pentostatin / Generic mfg. - LARVOL DELTA

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

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

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

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

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

Phase 2 trial of cladribine plus immediate rituximab for 1st-line treatment of hairy cell leukemia – long term follow-up of original and additional patient cohorts (ASH 2025) - "Itresponds well to purine analogs cladribine (CDA) and pentostatin, but minimal residual disease (MRD)and relapses are common. First-line CDAR is highly effective for HCL, achieving MRD-free CR in 54/59 (92%) total patientsat 6 months and 55/59 (93%) long term. The high MRD-free CR rate may be due to synergy of cladribineand rituximab starting the same day. Transient appearance of MRD which later resolved may be relatedto immune destruction."

Clinical • P2 data • Hairy Cell Leukemia • Hematological Malignancies • Leukemia • Thrombocytopenia

Impact of pre-transplant bone marrow cellularity and fibrosis on post-transplant outcomes in sickle cell disease (ASH 2025) - P1/2 | "All patients received alemtuzumab and TBI with post-HCT cyclophosphamide; some received additional pre-conditioning with pentostatin andcyclophosphamide. Our initial data suggest that neither baseline cellularity nor fibrosis significantly impacted HCT outcomes.Interestingly, all patients with fibrosis ratings > 2 demonstrated graft failure. Further, we observe thatbaseline cellularity is associated with the presence of DDR mutations before HCT. We will expand to ournon-myeloablative matched-sibling HCT cohort, increasing our overall study sample size and moredefinitively assessing the impact of baseline cellularity and fibrosis values on HCT outcomes and CH.Further studies are indicated to evaluate whether increased erythropoietic stress is associated with anincreased prevalence of baseline DDR-CH."

Post-transplantation • Pre-transplantation • Fibrosis • Genetic Disorders • Hematological Disorders • Immunology • Sickle Cell Disease • Transplant Rejection • Transplantation

Assessment of minimal residual disease with droplet digital polymerase chain reaction for BRAF V600E mutation in patients with hairy cell leukemia treated with purine analogs (ASH 2025) - "As frontline therapy, 31/35 patients (89%) receiveda single course of cladribine 0.14 mg/kg/daily for 5 days subcutaneously, 4/35 (11%) received pentostatinevery 15 days for 8 doses. In this study including 35 HCL patients treated with purine analogs frontline, we found that14% achieved an undetectable MRD. More importantly, we demonstrated that the clearance of BRAFmutation was associated with a better long-term outcome."

Clinical • Minimal residual disease • Polymerase Chain Reaction • Residual disease • Hairy Cell Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • B2M • BRAF

Pentostatin/TBI conditioning for allogeneic transplantation in T-cell lymphomas (ASH 2025) - "While most reduced-intensity conditioning regimens rely on fludarabine, pentostatin is a purine analog with a distinctmechanism of action and a favorable immunosuppressive profile that supports donor engraftment withreduced toxicity...All patients received calcineurin inhibitor–based GVHD prophylaxis,and 12% also received post-transplant cyclophosphamide... This 20-year institutional experience demonstrates that pentostatin and TBI is a well-tolerated and effective reduced-intensity conditioning platform for allogeneic transplant in T-celllymphomas. The regimen was associated with full engraftment, low early mortality, and a 5-year OS of49%—a result that compares favorably to published outcomes in this historically high-risk population.Notably, over 32% of patients underwent transplant not in remission and still experienced meaningfullong-term survival, suggesting this regimen offers GVL efficacy even in chemoresistant disease. Theseresults support the continued use and..."

Acute Graft versus Host Disease • Adult T-Cell Leukemia-Lymphoma • Chronic Graft versus Host Disease • Cutaneous T-cell Lymphoma • Dermatology • Extranodal Natural Killer/T-cell Lymphoma • Graft versus Host Disease • Hematological Malignancies • Hepatosplenic T-cell Lymphoma • Immunology • Infectious Disease • Leukemia • Lymphoma • Mycosis Fungoides • Natural Killer/T-cell Lymphoma • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma • Prolymphocytic Leukemia • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • Transplantation • ALK • CD4 • CD8

Real-Life Efficacy and Safety of Vemurafenib Plus Rituximab (V+R) in Relapsed or Refractory Hairy Cell Leukemia: A Multi-Center Retrospective Study (HCL-PG03R) (ASH 2023) - "Prior therapies (median 2; range 0-11) included chemotherapy with cladribine or pentostatin (94% of pts), interferon-alpha (29%), rituximab (31%), splenectomy (6%), BRAF inhibitor monotherapy (6%) and zanubrutinib (3%). Analysis of MRD by allele-specific PCR for BRAF-V600E in the bone marrow aspirate was performed in 30 pts and showed MRD clearance (<0.05% mutant alleles) at a high rate: 79% (22/28 CR pts; or 65%, 22/35 pts, by ITT), which raised to 82% (66% by ITT) when including 1 additional CR case untested by PCR which had negative bone marrow flow cytometry.At a median follow-up of 21 months after the end of treatment, RFS was high among the 31 responding pts, with just 1 relapse (3%) in the only case obtaining a PR post-therapy (Figure). CONCLUSIONSThis study validates in a real-life context the high efficacy and tolerability of the V+R chemo-free regimen delivered to R/R HCL pts, including the cost-saving use of biosimilar rituximab."

Retrospective data • Dermatology • Hairy Cell Leukemia • Hematological Disorders • Hematological Malignancies • Human Immunodeficiency Virus • Infectious Disease • Leukemia • Musculoskeletal Pain • Oncology • Respiratory Diseases • Tuberculosis

Serum Soluble Interleukin-2 Receptor Levels in Hairy Cell Leukemia As a Marker of Tumor Burden with Prognostic Value and As a Tool for Disease Monitoring (ASH 2023) - "Among treated patients, 47/54 (87%) received cladribine and 7/54 (13%) pentostatin...A similar decrease in sIL-2R levels after therapy was observed in 4 relapsed patients treated with rituximab-vemurafenib (median pre-therapy sIL-2R 11.460 vs. 467 kU/L after treatment, p = 0.03; median reduction 10.848 kU/L)...While more data is required to validate its use in clinical routine, sIL-2R could be used as an effective marker for disease monitoring. Moreover, given the prognostic significance of post-therapy levels, sIL-2R may represent a prognostic factor alongside MRD to identify those patients that are more likely to develop early relapse."

IO biomarker • Hairy Cell Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • CD38 • IL2

Maintenance Low-Dose BRAF Inhibition and Rituximab in Relapsed Hairy Cell Leukemia: A Therapeutic Alternative. (PubMed, Cureus) - "Purine analogs such as cladribine and pentostatin have been the mainstay of treatment for HCL. Despite high responsiveness to first-line therapy with purine analogs, almost half of the patients with HCL relapse and become progressively resistant to these medications. Treatment with a combination of BRAF V600E inhibitor and anti-CD20 monoclonal antibody has achieved durable responses in relapsed HCL. Here, we present a patient with relapsed and refractory HCL who achieved only partial response with three months of treatment with high-dose vemurafenib and rituximab, following which he was maintained on low-dose vemurafenib plus monthly rituximab for almost a year, after which he achieved complete morphologic and molecular response."

Journal • Hairy Cell Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

Biosynthesis and genome mining strategies for purine-derived N-nucleoside antibiotics. (PubMed, Front Microbiol) - "Understanding the biosynthesis and genetic organization of N-NAs not only sheds light on their structural diversity but also provides a framework for genome mining. Specific subclasses such as pentostatin-, angustmycin-, and deazapurine-type compounds exhibit Structure-Activity relationships that could guide the rational design and genome-based discovery of new nucleoside antibiotics."

Journal • Review

Enhancer regulator MLL4 controls skeletal muscle metabolic efficiency by limiting AMPK-mediated fuel catabolism. (PubMed, Nat Commun) - "Pharmacologic inhibition of AMP-metabolizing pathway by Pentostatin activates muscle AMPK, confers resistance to obesity and improves metabolic health. These findings identify an enhancer regulator limiting AMPK-mediated muscle fuel catabolism, offering a potential strategy for treating obesity-related disorders."

Journal • Genetic Disorders • Hematological Malignancies • Leukemia • Obesity • Oncology • AMPK • KMT2D

Survival and Therapeutic Outcomes in T-Cell Prolymphocytic Leukemia (T-PLL): A Collaborative Multi-Center Study Cohort (ASH 2024) - "Other active second-line treatments included : pentostatin (n=23; 44% ORR, 17% CR), ruxolitinib-based regimens (n=4; 25% ORR, 0% CR), venetoclax-based regimens (n=13; 39% ORR, 8% CR), bendamustine (n=10; 30% ORR, 0% CR), and nelarabine (n=4; 75% ORR, 50% CR)...Conclusions : In this large, multi-center study of T-PLL, frontline treatment with a combination of alemtuzumab/pentostatin improved response rates and OS...Intriguingly, TCL1A+, and CD4- T- PLL had worse OS/PFS, and scRNAseq confirmed unique molecular signatures in these populations, suggesting these represent novel molecular subtypes of T-PLL with prognostic significance. These studies form the foundation for future, targeted, therapeutic studies in this rare, aggressive disease with few treatment options."

Clinical • Hematological Malignancies • Leukemia • Oncology • Prolymphocytic Leukemia • CD4 • CD8 • TCL1A

Adenosine deaminase loss leads to purine metabolism dysfunction, senescence and reduced DNA repair mechanisms in sALS astrocytes (ALS-MND 2025) - "Senescence and DNA damage analysis were performed under physiological conditions and under purine stress conditions using the ADA inhibitor pentostatin.Results : We found that levels of CD73 and hypoxanthineguanine phosphoribosyltransferase two key purine metabolism enzymes were reduced in SALS iAstrocytes at the mRNA and protein level...SALS iAstrocytes showed purine metabolism dysfunction including reduced purine salvage and an altered senescent phenotype, which was reflected in the biofluid samples and motor cortex of SALS cases. ADA inhibition exacerbated this phenotype and resulted in astrocytes being more susceptible to adenosine induced DNA damage. Loss of ADA resulted in less 53BP1 mediated DNA repair in SALS iAstrocytes, which was mimicked in controls by ADA inhibition."

Metabolic Disorders • CD73 • CDKN1A • TP53 • TP53BP1

Real-World Evaluation of T-Prolymphocytic Leukemia Outcomes Using the 2019 T-PLL International Study Group Criteria (ASH 2023) - "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."

Clinical • HEOR • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Prolymphocytic Leukemia • CD4 • CD8 • TCL1A