Efficacy and safety of mitoxantrone hydrochloride liposome injection in treatment of peripheral T-cell lymphomas: a multicenter, non-interventional, ambispective cohort, real-world study (MOMENT) / 白血病·淋巴瘤

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Efficacy observation of lenalidomide in treatment of relapsed/refractory diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective:To explore the clinical efficacy of lenalidomide combined with second-line immunochemotherapy as a salvage regimen in the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of 37 relapsed/refractory DLBCL patients receiving lenalidomide combined with second-line immunochemotherapy as a salvage regimen who had recurrence after autologous hematopoietic stem cell transplantation or who were not eligible for transplantation or had no intention to transplant between January 2016 and December 2020 in the First Affiliated Hospital of University of Science and Technology of China were retrospectively analyzed. Among 37 patients, 6 cases with primary central nervous system (CNS) lymphoma and 3 cases with secondary CNS lymphoma. The short-term efficacy after treatment was evaluated. Kaplan-Meier method was used to analyze the overall survival (OS) and progression-free survival (PFS), and log-rank test was used for subgroup comparison.Results:The median follow-up time of 37 patients was 20.4 months (2.7-37.0 months). At the end of treatment, the overall response rate (ORR) of all patients was 64.9% (24/37), the complete response (CR) rate was 45.9% (17/37), and the median duration of response (DOR) of 24 patients who responded to treatment was 17.7 months (3.6-33.6 months). The median PFS time of all patients was 11.2 months, and the 1-year PFS rate was 48.6% (95% CI 32.5%-64.7%). The median OS time of all patients was not reached, and the 1-year OS was 67.6% (95% CI 52.5%-82.7%). Among 24 responding patients, 17 cases who received lenalidomide maintenance therapy after remission tended to have a better response compared with 7 cases who did not receive lenalidomide maintenance therapy after remission, although there was no significant difference in OS and PFS between both groups (both P > 0.05). Additionally, neutropenia was the most common adverse reaction with an incidence of 81.1% (30/37). Conclusions:Lenalidomide combined with the second-line immunochemotherapy may be an effective salvage therapy for patients with relapsed/refractory DLBCL, especially for patients with CNS involvement. The patients achieving remission after salvage therapy continue to receive lenalidomide maintenance therapy and could have a better prognosis.

Relationship between dynamic changes of Epstein-Barr virus and efficacy of lymphoma / 白血病·淋巴瘤

Objective To observe the relationship between the dynamic changes of Epstein-Barr virus (EBV) and the clinical efficacy of lymphoma. Methods The retrospective study was performed on 51 lymphoma patients with EBV-positive in Anhui Provincial Cancer Hospital from September 2015 to August 2017. The treatment effect of lymphoma was evaluated by the changes of EBV DNA, lactic dehydrogenase (LDH) and lymph nodes. Results Among the 51 lymphoma patients, EBV DNA elevated in 18 patients when the LDH was elevated, 23 cases presented with EBV DNA decrease and the LDH also decreased. EBV DNA decreased in 2 patients when the LDH was elevated. Eight patients were elevated when LDH was reduced. The quantification of EBV DNA and LDH had high consistency (κ = 0.609, P= 0.000). Among the 51 lymphoma patients, 20 patients with elevated EBV DNA were elevated with lymph nodeen largement, the lymph nodes in 22 cases with EBV DNA decrease were also decreased. EBV DNA decreased in 3 patients when the lymph nodes were enlarged. Six patients were elevated when lymph nodes were reduced. The quantification of EBV and lymph nodes had high consistency (κ = 0.648, P= 0.000). Patients with elevated EBV DNA during the course of treatment showed an increase in the mean value of LDH, and the patients with reduced EBV DNA during treatment also had lower average LDH. LDH levels were positively correlated with EBV DNA in patients with EBV-positive lymphoma (r= 0.627, P= 0.000). Conclusion Dynamic detection of EBV DNA and LDH can be used as the evaluation index of therapeutic effect and follow-up in patients with EBV-positive lymphoma.

Relationship between microRNAs and diffuse large B-cell lymphoma and its effect / 国际肿瘤学杂志

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma with a high degree of heterogeneity.Studies have shown that microRNAs (miRNAs) are involved in many biological processes and are closely related to lymphoid hematopoietic system and play an important role in various stages of B-cell differentiation and malignant transformation.miRNAs are increasingly concerned as a potential biomarker,which are closely related to the classification of DLBCL.miRNAs are of great values for the diagnosis of the disease and help to determine the prognosis of different patients,which may become new therapeutic targets.

Relationship between microRNAs and diffuse large B-cell lymphoma and its effect / 国际肿瘤学杂志

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma with a high degree of heterogeneity.Studies have shown that microRNAs (miRNAs) are involved in many biological processes and are closely related to lymphoid hematopoietic system and play an important role in various stages of B-cell differentiation and malignant transformation.miRNAs are increasingly concerned as a potential biomarker,which are closely related to the classification of DLBCL.miRNAs are of great values for the diagnosis of the disease and help to determine the prognosis of different patients,which may become new therapeutic targets.

Efficacy analysis of unrelated cord blood transplantation for 58 acute myelogenous leukemia patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the therapeutic efficacy and related risk factors of acute myelogenous leukemia （AML） patients treated with unrelated cord blood transplantation （UCBT）.</p><p><b>METHODS</b>A retrospective analysis was performed on the clinical data of 58 AML patients that consisted of 1 case of M0, 1 case M1, 35 cases M2, 3 cases M4, 14 cases M5, 3 cases M6, and 1 case acute mixed leukemia, respectively. Of them, 1 case AML secondary to myelodysplastic syndrome, and 36 in first complete remission （CR1）, 14 in second complele remission （CR2）, 8 in non- remission （NR）, 43 cases were refractory or high-risk patients（70.1%）. The median age was 14.5 years with the median weight of 45 kg, 49 patients received sUCBT and 9 dUCBT. All the patients conditioned with intensified myeloablative regimen and received a combination of Cyclosporine A（CsA）and mycophenolate mofetil（MMF）to prevent graft- versus- host disease（GVHD）.</p><p><b>RESULTS</b>56 out of 58 patients achieved engraftment with implantation rate 96.6%. The median time of ANC≥0.5×10⁹/L was 17（12-37）days, and that of PLT≥20× 109/L 33（17-140）days respectively. 24 cases developed acute GVHD（aGVHD）, the incidence rate of grade Ⅱ to Ⅳ aGVHD was 30.4%. The chronic GVHD（cGVHD）was occured in 7 patients of the 49 evaluable patients, all were limited. The estimated 3-year overall survival（OS）and disease-free survival （DFS）were（60.3±6.4）% and（60.1±6.5）% respectively. And the cumulative incidences of 3-year nonrelapse mortality（NRM）and relapse were 33.3% and 9.1% respectively. The 3- year OS rates of AML patients were（66.0 ± 6.7）% for CR and（25.0 ± 15.3）% for NR, differences were statistical significance.</p><p><b>CONCLUSION</b>For AML patients, UCBT was conducive to improve outcome with lower incidences of cGVHD and relapse, the patients after transplantation could obtain high quality of life.</p>

Expression of miR-339-5 p in diffuse large B-cell lymphoma and its significance / 临床与实验病理学杂志

Purpose To investigate the relevance between the expression of miR-339-5p and the clinicopathological characteristics in diffuse large B-cell lymphoma (DLBCL). Methods The level of miR-339-5p expression was detected in 123 cases of diffuse large B-cell lymphoma tissues and 20 cases of reactive lymphoid hyperplasia tissues by chromogenic in situ hybridization ( CISH) technique. The expression of Ki-67 and BCL-6 protein was examined in diffuse large B-cell lymphoma tissues by immunohistochemical technique (IHC) (EnVision two-steps), and the correlation between the expression of miR-339-5p and BCL-6 and the clinicopathological param-eters was also analyzed. Results The positive rates of miR-339-5p were 39. 8% (49/123) in DLBCL tissues, which was significantly lower than that in RH tissues (90%, 18/20). The positive rates of miR-339-5p were 31. 0% (22/71) for germinal center B-cell-like (ABC type) DLBCL, which was significantly lower than that in activated B-cell-like (GCB type) DLBCL (27/52, 51. 9%). The low-er expression of miR-339-5p in DLBCL was correlated with late Ann Arbor staging and high-risk group of international prognostic index (P<0. 05). The survival rates of miR-339-5p negative patients of ABC type and GCB type of DLBCL were significantly lower than that of the positive patients (P<0. 01). The levels of miR-339-5p expression in DLBCL were negatively correlated with the levels of BCL-6 expression in DLBCL (P<0. 01). Conclusion The low expression of miR-339-5p might be relatived with the progression and poor prognosis of DLBCL.

Study of implantation dynamics and discipline in unrelated double umbilical cord blood transplantation / 白血病·淋巴瘤

[Objective]To study the discipline of implantation and implantation dynamics in unrelated double umbilical cord blood transplantation(DUCBT).[Methods]Twenty-nine patients with hematologic malignancies who undergoing two-units unrelated donor cord blood transplantation were included in the study.After transplantation,hematopoietic chimerism of peripheral blood was evaluated by the Results of short tandem repeat with polymerase chain reactions(STR-PCR)which quantitatively determinated 16 specific alleles between donor and receptor, to find out their chimerism dynamic change, to judge whether transplantation was implanted and judge which one was implanted,and to study the discipline of implantation in DUCBT.At the same time,total nucleated cells(TNC),dose of CD34 cells,colony forming unit(CFU),colony forming unit-granulocyte and macrophage(CFU-GM),dose of CD; cells,dose of natural killer(NK)cells were compared between dominant units and non-dominant ones,to quest the discipline implantation dynamics of DUCBT.[Results]In 29 clinical cases,23 cases obtained engraftment,including 22 cases appearing one unit cord blood engraftment and 1 case appearing two units cord blood engraftment.Of 22cases with one dominant unit engraftment,at 14 days after DUCBT,the results of STR-PCR showed that 20cases appeared one dominant unit engraftment,other 2 cases appeared one dominant unit engraftment at 21days after DUCBT.Of 6 cases without engraftment,at 14 days after DUCBT,2 cases showed chimerism of two units cord blood,other 4 cases showed chimerism of two units cord blood or one unit cord mixed with receptor.At 30 days after DUCBT,their STR-PCR results of bone marrow showed full donor chimerism.Compared results at day 7,day 14,day 21 by peripheral blood,and day 30 by bone marrow with results of implantation after DUCBT,their coherence were kappa=0.112,P=0.198,kappa =0.811,P =0.001,kappa =0.900,P =0.001 and kappa =0.900,P =0.001,respectively.In addition,compared dominant unit with nondominant unit,TNC,doses of CD+34 cells,CFU,CFU-GM,CD; cells and NK cells were all no significant difference between them (P=0.783,0.455,0.615,0.534,0.114,0.463,respectively).[Conclusion]STR-PCR which quantitatively determinates 16 specific alleles between donor and receptor is sensitively and specifically to judge implant status.The 14 days after DUCBT was the time when implant is embedded.However,the implantation dynamics of DUCBT is still unknown which need further quest in the future.

Unrelated umbilical cord blood transplantation in the treatment of aggressive-phase chronic myeloid leukemia / 白血病·淋巴瘤

[Objective] To retrospectively analyze the outcome of unrelated umbilical cord blood transplantation in the treatment of aggressive-phase chronic myeloid leukemia.[Methods] Fourteen consecutive patients with aggressive-phase chronic myeloid leukemia were treated with unrelated umbilical cord blood transplantation,thirteen patients were treated with myeloablative unrelated CBT and one patients were treated with nonmyeloablative unrelated CBT.All patients received standard cyclosporine A (CsA) and mycophenolate mofetil(MMF) as a graft-versus-host disease (GVHD) prophylaxis.[Results] 14 patients were all successfully engrafted.The median times for their neutrophil returning to ≥0.5×109/L and for platelet returning to ≥20×109/L were 22.8 days and 37.8 days,respectively.Acute GVHD occurred in 10 of 13 evaluable patients.The grading of acute GVHD was gradeⅡ-Ⅳin 6 patients(46.2 ％).Chronic GVHD occurred in 7 of 11 evaluable patients(63.6％).Relapse occurred in 2 of 15 patients,lextramedullary relapse was included.9 of 14 patients were alive and event-free after CBT.The probability of OS rate at 5 years was 64.3 ％,the probability of DFS rate at 5 years was 5,7.1％.[Conclusion]Unrelated umbilical cord blood transplantation is effective in the treatment of aggressive-phase chronic myeloid leukemia.

Detection of platelet fibronectin from congenital fibrinogenopenic patients and its clinical significance / 中华血液学杂志

<p><b>OBJECTIVE</b>To assess the platelet and plasma concentrations of fibronectin (Fn) and fibrinogen (Fg) in congenital fibrinogenopenic (FgP) patients and explore their role in inducing platelet adhesion and aggregation.</p><p><b>METHODS</b>A FgP family was selected as study group and the platelets isolated and purified to assess concentrations of Fn and Fg in platelets, alpha-granules and plasma with Western blotting, immuofluoresence staining and flow cytometry (FACS), respectively, the expression of platelets GP II b/III a by FACS.</p><p><b>RESULTS</b>The concentration of platelets Fn in FgP patients is higher than that in controls, and is higher in homozygote than in heterozygote. In contrast, plasma Fn levels were identical in all samples. The amount of platelet Fg from FgP patients is lower than that from the controls and positively correlated with the concentration of their plasma Fg. No difference in the expression of platelet GP II b/III a had been found.</p><p><b>CONCLUSION</b>It suggested that increased platelet Fn could partially compensate the lack of Fg and lead the platelet adhesion and aggregation.</p>