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1.
Rinsho Ketsueki ; 65(5): 330-334, 2024.
Article in Japanese | MEDLINE | ID: mdl-38825509

ABSTRACT

A 53-year-old woman presented with shortness of breath and hyperleukocytosis and was admitted to our hospital. Shortly after, she went into cardiopulmonary arrest and was resuscitated. Her white blood cell count was 566,000/µl, with 94.5% cup-like blasts positive for MPO staining and FLT3-ITD positive, so she was diagnosed with acute myeloid leukemia (AML) M1. She also had disseminated intravascular coagulation and tumor lysis syndrome. Extracorporeal membrane oxygenation (ECMO) was started to manage bilateral pulmonary thromboembolism that had developed due to deep vein thrombosis, and induction therapy was performed under ECMO. On the third day of illness, the patient developed cerebral hemorrhage. Hematological remission was confirmed on the 39th day of illness. After consolidation therapy with chemotherapy and an FLT3 inhibitor, she underwent allogeneic hematopoietic stem cell transplantation, and remains alive. Case reports suggest strong evidence of mortality benefit from ECMO in patients with hematologic malignancies, particularly when ECMO served as a bridge through chemotherapy. Our patient suffered from cardiopulmonary arrest due to hyperleukocytosis and pulmonary thromboembolism, but was saved by induction of remission under ECMO. Improvements in supportive care should lead to reduction in early deaths during induction therapy.


Subject(s)
Extracorporeal Membrane Oxygenation , Leukemia, Myeloid, Acute , Humans , Female , Middle Aged , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/complications , Remission Induction , Treatment Outcome , Induction Chemotherapy , Hematopoietic Stem Cell Transplantation , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
2.
Am J Case Rep ; 25: e943577, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38760926

ABSTRACT

BACKGROUND Acute myeloid leukemia is characterized by dysregulated proliferation and maturation arrest of myeloid precursors, precipitating a spectrum of complications. Among these, leukemia cutis refers specifically to ectopic deposition and proliferation of malignant myeloid cells within the skin. This infiltration pathogenesis remains unclear. Although there are numerous reports of leukemia cutis in the setting of acute myeloid leukemia or primary acute myeloid leukemia, there are no specific reports of leukemia cutis in the setting of relapsed acute myeloid leukemia. CASE REPORT A 59-year-old woman, with a history of remission from poor-risk acute myeloid leukemia, previously treated with chemotherapy and allogenic bone marrow transplant, presented with shortness of breath, lethargy, anemia, thrombocytopenia, and subcutaneous nodules on lower extremities. Leukemia cutis was diagnosed, in the setting of relapsed acute myeloid leukemia. After unsuccessful salvage chemotherapy and being deemed unsuitable for further treatment, she pursued palliative care and died a month later. CONCLUSIONS Our case highlights a lack of reporting or making a distinction of those patients with relapsed acute myeloid leukemia and leukemia cutis. Consequently, it can be deduced that patients who simultaneously have relapsed acute myeloid leukemia and leukemia cutis are expected to fare worse in terms of clinical outcomes than those with primary acute myeloid leukemia and leukemia cutis. Relapsed acute myeloid leukemia patients with leukemia cutis should be classified as a distinct group, warranting further research into aggressive therapeutic targets and survival rates, while emphasizing the need for more vigilant follow-up and lower biopsy thresholds for cutaneous lesions in patients with treated hematologic malignancies.


Subject(s)
Leukemia, Myeloid, Acute , Leukemic Infiltration , Humans , Female , Middle Aged , Leukemia, Myeloid, Acute/pathology , Leukemia, Myeloid, Acute/complications , Leukemic Infiltration/pathology , Fatal Outcome , Recurrence , Skin Neoplasms/pathology , Skin Neoplasms/therapy
3.
BMC Infect Dis ; 24(1): 515, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38778275

ABSTRACT

BACKGROUND: Lagenidium deciduum is an oomycete that can cause infections in mammals that present similarly to pythiosis and mucormycosis. Most of the existing case reports have occurred in canines and have been fatal. In animals, medical therapy has not been successful, so surgical excision is the mainstay of treatment. Lagenidium sp. infections in humans are rare. There is only one case of a human Lagenidium sp. infection in the literature, and it presented as an ocular infection. The human ocular infection was resistant to medical therapy and required a penetrating keratoplasty for cure. Additional reports of effective therapy are needed to guide management of this emerging pathogen. We present the first case of a cutaneous Lagenidium deciduum infection in a human patient, which is also the first documented case of a Lagenidium deciduum infection in an immunocompromised host of any species. CASE PRESENTATION: An 18-year-old female with relapsed acute myeloid leukemia, awaiting a haploidentical stem cell transplant, presented with erythematous cutaneous lesions on her left hip and bilateral buttocks that enlarged and blackened over several days. About 1 week later, boil-like lesions appeared on her bilateral buttocks. The skin lesions were initially presumed to be bacterial in origin, so the patient was treated with clindamycin and cefepime with little improvement. Upon further investigation, fungal cultures and skin biopsies revealed aseptate hyphae, so the patient was switched to isavuconazole and amphotericin B due to concern for mucormycosis. Phenotypic characterization and DNA sequencing were performed by the Fungus Testing Laboratory, University of Texas Health Science Center at San Antonio, which identified the causal fungal organism as Lagenidium deciduum. All of her cutaneous lesions were surgically excised, and the patient was treated with micafungin, terbinafine, doxycycline, and azithromycin. Micafungin and terbinafine were continued until she achieved engraftment post-transplant. CONCLUSIONS: We report the first successful treatment of a human Lagenidium infection in an immunocompromised host through a combination of aggressive surgical excision and prolonged antifungal therapy during the prolonged neutropenia associated with allogeneic stem cell transplant. Prompt diagnosis and management may prevent disseminated oomycosis.


Subject(s)
Antifungal Agents , Lagenidium , Leukemia, Myeloid, Acute , Humans , Female , Leukemia, Myeloid, Acute/complications , Antifungal Agents/therapeutic use , Adolescent , Lagenidium/genetics , Dermatomycoses/microbiology , Dermatomycoses/drug therapy , Immunocompromised Host
4.
Clin Lab ; 70(4)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38623673

ABSTRACT

BACKGROUND: Infection may lead to agranulocytosis due to bone marrow suppression. However, a rare case with infection presented with morphological features of acute myeloid leukemia (AML). METHODS: We report a case of extreme agranulocytosis due to severe infection mimicking acute myeloid leukemia. The case was definitively diagnosed by subsequent morphology, flow cytometry, and bone marrow biopsy, and subsequent successful anti-infective treatment confirmed the diagnosis. CONCLUSIONS: To date, no case of a patient diagnosed with severe infection mimicking AML has been reported. The case emphasizes the importance of an integrated diagnostic work-up, especially careful clinical observation and differential diagnosis.


Subject(s)
Agranulocytosis , Leukemia, Myeloid, Acute , Humans , Bone Marrow/pathology , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/diagnosis , Diagnosis, Differential , Flow Cytometry , Agranulocytosis/diagnosis , Agranulocytosis/pathology
5.
Clin Lab ; 70(4)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38623681

ABSTRACT

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy arising from precursor dendritic cells. It is a rare and challenging clinical presentation. For decades, there has been no treatment course for managing BPDCN and its overall prognosis is poor. METHODS AND RESULTS: We report a 27-year-old man who was admitted to the hospital due to an orbital tumor as the first symptom. Progressive enlargement of the orbital tumor was accompanied by multiple purple circular nodules on the body trunk. Pathological confirmation of BPDCN after resection of the orbital mass. Bone marrow smear and flow cytometry on examination indicate AML-M5. Performance of chemotherapy and peripheral blood autologous stem cell transplantation. CONCLUSIONS: The clinical manifestations of blastic plasmacytoid dendritic cell neoplasms are diverse. The diagnosis of BPDCN can be difficult due to overlapping morphologic, immunophenotypic, and clinical features of other hematologic AML. Relapsed and refractory BPDCN remains an elusive therapeutic challenge. The future of new targeted therapeutic drugs is expected.


Subject(s)
Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Orbital Neoplasms , Skin Neoplasms , Male , Humans , Adult , Orbital Neoplasms/diagnosis , Orbital Neoplasms/complications , Orbital Neoplasms/pathology , Dendritic Cells , Transplantation, Autologous , Skin Neoplasms/pathology , Hematologic Neoplasms/diagnosis , Leukemia, Myeloid, Acute/complications
6.
Front Immunol ; 15: 1359113, 2024.
Article in English | MEDLINE | ID: mdl-38571944

ABSTRACT

Acute Myeloid Leukemia (AML) is the prototype of cancer genomics as it was the first published cancer genome. Large-scale next generation/massively parallel sequencing efforts have identified recurrent alterations that inform prognosis and have guided the development of targeted therapies. Despite changes in the frontline and relapsed standard of care stemming from the success of small molecules targeting FLT3, IDH1/2, and apoptotic pathways, allogeneic stem cell transplantation (alloHSCT) and the resulting graft-versus-leukemia (GVL) effect remains the only curative path for most patients. Advances in conditioning regimens, graft-vs-host disease prophylaxis, anti-infective agents, and supportive care have made this modality feasible, reducing transplant related mortality even among patients with advanced age or medical comorbidities. As such, relapse has emerged now as the most common cause of transplant failure. Relapse may occur after alloHSCT because residual disease clones persist after transplant, and develop immune escape from GVL, or such clones may proliferate rapidly early after alloHSCT, and outpace donor immune reconstitution, leading to relapse before any GVL effect could set in. To address this issue, genomically informed therapies are increasingly being incorporated into pre-transplant conditioning, or as post-transplant maintenance or pre-emptive therapy in the setting of mixed/falling donor chimerism or persistent detectable measurable residual disease (MRD). There is an urgent need to better understand how these emerging therapies modulate the two sides of the GVHD vs. GVL coin: 1) how molecularly or immunologically targeted therapies affect engraftment, GVHD potential, and function of the donor graft and 2) how these therapies affect the immunogenicity and sensitivity of leukemic clones to the GVL effect. By maximizing the synergistic action of molecularly targeted agents, immunomodulating agents, conventional chemotherapy, and the GVL effect, there is hope for improving outcomes for patients with this often-devastating disease.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/complications , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Graft vs Leukemia Effect , Recurrence
7.
Int J Hematol ; 119(6): 660-666, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38575822

ABSTRACT

Guidelines recommend rasburicase for high-risk patients to prevent tumor lysis syndrome (TLS). However, little information is available on the incidence and outcome of TLS in AML patients. We analyzed 145 patients with AML who underwent induction therapy before the approval of rasburicase to evaluate the incidence of TLS and the necessity of rasburicase as prophylaxis. Three patients had already developed clinical TLS (CTLS) at diagnosis of AML, and another three developed CTLS after the initiation of chemotherapy. In patients without TLS at diagnosis of AML, the risk for developing TLS was classified as high in 44 patients, intermediate in 41 and low in 57, according to the current guidelines. Allopurinol alone was administered to prevent hyperuricemia in all patients. All three patients who developed CTLS after diagnosis of AML were at high risk of TLS, and had elevated serum creatinine levels and a WBC count greater than 200,000 per microliter at diagnosis of AML. Allopurinol may be insufficient to prevent TLS in high-risk patients with renal dysfunction at diagnosis of AML, especially those with a high tumor burden and a WBC count of 200,000 or more, which indicates that prophylactic administration of rasburicase should be considered.


Subject(s)
Allopurinol , Leukemia, Myeloid, Acute , Tumor Lysis Syndrome , Urate Oxidase , Humans , Tumor Lysis Syndrome/etiology , Tumor Lysis Syndrome/prevention & control , Urate Oxidase/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/complications , Male , Female , Middle Aged , Allopurinol/therapeutic use , Allopurinol/administration & dosage , Aged , Adult , Induction Chemotherapy , Aged, 80 and over , Hyperuricemia/drug therapy , Adolescent , Incidence , Young Adult
8.
BMJ Case Rep ; 17(4)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38565228

ABSTRACT

We present a rare case of myeloid sarcoma in the stomach of an elderly woman initially diagnosed with anaemia. Myeloid sarcoma, an unusual extramedullary manifestation of acute myeloid leukaemia (AML), primarily affects lymph nodes, bones, spine and skin, with gastrointestinal involvement being infrequent. Despite normal results from the initial endoscopy, a follow-up examination after 4 months revealed multiple submucosal gastric tumours. These developments coincided with worsening of anaemia and an increase in peripheral myeloblasts. Pathological evaluation and immunohistochemical staining confirmed gastric extramedullary infiltration associated with AML. This case highlights the importance of comprehensive diagnostic processes when suspecting leukaemic transformations, especially in myelodysplastic syndrome (MDS). Due to financial constraints, additional critical studies such as cytogenetics and next-generation sequencing were not performed. Nonetheless, this rare case demonstrates the visual observation of rapid progression from MDS to AML and concurrent early myeloid sarcoma development in an elderly patient.


Subject(s)
Anemia , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Neoplasms, Connective Tissue , Sarcoma, Myeloid , Stomach Neoplasms , Female , Humans , Aged , Sarcoma, Myeloid/pathology , Stomach Neoplasms/diagnosis , Stomach Neoplasms/complications , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/pathology , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/pathology , Neoplasms, Connective Tissue/complications , Anemia/complications
9.
Rinsho Ketsueki ; 65(3): 169-174, 2024.
Article in Japanese | MEDLINE | ID: mdl-38569861

ABSTRACT

A 44-year-old woman was diagnosed with acute myeloid leukemia (RUNX1::RUNX1T1 translocation) and received induction chemotherapy with idarubicin hydrochloride and cytosine arabinoside. The pneumonia that had been present since admission worsened, and a drug-induced skin rash appeared. On day 17, she presented with respiratory failure and shock, complicated by hemoconcentration and hypoalbuminemia. This was considered capillary leak syndrome due to pneumonia and drug allergy, so she was started on pulse steroid therapy and IVIG, and was intubated on the same day. On day 18, venovenous-extracorporeal membrane oxygenation (VV-ECMO) was started due to worsening blood gas parameters despite ventilatory management. Bronchoalveolar lavage fluid was serous, and both blood and sputum cultures yielded negative. The patient was weaned from VV-ECMO on day 26 as the pneumonia improved with recovery of hematopoiesis. She was disoriented, and a CT scan on day 28 revealed cerebral hemorrhage. Her strength recovered with rehabilitation. After induction chemotherapy, RUNX1::RUNX1T1 mRNA was not detected in bone marrow. The patient received consolidation chemotherapy, and has maintained complete remission. Severe respiratory failure during induction chemotherapy for acute leukemia can be fatal, but VV-ECMO may be lifesaving.


Subject(s)
Capillary Leak Syndrome , Extracorporeal Membrane Oxygenation , Leukemia, Myeloid, Acute , Pneumonia , Respiratory Insufficiency , Humans , Female , Adult , Core Binding Factor Alpha 2 Subunit , Induction Chemotherapy , Capillary Leak Syndrome/complications , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/therapy
10.
BMC Nephrol ; 25(1): 113, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38519911

ABSTRACT

BACKGROUND: Women are counseled preconceptionally about the potential risks of rAML progression and chance of complications during and due to pregnancy. However, a systematic search investigating the evidence on which this advice is based does not exist. The aim of this systematic review is to determine the effect of pregnancy on renal angiomyolipoma (rAML) size and risk of haemorrhage in patients with tuberous sclerosis complex (TSC). METHODS: We searched PubMed, EMBASE, Medline and ClinicalTrials.gov using terms for "renal angiomyolipoma" and "pregnancy". English-language articles published between January 1st 2000, and December 31st 2020 of which full-text was available were included. The initial search resulted in 176 articles. After the screening process we included 45 case reports and 1 retrospective study. For the retrospective study we assessed the risk of bias using the Newcastle-Ottawa Scale. We included articles about renal AML and pregnancy with and without an established diagnosis of TSC. From these articles we recorded the rAML sizes and rAML complications. RESULTS: Seven case reports, from a total of 45 case reports, provided follow-up data on renal AML size (these were all cases of renal AML without a known diagnosis of TSC). Of these cases, renal AML size decreased in one patient, was stable in one patient, increased in three patients and fluctuated in two others. Renal AML size of women who suffered a haemorrhage were significantly larger (12.1 ± 4.6 cm) than rAMLs of women who did not suffer a haemorrhage (8.3 ± 3.2 cm). Data from the retrospective study showed no difference in renal complications between the women with and without a history of pregnancy. Haemorrhage occurred in 30% of the women with a history of pregnancy (n = 20) and in 11% in the patients without a history of pregnancy (n = 2), however this retrospective study had methodological limitations. CONCLUSION: The effect of pregnancy on renal AML size and complications in patients with TSC is unclear. More research is needed to determine the risk of pregnancy on TSC-associated kidney disease in TSC patient.


Subject(s)
Angiomyolipoma , Kidney Neoplasms , Leukemia, Myeloid, Acute , Tuberous Sclerosis , Humans , Female , Pregnancy , Angiomyolipoma/complications , Kidney Neoplasms/complications , Tuberous Sclerosis/complications , Retrospective Studies , Hemorrhage/etiology , Leukemia, Myeloid, Acute/complications
11.
Ann Hematol ; 103(5): 1775-1777, 2024 May.
Article in English | MEDLINE | ID: mdl-38556531

ABSTRACT

Pure red cell aplasia (PRCA) is a rare bone marrow (BM) disorder characterized by ineffective erythropoiesis, reduced reticulocyte count, normocytic anemia, and the absence of erythroid precursors. Here, we present a rare instance of PRCA occurring after ABO-matched allo-HSCT in a refractory/relapsed acute myeloid leukemia (R/R AML) patient. In this case, the patient received a combination treatment of Gilteritinib, Venetoclax, and Azacitidine. Remarkably, this treatment not only reduced myeloblasts but also facilitated the restoration of erythroid hematopoiesis.


Subject(s)
Aniline Compounds , Bone Marrow Diseases , Bridged Bicyclo Compounds, Heterocyclic , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Pyrazines , Red-Cell Aplasia, Pure , Sulfonamides , Humans , Azacitidine/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effects , Red-Cell Aplasia, Pure/etiology , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/complications , Bone Marrow Diseases/complications
12.
Front Immunol ; 15: 1335341, 2024.
Article in English | MEDLINE | ID: mdl-38545096

ABSTRACT

Introduction: Unmodified donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation (alloSCT) can boost the beneficial Graft-versus-Leukemia (GvL) effect but may also induce severe Graft-versus-Host-Disease (GvHD). To improve the balance between GvL and GvHD, it is crucial to identify factors that influence the alloreactivity of DLI. Methods: We investigated the effects of the presence of patient-derived antigen-presenting cells at time of DLI as estimated by the bone marrow (BM) chimerism status, lymphopenia as measured by the absolute lymphocyte count (ALC) at time of DLI, and the presence of a viral infection (de novo or reactivation) close to DLI on the risk of GvHD after DLI. The cohort consisted of patients with acute leukemia or myelodysplastic syndrome who prophylactically or pre-emptively received DLI as standard care after alemtuzumab-based alloSCT. In patients at high risk for relapse, DLI was administered at 3 months after alloSCT (n=88) with a dose of 0.3x106 or 0.15x106 T cells/kg in case of a related or unrelated donor, respectively. All other patients (n=76) received 3x106 or 1.5x106 T cells/kg, respectively, at 6 months after alloSCT. Results: For both DLIs, patients with reduced-intensity conditioning and an unrelated donor had the highest risk of GvHD. For DLI given at three months, viral infection within 1 week before and 2 weeks after DLI was an additional significant risk factor (hazard ratio (HR) 3.66 compared to no viral infection) for GvHD. At six months after alloSCT, viral infections were rare and not associated with GvHD. In contrast, mixed BM chimerism (HR 3.63 for ≥5% mixed chimerism compared to full donor) was an important risk factor for GvHD after DLI given at six months after alloSCT. ALC of <1000x106/l showed a trend for association with GvHD after this DLI (HR 2.05 compared to ≥1000x106/l, 95% confidence interval 0.94-4.45). Furthermore, the data suggested that the presence of a viral infection close to the DLI at three months or ≥5% mixed chimerism at time of the DLI at six months correlated with the severity of GvHD, thereby increasing their negative impact on the current GvHD-relapse-free survival. Conclusion: These data demonstrate that the risk factors for GvHD after DLI depend on the setting of the DLI.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Virus Diseases , Humans , T-Lymphocytes , Lymphocyte Transfusion/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Leukemia, Myeloid, Acute/complications , Unrelated Donors , Virus Diseases/complications
13.
Leuk Lymphoma ; 65(6): 816-824, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38475670

ABSTRACT

Cytomegalovirus (CMV) reactivation increases treatment-related mortality (TRM) after allogeneic hematopoietic cell transplantation (allo-HCT). We analyzed 141 adult acute leukemia (AL) patients suffered allo-HCT between 2017 and 2021, who developed CMV viremia post-HCT and treated with valganciclovir or foscarnet, to evaluate effectiveness and safety of both drugs. Viremia clearance rates (14 and 21 d post treatment) and toxicities were similar in two groups. However, valganciclovir was associated with a lower cumulative incidence of CMV recurrence within 180 days (16.7% vs. 35.7%, p=0.029) post CMV clearance. Finally, 2-year TRM was lower in valganciclovir group (9.7% ± 0.2% vs. 26.2% ± 0.3%, p = 0.026), result a superior 2-year overall survival (OS; 88.1% ± 5.2% vs. 64.4% ± 5.5%, p = 0.005) and leukemia-free survival (LFS; 82.0% ± 5.9% vs. 58.9% ± 5.6%, p = 0.009). Valganciclovir might decrease CMV viremia recurrence and led to better long-term outcome than foscarnet in adult AL patients developed CMV viremia post-HCT. Considering the inherent biases of retrospective study, well-designed trials are warranted to validate our conclusion.


Subject(s)
Antiviral Agents , Cytomegalovirus Infections , Cytomegalovirus , Foscarnet , Hematopoietic Stem Cell Transplantation , Transplantation, Homologous , Valganciclovir , Viremia , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Cytomegalovirus Infections/etiology , Valganciclovir/therapeutic use , Male , Female , Viremia/drug therapy , Adult , Antiviral Agents/therapeutic use , Foscarnet/therapeutic use , Middle Aged , Cytomegalovirus/drug effects , Retrospective Studies , Young Adult , Aged , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/mortality , Treatment Outcome , Leukemia/therapy , Leukemia/complications , Leukemia/mortality
15.
Vestn Oftalmol ; 140(1): 72-78, 2024.
Article in Russian | MEDLINE | ID: mdl-38450469

ABSTRACT

The article presents a clinical case of bilateral Terson syndrome caused by the manifestation of acute myeloid leukemia. A 32-year-old man complained of a sharp decrease in vision in both eyes. Spontaneous subarachnoid hemorrhage occurred secondary to acute myeloid leukemia. Uncorrected visual acuity (UCVA) amounted to OD=0.01, OS=0.005. The anterior segment was normal in both eyes, voluminous immobile white-gray mass measuring 7-9 DD that completely covered the macula (intense hyperechoic cell suspension with a volume of about 1/2 of the vitreous cavity, ultrasound B-scan) were visualized in the posterior pole of the vitreous body of both eyes under conditions of maximum drug-induced mydriasis. Diagnosis: vitreous hemorrhage due to subarachnoid hemorrhage in both eyes secondary to acute myeloid leukemia. Vitrectomy was performed in both eyes. UCVA increased to 0.05 in both eyes. Vitrectomy contributed to improvement of visual functions and patient quality of life.


Subject(s)
Leukemia, Myeloid, Acute , Vitreous Hemorrhage , Male , Humans , Adult , Vitreous Hemorrhage/diagnosis , Vitreous Hemorrhage/etiology , Vitreous Hemorrhage/surgery , Quality of Life , Vitreous Body , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/diagnosis , Vitrectomy
16.
Bone Marrow Transplant ; 59(4): 541-549, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38321271

ABSTRACT

This study aimed to address the prognostic impact of center experience based on the data of 7821 adults with acute myeloid leukemia who underwent allogeneic hematopoietic cell transplantation (HCT) from 2010 to 2019 in Japan, where medical care was provided within a uniform healthcare system. Center experience was defined based on the number of allogeneic HCTs performed for any indication during the study period, by which centers were divided into low-, intermediate-, and high-volume centers. After adjusting for known confounding factors, the risk of overall mortality was lowest for the high-volume centers and highest for the low-volume centers, with the difference between the center categories attributed primarily to the risk of relapse. Patients transplanted at high-volume centers had higher risks of acute and chronic graft-versus-host diseases but without an increased risk of non-relapse mortality (NRM). These findings reveal the presence of a center effect in allogeneic HCT conducted during the past decade in Japan, highlighting the difference in relapse based on center experience. The weaker effect on NRM compared with that on relapse suggests that the transplantation care quality is becoming equalized across the country.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Adult , Humans , Transplantation, Homologous/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia, Myeloid, Acute/complications , Prognosis , Recurrence , Retrospective Studies , Graft vs Host Disease/etiology , Transplantation Conditioning/adverse effects
17.
Exp Hematol ; 132: 104179, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38342295

ABSTRACT

Myeloid leukemia associated with Down syndrome (ML-DS) responds well to chemotherapy and has a favorable prognosis, but the clinical outcome of patients with refractory or relapsed ML-DS is dismal. We recently reported a case of relapsed ML-DS with an effective response to a DNA methyltransferase inhibitor, azacitidine (AZA). However, the efficacy of AZA for refractory or relapsed ML-DS remains uncertain. Here, we investigated the effects and mechanism of action of AZA on three ML-DS cell lines derived from relapsed cases. AZA inhibited the proliferation of all examined ML-DS cell lines to the same extent as that of AZA-sensitive acute myeloid leukemia non-Down syndrome cell lines. Transient low-dose AZA treatment exerted durable antileukemic effects on ML-DS cells. The inhibitory effect included cell cycle arrest, apoptosis, and reduction of aldehyde dehydrogenase activity. Comprehensive differential gene expression analysis showed that AZA induced megakaryocytic differentiation in all ML-DS cell lines examined. Furthermore, AZA induced activation of type I interferon-stimulated genes, primarily involved in antiproliferation signaling, without stimulation of the interferon receptor-mediated autocrine system. Activation of the type I interferon pathway by stimulation with interferon-α exerted antiproliferative effects on ML-DS cells, suggesting that AZA exerts its antileukemic effects on ML-DS cells at least partially through the type I interferon pathway. Moreover, the effect of AZA on normal hematopoiesis did not differ significantly between individuals with non-Down syndrome and Down syndrome. In summary, this study suggests that AZA is a potentially effective treatment option for ML-DS disease control, including relapsed cases, and has reduced side effects.


Subject(s)
Azacitidine , Down Syndrome , Enzyme Inhibitors , Interferon Type I , Leukemia, Myeloid, Acute , Humans , Azacitidine/pharmacology , Azacitidine/therapeutic use , Cell Line , DNA , Down Syndrome/complications , Down Syndrome/drug therapy , Down Syndrome/genetics , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Methyltransferases
18.
Thromb Res ; 236: 30-36, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38387301

ABSTRACT

Coagulation disorders frequently complicate the clinical course of acute myeloid leukemia (AML) patients. This study examined the frequency and prognostic significance, with regards of early mortality, of the presence of overt disseminated intravascular coagulation (DIC) at AML diagnosis and its correlation with clinical and biological characteristics. A retrospective analysis of 351 newly diagnosed non-promyelocytic AML patients was conducted, utilizing the 2018 ISTH DIC-Score criteria to evaluate the presence of overt DIC at AML onset. The study cohort had a median age of 65 years with a predominance of male gender (59 %). Overt DIC was present in 21 % of cases and was associated with advanced age, comorbidities, poor performance status, hyperleukocytosis, LDH levels, NPM1 mutations, expression of CD33 and CD4, and lack of expression of CD34. With a median follow-up of 72 months (3-147 months), the 6-year overall survival (OS) was 17.4 %, with patients having overt DIC showing significantly poorer outcomes (7.2 % compared to 20.3 % of those without DIC, p < 0.001). Patients with overt DIC showed markedly high early mortality rates at 30 (42.5 % vs 8 %), 60 (49.3 % vs 16.9 %), and 120 days (64.4 % vs 25.6 %) from disease onset. In multivariate analysis overt DIC retained its independent prognostic value for early mortality. In conclusion, the prevalence and clinical relevance of DIC in non-promyelocytic AML is not negligible, underlining its potential as an unfavorable prognostic marker. In newly diagnosed patients with AML, early recognition and measure to counteract coagulation disturbances might help mitigate the elevated mortality risk associated with DIC.


Subject(s)
Disseminated Intravascular Coagulation , Leukemia, Myeloid, Acute , Humans , Male , Aged , Female , Disseminated Intravascular Coagulation/etiology , Retrospective Studies , Leukemia, Myeloid, Acute/complications , Prognosis , Blood Coagulation
19.
PLoS One ; 19(2): e0297805, 2024.
Article in English | MEDLINE | ID: mdl-38363781

ABSTRACT

BACKGROUND: Leukemia cutis (LC) is an extramedullary acute myeloid leukemia (AML) infiltrate. No previous study has described the clinical characteristics and outcomes of Thai patients diagnosed with AML with LC. MATERIALS AND METHODS: We conducted a 7-year retrospective case-control study on Thai AML patients at Siriraj Hospital from November 2013 to July 2020. Patients were divided into LC and non-LC groups. Initial clinical presentations and laboratory findings were examined to identify LC-associated factors. Overall survival (OS) and relapse-free survival (RFS) were assessed. Pathological tissues underwent re-evaluation to validate the LC diagnoses. RESULTS: The study included 159 patients in a 2:1 ratio (106 non-LC and 53 LC). The LC group had a mean ± SD age of 54.3 ± 15.5 years; females were predominant. Three-fifths of the LC patients had intermediate-risk cytogenetics; 20.4% had an adverse risk, and 10.2% had a favorable risk. Most were classified as AML-M4 and AML-M5. Leukemic nodules were the primary finding in 58.5% of the cases, mainly on the legs. In the multivariate analysis of predictive factors associated with LC, organomegalies, specifically hepatomegaly, and lymphadenopathy, remained significant factors associated with LC [OR 4.45 (95%CI 1.20, 16.50); p = 0.026 and OR 5.48 (95%CI 1.65, 18.20); p = 0.005], respectively. The LC group demonstrated a significantly reduced OS (log-rank test p = 0.002) (median OS of 8.6 months vs. 32.4 months). RFS was considerably lower in the LC group (log-rank test p = 0.001) (median duration of 10.3 months vs. 24.4 months in the non-LC). CONCLUSIONS: AML patients who developed LC tended to experience notably poorer prognoses. Therefore, it is imperative to consider aggressive treatment options for such individuals. The presence of organomegalies in AML patients serves as a strong predictor of the possible occurrence of LC when accompanied by skin lesions.


Subject(s)
Leukemia, Monocytic, Acute , Leukemia, Myeloid, Acute , Skin Neoplasms , Female , Humans , Adult , Middle Aged , Aged , Retrospective Studies , Case-Control Studies , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/pathology , Skin Neoplasms/complications , Recurrence , Prognosis
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