and myeloid neoplasms

Zhao,

Ju,

Xiu

et al. 2024

Front. Immunol.

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Severe aplastic anemia preceding acute lymphoblastic leukemia

Matloub

Brunning

Arthur

et al. 1993

Cancer

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Background. Bone marrow aplasia preceding acute lymphoblastic leukemia (ALL) is a rare condition that usually affects children. The ALL generally follows the recovery of normal blood counts and most commonly occurs within 6 months of the onset of aplasia. The case of a patient with severe aplastic anemia is reported in whom ALL developed 15 months after the initial diagnosis of aplastic anemia. A literature search found 23 cases of ALL after a period of aplasia or hypoplasia. This patient's disease, however, was different from all previously reported ones. The severe aplasia lasted 15 months before being followed by ALL. There was no recovery of blood counts before the onset of ALL. Methods. A review of the literature found 23 case reports in which aplasia or hypoplasia preceded ALL; these patients also had pancytopenia of the peripheral blood. Excluded from this review were patients whose bone marrow was hypoplastic, but who did not have pancytopenia because these did not have “aplastic anemia” as their initial disease. Results. Analysis of the reported patients showed that most were girls 10 years of age or younger. There was an overwhelming prevalence of fever, which in several instances, might have had an infectious cause. ALL most commonly occurred within 6 months of the aplasia and usually followed the recovery of normal blood counts. Conclusions. Patients with ALL after a prolonged period of aplasia have several common characteristics including female sex, young age, and the prevalence of fever, often associated with an infectious illness. ALL usually follows the recovery of blood counts and occurs within 6 months of the onset of aplasia. The pathophysiology of this patient's disease(s) is still unclear. He could have had two unrelated disorders or a two‐step leukemic process that followed a stem cell “insult.” This patient had an antecedent hepatitis A infection 3 months before aplasia occurred. However, the authors were unable to identify with certainty any other event that might have caused additional bone marrow injury. Cancer 1993; 71:264‐8.

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Erythropoese

Remmele¹

1984

Pathologie

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The Aplasia-Leukaemia Syndrome

Cited by 11 publications

References 3 publications

When inflammatory stressors dramatically change, disease phenotypes may transform between autoimmune hematopoietic failure and myeloid neoplasms

When inflammatory stressors dramatically change, disease phenotypes may transform between autoimmune hematopoietic failure and myeloid neoplasms

Severe aplastic anemia preceding acute lymphoblastic leukemia

Erythropoese

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