Transient Spontaneous Remission of Acute Myeloid Leukemia with Mutated RUNX1: A Rare Report

Dear Editor,

Spontaneous remission(SR) is observed as a very rare phenomenon in acute myeloid leukemia(AML). To date, no more than 60 cases of AML with SR in adults have been reported completely since 1949 [1].The underlying mechanisms driving SR has yet to be determined. We experienced a case of AML with RUNX1 alteration that achieved complete remission after anti-infection and transfusion therapy.

In April 2023, a 70-year-old female patient presented with weakness, fever, and cough for four days. Laboratory findings showed white blood count (WBC) 1.63 × 10⁹/L, hemoglobin (Hb) 4.6 g/dL, and platelets (PLT) 23 × 10⁹/L. Bone marrow aspiration smear revealed 79.5% blasts, which had folded nuclei with fine chromatin and conspicuous nucleoli (Fig. 1a). Flow cytometry revealed that blasts expressed CD34,CD117,CD13,HLA-DR,MPO,CD38,CD11c and weakly expressed CD33.Cytogenetics was normal. Molecular testing performed RUNX1^F416Rfs*165 (VAF:46%), IDH1^R132C(VAF:36%) and SRSF2^P95L(VAF:27%)mutations. Based on the above, a diagnosis of acute myeloid leukemia was made(French American-British [FAB] classification: AML M5). The patient continued to experience daily fevers.And staphylococcus lugdunensis was detected in blood cultures. On physical exam, she had significant erythema and tenderness to the nose. A chest CT scan revealed pneumonia. So, the chemotherapy was postponed due to severe infection and neutropenia with absolute neutrophil count < 0.01 × 10⁹/L. The patient received leukocyte privative red blood cells(10 units), platelet transfusions (5 units), multiple antibiotics (biapenem, vancomycin, moxifloxacin, ceftazidime, daptomycin, minocycline, linezolid, ceftriaxone) and antifungal drug (fluconazole) treatment for 40 days. Hematologic status improved progressively with WBC of 4.3 × 10⁹/L, Hb of 8.0 g/dL, and PLT of 202 × 10⁹/L. Cytomorphologic and immunocytometric evaluation of bone marrow examination indicated complete remission(CR) (blasts < 5%), although some degree of myeloid dysplasia persisted (Fig. 1b). NGS showed IDH1^R132C(VAF:4%),SRSF2^p.P95L(VAF:4%), and TET2^I1873T(VAF: 3%). Leukemia relapse was observed four months later.

Fig. 1.

Bone marrow smears of the case. aThe bone marrow smear shows increasd blasts with irregular nuclei, fine chromatin, and prominent nucleoli. bAspirate smear showing megaloblastic change with no increased blasts. a, b,1000x, Wright-Giemsa stain

SR of AML is a rare phenomenon, mostly occurring following an inflammatory or infective episode which potentially leads to immune activation and an autologous anti-tumour effect [2]. The paper reported by Bradley reviewed 55 cases of acute leukemia with SR. Among the 55 cases studied, 42 patients (76.4%) had a documented infection with the most common infections being pneumonia, bacteremia, and skin/soft tissue infections [1].In our case, the patients also presented with fever and severe infection. The previous case reports have shown that the antileukemic effect of infectious diseases is the release of inflammatory cytokines, such as IL-1, IL-6, IL-2, and TNF-α, leading to an increase in NK cells and cytotoxic cells and helping in the initial blast clearance [3]. Maybe the increase in these factors was a transient phenomenon that rapidly disappeared. Nearly all the reported cases of SR relapsed after a short-term duration of remission with medians of 5 months [1, 4]. Nevertheless, not all cases can be traced to bacterial or viral infection [4]. In such scenarios, there must exist hitherto poorly understood mechanisms that heal the leukemia. Moreover, blood transfusion was suggested to associate with SR which was also administered in our case.

Past studies remained unclear about the association specific chromosomal abnormality or genetic mutation with SR. To our knowledge, this is the first case report of SR in AML with such mutations including RUNX1, IDH1, and SRSF2. When the patient achieved SR clinically, she did not reconstitute normal polyclonal hematopoiesis on the genetic level. It was similar to the cases reported by Grunwald [5]. Further studies are needed to investigate the mechanisms as it may lead to advances in treating of AML.

Author Contributions

Xinhong Yang and Xue Wu designed the study and made critical revision to the manuscript; Jingyuan Zhao and Yingying Chen collected data, performed statistical analyses, and drafted the manuscript; Zhihua Zhang helped with data collection, data checking, and data interpretation. All authors read and approved the final manuscript.

Funding

This work was funded by the Chengde Science and Technology Program (No.202303A058).

Declarations

Ethics Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all patients for being included in the study.

Conflict of Interest

The authors declare no competing interests.