ABSTRACT
【Objective】 To investigate the correlation between early immune reconstitution and clinical outcomes in patients with acute lymphoblastic leukemia (ALL) underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). 【Methods】 The basic information and treatment data of 99 patients with ALL undering allo-HSCT from December 2018 to February 2022 were collected. The proportions of CD3+ T, CD3+CD4+ T, CD3+CD8+ T and CD3-CD16+CD56+ NK cells were detected before and 30, 60 and 90 days after transplantation using flow cytometry. The correlation between early cellular immune reconstitution and neutrophil engraftment, platelet engraftment, infection, and acute and chronic graft-versus-host disease (GVHD) was analyzed. 【Results】 Among 99 ALL patients, the median time of neutrophil engraftment was day +11 (range, 8-28), and the median time of platelet engraftment was day +14 (range, 10-120). The cumulative incidence of blood stream infection (BSI) was 11.10% and the cumulative incidence of CMV within 100 days of transplantation was 40.40%. The cumulative incidence of EBV within 100 days was 7.10%. The cumulative incidence of acute graft-versus-host disease (aGVHD) was 22.30%. The cumulative incidence of chronic graft-versus-host disease (cGVHD) within 1 year of transplantation was 16.20%. 1 -year cumulative relapse rate was 13.84%. The 1 -year cumulative disease-free survival (DFS) for all patients was 80.60% and the 1-year overall survival (OS) was 90.30%. The CD4+/CD8+ ratio was positively associated with the development of aGVHD at 30 days post-transplant (OR 1.21, 95CI 1.01-1.45, P<0.05). The proportion of CD16+ CD56+ NK cell were higher in the group without BSI than that in the BSI group before and 30 days after transplantation (P < 0.05). The proportion of CD4+ T-cell were lower in the CMV infection group than that in the group without CMV infection at 60 and 90 days post-transplant(P<0.05). The higher level of CD4+ T-cells at 60 days post-transplant was a protective factor for CMV infection within 100 days (HR 0.91, 95CI 0.84-0.99, P<0.05). 【Conclusion】 Early immune reconstitution after allo-HSCT in patients with ALL is associated with aGVHD, CMV and BSI.
ABSTRACT
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) could effectively treat multiple hematological diseases. At present, with persistent improvement of transplantation techniques and rapid development of economy, more and more patients with hematological diseases are able to survive for a long time due to allo-HSCT treatment. Chronic ocular graft-versus-host disease (coGVHD) is the most common ocular complication after allo-HSCT, which is primarily manifested with refractory dry eye. In severe cases, it may cause imbalance of ocular surface homeostasis and limbal stem cell insufficiency, further leading to a series of complications that threaten the visual function and eye health, such as corneal perforation and symblepharon, etc. It is highly difficult to cure these symptoms. At present, relevant studies of clinical manifestations, diagnostic criteria, treatment specification and pathogenesis of coGVHD have been gradually deepened within the international community. However, related research and the establishment of clinical specification are still in the primary stage in China. In this article, research progress on clinical characteristics and related mechanisms of coGVHD was reviewed, aiming to deepen the understanding of this disease by ophthalmologists, especially specialists in corneal and ocular surface diseases, and provide novel ideas for subsequent in-depth research.
ABSTRACT
Immune deficiency of the host caused by allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the initial factor of reactivation of latent human cytomegalovirus (HCMV). The risk factors of reactivation of HCMV in allo-HSCT recipients consist of the serological status of HCMV in donors and recipients, the matching degree of human leukocyte antigen (HLA) and pretreatment patterns, etc. The reactivation of HCMV is associated with the expression of a series of viral cleavage and proliferation proteins induced by the overexpression of major immediate early promoter/enhancer (MIEP) in the viral genome. In this article, the risk factors of reactivation of HCMV after allo-HSCT, the molecular changes related to maintaining latent infection of HCMV, the key role of MIEP overexpression in reactivation of HCMV, and the molecular pathways involved in reactivation of HCMV after allo-HSCT were reviewed and the major molecular events of reactivation of HCMV after allo-HSCT were elucidated, aiming to provide reference for the prevention and treatment of cytomegaloviral disease (CMVD) after allo-HSCT.
ABSTRACT
Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a main question on treatment failure.Current strategies for management that usually include salvage chemotherapy,donor lymphocytic infusion and second transplantation.Our study assessed the efficacy of decitabine (DAC) for treating patients with acute lymphoblastic leukemia (ALL) who relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT).We retrospectively analyzed the outcomes of 12 patients with relapsed ALL after allo-HSCT who received DAC therapy.Nine patients received DAC combined with chemotherapy and donor stem cell infusion,and 3 patients received single-agent DAC.Ten of the 12 patients achieved complete remission (CR),1 achieved a partial remission (PR),and 1 had no response (NR) after treatment at the latest follow-up (LFU),the median survival was 11.2 months (range,3.8-34,7 months).The 1-and 2-year overall survival (OS) rates were 50％ (6/12) and 25％ (3/12),respectively.Five patients were still alive;4 had maintained CR and 1 was alive with disease.Patients with Philadelphia chromosome-positive ALL had higher survival rate than patients with Philadelphia chromosome-negative ALL (57.1％ vs.20％).No aggravated flares of graft-versus-host disease (GVHD) were observed during DAC treatment.Therefore,DAC may be a promising therapeutic agent for ALL recurrence after allo-HSCT.
ABSTRACT
Objective:To investigate the relationship between gene polymorphisms of disease-relevant multiple cytokines including TNF-α,IL-6,IL-10,TGF-β1,IFN-γand acute graft versus host disease(aGVHD) in allogeneic hematopoietic stem cell trans-plantation ( allo-HSCT ) . Methods:32 cases of recipients received allo-HSCT and 36 cases of normal groups in January 2014 to December 2015 were selected as objects of study. We detected genotypes on specific SNP of target genes by polymerase chain reation ( PCR) combined with gene sequencing and observed the occurrence of aGVHD in postoperative recipients. The influence of cytokine gene polymorphisms on prognosis of allo-HSCT patients was analyzed,and the potential relationship between specific SNP mutation of the disease-relevant cytokine genes and severity of aGVHD was discussed. Results:Distribution of cytokines gene polymorphism including TNF-α-308(G/A),IL-6-174(G/C),IL-10-1082(A/G),TGF-β1+915(G/C),IFN-γ(T/A) had no significant differences with incidence of severe aGVHD(P>0. 05). However,the occurrence of severe aGVHD in allo-HSCT recipients with C/T genotype was significantly higher than C/C and T/T in SNP of TGF-β1+869(P<0. 01). Conclusion:Gene polymorphism of TGF-β1+869(C/T) in allo-HSCT patients was closely related to the occurrence of severe aGVHD. The research show allo-HSCT patients with C/T genotype occurred severe aGVHD more frequently, which is an important potential risk factor to induce the incidence of severe aGVHD. Therefore,detecting gene polymorphism of TGF-β1+869 ( C/T ) in allo-HSCT recipients and developing the appropriate therapeutic regimen may be helpful to reduce the incidence of aGVHD.