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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 therapeutic efficacy of venetoclax combined with avapritinib in treatment of refractory/relapsed acute myeloid leukemia (AML) with KIT gene mutation.Methods:The clinical data of 2 AML patients with KIT gene mutation who received venetoclax combined with avapritinib admitted to Canglang Hospital of Suzhou in October 2022 and November 2022 were retrospectively analyzed, and the relevant literature was reviewed.Results:Both patients with high-risk relapsed/refractory AML and KIT gene mutation were females; the one was 53 years and the other was 17 years. Case 1 was diagnosed with AML-M 2, and genetic testing revealed positive mutations in ASXL1, KIT, and RUNX1. The patient relapsed after transplantation and then was treated with venetoclax combined with avapritinib achieving morphologic leukemia-free status (MLFS). Case 2 was diagnosed with AML, and RUNX1-RUNX1T1 (AML1-ETO) fusion gene and KIT and DX15 gene mutations were detected. The patient was treated with venetoclax combined with avapritinib regimen after relapse, and the treatment regimen significantly reduced the tumor load. Complete remission was achieved after bridging to allogeneic hematopoietic stem cell transplantation. Conclusions:AML with KIT gene mutation is heterogeneous and some patients are difficult to treat with very poor prognosis. Bridging (secondary) hematopoietic stem cell transplantation can be the better treatment choice for relapsed patients achieving MLFS or complete remission after venetoclax combined with avapritinib treatment regimen.
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NK/T cell leukemia/lymphoma is a type of malignancy originating from T cells or natural killer cells with low incidence and poor clinical prognosis. There is still no effective treatment strategy. In recent years, targeted therapy has made great progress in the treatment of hematological malignancies, including monoclonal antibody and chimeric antigen receptor T cells (CAR-T), among which CD30, CD7, CD5, CD52, CCR4 and other target antigens are effective in the treatment of NK/T cell leukemia/lymphoma, but its widespread application still faces a great challenge. This article reviews the progress of immunotherapy for NK/T cell leukemia/lymphoma.
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Objective:To investigate the effect of autologous hematopoietic stem cell transplantation (auto-HSCT) bridging to chimeric antigen receptor T cell (CAR-T) immunotherapy for follicular lymphoma (FL) transformed to B-lymphoblastic leukemia/lymphoma (B-LBL).Methods:The diagnosis and treatment of 1 patient with FL transformed to B-LBL admitted to the First Hospital of Soochow University in August 2020 were retrospectively analyzed and the literature was reviewed.Results:The male patient was 65 years old, and was diagnosed as FL (stage Ⅳ group A, FL international prognostic index -1 score 3 points, high-risk group) in August 2020. And then he was given 6 courses of RB (rituximab combined with bendamustine) regimen, with complete remission (CR) at mid-term and end-stage PET-CT, followed by regular maintenance therapy with rituximab every 2 months, and disease progressed after 4 courses of maintenance therapy. According to the results of histopathology and bone marrow aspiration in December 2021, he was diagnosed B-LBL involving the bone marrow. Partial remission was achieved after induction therapy with zanubnulindb combined with hyper CVAD (cyclophosphamide + doxorubicin + vindesine + dexamethasone) regimen, followed by auto-HSCT bridging to CAR-T treatment targeting CD19 and CD22, which proceeded smoothly with cytokine release syndrome grade 0, immune effector cell-associated neurotoxicity syndrome grade 0. The patient successfully underwent hematopoietic reconstruction and orally taken ibrutinib after discharge. PET-CT indicated CR 2 months after transplantation and he was still in disease-free survival state.Conclusions:The prognosis of FL transformed to B-LBL is poor, and auto-HSCT bridging to CAR-T can improve the prognosis and prolong the survival time of patients who cannot undergo allogeneic hematopoietic stem cell transplantation.
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Objective:To evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation(auto-HSCT)for the treatment of multiple myeloma(MM)in elderly patients aged over 65 years.Methods:In this retrospective analysis, the efficacy and safety of auto-HSCT for the treatment of MM was examined in 28 patients aged >65 years diagnosed and treated at Soochow Hopes Hematology Hospital between March 1, 2020 and October 31, 2022.The functions of the major organs of these patients were evaluated before transplantation.Results:The 28 patients had a median age of 67(66-72)at the time of transplantation, a median number of 2.985 × 10 6/kg(2.036-9.5 × 10 6/kg)of collected CD34+ hematopoietic stem cells, and a median number of 2(1-3)days of collection.The median time to neutrophil implantation after hematopoietic stem cell transfusion was 10(9-14)days, and the median platelet implantation time was 11(10-29)days.The median follow-up time was 25 months, but the median progression-free survival time was not reached.The 1-year PFS rate was 89.3% and 2-year PFS rate was 76.3%, with 2 patients' starting point of PFS set at the time of pre-transplantation re-induction therapy because needed salvage auto-HSCT.The overall survival time was not reached, the 1-year overall survival rate was 100.0%, and the 2-year overall survival rate was 90.5%. Conclusions:Auto-HSCT is a safe and effective treatment for elderly MM patients aged over 65 years after screening and assessment.
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Objective:To investigate the levels of sex hormone and fertility in female patients after hematopoietic stem cell transplantation (HSCT), as well as their correlation with conditioning regimens, and analyse the effect of hormone replacement therapy (HRT) in young women after HSCT.Methods:Retrospective case series study. The clinical data of 147 women who underwent HSCT in the First Affiliated Hospital of Soochow University from January 2010 to January 2021 were retrospectively analyzed. The sex hormone levels were measured and followed-up, and the survival, menstrual fertility and the use of HRT of the patients were also followed-up. The sex hormone levels were measured after transplantation, and the ovarian function was evaluated. Independent sample t test and χ2 test were used for comparison between the two groups. Results:The median age of the 147 patients was 26 (range, 10-45) years. Of them, 135 patients received allogeneic HSCT and 12 patients received autologous HSCT. Furthermore, 129 patients received myeloablative conditioning, and 18 patients received reduced conditioning dose. The median follow-up time was 50 months (range, 18-134 months). Five patients died of disease recurrence during follow-up. Of the 54 patients with subcutaneous injection of zoladex, three recovered menstruation spontaneously after transplantation, and all of them were myeloablative conditioning patients, one patient gave birth to twins through assisted reproductive technology. Ninety-three patients did not use zoladex before conditioning, two patients with aplastic anemia with non-myeloablative transplantation resumed menstruation spontaneously, and conceived naturally. The level of follicle stimulating hormone after transplantation in patients receiving myeloablative conditioning regimen was significantly higher than that in patients receiving reduced-dose conditioning regimen [(95.28±3.94) U/L vs. (71.85±10.72) U/L, P=0.039]. Among 147 patients, 122 patients developed premature ovarian failure, 83 patients received sex hormone replacement therapy after transplantation, and 76 patients recovered menstruation and improved endocrine function. Conclusions:The incidence of premature ovarian failure is high in female patients after HSCT, and patients have a chance at natural conception. Reducing the dose of conditioning regimen and the application of zoladex before transplantation can reduce ovarian of conditioning drugs. HRT after transplantation can partially improve the endocrine function of patients.
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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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【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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BACKGROUND@#Although the need for consolidation chemotherapy after successful induction therapy is well established in patients with acute myeloid leukemia (AML) in first complete remission (CR1), the value of consolidation chemotherapy before allogeneic hematopoietic stem cell transplantation remains controversial.@*METHODS@#We retrospectively compared the effect of the number of pre-transplant consolidation chemotherapies on outcomes of human leukocyte antigen-matched sibling stem cell transplantation (MSDT) for patients with AML in CR1 in multicenters across China. In our study, we analyzed data of 373 AML patients in CR1 from three centers across China.@*RESULTS@#With a median follow-up of 969 days, patients with ≥ 3 courses of consolidation chemotherapy had higher probabilities of leukemia-free survival (LFS) (85.6% vs . 67.0%, P < 0.001) and overall survival (89.2% vs . 78.5%, P = 0.007), and better cumulative incidences of relapse (10.5% vs . 19.6%, P = 0.020) and non-relapse mortality (4.2% vs . 14.9%, P = 0.001) than those with ≤ 2 courses of consolidation chemotherapy. Pre-transplantation minimal residual disease-negative patients with AML in CR1 who received MSDT with ≥ 3 courses of consolidation chemotherapy had a higher probability of LFS (85.9% vs . 67.7%, P = 0.003) and a lower cumulative incidence of relapse (9.6% vs . 23.3%, P = 0.013) than those with ≤ 2 courses.@*CONCLUSION@#Our results indicate that patients with AML in CR1 who received MSDT might benefit from pre-transplant consolidation chemotherapy.
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Humans , Retrospective Studies , Consolidation Chemotherapy/methods , Siblings , Hematopoietic Stem Cell Transplantation/methods , Leukemia, Myeloid, Acute/etiology , HLA Antigens , AllograftsABSTRACT
Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%-50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.
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The Asia-Pacific Blood and Marrow Transplantation Group (APBMT) has been conducting annual surveys on the activity of hematopoietic stem cell transplants since 2007. The APBMT Data Center collected the following data in 2017. A total of 21,504 transplants were registered from 733 transplant centers of 20 countries/regions in the Asia-Pacific (AP) region. Five countries/regions comprised 89.4% of all transplants - China (6,979), Japan (5,794), South Korea (2,626), India (2,034), and Australia (1,789). The number of centers in these five countries/regions also comprised 88.9% of all centers: Japan (373), China (123), India (66), Australia (45), and South Korea (44). The overall ratio between autologous and allogeneic transplants was 37.0% and 63.0%, respectively, but the ratios varied significantly among countries/regions. Autologous transplants have surpassed allogeneic transplants in Thailand, Australia, Vietnam, New Zealand, Singapore, and Iran. In contrast, the proportion of allogeneic transplants comprised over 70% of all transplants in Pakistan, China, and Hong Kong. These ratios were compared by the Data Center among countries/regions that performed more than 50 transplants. The proportion of related and unrelated transplants also differed among countries/regions. The number of unrelated transplants was more than related ones in Japan (2,551 vs. 1,202) and Australia (329 vs. 291), whereas more than 80% of all transplants were related transplants in Malaysia (90.9%), India (89.5%), Iran (87.2%), Vietnam (85.7%), China (80.9%), and Thailand (80.6%). All transplant activities were related transplants in Pakistan, the Philippines, Myanmar, and Nepal, and no allogeneic transplants were performed in Bangladesh and Mongolia. Regarding the indications for transplants, acute myeloid leukemia (AML) was the most common disease for allogeneic transplant (4,759, 35.1% of allogeneic transplants), while plasma cell disorder (PCD) was the most common disease for autologous transplant (3,701, 27.3% of all autologous transplants). Furthermore, the number of transplants for hemoglobinopathy has steeply increased in this region compared with the rest of disease indications (677, 3.1% of all transplants). APBMT covers a broad area globally, including countries/regions with diverse disease distribution, development of HSCT programs, population, and economic power. Consistent and continuous activity surveys considering those elements in each country/region revealed the HSCT field's diverse characteristics and background factors in this region.
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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 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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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 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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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 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 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 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 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.