Cure Research Articles

Remission rate, toxicity and pharmacokinetics of venetoclax-based induction regimens in untreated pediatric acute myeloid leukemia

The efficacy and safety of venetoclax in newly diagnosed pediatric acute myeloid leukemia (AML) are not well-established as they are in adults. Children newly diagnosed with AML were recommended for induction therapy with venetoclax and chemotherapy or hypomethylating agents (HMAs) as per for the ChiCTR1900027146 trial. Venetoclax was administered at a consistent dose of 200 mg/m2/day for 28 days, with adjustments when used concurrently with azoles. The study measured both the remission rates and the safety assessments of venetoclax. We enrolled 45 newly diagnosed pediatric patients with AML. The complete remission rates were 94.7% in the low/middle-risk group and 80.8% in the high-risk group; MRD-negative rates were 52.6% and 38.5% in the low/middle-risk group and high-risk group, respectively. Venetoclax based combination therapy was well tolerated by the majority of patients. The median duration of venetoclax dosing was 18 days (range 9–28), with hematological toxicity and infection being the most common adverse events. Venetoclax-based induction regimens demonstrated a high response rate and safety profile in newly diagnosed pediatric AML cases. This underscores the significance of venetoclax as a viable treatment option for untreated AML, extending beyond its role as salvage therapy for refractory/relapsed AML.

Clinical outcomes of conversion surgery after induction immunochemotherapy for borderline resectable T4 esophageal squamous cell carcinoma

BackgroundThe current treatment strategies for borderline resectable esophageal squamous cell carcinoma remain controversial. This study aimed to evaluate the efficacy and safety of programmed cell death 1 inhibitors combined with chemotherapy, followed by conversion surgery, for borderline resectable esophageal squamous cell carcinoma.MethodsPatients with borderline resectable esophageal squamous cell carcinoma treated with induction immunochemotherapy from January 1, 2020 to July 1, 2023 at our hospital were retrospectively analyzed. The primary study outcome was the R0 resection rate. Secondary study outcomes included progression-free survival (PFS), overall survival (OS), pathological complete remission (pCR) rate, and safety.ResultsForty patients with borderline resectable esophageal squamous cell carcinoma were included in the analysis. The R0 resection rate was 23/40 (57.5%); the conversion success rate was 27/40 (67.5%), and the pCR rate was 11/40 (27.5%). The median follow-up was 23.6 months (95% CI, 19.1–28.2). One-year OS and PFS rates were 77.7% and 71.8%, respectively. The incidence rate of Grade 3–4 adverse events was 10%. There was a significant difference in PFS between patients who underwent surgery and those who did not (P = 0.008, HR: 0.144 95%CI: 0.034–0.606). However, the difference in OS was not significant (P = 0.128, HR: 0.299 95%CI: 0.063–1.416). Patients who achieved clinical downstaging after induction therapy had significantly better OS (P = 0.004 h: 0.110 95%CI: 0.025–0.495) and PFS (P = 0.0016, HR: 0.106 95%CI: 0.026–0.426) compared to those who did not.ConclusionsConversion surgery after induction immunochemotherapy is a promising new strategy with a high conversion rate, inspiring R0 resection rate, significant pathological remission rate, and mild toxicity for borderline resectable esophageal squamous cell carcinoma.

Comprehensive Exploration of CRISPR and Gene Editing Technologies: Applications, Ethical Considerations, and Future Implications in Genetic Research

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and other gene-editing technologies have revolutionized genetic research by enabling precise, targeted modifications of DNA sequences. This paper provides a comprehensive exploration of CRISPR technology, detailing its development, mechanism of action, and versatility in diverse applications. From advancements in medicine, including therapeutic interventions for genetic disorders, to innovations in agriculture aimed at enhancing crop resilience and yield, CRISPR's transformative potential is vast. However, the rapid evolution of gene editing presents significant ethical and societal challenges, particularly concerning human germline editing, ecological impacts, and issues of accessibility and equity. This paper examines these ethical considerations, emphasizing the need for robust regulatory frameworks and responsible scientific practices. It also projects the future trajectory of gene editing technologies, speculating on emerging trends, possible breakthroughs, and the global implications of CRISPR in fields such as personalized medicine, synthetic biology, and biotechnology. By critically analyzing current applications and addressing ethical concerns, this study aims to provide a balanced perspective on CRISPR's potential to reshape genetic research while advocating for ethical governance and public engagement in its ongoing development. CRISPR’s ability to target specific genes with high accuracy has made it an invaluable tool not only in research laboratories but also in clinical settings, where it shows promise in treating previously incurable diseases. Recent advancements have extended CRISPR’s applications beyond simple gene knockout, allowing for base editing, prime editing, and epigenetic modifications that expand the possibilities for genetic correction and enhancement. As scientists explore using CRISPR in complex organisms, the precision and control required for safe and effective treatments become a key focus, particularly in addressing off-target effects that could lead to unintended genetic consequences.

Clinical findings, prognostic factors, and outcome of protein-losing nephropathy in cats: A retrospective study.

Primary glomerular disease resulting in protein-losing nephropathy (PLN) is an uncommon cause of chronic kidney disease in cats, yet is important to recognize because it warrants specific treatment that impacts outcome. Characterize clinicopathologic findings, prognostic indicators, and short- (≤30 days) and long-term survival of cats with PLN. Thirty-seven cats with naturally occurring PLN. Medical records of cats with PLN admitted to a veterinary teaching hospital were retrospectively reviewed. Median age was 3 years (range, 1.5-11.5 years) and 17/37 (46%) were males. Short-term survival was 57%. The estimated median survival time of all cats was 424 days (95% confidence interval [CI], 0-1098 days). Common clinical signs included lethargy (57%), edema (46%) and weight loss (35%). Edema was more common in short-term survivors compared with nonsurvivors (odds ratio [OR], 0.21; 95% CI, 0.05-0.86-20.4; P = .04). Serum creatinine concentration at presentation was negatively associated with long-term survival (OR, 1.3; 95% CI, 1.03-1.52; P = .01). Administration of immunosuppressive and antiproteinuric medications was more common among short-term survivors compared with nonsurvivors (18/20 [90%] vs 9/16 [56%]; OR, 7.0; 95% CI, 1.2-40.8; P = .05 and 17/20 [85%] vs 7/16 [44%]; OR, 7.3; 95% CI, 1.5-35.2; P = .01, respectively). Partial or complete remission was documented in 11/31 (36%) cats and was associated with both short (OR, 3.3; 95% CI, 1.7-6.5; P < .001) and long-term survival (P = .003). Cats with PLN have a guarded prognosis, but achieving remission improves outcome. Cats presented with edema rather than azotemia are more likely to respond to treatment.

Outcomes of children and young adults with B-cell acute lymphoblastic leukemia given blinatumomab as last consolidation treatment before allogeneic hematopoietic stem cell transplantation.

Blinatumomab has remarkable efficacy in patients with relapsed/refractory (r/r) or measurable residual disease (MRD)-positive B-cell acute lymphoblastic leukemia (B-ALL). In many patients, blinatumomab treatment is followed by allogeneic hematopoietic stem cell transplantation (HSCT). However, the influence of blinatumomab on HSCT outcomes in children and young adults (YA) remains to be fully elucidated. We conducted a single-center, retrospective analysis on patients given blinatumomab as last treatment before HSCT. Seventy-eight pediatric and YA patients were evaluated. With a median follow-up of 23.23 months, the 2-year disease-free (DFS) and overall survival (OS) probability were 72.2% and 89.2%, respectively, with a 2-year cumulative incidence (CI) of non-relapse mortality (NRM) of 2.6%. A trend toward improved 2-year DFS, but not OS, was noted in patients transplanted in first complete remission (CR1) (92.9%) compared to those in second or greater remission (CR2/3) (68.5%, p=0.18) due to a lower CI of relapse (0% vs. 29.9%, p=0.05). Among CR2/3 patients, those receiving the sequential combination of inotuzumab and blinatumomab had a significantly lower CI of relapse as compared to those who did not receive inotuzumab (9.5% vs. 40.4%, p=0.023). Relapse after HSCT occurred in 16 patients, all exhibiting CD19-positive blasts; 10 of them received anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy and 2 inotuzumab as salvage therapy, leading to a 2-year post-relapse OS of 52.7%. Our results indicate that HSCT following blinatumomab in children and YA with B-ALL is highly effective, being associated with low NRM and not affecting the efficacy of subsequent salvage immunotherapies, including CAR-T cells.

End-of-life management of multiple myeloma patients in the era of CD38 and immunotherapy

BackgroundIn spite of spectacular advances in the treatment of multiple myeloma, a majority of patients will die from this disease or related complications. While a great amount of focus has been dedicated to the development of novel therapies, little attention has been paid to latter stages of patient follow-up.Patients and methodsIn order to describe patient management during this critical period as well as the immediate causes and circumstances of death, we have analyzed a single center series of 100 patients diagnosed with myeloma who died between 2016 and 2021.ResultsPatients received a median of 3 lines of treatment, including 2 during their last year of life. Sixty per cent of patients had received daratumumab. Fifty patients had obtained complete remission or very good partial response at some time during the course of disease but 75 were refractory to the last treatment line. Eighteen patients died while their disease was stable or in remission while 77 had confirmed progressive disease at time of death. Thirty six patients had uncontrolled sepsis, 49 were in renal failure and 24 had hypercalcemia at the time of death. Seventy three patients presented with lymphopenia. Disease progression was documented in a majority of MM patients at the time of death and was associated with disease-related complications in a significant number of patients.ConclusionDisease progression remains the main cause of death in patients with multiple myeloma.

The Future of OOC on Neurological Diseases - Alzheimer's

Abstract: Neurological Diseases such as Alzheimer's and Parkinsons' have been deemed incurable diseases. The complexity of the human brain is an obstacle for scientists to understand how treatments could interact with human brain microenvironments. To this date, researchers have used traditional modeling methods, such as in vitro cell culture and in vivo animal models. These methods are unable to showcase the different layers of the blood-brain barrier or accurately represent the cellular interactions within the brain. The proposed solution is a new research technology, organ on a chip, a multi-organ system connected with microfluidics. This review explores the organ on a chip, what it is made for, and how it is the future of drug development. In addition, we explore the lymphatic system and the different organ-on-a-chip models that can simulate the lymphatic system and BBB. Organ on a chip has the potential to help efficiently develop drugs and treatment, which has the potential to improve neurological disease conditions.

A phase 2, multicenter, clinical trial of CPX-351 in older patients with secondary or high-risk acute myeloid leukemia: PETHEMA-LAMVYX.

LAMVYX was a multicenter, single-arm, phase 2 trial designed to validate the safety and efficacy of CPX-351 in patients aged 60-75 years with newly diagnosed, secondary acute myeloid leukemia and to generate evidence on key issues not addressed in the preceding regulatory pivotal trial. The primary end point of the study was the complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate after induction. Eligible patients were recommended to undergo allogeneic hematopoietic stem cell transplantation after the first consolidation cycle. Alternatively, patients could undergo up to six maintenance cycles with CPX-351. Twenty-nine patients (49%; 95% exact confidence interval [CI], 37%-62%) patients achieved a CR/CRi after one or two cycles of induction, with a measurable residual disease negativity rate of 67% as assessed by centralized, multiparameter flow cytometry. Among patients who had serial next-generation sequencing analyses available, clearance of somatic mutations that were present at diagnosis was achieved in 7 (35%). The median follow-up among survivors was 16.8 months (range, 8.7-24.3 months). The median event-free survival was 3.0 months (95% CI, 1.4-7.3 months), and the median overall survival was 7.4 months (95% CI, 3.7-12.7 months). In landmark analyses at day +100 from diagnosis, the 1-year overall and event-free survival rate among patients who underwent allogeneic hematopoietic stem cell transplantation was 70% (95% CI, 47%-100%) and 70% (95% CI, 47%-100%), respectively. The corresponding values were 89% (95% CI, 71%-100%) and 44% (95% CI, 21%-92%), respectively, for patients who entered the maintenance phase. No significant longitudinal changes were observed in severity index or quality-of-life visual analog scale scores. The current data provide novel insights that might inform the clinical positioning and optimal use of CPX-351, complementing previous results (ClinicalTrials.gov identifier NCT04230239).

FDA Approval Summary: Olutasidenib for Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia with an Isocitrate Dehydrogenase-1 Mutation.

On December 1st, 2022, the FDA approved the new molecular entity olutasidenib (Rezlidhia: Rigel Pharmaceuticals), a small-molecule inhibitor of isocitrate dehydrogenase-1 (IDH1), for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (R/R AML) with a susceptible IDH1 mutation as detected by an FDA-approved test. The efficacy of olutasidenib was established based on complete remission (CR) + CR with partial hematological recovery (CRh) rate, duration of CR + CRh, and conversion of transfusion dependence (TD) to transfusion independence (TI) in Study 2102-HEM-101. In the pivotal trial, 147 adult patients treated with 150mg twice daily (BID) of olutasidenib were evaluable for efficacy. With a median follow-up of 10.2 months, the CR/CRh rate was 35% (95% CI: 27-43%), with a median duration of response of 25.9 months (95% CI: 13.5 months, not reached [NR]). Of the 86 patients that were TD at baseline, 29 became TI (34%). The most common (≥20%) adverse reactions were nausea, fatigue, arthralgia, leukocytosis, dyspnea, pyrexia, rash, mucositis, diarrhea, and transaminitis. An assessment of long-term safety of olutasidenib is a condition of this approval.

Primary seminal vesicle diffuse large B-cell lymphoma: a case report and review of the literatures

Primary seminal vesicle lymphoma is a remarkably rare condition, predominantly manifesting as diffuse large B-cell lymphoma. Due to its rarity and nonspecific clinical presentations, it is often misdiagnosed or overlooked. Here, we report a case of a 68-year-old male diagnosed with primary seminal vesicle lymphoma, coinciding with prostate cancer. The diagnosis followed initial findings of elevated prostate-specific antigen levels and abnormal magnetic resonance imaging of the prostate and left seminal vesicle. Suspicion of prostate cancer led to a radical resection of both the prostate and seminal vesicle. Subsequent pathological examination and next-generation sequencing post-surgery confirmed the diagnosis of primary seminal vesicle diffuse large B-cell lymphoma, characterized by CD79B mutation type (MCD type). The patient was treated with six cycles of the R-CHOP regimen (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone), achieving complete metabolic remission as confirmed by positron emission tomography-computed tomography. Fifteen months post-treatment, the patient’s condition remains favorable. Through our literature review of additional six cases of primary seminal vesicle lymphoma, we aim to elucidate the typical clinical presentations, imaging features, pathological characteristics, genetic mutations, and therapeutic strategies, aiming to contribute to better detection and management of this rare malignancy. This case underscores the diagnostic challenges and emphasizes the necessity for heightened clinical suspicion and definitive pathological examination in the management of primary seminal vesicle lymphoma.

Translating molecular insights into clinical success: alkaloid-based therapies for leukemia.

Alkaloids, a diverse class of naturally occurring compounds, have shown significant potential in the treatment of leukemia by targeting key molecular pathways and cellular mechanisms. This review discusses several potent alkaloids, such as homoharringtonine, chaetominine, matrine, and jerantinine B, which induce apoptosis, cell cycle arrest, and autophagy and inhibit signaling pathways including PI3K/Akt/mTOR, MAPK, and NF-κB. For instance, homoharringtonine induces apoptosis in acute myeloid leukemia (AML) cells via the SP1/TET1/5hmC/FLT3/MYC axis, while chaetominine enhances chemosensitivity by inhibiting the PI3K/Akt/Nrf2 pathway. In addition, targeting leukemia stem cells (LSCs) with alkaloids such as zalypsis offers promise due to its ability to induce apoptosis without significantly affecting normal hematopoietic stem cells. The modulation of the immune response, such as the inhibition of NF-κB activation by noscapine, further underscores the potential of alkaloids in overcoming treatment resistance. Various studies have demonstrated the efficacy of alkaloids across different leukemia types. For example, jerantinine B targets AML cells, while vincristine has shown success in lymphocytic leukemia. Clinical trials have also highlighted the benefits of alkaloids, including homoharringtonine, which achieved a 79.9% complete remission rate in AML patients. However, adverse effects such as neutropenia and hepatotoxicity necessitate careful management. Collectively, these findings emphasize the need for further research into alkaloid-based combination therapies to enhance efficacy and minimize toxicity, providing a promising avenue for innovative leukemia treatments.

Forimtamig, a novel GPRC5D-targeting T-cell bispecific antibody with a 2+1 format, for the treatment of multiple myeloma.

Despite several approved therapies, multiple myeloma (MM) remains an incurable disease with high unmet medical need. "Off-the-shelf" T-cell bispecific antibodies (TCBs) targeting BCMA and GPRC5D have demonstrated high objective response rates (ORR) in heavily pre-treated MM patients, however, primary resistance, short duration of response and relapse driven by antigen shift frequently occurs. Although GPRC5D represents the most selective target in MM, recent findings indicate antigen loss occurs more frequently than with BCMA. Thus, anti-GPRC5D immunotherapies must hit hard during a short period of time to kill as many myeloma cells as possible. Here, we characterize forimtamig, a novel GPRC5D-targeting TCB with 2+1 format, using preclinical models of MM. Bivalent binding of forimtamig to the N-terminus of GPRC5D confers higher affinity as compared to classical 1+1 TCB formats correlating with formation of more stable immunological synapses and higher potency in tumor cell killing and T cell activation. Using an orthotopic mouse model of MM, forimtamig recruited T effector cells to the bone marrow and induced rapid tumor killing even after the introduction of step-up dosing to mitigate cytokine release. Combination of forimtamig with standard-of-care (SoC) agents including anti-CD38 antibodies, immunomodulatory drugs and proteasome inhibitors improved depth and duration of response. The combination of forimtamig with novel therapeutic agents including BCMA-TCB and Cereblon E3 Ligase Modulatory Drugs (CELMoDs) was potent and prevented occurrence of GPRC5D-negative tumor relapse. Forimtamig is currently being evaluated in Phase 1 clinical trials in relapsed and refractory myeloma (RRMM) patients for monotherapy and in combination treatments. NCT04557150.

Postoperative outcome of special primary aldosteronism undergoing surgery based on adrenal vein sampling results

To further demonstrate the gold standard role of adrenal vein sampling (AVS) in the subtyping diagnosis of primary aldosteronism (PA). In this study, 9 patients with special PA, whose functional advantages indicated by AVS were contrary to the results of CT examination, were selected. Laparoscopic adrenalectomy was performed based on AVS results, and the surgical outcome was followed up. Nine patients, aged[M(Q1, Q3)] 58.0 (52.0, 63.0) years, including 7 males and 2 females, were followed up for 12 (9, 12) months. CT revealed unilateral morphological abnormalities in 5 cases (the functional advantage side indicated by AVS was contrary to the results of CT examination), and bilateral abnormalities in 4 cases (AVS results confirmed unilateral abnormalities). During the follow-up, all 9 patients achieved complete biochemical remission, 4 patients achieved complete clinical remission, and 5 patients achieved partial clinical remission. The study indicates that compared with CT imaging, AVS has better accuracy in PA subtyping, and selecting surgical side based on AVS results is a reliable and effective strategy.

Colorectal Endoscopic Full-Thickness Resection: A Portuguese Multicenter Experience Based on a Retrospective Cohort

Introduction: Endoscopic full-thickness resection (EFTR) is a minimally invasive endoscopic technique that allows the resection of complex colorectal lesions, such as non-lifting, peri-appendicular, peri-diverticula, and subepithelial lesions. Published data suggest that EFTR has a technical success and R0 resection rates of 89 and 79%, respectively, and an adverse event rate of 12%. This study summarizes the EFTR experience in nine Portuguese centers with regard to its efficacy and safety. Methods: This was a multicenter uncontrolled retrospective study, including 129 colorectal EFTRs between March 2017 and September 2023. The main outcomes were procedural and technical success, R0 resection, curative resection, adverse events, and recurrence rate. Results: 129 EFTR procedures were conducted, with a technical success rate of 88.4% (114/129). Most lesions were in the right colon, with a median resection size of 25 [10–45] mm. R0 and curative resection rates were 75.9% (85/112) and 58.0% (65/112), respectively. Adverse events occurred in 13.2% (17/129) of patients, mostly due to immediate perforation, appendicitis, or delayed bleeding, needing surgery in 5.4% (7/129). Local recurrence occurred in 5.4% (5/92) of resections. Conclusion: This real-life multicenter study highlights the utility of colorectal EFTR for management of complex and carefully chosen lesions, with an acceptable adverse events rate and need for surgery.

Clinicopathological Features of Membranous Nephropathy Complicated by IgA Nephropathy: A Retrospective Analysis of Seven Cases.

Aims/Background Both membranous nephropathy (MN) and immunoglobulin A nephropathy (IgAN) are immune complex-mediated glomerular diseases, but the concurrent occurrence of these two conditions in the same patient is not common, a phenomenon that is currently not supported by clinical data in terms of treatment and prognosis. This study explores the clinical and pathological characteristics, as well as the treatment outcomes, of patients affected by MN and IgAN simultaneously. Methods The clinical data, pathological features, and diagnostic and therapeutic information of seven cases of MN complicated by IgAN, treated between December 2015 and December 2022, were retrospectively analyzed. Results Among the seven cases, there were two male and five female patients, with an average age of 57.3 ± 9.2 years. All patients presented with clinical manifestations of proteinuria and edema upon admission, with an average 24-hour urine protein of 3716.6 ± 1519.4 mg/24 h. Phospholipase A2 receptor (PLA2R) expression was detected in all seven cases, and nephrotic syndrome was clinically diagnosed in five cases. Additionally, all seven cases showed microscopic hematuria, with intermittent gross hematuria in two cases. All seven patients included in this study underwent renal biopsy. After disease staging, the patients had MN stages I-III and IgAN stages II-III. Pathological findings revealed abnormal glomerular basement membrane (GBM) and diffuse immunoglobulin G (IgG) deposition in the subepithelial space, predominantly of the IgG4 subtype. Simultaneously, there was diffuse mesangial zone deposition of immunoglobulin A (IgA) to varying degrees, co-localization of complement component C3 and IgA, and mesangial cell proliferation. Treatment strategies included angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in combination with steroids or immunosuppressive therapies such as tacrolimus, cyclophosphamide, and rituximab. After 2-6 months of treatment, all patients achieved complete remission with a favourable prognosis. Conclusion MN accompanied by IgAN tends to occur more frequently in middle-aged and elderly individuals, with a relatively low incidence. The latent feature of the comorbidities manifests as a form of IgAN superimposed on the background of MN. Utilizing ACEI or ARB in combination with steroids or various immunosuppressive therapies represents a potentially effective treatment strategy.

Neoadjuvant Chemotherapy With the Angiogenesis Inhibitor Bevacizumab for Locally Advanced Cervical Cancer.

We hypothesized that adding bevacizumab to platinum-based neoadjuvant chemotherapy - whose efficacy for patients with recurrent or metastatic cervical cancer has already been proven - could optimize the therapy regimen, leading to improved response rates and survival outcomes. Forty patients with histologically confirmed cervical cancer with FIGO stage IB3-IVA who received platinum-based neoadjuvant treatment between March 2008 and January 2019 in the Department of Obstetrics and Gynecology of University Hospital Cologne were analyzed. Twenty patients were treated with additional bevacizumab. The comparative cohort consisted of 18 patients treated with neoadjuvant chemotherapy alone. The response rates and clinical outcomes, including progression-free survival and overall survival, were evaluated. Neoadjuvant chemotherapy combined with bevacizumab significantly improved the response rate (p=0.046). The survival analysis showed that patients treated without bevacizumab had better progression-free survival up to FIGO stage IVA than patients treated with bevacizumab. However, overall survival was similar for both cohorts. For patients with advanced tumor stage, including FIGO IVB, progression-free survival and overall survival improved with the addition of bevacizumab. Pathological complete remission was a statistically significant prognostic factor for progression-free survival (p=0.039) but did not significantly affect overall survival (p=0.098). While bevacizumab did not demonstrate a significant improvement in overall survival rates, it was associated with a notable reduction in tumor size and showed a trend towards improved clinical response rates. These findings suggest that bevacizumab may have potential in optimizing the neoadjuvant treatment approach.

Secondary haematological dysplasia after CAR-T-cell therapy foracute lymphoblastic leukaemia in children.

The use of CAR-T is becoming more widespread in the treatment of haematological malignancies. In adults, secondary myelodysplastic syndromes (MDS) after CAR-T have been described. However, there are currently no data on the risk of MDS following CAR-T in children treated for acute lymphoblastic leukaemia (ALL). We studied all children treated with CAR-T cells at Hospital Sant Joan de Déu in Barcelona and those with persistent cytopenias were evaluated at the cytological, cytogenetic, and molecular levels to look for MDS. A total of 106 patients received CAR-T for ALL. Among 40 patients without early relapse or subsequent therapy after CAR-T, four fulfilled the WHO criteria for myelodysplasia. These four patients had received a haematopoietic stem cell transplantation (HSCT) prior to CAR-T and presented cytopenias with severe dysplastic changes in bone marrow after CAR-T. One patient had clonal MDS with high-risk cytogenetics arising from the host cells requiring a HSCT. Three patients had non-progressive dysplasia arising from the donor cells. Two are alive in complete remission with stable cytopenias and one succumbed to ALL relapse. This is the first description of post-CAR-T MDS and haematological dysplasia in children and highlights the need to monitor children with persistent post-CAR-T cytopenias.

Epstein-Barr virus positive post-transplant lymphoproliferative disorder with significantly decreased T-cell chimerism early after transplantation: A case report

BACKGROUND Post-transplant lymphoproliferative disorder (PTLD) is a rare but highly fatal complication occurring after allogeneic hematopoietic cell transplantation (allo-HCT) or solid organ transplantation (SOT). Unlike SOT, PTLD after allo-HCT usually originates from the donor and is rarely accompanied by a loss of donor chimerism. CASE SUMMARY We report a case of Epstein-Barr virus positive PTLD manifesting as diffuse large B-cell lymphoma (DLBCL) with significantly decreased T-cell chimerism early after allo-HCT. A 30-year-old patient with acute myeloid leukemia underwent unrelated allo-HCT after first complete remission. Nearly 3 mo after transplantation, the patient developed cervical lymph node enlargement and gastric lesions, both of which were pathologically suggestive of DLBCL. Meanwhile, the patient experienced a significant and persistent decrease in T-cell chimerism. A partial remission was achieved after chemotherapy with single agent rituximab and subsequent R-CHOP combined chemotherapy. CONCLUSION The loss of T-cell chimerism and the concomitant T-cell insufficiency may be the cause of PTLD in this patient.

Multiple Sclerosis and Subcutaneous Panniculitis-like T Cell Lymphoma with Hemophagocytic Syndrome: The Role of Treatment Sequencing in the Pathogenetic Mechanism

Introduction: Although panniculitis-like T cell lymphoma (SPTCL) and hemophagocytic syndrome (HSP) have been described as complications following immunosuppressive treatments, there are no reported cases of concomitant SPTCL/HSP and multiple sclerosis (MS). Materials and Methods: We describe the case of a patient affected by an aggressive phenotype of relapsing remitting MS, characterized by consecutive severe relapses with no complete remission. He developed panniculitis-like T cell lymphoma (SPTCL) and hemophagocytic syndrome (HSP) after receiving multiple immunosuppressive treatments in sequence. Despite the aggressive nature of these complications, the patient responded well to a combination of Gemcitabine and Cisplatin. Discussion and Conclusions: With this case, we suggest that physicians always consider blood diseases as possible MS therapy complications, especially in the sequencing setting, and also consider uncommon treatments in those with autoimmune predispositions.

Brainstem changes causing reversible RBD in patients with spontaneous intracranial hypotension: a longitudinal neuroimaging study.

This study aimed to investigate the prevalence of REM sleep behavior disorder (RBD) in patients with spontaneous intracranial hypotension (SIH) and longitudinally assess the effects of epidural blood patch (EBP) treatment on brainstem structures using a neuroimaging approach. Twenty-two participants (10 SIH patients and 12 controls) underwent 3-Tesla Magnetic Resonance Imaging (MRI) scans. Midbrain and pons areas were measured on T1-weighted scans at baseline in both groups and three months after the first EBP in SIH patients to determine any MRI structural changes. The RBD Single-Questionnaire was used to screen SIH patients with symptoms suggestive of RBD for polysomnographic (PSG) recording. Half of the SIH patients (5/10) exhibited PSG-confirmed RBD. Baseline evaluation revealed deep brain swelling (DBS) on MRI scans in SIH-RBD patients. Following EBP treatment, significant changes in midbrain and pons morphometry were associated with complete clinical remission of RBD. Cross-sectional analysis showed larger midbrain and pons areas in SIH patients (with and without RBD) compared to controls. A midbrain area of 200 mm2 was identified as a cut-off value distinguishing SIH patients (with and without RBD) from controls individually. Longitudinal analysis demonstrated lower midbrain areas at follow-up compared to baseline in SIH patients. The study suggests that brainstem morphometric changes may underlie reversible RBD in SIH patients. Midbrain area measurement could serve as a dynamic biomarker for SIH, particularly in the presence of RBD, offering insights for clinical practice.