Successful Treatment of an AML Patient Infected with Hypervirulent ST463 Pseudomonas Aeruginosa Harboring Rare Carbapenem-Resistant Genes blaAFM-1 and blaKPC-2 Following Allogeneic Hematopoietic Stem Cell Transplantation.

Background: Carbapenem-resistant P. aeruginosa (CRPA) is a common hospital-acquired bacterium. It exhibits high resistance to many antibiotics, including ceftazidime/avibactam and cefteolozane/tazobactam. The presence of carbapenem-resistant genes and co-existence Klebsiella pneumoniae carbapenemase (KPC) and metallo-ß-lactamases (MBLs) further inactivated all ß-lactams. Understanding the resistance genes of CRPA can help in uncovering the resistance mechanism and guiding anti-infective treatment. Herein, we reported a case of perianal infection with hypervirulent ST463 Pseudomonas aeruginosa. Case Presentation: The case is a 32-year-old acute myeloid leukemia (AML) patient with fever and septic shock during hematopoietic stem cell transplantation (HSCT), and the pathogen was finally identified as a highly virulent sequence type 463 (ST463) P. aeruginosa harboring carbapenem-resistant genes blaAFM-1 and blaKPC-2, which was detected in the bloodstream and originated from a perianal infection. The strain was resistant to ceftazidime/avibactam but successfully treated with polymyxin B, surgical debridement, and granulocyte engraftment after HSCT. The AML was cured during the 19-month follow-up. Conclusion: This case emphasizes the importance of metagenomic next-generation sequencing (mNGS) and whole-genome sequencing (WGS) in identifying microbes with rare resistant genes, and managing CRPA, especially in immunocompromised patients. Polymyxin B may be the least resistant option.

Prolonged haematologic toxicity in CAR-T-cell therapy: A review.

Chimeric antigen receptor-T-cell (CAR-T-cell) therapy is a novel immunotherapy with encouraging results for treatment of relapsed/refractory haematologic malignancies. With increasing use, our understanding of immune-mediated side effects such as cytokine release syndrome and neurotoxicity has improved; nevertheless, prolonged haematologic toxicity (PHT), with a high incidence rate, remains underrecognized. Owing to heterogeneity in populations, the CAR-T cells used and diseases treated as well as differences in the definition of PHT, its rate, risk factors and management vary across studies. In this review, we provide a narrative of PHT occurring in patients following CAR-T-cell therapy; evidence of PHT treatment strategies is also presented, with the aim of contributing to systematic understanding of PHT.

ß-Elemene suppresses tumor growth of diffuse large B-cell lymphoma through regulating lncRNA HULC-mediated apoptotic pathway.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is considered the most common aggressive subtype of lymphoma. A number of DLBCL patients fail to achieve a response to currently available therapies or develop resistance. ß-Elemene is derived from herb Curcuma wenyujin, and exhibits anti-tumor activity in both solid and non-solid tumors through modulating several molecular signaling pathways. We aimed to explore the role of ß-elemene in DLBCL treatment and elucidate the involved mechanism. MATERIALS AND METHODS: Cell viability, apoptosis and expressions of related proteins were assessed and in vivo study were performed to determine the tumor suppressive effect of ß-elemene and explore the molecular mechanisms. RESULTS: ß-Elemene significantly suppressed the viability of DLBCL cells, and ß-elemene down-regulated the lncRNA HULC expression and regulated key pro-apoptotic and anti-apoptotic proteins to induce significant apoptosis of DLBCL cells. HULC overexpression could decrease the ß-elemene induced apoptosis, while HULC knockdown increased the apoptosis in DLBCL cells. In vivo study further confirmed that ß-elemene could suppress the growth of DLBCL xenograft and regulate the HULC expression and the critical proteins of the apoptotic pathway. CONCLUSION: ß-Elemene performs as a tumor suppressor and modulator of HULC-mediated apoptotic pathway in DLBCL and will be an alternative candidate for clinical application.

Peripheral T cell lymphoma coexisting with Castleman's disease: A case report and literature review.

RATIONALE: Peripheral T cell lymphoma, coexisting with Castleman's disease (CD), is rarely seen in clinical practice and is not frequently reported in the literature. PATIENT CONCERNS: A 68-year-old female was admitted to our hospital for the first time due to "multiple lumps in the neck that progressively enlarged over 7 months". 1.5 years later, the patient returned to our hospital complaining of " difficulty breathing and purulent blood in the mouth for more than 20 days". DIAGNOSIS: The postoperative pathology from the (right) cervical lymph node biopsy confirmed the diagnosis of Castleman Disease (Vascular follicular type). 1.5 years after the diagnosis of CD, the patient developed secondary peripheral T cell lymphoma of unspecified type (PTCL-U). INTERVENTIONS: The patient received 5 courses of chemotherapy: 2 courses of CHOP, Chidamide combined with GemOx, GDP and Hyper CVAD Bregimen. OUTCOMES: After 3 courses of treatment, the curative effect was partly remitted (PR). The patient was discharged in a good condition and the follow-up was uneventful. LESSONS: The mechanism responsible for CD concurrent or secondary lymphoma is not clear. Epstein-Barr virus (EBV) infection may be the most common reason of CD and PTCL-U. Further understanding the mechanisms of the condition is needed.

Comparison of outcomes after human leukocyte antigen-matched and haploidentical hematopoietic stem-cell transplantation for multiple myeloma.

BACKGROUND: Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect. This multicenter investigation aimed to analyze the complications and survival of haploidentical SCT in patients with MM, and compare the main outcomes with matched-related donors (MRDs). METHODS: Haploidentical and MRD SCT was identified from a cohort of 97 patients with MM who received a myeloablative transplantation in 13 hospitals from May 2001 to December 2017. A matched-pair analysis was designed. For each haplo recipient, the recipients were randomly selected from the MRD group and were matched according to the following criteria: year of the hematopoietic SCT (±2 years), disease status at transplantation, and the length of follow-up. RESULTS: Seventy cases received MRD and 27 received haploidentical transplantation. The two groups showed no significant differences regarding age, gender, cytogenetic risk, and diagnostic stage. The cumulative incidences of non-relapse mortality (NRM) at 1 and 3 years based on donor type were 20.5% (95% confidence interval [CI], 10.90-30.10%) and 24.2% (95% CI, 13.81-34.59%) for the MRD group and 16.80% (95% CI, 1.71-31.89%) and 28.70% (95% CI, 8.71-48.69%) for the haplo group, respectively. Cumulative incidence of NRM did not differ significantly between the two groups (χ = 0.031, P = 0.861). The cumulative incidences of progression-free survival (PFS) and 1 year and 3 years by type of donors were 59.8% (95% CI, 48.24-71.36%) and 45.4% (95% CI, 33.44-57.36%), and 65.6% (95% CI, 47.18-84.02%) and 26.8% (95% CI, 7.59-46. 01%) for MRD and haploidentical donor, respectively. Cumulative incidence of PFS did not differ significantly between the two groups (χ = 0.182, P = 0.670). In multivariate analyses, no statistically significant differences were observed between haploidentical and MRD for relapse, NRM, PFS, and overall survival. There were no statistically differences on main outcomes after haploidentical and MRD. CONCLUSION: Haploidentical SCT could be performed safely and feasibly for patients with MM in need.

Multiple myeloma secondary to acute lymphoblastic leukemia: A case report.

RATIONALE: Acute lymphoblastic leukemia (ALL) secondary to multiple myeloma (MM) is rare. Here we report a rare case of secondary ALL transformed from MM. PATIENT CONCERNS: A 64-year-old woman was diagnosed as MM IgG light chain type in 2001. She achieved complete remission after 2 cycles of therapy, and received maintenance therapy with thalidomide. The patient suffered from MM relapse in September 2011. Bone marrow examination showed that the percentage of primary lymphocytes was 59%, indicating ALL-L2 (Pre-B-ALL). The patient reached complete remission after 1 cycle of chemotherapy, and has been maintained for more than 6 years. DIAGNOSES: Immunophenotyping analysis revealed that the abnormal cell population accounted for approximately 66% which expressed HLA-DR, CD4, CD22, CD33, CD34, and cCD79a. These results indicated acute B lymphoblastic leukemia. Chromosome presented 47, XX, +5, -7, +19. Leukemia fusion gene analysis demonstrated positive EVI1 and negative IgH and TCR gene rearrangement. INTERVENTIONS: The patient accepted 1 cycle of VDCLP chemotherapy and reached complete remission, followed with consolidation therapies with VDCLP, MA, CAG and other chemotherapy regimens. OUTCOMES: This patient has maintained CR1 of ALL for more than 6 years. LESSONS: Even secondary lymphoblastic leukemia has been rarely reported in patients with MM, we still need perform bone marrow examination, flow cytology, and gene tests, especially during maintenance therapy.

ß-elemene against Burkitt's lymphoma via activation of PUMA mediated apoptotic pathway.

Burkitt's lymphoma is a type of highly aggressive Non-Hodgkin's lymphoma. Although advanced Burkitt's lymphoma is responsive to high-intensity chemotherapy regimens, increasing systemic toxicity, tumor recurrence and metastasis significantly reduce the patient survival. Thus, it is important to investigate novel antitumor agents with safety and effectiveness. ß-elemene shows anti-proliferative effect on cancer cells by triggering apoptosis through regulating several molecular signaling pathways. However, its role in the suppression of Burkitt's lymphoma has not yet been fully elucidated. The inhibitory effect of ß-elemene in Burkitt's lymphoma was studied in vitro and in vivo, as well as the involved molecular mechanism. The results demonstrated that ß-elemene effectively inhibited the growth and induced the apoptosis of Burkitt's lymphoma cells through upregulation of PUMA expression and modulating PUMA related apoptotic signaling pathway. The in vivo data confirmed the anti-tumor effect of ß-elemene in the xenografts, suggesting that ß-elemene is associated with PUMA activation, leading to Bax and caspase induction and onset of mitochondrial apoptosis.

Efficiency of treatment with rituximab in platelet transfusion refractoriness: a study of 7 cases.

OBJECTIVE: The purpose of our study was to evaluate the efficacy and safety of rituximab in treatment of immune PR. METHODS: We retrospective analysis 7 paitents (5 aplastic anemia, 2 myelodysplastic syndrome) with immune PR who received at least 3 weekly infusions of rituximab (375 mg/m(2)). RESULTS: All enrolled patients acquired improvement of platelets transfusion more than 2 months (CCI ≥ 4.5 × 10(9)/L). We first found that there were 2 patterns of response to rituximab treatment in patients with immune PR, which the early but transient after the first rituximab administration and the late but continuous beginning to appear at 3 weeks from the start of treatment. CONCLUSION: Rituximab is a promising treatment in patients with immune PR and giving the opportunity and time for cure the disease.