Five-Year Follow-Up of Standard-of-Care Axicabtagene Ciloleucel for Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium.

Purpose: Axicabtagene ciloleucel (axi-cel) is an autologous CD19 chimeric antigen receptor (CAR) T-cell therapy that is approved for the treatment of relapsed or refractory large B-cell lymphoma. Little is known about the long-term survivorship after CAR T-cell therapy.

Methods: We previously reported the results of 298 patients who were leukapheresed with the intent to receive standard-of-care axi-cel (n = 275 infused) after two or more previous lines of therapy at a median follow-up of 12.

Control of acute myeloid leukemia and generation of immune memory in vivo using AMV564, a bivalent bispecific CD33 x CD3 T cell engager.

Off-the-shelf immunotherapeutics that suppress tumor growth and provide durable protection against relapse could enhance cancer treatment. We report preclinical studies on a CD33 x CD3 bivalent bispecific diabody, AMV564, that not only suppresses tumor growth, but also facilitates memory responses in a mouse model of acute myelogenous leukemia (AML). Mechanistically, a single 5-day treatment with AMV564 seems to reduce tumor burden by redirection of T cells, providing a time window for allogeneic or other T cells that innately recognize tumor antigens to become activated and proliferate.

Immune Adjuvant Therapy With Interleukin-7 in a Lymphopenic Patient With Aplastic Anemia and Mucormycosis.

Background: We report the case of a patient with aplastic anemia and pancytopenia on immune-suppressive therapy who developed invasive pulmonary infection with mucormycosis and was treated with immune adjuvant therapy.

Case Summary: Given the patient's profound lymphopenia and progressive invasive mucor despite dual antifungal drug therapy, interleukin (IL)-7, a cytokine that induces lymphocyte activation and proliferation, was instituted and resulted in normalization of absolute lymphocyte counts and was temporally associated with clearance of fungal pathogens and resolution of clinical symptoms.

Conclusion: Patients with life-threatening fungal infections are frequently immune suppressed and immune adjuvant therapies should be considered in patients who are not responding to antifungal drugs and source control.

SOHO State of the Art Updates and Next Questions: Tailoring Upfront Therapy in Mantle Cell Lymphoma.

In this article, we will review current strategies for the front-line management of mantle cell lymphoma, an uncommon and biologically and clinically heterogeneous subtype of non-Hodgkin lymphoma that remains incurable with current therapies. Patients invariably relapse with time, and as a result, treatment strategies involve persistent therapy over the course of months to years, including induction, consolidation, and maintenance. Topics discussed include the historical development of various chemoimmunotherapy backbones with continued modifications to maintain and improve efficacy while limiting off-target, off-tumor effects.

Acute Graft-versus-Host Disease: An Update on New Treatment Options.

Acute graft-versus-host disease (GVHD) occurs in approximately 50% of patients and remains a primary driver of non-relapse and transplant-related mortality. The best treatment remains prevention with either in vivo or ex vivo T-cell depletion, with multiple strategies used worldwide based on factors such as institution preference, ability to perform graft manipulation, and ongoing clinical trials. Predicting patients at high risk for developing severe acute GVHD based on clinical and biomarker-based criteria allows for escalation or potential de-escalation of therapy.

Bendamustine/Rituximab Plus Cytarabine/Rituximab, With or Without Acalabrutinib, for the Initial Treatment of Transplant-Eligible Mantle Cell Lymphoma Patients: Pooled Data From Two Pilot Studies.

Introduction: Mantle cell lymphoma (MCL) is a moderately aggressive lymphoma subtype, generally viewed as incurable. For younger, fit patients, the standard of care remains various high-dose cytarabine-based induction regimens followed by autologous hematopoietic cell transplant and 3 years of rituximab maintenance. Despite reasonably good outcomes, with median progression-free survival in the range of 7 to 9 years, most patients eventually relapse, indicating a need to improve the safety and tolerability of remission induction strategies.

Top advances in lymphoma for 2021.

Chimeric antigen receptor (CAR) T-cell therapy, antibody-drug conjugates, bispecific T-cell redirectors, and agents targeting tonic B-cell receptor signaling have altered the paradigm for three of the most common lymphomas in the year 2021. For diffuse large B-cell lymphoma, the POLARIX study has shown improvement on the standard backbone of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in the frontline setting, a feat that had not been achieved despite great efforts over the past 20 years. In the relapsed and refractory setting, two unique CAR T-cell products have displaced autologous transplantation to the third line, and they allow patients with chemotherapy-resistant disease to receive approved therapy earlier.

Current practice for primary headache disorders and perspectives on peripheral nerve blocks among emergency physicians in Canada: A national survey.

Objective: This national postal survey aimed to examine Canadian emergency physicians' practice patterns with respect to drug treatment and perspectives on peripheral nerve blocks.

Background: The treatment of primary headache disorders in the emergency department is variable.

Methods: We surveyed 500 emergency physicians listed in the Canadian Medical Directory according to a modified Dillman's method: an initial invitation was followed by up to four reminders to nonresponders.

Mouse models of graft-versus-host disease.

Transplantation of allogeneic hematopoietic stem and progenitor cells (allo-HCT) allows for cure of life-limiting malignant and non-malignant hematologic diseases. Crossing the human leukocyte antigen (HLA) barrier, however, comes at the cost of graft-versus-host disease (GVHD), a life-threatening syndrome mediated in part by the same donor T-lymphocytes that eliminate malignant cells. Acute GVHD occurs in the skin, gut, and/or liver in 25-55% of patients with a mortality rate of 15-40%, while chronic GVHD develops in 30-65% of patients who survive at least 3 months following allo-HCT and is highly debilitating in its extensive form, with a 30-50% 5year mortality rate stemming in part from immune dysregulation and opportunistic infections.

Integrating sex and gender in studies of cardiac resynchronization therapy: a systematic review.

Aims: To examine the prevalence, temporal changes, and impact of the National Institute of Health (NIH) Sex as a Biological Variable (SABV) policy on sex and gender reporting and analysis in cardiac resynchronization therapy (CRT) cohort studies.

Methods And Results: We searched MEDLINE, EMBASE, and Web of Science for cohort studies reporting the effectiveness and safety of CRT in heart failure patients from January 2000 to June 2020, with no language restrictions. Segmented regression analysis was used for policy analysis.

Effectiveness of Peripheral Nerve Blocks for the Treatment of Primary Headache Disorders: A Systematic Review and Meta-Analysis.

Study Objective: Primary headache disorders are prevalent and account for 2% of all emergency department visits. Current treatment options are effective; however, time to pain relief is suboptimal. Alternatives such as peripheral nerve blocks have shown promising results.

Sodium Valproate Versus Dopamine Antagonists for Acute Migraine in the Emergency Department: A Systematic Review.

Background: Migraine is a common primary headache disorder diagnosed in the emergency department (ED). This systematic review sought to compare the efficacy of sodium valproate (SV) to dopamine antagonists (DA) in relieving pain due to acute migraine.

Methods: Two research librarians helped create a search strategy including Embase, Ovid Medline, and the Cochrane Database of Clinical Trials from inception to June 1, 2020, updated May 19, 2021.

New-onset post-transplant diabetes mellitus after haploidentical hematopoietic cell transplant with post-transplant cyclophosphamide.

Haploidentical hematopoietic cell transplant (haplo-HCT) with post-transplant cyclophosphamide (PTCY) is utilized for patients with hematological disorders but without conventional donors. The effects of new-onset post-transplant diabetes mellitus (PTDM) following haplo-HCT are unknown. We examined PTDM incidence and outcomes after haplo-HCT with PTCY.

Association between mortality and frailty in emergency general surgery: a systematic review and meta-analysis.

Purpose: The purpose of this review was to determine the association between frailty and mortality among adults ≥ 65 years old undergoing emergency general surgery (EGS).

Methods: This systematic review followed the PRISMA guidelines (CRD42020172482 on PROSPERO). A search in MEDLINE, PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Database of Systematic Reviews was conducted from inception to March 5, 2020.

Dural Marginal Zone Lymphoma in a Patient With a Hepatitis C Virus Infection.

Primary dural marginal zone lymphomas (MZLs) are exceptionally rare, with fewer than 100 cases reported to date. While the association between hepatitis C virus (HCV) infection and lymphoma is well established, it is unclear if this association extends to all anatomic sites. Here we report a case of dural MZL in a 61-year-old woman with an HCV infection.

Haploidentical bone marrow transplant with posttransplant cyclophosphamide for sickle cell disease: An update.

Hematopoietic cell transplant (HCT) can cure both children and adults with sickle cell disease. Outcomes have historically been poor for the vast majority of patients who lack a matched sibling donor. However, the development of haploidentical HCT (haplo-HCT) with high doses of posttransplant cyclophosphamide (PTCy) has allowed for curative long-term potential with favorable transplant-related outcomes, though this has not obviated the potential for graft rejection from human leukocyte antigen mismatch and repeated red blood cell transfusions.

Overcoming Proteasome Inhibitor-Refractory Multiple Myeloma With Elotuzumab, Bortezomib, Nelfinavir, and Dexamethasone.

Multiple myeloma is a common plasma cell malignancy with a median overall survival of fewer than 10 years. Proteasome inhibitors comprise an important part of the treatment regimen for this disease. The present study reports the case of a 57-year-old man who experienced a second relapse of multiple myeloma 6 years after initial treatment with bortezomib, lenalidomide, dexamethasone (VRD) followed by autologous hematopoietic cell transplant.

Minimal residual disease negativity and lenalidomide maintenance therapy are associated with superior survival outcomes in multiple myeloma.

Modern combinations of therapies for multiple myeloma have led to improvement in survival outcomes with near 100% overall response rate and 25% complete response rates, particularly with autologous hematopoietic cell transplant (AHCT). Minimal residual disease (MRD) assessment with multiparameter flow cytometry is a valid prognostic biomarker for progression-free survival (PFS) and overall survival (OS). However, few data exist regarding whether MRD positivity or negativity will meaningfully influence treatment decisions.

Early viral reactivation despite excellent immune reconstitution following haploidentical Bone marrow transplant with post-transplant cytoxan for sickle cell disease.

Background: Haploidentical bone marrow transplant (haplo-BMT) offers near universal donor availability as a curative modality for individuals with severe sickle cell disease (SCD). However, the required intense immunodepletion is associated with increased infectious complications. A paucity of data exists on immune reconstitution following haplo-BMT for SCD.

Implication of Rituximab Infusion Reactions on Clinical Outcomes in Patients With Diffuse Large B-cell Lymphoma: A Single Institution Experience.

Background: The addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy for diffuse large B-cell lymphoma (DLBCL) has led to improvements in progression-free survival and overall survival, although the exact mechanism of rituximab is not known. Rituximab administration often results in transient, non-life-threatening infusion reactions (IRs). We report a retrospective cohort of patients with DLBCL who received rituximab to determine the significance of IRs on clinical outcomes.

T-cell deplete versus T-cell replete haploidentical hematopoietic stem cell transplantation for sickle cell disease: where are we?

: Severe sickle cell disease is associated with progressive end-organ damage and early mortality in adults. While allogeneic hematopoietic cell transplant from a matched related donor is curative, the vast majority of patients do not have a compatible sibling. Accordingly, platforms using haploidentical donors have been developed, which provide near-universal availability.