Successful mechanical thrombectomy in acute bilateral M1 middle cerebral artery occlusion: a case report and literature review.

BACKGROUND: Acute bilateral occlusion of the middle cerebral artery (MCA) is a very rare condition, and most cases are accompanied by a poor prognosis. However, mechanical thrombectomy (MT) for bilateral MCA is challenging. Here, we report a case of acute unilateral MCA occlusion with sequential acute occlusion of the bilateral MCA during intravenous thrombolysis (IVT). We urgently performed bilateral MT of the MCA and effective recanalization. CASE PRESENTATION: The patient is a 73-year-old man who complained of a sudden adverse influence on speech and an inability to move his left limb for 2 h. He had a history of paroxysmal atrial fibrillation, but had never used any anticoagulants before. Head and neck computed tomography angiography (CTA) showed embolism in the right M1 MCA. During intravenous alteplase thrombolytic therapy, the patient suddenly became unconscious. Cerebral angiography showed occlusion of the M1 segment of the bilateral MCA in the patients. MT of the bilateral MCA was performed using a combination of a stent retriever and an aspiration catheter with mTici 3 revascularization. On the second day, the patient became conscious, although he had remaining symptoms of speech insufficiency and weakness of the left limb. The mRS score was 2 90 days after the operation. CONCLUSIONS: Acute bilateral occlusion of the M1 segment of the MCA is extremely rare and is accompanied by high morbidity and high mortality. Intravenous alteplase thrombolysis can increase the risk of atrial thrombus shedding in patients with atrial fibrillation, so patients with acute bilateral MCA occlusion in the M1 segment chose direct MT or bridging therapy, which remains controversial, and the sequence of MT remains to be discussed. Nevertheless, early endovascular treatment can decrease the morbidity and mortality of such patients.

MitraClip as bridge to mitral valve replacement in the setting of ischemic cardiogenic shock and papillary muscle rupture.

MitraClip implantation has been reported in severe mitral regurgitation following ischemic papillary muscle rupture in surgically high-risk patients with cardiogenic shock. Here we present a case of a 68-year-old female patient who suffered an ischemic papillary muscle rupture resulting in severe mitral prolapse and had a MitraClip implanted. Three months later, due to progressive symptoms, she was taken to surgery and had an elective minimally invasive mitral valve replacement. Informed consent was given and ethics board approval was obtained.

MitraClip as bridge to mitral valve replacement in the setting of ischemic cardiogenic shock and papillary muscle rupture.

MitraClip implantation has been reported in severe mitral regurgitation following ischemic papillary muscle rupture in surgically high-risk patients with cardiogenic shock. Here we present a case of a 68-year-old female patient who suffered an ischemic papillary muscle rupture resulting in severe mitral prolapse and had a MitraClip implanted. Three months later, due to progressive symptoms, she was taken to surgery and had an elective minimally invasive mitral valve replacement. Informed consent was given and ethics board approval was obtained.

Carfilzomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma patients: the real-life experience of Rete Ematologica Pugliese (REP).

Carfilzomib, lenalidomide, and dexamethasone (KRd) have been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) based on ASPIRE clinical trial. However, its effectiveness and safety profile in real clinical practice should be further assessed. We retrospectively evaluated 130 consecutive RRMM patients treated with KRd between December 2015 and August 2018, in 9 Hematology Departments of Rete Ematologica Pugliese (REP). The overall response rate (ORR) was 79%, with 37% complete response (CR). Treatment with KRd led to an improvement in response regardless of age, refractory disease, and number and type of previous therapies. After a median follow-up of 18 months, median PFS was 24 months and 2y-PFS was 54%. PFS was longer in patients achieving a very good partial response (VGPR) with median PFS of 32.4 months. The relapses after prior autologous transplant (ASCT) positively impact median PFS. Several baseline disease characteristics, such as III ISS scoring or elevated LDH, and prior exposure to lenalidomide were found to negatively impact PFS. Primary refractory or relapsed myeloma patients have been treated with KRd as bridge to ASCT with a great benefit. Thirty-four (83%) reached at least a partial response after KRd and 21 (61%) performed ASCT. In transplanted patients, median PFS was not reached and 2y-PFS was 100%. The treatment discontinuation rate due to adverse events (AEs) was 18%, most commonly for lenalidomide (11%). Overall, in 10% of patients, a KRd dose reduction was necessary at least once (2.5% for carfilzomib and 8% for lenalidomide). The most frequent AE was neutropenia (44%) and anemia (41%). Infections occurred in 14% of patients. Cardiovascular events occurred in 11% of patients. Elderly patients have tolerated therapy very well, without additional side effects compared to younger patients, except for cardiac impairment. Our analysis confirmed that KRd is effective in RRMM patients. It is well tolerated and applicable to the majority of patients outside clinical trials. A longer PFS was shown in patients achieving VGPR, in those lenalidomide naïve and in patients relapsing after previous ASCT. Previous ASCT should not hamper the option for KRd therapy. Accordingly, KRd should be used as bridge regimen to ASCT with remarkable improvement in response and PFS rates. Further clinical studies are needed.

Initial experience with high-volume plasma exchange in patients with acute liver failure.

BACKGROUND/AIMS: High-volume plasma exchange (HVPE), defined as an exchange of 8 to 12 L per day per procedure or 15% of the ideal body weight with fresh frozen plasma, has shown promising results in improving the survival of patients with acute liver failure (ALF). However, clinical evidence is limited. The aim of this study was to report our initial experience using HVPE as a bridge treatment in patients with ALF. METHODS: We retrospectively reviewed 32 consecutive patients awaiting liver transplantation (LT) due to ALF between 2013 and 2020 at Samsung Medical Center in Korea. HVPE has been used for patients with ALF since May 2016 at our institution. RESULTS: During the study period, 16 patients received HVPE. After HVPE, coagulopathies (INR, 4.46 [2.32-6.02] vs 1.48 [1.33-1.76], P < .05), total bilirubin (22.6 [9.1-26.4] vs 8.9 [5.6-11.3], P < .05), alanine aminotransferase (506 [341-1963] vs 120 [88-315], P < .05), and ammonia levels (130.6 [123.7-143.8] vs 98.2 [84.2-116.5], P < .05) were improved. Improvement in the hepatic encephalopathy grade was observed in four patients. Among 16 patients who received HVPE, 12 patients were bridged to LT, and three patients recovered spontaneously. The overall survival was 94% and 69%, respectively at 30 days in patients who received and did not receive HVPE (P = .068). Among 18 patients with high chronic liver failure-sequential organ failure assessment scores (≥13), the overall survival was significantly better for those who received HVPE than for those who did not (91% vs 29%, respectively, at 30 days, P < .05). CONCLUSIONS: Our initial clinical experience with HVPE suggests that HVPE can be a viable option in improving the outcomes of patients presenting with ALF.

[Prevention of thromboembolic and hemorrhagic events in patients with atrial fibrillation undergoing elective surgery]. / Profilaktika tromboémbolicheskikh i gemorragicheskikh oslozhnenii u patsientov s fibrilliatsiei predserdii pri provedenii planovogo khirurgicheskogo lecheniia.

OBJECTIVE: To compare incidence of thromboembolic and hemorrhagic complications in patients with atrial fibrillation (AF) undergoing elective surgery on different schemes of perioperative anticoagulant therapy (ACT). MATERIAL AND METHODS: There were 86 patients (56 (65.1%) men and 30 (34.9%) women, mean age was 69 (64; 78) years) with non-valvular AF who underwent elective interventions. Forty (46.5%) patients underwent abdominal surgery, 34 (39.5%) - cardiovascular procedures, 12 (14.0%) patients underwent surgery for malignant diseases. We have analyzed incidence of thromboembolic and hemorrhagic events and compliance of perioperative ACT modes with current international guidelines. RESULTS: Thromboembolic and hemorrhagic events developed in 14 (16.3%) patients. Thromboembolic complications were noted in 6 (7.0%) patients, hemorrhagic events - in 8 (9.3%) cases. Maximum complication rate was observed in case of bridge-therapy (n=12, 20.0%). Cancellation of ACT was followed by 2 (9.5%) complications, bridge-therapy - by 4 (6.7%) thromboembolic complications. Hemorrhagic events were 2 times more common in case of this therapy (n=8, 13.3%). It was found that ESC guidelines for perioperative ACT were applied in less than half of patients (41, 47.7% patients with AF undergoing elective surgery). Half of complications (8 out of 16) occurred if unapproved modes of ACT were used (including 7 cases of bridge-therapy was not necessary). The causes of these complications were inadequate assessment of perioperative risk of thromboembolic and hemorrhagic events; unreasonable administration of bridge therapy. CONCLUSION: An unambiguous clinical effect of bridge therapy has not been confirmed in patients with high risk of thromboembolic complications. Cancer patients have higher risk of complications compared with others. These events occur mainly due to non-compliance with clinical guidelines and insufficient prevention of thromboembolic events.

Incidence, Predictors, and Midterm Clinical Outcomes of Myocardial Injury After Transcatheter Aortic-Valve Implantation.

Our aim was to assess the clinical effects of myocardial injury after transcatheter aortic-valve implantation (TAVI). Between October 2013 and July 2016, 157 patients underwent TAVI with Sapien XT, Sapien 3, or CoreValve prostheses at our institute. Of these, 130 patients for whom the transapical approach was not used were included in this study. Myocardial injury was defined as a peak troponin I level of ≥1.5 ng/mL within 48 hours after TAVI. We evaluated the predictors of myocardial injury and compared the clinical outcomes of 82 patients classified as the myocardial injury group and 44 patients classified as the non-myocardial injury group. The patients were aged 85 ± 6 years. Myocardial injury occurred in 82 patients (65.1%). Age (per 1 increase) (odds ratio [OR]: 1.11, 95% confidence interval [CI]: 1.01-1.22, P = 0.041), female sex (OR: 3.88, 95% CI: 1.23-12.22, P = 0.021), valve type (Sapien XT; OR: 4.22, 95% CI: 1.15-15.47, P = 0.03, Core valve; OR: 18.12, 95% CI: 2.86-114.59, P = 0.002), balloon aortic valvuloplasty as a bridge therapy (OR: 0.10, 95% CI: 0.02-0.42, P = 0.002), and left ventricular end-diastolic volume (LVEDV) (per 1 increase) (OR: 0.97, 95% CI: 0.95-0.99, P = 0.003) were associated with myocardial injury in a multivariate model. The myocardial injury group did not have a higher rate of midterm (365-day) mortality (log-rank test P = 0.57) than the non-myocardial injury group on Kaplan-Meier analysis. Myocardial injury after TAVI was not associated with midterm mortality.

Effect of direct oral anticoagulants on the risk of delayed bleeding after gastric endoscopic submucosal dissection.

BACKGROUND AND AIM: Anticoagulants are used to prevent thromboembolic events. Direct oral anticoagulants (DOAC) are our new choice; however, their effect on bleeding risk for endoscopic treatment has not been reported. We aimed to assess the clinical effect of DOAC compared to warfarin for gastric endoscopic submucosal dissection (ESD). METHODS: We retrospectively studied 97 patients on anticoagulants and treated 108 gastric neoplasms with ESD in three referral institutes. Twenty-four patients were taking DOAC, including dabigatran (12), rivaroxaban (11), and apixaban (one) and 73 were taking warfarin. RESULTS: In the DOAC group, delayed bleeding rate was significantly higher in patients on rivaroxaban than in patients on dabigatran (45% vs 0%, P < 0.05) without relation to heparin bridge therapy (HBT). In the warfarin group, 78% of patients underwent HBT, and delayed bleeding rate was significantly higher in patients with HBT than in those without (36% vs 0%, P < 0.05). Delayed bleeding rate increased as intake of antithrombotic agents increased (P < 0.05). HBT period was shorter (P < 0.05) in DOAC because DOAC achieve the maximum effect quicker, and hospitalization period was shorter (P < 0.05), compared with warfarin. Multivariate analysis showed that HBT (OR, 10.7), rivaroxaban (OR, 6.00) and multiple antithrombotic agents (OR, 4.35) were independent delayed bleeding risk factors. CONCLUSIONS: The DOAC effect differs in each agent. Dabigatran is a feasible alternative to warfarin for shortening the hospitalization period and decreasing delayed bleeding rate, although rivaroxaban has a significantly higher delayed bleeding risk.

Survey of pharmacists' subtherapeutic INR management and anticoagulation bridging practices.

WHAT IS KNOWN AND OBJECTIVE: Despite extensive warfarin use, optimal management of subtherapeutic international normalized ratios (INRs) remains unclear. This study assessed the differences in bridging practices among pharmacists with varying levels of experience, residency training and prescribing privileges. METHODS: An electronic survey was distributed to two ambulatory care pharmacist e-mail lists. Respondents indicated if they would utilize parenteral anticoagulation bridging in 16 clinical scenarios at three therapeutic time points. The scenarios included patients with atrial fibrillation (AFib) (CHADS2 score of 3-4), AFib (CHADS2 score of 5-6) and venous thromboembolism (VTE). The AFib time points were as follows: anticoagulation initiation, early phase (<1 month) and maintenance phase (>1 month). VTE time points included early phase (<1 month), months 2-3 and maintenance phase (>3 months). RESULTS AND DISCUSSION: The survey was completed by 143 respondents. In only three of the scenarios did >50% of respondents indicate they would utilize parenteral anticoagulation bridging. No statistically significant differences in bridging practices were identified between pharmacists providing anticoagulation services in different clinic settings. However, there were significant differences in bridging practices between pharmacists with varying levels of experience, residency training and prescribing privileges in some, but not all of the scenarios. WHAT IS NEW AND CONCLUSION: The standards of care for subtherapeutic INRs warrant further definition.

Efficient combination of radiotherapy and CAR-T - A systematic review.

Chimeric antigen receptor T (CAR-T) cell therapy, a groundbreaking immunotherapy. However, it faces formidable challenges in treating solid tumors, grappling with issues like poor trafficking, limited penetration, and insufficient persistence within the tumor microenvironment (TME). CAR-T cells are engineered to express receptors that target specific cancer antigens, enhancing their ability to recognize and eliminate cancer cells. This review paper explores the intricate interplay between CAR-T therapy and radiotherapy (RT), investigating their synergistic potential. Radiotherapy, a standard cancer treatment, involves using high doses of radiation to target and damage cancer cells, disrupting their ability to grow and divide. We highlight that RT modulates the TME, augments antigen presentation, and promotes immune cell infiltration, bolstering CAR-T cell-mediated tumor eradication. Molecular insights shed light on RT-induced alterations in tumor stroma, T cell recruitment promotion, and induction of immunogenic cell death. Noteworthy, strategies, such as combining hypofractionated radiotherapy with myeloid-derived suppressor cell blockade, underscore innovative approaches to enhance CAR-T cell therapy in solid tumors. Bridging indications for RT and CAR-T cells in hematological malignancies are discussed, emphasizing scenarios where RT strategically enhances CAR-T cell efficacy. The paper critically evaluates the RT as a bridge compared to traditional chemotherapy, highlighting timing and dosage considerations crucial for optimizing CAR-T therapy outcomes. In summary, the paper provides valuable insights into the intricate molecular mechanisms activated by RT and innovative strategies to improve CAR-T cell therapy, fostering a deeper understanding of their combined potential in cancer treatment.

Association of Different Anticoagulation Strategies With Outcomes in Patients Hospitalized With Acute Pulmonary Embolism.

Background Therapeutic anticoagulation is the cornerstone of treatment for pulmonary embolism (PE), but the impact of different anticoagulation strategies on patient outcomes remains unclear. In this study, we assessed the association of different anticoagulation strategies with the outcomes of patients with acute PE. Methods A retrospective chart review of 207 patients with acute PE who were admitted to one of three urban teaching hospitals in the Mount Sinai Health System (in New York City) from January 2020 to September 2022 was performed. Demographic, clinical, and radiographic data were recorded for all patients. Multivariate regression analyses were performed to assess the association of different outcomes with the approach of therapeutic anticoagulation used. Results The median age of the included patients was 65 years, and 50.2% were women. The most common approach (n = 153, 73.9%) to therapeutic anticoagulation was initial treatment with unfractionated or low molecular weight heparin followed by a direct-acting oral anticoagulant (DOAC), while heparin alone (either unfractionated or low molecular weight heparin) was used in 37 (17.9%) patients, and another 17 (8.2%) patients were treated with heparin followed by bridging to warfarin. Hospital length of stay was longer for patients in the "heparin to warfarin" group (risk-adjusted incidence rate ratio of 2.52). The rates of in-hospital bleeding, all-cause 30-day mortality, and all-cause 30-day re-admissions did not have any significant association with the therapeutic anticoagulation approach used. Conclusion Patients with acute PE who were initially treated with heparin and subsequently bridged to warfarin had a longer hospital stay. Rates of in-hospital bleeding, 30-day mortality, and 30-day re-admission were not associated with the strategy of therapeutic anticoagulation employed.

Role of Stereotactic Body Radiation Therapy in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC)is a common type of liver cancer with a poor prognosis, especially in patients with advanced stages or underlying liver disease. While surgical resection, liver transplantation, and ablation therapies have traditionally been the mainstay of treatment for HCC, radiation therapy has become increasingly recognized as an effective alternative, particularly for those who are not surgical candidates. Stereotactic Body Radiation Therapy (SBRT) is a highly precise form of radiation therapy that delivers very high doses of radiation to the tumor while sparing surrounding healthy tissue. Several studies have reported favorable outcomes with SBRT in HCC treatment. Moreover, SBRT can be used to treat recurrent HCC after prior treatment, offering a potentially curative approach in select cases. While SBRT has demonstrated its efficacy and safety in treating HCC, future studies are needed to further investigate the potential role of SBRT in combination with other treatments for HCC.

Balloon aortic valvuloplasty bridge to transcatheter aortic valve replacement is associated with worse in-hospital mortality.

BACKGROUND: Balloon aortic valvuloplasty (BAV) has gained renewed interest as a bridge to transcatheter aortic valve replacement (TAVR) for patients with aortic stenosis (AS). However, it is unclear whether they patients should undergo TAVR directly or receive a staged bridge to BAV before TAVR is unclear. We used a national database to examine the association between BAV and TAVR in patients with TAVR and its effect on in-hospital mortality. METHODS: Using the nationwide inpatient database of the Japanese registry of all cardiac and vascular diseases and the combination of the diagnosis procedure combination, we retrospectively analyzed 27,600 patients with AS who underwent TAVR between October 2013 and March 2021. Outcomes of the direct TAVR group (n = 27,387) were compared with those of the BAV bridge to TAVR group (n = 213), which received BAV at least 1 day before TAVR. RESULTS: The median age was 85 (interquartile range: 82-88) years, with 33.3% (n = 9188) being male. Unplanned/emergent admissions increased with TAVR, whereas the use of BAV bridge to TAVR decreased. The in-hospital mortality rate was 1.3% and decreased over time. However, the BAV bridge to TAVR had a significantly higher in-hospital mortality than direct TAVR (5.6% vs. 1.3%; p < .0001). Factors associated with in-hospital mortality included age, body mass index, chronic renal disease, percutaneous coronary intervention, and BAV bridge to TAVR. CONCLUSIONS: In unplanned/emergent and planned admission settings, the in-hospital mortality rate for BAV bridge to TAVR is worse than that for direct TAVR. Practical criteria for BAV bridge to TAVR should be proposed to improve outcomes.

Stability Study of Fosfomycin in Elastomeric Pumps at 4 °C and 34 °C: Technical Bases for a Continuous Infusion Use for Outpatient Parenteral Antibiotic Therapy.

BACKGROUND: Fosfomycin acts against aerobic Gram-/+ bacteria by blocking the synthesis of peptidoglycan. Its use has been currently re-evaluated for intravenous administration for the treatment of systemic infections by multidrug-resistant bacteria. Concentration-/time-dependent activity has been suggested, with potential clinical advantages from prolonged or continuous infusion. Nevertheless, little is known about Fosfomycin stability in elastomeric pumps. The aim of the present work was stability investigation before administration at 4 °C and during administration at 34 °C. METHODS: InfectoFos® (InfectoPharm s.r.l., Milan, Italy) preparation for intravenous use in elastomeric pumps at 4 °C and 34 °C was analyzed following EMA guidelines for drug stability. Samples were analyzed with an ultra-high performance liquid chromatography coupled with tandem mass spectrometry method on a LX50® UHPLC system equipped with a QSight 220® (Perkin Elmer, Milan, Italy) tandem mass spectrometer. RESULTS: Fosfomycin in elastomeric preparation is stable for at least 5 days at a storage temperature of 4 °C and 34 °C. CONCLUSIONS: The results suggest Fosfomycin eligibility for continuous infusion even in the context of outpatient parenteral antibiotic therapy. Therefore, this approach should be tested in clinical and pharmacokinetic studies, in order to evaluate the possible gains in the pharmacokinetic profile and the clinical effectiveness.

Neoadjuvant Therapy With Cabozantinib as a Bridge to Liver Transplantation in Patients With Hepatocellular Carcinoma (HCC): A Case Report.

Liver transplant (LT) is the treatment of choice for unresectable, localized hepatocellular carcinoma (HCC). However, transplant is not recommended for patients who have extensive tumor growth and do not meet specific criteria. For these cases, "bridging" therapies are often used to either downstage or prevent tumor progression while patients are on the transplant list. Various pre-transplant therapies have been used, including transarterial chemoembolization, radiofrequency ablation, and systemic therapies. Sorafenib is a well-known systemic agent used for HCC, but research is limited on its use as well as the use of newer agents as bridging therapy. Prospective studies are also lacking. We discuss cases of two patients diagnosed with HCC and treated systemically with cabozantinib prior to transplant without treatment-related complications. This suggests that cabozantinib could be safely used after sorafenib therapy to control disease related to HCC while awaiting liver transplantation.

Heart and Kidney Transplant in a Patient on Total Artificial Heart Bridge Therapy for 318 Days.

There are few cases in the current literature that describe simultaneous heart and kidney transplant (HKTx) while on total artificial heart (TAH) bridge therapy. We present a case of successful HKTx after 318 days on TAH bridge therapy and renal replacement therapy. This case demonstrates that TAH placement is a unique and up-and-coming option for bridging patients with heart and kidney failure to HKTx. TAH is a promising bridging option for patients who do not qualify for left ventricular assist device placement. The survival rates to heart transplant and long-term outcomes after heart transplant on TAH bridge therapy are encouraging as well. However, it is crucial for clinicians to be vigilant of the wide variety of complications associated with TAH when managing patients on TAH bridge therapy.

Case report: Ponatinib as a bridge to CAR-T cells and subsequent maintenance in a patient with relapsed/refractory Philadelphia-like acute lymphoblastic leukemia.

Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) constitutes a heterogeneous subset of ALL with a uniformly unfavorable prognosis. The identification of mutations amenable to treatment with tyrosine kinase-inhibitors (TKIs) represents a promising field of investigation. We report the case of a young patient affected by relapsed/refractory Ph-like ALL treated with chimeric antigen receptor T (CAR-T) cells after successful bridging with compassionate-use ponatinib and low-dose prednisone. We restarted low-dose ponatinib maintenance three months later. Twenty months later, measurable residual disease negativity and B-cell aplasia persist. To the best of our knowledge, this is the first case reporting the use of ponatinib in Ph-like ALL as a bridge to and maintenance after CAR-T cell therapy.

Wound vacuum-assisted closure as a bridge therapy in the treatment of infected cranial gunshot wound in a pediatric patient: illustrative case.

BACKGROUND: The authors reported the first pediatric case of a craniocerebral gunshot injury successfully treated with a wound vacuum-assisted closure (VAC) device after dehiscence and infection of the initial cranial wound. OBSERVATIONS: A 17-year-old boy suffered several gunshots to the left hemisphere, resulting in significant damage to the scalp, calvaria, and brain. Emergency hemicraniectomy was performed, with reconstruction of a complicated scalp wound performed at the initial surgery. The scalp was devitalized and ultimately dehisced, resulting in a cranial infection. It was treated first with a repeated attempt at primary closure, which failed because of persistent devitalized tissue, and was then treated with aggressive debridement followed by placement of a wound VAC device over the exposed brain as a bridge therapy to reconstruction. This procedure was deemed necessary given the active infection. LESSONS: The patient received delayed reconstruction with a free split-thickness skin graft and made a remarkable recovery, with cranioplasty performed 6 months later. The authors reviewed the literature on wound VAC use in cranial wound treatment and proposed it as a legitimate bridge therapy to definitive reconstruction in the setting of dirty wounds, active infection, or even hemodynamically unstable patients.

Case Report: Subtotal Lymphoid and Total Marrow Irradiation as Bridge Therapy to CD19-Directed CAR T Cells in a Chemorefractory DLBCL With Leukemic Involvement.

CAR T cell therapy has transformed the salvage approach for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Maintaining disease control before CAR T cell infusion during product manufacturing (so-called bridging therapy) is an important step to optimizing outcome. Among possible bridging therapies, radiation therapy (RT) represents a valuable option, particularly when the disease is limited. Here, we report for the first time on a patient with chemorefractory-transformed DLBCL showing nodal, extranodal, and massive bone marrow (BM) lymphoma infiltration associated with leukemic involvement, a successful bridge therapy to CD19-directed CAR T cell therapy by subtotal lymphoid/total marrow irradiation plus thiothepa followed by reinfusion of CD34+ autologous hematopoietic stem cells. Such a novel bridging regimen allowed a significant reduction of nodal and BM tumor volume while improving blood cell count before CAR T cell infusion. The PET-CT scan and BM evaluation performed at 1, 3, and 6 months after treatment showed complete remission of the disease. A relapse occurred at almost 1 year in lymph nodes because of CD19 antigen escape while the BM remained free of disease. This extended radiotherapy approach may be an effective bridging therapy for chemorefractory DLBCL patients eligible for CAR T cells who present with a high tumor burden, including massive BM involvement associated with leukemic involvement. This preliminary evidence is worth confirming in additional patients.