Prolymphocytic Leukemia

He was administered alemtuzumab twice (at the time of initial treatment and relapse) and cyclophosphamide, vincristine, and hydrocortisone chemotherapy. Furthermore, novel therapeutic drugs (venetoclax and tofacitinib) were administered based on previous case reports...Consideration should be given to suspending treatment, adjusting the administration interval, or administering G-CSF if necessary. The treatment interval can be appropriately adjusted, making it a valuable treatment option for refractory T-PLL.

P1, N=120, Active, not recruiting, Kymera Therapeutics, Inc. | Recruiting --> Active, not recruiting

P=N/A, N=200, Recruiting, Masonic Cancer Center, University of Minnesota | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2025

P1, N=23, Active, not recruiting, Ohio State University Comprehensive Cancer Center | Recruiting --> Active, not recruiting | N=10 --> 23 | Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2024

P=N/A, N=50, Recruiting, French Innovative Leukemia Organisation | Trial primary completion date: Jun 2023 --> Jun 2025

P1, N=6, Active, not recruiting, Washington University School of Medicine | Recruiting --> Active, not recruiting | N=54 --> 6

P1, N=15, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Dec 2026 --> Sep 2024 | Trial primary completion date: Dec 2026 --> Sep 2024

P1, N=18, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Jun 2024 --> Dec 2024

The clinical presentation, morphology, immunophenotype, and molecular genetic findings are most consistent with a diagnosis of SMZL with prolymphocytic transformation and cyclin D1 expression. Here, we present this case along with a review of the literature, and summarize the clinicopathological characteristics of SMZL with prolymphocytic transformation.

This review explores the rationale for discontinuing B-PLL and HCLv diagnoses. It then examines the concept of SBLPN, offers practical guidance for diagnosis and discusses future directions in classifying splenic B-cell lymphomas.

We present a patient diagnosed with T-PLL with MTCP1 rearrangement who was successfully treated with alemtuzumab followed by consolidative allogeneic unrelated donor stem cell transplantation...However, the lymphoma cells were clonally related to those at presentation. Currently, literature on T-PLL-like cases lacking the rearrangement of TCL1A is limited, and the possibility of whether a proportion of such cases could represent PTCL, NOS (with leukemic involvement) needs consideration.

P2, N=78, Recruiting, Ascentage Pharma Group Inc. | N=36 --> 78 | Trial completion date: May 2025 --> May 2027 | Trial primary completion date: May 2024 --> May 2026

Herein we describe the identification of a novel gene fusion SMCHD1::JAK2 resulting from a translocation between chromosome 9 and 18 involving SMCHD1 exon 45 and JAK2 exon 14 (t(9;18)(p24.1;p11.32)(chr9:g.5080171::chr18:g.2793269)), a previously undescribed genetic event in a patient with T-PLL harboring the key disease defining inv(14) resulting in rearrangement of TCL1 and TRA/D. In this manuscript, we describe the clinical and genetic features of the patient's disease course over a 25-month post-treatment duration using ruxolitinib and duvelisib.

No pathogenic mutations in 25 lymphoma-related genes were found. Due to her asymptomatic T-PLL disease, we observed her clinical situation and blood count every three months for at least one year.

We present two cases of MF with clinical urticarial lesions and a striking blood involvement that responded to mogamulizumab treatment...Differential diagnoses included urticarial lymphomatoid drug reactions and other lymphomas, like T-cell prolymphocytic leukemia, atypical Sézary syndrome, or adult T-cell lymphocytic leukemia. A low suspicion threshold is necessary for the diagnosis of atypical presentations of MF.

P1/2, N=60, Recruiting, Essen Biotech | Not yet recruiting --> Recruiting

Extrapulmonary Pneumocystis jirovecii pneumonia (PJP) infection can happen while receiving pentamidine prophylaxis.It is extremely rare to see a cutaneous infection, and no case has been reported in the last two decades.Trimethoprim-sulfamethoxazole (TMP-SMX) remains the first-line treatment for pulmonary and extrapulmonary PJP.

P2, N=150, Active, not recruiting, Fred Hutchinson Cancer Center | Recruiting --> Active, not recruiting | Trial completion date: Oct 2026 --> May 2025 | Trial primary completion date: Oct 2026 --> May 2025

TCL1 family-negative T-PLL cases have morphologic and immunophenotypic features that are similar to prototypic T-PLL. They are characterized by neoplastic proliferation of small to medium-sized mature T cells with CD4-positive T-cell receptor αβ phenotype. Tumor cells frequently maintain pan-T antigen expression. Recognizing these morphologic and immunophenotypic features will aid in accurately diagnosing this rare subset of T-PLL.

Current treatments, i.e. the CD52-antibody alemtuzumab, offer transient responses, with relapses being almost inevitable without consolidating allogeneic transplantation...Overall, the most efficient/selective single-agents and combinations (in vitro and in mice) in-cluded Cladribine, Romidepsin ((H)DAC), Venetoclax (BCL2), and/or Idasanutlin (MDM2)...Our data emphasize the therapeutic potential of pharmacologic strategies to reinstate P53-mediated apoptotic responses. The identified efficacies and their synergies provide an informative background on compound and patient selection for trial designs in T-PLL.

P1, N=36, Recruiting, Sumithira Vasu | Trial completion date: Dec 2024 --> Jul 2026 | Trial primary completion date: Dec 2024 --> Apr 2025

P2, N=6, Active, not recruiting, Ohio State University Comprehensive Cancer Center | Recruiting --> Active, not recruiting | N=25 --> 6 | Trial primary completion date: Dec 2024 --> Apr 2024

P2, N=41, Active, not recruiting, Ohio State University Comprehensive Cancer Center | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1/2, N=60, Not yet recruiting, Essen Biotech

P2, N=66, Active, not recruiting, M.D. Anderson Cancer Center | N=208 --> 66 | Trial completion date: Jun 2024 --> Jun 2026 | Trial primary completion date: Jun 2024 --> Jun 2026

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, N=100, Recruiting, Newave Pharmaceutical Inc | Trial completion date: Aug 2024 --> Oct 2025 | Trial primary completion date: Aug 2024 --> Oct 2025

P1, N=49, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

P1, N=32, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Phase classification: P1a/1b --> P1

P1, N=36, Recruiting, Sumithira Vasu | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=36, Completed, City of Hope Medical Center | Active, not recruiting --> Completed

These are 3 cases in a series of several other concordant results, nevertheless, elucidate limitations when interpreting FISH results in clinical applications, particularly when other genes are included in probe design. In addition, when the observed FISH signals are atypical, this study illustrates the necessity to perform complementary laboratory assays, such as NGS and/or RNASeq, to accurately identify fusion genes in tumorigenic translocations.

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

P1, N=37, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=19, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=62 --> 19

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.

P1, N=69, Active, not recruiting, Acerta Pharma BV | Phase classification: P1b --> P1

Our findings suggest the potential benefit of a broader treatment strategy combining therapeutic antibodies with PI3Ki for the treatment of patients with mature T-cell and NK-cell neoplasms.

© 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

P2, N=135, Active, not recruiting, Fred Hutchinson Cancer Center | Trial completion date: Dec 2025 --> Dec 2024

P1, N=18, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Jun 2024 | Trial primary completion date: Dec 2023 --> Jun 2024

We review the diagnostic criteria including clinical, immunophenotypic and molecular characteristics of patients with HCL-V and other HCL-like disorders including HCL, SDRPL, SMZL, B-PLL and the Japanese form of HCL. We also discuss the different criteria allowing us to separate these different entities and we will update the recent therapeutic options that have emerged, in particular the advances with chemoimmunotherapy and/or targeted therapies.