History Of Acute Myeloid Leukemia Research Articles

DEVELOPMENT OF SYSTEMIC MASTOCYTOSIS AFTER BONE MARROW TRANSPLANTATION FOR AN ACUTE MYELOID LEUKEMIA: DONOR DERIVEN DISEASE OR SYSTEMIC MASTOCYTOSIS WITH AN ASSOCIATED MYELOID NEOPLASM

Abstract Introduction/Objective Systemic mastocytosis may have variable presentation ranging from an indolent disease to an aggressive form. Systemic mastocytosis with an associated myeloid neoplasm can occur simultaneously, or within an interval of a myeloid neoplasm and should meet the diagnostic criteria of both entities. Methods/Case Report Herein, we present a patient with history of acute myeloid leukemia with KMT2A(11q23) amplification who initially underwent an allogeneic hematopoietic stem cell transplantation from a matched sibling donor. One year later, the patient developed isolated central nervous system relapse, as well as evidence of molecular relapse in the bone marrow and underwent a second allogeneic transplantation, but this time, from a matched unrelated donor. The 100 days post second transplant bone marrow biopsy was negative for involvement by acute myeloid leukemia and the chimerism study revealed evidence of total engraftment with 100% donor cells. Additionally, Fluorescence in situ hybridization analysis detected no evidence of KMT2A amplification. However, morphologic examination of the bone marrow biopsy demonstrated involvement by systemic mastocytosis with multiple dense aggregates of CD117 and tryptase positive mast cells showing spindled cell morphology. Mast cells were positive for CD25 and demonstrated negative expression of CD2 and CD30. PCR analysis of the peripheral blood did not detect evidence of KIT mutation, but serum tryptase was elevated. Results (if a Case Study enter NA) NA Conclusion This case highlights a rare instance of systemic mastocytosis in the setting of remission from an acute myeloid leukemia in a post transplantation bone marrow and represents a diagnostic challenge. While development of systemic mastocytosis in a patient with prior history of an acute myeloid leukemia suggests the possibility of systemic mastocytosis with an associated myeloid neoplasm, some other features including the complete remission and total engraftment of the post transplantation bone marrow with 100% donor cells, raise the possibility of a donor driven disease.

Management of Spinal Myeloid Sarcoma in a 23-Year-Old Woman With a History of Acute Myeloid Leukemia

Myeloid sarcoma (MS) is an uncommon extramedullary tumor comprising immature myeloid cells, primarily associated with acute myeloid leukemia (AML). Spinal involvement is observed in fewer than 1% of cases. We present an unusual case of extramedullary MS in a patient with AML. A 23-year-old woman with a history of AML presented with neurological symptoms, including limb pain, weakness, and numbness. Imaging revealed an intramedullary enhancing mass at the cervical level. Partial laminectomy and microsurgical resection were performed, followed by laminoplasty. Immunohistochemistry supported the diagnosis, confirming MS. The patient was subsequently transferred to the hematologic department and received tailored treatment. The diverse clinical manifestations of spinal MS pose diagnostic challenges. In this case, an atypical intramedullary location led to incorrect initial diagnostic impressions. Comprehensive evaluations, including repeated biopsies and immunohistochemistry, were crucial for an accurate diagnosis. Treatment strategies vary based on systemic involvement, and prompt diagnosis is important for favorable outcomes. MS, especially in the spine, presents diagnostic and therapeutic complexities. Timely recognition, an accurate diagnosis through comprehensive evaluations, and tailored treatment strategies are crucial for positive outcomes in this rare hematologic entity.

Severe Sepsis During Treatment for Childhood Leukemia and Sequelae Among Adult Survivors

Children undergoing treatment for leukemia are at increased risk of severe sepsis, a dysregulated immune response to infection leading to acute organ dysfunction. As cancer survivors, they face a high burden of long-term adverse effects. The association between sepsis during anticancer therapy and long-term organ dysfunction in adult survivors of childhood cancer has not been examined. To determine whether severe sepsis during therapy for leukemia in childhood is associated with subsequent chronic health conditions in adult survivors. This cohort study included 644 adult survivors of childhood leukemia who were diagnosed between January 1, 1985, and July 19, 2010, and participated in the St Jude Lifetime Cohort Study. Participants were excluded if they received hematopoietic cell transplant or had relapsed leukemia. Data collection ended June 30, 2017. Data were analyzed from July 1, 2020, to January 5, 2024. Severe sepsis episodes, defined according to consensus criteria as septic shock, acute respiratory distress syndrome, or multiorgan dysfunction associated with infection occurring during anticancer therapy, were abstracted by medical record review for all participants. Common Terminology Criteria for Adverse Events-defined chronic health condition outcomes were independently abstracted. Associations between sepsis and cumulative incidence of chronic health conditions (eg, cardiovascular, pulmonary, kidney, neurological, and neurocognitive outcomes) were compared by adjusted hazard ratios from Cox proportional hazards logistic regression. Inverse propensity score weighting was used to adjust for potential confounders, including age, year of diagnosis, and leukemia type. The study sample consisted of 644 adult survivors of pediatric leukemia (329 women [51.1%] and 315 men [48.9%]; including 56 with a history of acute myeloid leukemia and 585 with a history of acute lymphoblastic leukemia) who were most recently evaluated at a median age of 24.7 (IQR, 21.2-28.3) years at a median time after leukemia diagnosis of 17.3 (IQR, 13.7-21.9) years. Severe sepsis during treatment of acute childhood leukemia occurred in 46 participants (7.1%). Participants who experienced severe sepsis during treatment were more likely to develop moderate to severe neurocognitive impairment (29 of 46 [63.0%] vs 310 of 598 [51.8%]; adjusted hazard ratio, 1.86 [95% CI, 1.61-2.16]; P < .001) significantly affecting attention, executive function, memory and visuospatial domains. Sepsis was not associated with long-term risk of cardiovascular, pulmonary, kidney, or neurological chronic health conditions. In this cohort study of long-term outcomes in survivors of pediatric leukemia, severe sepsis during anticancer therapy for leukemia was associated with a selectively increased risk for development of serious neurocognitive sequelae. Efforts to reduce the effects of anticancer therapy on long-term function and quality of life in survivors might include prevention of severe sepsis during therapy and early detection or amelioration of neurocognitive deficits in survivors of sepsis.

ENT manifestations of myeloid sarcoma

Myeloid sarcoma (MS) is a rare extra-medullary manifestation of acute myeloid leukaemia (AML) in the form of a first manifestation, progression or recurrence. Mostly located in the bones, it has the particularity of reaching the ENT sphere by mimicking common patho-logies, leading to a delay in diagnosis and treatment. The -mastoid involvement that we have encountered in our clinical -practice (clinical vignette) shows the complexity of identifying this pathology, with very few cases reported in the literature. The anamnesis, including a -history of AML, and the clinical examination help to guide the investigations. Targeted imaging, in this case CT/MRI combined with a biopsy of the lesion and a marrow puncture, is used to make the -diagnosis. Treatment with chemotherapy is indicated and rapidly initiated.

Abstract 14694: An Uncommon Mass, in an Uncommon Location, in a Common Patient?

Background: Myeloid sarcomas (MS) are rare extramedullary tumors composed of mature or immature myeloid cells. The heart is an uncommon site for this neoplasm. Case Presentation: A 68-year-old woman with a remote history of acute myeloid leukemia (AML) and allogeneic stem cell transplant presented with dyspnea. Her oxygen saturation was 70% on room air. Transthoracic echocardiography (TTE) revealed a nonhomogeneous intrapericardial mass measuring 6.3 cm by 10.0 cm, invading the right atrium and compressing the right ventricle (Figure 1). Due to persistent hypoxia, additional investigation with agitated saline contrast revealed a right-to-left intra-cardiac shunt. Cardiac magnetic resonance imaging showed invasion of the right and left ventricles, extension into the superior vena cava, and encasement of the right coronary artery. Due to worsening hypoxemia, vasopressin infusion and inhaled epoprostenol were initiated to reduce intracardiac shunting. Direct cardiac mass biopsy was considered prohibitive risk, however, a pericardiocentesis allowed for cytologic analysis of pericardial fluid which revealed atypical white blood cells, and subsequent flow cytometry indicated an aberrant myeloid population with monocytic features consistent with MS. She initiated chemotherapy with decitabine and low dose cytarabine. On day 6 of chemotherapy, she started external beam radiation therapy. A repeat TTE on day 10 of therapy showed a marked reduction in tumor size and intracardiac shunting. Discussion: MS can manifest before the development of bone marrow disease, following treatment for bone marrow disease, as relapse or progression of previous myelodysplastic or myeloproliferative neoplasms. With approximately fifty cases reported in the literature, most achieved temporary remission. Our approach to management included chemotherapy with decitabine and cytarabine and subsequent external-beam radiotherapy.

FORTITUDE: A Phase 2 Open-Label Study in Progress to Evaluate Etavopivat for the Treatment of Anemia in Patients with Lower-Risk Myelodysplastic Syndromes

Background: Most patients with lower-risk myelodysplastic syndrome (LR-MDS) develop anemia and a high proportion of patients become dependent on red blood cell (RBC) transfusions. MDS-related anemia is associated with low hemoglobin (Hb) levels, iron overload and poor quality of life. Erythropoiesis-stimulating agents and other drugs, including lenalidomide, luspatercept and imetelstat (an investigational product), can lead to RBC transfusion independence and improve Hb levels in many patients; however, responses are generally transient and novel treatments are needed for this population. Etavopivat is an investigational, once-daily, selective erythrocyte pyruvate kinase (PKR) activator in development for the treatment of sickle cell disease (SCD) and anemia in patients with LR-MDS. In a phase 1 study in adult and adolescent patients with SCD by Saraf et al. HemaSphere. (2022), etavopivat 400 mg once daily was considered well tolerated and showed sustained Hb increases up to 12 weeks for most patients. Additional studies in healthy volunteers and patients with SCD support an acceptable safety profile together with improved RBC health and function during continuous treatment with etavopivat. In patients with LR-MDS, ineffective hematopoiesis may be due, in part, to insufficient ATP production, leading to increased erythroid lineage apoptosis. By activating PKR, etavopivat may improve RBC health and function by stimulating energy production (increasing ATP levels), increasing Hb levels (decreasing anemia), and decreasing erythroid lineage apoptosis. Aims:Describe the design of a multicenter, open-label, phase 2 study (FORTITUDE; NCT05568225) evaluating hematologic improvements in patients with very low-, low- and intermediate-risk MDS during treatment with etavopivat. Study design:Key eligibility criteria include age ≥18 years; very low-, low- and intermediate-risk MDS per the Revised International Prognostic Scoring System; and anemia defined by mean Hb &amp;lt;10.0 g/dL and &amp;lt;3 RBC transfusions &amp;lt;16 weeks prior to first dose for non-transfusion-dependent (NTD) patients or ≥3 units of RBCs for anemia &amp;lt;16 weeks prior to first dose for transfusion-dependent (TD) patients. Key exclusion criteria include MDS associated with del 5q cytogenetic abnormality and known TP53 abnormality, history of acute myeloid leukemia, and an absolute neutrophil count &amp;lt;0.5 × 10 9/L. Additional exclusion criteria include prior treatment with azacitidine; decitabine; erythropoietin, other hematopoietic growth factor treatment or lenalidomide within 30 days of Day 1 or anticipated to be required during the study; and luspatercept within 30 days of Day 1 for NTD patients and within 16 weeks of Day 1 for TD patients. Patients will receive etavopivat 400 mg once daily for at least 48 weeks. Treatment may be continued beyond 48 weeks in patients demonstrating clinical benefit. The primary objective of the study is to assess hematologic improvements based on an erythroid response over any continuous period ≥8 weeks within 24 weeks on etavopivat treatment in patients with LR-MDS. The primary endpoint will be based on the combined incidence of: ≥1.5 g/dL increase in Hb from baseline maintained for ≥8 consecutive weeks for NTD patients; absence of any transfusion for ≥8 consecutive weeks for low transfusion-burden patients; and reduction by ≥50% of RBC units for ≥8 consecutive weeks for high transfusion-burden patients. Safety, tolerability, pharmacokinetic, and pharmacodynamic properties of etavopivat will be evaluated. FORTITUDE is open for enrollment in Canada, France, Germany, and the USA. Planned enrollment includes approximately 15 patients in each of the three transfusion requirement-based groups (Figure). Statistical analysis: The primary endpoint (pooled incidence) will be tested with a one-sided Fisher's exact test at the significance level of 0.025 where 0.2 is the assumed null proportion. Summary:Etavopivat is a novel, investigational, once-daily, selective PKR activator with the potential to improve RBC health and lifespan. This phase 2 study will assess the safety of etavopivat and its impact on Hb levels and RBC transfusion burden in patients with LR-MDS and anemia.

Aeromonas hydrophila infection in acute myeloid leukemia: A case report

Rationale: Aeromonas hydrophila, a bacterium commonly found in a variety of soils, aquatic habitats, and other natural environments, is known for causing infections and hemorrhagic diseases in both aquatic and terrestrial animals. Patients with leukemia, when infected by Aeromonas hydrophila following chemotherapy, face an increased risk of developing necrotizing fasciitis. Patient concerns: A 48-year-old male with a history of acute myeloid leukemia presented with swelling and pain in his right hand after being stabbed by a grass carp two days ago. The injury occurred on the fifth day after his last chemotherapy session when he was accidentally punctured in the right thumb and ring finger by a carp while fishing. Two days following the injury, the skin isurrounding the wound turned black immediately, while the rest of his hand was reddened, swollen, and bleeding. Diagnosis: Aeromonas hydrophila infection in the soft tissue of the right hand. Interventions: Intravenous antibiotics and local debridement. Outcomes: The patient experienced an alleviation of systemic poisoning symptoms, effective control of the local wound infection. Lessons: It is important for physicians to appreciate the potential for highly unusual and life-threatening infections in patients with acute myeloid leukemia. Early diagnosis and prompt treatment can prevent the development of necrotizing fasciitis and save patients' lives.

Intracranial Myeloid Sarcoma Mimicking Hypertensive Intracerebral Hemorrhage.

We herein report a case of intracranial myeloid sarcoma mimicking hypertensive intracerebral hemorrhage. A 71-year-old man with a history of acute myeloid leukemia was admitted with acute-onset dysarthria. A hematoma-like lesion was found on computed tomography in the left putamen. Magnetic resonance imaging (MRI) and cerebrospinal fluid cytology confirmed the diagnosis of intracranial myeloid sarcoma. The patient showed a favorable response to chemotherapy, and follow-up MRI revealed shrinkage of the tumor. Since the computed tomography findings resemble those of intracerebral hemorrhage, it is important to suspect intracranial neoplasm, particularly in cases with a history of hematologic diseases.

BCL2 Inhibition: A New Paradigm for the Treatment of AML and Beyond.

Altering the natural history of acute myeloid leukemia (AML) in unfit and older patients has proved a highly challenging hurdle, despite several decades of concerted clinical trial effort. The arrival of venetoclax (VEN) to the clinical stage represents the most important therapeutic advance to date for older patients with AML. In this review, we will explain how and why VEN works, summarize its remarkable pathway to regulatory approval, and highlight the key milestones that have been important for its successful development in AML. We also provide perspectives on some of the challenges associated with using VEN in the clinic, emerging knowledge regarding mechanisms of treatment failure, and current clinical research directions likely to shape how this drug and others in this new class of anticancer agents are used in the future.

GVHD in its sclerodermiform form revealing type 1 diabetes: A case report

Sclerodermiform syndrome is Common in diabetic, it encompasses a set of manifestations that preferentially affect the hands and back, but the association of type 1 diabetes with systemic sclerosis is a rare entity. We report the case of 18-year-old patient from a consanguineous marriage, with a history of acute myeloid leukemia which he was treated by an allograft in France associated with chemotherapy 9 session and immunosuppressants currently in complete remission, diabetic type 1 for 4 years, hypothyroidism under levothyrox 50ug / d. At the interrogation the patient reported the consequences of the graft were marked by stage I cutaneous GVHD confirmed by skin biopsy of which he received corticosteroid therapy at a dose of 10mg / day in addition to neoral or slightly atrophic hyperpigmented macules not sclerotic at the level of the back and the lateral surface of the left foot. The patient also had corticosteroid-induced complications, including diabetes and osteoporosis. On physical examination tendon retraction, elbows and finger, Amyotrophy of the hands, palpable thyroid not increased volume allowed for glycemic imbalance. At TSH biology = 6uui / ml, HBA1C = 8%, anti-GAD antibody negative to cervical ultrasound: thyroid hypotrophy with thyroid nodules classified EUTIRADS 2. The patient is referred for follow-up in dermatology. The association of sweet diabetes and sclerodermiform lesions is frequently linked to the glycemic imbalance responsible for an accumulation of extracellar matrix and excessive glycation of collagen. The search for signs of scleroderma should be evoked in front of a diabetic hand syndrome to Watch for and treat associated pathologies.

73 WHICH IS THE CULPRIT OF THIS MYOCARDIAL INFILTRATION?

Abstract Introduction Myocardial infiltration by primary cardiac neoplasm is a rare condition and the pathological spectrum includes more widespread benign cell types, providing exceptional diagnostic and therapeutic challenges. Refractory heart failure, pericardial effusion and arrhythmias due to infiltrative mass are the most common clinical manifestations. Multimodality imaging, with echocardiography, computed tomography and magnetic resonance imaging, is essential to determine the characteristics of a cardiac tumor. Clinical case: A 35-year-old man without cardiovascular risk factors presented with two months of shortness of breath and weight loss. A previous history of acute myeloid leukemia undergoing allogenic bone marrow transplant was reported. Transthoracic echocardiography revealed an apical thrombus in left ventricle with inferior and septal hypokinesia conditioning mildly reduced ejection fraction, circumferential pericardial effusion without cardiac tamponade and abnormal right ventricular thickening (Figure 1). The cardiac magnetic resonance imaging confirmed diffuse thickening of the right ventricular free wall (maximum diameter 30 mm), suspected for myocardial infiltration, extending to the right atrium and left ventricle with an ischemic pattern of the inferior wall (Figure 2). No coronary artery disease was found by coronary angiography, but the right coronary artery was incorporated by the pathological tissue in chest computed tomography scan. Cardiac positron emission tomography demonstrated the presence of neoplastic tissue with increased metabolic activity, whose similar characteristics were also evident in the ascending aorta and aortic arch. Being the percutaneous endomyocardial biopsy inconclusive, a pericardiectomy was performed through a median sternotomy incision, showing widespread cardiac neoplastic infiltration. Histopathological analysis, done on samples taken by surgical myocardial biopsy, revealed tissue involvement by a rare and aggressive cardiac anaplastic large T-cell non-Hodgkin lymphoma (ALK -, Ki-67 90%). Few days after surgery, the patient developed a refractory cardiogenic shock and unluckily died before establishing an adequate therapy. Conclusion Primary cardiac lymphoma is very infrequent and the non-specificity of the symptoms makes the diagnosis extremely challenging and often limited to autopsy findings. Our case highlights the importance of an appropriate diagnostic algorithm that can allow an early diagnosis and an adequate therapy of this otherwise fatal pathology. In this condition surgical removal of the tumor in not indicated, being chemotherapy the only effective treatment. However, because of rarity, data are lacking to produce definitive regarding guidelines.

123. Chromosomal microarray assists interpretation of cytogenetic abnormalities in hematopoietic malignancies

Chromosome analysis is a first-line ancillary test performed on bone marrows to evaluate for hematopoietic malignancy. While characteristic cytogenetic findings correlate with pathology in most cases, the chromosomal abnormalities are sometimes too complex for complete characterization, limiting interpretation of the results. Additionally, chromosomal abnormalities may lack correlation with the hematopathology findings. Here, we present two cases where chromosomal microarray was performed, which aided interpretation of chromosome analysis. Case 1: A patient with a history of acute myeloid leukemia (AML) with NPM1 mutation had a bone marrow evaluated for residual disease. Although chromosome analysis identified a mosaic balanced translocation between chromosomes 7 and 17, concurrent ancillary studies were unrevealing. The significance of this finding was unclear given the unremarkable morphology and flow cytometry. Chromosomal microarray identified deletions of NF1 and SUZ12 on chromosome 17 as well as deletion of ASXL1 on chromosome 20, which may be a driver for leukemogenesis in this case. Case 2: A patient presented with circulating blasts and was diagnosed with AML. Chromosome analysis demonstrated deletion of chromosome 5q and loss of chromosome 7. However, additional complex chromosomal abnormalities were also identified, including a jumping translocation. Chromosomal microarray showed complex abnormalities of chromosome 1p, gain of chromosome 5p including TERT and IL7R, deletion of IKZF1 on chromosome 7, and deletion of TP53 on chromosome 17. These chromosomal microarray findings provide greater insight toward AML pathogenesis. These case reports demonstrate the utility of chromosomal microarray in further defining chromosomal findings with unclear significance to further understand disease pathogenesis.

P244 Catheter-associated blood stream infections due to Wickerhamiella pararugosa in a patient with acute myeloid leukemia: Review of lit eratures

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM ObjectivesThis report aims to present a case of Candida pararugosa bloodstream infection, review previous cases with C. pararugosa infections, and provide a concise review of the clinical background, risk factors, and brief the management of infections.MethodsA 3-year-old boy with a history of acute myeloid leukemia was hospitalized in Omid Hospital, Isfahan, Iran. Two consecutive blood cultures were taken from the peripheral vein and port catheter; after that empirically meropenem was administered.Results Candida pararugosa were isolated from blood based on conventional and molecular assays. Furthermore, the antifungal susceptibility profiles of the isolate were determined, which exhibited resistance to fluconazole (8 μg/ml). Antifungal therapy with caspofungin and removing the patient's port led to a significant clinical improvement of the patient's conditions. So far, in the literature review, 10 cases of clinical C. pararugosa isolates were found, of which 5 points had bloodstream infections.ConclusionInfections caused by uncommon Candida species have dramatically increased in recent decades, mostly among hematological malignancies. Most patients with C. pararugosa infection presented with specific underlying conditions, such as malignancy, sarcoma, surgery, and adult acute myeloid leukemia. Patients with indwelling catheters run a high risk of acquiring C. pararugosa bloodstream infection. Therefore, special consideration should be given to opportunistic fungal infections in immunocompromised individuals using catheters.

Relapsed acute myeloid leukemia presenting as conjunctival myeloid sarcoma: a case report

BackgroundConjunctival myeloid sarcoma (MS) as an isolated presentation of acute myeloid leukemia (AML) relapse is rare. Here, we report a case of unilateral conjunctival MS revealed as a sign of AML relapse.Case presentationA 50-year-old man with a history of AML in remission visited our clinic presenting with a left conjunctival injection persisting for 1 month. Diffuse subconjunctival thickening with conjunctival vascular engorgement was observed. Ultrasound biomicroscopy revealed a hyper-reflective, thickened conjunctiva in his left eye. During the incisional biopsy, the lesion was strongly attached to the underlying sclera; histopathologic examination revealed infiltration of leukemic blasts. The relapse of AML was confirmed by a successive bone marrow biopsy. The ocular lesion disappeared after allogeneic peripheral blood stem cell transplantation (PBSCT) and concomitant salvage radiotherapy on the left eye. The patient has remained in remission for 3 years after allogeneic PBSCT.ConclusionsIncidental conjunctival lesions can indicate AML relapse in patients treated earlier for AML. An ophthalmologist may have a role in the early detection of AML when a patient presents with an atypical conjunctival lesion.

Myeloid Sarcoma Involving the Testis in Adults: Clonal Evolution of Acute Myeloid Leukemia.

To describe the clinical, histologic, immunophenotypic, and genetic characteristics of myeloid sarcoma (MS) diagnosed in the testes of adults, 3 cases were identified, and information on their presentation, clinical features, treatment, and outcome was retrieved from the medical records. In addition, histologic, immunophenotypic, and molecular characteristics were reviewed. This showed that all patients had a previous history of acute myeloid leukemia (AML), in 2 cases diagnosed >10 years before the testicular lesions. In 1 case, there was bilateral involvement, while in 2, involvement was unilateral. The neoplastic cells showed evidence of cytogenetic/molecular clonal evolution in all cases, 1 of which also had significant immunophenotypic changes. A mutational profile including NPM1 p.Trp288Cysfs*12, IDH1 p.Arg132His NRAS p.Gly12Asp was seen in 2 of the 3 cases. Concurrent bone marrow involvement by a myeloid neoplasm was diagnosed in 2 patients, in 1, there was AML in the second 8% blasts. These patients progressed rapidly after MS and had a dismal outcome. The patient with no concurrent bone marrow disease had a favorable outcome. In conclusion, MS involving the testes of adults is a rare event, and it may represent the clonal evolution of AML.

Atypical Targetoid Lesions as the Presenting Sign of Myeloid Sarcoma

Myeloid sarcoma (MS), also known as chloroma or granulocytic sarcoma, is a rare extramedullary tumor mass that commonly occurs in acute myeloid leukemia (AML). MS may occur before other clinical signs of AML, or alongside other known AML symptoms. MS can also appear in isolation, which makes diagnosis challenging. Clinical knowledge about a typical presentation of myeloid sarcoma is limited, given the heterogeneity in the location and size of MS lesions. We describe a patient with a history of AML who developed an eruption of atypical targetoid purpuric lesions. Diagnostic workup, including laboratory and histologic specimen from the skin were consistent with MS. MS should be suspected in a patient with a history of myeloproliferative disorder who develops atypical targetoid purpuric papules.

Bone marrow-derived mesenchymal stem cells promote Helicobacter pylori-associated gastric cancer progression by secreting thrombospondin-2.

ObjectivesBone marrow‐derived cells (BMDCs), especially mesenchymal stem cells (MSCs), may be involved in the development of Helicobacter pylori‐associated gastric cancer (GC) in mice, but the specific mechanism remains unclear, and evidence from human studies is lacking.Materials and MethodsTo verify the role of BM‐MSCs in H pylori‐associated GC, green fluorescent protein (GFP)‐labelled BM‐MSCs were transplanted into the subserosal layers of the stomach in a mouse model of chronic H pylori infection. Three months post‐transplantation, the mice were sacrificed, and the gastric tissues were subjected to histopathological and immunofluorescence analyses. In addition, we performed fluorescence in situ hybridization (FISH) and immunofluorescence analyses of gastric tissue from a female patient with H pylori infection and a history of acute myeloid leukaemia who received a BM transplant from a male donor.ResultsIn mice with chronic H pylori infection, GFP‐labelled BM‐MSCs migrated from the serous layer to the mucosal layer and promoted GC progression. The BM‐MSCs differentiated into pan‐cytokeratin‐positive epithelial cells and α‐smooth muscle actin‐positive cancer‐associated fibroblasts (CAFs) by secreting the protein thrombospondin‐2. FISH analysis of gastric tissue from the female patient revealed Y‐chromosome‐positive cells. Immunofluorescence analyses further confirmed that Y‐chromosome‐positive cells showed positive BM‐MSCs marker. These results suggested that allogeneic BMDCs, including BM‐MSCs, can migrate to the stomach under chronic H pylori infection.ConclusionsTaken together, these findings imply that BM‐MSCs participate in the development of chronic H pylori‐associated GC by differentiating into both gastric epithelial cells and CAFs.

Brentuximab Vedotin with R-CHP Chemotherapy As Frontline Treatment for Patients with CD30 Positive Primary Mediastinal Large B-Cell, Diffuse Large B-Cell, and Grey Zone Lymphomas: Results of a Phase I/II Multisite Trial

Brentuximab Vedotin with R-CHP Chemotherapy As Frontline Treatment for Patients with CD30 Positive Primary Mediastinal Large B-Cell, Diffuse Large B-Cell, and Grey Zone Lymphomas: Results of a Phase I/II Multisite Trial

Use of a Hemoglobin Substitute (HBOC-201) to Treat Acute Anemia in a Leukemic Patient with Anti-Vel Antibodies

BackgroundThe Vel-negative blood type is a rare autosomal recessive trait, occurring in 1 in 4000 persons. It is extremely difficult to supply blood to patients with anti-Vel antibodies, and the situation is even more challenging for Vel-negative patients with leukemia who may have high transfusion needs. There are case reports of treatment with hemoglobin substitutes in Jehovah's Witnesses and surgical patients. To the best of our knowledge, we report the first use of a hemoglobin substitute, HBOC-1201 (HemoPure) to treat a patient with refractory acute myeloid leukemia (AML) and anti-Vel antibodies.Case ReportOur patient is a 67-year-old Caucasian man with a one-year history of acute myeloid leukemia, refractory to multiple hypomethylator- and chemotherapy-based regimens. History is also significant for coronary artery disease with type 2 NSTEMI due to severe anemia. He has experienced prolonged pancytopenia due to leukemia and chemotherapy and required blood transfusions approximately weekly. Anti-Vel antibodies make transfusion of compatible blood challenging, and we utilized a hemoglobin transfusion threshold of 5 g/dL. Working with the American Red Cross and the American Rare Donor Program (ARDP), we transfused 44 units of Vel-negative blood over a one-year period, depleting the available Vel-negative units in North America. He presented to the hospital with productive cough and dyspnea. Initial labs revealed acute on chronic anemia with hemoglobin 3.5 g/dL. CT of the chest revealed right lower lobe pneumonia. Given critical anemia in the setting of pneumonia and possible sepsis, the patient needed immediate blood transfusion. Compatible Vel-negative blood was not available in North America. While awaiting availability of international blood units through the Red Cross and ARDP, we considered the choices of 1) transfusing incompatible blood or 2) administering a blood substitute. Because individuals with anti-Vel antibodies may develop severe acute hemolytic transfusion reactions when transfused incompatible blood, we chose to treat with HBOC-1201 (Biopure Corporation, Cambridge, MA), a bovine hemoglobin polymer that lacks a red blood cell membrane and thus red cell antigens such as Vel. We obtained an emergency IND from the FDA and local IRB approval. Three 32-gram units of HBOC-1201 were successfully transfused, with hemoglobin rise from 3.5 to 4.5 g/dL. Common adverse effects associated with the use of acellular hemoglobin substitutes include increase in concentration of methemoglobin and vasopressor effects leading to elevated blood pressure, fluid overload, and myocardial infarction. Our patient was monitored closely and tolerated the transfusion without any apparent adverse events.ConclusionDuring a challenging clinical situation, we successfully treated severe acute anemia in a patient with refractory AML and anti-Vel antibodies, using the acellular bovine hemoglobin-based blood substitute HBOC-1201, when compatible blood was not available. The infusion was tolerated without complications. Hemoglobin substitutes may be considered as bridging treatments in critically anemic patients such as those with hematologic malignancies when red blood cell transfusion is not an option. DisclosuresNo relevant conflicts of interest to declare.

Oral myeloid sarcoma as an uncommon manifestation of acute myeloid leukemia: A case series and review of the literature

Background and OverviewOral myeloid sarcoma (MS) is an extramedullary tumor that can occur in the setting of acute myeloid leukemia, either as the first sign of an underlying disease or later in the course of disease. The authors’ aim was to present the clinical features of oral MS and review the literature. Case DescriptionCase 1 was an 82-year-old woman with an asymptomatic erythematous swelling on the maxillary gingiva and no history of hematologic malignancy. Case 2, a 65-year-old man, and case 3, a 58-year-old woman, each had a history of acute myeloid leukemia and a painful ulcer on the palatal mucosa and an asymptomatic ulcer on the lower lip mucosa, respectively. Case 1 was treated with focal radiation then chemotherapy and achieved complete remission initially, but died of relapse 2 years after diagnosis. Case 2 received radiotherapy and immunotherapy and had a complete response. Case 3 received chemotherapy and achieved remission initially, but relapsed and is undergoing investigational targeted therapies. Conclusions and Practical ImplicationsOral MS can manifest as gingival or mucosal swelling or ulceration and can indicate onset or relapse of associated hematologic malignancies, which often have a poor prognosis. Because patients with oral findings are likely to seek treatment from their dentists first, oral clinicians should maintain a broad differential diagnosis list when evaluating oral lesions, especially if treatment prescribed for a more common diagnosis fails to resolve the lesion.