Suspected coexistence of perianal necrotizing sweet syndrome in chronic myelomonocytic leukemia:A case report

BACKGROUND Chronic myelomonocytic leukemia(CMML)complicated with Sweet syndrome(SS)is a rare hematological neoplasm.However,cases of concomitant development of perianal necrotizing SS(NSS)have not been reported.CASE SUMMARY We report a case of a 49-year-old male patient who underwent sequential procedures for hemorrhoids and perianal abscess.He developed postoperative incision infection and was referred to the department where the authors work.Initially,perianal necrotizing fasciitis secondary to incision infection after perianal abscess surgery was suspected.Despite receiving antibiotic therapy and undergoing surgical debridement,deeper necrotic areas formed in the patient’s perianal wounds,accompanied by persistent high fever.Blood and fungal cultures yielded negative results.The final diagnosis was corrected to be CMML with suspected concomitant perianal NSS.CONCLUSION CMML with perianal NSS is a rare condition,often misdiagnosed as perianal abscess or perianal necrotizing fasciitis.Conventional antibiotic therapy and surgical debridement are ineffective in managing this condition.

Co-existing squamous cell carcinoma and chronic myelomonocytic leukemia with ASXL1 and EZH2 gene mutations:A case report

BACKGROUND Chronic myelomonocytic leukemia(CMML),a rare clonal hematopoietic stem cell disorder characterized by myelodysplastic syndrome and myeloproliferative neoplasms,has a generally poor prognosis,and easily progresses to acute myeloid leukemia.The simultaneous incidence of hematologic malignancies and solid tumors is extremely low,and CMML coinciding with lung malignancies is even rarer.Here,we report a case of CMML,with ASXL1 and EZH2 gene mutations,combined with non-small cell lung cancer(lung squamous cell carcinoma).CASE SUMMARY A 63-year-old male,suffering from toothache accompanied by coughing,sputum,and bloody sputum for three months,was given a blood test after experiencing continuous bleeding resulting from a tooth extraction at a local hospital.Based on morphological results,the patient was diagnosed with CMML and bronchoscopy was performed in situ to confirm the diagnosis of squamous cell carcinoma in the lower lobe of the lung.After receiving azacitidine,programmed cell death protein 1,and platinum-based chemotherapy drugs,the patient developed severe myelosuppression and eventually fatal leukocyte stasis and dyspnea.CONCLUSION During the treatment and observation of CMML and be vigilant of the growth of multiple primary malignant tumors.

Acute myelomonocytic leukemia and T-lymphoblastic lymphoma as simultaneous bilineage hematologic malignancy treated with decitabine:A case report

BACKGROUND Simultaneous bilineage hematologic malignancies are rare;however,several cases of acute myeloid leukemia(AML)and T-lymphoblastic lymphoma(T-LBL)cooccurrence have been reported.A standard treatment for simultaneous AML and T-LBL has not yet been established,and its prognosis is very poor.Further studies to develop standard treatments are required to increase patient survival rates.CASE SUMMARY A 69-year-old man complaining of pleuritic chest pain visited the emergency room.Computed tomography revealed multiple enlarged lymph nodes(LNs)in the neck and groin and pulmonary thromboembolism with pulmonary infarction.Furthermore,a peripheral blood smear performed due to leukocytosis revealed circulating blasts.Acute myelomonocytic leukemia(AMML)was diagnosed after bone marrow examination,and T-LBL positivity for terminal deoxynucleotidyl transferase,cluster of differentiation(CD)34,and CD4 was confirmed by cervical LN biopsy.Decitabine and dexamethasone were administered because he could not receive intensive chemotherapy due to poor performance status.Complete remission of AMML and T-LBL was achieved after 4 cycles of decitabine plus dexamethasone.CONCLUSION We report the therapeutic effect of decitabine,a hypomethylating agent(HMA),in patients with concurrent bilineage hematologic malignancies and suggest that further studies are required to evaluate the therapeutic effect of HMAs on both lymphoid and bilineage hematologic malignancies.

Initial Study on Immune Escape Mechanism of Mouse Acute Myelomonocytic Leukemic Cell Line WEHI-3

Objective： To investigate the expression of Fas, Fas ligand （FasL） and CD80 on the cell surface of mouse acute myelomonocytic leukemia cell line WEHI-3 and the function of FasL. Methods： The expression of Fas, FasL and CD80 was detected on WEHI-3 cell surface by flow cytometry. Simultaneously the function of FasL was determined by Thymidine （^3H-TdR） Incorporation. Results： The expression of CD80 and Fas on WEHI-3 cell surface was 5.06%±0.41% and 6.75%±2.31% （n=5） respectively, and the expression of FasL was up to 63.73%±5.23% （n=5）. The apoptotic rate of YAC-1 cells was 26%±4.5%, 35%±3.2% and 43%±2.7% （n=5） respectively when WEHI-3 （effector cell, E） and Fas^＋ YAC-1 cells （target cell, T） were cultured in the ratio of 3：1, 10：1 and 30：1. Conclusion： WEHI-3 cells express high FasL, low Fas and CD80, and can induce apoptosis of Fas^＋ YAC-1 cells.

Gene mutations in a patient with chronic myelomonocytic leukemia and changes upon progression to acute myeloid leukemia and during treatment

Objective Chronic myelomonocytic leukemia(CMML) has been categorized as an uncommon hematological malignancy with overlapping features of myelodysplastic syndromes(MDS) and myeloproliferative neoplasms that have an inherent risk of progressing to acute myeloid leukemia(AML). Methods This study presents a case of confirmed CMML combined with M protein, in which the molecular changes upon progression to AML and under decitabine(DAC) plus bortezomib therapy were reported by tracking variant allele frequency(VAF) of mutations in a series of bone marrow samples. Results First, variable sensitivity of clones was observed during DAC treatment, and incomplete mutation clearance may be associated with low overall response rate and unsustained response. Secondly, DAC cannot prevent the new genetic alterations and accumulation of genetic progression on treatment, leading to acute transformation. Finally, autoimmunity was found to have acted as an important pathogenetic factor, increasing the additive mutations that further drive the clonal evolution in CMML. Conclusion Overall, changes in mutations and clonal architecture during CMML progression or treatment are predictive of an early evaluation of therapeutic strategies in CMML.

Chronic myelomonocytic leukemia-associated pulmonary alveolar proteinosis:A case report and review of literature

BACKGROUND Pulmonary alveolar proteinosis(PAP)is a rare condition that can cause progressive symptoms including dyspnea,cough and respiratory insufficiency.Secondary PAP is generally associated with hematological malignancies including chronic myelomonocytic leukemia(CMML).To the best of our knowledge,this is the first reported case of PAP occurring secondary to CMML.CASE SUMMARY We report the case of a 63-year-old male who presented with a recurrent cough and gradually progressive dyspnea in the absence of fever.Based upon clinical symptoms,computed tomography findings,bone marrow aspiration,flow cytometry studies and cytogenetic analyses,the patient was diagnosed with PAP secondary to CMML.He underwent whole lung lavage in March 2016 to alleviate his dyspnea,after which he began combined chemotherapeutic treatment with decitabine and cytarabine.The patient died in January 2020 as a consequence of severe pulmonary infection.CONCLUSION This case offers insight regarding the mechanistic basis for PAP secondary to CMML and highlights potential risk factors.

Chronic Myelomonocytic Leukemia with t （3; 9） （p21; p13） as a Sole Abnormal Appearance： One Case Report

Chronic myelomonocytic leukemia, （CMML） is a clinically rare chronic myeloid leukemia, with an incidence rate of about 1-2/ 100,000/year, and the age of the predominant cases is over 60 years. The median age of onset is 65-70 years, and the ratio of the incidence between male and female is about 1.5 ： 3.1. Specific etiological factors of the disease are not clear, but may be associated with the exposure to ionizing radiation,

Efficacy and safety of combined decitabine and ruxolitinib in the treatment of chronic myelomonocytic leukemia

Objective The aim of the study was to evaluate the clinical efficacy of decitabine(DEC)combined with ruxolitinib(RUX)in the treatment of chronic myelomonocytic leukemia(CMML).Methods The clinical characteristics of 12 patients with CMML were analyzed retrospectively and subsequent target sequencing was performed to investigate the efficacy of the combined treatment with DEC and RUX and the molecular signatures therein.Results Among the 12 cases,clinical improvement was observed in all patients(100%),spleen reduction was observed in six patients(67%),and hematologic improvement was observed in four patients(33%).In the CMML-1 group,the overall response was 50%(3/6),one case achieved complete response,one achieved bone marrow remission,and one achieved hematological improvement.In the CMML-2 group,the overall response was 17%(1/6),one case achieved complete response,four showed disease progression(PD),and one exhibited no response.As expected,ASXL1 mutation was predictive for the outcome of CMML(hazard ratio of 2.97,95%confidence interval of 1.21–7.06;P=0.02).Conclusion The use of DEC combined with RUX in the treatment of CMML effectively improved the clinical response and quality of life,especially for CMML-1 patients.Ongoing clinical trials will further evaluate the safety and efficacy of this novel therapeutic approach.

Glomerular chemokine expression and the effect of steroid and cyclophosphamide pulse therapy in human crescentic glomerulonephritis

OBJECTIVE: To study glomerular expression of C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha and beta (MIP-1alpha, MIP-1beta) and the effect of steroid and cyclophosphamide (CTX) intermittent intravenous pulse therapy on expression in patients with crescentic glomerulonephritis (CGN) to further investigate the underlying mechanism of the treatment. METHODS: Twelve patients with initial biopsy-proven CGN(2), 6 with lupus nephritis (lupus-CGN, LN-CGN) and 6 with vasculitis, (vasculitis-CGN, V-CGN) were enrolled in this study. They underwent an initial biopsy before steroid and CTX intermittent intravenous pulse therapy and were biopsied again one to three months later. Expression of MCP-1, MIP-1alpha, MIP-1beta, and CD68 in glomeruli with cellular and fibrocellular crescents were examined by immunohistochemical analysis in serial sections of renal biopsies. The effect of the pulse therapy on histopathological changes was also observed. RESULTS: Although steroid and CTX intermittent intravenous pulse therapy markedly reduced the degree of glomerular crescent formation both in LN-CGN and V-CGN, the effect of the therapy on glomerular chemokine expression was significantly different between LN-CGN and V-CGN. It was found that steroid and CTX intermittent intravenous pulse therapy reduced the expression of CD68, MCP-1, and MIP-1alpha, but had no effect on MIP-1beta in glomeruli with cellular crescents of patients with LN-CGN. In patients with V-CGN, the therapy also reduced the expression of CD68, but had no effect on MCP-1, MIP-1alpha, and MIP-1beta in glomeruli with cellular crescents. It was noted that the degree of glomerulosclerosis and tubular interstitial fibrosis increased more significantly at the second biopsy in V-CGN as compared to LN-CGN. CONCLUSIONS: The efficacy of steroid and CTX intermittent intravenous pulse therapy in CGN might be affected by reduction of glomerular chemokine expression. The different changes in glomerular expression of MCP-1 and MIP-1alpha in patients with LN-CGN and V-CGN after pulse therapy may correlate to different responses to treatment and prognosis.

Immunophenotype of myeloid cells in myelodysplastic syndromes and its clinical implications

OBJECTIVE: To explore the immunophenotype of myeloid cells in myelodysplastic syndyomes (MDS) and its clinical implications. METHODS: A panel of monoclonal antibody was used to detect CD13+, CD33+, CD15+ and CD14+ antigens on the membrane surfaces of myeloid cells in the bone marrow from 51 MDS, 21 aplastic anemia (AA), 21 paroxysmal nocturnal hemoglobinuria (PNH) patients. 10 acute myeloblastic leukemia (AML) patients and 15 normal subjects by immunoenzymatic assay. The morphology and chromosome karyotype of bone marrow cells of MDS patients were also examined. RESULTS: CD14+, CD13+ and CD33+ cells in the bone marrow were more in MDS patients than in normal controls, AA patients and PNH patients. CD15+ cells in the bone marrow were less in MDS patients than in normal controls. CONCLUSIONS: The percentages of CD14+, CD13+ and CD33+ positive cells in the bone marrow of MDS patients were related to the percentage of myeloblasts, the chromosomal aberrations and the response to treatment. It indicated that there is immunophenotypic misexpression of myeloid cells in MDS patients. Immunophenotype analysis of myeloid cells might be useful for the diagnosis and treatment of MDS patients.

Clinical manifestation of the SRSF2 gene mutation in Chinese patients with chronic myelomonocytic leukemia

Background Spliceosome mutations have been recently identified and associated with hematological malignancies. SRSF2, one of components of the splicing machinery, has a high mutation frequency during chronic myelomonocytic leukemia, according to previous reports. However, the relevance of this finding in Chinese populations remains unknown. Methods We recruited 50 Chinese patients with chronic myelomonocytic leukemia to analyze the state of SRSF2 and to assess the corresponding clinical features by polymerase chain reaction followed by direct sequencing. Results Ten of 50 patients （20%） harbored SRSF2 mutations, including five P95R, two 95H, and three P95L point mutations. The patient group was older than the wild type group （P 〈0.01）. No significant statistical differences were observed with regard to the other clinical characteristics （sex, peripheral blood count, serum lactate dehydrogenase, karyotype, World Health Organization classification, etc.） between these two groups. Two of the patients showed an early evolution to acute myeloid leukemia. Conclusions SRSF2 mutations are frequent in chronic myelomonocytic leukemia patients, but show a relatively lower incidence in Chinese patients. Moreover, the mutation can be related to old age and an unfavorable prognosis. Our results provide valuable insights for the development of a diagnostic marker, or for the identification of a therapeutic target for chronic myelomonocytic leukemia.