- |||||||||| Novel Drugs in the Treatment of Steroid Refractory Acute Graft Versus Host Disease () - Nov 29, 2022 - Abstract #ASH2022ASH_7880;
treated 62 patients with daclizumab in a phase II trial with reportef ORR of 68.80% at 44 months follow up.Groth et al...Monoclonal antibodies in particular showed good treatment outcomes with tolerable safety profile. Further studies are required to identify a valuable therapeutic option, SR-aGVHD.
- |||||||||| Journal: Bacteria as a treasure house of secondary metabolites with anticancer potential. (Pubmed Central) - Nov 18, 2022
Furthermore, we have also discussed some of the major secondary metabolites that are currently in the clinical trials or which have demonstrated potent anticancer activity in preclinical models. Besides, we have elaborated on the application of metagenomics in drug discovery and briefly described about anticancer agents identified through the metagenomics approach.
- |||||||||| cyclophosphamide / Generic mfg., pentostatin / Generic mfg.
Pentostatin Plus Cyclophosphamide Decrease Graft Rejection in Nonmyeloablative Haploidentical Hematopoietic Cell Transplantation for Sickle Cell Disease (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_4754;
The HCT conditioning included pentostatin, oral cyclophosphamide, alemtuzumab, and 400cGy total body irradiation (Figure 1).Graft-vs-host disease (GVHD) prophylaxis included post-transplant cyclophosphamide and sirolimus...Though frank viral disease occurred in three patients (EBV post-transplant lymphoproliferative disorder requiring rituximab, chemotherapy, and viral-specific t-cell therapy), viral reactivation was a common complication, occurring in 12 patients (63%; EBV n=4, CMV n=7, HSV n=1) and was controlled with weaning immunosuppression, antiviral therapy, or both...Further exploration is required to examine the causal role of pentostatin plus cyclophosphamide versus other factors, such as the mixed chimerism state, in these complications. We have amended the protocol to increase myelosuppression with the goal of decreasing autoimmune complications and late graft failure.
- |||||||||| Campath (alemtuzumab) / Sanofi
Characteristics and Outcomes of Adult Patients with T Prolymphocytic Leukemia: A Real World Study of the French Innovative Leukemia Group (FILO) (ENMCC - 393-396) - Nov 4, 2022 - Abstract #ASH2022ASH_3651;
Bendamustine (benda) showed encouraging results, particularly in alem-refractory patients (pts)...Thirty pts (23.6%) received first line benda 90 mg/m2 on D1 then 2x6 cycles every 28 days (median 3; 1-6), 15 (11.8%) received pentostatin, 11 (8.6%) had a CHOP-like regimen...Prospective trials are needed to define the most effective therapeutic strategy and improve clinical responses to frontline therapy. New approaches using well-tolerated targeted therapies involving growth and survival signals are needed for the majority of patients unable to receive intensive chemotherapy.
- |||||||||| pentostatin / Generic mfg.
Journal: Temperature-dependent hydrogen deuterium exchange shows impact of analog binding on adenosine deaminase flexibility but not embedded thermal networks. (Pubmed Central) - Sep 30, 2022
We extended TDHDX to a function-altering mutant of adenosine deaminase in the presence of pentostatin and revealed a protein thermal network that is highly similar to that previously reported for the apo-enzyme (Gao et al., 2020, JACS 142, 19936-19949). Finally, we discuss the differential impacts of pentostatin binding on overall protein flexibility vs. site-specific thermal transfer pathways in the context of models for substrate-induced changes to a distributed protein conformational landscape that act in synergy with embedded protein thermal networks to achieve efficient catalysis.
- |||||||||| fludarabine IV / Generic mfg., cyclophosphamide / Generic mfg., pentostatin / Generic mfg.
Journal: Beyond fludarabine: pentostatin plus cyclophosphamide are a well-tolerated alternative in reduced intensity conditioning. (Pubmed Central) - Sep 21, 2022
Finally, we discuss the differential impacts of pentostatin binding on overall protein flexibility vs. site-specific thermal transfer pathways in the context of models for substrate-induced changes to a distributed protein conformational landscape that act in synergy with embedded protein thermal networks to achieve efficient catalysis. No abstract available
- |||||||||| Remicade (infliximab) / Merck (MSD), Mitsubishi Tanabe, J&J, Campath (alemtuzumab) / Sanofi, Jakafi (ruxolitinib) / Novartis, Incyte
Hepatic Graft vs Host Disease in Patients Post Stem Cell Transplant (Crown Ballroom) - Sep 4, 2022 - Abstract #ACG2022ACG_3694;
Ruxolitinib (JAK inhibitor) is one of the newest therapies used for steroid refractory GVHD. Figure: A. Bile duct injury identified by intraepithelial lymphocytes, cytoplasmic vacuolization, and nuclear disarray (H&E, 200x) B. CK7 immunohistochemical stain showing loss of bile duct and biliary hepatic metaplasia(CK7, 200X)
- |||||||||| 1. HCL 2. enlargement of the spleen,systemic symptoms, cytopenias 3. CD19, CD20, CD11c, CD25, CD103, CD123, CD200 4. BRAF mutation 5. initial therapy: cladribine+/- rituximab, pentostatin; relapsed/refractory: vemurafenib+/-rituximab,moxetumomab,ibrutunib 6. Indolent (Twitter) - Aug 7, 2022
- |||||||||| pentostatin / Generic mfg.
Journal: CoCl-Mimicked Endothelial Cell Hypoxia Induces Nucleotide Depletion and Functional Impairment That Is Reversed by Nucleotide Precursors. (Pubmed Central) - Jul 29, 2022
Mouse (H5V) and human (HMEC-1) microvascular ECs were exposed to CoCl-mimicked hypoxia for 24 h in the presence of nucleotide precursors: adenine and ribose, and adenosine deaminase inhibitor, 2'deoxycoformycin...Endothelial protective effects of adenine and ribose were further enhanced by adenosine deaminase inhibition, that increased adenosine concentration. This work points to a novel strategy for protection of hypoxic ECs by replenishing the adenine nucleotide pool and promoting adenosine signaling.
- |||||||||| Journal: Large granular lymphocytic leukemia cured by allogeneic stem cell transplant: a case report. (Pubmed Central) - Jun 15, 2022
The significant importance of this case report is the introduction of a new treatment algorithm for challenging cases of T-cell large granular lymphocytic leukemia in which standard care fails. We hope that this case report will raise awareness of the potential benefits of allogeneic stem cell transplant in the treatment of aggressive forms of T-cell large granular lymphocytic leukemia.
- |||||||||| cladribine / Generic mfg., pentostatin / Generic mfg.
EXPERIENCE IN THE TREATMENT OF HAIRY CELL LEUKEMIA IN KAZAKHSTAN. () - May 13, 2022 - Abstract #EHA2022EHA_1205;
It is necessary to consider the issue of vaccination of this category of patients with anti-pneumococcal vaccine and also to conduct continuous monitoring. Ten patients with CR were vaccinated against coronavirus infection.
- |||||||||| Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
PURINE ANALOGS ON HAIRY CELL LEUKAEMIA TREATMENT () - May 13, 2022 - Abstract #EHA2022EHA_1204;
Cladribine (Cld) and Pentostatin (Pt) are described to induce similar response and relapse rates and safety profile...From the relapsed patients 7 received Cld as second line treatment, 1 received Pt and 1 Pt plus rituximab...However, Cld induced higher complete remission rates, although of similar duration, compared to Pt. Additional studies are needed for adequate stratification and identification of patients with higher risk of relapse in order to further improve response monitoring and treatment of these patients.
- |||||||||| Journal: How I treat refractory/relapsed hairy cell leukemia with BRAF inhibitors. (Pubmed Central) - Apr 19, 2022
Hairy cell leukemia (HCL) responds very well to frontline chemotherapy with purine analogs (cladribine and pentostatine)...At progression, standard therapeutic options include a second course of purine analogs alone or in combination with rituximab and, upon second relapse, therapy with the anti-CD22 immunotoxin moxetumomab pasudotox...Other treatments explored in clinical trials are BTK inhibition with ibrutinib and co-inhibition of BRAF (through dabrafenib or vemurafenib) and its downstream target MEK (through trametinib or cobimetinib). Here, we focus on our experience with BRAF inhibitors in clinical trials and as off-label use in routine practice by presenting three challenging clinical cases to illustrate their management in the context of all available treatment options.
- |||||||||| pentostatin / Generic mfg.
Biomarker, Journal: Integrative Analysis of Biomarkers and Mechanisms in Adamantinomatous Craniopharyngioma. (Pubmed Central) - Apr 19, 2022
ACP with high CXCL6 showed remarkable drug sensitivity to Pentostatin and Wortmannin via CellMiner database analysis. Our results deepened the understanding of the molecular immune mechanism in ACP and provided potential biomarkers for the precisely targeted therapy for ACP.
- |||||||||| Lumoxiti (moxetumomab pasudotox) / AstraZeneca, Innate, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Review, Journal, IO biomarker: Hairy Cell Leukemia (HCL) and HCL Variant: Updates and Spotlights on Therapeutic Advances. (Pubmed Central) - Apr 12, 2022
Good results were recently published and achieved with moxetumomab pasudotox (Moxe), an anti-CD22 immunoconjugate. In this review, we will present an update on HCL and HCL-V, focusing on pathophysiology and recent therapeutic advances.
- |||||||||| Campath (alemtuzumab) / Sanofi
Journal: Alemtuzumab Clearance, Lymphocyte Count, and T-Cell Chimerism After Hematopoietic Stem Cell Transplant in Sickle Cell Disease. (Pubmed Central) - Jan 29, 2022
These results suggest that RIC regimen is feasible and safe for patients with DKC and does not accelerate pulmonary damage in the short-to-medium term after HCT. Between 2 to 4 months after transplant, higher alemtuzumab levels measured 14 days after transplant correlated with patients having better engraftment, suggesting more lymphodepletion may be needed to reduce graft failure in these two non-myeloablative matched related donor HSCT regimens.
- |||||||||| pentostatin / Generic mfg.
Journal: Advances in the biosynthesis of pentostatin (Pubmed Central) - Jan 12, 2022
This review starts by introducing the various chemical route for production of pentostatin, followed by summarizing the mechanisms of pentostatin biosynthesis in different microorganisms. Finally, challenges for biosynthesis of pentostatin were discussed, and strategies for regulating and improving the microbial synthesis of pentostatin were proposed.
- |||||||||| cyclophosphamide / Generic mfg.
Sars-Cov-2 Infection and Vaccination in Recipients of Reduced-Intensity Conditioning, Posttransplantation Cyclophosphamide (PTCy)-Based Allogeneic Hematopoietic Cell Transplantation (HCT) (Salt Palace Convention Center Hall A) - Jan 9, 2022 - Abstract #TCTASTCTCIBMTR2022TCT_ASTCT_CIBMTR_1194;
Patients with primary immunodeficiency (n=46) or peripheral T cell lymphoma (n=18) received a reduced intensity conditioning platform consisting of pentostatin, hyperfractionated cyclophosphamide and 2 days of busulfan with or without equine ATG, T cell replete marrow or peripheral blood allografts, and PTCy-based graft-versus-host disease prophylaxis, Fig 1...Only one patient, who had received rituximab 6 months prior, failed to respond...Incidence of severe infection has been low in the context of widespread and early vaccination. Currently available vaccines appear to be both safe and effective in the majority of HCT recipients, but further study is required to finetune timing during the dynamic process of post-HCT immune recovery.
- |||||||||| cyclophosphamide / Generic mfg., mycophenolate mofetil / Generic mfg.
Prospective Clinical Trial of Mycophenolate Mofetil (MMF) De-Escalation in Allogeneic Hematopoietic Cell Transplantation (HCT) for Primary Immunodeficiency (PID): MMF Is Dispensable in Reduced-Intensity Conditioning, Posttransplantation Cyclophosphamide(PTCy)-Based HCT (Salt Palace Convention Center Ballroom I) - Dec 3, 2021 - Abstract #TCTASTCTCIBMTR2022TCT_ASTCT_CIBMTR_462;
PID patients (n=38) received a serotherapy-free, radiation-free reduced intensity conditioning platform consisting of pentostatin, hyperfractionated cyclophosphamide and 2 days of busulfan, with PTCy, sirolimus, and MMF as GVHD prophylaxis...Viral complications were similar across cohorts, although CMV data interpretation is confounded by recent use of letermovir, Fig 1...Mismatched HCT outcomes and the role of PBSC vs. marrow graft receipt require further study with larger patient numbers. Across patients, reducing MMF exposure is associated with earlier lymphocyte reconstitution and conversion to full T donor chimerism, but no apparent increase in severe GVHD or graft failure.
- |||||||||| pentostatin / Generic mfg.
Journal: Understanding the mode of inhibition and molecular interaction of taxifolin with human adenosine deaminase. (Pubmed Central) - Dec 2, 2021
Comparative analysis indicated that taxifolin and deoxycoformycin share a common binding space in the active site of human ADA and inhibit its catalytic activity similarly. The work emphasises the need of employing taxifolin as a lead chemical in order to produce a more precise and effective inhibitor of the human ADA enzyme with therapeutic potential.Communicated by Ramaswamy H. Sarma.
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