pentostatin / Generic mfg. - LARVOL DELTA

Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma. (PubMed, J Immunother Cancer) - P2 | "Consistent with our hypothesis, ex vivo manufacturing using mTOR inhibition and IFN-α polarization consistently yielded a novel RAPA-201 DP that possessed a desirable phenotype relative to cytokine phenotype, memory status, and checkpoint expression. RAPA-201 recipients had preservation of T cell counts and Th1 cytokine secretion yet had increased T cell receptor clonality that associates with antitumor responses in the setting of monoclonal antibody checkpoint therapy. RAPA-201 therapy overcomes previous barriers to effective autologous polyclonal T-cell therapy, as it is feasible to manufacture, exquisitely safe to administer, and mediates remission in patients with RRMM."

IO biomarker • Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • CD73 • IFNA1 • LAIR1 • PD-1

Shared-Output Aptamer-Gated DNA Nanodevices Program NbaSPARDA Trans-Cleavage for Metabolite and Drug Sensing. (PubMed, Small) - "Adenosine-gated devices achieve detection limits of 0.28 and 0.40 µM in buffer, while Ade-SSA14 supports matrix-spiked relative readout of pentostatin-induced adenosine-related changes in processed HeLa lysate filtrates. A mefloquine aptamer reconfigured with the same 16 nt output achieves detection limits of 0.018 µM in buffer and 0.061 µM by matrix-matched calibration in an acetonitrile-processed blank-serum extract...An exploratory estradiol construct accesses the output channel. Together, these results establish a shared-output interface for programming NbaSPARDA trans-cleavage in metabolite and drug analysis."

Journal

Phase 2 trial of rituximab with either pentostatin or bendamustine for multiply relapsed or refractory hairy cell leukemia. (PubMed, Blood) - P2 | "Possible DCFR superiority was hypothesis-generating, given uneven baseline risks and trial design. NCT01059786."

Journal • P2 data • Hairy Cell Leukemia • Hematological Malignancies • Leukemia • Oncology

Pharmacophore-Based Virtual Screening for Identification of Adenosine Deaminase Inhibitors. (PubMed, Iran J Pharm Res) - "Two crystal structures of ADA co-crystallized with erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) and pentostatin were used to develop a pharmacophore model...Compared with reference ADA inhibitors, compound 154 exhibited similar drug-likeness and pharmacokinetic properties, although further toxicity optimization may be required. These results suggest that compound 154 is a promising lead for developing new ADA inhibitors and underscore the effectiveness of computational methods in drug discovery."

Journal • CNS Disorders • Genetic Disorders • Hepatology • Immunology • Oncology • Primary Immunodeficiency

Construction and systematic engineering of Saccharomyces cerevisiae for efficient de novo biosynthesis of pentostatin. (PubMed, J Biotechnol) - "Furthermore, transcriptomics demonstrated that Cns4 globally reprograms carbon and energy metabolism to boost precursor supply and cellular robustness. This work integrates structural insights with systems metabolic engineering, providing a generalizable paradigm for biosynthesizing toxic nucleoside natural products."

Journal

Randomized Phase II Trial of Rituximab With Either Pentostatin or Bendamustine for Multiply Relapsed or Refractory Hairy Cell Leukemia (clinicaltrials.gov) - P2 | N=69 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2027 ➔ Jun 2031

Trial completion date • Hairy Cell Leukemia • Hematological Malignancies • Leukemia • Neutropenia • Oncology • CD20 • CD22 • IGH • IL2RA • ISG20 • ITGAE • ITGAX

A novel corneal epithelial cell culture assay for assessing topical antivirals against herpes simplex virus keratitis. (PubMed, Biochem Biophys Rep) - "Specifically, acyclovir and its prodrug, valaciclovir, exerted comparable effects after direct application to HCE cells...Notably, 2'-deoxycoformycin, an adenosine deaminase inhibitor, only partially restored its activity, indicating that factors other than adenosine deaminase contribute to the limited efficacy of vidarabine...Our system also supported assays with thymidine kinase-deficient HSV-1, showing high application potential. Overall, the developed immortalized HCE cell-based model provides a practical platform for topical antiviral evaluation that can reduce the reliance on animal experiments for preclinical drug development."

Journal • Preclinical • Herpes Simplex • Infectious Disease • Keratitis • Ocular Infections • Ocular Inflammation • Ophthalmology

T-cell prolymphocytic leukemia: A review of induction therapies. (ASCO 2026) - "While intravenous (IV) alemtuzumab has emerged as the primary induction therapy, combination therapies including pentostatin, fludarabine, cyclophosphamide, and mitoxantrone (FMC), and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) remain under-evaluated. IV alemtuzumab monotherapy is a superior induction agent compared to SubQ administration and prior cytotoxic regimens. Although FMC-A achieves high response rates, it is associated with an increased risk of grade 3–4 AEs, particularly cytomegalovirus morbidity and neutropenia. As long-term survival depends on successful HCT, rapid remission is preferred to facilitate transplant bridging."

Review • Cytomegalovirus Infection • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Prolymphocytic Leukemia

Prospective Clinical Trial of Mycophenolate Mofetil (MMF) Duration De-Escalation in Allogeneic Hematopoietic Cell Transplantation (HCT) for Inborn Errors of Immunity: Is MMF Dispensable After Reduced Intensity Conditioning, Posttransplantation Cyclophosphamide(Ptcy)-Based HCT? (CIS 2026) - "Recipients of T cell-replete HLA-matched (related or unrelated) or HLA-haploidentical grafts (n = 44) received serotherapy-free, radiation-free reduced-intensity conditioning (pentostatin/cyclophosphamide/2 days busulfan), with PTCy, sirolimus, plus/minus mycophenolate mofetil (MMF) as GVHD prophylaxis. Across patients, reducing MMF exposure is associated with earlier donor T cell reconstitution and no adverse effect on survival or engraftment. Tabular data are included as downloadable supplement files."

Clinical • Post-transplantation • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Infectious Disease • Pneumonia • Respiratory Diseases • Transplantation

The dynamic interplay of M1/M2-like macrophages and adenosine deaminase activity modulates COVID-19 severity. (PubMed, Open Med (Wars)) - "The relationship between ADA2 activity and macrophage polarization was functionally assessed using pentostatin, whereas EHNA was used exclusively for the differential measurement of ADA isoenzyme activities...Overall, our findings suggest that ADA2 regulates macrophage plasticity in COVID-19, promoting M1/M2 hybrid polarization and contributing to immune dysregulation. ADA2 may serve as a biomarker for disease progression and a therapeutic target to modulate macrophage-driven inflammation in severe COVID-19."

Journal • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • CD86 • MRC1

Transplant in Hemophagocytic Lymphohistiocytosis (HLH) Patients: A Single-Center Experience Over Twenty Years (ASPHO 2026) - "Conditioning regimens most commonly included alemtuzumab/fludarabine/melphalan combination (41%) or busulfan (target exposure 4600 µmol·min/L) /pentostatin/cyclophosphamide combination (29%). Patients with HLH requiring HSCT are conditioned with a variety of regimens. Both conditioning approaches most utilized at our institution were associated with infectious complications and GvHD, as well as transplant-related mortality, with an overall survival comparable to that reported in the literature [3]. Reduced-intensity fludarabine-based conditioning was associated with a higher incidence of mixed chimerism, consistent with prior reports [3]."

Clinical • Bone Marrow Transplantation • Endocrine Disorders • Epstein-Barr Virus Infections • Graft versus Host Disease • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Lymphoma • Nephrology • Otorhinolaryngology • Rare Diseases • T Cell Non-Hodgkin Lymphoma • Transplantation • STXBP2 • XIAP

Host adenosine deaminase reprograms purinergic immunoregulation in Leishmania braziliensis infection. (PubMed, Cytokine) - "Functional inhibition of ADA with pentostatin significantly increased intracellular parasite load and reduced ROS, TNF-α, and IL-1β production, demonstrating a critical role for ADA in sustaining macrophage microbicidal activity. These findings suggest that ADA activity is central to modulating adenosine-mediated immunosuppression in CL and may serve as both a biomarker of disease activity and a potential therapeutic target."

Journal • Dermatology • Immune Modulation • Immunology • Infectious Disease • Inflammation • ADORA2A • IL1B • TNFA

Functional shifts of the dual-substrate phosphoribosyl isomerase PriA from primary to specialized metabolism in rare Actinomycetota. (PubMed, Microb Genom) - "Phylogenomic analysis revealed additional recruitments of priA and hisG homologues into diverse uncharacterized biosynthetic gene clusters taxonomically related to the nucleoside antibiotics adechlorin, pentostatin and pyrazomycin. These findings highlight how enzyme family expansions and recruitment drive metabolic functional innovation in Actinomycetota, involving both gene loss and gain throughout central and specialized metabolism, and how evolutionary genome mining allows unbiased natural product discovery."

Journal

BRAF-Mutated Hairy Cell Leukemia: Survival Trends and Treatment Patterns Using SEER Database (NCCN 2026) - "HCL is exquisitely sensitive to chemotherapy over the last three decades with the use of alpha interferon (IFN-α), the purine nucleoside analogues pentostatin, and cladribine. In conclusion, our study shows that in BRAF-mutated hairy cell leukemia, survival varies across gender, race, and income, highlighting the real-world impact of demographic and socioeconomic factors. Chemotherapy continues to be highly effective, with markedly improved survival benefits, while radiation provides more limited improvement. These results emphasize the importance of early diagnosis and timely treatment, ensuring all patients have access to effective therapies to achieve the best possible outcomes."

Hairy Cell Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • BRAF • IFNA1

Nonmyeloablative pentostatin-cyclophosphamide preconditioning improves rates of engraftment in adults undergoing haploidentical HCT for sickle cell disease. (PubMed, PLoS One) - P1/2 | "Further study to determine an optimal nonmyeloablative haploidentical regimen for SCD patients with compromised organ function is imperative."

Journal • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Chronic Kidney Disease • Fibrosis • Genetic Disorders • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Nephrology • Oncology • Sickle Cell Disease • Transplant Rejection • Transplantation

A Blood Stem Cell Transplant for Sickle Cell Disease (clinicaltrials.gov) - P1 | N=3 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Feb 2026 ➔ Jan 2027 | Trial primary completion date: Feb 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Anemia • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation • HLA-B • HLA-C • HLA-DRB1

Allogeneic hematopoietic cell transplantation for partial RAG deficiency in children and adults: excellent outcomes with a reduced intensity, posttransplantation cyclophosphamide-based approach. (PubMed, J Allergy Clin Immunol) - "RIC allo-HCT with PTCy-based GVHD prophylaxis is safe and effectively reverses immune dysfunction in patients with pRD."

Journal • Acute Graft versus Host Disease • Bronchiectasis • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Infectious Disease • Primary Immunodeficiency • Pulmonary Disease • Respiratory Diseases • Septic Shock • Transplantation

Molecular Mechanisms of Temperature-Regulated Cordycepin Biosynthesis in Cordyceps militaris. (PubMed, J Fungi (Basel)) - "Multi-omics analysis indicated that high temperature promotes cordycepin accumulation through the synergistic regulation of multiple pathways: upregulating genes in the pentose phosphate pathway, purine metabolism, and cordycepin biosynthetic gene cluster (Cns1-Cns3), increasing protective agent pentostatin content, downregulating cordycepin-degrading genes, and enhancing cordycepin transmembrane transport. This study clarifies the molecular mechanism of temperature-mediated cordycepin accumulation, providing a theoretical basis for improving cordycepin production via temperature regulation, optimizing Cordyceps militaris strain quality, and facilitating efficient industrial production."

Journal

Allogeneic Transplantation for Older Adults with Acute Lymphoblastic Leukemia Using Pentostatin and Low-Dose Total Body Irradiation (TCT-ASTCT-CIBMTR 2026) - "Donor type, disease status, and post-transplant cyclophosphamide (PTCy) use were recorded. Pentostatin combined with low-dose TBI achieved consistent engraftment, low early mortality, and manageable GVHD rates in older adults with ALL. This regimen provided effective disease control with acceptable toxicity, supporting its use as a feasible reduced-intensity platform for patients not eligible for myeloablative conditioning. Although long-term survival remains limited in this high-risk population, these results highlight the potential role of pentostatin/TBI as a well-tolerated conditioning strategy that preserves the biologic advantages of TBI in ALL."

Clinical • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Chronic Graft versus Host Disease • CNS Disorders • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Transplantation

Allogeneic Hematopoietic Cell Transplantation (HCT) Improves Immune Deficiency/Dysregulation with Low Toxicity in Patients with Partial RAG Deficiency (TCT-ASTCT-CIBMTR 2026) - "Conditioning consisted of pentostatin, low-dose cyclophosphamide and 2 days of busulfan, and GVHD prophylaxis was post-transplantation cyclophosphamide-based. 3. The IDDA2.1 score may be applicable to assessing and comparing disease activity in pRD patients pre- and post-HCT."

Clinical • Acute Graft versus Host Disease • Bronchiectasis • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Neutropenia • Primary Immunodeficiency • Pulmonary Disease • Respiratory Diseases • Septic Shock • Transplantation • RAG1

Allogeneic Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia: A 17-Year Single-Center Experience (TCT-ASTCT-CIBMTR 2026) - "Conditioning regimens included fludarabine- or pentostatin-based RIC with low-dose total body irradiation (TBI) and myeloablative (MA) regimens using busulfan- or TBI-based platforms. GVHD prophylaxis consisted of calcineurin inhibitor–based therapy, with post-transplant cyclophosphamide (PTCy) in a subset... In this 17-year single-center experience, allo-HCT provided durable long-term survival in adults with ALL, with low early NRM and manageable GVHD. Myeloablative conditioning was associated with superior outcomes, while older age, higher CIBMTR risk, and transplantation beyond CR1 predicted worse survival. These data reflect consistent, long-term results within our institutional program and reinforce the value of myeloablative approaches when clinically feasible."

Clinical • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • T Acute Lymphoblastic Leukemia • Transplantation

Impact of ruxolitinib on corticosteroid treatment patterns in 1147 patients with chronic graft-versus-host disease in real-world practice in the United States: A long-term follow-up analysis (ASH 2025) - "Prescription refills in pharmacy claim records wereused to determine RUX and prednisone-equivalent CS dosing and treatment length. Line of therapy forcGVHD medications was based on claims for CS, belumosudil, abatacept, alemtuzumab, RUX, etanercept,hydroxychloroquine, ibrutinib, imatinib, interleukin-2, methotrexate, mycophenolate mofetil, pentostatin,and rituximab after cGVHD diagnosis... Patients treated with RUX for cGVHD in real-world clinical practice remained on treatmentfor a median of 8 months; 40.9% remained on RUX for 1 year and 21.3% for 2 years, suggesting long-termpersistence of safety and ongoing clinical benefit. Median time from earliest CS fill for cGVHD todiscontinuation or reduction to low-dose CS was 77 days. By the end of 1-year follow-up, 90% of patientsachieved discontinuation or reduction to low-dose CS."

Clinical • Real-world • Real-world evidence • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • IL2

Phase 2 trial of encorafenib plus binimetinib for patients with BRAF V600 mutated relapsed/refractory hairy cell leukemia (ASH 2025) - "Background : Hairy cell leukemia (HCL) is an indolent B-cell leukemia characterized by durable completeremissions to purine analogs cladribine or pentostatin, but repeated relapses and cumulative toxicity torepeated purine analog courses...Vemurafenib was combined with rituximab,achieving 57% MRD-free CRs... Encorafenib-binimetinib is highly effective in relapsed/refractory HCL and was well toleratedwhen dose reductions occurred as needed. Compared to dabrafenib-trametinib, the lower incidence offever (11% vs 58%, p<0.0001) is a major advantage. The CR rate of 93% without rituximab isunprecedented for BRAF inhibition in HCL."

Clinical • P2 data • Hairy Cell Leukemia • Hematological Malignancies • Leukemia • Melanoma • Musculoskeletal Pain • Pancreatitis • Retinal Disorders • Solid Tumor • BRAF

Live imaging of human xenogeneic CART cells in a clinical trial of companion dogs with lymphoma (ASH 2025) - "First, we tested and optimized a chemotherapy regimen to achieve optimal lymphodepletion in dogs.Healthy beagles were treated with pentostatin (pen) on days 2-4 (0.125, 0.25, or 0.5 mg/kg i.v.),cyclophosphamide (cy) on day 4 (400 mg/m2 i.v.), or combination cy/pen. In summary, this study demonstrated that xenogeneic CART cells were well-tolerated, induced remission,and were visualized via PET imaging in companion dogs with lymphoma. These results are promising bothfor the treatment of companion dogs with novel cell therapies and for the translation of novel CART celltherapies into human clinical trials."

CAR T-Cell Therapy • Clinical • IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • B2M • HLA-C

Venetoclax-based therapies in patients with Relapsed/Refractory T-cell prolymphocytic leukemia (ASH 2025) - "The median number of prior lines of therapy before VEN initiation was 1(range, 1–5); 19 pts (54%) were treated with VEN-based therapy in 1st salvage while 16 pts (46%) weretreated in 2nd or later salvage.VEN was combined with cladribine (+/- additional agents) in 17 pts (49%), including 8 (23%) who alsoreceived ruxolitinib. Nine pts (26%) were treated with VEN and pentostatin (+/- alemtuzumab), 3 (9%) withFCM (fludarabine, cyclophosphamide, mitoxantrone), 2 (6%) with alemtuzumab alone, 2 (6%) withruxolitinib alone, and 1 (3%) each with bendamustine or as monotherapy... Pts with R/R T-PLL continue to face poor prognosis. VEN-based therapies demonstrateencouraging response rates in this refractory, proliferative, heavily pretreated population, with improvedsurvival observed among responders and those with longer duration of 1st remission. However, OSremains short, highlighting the need for prospective trials to optimize VEN-based treatment and postremission strategies in..."

Clinical • IO biomarker • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Prolymphocytic Leukemia • Thrombocytopenia • JAK1 • JAK3 • STAT5B