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Objective:To explore the efficacy of tislelizumab combined with umbilical cord blood transplantation (UCBT) in relapsed/refractory acute myeloid leukemia (R/R AML) patients.Methods:The diagnosis and treatment of 1 patient with R/R AML who received tislelizumab bridging to UCBT after the failure of re-induction treatment in the First Affiliated Hospital of Soochow University in November 2021 was retrospectively analyzed.Results:The 59-year-old male patient with R/R AML achieved a complete remission after initial induction chemotherapy regimen of decitabine and venetoclax, and then additional consolidation therapy regimens of decitabine and middle-dose cytarabine, middle-dose cytarabine and idarubicin were performed. The patient relapsed 16 months later and failed to achieve a second remission after re-induction therapy regimens of cladribine, azacitidine, venetoclax combined with chemotherapy, and homoharringtonine, cytarabine combined with granulocyte colony-stimulating factor. Tislelizumab significantly reduced tumor burden and the patient achieved the complete remission after bridging to UCBT. After transplantation, the patient was given maintenance treatment with azacitidine and he had sustained remission without severe transplant-related complications during 9-month follow-up.Conclusions:The use of tislelizumab bridging UCBT can be a potential therapeutic strategy for R/R AML patients.
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【Objective】 To investigate the situation of carbapenem-resistant Enterobacteriaceae(CRE) colonization in patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). 【Methods】 A total of 241 consecutive patients who underwent haplo-HSCT in the First Affiliated Hospital of Soochow University from June 1, 2021 to June 1, 2022 were enrolled. Anal swab screening was performed within 48 hours of admission and blood cultures were taken when the patient developed fever. Univariate and multivariate analysis were used to analyze the colonization rate, distribution, risk factors and the correlation between CRE colonization and post-transplant bloodstream infection(BSI). 【Results】 Among 241 patients with haplo-HSCT, there were 90 cases in CRE colonization positive group, with a colonization rate of 37.3% (90/241). Multivariate logistic regression analysis showed that sex (OR 2.42, 95% CI 1.38-4.22, P<0.05) and history of infection within 30 days before transplantation (OR 3.37, 95% CI 1.59-7.17, P<0.05) may be independent risk factors for CRE intestinal colonization. Of the 95 CRE strains, the top five species were carbapenem-resistant Klebsiella pneumoniae (38/95, 40.0%), carbapenem-resistant Escherichia coli (29/95, 30.5%), carbapenem-resistant Enterobacter cloacae (13/95, 13.6%), carbapenem-resistant Klebsiella acidophilus (6/95, 6.3%) and carbapenem-resistant Proteus mirabilis (3/95, 3.1%). The incidence of post-transplant BSI was 12.0% (29/241) in the CRE-colonized group and 3.3% (8/241) in the non-colonized group. In the colonization group, 100% of the pathogens of BSI were identical with those of CRE colonization. 【Conclusion】 Bacterial culture of anal swab during haplo-HSCT is helpful for detection of CRE colonization in intestinal tract, which provides some clinical basis for active monitoring of key flora, prevention and control of infection.
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Primary central nervous system lymphoma (PCNSL) is a rare and aggressive non-Hodgkin’s lymphoma that affects the brain, eyes, cerebrospinal fluid, or spinal cord without systemic involvement. The outcome of patients with PCNSL is worse compared to patients with systemic diffuse large B-cell lymphoma. Given potential mortality associated with severe immune effector cell-associated neurotoxicity syndrome (ICANS), patients with PCNSL have been excluded from most clinical trials involving chimeric antigen receptor T-cell (CAR-T) therapy initially. Here, we report for the first time to apply decitabine-primed tandem CD19/CD22 dual-targeted CAR-T therapy with programmed cell death-1 (PD-1) and Bruton’s tyrosine kinase (BTK) inhibitors maintenance in one patient with multiline-resistant refractory PCNSL and the patient has maintained complete remission (CR) for a 35-month follow-up period. This case represents the first successful treatment of multiline resistant refractory PCNSL with long-term CR and without inducing ICANS under tandem CD19/CD22 bispecific CAR-T therapy followed by maintenance therapy with PD-1 and BTK inhibitors. This study shows tremendous potential in the treatment of PCNSL and offers a look toward ongoing clinical studies.
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Blinatumomab, as a novel bispecific antibody targeting CD19 and CD3, can induce T lymphocytes to precisely target CD19 positive B lymphocytes to apoptosis. At present, it is the only bispecific antibody approved for the treatment of hematological malignancies in China. Blinatumomab is effective in the treatment of newly diagnosed, relapsed/refractory, minimal residual disease positive patients with B-cell acute lymphoblastic leukemia (B-ALL) . It can improve the survival of the patients and is well tolerated. The further study of blinatumomab can provide theoretical basis and new ideas for induction therapy, salvage therapy and subsequent hematopoietic stem cell transplantation in patients with B-ALL.
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Objective:To observe the efficacy and safety of decitabine combined with chemotherapy in treatment of relapsed/refractory T lymphoblastic lymphoma/leukemia (T-LBL/ALL) with TP53 mutation.Methods:The clinical data of a T-LBL/ALL patient with TP53 mutation who had recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) treated with decitabine combined with chemotherapy in the First Affiliated Hospital of Soochow University in June 2018 were retrospectively analyzed and the relevant literature was reviewed.Results:The patient, a 42-year-old male, diagnosed as T-LBL/ALL with TP53 mutation by comprehensive examination underwent sibling-matched donor allo-HSCT after a second complete remission. The patient relapsed 8 months later and was treated with decitabine combined with CLAG regimen to achieve complete remission again. And then, he had leukemia-free survival until now through maintenance treatment with decitabine.Conclusion:Decitabine combined with chemotherapy may be a safe and effective treatment option for relapsed T-LBL/ALL patients with TP53 mutation after allo-HSCT.
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Objective:To investigate the clinical characteristics of steroid-resistant chronic graft-versus-host disease (cGVHD) patients and the therapeutic effect of ibrutinib.Methods:The clinical data of 3 steroid-resistant cGVHD patients treated with ibrutinib after allogeneic hematopoietic stem cell transplantation in the First Affiliated Hospital of Soochow University from December 2017 to March 2018 were retrospectively analyzed, and the literature was reviewed.Results:All 3 patients had different degrees of skin and oral cGVHD. One patient's oral symptom improved after the application of prednisone, and the skin symptom was better after oral ibrutinib; one patient's oral symptom improved after oral ibrutinib, but skin symptom did not improve significantly; one patient's skin symptom did not improve significantly. None of the 3 patients presented with adverse reactions such as hemorrhage, infection and cytopenia.Conclusions:Ibrutinib has a certain effect on the improvement of symptoms in steroid-resistant cGVHD patients.
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Objective:To compare the efficacy and safety of venetoclax (VEN) combined with azacitidine (AZA) versus CAG regimen combined with decitabine (DAC) in elderly patients with relapsed acute myeloid leukemia (AML).Methods:From January 2018 to August 2020, the clinical data of forty-five elderly patients with relapse AML at the First Affiliated Hospital of Soochow University were retrospectively analyzed, including 31 males and 14 females. The median age was 66 (60-80) years old. Eighteen patients were administrated with VEN and AZA, while the other 27 were in CAG with DAC. The complete remission (CR) rate, partial remission (PR) rate, total remission rate (ORR), adverse events and overall survival (OS) were compared between the two groups.Results:At the end of the treatment, the ORR in VEN with AZA group was 77.8% (14/18); including 11 CR and 3 PR. In CAG with DAC group, the ORR was 37.0% (10/27); including 8 CR and 2 PR ( P=0.007). Subgroup analysis suggested that VEN with AZA had a higher ORR in patients stratified as intermediate and poor-risk ( P=0.013) or with DNA methylation mutations ( P=0.007). Main adverse events in both groups were bone marrow suppression, infections, nausea and vomiting, anorexia and fatigue. Grade Ⅲ-Ⅳ cytopenia developed in lower incidence of VEN with AZA group, such as leukopenia (66.7% vs. 100%, P=0.002), anemia (50.0% vs. 92.6%, P=0.002), thrombocytopenia (72.2% vs. 96.3%, P=0.031) and neutropenia (61.1% vs. 92.6%, P=0.014). In addition, less grade Ⅲ-Ⅳ infections occurred in VEN with AZA group (66.7% vs. 33.3%, P=0.028), as well as grade Ⅲ-Ⅳ gastrointestinal events (40.7% vs. 11.1%, P=0.032), grade Ⅲ-Ⅳ fatigue (55.6% vs.11.1%, P=0.003) compared with CAG with DAC group. The 1-year OS in VEN with AZA group versus CAG with DAC group was 42.9% and 31.6% respectively ( P=0.150). Conclusion:VEN combined with AZA proves favorable efficacy and tolerablity in elderly patients with relapsed AML.
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To investigate the efficacy and safety of total oral regimen containing ixazomib in multidrug-resistant relapsed and refractory multiple myeloma(RRMM). A total of 38 patients were retrospectively analyzed from August 2018 to January 2020 in the First Affiliated Hospital of Soochow University. The overall response rate (ORR)was 36.8%. Among them, the very good partial response (VGPR) or better rate was 23.7%, and the complete response (CR) rate was 5.3%. The ORR was 41.7% in patients receiving ixazomib-lenalidomide-dexamethasone (IRD) regimen. Median PFS was 5 months and median OS was 7.5 months. The ORR was 50% after second-line therapy, 40% after third-line therapy and 12.5% after forth-line therapy or more. The ORR was 29.0% in bortezomib-refractory patients, 38.0% in lenalidomide-refractory patients, 21.4% in bortezmoib & lenalidomide dual refractory patients. Grade 3-4 hematological adverse events (AEs) were reported in 21% patients. Common hematological AEs included lymphopenia, neutropenia, thrombocytopenia. Other usual AEs were fatigue and diarrhea. No grade 3-4 peripheral neuropathy was recorded. In the treatment of relapsed/refractory multiple myeloma patients with multidrug resistance, the total oral regimens containing ixazomib demonstrate reliable efficacy and safety. Early administration of ixazomib at first or second relapse is suggested for more favorable clinical outcome.
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Objective:To examine the efficacy of haploidentical stem-cell transplantation (haplo-SCT) for patients with refractory relapsed (R/R) non-Hodgkin lymphoma (NHL) by comparing with those contemporaneously undergoing HLA-matched SCT in myeloablative conditioning settings.Methods:Between January 2006 and December 2018, a total of 151 patients undergoing haplo-SCT ( n=81) or HLA-matched SCT ( n=70, sibling or unrelated) were enrolled. Median age of alloSCT was 30(5-59) years. And 150 patients received myeloablative conditioning (MAC) consisting of total body irradiation (12 Gy) plus cyclophosphamide or busulfan plus cyclophosphamide. Only one case had reduced intensity conditioning (RIC) with R-FBA (fludarabine, busulfan & cytarabina). It was followed by an infusion of granulocyte-colony stimulating factor-primed bone marrow (G-BM) and/or peripheral blood stem cells without in vitro T cell depletion. In haplo-SCT and HLA-matched unrelated donor for SCT, GVHD prophylaxis consisted of antithymocyte globulin, cyclosporine A, mycophenolate mofetil and a short course of methotrexate. Clinical efficacy, hematopoietic reconstitution and transplant-related complications were retrospectively analyzed. Results:Among them, 146(96%) patients engrafted with a median time to neutrophil and platelet recovery of 12 and 15 days respectively. During a median follow-up period of 19 months, 66 of them survived (43.7%) and 67 (44.4%) died (39 disease recurrence, 27 transplantation-related mortality). Between haplo-SCT and HLA-matched SCT groups, progression-free survival (PFS) rate was 49.4% and 50.5% ( P=0.577); overall survival (OS) rate 56.7% and 57.4% respectively ( P=0.963). The cumulative incidences of relapse (CIR) were 36.6% and 37.7% ( P=0.836) and those of cumulative incidences of non-relapse mortality (NRM) 22.0% and 24.7% ( P=0.530). And the cumulative incidences of chronic GVHD were 42.3% and 39.6% ( P=0.46) respectively. Conclusions:No inter-group difference exists in each major HSCT endpoint. Multivariate analysis reveals that occurrence of grade Ⅲ-Ⅳ aGVHD has a significantly worse prognosis. And primary chemorefractoriness is a strongest relapsing factor.
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Objective:To evaluate the outcomes and prognostic factors of myelodysplasia syndrome with excess blasts (MDS-EB) patients on intensive chemotherapy or hypomethylating agent treatment prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A total of 108 MDS-EB patients undergoing allo-HSCT from April 2015 to September 2019 were collected retrospectively, intensive chemotherapy or hypomethylating agent treatment (IC/HAM) group, n=72; support care (SC) group, n=36. Clinical outcomes and prognostic risk factors were analyzed. Results:Intensive chemotherapy or hypomethylating agent treatment pre-HSCT had no effects on overall survival (OS) ( P=0.725), relapse-free survival (RFS)( P=0.658), cumulative incidence rate (CIR) ( P=0.121) or non-relapse mortality (NRM)( P=0.236). Univariate and multivariate analysis of an entire cohort showed that poor cytogenetics was an independent risk factor for OS ( P=0.005), DFS ( P=0.001) and CIR( P=0.032); grade Ⅱ-Ⅳ acute graft venous host disease was independently correlated with unfavorable DFS( P=0.004). Conclusions:IC/HAM treatment pre-HSCT fails to yield discrepant post-HSCT outcomes in MDS-EB patients. The pooling of more patients in a well-designed multi-center clinical trial will further demonstrate the efficacy of treatment pre-HSCT in MDS-EB patients.
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Objective:To investigate the predictive value of blood routine and blood biochemical indicators for immunotherapy combined with chemotherapy-related interstitial pneumonia (IP) in patients with diffuse large B-cell lymphoma (DLBCL).Methods:The data of 151 newly-diagnosed DLBCL patients treated with rituximab combined with chemotherapy in the First Affiliated Hospital of Soochow University from December 2017 to October 2020 were retrospectively analyzed. According to whether IP occurred, the patients were divided into IP group and non-IP group. The patient's clinical data and baseline laboratory test results were collected. The differences in clinicopathological features and laboratory indicators between IP group and non-IP group were analyzed. In addition, the relationship between the variety of blood routine and blood biochemical indicators and the occurrence of IP was analyzed. The receiver operating characteristic (ROC) curve of the selected indicators to predict the occurrence of IP was drawn, and the predictive performance of each indicator was analyzed.Results:The incidence of IP was 9.3% (14/151) in DLBCL patients after receiving immunotherapy combined with chemotherapy. The lymphocyte count (LYM) in IP group at the first diagnosis was higher than that in non-IP group [1.60×10 9/L (1.40×10 9/L, 2.51×10 9/L) vs. 1.28×10 9/L (0.89×10 9/L, 1.78×10 9/L), U=-2.194, P=0.028], but there was no significant difference in the levels of platelet count, neutrophil count, monocyte count, lactate dehydrogenase (LDH), α-hydroxybutyrate dehydrogenase (α-HBDH), serum albumin (ALB) and the proportion of patients with elevated C-reactive protein (CRP) between the two groups (all P > 0.05). Compared with the laboratory indicators in non-IP group before the 4th cycle of treatment, LYM and ALB in IP group were significantly reduced at IP onset [0.72×10 9/L (0.46×10 9/L, 0.92×10 9/L) vs. 0.93×10 9/L (0.71×10 9/L, 1.15×10 9/L), 32.9 g/L (28.6 g/L, 34.9 g/L) vs. 40.3 g/L (36.1 g/L, 43.1 g/L)], but LDH and α-HBDH increased [332 U/L (255 U/L, 396 U/L) vs. 233 U/L (200 U/L, 286 U/L), 277 U/L (206 U/L, 315 U/L) vs. 189 U/L (159 U/L, 229 U/L)], and the differences were statistically significant (all P<0.05). The proportion of patients with elevated CRP in IP group was high than that in non-IP group [100.0% (14/14) vs. 56.9% (78/137), P=0.001]. The area under ROC curve of LYM, ALB, LDH and α-HBDH alone for predicting the occurrence of IP was 0.668, 0.820, 0.789 and 0.802. The best cut-off values of ALB, LDH and α-HBDH was 34.6 g/L, 241 U/L and 199 U/L. ALB had the highest sensitivity for predicting the occurrence of IP (81.8%). The areas under ROC curve of ALB+LDH, ALB+α-HBDH, LDH+α-HBDH, ALB+LDH+α-HBDH for predicting the occurrence of IP was 0.850, 0.844, 0.777 and 0.851, respectively. LDH+α-HBDH had the highest predictive sensitivity (92.9%), but the specificity was low (53.3%). The prediction sensitivity (both 78.6%) and specificity (both 86.1%) of ALB+LDH and ALB+LDH+α-HBDH were high. Conclusions:DLBCL patients are at risk of IP during immunotherapy combined with chemotherapy. The increased LYM at initial diagnosis is a risk factor for the occurrence of IP. The variety of LYM, ALB, LDH, α-HBDH and CRP during the treatment may be related to the occurrence of IP. Among them, ALB, LDH and α-HBDH have important predictive values for the occurrence of IP.
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Objective:To explore the application of venetoclax in transplantation of patients with refractory acute myeloid leukemia (AML).Methods:The diagnosis and treatment process of a patient with refractory AML who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) under venetoclax and hypomethylating agents bridging myeloablative preconditioning regimen after induction therapy failure in the First Affiliated Hospital of Soochow University in March 2020 were retrospectively analyzed.Results:The patient was a 28-year-old female who was diagnosed with refractory AML. The patient was initially given induction chemotherapy with IA (idarubicin+cytarabine) (3+7) regimen, but the disease did not relieve, then the induction chemotherapy with CLAG (cladribine+cytarabine+granulocyte colony stimulating factor) regimen was given, but the disease still did not relieve. After chemotherapy with venetoclax and hypomethylating agents bridging myeloablative preconditioning regimen, salvage haploid allo-HSCT was performed. Re-examination of bone marrow showed remission, and implantation was successful. The patient was followed up for 100 days and had sustained remission, and no transplantation complications occurred.Conclusion:For refractory AML patients who have failed primary induction therapy, the use of venetoclax and hypomethylating agents bridging myeloablative preconditioning regimen can be used as a preferred solution for salvage allo-HSCT.
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Objective:To investigate the effect and prognostic factors of rituximab-containing chemotherapy regimen in treatment of patients with mantle cell lymphoma (MCL).Methods:The clinical data of 56 patients aged ≤65 years in the First Affiliated Hospital of Soochow University from June 2007 to November 2018 were retrospectively analyzed. Rituximab-containing chemotherapy regimen was used, and the effects of clinical features, treatment regimen and biological indexes on overall survival (OS) and progression-free survival (PFS) were observed.Results:The median age of 56 patients was 57 years old, including 43 males and 13 females. Among these cases, 24 patients received R-CHOP chemotherapy regimen; 29 patients received cytarabine-containing chemotherapy regimen, including R-hyper CVAD/R-MA regimen used in 15 patients and R-CHOP alternating with R-DAHP regimen used in 14 patients; and 3 patients received other treatment regimens. Among 56 patients, 19 patients received autologous hematopoietic stem cell transplantation (ASCT) consolidation therapy. The median OS time was 74 months, 2-year OS rate was 83.8%, 3-year OS rate was 70.9%, 2-year PFS rate was 72.0% and 3-year PFS rate was 49.7%. International prognostic index (IPI) high-risk and receiving ASCT or not during the treatment were independent influencing factors of OS and PFS in MCL patients. The overall response rate (ORR) in cytarabine-containing regimen group was higher compared with that in R-CHOP regimen group (93.1% vs. 83.3%), and there was no statistically significant difference ( χ2=0.465, P=0.495). In addition, there were no significant differences between two groups in both OS ( χ2=0.291, P=0.590) and PFS ( χ2=0.912, P=0.339). ASCT consolidation prolonged the median OS time (72 months vs.124 months, χ2=3.973, P=0.040) and the median PFS time (34 months vs. 90 months, χ2=3.984, P=0.046) in MCL patients achieving remission after induction therapy. Among patients in simplified MCL IPI (sMIPI) score middle-high risk group, compared with those not receiving ASCT, patients receiving ASCT therapy could obtain better OS and PFS (OS: χ2=5.037, P=0.025; PFS: χ2=6.787, P=0.009); among patients of sMIPI score low risk, there were no statistically significant differences in OS and PFS between the group receiving ASCT and not (all P > 0.05). Conclusions:Cytarabine-containing chemotherapy regimen has no predicatively satisfactory value in improving the prognosis and survival for MCL patients. For MCL patients who have achieved remission after reduction therapy and those in sMIPI score middle-high risk group, ASCT consolidation therapy can improve the prognosis and can be taken as the first-line consolidation treatment in young patients.
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Objective:To investigate the incidence, risk factors and survival of cGVHD patients in combination of a haploidentical donor supported with an unrelated umbilical cord blood for hematopoietic stem cells transplantation (haplo-cord-HSCT).Methods:300 hematological malignancies individuals who received dual transplantation were enrolled in the study between January 2012 and July 2016 at the department of Hematology in the First Affiliated Hospital of Soochow University. The clinical diagnosis and scoring the severity of cGVHD syndromes according the National Institutes of Health (NIH) consensus conference in the 2014 update. Cox proportional hazards regression was used to identify risk factors associated with transplant outcomes.Results:During follow-up with a median time of 26.4 months (range 0.2-61.8) post transplantation, the 1-year, 3-year and 5-year cumulative incidence of cGVHD was 26.3 % (95 % confidence interval [CI], 23.5 %~29.1 %), 30.3 % (95 % CI, 27.3 %~33.3 % ) and 32.2 % (95 % CI, 28.7 %~35.7 %). For all 73 patients with cGVHD, first-line or second-line treatment were given. During the follow-up period, 53 patients survived, and 20 patients died. In multivariate analysis, the cGVHD overall survival (GOS) were associated with thrombocytopenia(<100×109/L)(HR=0.103, 95 % CI 3 %-36.1 %, P<0.001). Conclusions:Our data suggest that, the 5-year cumulative incidence of cGVHD was 32.2 % after haplo-cord-HSCT with hematological malignancies. Thrombocytopenia (<100×109/L)was independent risk factors for GOS.
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The first-generation Bruton tyrosine kinase inhibitor (BTKi) ibrutinib significantly improved the survival and prognosis of patients with chronic lymphocytic leukemia (CLL), but its adverse reactions such as bleeding, infection, cardiovascular events, etc., limited the long-term compliance of patients. It has been considered that the new generation of BTKi could significantly reduce the adverse reactions caused by ibrutinib because of their higher selectivity and specificity. Among them, the efficacy and safety of acalabrutinib in untreated and relapsed/refractory patients with CLL have been confirmed in phase Ⅲ clinical trials. In addition, zanubrutinib and orelabrutinib, which were independently developed in China, have also been proven their preliminary safety and therapeutic effects in pre-clinical and phase Ⅰ and Ⅱ clinical trials, while the data from large phase Ⅲ clinical trials are still lacking. Currently, more BTKi are also under active exploration. The future therapeutic strategies of CLL may be converted to combining with a wide range of drugs to achieve the goal of drug discontinuation when minimal residual disease (MRD) is negative, or use MRD to guide the treatment. In this trend, the new generation of BTKi will provide more optimized options for the combination therapy regimens.
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Objective:To evaluate the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of elderly patients with acute myeloid leukemia (AML).Methods:The clinical data of 53 elderly patients (≥55 years old) with AML who received allo-HSCT in the First Affiliated Hospital of Soochow University from June 2008 to March 2019 were retrospectively analyzed. All the patients included haplo-HSCT (26 cases), matched-sibling donors (MSD)-HSCT (18 cases), matched or mismatched unrelated donors (9 cases). The efficacy of allo-HSCT for elderly patients with AML was analyzed, and the efficacy and safety of haplo-HSCT and MSD-HSCT were compared.Results:There were 35 males and 18 females among 53 elderly AML patients. The median age was 57 years old (55-67 years old), and 45 patients received myeloablative conditioning (MAC) regimen while 8 patients received reduced intensity conditioning (RIC) regimen. There were 52 patients who were successfully implanted in granulocyte, and the median time for engraftment was 12 d (10-23 d). There were 50 patients who were successfully implanted in megakaryocyte and the median time for engraftment was 13 d (10-76 d). The incidence of acute graft-versus-host disease (GVHD) was 49.1% (26/53), and the incidence of grade Ⅲ-Ⅳ acute GVHD was 15.1% (8/53), respectively. The median follow-up time was 14.7 months (0.4-136.8 months), and 32 patients survived. The rate of 2-year overall survival (OS), disease-free survival (DFS) and graft-versus-host-free-relapse free survival (GRFS) was 63.1%, 59.5% and 46.1%, respectively. Multivariate analysis showed that non-complete remission (CR) state before transplantation was an independent prognostic factor for OS ( HR = 3.600, 95% CI 1.213-10.684, P = 0.021), DFS ( HR = 2.596, 95% CI 1.098-6.138, P = 0.030) and relapse ( HR = 3.957, 95% CI 1.099-14.245, P = 0.035). Donor age > 45 years old was an independent risk factor for OS ( HR = 3.687, 95% CI 1.343-10.215, P = 0.011). Time from diagnosis to transplantation ≥6 months was an independent risk factor for GRFS ( HR = 2.308, 95% CI 1.083-4.918, P = 0.030). There were no statistical differences in OS rate, DFS rate, cumulative relapse rate, the incidence of grade Ⅲ-Ⅳ acute GVHD and moderate to severe chronic GVHD between haplo-HSCT and MSD-HSCT (all P > 0.05). Conclusions:The preliminary results show that allo-HSCT is an effective and safe treatment for elderly AML patients. In addition, haplo-HSCT is similar to MSD-HSCT in the efficacy and safety, indicating that haplo-HSCT could be a better treatment option for elderly AML patients under the circumstance without non-identical donor.
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Objective@#To evaluate the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of elderly patients with acute myeloid leukemia (AML).@*Methods@#The clinical data of 53 elderly patients (≥55 years old) with AML who received allo-HSCT in the First Affiliated Hospital of Soochow University from June 2008 to March 2019 were retrospectively analyzed. All the patients included haplo-HSCT (26 cases), matched-sibling donors (MSD)-HSCT (18 cases), matched or mismatched unrelated donors (9 cases). The efficacy of allo-HSCT for elderly patients with AML was analyzed, and the efficacy and safety of haplo-HSCT and MSD-HSCT were compared.@*Results@#There were 35 males and 18 females among 53 elderly AML patients. The median age was 57 years old (55-67 years old), and 45 patients received myeloablative conditioning (MAC) regimen while 8 patients received reduced intensity conditioning (RIC) regimen. There were 52 patients who were successfully implanted in granulocyte, and the median time for engraftment was 12 d (10-23 d). There were 50 patients who were successfully implanted in megakaryocyte and the median time for engraftment was 13 d (10-76 d). The incidence of acute graft-versus-host disease (GVHD) was 49.1% (26/53), and the incidence of grade Ⅲ-Ⅳ acute GVHD was 15.1% (8/53), respectively. The median follow-up time was 14.7 months (0.4-136.8 months), and 32 patients survived. The rate of 2-year overall survival (OS), disease-free survival (DFS) and graft-versus-host-free-relapse free survival (GRFS) was 63.1%, 59.5% and 46.1%, respectively. Multivariate analysis showed that non-complete remission (CR) state before transplantation was an independent prognostic factor for OS (HR = 3.600, 95% CI 1.213-10.684, P = 0.021), DFS (HR = 2.596, 95% CI 1.098-6.138, P = 0.030) and relapse (HR = 3.957, 95% CI 1.099-14.245, P = 0.035). Donor age > 45 years old was an independent risk factor for OS (HR = 3.687, 95% CI 1.343-10.215, P = 0.011). Time from diagnosis to transplantation ≥6 months was an independent risk factor for GRFS (HR = 2.308, 95%CI 1.083-4.918, P = 0.030). There were no statistical differences in OS rate, DFS rate, cumulative relapse rate, the incidence of grade Ⅲ-Ⅳ acute GVHD and moderate to severe chronic GVHD between haplo-HSCT and MSD-HSCT (all P > 0.05).@*Conclusions@#The preliminary results show that allo-HSCT is an effective and safe treatment for elderly AML patients. In addition, haplo-HSCT is similar to MSD-HSCT in the efficacy and safety, indicating that haplo-HSCT could be a better treatment option for elderly AML patients under the circumstance without non-identical donor.
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Chimeric antigen receptor T cell (CAR T) therapies have achieved unprecedented efficacy in B-cell tumors, prompting scientists and doctors to exploit this strategy to treat other tumor types. Acute myeloid leukemia (AML) is a group of heterogeneous myeloid malignancies. Relapse remains the main cause of treatment failure, especially for patients with intermediate or high risk stratification. Allogeneic hematopoietic stem cell transplantation could be an effective therapy because of the graft-versus-leukemia effect, which unfortunately puts the patient at risk of serious complications, such as graft-versus-host disease. Although the identification of an ideal target antigen for AML is challenging, CAR T therapy remains a highly promising strategy for AML patients, particularly for those who are ineligible to receive a transplantation or have positive minimal residual disease. In this review, we focus on the most recent and promising advances in CAR T therapies for AML.
Subject(s)
Humans , Hematopoietic Stem Cell Transplantation , Immunotherapy, Adoptive , Leukemia, Myeloid, Acute/therapy , Receptors, Chimeric Antigen , T-LymphocytesABSTRACT
BACKGROUND: Acute myeloid leukemia (AML) patients with non-remission (NR) after the first cycle of standard induction chemotherapy remain a challenge owing to poor response and tolerance to re-induction regimen. We retrospectively evaluated the efficacy and safety of three regimens in AML patients refractory to the first course of standard induction regimen. MATERIALS AND METHODS: The three regimens consisted of (1) High-dose cytarabine, aclarubicin and granulocyte colony-stimulating factor (HD-CAG) regimen (n = 44); (2) intermediate/high-dose cytarabine (I/HDAC) regimen (n = 30); and (3) standard-dose cytarabine (SDAC) combination regimen that was identical to the first course of standard induction regimen (n = 27). RESULTS: Results indicated that after the second course, the overall response (OR), i.e., complete remission [CR]+partial remission [PR]) rates in HD-CAG was higher than in the I/HDAC group (84.1% vs. 56.7%, P = 0.009), whereas the CR rates among 3 groups were not statistically different (P = 0.541). Meanwhile, the proportion of subjects reporting certain adverse effects in the HD-CAG group was lower than the I/HDAC or SDAC groups. There were no significant differences in overall survival (OS) and disease-free survival (DFS) rates among the 3 groups (P = 0.881 and P = 0.872, respectively). CONCLUSION: Our preliminary results indicate that HD-CAG regimen may represent a better alternative option for AML patients with NR after the first course of standard induction chemotherapy.
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Objective@#To investigate the safety and efficacy of allogeneic CAR-T cells in the treatment of relapsed/refractory multiple myeloma (RRMM) .@*Methods@#CAR-T cells were prepared from peripheral blood lymphocytes of HLA mismatch healthy donors. Median age was 55 (48-60) . Allogeneic cells were derived from 3 HLA haploidentical donors and 1 HLA completely mismatch unrelated donor. Four patients with RRMM were conditioned with FC regimen followed by CAR-T cell transfusion. They were infused into CART-19 (1×107/kg on day 0) and (4.0-6.8) ×107/kg CART-BCMA cells as split-dose infusions (40% on day 1 and 60% on day 2) . The adverse reactions and clinical efficacy were observed during follow-up after infusion, and the amplification and duration of CAR-T cells in vivo were monitored by PCR technique.@*Results@#CAR-T cells were successfully infused in 3 of the 4 RRMM patients according to the study plan, and the infusion in one patient was delayed by 1 day due to high fever and elevated creatinine levels on day 3. The side effects included hematological and non-hematological toxicity, grade 3 hematological toxicity in 2 patients, grade 3 CRS in 1 one, grade 1 CRES in 1 one, prolonged APTT in 3 ones, tumor lysis syndrome in 1 one, mixed chimerism detected STR and clinical GVHD manifestation in 1 one. According to the efficacy criterias of IMWG, 2 patients acquired PR, 1 MR, and 1 SD respectively. Progression-free survival was 4 (3-5) weeks and overall survival was 63 (3-81) weeks. CAR T cells were amplified 2.2 (2-14) times in the patients with a median survival time of 10 (8-36) days.@*Conclusions@#Small sample studies suggested that GVHD may be present in the treatment of RRMM with allogeneic CAR-T cells. There were early clinical transient events after transfusion. Low amplification and short duration of CAR-T cells in vivo may be the main factors affecting the efficacy.