Blinatumomab-induced macrophage activating syndrome (MAS) in adult with B-cell acute lymphoblastic leukemia (B-ALL).

Blinatumomab as a single agent has demonstrated superiority over salvage chemotherapy in patients with relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL), with manageable safety and efficacy. Though known to have anticipated drug toxicities including cytokine release syndrome (CRS) and neurotoxicity, there is only one prior report of macrophage activating syndrome (MAS) due to blinatumomab. Case Presentation: We report the first case of blinatumomab-induced MAS in an adult. The patient presented with fever, cough, and weakness on the second cycle of blinatumomab. Complete blood count was notable for severe leukopenia, with comprehensive metabolic panel notable for elevated alkaline phosphatase, AST, ALT, LDH, and hyperferritinemia consistent with MAS. The patient was already in MRD-negative remission at presentation with MAS. She responded rapidly to withholding the drug and administration of both tocilizumab and dexamethasone. She was able to restart therapy with blinatumomab dosed at 9 mcg/day with no recurrence of symptoms. Though MAS is not an expected association with blinatumomab, the risk for CRS is. Secondary MAS in this case likely shares a mechanism with other hyperinflammatory conditions. Management includes holding the offending agent, like blinatumomab, and administering tocilizumab and dexamethasone. Future research will be needed to predict which patients are at highest risk to develop MAS after similar T-cell therapies.

Early adverse life events and resting state neural networks in patients with chronic abdominal pain: evidence for sex differences.

BACKGROUND: Early adverse life events (EALs) and sex have been identified as vulnerability factors for the development of several stress-sensitive disorders, including irritable bowel syndrome (IBS). We aimed to identify disease and sex-based differences in resting state (RS) connectivity associated with EALs in individuals with IBS. METHOD: A history of EALs before age 18 years was assessed using the early trauma inventory. RS functional magnetic resonance imaging was used to identify patterns of intrinsic brain oscillations in the form of RS networks in 168 people (58 people with IBS, 28 were female; 110 healthy controls, 72 were female). Partial least squares, a multivariate analysis technique, was used to identify disease and sex differences and possible correlations between EALs and functional connectivity in six identified RS networks. RESULTS: Associations between EALs and RS networks were observed. Although a history of EALs was associated with altered connectivity in the salience/executive control network to a similar extent in male and female patients with IBS (bootstrap ratio = 3.28-5.61; p = .046), male patients with IBS demonstrated additional EAL-related alterations in the cerebellar network (bootstrap ratio = 3.92-6.79; p = .022). CONCLUSIONS: This cross sectional study identified correlations between RS networks and EALs in individuals with IBS. These results suggest that exposure to EALs before age 18 years can shape adult RS in both male and female patients in the salience/executive control network, a brain network that has been implicated in the pathophysiology of central pain amplification.

Advanced stage classic Hodgkin lymphoma (cHL): biology, clinical features, therapeutic approach, and management at relapse.

As the integration of novel agents in the frontline therapy has primarily impacted upfront therapy of advanced stage classic Hodgkin lymphoma (cHL), this review will outline current management of advanced stage cHL at first line and at progression and relapse, focusing on the biology, clinical features, and therapeutic approaches. Due to S1826, HD21, and ECHELON-1, the first-line treatment of advanced cHL has dramatically changed, with novel agents part of standard frontline therapy. BV-AVD, BrECADD, and Nivo-AVD are now standard first-line regimens for patients with stage III-IV cHL, with improved outcomes compared to historical data in cHL. The addition of BV and PD-1 inhibitors to relapsed/refractory (r/r) cHL chemotherapy regimens improved outcomes in this population. Now, there is a paradigm shift with PD-1 moving into frontline therapy, so new studies to evaluate the role of these novel agents in salvage will be required to determine the optimal salvage approach in r/r cHL.

Bispecific Antibody Use in Patients With Lymphoma and Multiple Myeloma.

This article endeavors to navigate the clinical journey of bispecific antibodies (BsAbs), from elucidating common toxicities and management strategies to examining novel agents and broadening access in community health care. These drugs, commonly through T-cell activation, result in shared adverse events such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. Variations in target antigens and designs, however, might introduce unique toxicities for different BsAbs, warranting specific management approaches. Recent US Food and Drug Administration approvals of BsAbs targeting CD3+ T cells linked to CD20 for non-Hodgkin lymphoma and to B-cell maturation antigen or GPRC5D for multiple myeloma have transformed the treatment landscape for hematologic malignancies. Emerging new agents promise further enhancement and safety, exploring novel antigen targets, innovative structures such as trispecific antibodies, and the engagement of diverse immune cells. Simultaneously, the expansion of BsAbs into community practices is underway, demanding a multifaceted strategy that encompasses educational initiatives, operational adaptations, and collaborative frameworks. This ensures comprehensive treatment access, allowing every patient, irrespective of geographical or socioeconomic status, to benefit from these advancements in cancer therapy.

Impact of spliceosome mutation on outcomes of myelodysplastic syndrome and chronic myelomonocytic leukemia patients undergoing allogeneic hematopoietic cell transplantation.

INTRODUCTION: Allogeneic Hematopoietic cell transplantation (allo-HCT) remains the only curative therapy for myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). The impact of spliceosome mutations on allo-HCT outcome is unclear and further understanding is needed to assess the implications of this class of mutations on risk of relapse, overall survival (OS) and non-relapse mortality (NRM) in order to make decision regarding timing of allo-HCT. We examined the allo-HCT outcomes of MDS/CMML patients based on their spliceosome mutation profile to understand the impact of these mutations on transplant outcomes. OBJECTIVE: To compare outcomes of MDS/CMML patients with and without spliceosome mutations undergoing allo-HCT. METHODS: This is a single institution, retrospective study of MDS/CMML patients who underwent allo-HCT with myeloablative or reduced intensity conditioning (RIC) regimen at City of Hope from January 2016 to December 2021. Among them, patients who underwent molecular mutation profiling by NGS (Next Generation Sequencing) for a set of genes known to be mutated in myeloid neoplasms are included in this analysis. We compared OS, relapse free survival, NRM and acute/chronic graft versus host disease (GVHD) incidence between the spliceosome-mutated and unmutated groups. RESULTS: We identified 258 consecutive MDS/CMML patients who underwent allo-HCT. Of these, 126 (48.8 %) patients had molecular profiling done among whom 57 (45.2 %) patients carried a spliceosome mutation. 84.9 % of patients had MDS and 55.6 % underwent a matched unrelated donor transplant. The median age for the whole cohort was 66 years (range 12-77).78.6 % and 73.7 % received RIC in the spliceosome and non-spliceosome groups, respectively. The 2-year OS for the whole cohort was 66.5 % (95 %CI 0.55-0.75) with a day 100 NRM of 7.1 % and 2-year cumulative incidence of relapse of 20 %. Grade II-IV acute GVHD at day 100 was 36.3 % (95 % CI 0.27-0.44) and any chronic GVHD at 2-years was 48.4 % (95 % CI 0.37-0.58). Patients who carried a spliceosome mutation had a significantly better 2-year survival of 83.8 % vs 55.9 % in the non-spliceosome group (P=0.002) and a better PFS of 73.7 % vs 50.0 % (P=0.007). There was no difference in the cumulative incidence of relapse at 2-years 15.9 % vs 18.5 % (P=0.59) between two groups but the spliceosome group had a significantly lower NRM at 2-years 10.4 % vs 31.5 % (P=0.009). There was no difference in incidence of acute or chronic GVHD between the two groups. CONCLUSIONS: Among patients with MDS or CMML who underwent allo-HCT, our study shows better OS for patients who have spliceosome mutations due to lower NRM compared to those carrying non- spliceosome mutations. This favorable outcome of the spliceosome-mutated patients could have implications for timing of allo-HCT, particularly for patients in the intermediate MDS prognostic risk groups.

Haploidentical hematopoietic cell transplant recipient presents with late-onset Epstein Barr virus-associated posttransplant lymphoproliferative disorder.

Posttransplant lymphoproliferative disease (PTLD) is a potentially life-threatening complication of hematopoietic cell transplantation. With improvements in Epstein-Barr virus (EBV) monitoring and supportive care, PTLD incidence has decreased throughout the history of bone marrow transplantation. It is rare to develop PTLD after the first year following transplant, across all donor categories. In this case, we hope to elucidate details that may have predisposed to this unusual presentation. We present the case of a 55-year-old gentleman with acute myeloid leukemia who underwent a haploidentical transplant for consolidation and presented with fatigue, lethargy and presumed septic shock nearly 7 years after transplant.

Minor Salivary Gland Carcinoma of the Oropharynx: A Population-Based Analysis of 1426 Patients.

Objective We sought to describe the patient, tumor, and survival characteristics of minor salivary gland carcinoma (MSGC) of the oropharynx using a large, population-based database. Study Design Cross-sectional analysis of the National Cancer Institute's SEER database (Surveillance, Epidemiology. and End Results). Subjects and Methods We reviewed the SEER database for all cases of MSGC of the oropharynx from 1988 to 2013. Relevant demographic, clinicopathologic, and survival variables were extracted and analyzed. Cox multivariate regression was performed to identify prognostic factors. Results We identified 1426 cases of MSGC of the oropharynx (mean age, 58 years; 51% female). The soft palate (39.2%) and base of tongue (38.6%) were the most commonly involved sites. The most common histologic subtypes were mucoepidermoid carcinoma (32.1%), adenocarcinoma (25.9%), and adenoid cystic carcinoma (23.3%). Five- and 10-year rates of disease-specific survival were 75.1% and 61.6%, respectively. Independent prognostic factors included tumor grade, T stage, N stage, and age >70 years. Conclusions This study represents the largest multivariate survival analysis of MSGC of the oropharynx to date. Independent prognosticators include tumor grade, T stage, N stage, and age.