P1, N=15, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2023 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2026

P1/2, N=15, Recruiting, University of Illinois at Chicago | Trial primary completion date: Jan 2024 --> Jan 2025

However, increased infections and relapse resulted in a lack of survival benefit after long-term follow-up. ClinicalTrials.gov identifier: NCT00520130.

This study of ex vivo T-cell depleted SCT's demonstrates that NK cells recover quicker when compared to those receiving unfractionated grafts. These results may have implications for GvHD and the GvL effect which warrants further study.

P2, N=53, Active, not recruiting, Northwestern University | Trial completion date: May 2023 --> May 2027

P=N/A, N=15, Active, not recruiting, Queen Mary University of London

P1/2, N=130, Active, not recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Recruiting --> Active, not recruiting | Trial completion date: Jan 2024 --> Jan 2026

P2, N=75, Active, not recruiting, Children's Hospital of Philadelphia | Recruiting --> Active, not recruiting

P=N/A, N=25, Recruiting, Erasmus Medical Center | Not yet recruiting --> Recruiting

P2, N=25, Recruiting, Ohio State University Comprehensive Cancer Center | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=162, Recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Trial primary completion date: Dec 2024 --> Dec 2023

P2, N=40, Active, not recruiting, Boston Children's Hospital | Trial primary completion date: Jan 2024 --> Apr 2024

Abnormal cells in BM and PB became undetectable on microscopy and FCM, and the CNS lesion disappeared on MRI after second-line therapy with alemtuzumab...Allogeneic hematopoietic stem-cell transplantation was performed, and the fusion mRNA has now been undetectable for more than 5 years since transplantation. This is the first report of a T-PLL case with a CLEC16A::IL2 fusion gene.

P=N/A, N=30, Recruiting, Masonic Cancer Center, University of Minnesota | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

Analysis of such a gene signature uncovers a specific transcriptional program associated with mPMN-MDSC differentiation and allows us to identify that, in patients with either solid or hematologic tumors and in GDs, CD52, CD84, and prostaglandin E receptor 2 (PTGER2) represent potential mPMN-MDSC-associated markers. Altogether, our findings indicate that mature PMN-MDSCs distinctively undergo specific reprogramming during differentiation and lay the groundwork for selective immunomonitoring, and eventually targeting, of mature PMN-MDSCs.

P2, N=162, Recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1/2, N=72, Recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Not yet recruiting --> Recruiting

P2, N=22, Completed, Randy Windreich | Active, not recruiting --> Completed | Trial completion date: Nov 2023 --> Apr 2023 | Trial primary completion date: Nov 2023 --> Apr 2023

P2, N=30, Recruiting, Robert Nickel | Trial primary completion date: Dec 2024 --> Nov 2025

Approaches to prevent GVHD include pharmacologic strategies such as calcineurin inhibitors (cyclosporine, tacrolimus) combined with methotrexate or mTOR inhibitors (sirolimus), and IMP dehydrogenase inhibitors (mycophenolate mofetil). Increasingly, posttransplant cyclophosphamide is emerging as a promising strategy for GVCHD prevention especially in a setting of reduced intensity conditioning. Other approaches include serotherapy (ATG, Campath) and graft manipulation strategies...Targeted therapies including Bruton's tyrosine kinase inhibition, JAK1/2 inhibition, and ROCK2 inhibitors have improved cGVHD therapy, especially in the steroid refractory setting. Continued improvement in prophylactic strategies for cGVHD, identification of accurate cGVHD treatment endpoints, and access to novel therapeutic agents are expected to improve cGVHD outcomes.

Conditioning was myeloablative busulfan with pharmacokinetic monitoring and fludarabine +/- cyclophosphamide/thiotepa or a reduced intensity melphalan-based regimen with fludarabine. All patients received serotherapy with ATG or alemtuzumab. Post-PSCT immune suppression was none or mycophenolate mofetil (MMF) and/or a calcineurin inhibitor (CNI)... 41 patients with a variety of IEIs were included (Figure 1). At a median follow-up of 2.5 years, OS was 85% (95% CI 75-97%) and EFS 80% (95% CI 69-94%), but was variable by underlying disease (Figure 2). Three patients experienced graft failure (7.3%), two requiring a second transplant and one receiving donor lymphocyte infusion only.

P2, N=12, Recruiting, University of Calgary | Trial completion date: Jul 2024 --> Jul 2028 | Trial primary completion date: Jul 2023 --> Jul 2028

MethodA randomized controlled phase 2 trial was conducted in patients with hematological malignancies after HLA-identical sibling alloSCT with alemtuzumab added to the graft...Front Immunol, 2018) However, most patients did not convert to FD in the T-cell compartment, suggesting the GvL-effect of CD4+ DLI was limited. We considered this GvL-effect insufficient to prevent relapse and stress the importance of CD8+ donor T cells as main drivers of alloreactivity after DLI following HLA-identical alloSCT.

Introduction: T-Cell Prolymphocytic Leukemia (T-PLL) is a rare, aggressive T-cell malignancy with very poor prognosis. No substantial differences in T-PLL response rates or survival were observed when using the TPLL-ISG criteria when compared to historical reports. Patients who had a CR or CRi to alemtuzumab that proceeded with allo-SCT had a significantly prolonged OS and PFS. Patients with CD4-CD8+ T-PLL had inferior survival , but this will need to be validated in a larger sample set.

HLH diagnosis was established, and patient was started on HLH-94 protocol with etoposide and dexamethasone. Immunosuppressive therapies with steroids, and etoposide are the conventional first-line agents based on the HLH94 protocol; however, refractory cases have been shown to respond to other immunosuppressive agents and biologics including ruxolitinib, alemtuzumab, and emapalumab. Figure 1: A. Hemophagocytosis (Macrophage ingesting lymphocyte) B. Hemophagocytosis, more specifically-erythrophagocytosis (macrophage ingesting red blood cell).

P1/2, N=23, Active, not recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Trial completion date: Sep 2023 --> Sep 2026

P1/2, N=72, Not yet recruiting, National Heart, Lung, and Blood Institute (NHLBI)

CD52 expression is associated with features of ICB response in melanoma. Concomitant ICB and anti-CD52 treatment requires critical review.

Ruxolitinib, a JAK2 inhibitor, provided a promising therapeutic effect in a phase II study...Anti-CD52 antibody, alemtuzumab, or anti-IL-5 antibody, mepolizumab, are promising drugs to control symptoms that are associated with hypereosinophilic syndrome. Allo-SCT is anticipated as a curative treatment for CEL, but the evidence of Allo-SCT for CEL is still limited. Further study is required to define the treatment strategy.

Other first-line treatments and their corresponding median duration of response (months) included cyclosporine (n=7, 72 months), cyclophosphamide (n=5, 72 months), IVIG (n=1, 16 months), and methotrexate (n=11, 21 months). Subsequent lines of therapy included campath (n=9), cyclosporine (CSA) (n=4), cyclophosphamide (n=9), intravenous immunoglobulin (IVIG) (n=2), MTX (n=4), rituximab (n=1), sirolimus (n=1), tacrolimus (n=2), and tofacitinib (n=2)...These significant findings contribute substantially to advancing our comprehension of LGLL-associated HA and its optimal management strategies. AIHA in patients with LGLL points towards a global immune dysfunction in this disease beyond clonal cytotoxic T/NK cell expansion.

Early SMN occurred in 3.2% of participants by 5-years post-HCT and was associated with cGVHD occurrence (HR=2.14, 95% CI 1.06-4.33) and older age (>18 v <9 years, HR=6.35, 95% CI 2.66-15.14), but not ex-vivo depletion or use of ATG or alemtuzumab...Use of CD34 selection or T-cell depletion may reduce the risk of GVHD in transplant FA patients, but does not appear to impact 5-yr OS. Risk for early SMN development in FA patients receiving HCT associates with older age and cGVHD.

Pts with RT occurring as large B-cell lymphoma who did not previously receive CIT (e.g., fludarabine, cyclophosphamide, bendamustine, chlorambucil) for their CLL/SLL were included...The remaining 14% had been treated with an anti-CD20 monoclonal antibody (MoAb), steroids, lenalidomide, radiation, or alemtuzumab... This is the largest cohort of pts who developed RT having received only SMI with no CIT for their CLL reported, thus reflecting the current treatment landscape. Despite being CIT-naïve, pts in our series who received tx for their CLL/SLL and then developed RT had a short OS, underscoring the need to develop better therapies for these pts. In contrast, as in other published analyses (Wang Haematologica 2020), pts w/o prior tx for CLL/SLL had more favorable outcomes, with a median OS of approximately 5 years.

P1, N=120, Recruiting, Allogene Therapeutics | Trial primary completion date: Dec 2022 --> Aug 2025

P1/2, N=55, Active, not recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Recruiting --> Active, not recruiting | N=98 --> 55 | Trial primary completion date: Sep 2025 --> Jul 2023

P=N/A, N=25, Not yet recruiting, Erasmus Medical Center

P2, N=20, Not yet recruiting, Case Comprehensive Cancer Center

Treatment with alemtuzumab resulted in the depletion of JMML HSCs, pan-hematopoietic clearance of leukemia cells, and improved survival of 2° recipient mice. In conclusion, onco-fetal reprogramming is a hallmark of high-risk JMML resulting in unique molecular profiles. The characterization of epitype-specific aberrations of HSCs from high-risk JMML revealed novel prognostic biomarkers and pre-clinical evidence for the efficacy of anti-CD52 immunotherapy.

Given the patient’s clinical fragility in a multidisciplinary meeting, we opted for therapy aimed at symptomatic relief and containment of the disease with chlorambucil and prednisolone, with progressive clinical improvement until the 3rd cycle of treatment. This case illustrates the natural history of many cutaneous T-cell lymphomas, which exhibit an initial phase clinically and histologically indistinguishable from eczema. Although, rapid evolution to an aggressive primary cutaneous T-cell lymphoma, as described in our case, is not the commonly described evolutionary pattern. Treatment of PCTCL-NOS includes systemic chemotherapy, autologous bone marrow transplantation, and eventually, brentuximab vedotin or alemtuzumab.

Therefore, we investigated the complex associations between the T-cell kinetics and alloimmune responses in a cohort of 166 acute leukemia patients receiving alemtuzumab-based TCD alloSCT...Similar models showed that natural killer cells recovered rapidly after alloSCT and were associated with a lower risk of relapse (HR 0.62, 95%-CI 0.41-0.93). The results of this study advocate the use of joint models to further study immune cell kinetics in different settings.

Despite improved understanding of disease pathogenesis, alemtuzumab remains the frontline therapy in the treatment of naïve patients with indications for treatment given its high response rate. Unfortunately, the responses achieved are rarely durable, and the majority of patients are not candidates for consolidation with hematopoietic stem cell transplantation. Improved understanding of T-PLL pathogenesis has unveiled novel therapeutic vulnerabilities that may change the natural history of this lymphoproliferative neoplasm and will be the focus of this concise review.

However, CD40-stimulated CLL cells treated with the SRK-kinase inhibitor dasatinib were unable to restore T-cell function when co-cultured again with T cells, despite high expression of co-stimulatory receptors on CLL cells... These results demonstrate that CLL-derived T cells are not terminally dysfunctional, but that TCR-mediated activation is suppressed by CLL cells in a contact-dependent manner. By blocking CD24 and CD52, (CAR-)T cell function could be efficiently restored even without transforming CLL cells into efficient APC through CD40 stimulation. Manipulating interactions of CD24 and CD52 with Siglec-10 may represent a therapeutic window of opportunity to enhance autologous based therapies in CLL such as CAR-T cell therapy.