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.

Analysis of the genomic landscape of primary central nervous system lymphoma using whole-genome sequencing in Chinese patients / 医学前沿

Primary central nervous system lymphoma (PCNSL) is an uncommon non-Hodgkin's lymphoma with poor prognosis. This study aimed to depict the genetic landscape of Chinese PCNSLs. Whole-genome sequencing was performed on 68 newly diagnosed Chinese PCNSL samples, whose genomic characteristics and clinicopathologic features were also analyzed. Structural variations were identified in all patients with a mean of 349, which did not significantly influence prognosis. Copy loss occurred in all samples, while gains were detected in 77.9% of the samples. The high level of copy number variations was significantly associated with poor progression-free survival (PFS) and overall survival (OS). A total of 263 genes mutated in coding regions were identified, including 6 newly discovered genes (ROBO2, KMT2C, CXCR4, MYOM2, BCLAF1, and NRXN3) detected in ⩾ 10% of the cases. CD79B mutation was significantly associated with lower PFS, TMSB4X mutation and high expression of TMSB4X protein was associated with lower OS. A prognostic risk scoring system was also established for PCNSL, which included Karnofsky performance status and six mutated genes (BRD4, EBF1, BTG1, CCND3, STAG2, and TMSB4X). Collectively, this study comprehensively reveals the genomic landscape of newly diagnosed Chinese PCNSLs, thereby enriching the present understanding of the genetic mechanisms of PCNSL.

Challenges and optimal strategies of CAR T therapy for hematological malignancies / 中华医学杂志(英文版)

Remarkable improvement relative to traditional approaches in the treatment of hematological malignancies by chimeric antigen receptor (CAR) T-cell therapy has promoted sequential approvals of eight commercial CAR T products within last 5 years. Although CAR T cells' productization is now rapidly boosting their extensive clinical application in real-world patients, the limitation of their clinical efficacy and related toxicities inspire further optimization of CAR structure and substantial development of innovative trials in various scenarios. Herein, we first summarized the current status and major progress in CAR T therapy for hematological malignancies, then described crucial factors which possibly compromise the clinical efficacies of CAR T cells, such as CAR T cell exhaustion and loss of antigen, and finally, we discussed the potential optimization strategies to tackle the challenges in the field of CAR T therapy.

Prognostic significance of proteins expression by immunohistochemical method in diffuse large B cell lymphoma / 中华血液学杂志

Objective@#To analyze the prognostic significance of TP53, Bcl-2, Bcl-6, Myc proteins expression by immunohistochemical method (IHC) in diffuse large B cell Lymphoma (DLBCL) .@*Methods@#Clinical and pathologic data of 223 patients with DLBCL hospitalized in Zhejiang First Hospital from March 2009 to June 2015 were retrospectively analyzed.@*Results@#The 223 cases, a median age of 56 years old with a male predominance, had shown a 39.0% of TP53 positive expression, 38.6% of Myc, 69.1% of Bcl-2, 56.5% of Bcl-6, and 22.7% of Myc/Bcl-2 double expression. According to Hans’ classification, 27.4% were GCB and 72.6% were non-GCB. With a median follow-up of 38 (2-97) months, the 3 and 5 years survival rates were 70% and 66% , respectively. By multivariate analysis, TP53 over-expression and Myc/Bcl-2 double expression were independently associated with poor outcomes. 3-year and 5-year overall survival were 59% and 57% for patients with TP53 positive, 77% and 71% for patients with TP53 negative expression. Patients with non-GCB subtype receiving chemotherapy combined with rituximab had a higher OS than those without rituximab. But rituximab did not improve the prognosis of patients with TP53 positive.@*Conclusion@#Myc/Bcl-2 double expression and TP53 over-expression are poor prognosis for DLBCL patients. Patients with Myc/Bcl-2 double expression have shorter OS. Patients with non-GCB subtype who received chemotherapy combined with rituximab have a better OS than those without rituximab. But rituximab does not improve the prognosis of patients with TP53 positive.

Clinical prognosis of myelodysplastic syndrome in the elderly and its influencing factors / 中华老年医学杂志

Objective To analyze the clinical prognosis and its influencing factors in elderly patients with myelodysplastic syndrome.Methods A total of 36 elderly patients with myelodysplastic syndrome were included in this study,who were diagnosed and treated at our hospital from January 2013 to August 2016.The Kaplan-Meier method was used to analyzed the survival of these patients,and the effects of gender,age,WHO classification,white blood cell count,platelet count,hemoglobin and IPSS grouping on survival were analyzed.The independent risk factors associated with the clinical prognosis of patients were identified by using multivariate Cox regression analysis.Results Patients were followed up until March 31,2017 with a follow-up time ranging from 8 to 31 months.During the follow-up period,19(58.3％)deaths and 17(41.7％) survivals were reported.The average survival time was(19.17±1.47)months.Kaplan-Meier survival analysis showed that age,WHO classification,white blood cell count,platelet count and IPSS grouping were closely associated with survival in elderly patients with myelodysplastic syndrome.Multivariate Cox regression analysis showed that age and IPSS grouping were independent prognostic factors in elderly patients with myelodysplastic syndrome.Conclusions Age,WHO classification,white blood cell count,platelet count and IPSS grouping are closely related to the prognosis of myelodysplastic syndrome in elderly patients.

Efficacy of HAA regimen in the treatment of 64 patients with refractory/relapsed acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of the HAA regimen (homoharringtonine,cytarabine and aclarubicin)as salvage chemotherapy in the treatment of refractory/relapsed acute myeloid leukemia (AML).</p><p><b>METHODS</b>We retrospectively analyzed 64 patients with refractory/relapsed AML who received the HAA regimen as salvage chemotherapy. The complete remission (CR)rate was analyzed. Kaplan-Meier method was used to estimate overall survival (OS) and relapse free survival (RFS), and the differences were compared by Log-rank test.</p><p><b>RESULTS</b>The overall CR rate was 70.1%, and 67.1% of the patients attained CR after the first induction course. The early death rate was 0. The median follow-up time was 61 (range:6-120) months. The estimated 3-year OS rate was 46.8% and the estimated 3-year RFS rate was 42.8%. The CR rates of patients with favorable/intermediate and unfavorable cytogenetics were 76.4% and 33.3%, respectively. The 3-year OS of favorable/intermediate and unfavorable group were 53.7% and 10.0%, respectively. The median survival time of unfavorable group was only 8 months. The side effects associated with the HAA regimen were tolerable, in which the most common toxicities were myelosuppression and infection.</p><p><b>CONCLUSION</b>HAA regimen is associated with a higher rate of CR and longer-term survival and its toxicity can be tolerated. The regimen is suitable for refractory/relapsed AML patients with favorable or intermediate risk .</p>

The clinical efficacy of all-trans retinoic acid plus arsenic trioxide in 177 newly diagnosed acute promyelocytic leukemia patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical efficacy of all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) in induction and maintenance therapy in newly diagnosed acute promyelocytic leukemia (APL).</p><p><b>METHODS</b>A retrospective analysis of 298 newly diagnosed APL patients from the department of hematology, First Affiliated Hospital of Zhejiang University since September 2004 to December 2013, including 177 cases with ATRA plus ATO and 116 ATRA plus chemotherapy (CT), was performed to investigate the clinical efficacy between the low-intermediate (WBC≤10×10⁹/L) and high (WBC>10×10⁹/L) risk APL patients, respectively.</p><p><b>RESULTS</b>For the low-intermediate risk patients, the relapse rate in ATRA plus CT and ATRA plus ATO are 22.0% and 6.1% (P=0.004), respectively; the 3 years estimated relapse-free survival (RFS) are 78.0% and 92.9% (P=0.021), respectively. For the high risk patients, the relapse rate in ATRA plus CT and ATRA plus ATO are 25.0% and 5.2% (P=0.035), respectively; the 3 years estimated RFS rate were 80.8% and 93.0% (P=0.021), respectively. But the rate of early death (ED), complete remission (CR) and overall survival (OS) between the two therapy protocols had no statistical difference (P>0.05).</p><p><b>CONCLUSION</b>ATRA plus ATO in induction and maintenance therapy might prolong the RFS time of the low-intermediate risk APL patients and decrease the relapse rate of the low, intermediate and high risk APL patients.</p>

Efficacy and safety of anagrelide in treatment of essential thrombocythemia: multicenter, randomized controlled clinical trial / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of anagrelide in essential thrombocythemia (ET).</p><p><b>METHODS</b>Patients who diagnosed as ET according to the World Health Organization classification were enrolled. Each patient was assigned to take anagrelide hydrochloride capsule or hydroxyurea tablet by random 1∶1 ratio. Dose of anagrelide started at 2 mg/d, then increased gradually and the maximum dose was 10 mg/d until the platelet counts dropped to (100-400) × 10⁹/L, one month later gradually reduced to maintain dose. The dose of hydroxyurea was 1000 mg/d at beginning, then increased gradually, when platelet counts dropped to (100-400)×10⁹/L and kept for one month, reduced to maintain dose as 10 mg·kg⁻¹·d⁻¹. The observation period was 12 weeks.</p><p><b>RESULTS</b>A total of 222 patients were enrolled in seventeen centers (including 113 patients treated with anagrelide and 109 with hydroxyurea). Therapy efficacy can be evaluated in 198 patients (including 97 patients administered with anagrelide and 101 with hydroxyurea). At 12th weeks of therapy, the hematologic remission rate was 87.63% (85/97) in anagrelide group and 88.12% (89/107) in hydroxyurea group, the differences between the two groups were not significant (P=0.173). Treatment with anagrelide lowered the platelet counts by a median of 393 (362-1 339) × 10⁹/L from a median of 827 (562-1657) × 109/L at the beginning of the observation to 400(127-1130)×10⁹/L after 12 weeks (P<0.001), which were similar to the treatment result of hydroxyurea by a median drop of 398 (597-1846)× 10⁹/L (P=0.982). The median time to achieving response of anagrelide group was 7 (3-14) days, superior to that of hydroxyurea for 21 (14-28) significantly (P=0.003). Frequency of anagrelide related adverse events was 65.49 % (74/113), including cardiopalmus (36.28% ), headache (21.24% ), fatigue (14.16% ) and dizzy (11.50% ).</p><p><b>CONCLUSION</b>Anagrelide was effective in patients with ET which had similar hematologic remission rate to hydroxyurea and could take effect more quickly than hydroxyurea. Incidence of adverse events was undifferentiated between anagrelide and hydroxyurea, but anagrelide treatment had tolerable adverse effects and no hematologic toxicity.</p>

Clinical significance of TET2 gene expression in 157 adult acute myeloid leukemia patients with normal cytogenetics / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical significance of ten-eleven-translocation methylcytosine dioxygenase 2 (TET2) mRNA expression levels in adult acute myeloid leukemia patients with normal cytogenetics (CN-AML).</p><p><b>METHODS</b>Expression levels of TET2 mRNA were measured by real-time PCR in 157 adult CN-AML, and its clinical impact in CN-AML was evaluated as well.</p><p><b>RESULTS</b>TET2 gene expression levels from bone marrow mononuclear cells (BMMNCs) [7.29(3.41-9.99)] and CD34+ cells [6.02(5.64-6.54)] in CN-AML were significantly lower than those [BMMNCs: 8.13(6.68-9.04), P=0.026; CD34+ cells: 6.48(5.97-7.12), P=0.034] in healthy control. And TET2 mRNA level at diagnosis [7.32(6.11-8.41)] was obviously lower than that at complete remission [8.39(7.76-8.79), P<0.01]. CN-AML patients with lower levels of TET2 mRNA showed worse survival rate [(32.7±5.9)%] at 18-month than those with higher levels [(48.6±6.9)%, P=0.041]. In multivariate analysis, lower level of TET2 mRNA was an independent prognostic factor for OS [hazard ratio(HR)2.032, 95% confidence interval (CI)1.272-3.247, P=0.003] and event-free survival [HR 1.532, 95% CI 1.014-2.314, P=0.043].</p><p><b>CONCLUSION</b>The level of TET2 mRNA is significantly lower in patients with CN-AML and it is an independent negative prognostic factor. TET2 could be an important factor for the molecular-based risk stratification in CN-AML.</p>

Expression level of SET gene in acute myeloid leukemia and its clinical significance / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression level of SET gene in patients with acute myeloid leukemia (AML) and evaluate its significance.</p><p><b>METHODS</b>The expression level of SET gene in 141 de novo AML patients was determined by real time quantitative PCR (RQ-PCR), and its relationship with the clinical features and outcomes of these patients were analyzed.</p><p><b>RESULTS</b>SET gene transcript level was detected in 141 AML patients with the median expression level of 0.86(range 0.02-15.69). AML patients with higher SET gene expression had a higher level of white blood cell (WBC ≥ 100 × 10⁹/L) count than of lower SET gene expression ones (31.0% vs 11.4%, P=0.005). In the 136 patients who received treatment after diagnosis, higher SET gene expression group had lower complete remission rate (50.0%) than of lower expression cohort (73.5%) after two cycles of chemotherapy (P=0.005). Survival analysis showed that patients with higher SET gene expression had significantly shorter overall survival(OS) (10 months vs 22 months, P=0.001) and event-free survival (EFS) (2 months vs 14 months, P=0.005) than of lower SET gene expression ones. Multivariate COX regression analysis showed SET overexpression was an independent prognostic factor for OS. In the patients with the normal karyotype, higher SET expression group also had significantly shorter OS (12 months vs 35 months, P=0.010) and EFS (4 months vs 14 months, P=0.026) than of lower SET expression ones.</p><p><b>CONCLUSION</b>High expression of SET gene was associated with poor prognosis and might be a prognostic molecular marker of AML.</p>

Evaluation of methods for collection of peripheral blood stem cells in children / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To evaluate the methods for collection of peripheral blood stem cells (PBSC) in children.</p><p><b>METHODS</b>Peripheral blood stem cells were collected from 20 child patients and 11 donors. The patients treated with chemotherapy, received G-CSF or GM-CSF and the donors received G-CSF for mobilization. When the peripheral blood (PB) leukocyte count reached to 5 X10(9)/L,the hematopoietic stem cells were collected with CS-3000 Plus, COM TEC or COBE Spectra blood cell separators from patients and donors. For children whose weight <20 kg,HCT <24% or TBV <1 100-1 650 ml,blood cell separators were pre-injected with the same type RBCs irradiated by 25 Gy of gamma-ray and with low flow rate (10-30 ml/min). The number of CD34(+) cell was detected by flow cytometry. The relationship of number of CD34(+) cell with mononuclear cell (MNC) and processed blood volume was analyzed.</p><p><b>RESULTS</b>Successful collection of the PBSCs with the CS- 3000 Plus (n=10), the COM TEC (n=3) and the COBE Spectra (n=18) was achieved in all the 31 cases with 1-5 aphereses used. Number of CD34(+) cells was (7.9 ±2.9) X 10(6)/kg and that of MNCs was (7.4 ±3.1) X 10(8)/kg. The total CD34(+) cell count was correlated with MNCs before aphaeresis and processed blood volume.</p><p><b>CONCLUSION</b>For collection of high quality PBSCs, the appropriate methods should be chosen according to the body weight, TBV, mobilization of child patients/donors.</p>

The efficacy and safety of HAA regimen as induction chemotherapy in 150 newly diagnosed acute myeloid leukemia / 中华内科杂志

Objective To explore the efficacy and safety of HAA regimen (homoharringtonine,cytarabine and aclarubicin) in the treatment of 150 newly diagnosed adult acute myeloid leukemia (AML).Methods All patients entered the study from May 1999 to June 2008 were treated with HAA regimen. Coxsurvival analysis was used to estimate the survival rate and differences between M1/M2 and M4/M5 were compared with 2-sided log-rank test. Results Out of the 150 patients, 121 (81%) achieved complete remission (CR). After the first course, CR rate was 68%. The CR rates of 97%, 84% and 38% were achieved in patients with favorable, intermediate and unfavorable cytogenetics, respectively. For the patients with CR, the median follow-up time was 16.5 ( 1.5-100.5 ) months, and the estimated 3-year survival rate was 45%. The estimated 3-year relapse free survival rate was 52% for the 121 patients with CR.Conclusions HAA regimen may be an efficacious and safe regimen with a good toleration in the induction therapy for newly diagnosed AML, and a high CR rate could be achieved with only one or two courses.

Clinical and cytogenetic features of hematologic malignancies associated with acquired trisomy 21 / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association between trisomy 21 abnormalities and the clinical and cytogenetic features of hematologic malignancies.</p><p><b>METHODS</b>Chromosome preparations were made on bone marrow cells by using direct method and/or unstimulated short-term cultures. Karyotypes were analyzed by R-banding.</p><p><b>RESULTS</b>Thirteen patients (1.5%) with acute myeloid leukemia (AML) including 6 cases of M5b, 8 (2.2%) with acute lymphoblastic leukemia (ALL) and 4 cases with other hematologic malignancies had acquired trisomy 21, and in 13 patients it occurred as the sole cytogenetic abnormality. The remaining had combination with other abnormalities. The median survival for the 19 patients with trisomy 21 was 9 months.</p><p><b>CONCLUSION</b>M5b was the major type in AML with sole acquired trisomy 21.Trisomy 21 as the sole abnormality appeared to have a poor prognosis.</p>