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Follow-up bone marrow biopsies and aspirates. (a, b) Day 21 from the original bone marrow biopsy. The core biopsy showed trilineage maturing hematopoiesis and no increase in blasts by H&E (400 ×) or CD34 immunohistochemical stain (inset, 400 ×) or the aspirate smear (1000 × oil immersion); however, a small abnormal blast population was detected by flow cytometry. (c, d) Day 49 from the original bone marrow biopsy similarly showing trilineage maturing hematopoiesis and no increase in blasts on the core biopsy by H&E (400 ×) or CD34 immunohistochemical stain (inset, 400 ×) or the aspirate smear (1000 × oil immersion) and no abnormal blast population detected by flow cytometry. H&E: hematoxylin-eosin staining.
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Although rare, spontaneous remission (SR) of acute myeloid leukemia (AML) has been reported in the literature, the underlying mechanisms driving remission remain unknown. However, it is most commonly associated with a preceding severe infection. We present a case of a 40-year-old man with no past medical history who presented to our hospital with s...
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Context 1
... waiting to begin induction chemotherapy, his fevers resolved and his peripheral blood counts improved. A repeat bone marrow biopsy was performed 3 weeks from the original bone marrow biopsy (day 21), revealing a normocellular marrow (60-70%) with trilineage maturing hematopoiesis with no overt increase in blasts (Fig. 3). Flow cytometry identified a small abnormal myeloid blast population comprising only 0.08% of the total cells analyzed, having abnormal expression of CD11b, CD56 (partial), CD13 (absent), CD33 (dim to absent), and CD117 (dim to absent) ( Fig. ...
Context 2
... waiting to begin induction chemotherapy, his fevers resolved and his peripheral blood counts improved. A repeat bone marrow biopsy was performed 3 weeks from the original bone marrow biopsy (day 21), revealing a normocellular marrow (60-70%) with trilineage maturing hematopoiesis with no overt increase in blasts (Fig. 3). Flow cytometry identified a small abnormal myeloid blast population comprising only 0.08% of the total cells analyzed, having abnormal expression of CD11b, CD56 (partial), CD13 (absent), CD33 (dim to absent), and CD117 (dim to absent) ( Fig. ...
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Citations
... To our knowledge, this is the third reported case of spontaneous complete resolution of CML in the literature overall and the first described case in the era of quantifications of BCR::ABL1 by real-time quantitative PCR. The mechanism of spontaneous remission in our case, as in other reported cases, is unknown, and it remains one of the unanswered questions and the unmet needs in CML which requires further investigations [17]. ...
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm in which granulocytic cells are the main proliferative component. At diagnosis, more than 90% of CML cases have the characteristic Philadelphia chromosome, containing the BCR::ABL1 fusion gene. The natural history of untreated CML is an initial indolent chronic phase which will be followed by an accelerated phase, blast phase, or both. Tyrosine kinase inhibitors (TKIs) have dramatically altered the natural history of CML. TKI discontinuation with the goal of treatment-free remission is currently part of current management recommendations. However, spontaneous remission without receiving any treatment is extraordinarily rare in CML patients. Herein, we report a 56-year-old male who presented with leukocytosis and was diagnosed as a case of CML in the chronic phase; however, treatment with TKIs was not initiated due to spontaneous hemato-logical as well as molecular remission.
... 202 The rare spontaneous remissions of established MPN involve various genotypes, including BCR::ABL1, FLT3 ITD , and JAK2 V617F , and likely reflect involvement of host immunity. [203][204][205][206][207] However, the detection of BCR::ABL1 transcripts in the blood of healthy volunteers and the subsequent discovery of CH are evidence that mutant clones frequently arise. 208,209 It is intriguing to speculate that many more mutant clones become exhausted before they reach detectability. ...
Chronic or recurrent episodes of acute inflammation cause attrition of normal hematopoietic stem cells (HSCs) that can lead to hematopoietic failure, but they drive progression in myeloid malignancies and their precursor clonal hematopoiesis (CH). Mechanistic parallels exist between hematopoiesis in chronic inflammation and the continuously increased proliferation of myeloid malignancies, particularly myeloproliferative neoplasms (MPNs). The ability to enter dormancy, a state of deep quiescence characterized by low oxidative phosphorylation, low glycolysis, reduced protein synthesis, and increased autophagy is central to the preservation of long term HSCs and likely MPN SCs. The metabolic features of dormancy resemble those of diapause, a state of arrested embryonic development triggered by adverse environmental conditions. To outcompete their normal counterparts in the inflammatory MPN environment, MPN SCs co-opt mechanisms used by HSCs to avoid exhaustion, including signal attenuation by negative regulators, insulation from activating cytokine signals, anti-inflammatory signaling, and epigenetic reprogramming. We propose that new therapeutic strategies may be derived from conceptualizing myeloid malignancies as an ecosystem out of balance, where residual normal and malignant hematopoietic cells interact in multiple ways, only few of which have been characterized in detail. Disrupting MPN SC insulation to overcome dormancy, interfering with aberrant cytokines circuits that favor MPN cells and directly boosting residual normal HSCs are potential strategies to tip the balance in favor of normal hematopoiesis. While eradicating the malignant cell clones remains the goal of therapy, this may be a more attainable objective in the short term.
... 26,27 Similar phenomena and mechanisms have been discussed and reported in several cases and case series in acute myeloid leukemia patients. 28,29 Our patient's long-term remission may be attributed to a combination of the two phases of chemotherapy per ALL R3 protocol with the systemic stress related to his multiple severe infections. ...
DS‐ALL has a higher rate of relapse and treatment‐related mortality. The newer immunotherapies are potentially better options. Relapsed ALL with positive MRD has a poor prognosis. Transient long‐term remission after ALL relapse due to partial chemotherapy combined severe infection is rare. DS‐ALL has a higher rate of relapse and treatment‐related mortality. The newer immunotherapies are potentially better options. Relapsed ALL with positive MRD has a poor prognosis. Transient long‐term remission after ALL relapse due to partial chemotherapy combined severe infection is rare.
... Cytokines, including tumor necrosis factoralpha, interferon-alpha, and interleukin-2, released during infection can directly inhibit the residual blast proliferation or through increased activity of T lymphocytes, macrophages, and natural killer cells leading to an anti-leukemia effect 26,27 . Similar phenomena and mechanisms have been discussed and reported in several cases and case series in acute myeloid leukemia patients 28,29 . Our patient's long-term remission may be attributed to a combination of the two phases of chemotherapy per ALL R3 protocol with the systemic stress related to his multiple severe infections. ...
Background: Spontaneous remission (SR) has been reported in different hematological malignancies. It has been observed in adult T-cell lymphoma, chronic lymphocytic leukemia (CLL) and myelodysplastic syndrome (MDS). It is generally associated with recovery from an infectious or immunological process, and more recently possibly with clonal hematopoiesis.
Case: We reviewed the literature and reported a new case of a 40 year-old man with a morphologic and cytogenetic diagnosis of early T-cell precursor acute lymphoblastic leukemia (ALL) associated with an appendicular abscess. During his hospitalization and surgical management of his appendicitis, we noted SR of the rate of blast cells until cytological and cytogenetic remission of his ALL but unfortunately it did not last too long, moreover our patient relapsed after nine months, received intensive chemotherapy, underwent a placental blood allograft but relapsed again and died.
Conclusions: In contrast to SR in other types of cancer, all documented cases of SR in ALL were only transient, so is there a need for early cytotoxic therapy in SR in ALL to delay relapse?
Background:
Leukemic hematopoietic cells acquire enhanced self-renewal capacity and impaired differentiation. The emergence of symptomatic leukemia also requires the acquisition of a clonal proliferative advantage. Untreated leukemia patients usually experience an aggressive process. However, spontaneous remission occasionally occurs in patients with acute myeloid leukemia (AML), most frequently after recovery from a febrile episode, and this is generally attributed to the triggering of antineoplastic immunity. There may be another explanation for the spontaneous remission as implicated in this paper.
Case summary:
A 63-year-old Chinese man presented with high fever, abdominal pain and urticaria-like skin lesions. He was diagnosed with AML-M4 with t(8;21) (q22;q22)/RUNX1-RUNX1T1 based on morphological, immunological, cytogenetic and molecular analyses. He had a complex chromosome rea-rrangement of 48,XY,t(8;21)(q22;q22),+13,+13[9]/49,idem,+mar[9]/49,idem,+8[2]. He also had a mutated tyrosine kinase domain in fms-like tyrosine kinase 3 gene. He was treated with antibiotics and glucocorticoids for gastrointestinal infection and urticaria-like skin lesions. The infection and skin lesions were quickly resolved. Unexpectedly, he achieved hematological remission along with resolution of the febrile episode, gastrointestinal symptoms and skin lesions. Notably, after relapse, repeating these treatments resulted in a return to hematological remission. Unfortunately, he demonstrated strong resistance to antibiotic and glucocorticoid treatment after the second relapse and died of sepsis from bacterial infection with multidrug resistance. The main clinical feature of this patient was that symptomatic AML emerged with flaring of the gut inflammatory disorder and it subsided after resolution of the inflammation. Learning from the present case raises the possibility that in a subgroup of AML patients, the proliferative advantage of leukemia cells may critically require the presence of inflammatory stresses.
Conclusion:
Inflammatory stresses, most likely arising from gastrointestinal infection, may sustain the growth and survival advantage of leukemic cells.
Cancer testis antigen PRAME is over-expressed in a variety of malignant cells but is not or minimally expressed in normal non-germ line cells. Adoptive transfer of PRAME-specific T cells is thus under investigation in clinical trials as an innovative therapeutic option for acute myeloid leukemia (AML). However, their senescence-inducing activity has not been studied. This study therefore examines senescence induction in AML cells by PRAME-specific TH1 cells. Analysis of cell cycle and marker expression demonstrate that the supernatants of antigen-stimulated PRAME-specific TH1 cells induce senescence in AML cell lines Kasumi and Nomo-1 through combinative IFN-γ and TNF-α. Additionally IFN-γ and TNF-α secreted by TCR-activated Vδ2⁺ or CMV-specific T cells can also drive these AML cell lines into terminal growth arrest. G1/0 arrest is also suggested in patient-derived AML by TH1 cytokines or supernatants from Zoledronate-stimulated or aCD3/aCD28-stimulated PBMCs. Thus, we show for the first time that senescence is induced in AML cells by combined IFN-γ and TNF-α, and that these cytokines can be derived either from TCR-engineered CD4⁺ T cells, or intriguingly from Virus-specific as well as innate Vδ2⁺ T cells responding to their cognate antigens, namely T-cell responses targeting an antigen that is NOT expressed by the leukemic cells.
Objective: To explore the clinical features and possible pathogenesis of spontaneous remission of acute myeloid leukemia (AML) . Methods: We retrospectively analyzed the clinical data of a patient with spontaneous remission of AML, MLL-AF9 rearrangement, and abnormal liver function in the First Affiliated Hospital of Zhengzhou University, and the relevant pieces of literature were summarized. Results: The patient experienced lung infection, fever, and liver dysfunction and was treated with anti-infection and blood transfusion. After complete response (CR) , the patient remained in CR with mild, indirect bilirubin elevation at 35 months of follow-up. Additionally, 56 cases of adult AML (non-acute promyelocytic leukemia) were reported in the literature from 1990 to June 2021. The cases were checked by bone marrow aspiration, and our patients were summarized and analyzed. Furthermore, 57 patients, including 37 males and 20 females, with a median age of 51 (20-83) years and a median remission time of five months; 52 patients achieved complete remission. In addition, there were five cases with long-term remission and a chromosomal record, with no recurrence so far, three with normal karyotype and two with t (9;11) (q21;q23) . Conclusion: The spontaneous remission of leukemia is rare and may be related to immunosuppression and genes.
