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Objective To investigate the efficacy and survival effects of cladribine（CLAD） combined with cytarabine and BuCy pretreatment regimen on autologous hematopoietic stem cell transplantation in patients with acute myeloid leukemia.Methods Patients with acute myeloid leukemia with complete remission and negative residual lesions were selected for autologous hematopoietic stem cell transplantation using CLAD combined with cytarabine and BuCy pretreatment regimen, and the therapeutic effect, transplantation complications and prognosis were observed.Results The transplantation complications of three patients were mild and the hematopoietic reconstruction time was early.The continuous remission time of three patients was 25,20,12 months, respectively, and there was still no recurrence.Conclusion For adult patients with acute myeloid leukemia, CLAD combined with cytarabine and BuCy pretreatment regimen can promote implantation, reduce recurrence rate, and improve the overall quality of life of patients. [ABSTRACT FROM AUTHOR]

Objective To determine the therapeutic efficacy of cladribine combined with BuCy conditioning regimen for childhood acute leukemia, and compare it with fludarabine. Methods The clinical data of 70 children with acute leukemias who underwent all-HSCT from August 2018 to June 2020 were collected. The data of pretreatment-related toxicity, hematopoietic reconstitution, graft-versus-host disease, virus infection, relapsed and survival between CLAG and FLAG group were statistically analyzed. Results EBV infection in CLAG group was significantly more than that in FLAG group(P0.05). Multivariate analysis showed that there was no significant difference in the effect of conditioning regimen on relapsed and survival. Among other risk factors, types of diseases were significantly correlated with OS (P

Objective: To investigate the safety and the short-term efficacy of venetoclax combined with azacitidine followed by cladribine (VAC regimen) in children with refractory/ relapsed acute myeloid leukemia (AML)., Methods: The clinical data, treatment outcomes, complications, and blood product consumption of 6 children with refractory/relapsed AML treated with VAC regimen in the Children's Hospital of Soochow University from August 2021 to December 2021 were retrospectively analyzed., Results: Among the 6 children, there were 1 male and 5 females. 5 cases were refractory AML, and 1 case was relapsed AML, which recurred again 16 months after allogeneic hematopoietic stem cell transplantation. 4 children were accompanied by chromosomes or genes that predicted poor prognosis, such as RUNX1, FLT3-ITD, KMT2A exon 2-exon 8 dup, MLL-AF6 , 7q-, KMT2A exon 2-exon 10 dup, etc. After received VAC regimen, 4 cases achieved CR+CRi, 1 case achieved PR (only MRD did not relieve, MRD was 0.59%), and 1 case was NR (but the proportion of bone marrow blasts decreased). All 6 patients had grade Ⅳ neutropenia, and 4 patients had grade Ⅳ thrombocytopenia. During the period of neutropenia, none of the 6 children developed symptoms of infection such as fever, cough, and diarrhea. No treatment-related death occurred., Conclusion: Venetoclax combined with azacitidine followed by cladribine provides a new treatment option for patients with relapsed/refractory AML who have poor efficacy in early induction remission theragy, showing good efficacy and safety.

Objective: N-deoxyribosyltransferase II(NDT) was produced by recombinant strain E.coli BL21/pET-NDT. This recombinant strain was used as catalysis to synthesize cladribine. High-throughput screening system was established to engineer NDT, in order to increase the yield of cladribine. Methods: First, synthesize cladribine with wild NDT. Then combine Xanthine Oxidase with Horseradish Peroxidase to assay the activity of NDT in a high-throughput manner. Finally, construct a random mutant library of NDT,and screen the mutants of interest. Results: In the reaction mixture of 10 % DMSO, wild NDT catalysed the synthesis of cladribine, and the yield was 93%. The constructed random library was screened, and a mutant with altered activity was found. Conclusion: In this study,NDT was employed as a catalyst, and cladribine was synthesized successfully in one step. And the high-throughput screening system constructed in this study was successfully applied to the alternation of the NDT activity, which offers a new way to expand the ability of NDT in preparation of unnatural nucleoside analogs. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare the efficacy and safety of cladribine, smustine, etoposide, cyclophosphamide, and cytarabine (C+SCAV) and smustine, etoposide, cytarabine, and melphalan (SEAM) conditioning regimens in autologous stem cell transplantation (auto-HSCT) for non-Hodgkin's lymphoma (NHL) . Methods: A retrospective analysis was conducted on 61 NHL patients who received auto-HSCT in the Department of Hematology, the First Affiliated Hospital of Suzhou University, from March 2018 to May 2021. The C + SCAV group and SEAM group had 19 and 42 patients, respectively. Results: ① Among the 61 patients with NHL, 37 were male and 24 were female. The median age was 48 (21-66) years old. There were 19 cases in the C+SCAV group and 42 cases in the SEAM group. There was no significant difference in the baseline characteristics between the two groups ( P >0.05) . ② The median time to neutrophil and platelet engraftment in the C+SCAV cohort were 10 (8-15) days and 13 (9-22) days, respectively, which does not differ from the SEAM group ( P =0.103, P =0.403) . ③ No differences existed between the two groups in terms of survival. The 1-year progression-free survival (PFS) was (76.5±10.3) % for patients receiving C+SCAV and (78.4±6.8) % for those who received SEAM ( P =0.841) . The 1-year overall survival was 100.0% for the C+SCAV group and 95.2±3.3% for the SEAM group ( P =0.339) . ④The 1-year PFS of patients with complete remission in the C+SCAV group was similar to those who in the SEAM group [ (92.3±7.4) % vs (82.5±7.2) %, P =0.406]. ⑤ The incidence of non-hematological serious adverse events (≥ grade 3) in the C+SCAV group and SEAM group were 10.5% (2/19) and 40.5% (17/42) ( P =0.013) , the incidence of severe mucositis was 5.3% (1/19) and 31.0% (13/42) ( P =0.015) , and the incidence of severe infection (≥ grade 3) was 10.5% (2/19) and 19.0% (8/42) ( P =0.389) , respectively. Conclusion: C + SCAV conditioning regimen appeared to be no different from the SEAM regimen in terms of survival. It can lower the incidence of SAE and does not increase the risk of severe infection. As a result, it can be used as an alternative conditioning regimen for lymphoma patients undergoing auto-HSCT.

Objective: To observe the efficacy and prognosis of cladribine (2-CdA) combined with cytarabine (Ara-C) regimen in the treatment of relapsed refractory Langerhans cell histiocytosis (LCH) in children., Methods: Nine patients with relapsed refractory LCH treated with the 2-CdA combined with Ara-C regimen in the Department of Hematology and Oncology of Wuhan Children's Hospital from July 2014 to February 2020 were retrospectively analyzed, and the efficacy and disease status were evaluated according to the Histiocyte Society Evaluation and Treatment Guidelines (2009) and the Disease Activity Score (DAS), the drug toxicity were evaluated according to the World Health Organization（WHO） grading criteria for chemotherapy. All patients were followed up for survival status and disease-related sequelae., Results: Before the treatment combining 2-CdA and Ara-C, 7 of 9 patients were evaluated as active disease worse (ADW), and 2 as active disease stable (ADS) with a median disease activity score of 8 (4-15). Of 9 patients, 6 cases achieved non active disease (NAD) and 3 achieved active disease better (ADB) with a median disease activity score of 0 (0 to 5) after 2-6 courses of therapy. All 9 patients experienced WHO grade IV hematologic toxicity and 3 patients had hepatobiliary adverse effects (WHO grade I～II) after treatment. The median follow-up time was 31(1 to 50) months with all 9 patients survived, 3 of the 9 patients experienced sequelae to the disease with 2 combined liver cirrhosis as well as cholestatic hepatitis and 1 with oral desmopressin acetate tablets for diabetes insipidus., Conclusion: 2-CdA combined with Ara-C is an effective regimen for the treatment of recurrent refractory LCH in children, and the main adverse effect is hematologic toxicity, which is mostly tolerated in children. Early treatment with this regimen may be considered for patients with multisystem LCH with risky organ involvement who have failed first-line therapy and for patients with relapse.

Objective: To investigate the efficacy, safety and the risk factors affecting prognosis of high-risk acute myeloid leukemia (AML) patients treated by cladribine-based intensified conditioning regimen., Methods: The clinical data of 28 patients with high-risk AML treated by cladribine in combination with busulfan plus cyclophosphamide (BuCy) intensified conditioning regimen before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Zhujiang Hospital, Southern Medical University from October 2016 to June 2020 were analyzed retrospectively. The overall survival (OS) rate, cumulative progression-free survival (PFS) rate, relapse rate, non-relapse mortality (NRM), regimen related toxicity (RRT) and risk factors affecting prognosis of the patients were analyzed., Results: The 1-year OS and PFS of the patients after implantation was (78.8±8.6)% and (79.8±8.1)%, while the 1-year cumulative relapse rate and NRM of the patients was 9.3% and 22.0%, respectively. The 1-year expected OS of MRD - high-risk patients before HSCT was 100%. The 1-year expected OS and PFS of the patients in pre-transplant relapse group was (46.9±18.7)% and (50.0±17.7)%, respectively. The incidence of I/II grade RRT was 39.3%. NO III/IV grade RRT were found in 28 patients. Multivariate analysis showed that pre-transplant relapse was the independent risk factor affecting OS and PFS of the patients., Conclusion: The intensified conditioning regimen of cladribine in combination with BuCy can reduce the relapse rate of high-risk AML transplantation, and its RRT is mild, exhibiting good safety. MRD - high-risk patients before HSCT can achieve better transplant benefits, but the prognosis of patients with relapse before transplantation is not significantly improved. Therefore, for non-relapsed high-risk AML patients, this intensified conditioning regimen deserves to be considered.

Objective: To investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) containing cladribine sequential busulfan regimen for refractory/relapsed acute myeloid leukemia (AML) . Methods: The clinical data of 12 refractory/relapsed AML patients received allo-HSCT with cladribine sequential busulfan regimen. Results: ① Of the 12 patients, 9 were males and 3 females, with a median age of 36 (27-50) years. The donors were identical sibling (3) , matched unrelated (1) and haploidentical family member (9) respectively. Nine patients reached partial remission and other remained no remission after chemotherapy before allo-HSCT. The median previous chemotherapy courses before allo-HSCT were 6 (2-13) . ② Conditioning regimen: Smostine 250 mg·m(-2)·d(-1), d-7; Cladribine 5 mg·m(-2)·d(-1), d-6 to d-2; Cytarabine Arabinoside 2 g·m(-2)·d(-1), d-6 to d-2; Busulfan 3.2 mg·m(-2)·d(-1), d-6 to d-3; Rabbit anti-human thymocyte immunoglobulin (ATG) 1.5 mg·m(-2)·d(-1) (unrelated donor transplantation) or 2.0-2.5 mg·m(-2)·d(-1) (haplo-HSCT) , d-4 to d-1. ③ Of the 12 patients, 11 patients attained complete haploidentical engraftment, one case occurred primary graft failure. The median durations for neutrophils and platelet implantations were 15 (15-21) and 19 (17-30) days respectively. ④After conditioning, no hepatic veno-occlusive diseases were observed, hemorrhagic cystitis occurred in 2 patients, 8 patients had fever, 3 cases experienced acute GVHD grade II, localized chronic GVHD occurred in 8 patients. ⑤The median follow-up was 8 (4-12) months. Leukemia relapse occurred in 2 patients at time of 6, 12 months after allo-HSCT. The estimated 1-year OS and DFS were (71.1±1.8) % and (62.2±1.8) %, respectively. Conclusions: allo-HSCT with cladribine sequential busulfan regimen was a feasible choice with favorable outcome for refractory/relapsed AML.

Objective: To investigate the curative effect of hairy cell leukemia by clatabine. Methods: The clinical data of 24 patients with hairy cell leukemia treated by cladribine from November 2006 to October 2017 were analyzed retrospectively, then the curative effect and adverse drug reaction were analyzed. Results: ① A total of 24 patients including 22 male and 2 female, and the median age was 49.5 years (range 33 to 76) at diagnosis. There were 20 patients with of splenomegaly (4 patients with mild splenomegaly, 4 moderate splenomegaly, and 12 massive splenomegaly), 3 patients with enlargement of lymph nodes, and 1 patients who had undergone splenectomy. Five patients were pancytopenia, 15 were cytopenia in 2 lineages, and 4 patients were cytopenia only in one lineage. The median ratio of HCL cells detected by flow cytometry in bone marrow was 21.79% (0.69%-68.96%). BRAF mutation was detected in 15 patients by first generation or next generation sequencing technology. ② Among 24 patients, 20 were treated with cladribine alone (one course in 19 patients, 2 courses in 1 patient), and 4 patients were treated with cladribine combined with rituximab (one course in 3 patients, 2 courses in 1 patient). Excepting 5 patients whose follow-up time was not reaching 6 months, 19 patients were evaluated for efficacy in 6-12 months after treatment: 9 patients obtained CR, 9 obtained unconfirmed CR (Cru), the other 1 obtained PR, the CR/CRu rate was 94.7%, the overall response rate (ORR) was 100.0%. ③ All the 24 patients appeared 2-4 grade hematological adverse reactions after cladribine treatment, which were mainly grade 3/4 neutropenia (66.67%) and grade 3/4 thrombocytopenia (29.2%). All the adverse reactions were controlled or recovered spontaneously. ④ After the median follow-up time of 15 (3-133) months, no progression, recurrence or death occurred in the patients. Both median OS and PFS were not reached. Conclusion: This study suggests that treatment of HCL with cladribine has high response rate, controllable adverse reactions and the good prognosis.