8025 Background: Relapsed/refractory (RR) multiple myeloma (MM), RRMM, remains as an incurable disease and has a 5-year survival rate of nearly 50%. To address the unmet medical need, an autologous CAR-T cell therapy was developed previously with a humanized single-domain antibody (sdAb) targeting BCMA as the antigen binding domain, 4-1BB and CD3ζ as cytoplasmic domain. Methods: An investigator-initiated clinical trial (IIT) was conducted in China to assess the safety and efficacy of the sdAb-based CAR-T. The trail was started in June 2018 and the last patient infused in June 2019. As of 1 February 2021, 34 were treated and followed up. The patients had received multiple lines of prior treatment (including bortezomib, lenalidomide, and others). Following a lymphodepleting regimen of cyclophosphamide (300-600 mg/m 2 , d-5, -4) and fludarabine (25-30 mg/m 2 , d-5 to d-3), patients were infused with 2.5-10.0 × 10 6 CAR + cells/kg body weight. CAR-T was infused immediately after preparation and quality control performed in all patients except one, who was infused a 10.0 × 10 6 CAR + cells/kg dose of frozen cells. Efficacy was assessed based on the IMWG criteria, toxicity was graded by CTCAE 4.02, and CRS grading was based on the grading system by CARTOX working group. Results: All 34 patients had the tumor burden of plasma cells in bone marrow, or M protein or free light chains (FLCs) in serum, 7 patients were accompanied with extramedullary diseases. The efficacy shows the best ORR is 88.2% (30/34), sCR rate is 55.9% (19/34). The mPFS was 12.1 months, several patients shows continuous sCR after 2 years. No obvious correlation between efficacy and dosage were found in three dose groups of 2.5×10 6 CAR + cells/kg (6 pts), 5.0×10 6 CAR + cells/kg (23 pts) or 10.0×10 6 CAR + cells/kg (5 pts). The observed adverse events include thrombocytopenia (≥grade 3, 38.2%), neutropenia (≥grade 3, 44.1%), leukopenia (≥grade 3, 32.4%), lymphopeniPa (≥grade 3, 26.5%), and anemia (≥grade 3, 20.6%). CRS was monitored occurring in 29 patients (any grade, 85.3%, ≥grade 3, 2.9%). Conclusions: Our result demonstrates that the CART employing one humanized sdAb targeting BCMA is safe and efficacious for clinical application. The phase I clinical trial has been initiated in China for searching the RP2D using the cryopreserved CAR-T cells. Clinical trial information: NCT03661554.
Objective To study the efficacy and safety of continuous intravenous infusion of 2-Chlorodeoxyadenosine (2-CdA) combined with high-dose cytarabine (Ara-C) and granulocyte colony-stimulating factor (G-CSF) (CLAG regiem) in the treatment of relapsed/refractory acute myeloid leukemia (AML). Methods Fifteen patients with refractory/relapsed AML hospitalized in 5 medical units such as Department of Hematology, the Affiliated Tumor Hospital of Zhengzhou University and received one course of CLAG regimen from June 2014 to August 2019 were analyzed retrospectively (specifically: cladribine 5 mg/M2, day 1 to day 5, continuous 24-hour intravenous infusion; Ara-C 2 g/M2, 1 time/day, day 1 to day 5, intravenous infusion; G-CSF 300 mg, 1 time/day, day 0 to day 5, subcutaneous injection). Results Among the 15 patients with refractory/relapsed AML, 9 males and 6 females, the median age was 35 (13-63) years old. FAB classification: 1 case of M1, 3 cases of M2a, 4 cases of M2b (including 1 case with extramedullary invasion), 1 case of M4 with extramedullary invasion, 5 cases of M5, 1 case of HAL; NCCN classification: 6 cases in intermediate risk group, 9 cases in high risk group; 8 cases refractory, 7 cases relapsed. The median time of pre-chemotherapy was 4 (2-8) (of which NO.15 had received 8 cycles of chemotherapy and received CLL1-CAR-T), and the median white blood cell count before chemotherapy was 12.27 (from 0.78 to 5.29)×109/L. After 1 course of treatment with CLAG regimen, 12 patients achieved complete remission (12/15, 80%), and the median duration of CR was 65 days (0-528) days. IV grade leukopenia and thrombocytopenia was found in all the patients after chemotherapy. The median duration of granulocytosis was 20 (14 to 33) days, and 1 patient died. Seven patients received allogeneic hematopoietic stem cell transplantation. The median EFS and OS time of 15 patients was 85 (19-558) days and 117 (19-558) days, respectively. Conclusion The CLAG regimen consisting of continuous intravenous infusion of cladribine shows high CR in the treatment of AML patients, but the duration of CR is short, myelosuppression is sever, so that infection control is the key. Allogeneic hematopoietic stem cells transplantation should be performed as soon as possible after CR.
Objective
To observe the clinical efficacy and adverse events of decitabine combined with full-dose and long-term pre-excitation regimen as a induction therapy for relapsed/refractory acute myeloid leukemia (AML).
Methods
A total of 32 patients with relapsed/refractory AML in Henan Provincial Cancer Hospital from May 2013 to February 2018 were enrolled. All the patients were treated with decitabine combined with full-dose and long-term pre-excitation regimen, including 15 patients who received decitabine combined with CAG regiemtn, and 17 patients who received decitabine combined with CHAG regimen: 25 mg decitabine, intravenous drip, from day 1 to day 3; cytarabine (10-15 mg/m2) administered subcutaneously every 12 h one time, from day 4 to day 17 or more; homoharringtonine (1 mg/m2) intravenous drip, administered intravenously from day 4 to day 10 or more; aclacinomycin (8-10 mg/m2), intravenous drip, administered intravenously from day 4 to day 11 or more; granulocyte colony-stimulating factor (G-CSF) (100-200 μg/m2), subcutaneous injection, and it began 1 day before chemotherapy, adjusted according to the blood cell count; the therapeutic effect and adverse reactions of the patients were observed.
Results
There were 29 patients (90.6%) with complete remission (CR), 3 patients (9.4%) with partial remission (PR), and the overall response (CR+PR) rate was 100.0% (32/32). In decitabine combined with CAG regimen group, 13 patients achieved CR; in decitabine combined with CHAG regimen group, 16 patients achieved CR, and there was no statistically significant difference in the efficacy between the two groups (P= 0.589). The main adverse reactions were agranulocytosis, thrombocytopenia, secondary infection and fever, and no serious adverse events occurred.
Conclusion
Decitabine combined with full-dose and long-term pre-excitation regimen has a favorable efficacy and safety, which provides a new therapy for relapsed/refractory AML.
Key words:
Leukemia, myeloid, acute; Refractory; Relapsed; Decitabine; Pre-excitation regimen
Objective
To study the influence of the combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) on liver function in newly diagnosed patients with acute promeylocytic leukemia (APL).
Methods
Eighty newly diagnosed patients were involved in this retrospective study. Among them, thirty-eight patients were treated with ATRA and ATO, while forty-two were treated with ATRA or ATO alone. The efficiency and liver dysfunction rate in two groups were compared.
Results
There was no significantly statistical difference in CR rates between the combination group and one drug group [94.7 % (36/38) vs 90.5 % (38/42), P> 0.05], while the difference was significant in time to remission [27 d (20-36 d) vs 35 d (25-49 d), P 0.05).
Conclusion
More serious hepatotoxicity is observed in patients treated with ATRA and ATO, indicating that monitoring of liver function and simultaneous liver protection therapy are necessary when treated with combination of ATRA and ATO.
Key words:
Leukemia, promyelocytic, acute; All-trans retinoic acid; Arsenic trioxide; Drug-induced liver injury
Outcome of patients with adult acute lymphoblastic leukemia(ALL)is poor, and even worse among patients with relapsed/refractory ALL(R/R ALL). New treatments must be taken to overcome drug-resistance to conventional chemotherapy for ALL. Humanized monoclonal antibody and chimeric antigen receptor gene modified T cells have become the focus of treatment in ALL. Lots of clinical trials in multiple research centers are in progress, and the results constantly upgrade which is effectively bring better curative effect and prognosis for R/R ALL patients. This is one of the hot topics at the 56th ASH annual meeting.
Key words:
Leukemia, lymphocytic, acute; Philadelphia chromosome; Immunotherapy; American Society of Hematology annual meeting
Opinion statement Pyroptosis is a kind of programmed cell death dependent on the caspase pathway that is different from apoptosis and necrosis. Recent studies have shown that pyroptosis can be involved in the pathological processes of many diseases, such as cancers, atherosclerosis, diabetic nephropathy, and blood diseases. However, the specific mechanisms by which pyroptosis participates in the occurrence and development of hematological malignant tumors still need further exploration. This article reviews the characteristics of pyroptosis and the regulatory mechanisms promoting or inhibiting pyroptosis and discusses the role of pyroptosis in hematological malignant tumors, which could provide ideas for the clinical treatment of such tumors in the future.
Abstract The neutrophil-to-lymphocyte ratio (NLR) as an inflammatory marker may represent changes between inflammation and host immunity that affect the prognosis of peripheral T-cell lymphoma (PTCL). To comprehensively evaluate the NLR in PTCL, we performed a meta-analysis to investigate the relationship between the NLR and overall survival (OS) and progression-free survival (PFS). PubMed, Embase, Cochrane library, and China National Knowledge Infrastructure (CNKI) were searched for all relevant studies. Hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained from each study. Heterogeneity among the included studies was checked to determine whether fixed or random effects model was used. In total, 8 studies with 921 patients were included for the meta-analysis. High NLR significantly correlated with worse OS (HR = 2.20, 95% CI 1.71–2.83, P < 0.05) regardless of region (Asian or non-Asian), sample size (< 60 or ≥ 60), median age (< 60 or ≥ 60), disease type, or cut-off value (NLR < 3.9 or NLR ≥ 3.9). In terms of PFS, the NLR had no prognostic impact for patients with PTCL (HR = 1.12, 95% CI 0.57–2.20, P = 0.742). Our findings suggest that PTCL patients with high NLR are more likely to have worse OS compared to those with low NLR. Therefore, the NLR can serve as a prognostic marker in PTCL.
To explore the clinical and survival significance of CD20 positive adult patients with B-lineage acute lymphoblastic leukemia (B-ALL).The clinical features and survival of 168 adult patients with B-ALL diagnosed and treated in our department from May 2007 to July 2011 were analyzed retrospectively, 58 expressed CD20 and 110 not.The sex, distribution of age, anemia, thrombocytopenia, infiltration of liver, spleen and lymph nodes, the expression of myeloid lineage marker, incidence of Ph chromosome, complete remission within 4 weeks showed no significant differences in CD20 positive and negative groups (P>0.05); median white blood cell count at diagnosis and the rate of patients with high white blood cell count in CD20 positive group were 19.2×10⁹/L and 37.9% respectively, which were significantly higher than those of 6.93 × 10⁹/L and 20.9% in CD20 negative group (P<0.05); cumulative incidence of relapse between two groups showed significant difference (P<0.05); multivariable analysis for overall survival and progress-free survival identified CD20 positivity as independent predictor.The expression of CD20 in adult patients with B-ALL appeared to be associated with high white blood cell count and poor prognosis.
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