Efficacy and safety of secondary allogeneic hematopoietic stem cell transplantation in 70 patients with recurrent hematologic malignancies after transplantation / 中华血液学杂志

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.

Idiopathic inflammatory demyelinating diseases of the central nervous system in patients following allogeneic hematopoietic stem cell transplantation: a retrospective analysis of incidence, risk factors and survival / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for many hematological diseases, but there are many complications following allo-HSCT, among which neurological complications (NC) are one of the most commonly described ones. However, little is known about idiopathic inflammatory demyelinating diseases (IIDDs) of the central nervous system (CNS) in patients following allo-HSCT.</p><p><b>METHODS</b>A nested case-control study was conducted in a large cohort of 1365 patients, who underwent allo-HSCT at the Institute of Hematology and Peking University People's Hospital, between January 2004 and December 2009, 36 patients of whom developed CNS IIDDs. Kaplan-Meier method, univariate and multivariate Cox regression were applied in our statistical analysis using SPSS 16.0.</p><p><b>RESULTS</b>The cumulative incidence of all cases of IIDDs at 6 years posttransplantation was 3.6%. Thirty-five patients (97.2%) suffered IIDDs after transplantation, 16 patients (44.4%) between day 0 to day 100 post-transplantation, 10 patients (27.8%) between day 100 to 1 year post-transplantation, and 9 patients (25.0%) 1 year post-transplantation. Multivariate regression analysis identified donor type (P = 0.031), infection (P = 0.009), and acute lymphatic leukemia (P = 0.017) as independent risk factors for posttransplantation IIDDs. The median survival time of patients with IIDDs was 514 days after transplantation (95%CI: 223 - 805). Survival at 6 years was significantly lower in patients who developed the diseases compared to those who did not (26.6% vs. 73.5%, P < 0.001). Of the 36 patients experiencing IIDDs, 58.3% (n = 21) died. The causes of death were graft-versus-host disease (GVHD) (n = 4), underlying disease relapse (n = 3), infections (n = 12), and other causes (n = 2).</p><p><b>CONCLUSIONS</b>IIDDs is an uncommon but serious complication of allo-HSCT, especially in patients with a primary diagnosis of acute lymphatic leukemia, mismatched transplants, and infections. Our study results indicate that patients with IIDDs tend toward a poor prognosis following allo-HSCT.</p>

Allo-hematopoietic stem cell transplantation is a potential treatment for a patient with a combined disorder of hereditary spherocytosis / 中华医学杂志(英文版)

Both human hereditary spherocytosis (HS) and chronic myelogenous leukemia (CML) are life threatening. Herein we have reported the case of a woman with a combined disorder of HS and CML who underwent the matched sibling allogeneic stem cell transplantation. The complete donor erythroid cells were obtained. The red blood cell counts significantly improved throughout life comparing with pre-hematopoietic stem cell transplantation (HSCT). Reticulocyte counts normalized, and BCR-ABL was cleared away. The total bilirubin level was also corrected in this recipient. Our case is a rare example with a combined disorder of HS and CML following allogeneic stem cell transplantation. HS was not a contraindication for patient in the matched sibling transplant setting.

Angiotensin(1-7) attenuates left ventricular dysfunction and myocardial apoptosis on rat model of adriamycin-induced dilated cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of Angiotensin(1-7) [Ang(1-7)] on left ventricular dysfunction and myocardial apoptosis on rat model of adriamycin-induced dilated cardiomyopathy (ADR-DCM).</p><p><b>METHODS</b>Weight-matched adult male Wistar rats were randomly divided into 3 groups: (1) the ADR-DCM group (n = 25), in which 2.5 mg/kg of ADR was weekly intravenously injected for 10 weeks. (2) Ang(1-7) group (n = 25), in which ADR rats were simultaneously treated with angiotensin-(1-7) (24 µg×kg(-1)×h(-1), ip.) for 12 weeks. (3) normal control group (n = 10). Hemodynamics and echocardiography examination were performed at 12 weeks. The malondialdehyde (MDA) was measured by TBA methods. The plasma concentration of AngII was determined by immunoradiometric assay. The pathological change was analyzed by histological hematoxylin-eosin staining. Myocardial apoptosis was assessed by TUNEL method. The protein expression of pro-apoptotic protein caspase-3, Bax and anti-apoptotic protein Bcl-xl in cardiomyocytes were detected by Western blot.</p><p><b>RESULTS</b>Mortality was significantly lower in Ang(1-7) group than in ADR-DCM group (16% vs. 40%, P < 0.01). Compared to the control group, left ventricular end-diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD) and left ventricular end-diastolic pressure (LVEDP) were significantly increased in ADR-DCM group (all P < 0.01) while fractional shorting (FS), +dp/dtmax and -dp/dtmax were significantly reduced in ADR-DCM group (all P < 0.01). LVEDD, LVESD and LVEDP were significantly reduced while FS, +dp/dtmax and -dp/dtmax were significantly higher in Ang(1-7) group compared to the ADR-DCM group, but still higher than the control group (all P < 0.01). The concentrations of AngII and MDA were higher in the ADR-DCM group than in the control group (P < 0.01), which were significantly reduced by Ang(1-7) treatment (P < 0.01). The TUNEL-positive cells and apoptosis index, the expression of pro-apoptotic protein caspase-3 and Bax were significantly higher while the expression of anti-apoptotic protein Bcl-xl was significantly lower in the ADR-DCM group than in the control group (all P < 0.01) which could all be partially reversed by Ang(1-7) treatment (all P < 0.01).</p><p><b>CONCLUSION</b>Ang(1-7) could significantly attenuate left ventricular dysfunction and myocardial apoptosis in this model by downregulating pro-apoptotic protein caspase-3 and Bax and upregulating anti-apoptotic protein Bcl-xl expression.</p>

Outcome of haploidentical hematopoietic stem cell transplantation for refractory/relapsed acute leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the outcome of human leukocyte antigen (HLA)-mismatched/haploidentical hematopoietic stem cell transplantation (HSCT) for refractory/relapsed acute leukemia (AL) patients and its related risk factors.</p><p><b>METHODS</b>96 refractory/relapsed AL patients who received HLA-mismatched/haploidentical HSCT following conditioning regimen comprised of modified busulfan/cyclophosphamide (BU/CY) plus thymoglobulin (ATG) from Jan 2003 to Jun 2011 were analyzed retrospectively.</p><p><b>RESULTS</b>Of the 96 patients, 61 suffered from acute myeloid leukemia (AML), and 35 acute lymphoid leukemia (ALL), all of them in non-remission (NR) or relapse before transplantation. With a median follow-up of 373 (34 - 3157) d, 33 cases (34%) survived, 31 survived without leukemia, and 35 relapsed. The estimated 3-year overall survival (OS) and disease-free survival (DFS) rate was 30.2% and 29.0%, respectively. The 3-year OS rate was significantly higher for AML patients (39.2%) than for ALL patients (15.4%) (P = 0.005). The estimated 3-year OS probabilities for patients with and without prophylactic donor lymphocyte infusion (DLI) were 38.0% and 11.8%, respectively (P = 0.001). Sex, age, conditioning regimen (BU/CY or not, dosage of ATG), the number of HLA mismatches between the donor and recipient, and the number of infused mononuclear cells were not independent factors affecting OS, DFS and relapse. Multivariate analysis showed that DFS rate was significantly higher in patients receiving prophylactic DLI (P = 0.003), in patients with AML (vs with ALL) (P = 0.037) and with chronic GVHD (P = 0.006).</p><p><b>CONCLUSIONS</b>Haploidentical HSCT may prolong DFS in part refractory/relapsed AL patients and even cure them. Prophylactic DLI may reduce relapse and increase survival; for patients with refractory/relapsed ALL, other therapy for prevention and treatment of post-transplant relapse should be explored.</p>

Higher proportions of peripheral CD19+CD5+ B cells predict the effect of corticosteroid in patients with late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The cause of late-onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains obscure. In clinical practice, some LOHC patients respond to immunosuppression. The aim of this study was to determine the immune pathogenesis of LOHC post allo-HSCT.</p><p><b>METHODS</b>With the diagnosis of LOHC, patients were given initial treatment consisting of fluid hydration, alkalization and forced diuresis, and empirical anti-viral therapy for 10 - 14 days or until a week after the virus became negative. The nonresponders were applied corticosteroid. Seven to ten days later, patients' response was evaluated. Along with treatment, CD19(+) B lymphocyte subsets were measured at various study points.</p><p><b>RESULTS</b>From October 2009 to March 2010, we found 28 cases of LOHC occurred in 25 patients who underwent allo-HSCT in our hospital. Except that three cases were not treated according to the protocol, the other 25 cases were divided into three groups: anti-virus responders (Group A, n = 6), corticosteroid responders (Group B1, n = 16), corticosteroid and anti-virus nonresponders (Group C, n = 3) according to their clinical response. Percentages of CD19(+)CD5(+) B lymphocytes were not significantly different among three groups at onset of LOCH. However, in Group B1 after the first anti-virus phase, percentages of CD19(+)CD5(+) lymphocytes significantly increased comparing with those at onset (P = 0.022), and then significantly decreased at PR (P = 0.003) and CR (P = 0.002) with corticosteroid treatment. But significant change was not observed in Groups A and C.</p><p><b>CONCLUSION</b>The immune etiology seems to be involved in the development of LOHC and the proportion of CD19(+)CD5(+) lymphocytes may serve as a cellular biomarker to predict the response to corticosteroid in LOHC.</p>

Construction and identification of ha1 recombinant lentiviral vector / 中国实验血液学杂志

This study was aimed to construct a lentiviral vector of ha1 gene and obtain a stable packaging cell lines, which will be beneficial to guiding further study on the foundation of ha1 on the dissociation of graft versus host disease (GVHD) and graft versus leukemia (GVL) effect after allogenic hematopoietic stem cell transplantation (allo-HSCT). The targeting ha1 gene was obtained from plasmid T-ha1 by digesting. Then the ha1 gene was subcloned into the lentiviral vector pRRLSIN, cPPT, PGK/GFP, WPRE to construct a lentiviral vector carrying ha1 gene named pLenti-ha1 plasmid. And the pLenti-ha1 plasmid was confirmed by PCR, digesting and sequencing. 293T cells were co-transfected with lentiviral vector pLenti-ha1 and packaging system. The titer of virus was tested by real-time PCR. The results indicated that the construction of ha1 recombinant lentiviral vector was confirmed to be exact by PCR assay, digesting and sequencing; the assayed titer of virus was 2.0 × 10(8) TU/ml. In conclusion, the lentiviral vector of ha1 gene is constructed successfully.

Clinical study on the relapsd leukemia patients with graft versus host disease after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the dissociation of graft-versus-leukemia (GVL) effects from graft-versus-host disease (GVHD) in the patients who experienced GVHD during leukemia relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>The primary disease, disease status, GVHD, response to donor lymphocyte infusion (DLI) and prognosis were analysed in 11 leukemia patients who relapsed with GVHD after allo-HSCT.</p><p><b>RESULTS</b>Of the 11 relapsed, 5 were acute lymphoblastic leukemia and 6 acute myeloid leukemia. Five received DLI before relapse and all developed post-DLI GVHD, including 2 grade II acute GVHD (aGVHD), 1 limited chronic GVHD (cGVHD) plus grade II aGVHD, and 2 extensive cGVHD. After relapse of the 5 patients, 2 received Chemo-DLI, one achieved CR with extensive cGVHD and then relapsed again, the other didn't achieved CR. The other 6 patients didn't received DLI before relapse and also developed post-HSCT GVHD while relapsing, including 3 extensive cGVHD, 1 grade I aGVHD and 2 grade II-IV aGVHD. After relapse, these 6 patients received Chemo-DLI, 2 achieved CR and then relapsed again, 4 didn't achieved CR.</p><p><b>CONCLUSION</b>The elicited GVHD after allo-HSCT may not accompany effective GVL effects inhibiting leukemic relapse.</p>

Reconstitution kinetics of dendritic cells following allogeneic hematopoietic stem cell transplantation / 中国实验血液学杂志

As the most important antigen present cells in the processes of post-transplant complications in vivo, dendritic cells (DCs) play an important role in graft versus host disease (GVHD), infection, and relapse. DCs have became one of the most critical problems in the transplantation immune research recently. The reconstitution kinetics of circulating DCs after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its relationship with the post-transplant complications, even the promoter or inhibitor affecting this process are summarized in this review.

Study on linkage between polymorphism of interleukin 6 gene -572C/G and susceptibility to myocardial infarction / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To observe the polymorphism and gene frequency of interleukin 6 (IL6) gene -572C/G in Chinese Han nationality population, that associating with susceptibility to myocardial infarction(MI) and impacting on the extent of coronary artery lesions; to analyze the function of IL6 gene -572C/G polymorphism.</p><p><b>METHODS</b>With PCR-RFLP method, IL6 gene -572C/G polymorphism was genotyped to 232 MI patients and 260 healthy adults. The effect of IL6 gene -572C/G polymorphism was observed to the extent of coronary artery lesions and the ability of IL6 production from peripheral blood mononuclear cells (PBMC).</p><p><b>RESULTS</b>There was IL6 gene -572C/G polymorphism in Chinese Hans. -572CG+GG genotype and G allele were more frequent in patients than in controls (P< 0.01). The relative risk for G allele carrier to suffer from MI was 1.68 times of CC genotype individual (95%CI 1.17-2.41, P< 0.01). However, the distribution of IL6 gene -572C/G polymorphism was no significant difference among patients with single-vessel, two-vessel and three-vessel lesions (P> 0.05). After PBMC cultured for 24 hours, the IL6 concentration in supernatant was significantly higher in subjects with CG genotype than those with CC genotype (P< 0.05).</p><p><b>CONCLUSION</b>IL6 gene -572G allele may be a genetic susceptibility factor to MI attack of Chinese Hans population, and related to the high expression of IL6.</p>

Interleukin-6-597G/A and -572C/G polymorphisms and risk of coronary heart disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the relationship between interleukin-6 (IL-6) gene polymorphisms and the risk of coronary heart disease (CHD).</p><p><b>METHODS</b>IL-6/-597G/A and -572C/G polymorphisms were genotyped in 245 CHD patients and 260 healthy adults by PCR-RFLP. Serum IL-6 level was examined by ELISA. Logistic regression was performed to observe the relationship between IL-6/-572C/G polymorphism and other risk factors of CHD.</p><p><b>RESULTS</b>IL-6/-597G/A genotype was similar between the two groups. The frequencies of IL-6/-572C/G genotype and G allele were more frequent in patients with CHD than that in controls (P < 0.01). Compared with CC genotype, the relative risk for CHD in people with CG and GG genotypes was 1.46 (95% CI: 1.01 - 2.10, P < 0.05) and 5.19 (95% CI: 1.69 - 15.89, P < 0.01), respectively. The serum levels of IL-6 were similar between carriers of the IL-6/-572G allele and patients with CC genotype (P > 0.05). IL-6/-572 C/G is related to total cholesterol (OR 1.76, 95% CI: 1.05 - 3.16, P < 0.05) and triglyceride (OR = 2.51, 95% CI: 1.04 - 6.45, P < 0.05), respectively.</p><p><b>CONCLUSION</b>IL-6/-597G/A polymorphism was not associated with susceptibility to CHD, but IL-6-572C/G polymorphism may be a possible genetic susceptibility factor for CHD in Chinese Hans population.</p>