Azacitidine maintenance therapy for blastic plasmacytoid dendritic cell neoplasm allograft: A case report

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research.It is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence rate.We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature.CASE SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’duration.BPDCN was diagnosed by combined clinical assessment and laboratory examinations.Following diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging allo-HSCT.Post-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy cycle.After 10 cycles,the patient has been disease free for 26 mo after transplantation.Regular assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities detected.CONCLUSION Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.

Azacitidine decreases reactive oxygen species production in peripheral white blood cells:A case report

BACKGROUND In myelodysplastic syndrome(MDS),oxidative stress is closely related to iron overload and DNA damage.A recent study suggested the possibility that increased oxidative stress causes not only iron overload but also disease progression of MDS with DNA damage.We present a case of MDS with decreased reactive oxygen species(ROS)production in peripheral white blood cells(WBCs)and decreased diacron-reactive oxygen metabolites(d-ROMs)in serum after azacitidine therapy.CASE SUMMARY A 74-year-old man presented to the hematological department with the chief complaint of anemia.His vital signs were within normal limits at admission with a heart rate of 80 bpm and blood pressure of 135/60 mmHg.Laboratory tests indicated pancytopenia,a WBC count of 2190 cells/μL,a hemoglobin level of 6.2 g/dL and a platelet count of 7.4×104/μL.The patient was diagnosed with MDS with fibrosis after a bone marrow examination.This case showed decreased ROS production in WBCs,d-ROMs in serum and Wilms’tumor 1 after azacitidine therapy,after which his hematopoiesis recovered.CONCLUSION Azacitidine therapy can improve hematopoiesis and decrease ROS and d-ROM production.

Determination of Azacitidine by Spectrophotometric Method

Simple, selective and sensitive spectrophotometric method has been developed for the determination of Azacitidine in pharmaceutical formulations and blood with MBTH (3-methyl-2-benzothiazolone hydrazone hydrochloride) reagent, at PH-4.0 which is extractable at 620 nm. Beer’s law is obeying in the concentration ranges 10 - 35 μg·ml-1 for formulations and 4 - 24 μg·ml-1 for blood sample. %R.S.D was found to be 0.0240%, 0.0610 and Recovery 99.82% 99.24% respectively. The method was completely validated and proven to be rugged. The interferences of the other ingredients and excipients were not observed. The repeatability and the performance of the proven method were conventional by point and interior proposition and through recovery studies.

Clinical Efficacy of Decitabine/Azacitidine in Combination with HAG in the Treatment of Elderly Patients with Acute Myeloid Leukemia

This study was conducted to investigate the clinical effect of combining decitabine/azacitidine with HAG in the treatment of single elderly patients with acute myeloid leukemia.Patients in Shaanxi Provincial People’s Hospital were selected for this study from January 2020 to January 2022,and all of the patients were elderly patients with acute myeloid leukemia.Around 23 patients were selected for this study,subsequently the patients were divided into two groups;Group A contained 11 patients and was given decitabine in combination with HAG;and Group B contained 12 patients,and was given azacitidine in combination with HAG.This study showed that the treatment effective rates of patients in both groups were 90.91%and 58.33%,respectively,with a small difference(p>0.05)in the data comparison.The incidence of adverse reactions in the two groups was 63.64%and 16.67%,respectively,with the incidence in group B is significantly(p<0.05)lower compared with group A.Meanwhile,compared with group B,patients in group A had a significantly(p<0.05)shorter mean time to WBC normalization,higher HB and PLT levels,lower WBC levels were lower,all the survival duration times were longer,and subpopulation indicators of peripheral blood T lymphocytes were more in line with normal values.In summary,this study demonstrated that the combination of azacitidine and HAG therapies for the treatment of elderly patients with acute myeloid leukemia is more effective,furthermore can reduce significantly the incidence of adverse treatment effects in patients.

Osteonecrosis of the jaw in a patient with acute myeloid leukemia,who received azacitidine

The first case of osteonecrosis of the jaw(ONJ)related to azacitidine therapy was reported.A 64-year-old male with acute myeloid leukemia,who received 5-azacitidine,presented with pain and purulence of the right second premolar.An unsuccessful endodontic therapy resulted in dental extraction 6 months later.The post-extraction non-healing socket was managed with antibiotics and multiple surgical debridements without response.ONJ stage 2 was diagnosed 12 months after the initial symptoms of pain and purulence and was managed conservatively.Currently the patient is still receiving 5-azacitidine therapy,while ONJ remains asymptomatic.This case highlights the presence of alveolar bone disease prior to the appearance of ONJ.Osteonecrosis in chemotherapy,although rare,may increase as long-term survival of cancer patients,who receive those medications increases.Health care professionals need to be alert,while collaboration with an experienced oral/dental oncologist would be beneficial to the patient.

联合应用组蛋白脱乙酰基酶抑制剂对治疗相关髓系肿瘤疗效不佳

1文献来源Prebet T,Sun Z,Ketterling RP,et al.Azacitidine with or without Entinostat for the treatmentof therapy-related myeloid neoplasm：Further resultsof the E1905 North American Leukemia IntergroupStudy[J].Br J Haematol,2016,172（3）：384-391.2证据水平1b。3背景·治疗相关髓系肿瘤（therapy related myeloidneoplasm,t-MN）,

Del(5q) and inv(3) in myelodysplastic syndrome: A rare case report

BACKGROUND Del(5q)is the most common molecular event in myelodysplastic syndrome(MDS),accounting for 10%-15%of cases.Inv(3)is an adverse cytogenetic abnormality observed in less than 1%of MDS patients.Few studies have reported the coexistence of del(5q)and inv(3)in MDS.Therefore,the pathological mechanism,treatment strategy and prognosis of this subtype need to be elucidated.CASE SUMMARY A 66-year-old woman was admitted to the hospital due to chest tightness and shortness of breath.Combining clinical assessments with laboratory examinations,the patient was diagnosed with MDS containing both del(5q)and inv(3).Considering the deletion of chromosome 5q,we first treated the patient with lenalidomide.When drug resistance arose,we tried azacitidine,and the patient had a short remission.Finally,the patient refused treatment with haematopoietic stem cell transplantation and died of severe infection four months later.CONCLUSION MDS patients with del(5)and inv(3)have a poor prognosis.Azacitidine may achieve short-term remission for such patients.

Resistance to venetoclax and hypomethylating agents in acute myeloid leukemia

Despite the success of the combination of venetoclax with the hypomethylating agents(HMA)decitabine or azacitidine in inducing remission in older,previously untreated patients with acute myeloid leukemia(AML),resistance-primary or secondary-still constitutes a significant roadblock in the quest to prolong the duration of response.Here we review the proposed and proven mechanisms of resistance to venetoclax monotherapy,HMA monotherapy,and the doublet of venetoclax and HMA for the treatment of AML.We approach the mechanisms of resistance to HMAs and venetoclax in the light of the agents’mechanisms of action.We briefly describe potential therapeutic strategies to circumvent resistance to this promising combination,including alternative scheduling or the addition of other agents to the HMA and venetoclax backbone.Understanding the mechanisms of action and evolving resistance in AML remains a priority in order to maximize the benefit from novel drugs and combinations,identify new therapeutic targets,define potential prognostic markers,and avoid treatment failure.

Venetoclax resistance:mechanistic insights and future strategies

Acute myeloid leukemia(AML)is historically associated with poor prognosis,especially in older AML patients unfit for intensive chemotherapy.The development of Venetoclax,a potent oral BH3(BCL-2 homology domain 3)mimetic,has transformed the AML treatment.However,the short duration of response and development of resistance remain major concerns.Understanding mechanisms of resistance is pivotal to devising new strategies and designing rational drug combination regimens.In this review,we will provide a comprehensive summary of the known mechanisms of resistance to Venetoclax and discuss Venetoclax-based combination therapies.Key contributing factors to Venetoclax resistance include dependencies on alternative anti-apoptotic BCL-2 family proteins and selection of the activating kinase mutations.Mutational landscape governing response to Venetoclax and strategic approaches developed considering current knowledge of mechanisms of resistance will be addressed.