Doxycycline Combined With Bortezomib-Cyclophosphamide-Dexamethasone Chemotherapy for Newly Diagnosed Cardiac Light-Chain Amyloidosis: A Multicenter Randomized Controlled Trial.

BACKGROUND: Doxycycline was demonstrated in a retrospective study to be associated with greater survival in patients with light chain amyloidosis. Therefore, we prospectively compared the efficacy of bortezomib-cyclophosphamide-dexamethasone (CyBorD) and CyBorD combined with doxycycline for cardiac light chain amyloidosis. METHODS: This was a multicenter, open-label, randomized controlled trial. Patients with Mayo 2004 stage II to III light chain amyloidosis were included. Patients were randomized to doxycycline 100 mg twice daily along with 9 cycles of CyBorD (doxycycline group) or to 9 cycles of CyBorD alone (control group). The primary outcome was 2-year progression-free survival (PFS). PFS was defined as the time from randomization to death, hematologic progression, or organ progression (heart, kidney or liver). Hematologic progression was defined on the basis of a substantial increase in free light chain. An increase in either NT-proBNP (N-terminal pro B-type natriuretic peptide) or cardiac troponin was the main criterion for defining cardiac progression. Cardiac PFS, defined as the time from randomization to cardiac progression or death, was compared between groups in an exploratory analysis. The corresponding treatment hazard ratio was estimated with a Cox regression model. RESULTS: One hundred forty patients underwent randomization, with 70 in each group. The median age was 61 years (range, 33-78 years) with a male:female ratio of 1.75:1. Stage II disease was present in 34 (48.6%) and 33 (47.1%) patients in the doxycycline and control groups, respectively. After a median follow-up duration of 24.4 months, 32 of 70 (45.7%) patients in the doxycycline group and 30 of 70 (42.9%) patients in the control group experienced progression. PFS was not significantly different between groups (hazard ratio, 0.97 [95% CI, 0.59-1.60]; P=0.91). Cardiac progression occurred in 29 of 70 (41.4%) patients in the doxycycline group and 26 of 70 (37.1%) patients in the control group. The death rates for both groups by the end of follow-up was the same, 25 of 70 (35.7%). No significant differences were observed for either cardiac PFS (hazard ratio, 0.91 [95% CI, 0.54-1.55]; P=0.74) or overall survival (hazard ratio, 1.04 [95% CI, 0.60-1.81]; P=0.89). CONCLUSIONS: Our trial demonstrated that doxycycline combined with CyBorD failed to prolong PFS or cardiac PFS compared with CyBorD alone in cardiac light chain amyloidosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03401372.

Allo-HSCT for acute leukemia of ambiguous lineage in adults: the comparison between standard conditioning and intensified conditioning regimens.

Knowledge concerning the clinical and biological characteristics of acute leukemia of ambiguous lineage (ALAL) is limited so that there has been a lack of uniformity in treatment. In this report, we retrospectively investigated the effect of intensified conditioning on adult ALAL undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). A total of 59 patients with ALAL (male in 37 cases and female in 22 cases) were consecutively enrolled in the data analyses. Twenty-four patients received the standard conditioning (total body irradiation (TBI) + cyclophosphamide (CY) or busulfan + CY protocol) and 35 received the intensified conditioning (TBI + CY + etoposide or fludarabine + cytarabine plus TBI + CY + etoposide protocol). Five-year transplant-related mortality was 17.6 ± 9.6 % and 25.5 ± 8.0 %, the 5-year overall survival (OS) post-transplantation was 23.8 ± 8.9 % and 64.0 ± 8.4 %, disease-free survival was 16.7 ± 7.6 % and 55.8 ± 9.4 %, the 5-year cumulative incidence of relapse was 80.8 ± 8.5 % and 28.8 ± 9.9 %, respectively, in the standard and the intensified group (P = 0.380, P = 0.029, P = 0.005, and P < 0.001). Both univariate and multivariate analysis indicated that the intensified conditioning regimen and acute graft-versus-host disease were favorable factors to reduce the relapse. The younger patients, patients with CR at the time of transplantation, and the intensified conditioning regimen were favorable factors to elevate the survival. In conclusion, intensified conditioning regimens followed by allo-HSCT might improve long-term survival and decrease relapse of leukemia in adult ALAL compared to the standard conditioning regimens.

[Treatment efficacy of imatinib mesylate versus allogeneic hematopoietic stem cell transplantation for patients with chronic myeloid leukemia in chronic phase].

OBJECTIVE: To compare the treatment efficacy of imatinib mesylate versus allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with chronic myeloid leukemia in chronic phase. METHODS: The efficacy, overall survival, progression-free survival and adverse events were evaluated in 198 patients on these two therapies from February 2002 to December 2012 at our hospital. One hundred and fifteen cases in imatinib group (n = 115) received imatinib at an initial daily dose of 400 mg and then dose was adjusted according to blood routine test and therapy response. All patients were evaluated for hematologic, cytogenetic and molecular responses every 1-3 months. The allo-HSCT group (n = 83) received myeloablative preconditioning regimen and methotrexate (MTX) and cyclosporine A (CsA) were used for graft-versus-host disease (GVHD) partially plus mycophenolate mofetil (MMF) and antihuman thymocyte globulin (ATG). The engraftment evidence and evolution of cytogenetic and molecular response was conventionally detected after allo-HSCT. RESULTS: In imatinib group, 59 of 86 (68.6%) cases achieved complete cytogenetic response (CCyR) in the 12 months after therapy, while 67 of 70 (95.7%) cases achieved CCyR in allo-HSCT group. The relapse rates of two groups were 14.8% (17/115) , 12.3% (10/81) respectively. The adverse reaction of imatinib in imatinib group was obviously much more tolerable for patients compared with frequently occurred GVHD and infection in allo-HSCT group. The 10-year cumulative overall survival (OS) rate was 93.9% in imatinib group and 77.1% in allo-HSCT group (P = 0.015). And the 10-year cumulative progression-free survival (PFS) rate was 86.1% in imatinib group versus 88.0% in allo-HSCT group (P = 0.508) . For Sokal rating stratified analysis, the cumulative OS rates of two groups were 96.4% and 68.0% (P = 0.049) for intermediate-risk patients, 92.6% and 57.1% (P = 0.017) for high-risk patients while the cumulative PFS rates of two groups were 89.3% and 88.0% for intermediate-risk patients (P = 0.942), 70.4% and 85.7% for high-risk patients (P = 0.405). The rates of OS and PFS were not significantly different for low-risk patients. The cumulative OS rates of two groups were 94.7% and 73.5% (P = 0.009) for those ≥ 30 years old and the cumulative PFS rates of two groups 84.2% and 94.1% respectively (P = 0.147). CONCLUSION: Imatinib mesylate is superior to allo-HSCT for patients with chronic myeloid leukemia in chronic phase.

A national, multicenter, retrospective study of Castleman disease in China implementing CDCN criteria.

Background: Castleman disease (CD) is a group of rare and heterogenous lymphoproliferative disorders including unicentric CD (UCD), human herpesvirus-8(HHV-8)-associated multicentric CD (HHV8-MCD), and HHV-8-negative/idiopathic multicentric CD (iMCD). Knowledge of CD mainly comes from case series or retrospective studies, but the inclusion criteria of these studies vary because the Castleman Disease Collaborative Network (CDCN) diagnostic criteria for iMCD and UCD were not available until 2017 and 2020, respectively. Further, these criteria and guidelines have not been systematically evaluated. Methods: In this national, multicenter, retrospective study implementing CDCN criteria, we enrolled 1634 CD patients (UCD, n = 903; MCD, n = 731) from 2000 to 2021 at 40 Chinese institutions to depict clinical features, treatment options, and prognostic factors of CD. Findings: Among UCD, there were 162 (17.9%) patients with an MCD-like inflammatory state. Among MCD, there were 12 HHV8-MCD patients and 719 HHV-8-negative MCD patients, which included 139 asymptomatic MCD (aMCD) and 580 iMCD meeting clinical criteria. Of 580 iMCD patients, 41 (7.1%) met iMCD-TAFRO criteria, the others were iMCD-NOS. iMCD-NOS were further divided into iMCD-IPL (n = 97) and iMCD-NOS without IPL (n = 442). Among iMCD patients with first-line treatment data, a trend from pulse combination chemotherapy toward continuous treatment was observed. Survival analysis revealed significant differences between subtypes and severe iMCD (HR = 3.747; 95% CI: 2.112-6.649, p < 0.001) had worse outcome. Interpretation: This study depicts a broad picture of CD, treatment options and survival information in China and validates the association between the CDCN's definition of severe iMCD and worse outcomes, requiring more intensive treatment. Fundings: Beijing Municipal Commission of Science and Technology, CAMS Innovation Fund and National High Level Hospital Clinical Research Funding.

Nephrotic syndrome after allogeneic hematopoietic stem cell transplantation: etiology and pathogenesis.

In this study we investigated the etiology and pathogenesis of nephrotic syndrome (NS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 257 patients with hematopoietic malignancies who survived more than 2 months post allo-HSCT. Associations of NS with the conditioning regimen, graft versus host disease (GVHD), and other variables were analyzed. Pathologic features of the kidney, regulatory T cells (Tregs), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were studied. NS was identified in 9 patients. The number of Tregs at day+30, 60, 90, and 180 was lower in NS patients than non-NS patients (P=0.001, 0.001, 0.007, 0.003). Serum levels of IFN-γ and TNF-α were higher in NS patients (P=0.032, 0.001, respectively). NS post allo-HSCT was associated with the occurrence of chronic GVHD (P=0.02). NS post-HSCT is an immune disorder that may involve immune complex deposition, Th1 cytokines, and Tregs.

Long-term outcomes of HLA-matched sibling compared with mismatched related and unrelated donor hematopoietic stem cell transplantation for chronic phase chronic myelogenous leukemia: a single institution experience in China.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative therapy for chronic myelogenous leukemia (CML). In this study, the long-term outcomes of HLA-matched sibling donor (MSD) with mismatched related donor (MRD) and unrelated donor (URD) transplantation for CML in the first chronic phase (CML-CP1) using different graft vs. host disease (GVHD) prophylaxis regimens according to donor source and the degree of HLA matching were compared. The data of 91 patients with CML-CP1 were analyzed with respect to GVHD, overall survival (OS), and transplant-related mortality (TRM). The incidence of grade II-IV acute GVHD was 25.5% in the MSD and 40.5% in the MRD/URD group (P = 0.133). The 1-year cumulative incidence of chronic GVHD was not different between the MSD and the MRD/URD groups, while extensive chronic GVHD was different between the two groups (31.9% vs. 10.8%, P = 0.023). The 5-year cumulative relapse rate was not different between the MSD and the MRD/URD groups, while TRM was different between the two groups (6.6% vs. 26.3%, P = 0.010). The 5-year cumulative OS was 90.9%, 71.5%, and 85.4% in the MSD, the MRD/URD, and the HLA allele-matched URD transplantation, respectively (MSD vs. MRD/URD, P = 0.013; MSD vs. HLA allele-matched URD, P = 0.437). In conclusion, survival in HLA allele-matched URD is equivalent to MSD, but in MRD and mismatched URD is inferior to MSD in patients with CML-CP1 undergoing allo-HSCT using different GVHD prophylaxis regimens according to donor source and degree of HLA matching. Patients undergoing MRD/URD transplantation have an equal quality of life as patients undergoing MSD transplantation.

[Serum α1-acid glycoprotein, imatinib concentration and efficacy in chronic myeloid leukemia patients].

OBJECTIVE: To explore the relationship between serum α1-acid glycoprotein (AGP), disease progression, imatinib plasma trough concentration and efficacy in the patients with chronic myeloid leukemia (CML). METHODS: A total of 112 CML patients were recruited from August 2008 to February 2010 in our hospital. There were 72 males and 40 females with a median age of 39 years old (range: 6 - 76 years old). Among them, 102 patients were in chronic phase, 4 in accelerated phase and 6 in blastic phase. Ninety-nine patients were treated with imatinib while 13 patients received hydroxyurea. Twenty healthy blood donors were designated as the control group. The serum AGP levels of all patients were detected by immuno-turbidimetric assay. And the concentrations of AGP and imatinib were detected in 12 patients before and after 3 months of imatinib therapy respectively. For 84 CML patients, their plasma trough concentrations of imatinib were detected by high performance liquid chromatography-tandem mass spectrometry simultaneously. All patients were divided into 5 groups by efficacy to evaluate the significance of serum AGP and its relationship with imatinib concentration. RESULTS: Serum AGP of no response (NR) group [(1.18 ± 0.26) g/L] was significant higher than that of complete cytogenetic response (CCR), complete hematologic response (CHR) and control group [(0.60 ± 0.21), (0.71 ± 0.17), (0.52 ± 0.15) g/L, all P < 0.05]. Serum AGP of accelerated/blastic phase group [(1.28 ± 0.50) g/L] was significant higher than CCR or control group (P < 0.05). Serum AGP of CHR group was higher than that of control group (P < 0.05). No significant difference existed between CCR, CHR or control group (P > 0.05). There were no significant differences between NR, relapse or accelerated/blastic phase group (P > 0.05). The serum AGP of 12 patients on a 3-month therapy of imatinib were lower than that of patients at pre-treatment [(0.54 ± 0.17) g/L vs (0.83 ± 0.31) g/L, P < 0.01]. The plasma trough concentration of imatinib was (1307 ± 586) µg/L (range: 109 - 3400 µg/L) in 84 patients. And it was positively correlated with the serum level of AGP (r = 0.443, P < 0.01). CONCLUSION: The serum level of AGP can reflect the in vivo loads of leukemic cells for CML patients. There is a positive correlation between the serum level of AGP and the plasma trough concentration of imatinib. Serum AGP can be used as a monitoring index of efficacy for CML patients.

Treatment and outcome patterns of patients with Waldenström's macroglobulinemia: a large, multicenter retrospective review in China.

In this study, we aimed to investigate treatment options and the prognosis of patients with WM in China. This retrospective study included 1141 patients diagnosed with symptomatic WM between January 2003 and December 2019 at 35 tertiary hospitals in 22 provinces of China. Fifty-four patients (7.3%) received monotherapy, 264 (36.0%) received chemoimmunotherapy, 395 (53.8%) received other combination regimens without rituximab, and 21 (2.9%) received ibrutinib. Using a multivariable Cox regression model, age > 65 years old, platelets <100 × 109/L, serum albumin <3.5 g/dl, ß2 microglobulin concentration ≥4 mg/L and LDH ≥250 IU/L predicted poor OS. In summary, our study showed that frontline treatment choices for WM are widely heterogeneous. We validated most of the established prognostic factors in the rIPSS (age >65 years, LDH ≥250 IU/L, ALB <3.5 g/dl and ß2 microglobulin ≥4 mg/L) together with PLT ≤ 100 × 109/L indicate a poor prognosis for patients with WM.

[Association between acute graft versus host disease and lung injury after allogenic hematopoietic stem cell transplantation].

OBJECTIVE: To investigate the characteristics of chest high-resolution computed tomography (HRCT) and pathogenesis of acute graft versus host disease (aGVHD)-induced lung injury after allogenic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Chest HRCT was performed in 47 patients with aGVHD of grade II - IV after allo-HSCT. Twenty-four of the patients underwent different treatment regimens against aGVHD. Before the treatment peripheral blood samples were collected to detect the serum interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). Transbronchial biopsy was performed in 4 patients that failed to recover completely after treatment. Pulmonary function was examined in the patients who survived more than 6 months in every 3 months. RESULTS: Twenty of the 47 patients showed abnormal images by chest HRCT and 17 of the 20 patients were suspected to be with aGVHD-induced lung injury. The HRCT images were characterized by diffused interstitial infiltrate in 5 cases, diffused interstitial and alveolar infiltrate in 7 cases, and diffused interstitial and segmental lobar alveolar infiltrate in 5 cases. Nine cases had bilateral pleural effusion and hydropericardium, including 4 cases accompanied by myocardial hypertrophy. The levels of serum IFN-gamma and TNF-alpha of the patients with lung injury were (6.9 +/- 1.8) microg/L and (400 +/- 102) microg/L respectively, both not significantly different from those of the patients without lung injury [(6.3 +/- 1.2) microg/L and (428 +/- 83) microg/L respectively, P = 0.202, 0.306]. The histopathology of the lung tissue was characterized by disorganization, epithelial cell damage, interstitial fibroplasia, and interstitial T lymphocyte or macrophage infiltrate. The effective rate of treatment for aGVHD-induced lung injury was positively correlated with that for aGVHD (r = 0.771, P = 0.01). Eleven of the 24 patients who survived more than 6 months had abnormal pulmonary function, including 7 out of the 9 patients with aGVHD-induced lung injury and 4 out the 15 patients without aGVHD-induced lung injury. There was no significant difference in the incidence of abnormal pulmonary function between the patients with and without lung injury (P = 0.033). CONCLUSIONS: Lung is one of the target organs of aGVHD. IFN-gamma and TNF-alpha may play a role in the pathogenesis of aGVHD-induced lung injury. Acute GVHD-induced lung injury may progress to late-onset non-infectious lung injury.

[A clinical analysis of severe cyclosporine A-related neurotoxicity after allogenic hematopoietic stem cell transplantation].

OBJECTIVE: To investigate the morbidity, clinical manifestations, and imageology characteristics, and the influencing factors of severe cyclosporine A (CsA)-related neurotoxicity (SNCT) in the patients after allogenic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Finding of SNCT was carried out in 164 allo-HSCT recipients from January 2003 to June 2006. Clinical characteristics were analysed, including precursory symptoms and clinical manifestations. Associations between the onset of SNCT with blood CsA levels, age, transplant types, human leucocyte antigen (HLA) matching, conditioning regimens, antihuman thymocyte globulin (ATG) used in the prevention and treatment for graft-versus-host disease (GVHD) and intravenous corticosteroid used for acute GVHD were analyzed. Statistical analysis was performed with Binary Logistic Regression using SPSS/PC version 11.0. RESULTS: Thirteen patients (7.93%) were identified to have SNCT, including seizures (n = 8, 4.88%), paralysis (n = 6, 3.66%), coma (n = 2, 1.22%), cerebellar ataxia (n = 3, 1.83%) and chondroid encephalomyopathy (n = 1, 0.61%). All the patients had precursory symptoms prior SNCT including headache (n = 8), agitation (n = 4) and hypertension (n = 6). Magnetic resonance imaging (MRI) performed in twelve patients after SNCT showed that eleven patients had signal abnormalities in cerebral cortex and cerebral white matter. Six patients examined with computerized tomography (CT) had no abnormal findings. After extenuation or withdrawal of CsA, ten patients had complete recovery, two had partial recovery and one died of SNCT. Simple effect analysis of Binary Logistic Regression showed that the associations between the onset of SNCT with blood CsA levels, transplant types, HLA matching, ATG used in the prevention and treatment for GVHD and intravenous corticosteroid used for acute GVHD were of statistical significance. The multiple effect analysis of Binary Logistic Regression showed that the associations of the onset of SNCT with blood CsA levels and ATG used had statistical significance and the odds ratio (OR) was 1.007 (P = 0.006) and 6.727 (P = 0.030), respectively. CONCLUSIONS: 91.67% of the allo-HSCT recipients with SNCT have MRI abnormalities. High blood CsA levels and the use of ATG can elevate the risk of the occurrence of SNCT.

[Immunol reconstitution after autologous purified CD34+ cells transplantation in patients with systemic lupus erythematosus].

OBJECTIVE: To investigate the variation of immune index in patients with systemic lupus erythematosus (SLE) treated with autologous purified CD34+ cells transplantation and to clarify the relationship with pathogenesis and prognosis. METHODS: Flow cytometry (FCM) and enzyme linked immunosorbent assay (ELISA) were used to test lymphocyte subsets, C3, C4, CH50, autoantibodies and immunoglobulin for 18 cases of SLE before and after transplantation. RESULTS: The results showed that the ratio of all the T cell subsets reduced obviously in early post graft and recovered gradually in 1 to 3 months after transplantation except CD45RO(+)CD4(+) cells. The levels of serum C3, C4, CH50 increased significantly after transplantation. No case relapsed within one year after transplantation, but 2 patients relapsed one year after transplantation. The levels of the indexes in the patients with relapse were significantly lower than those in the patients with persistent remission, including C(4) in the entire course, CH(50) in the 3rd and 12th month after transplantation and CD(45)RA(+)CD(8)+ cells in the 6th month after transplantation. However, the ratio of CD45RO(+)CD(4)+ cells in the first month after transplantation in the patients with relapse was higher than that in the patients with persistent remission. CONCLUSION: Autologous purified CD(34)+ cells transplantation is effective for treating SLE. Survey of immune indexes before and after transplantation is important to investigate the pathogenesis of SLE. Moreover, these immune indexes can be used to predict therapeutic efficacy of SLE.

[A clinical study of chronic disseminated candidiasis in patients with acute leukemia].

OBJECTIVE: To deepen the understanding of chronic disseminated candidiasis (CDC) in patients with acute leukemia (AL). METHODS: CDC was investigated in 119 AL patients who received induction chemotherapy from August 2004 to May 2005. Clinical manifestations, laboratory tests, imaging modalities, diagnosis and treatment were investigated retrospectively. RESULTS: Three patients (2.5%) were identified to be suffering from CDC. All the three patients had an absolute neutrophil count (ANC) <0. 5 x 10(9)/L for more than 15 days. Two patients had normal ANC when they were diagnosed to have CDC. The common manifestations in these three patients were persistent fever, splenohepatomegalia and percussion pain in hepatic region. Meanwhile, 2 of them were accompanied with cough, expectoration and dyspnoea. The abnormal laboratory test observed during the course of infection in two of them was increase of alkaline phosphatase. Computed tomography scan showed multiple hypodense lesions in the liver and spleen in all the three patients; two of them showed multiple nodular patchy shadows in lungs. Nuclear magnetic resonance imaging showed multiple abnormal signal in liver, spleen and kidneys in one of the patients. Two patients had positive bleed fungal cultures and histologic examination in one of the patients were positive for Candida tropicalis. Two patients received amphotericin B therapy empirically, but it was replaced by amphotericin B colloid dispersion (ABCD) later in one and combined with voriconazole in another because of unresponsiveness to the drug. One patient took a favorable turn after receiving ABCD therapy for 45 d, which was replaced by voriconazole because of the emergence of fever after discontinuation of ABCD. All the three patients received further chemotherapy smoothly after the diagnosis of CDC. CONCLUSION: The diagnosis of CDC remains difficult. Fungal blood cultures and histologic examination have been considered in many studies as the golden standard for the diagnosis of CDC. Amphotericin B is the cornerstone of treatment in patients with CDC and lipid formulations of amphotericin B can be used in CDC patients who are intolerant of or refractory to conventional amphotericin B. Voriconazole has a favorable response for refractory/relapse patients and could be used for second line treatment. The development of CDC in patients with acute leukemia does not preclude further chemotherapy.

[A comparison of the therapeutic effects between related donor and unrelated donor allogeneic hematopoietic stem cell transplantation in treatment of leukemia].

OBJECTIVE: To compare the therapeutic effect for leukemia between related donor hematopoietic stem cell transplantation (RD-HSCT) and unrelated donor hematopoietic stem cell transplantation (URD-HSCT). METHODS: 115 patients received allo-HSCT, of whom 68 received RD-HSCT and 47 received URD-HSCT. All patients were HLA serologically matched. Total body irradiation plus cyclophosphamide was adopted in 56 cases and busulfan, Ara-C, cyclophosphamide conditioning regimen (modified BuCY) in 59 cases. T and B cell reconstitution at different time points was assayed with flow cytometer one year after transplantation. Graft versus host disease (GVHD) and early infection were observed after transplantation. The difference of haematopoietic and immunological reconstitution between the two groups were estimated with Independent-Samples T test. Kaplan-Meier survival analysis model was used to estimate the overall survival and the disease-free survival in the two groups. RESULTS: The time in WBC>1.0x10(9)/L was (13.1+/-2.4) d and (16.3+/-3.0) d (P=0.003), the time in PLT>20x10(9)/L was (14.9+/-6.6) d and (20.2+/-7.3) d (P=0.042), respectively, RD-BMT and URD-BMT. The time with WBC>1.0x10(9)/L was (12.5+/-2.9) d and (13.1+/-4.1) d (P=0.488), the time with PLT>20x10(9)/L was (12.2+/-4.2) d and (15.7+/-7.1) d (P=0.020), respectively, in RD-PBSCT and URD-PBSCT. The reconstitution of CD4+CD3+ at 1st, 3rd, 6th, 9th, 12th month, CD45RA+CD4+ at 1st month and CD8+CD3+ at 3rd month was different significantly between RD-HSCT and URD-HSCT. The incidence of II-IV acute GVHD, chronic GVHD and lethality of GVHD was 45.5% and 52.3%, 45.3% and 63.2%, 6.1% and 15.9%, respectively, in RD-HSCT and URD-HSCT groups. The relapse rate was 18.2% and 11.4%, respectively, in RD-HSCT and URD-HSCT groups. The incidence of early infection was 42.4% and 47.7% (P=0.696), respectively, in RD-HSCT and URD-HSCT groups. The overall survival and the disease-free survival rates at three-year follow-up were (67.8+/-6.9)% and (61.6+/-7.7)% (P=0.133), (62.3+/-6.9)% and (56.8+/-7.9)% (P=0.177), respectively, in RD-HSCT and URD-HSCT groups. CONCLUSION: The therapeutic effect for leukemia is proximate in RD-HSCT and URD-HSCT.

[Clinical analysis of late-onset nephrotic syndrome after allogenic hematopoietic stem cell transplantation].

OBJECTIVE: To investigate the clinical manifestations, pathology, diagnosis, treatment, and pathogenesis of late-onset nephrotic syndrome (NS) after allogenic hematopoietic stem cell transplantation (allo-HSCT). METHODS: NS post-HSCT was investigated in 167 patients with hematopoietic malignancies who survived more than 3 months after allo-HSCT. The clinical manifestations, pathology, diagnosis, and treatment were investigated in a retrospective study. The association of the onset of NS post-HSCT with sex, age, transplant type, conditioning regiments, human leucocyte antigen (HLA) matching, donor-recipient relationship, acute graft versus host disease (aGVHD), chronic graft versus host disease (cGVHD), and cytomegalovirus infection were analyzed. RESULTS: Five patients (2.99%) were diagnosed as with NS post-HSCT, 4 with membranous glomerulonephritis (MGN) and 1 with minimal change disease (MCD). Immunohistochemistry of glomerular lesions revealed that the immunoglobulin (Ig) of immune complex deposition included IgG in 3 patients, IgM in 1 patient, and co-existence of IgG/IgM in 1 patient. Serum ANA was positive in 2 patients and serum IgG and IgM were in high levels in 2 patients. Glucocorticoid combined with cyclophosphamide (CTX) was fundamentally effective treatment for NS post-HSCT. 1 patient got complete response, 3 got partial response, and 1 was stable after the treatment. Binary logistic regression showed that the he onset of NS post-HSCT was not significantly associated with sex, age, transplant type, conditioning regimen, HLA matching, donor-recipient relation, aGVHD, cGVHD and CMV infection. CONCLUSION: The predominant pathological type of NS post-HSCT is MGN, followed by MCD. The pathogenesis of NS post-HSCT may be related to the abnormality of humoral immunity. Glucocorticoid combined with CTX is an effective treatment.

[Non-infectious pulmonary complications after allogeneic hematopoietic stem cell transplantation: analysis of 17 cases].

OBJECTIVE: To analyze the clinical feature, cause, treatment and outcome of late onset non-infectious pulmonary complications (LONIPC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The clinical data of 17 patients with malignant hematological diseases who survived for at least 3 months and suffered from LONIPC after allo-HSCT were retrospectively analyzed. RESULTS: The incidence of LONIPC was 17.7% in allo-HSCT recipients. The median of onset of respiratory symptoms was 6.5 months (3-13.5 months). Seven patients came down with LONIPC during fast tapering of cyclosporine A prophylaxis and 15 patients had already chronic graft versus host disease (cGVHD) before the occurrence of respiratory symptoms. The initial symptoms were non-productive cough and dyspnoea in all patients; five of them had low grade or moderate fever. CT scans revealed patchy ground-glass opacities, irregular patchy consolidation, band-like opacities, and micronodular densities. Histological examination of transbronchial biopsy showed infiltration of lymphocyte and monocytes in interstitium, peribronchiolar fibrosis and alveoli pulmonis obliteration. The response rate of corticosteroids in addition to cyclosporine therapy was 70.6%. Treatment beginning at the early stage was more effective than that beginning late. The mortality rate of LONIPC was 35.3%. Chest CT scanning showed lung fibrosis in the patients with protracted LONIPC. CONCLUSION: The clinical manifestations and radiological changes of LONIPC are non-specific. The diagnosis is made by combination of functional and histological examinations and exclusion of pathogen infection. Examination of transbronchial biopsy is of significance for the diagnosis. LONIPC may be considered as pathognomonic of cGVHD in the lung of patients after allo-HSCT; and cGVHD should be regarded as a useful diagnostic proof for LONIPC. Earlier treatment with corticosteroids and maintenance treatment may result in improved survival and decrease of the fibrotic residue.

[Influence of L-asaraginase and Pegaspargase on Coagulation Function of Adult Patients with Acute Lymphoblastic Leukemia and Analysis of Related Factors].

OBJECTIVE: To analyze the coagulation function and relevant factors of adults patients with acute lymphoblastic leukemia treated with pegasparase (PEG-ASP) or L-asaraginase (L-ASP). METHODS: The clinical features of 153 patients with acute lymphoblastic leukemia (ALL) received L-ASP or PEG-ASP in our hospital from January 2010 to January 2015 year were analyzed retrospectively. Among 153 patients, 108 patients received L-ASP treatment and 45 patients received PEG-ASP treatment. The change of coagulation function and the incidence of complications of 2 treated groups were compared, and the influence of differenent using time of L-ASP on above mentioned factors were analyzed. RESULTS: The age, sex, white blood cell count (WBC) at diagnosis, subtype and risk factors of disease, total effective rate and complication rates showed no significant difference in the 2 groups (P > 0.05). The total infusion of fresh frozen plasma (FFP), cryoprecipitate and fibrinogen (FIB) also showed no significant difference (P = 0.12, 0.65, 0.09). FIB levels decreased slower after treatment of PEG-ASP (9.49 vs 6.90) (P = 0.000) than that after treatment of L-ASP. When L-ASP used at interval, FIB level decreased slower than that of continuous use. However, the risk of bleeding is higher when used at interval early (P = 0.01, 0.013). CONCLUSION: Using PEG-ASP can better monitor the coagulation function than L-ASP. L-ASP used at interval can monitor the coagulation function easily, but its early use may cause an increased incidence of complications.

[Clinical analysis of acute heart failure's risk factor for chronic myelogenous leukemia patient during the early stage of allogeneic hematopoietic stem cell transplantation].

OBJECTIVE: The study was to analyze the acute heart failure's risk factors and clinical characteristics for the patient with chronic myelogenous leukemia (CML) during the early stage (within 100 d) of allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 106 cases of CML received allo-HSCT were retrospectively studied in Nanfang Hospital from May 2003 to May 2013. On the basis of existence or absence of acute heart failure during early stage of allo-HSCT (100 d), the patients were divided into heart failure (15 cases) and control group (91 cases). Using Logistic univariate analysis, Fisher' exact test and Pearson X(2) test, the acute heart failure's risk factors and clinical characteristics of both groups were analyzed. RESULTS: The median occurrence time of acute heart failure was 3 d (1 d before transplantation to 84 d after transplantation). Logistic univariate analysis indicated that the imatinib treatment history and time, and the prophylaxis regimens for GVHD with anti-thymocyte globulin (ATG) were all the poor prognostic factors for acute heart failure. Incidence of hepatic veno-occlusive disease (HVOD), bacterial infection and adverse prognostic events including death in the heart failure group patients were statistically higher than that in control group (P < 0.05). CONCLUSION: Acute heart failure mostly happened in the early stage after allo-HSCT, imatinib treatment and GVHD prophylaxis regimens with ATG are the poor prognostic factors for acute heart failure. The patients of heart failure group seem to have higher incidence of hepatic veno-occlusive disease (HVOD), bacterial infection and deaths.

[Establishment of two-dimensional gel electrophoresis profiles of proteome from CD34(+) hematopoietic stem/progenitor cells].

OBJECTIVE: To investigate the differential expression of proteins in bone marrow (BM) and mobilized peripheral blood (MPB) CD34+ cells. METHODS: Immunomagnetic beads were used to separate and purify CD34+ cells from the BM and the MPB mononuclear cells (MNCs) mobilized by granulocyte colony-stimulating factor (G-CSF) of normal subjects. The whole cell proteins in CD34+ cells were extracted by freeze-thaw lysis, and applied for two-dimensional electrophoresis (2-DE), the results analyzed with image analysis software. RESULTS: The average purity of CD34+ cells was 92.33%+/-2.65% in output, with an average cell number of (1.12+/-0.42) x 10(6). 2-DE techniques were optimized, which yielded satisfactory 2-DE profiles of the proteome, showing the different expressions of the proteins between different CD34+ cells. CONCLUSIONS: Immunomagnetic beads in combination with 2-DE is applicable for research of hematopoietic stem/progenitor cells proteome. There are differences in the protein expressions between BM- and MPB-derived CD34+ cells.

[Analysis of T cell receptor V gamma I-J gamma gene rearrangement in elderly patients with acute leukemia].

OBJECTIVE: To obtain insight into the molecular mechanism of acute leukemia in elderly patients in relation to the clinical features of the disease. METHODS: DNA specimens were obtained from 34 elderly patients with acute nonlymphoblastic leukemia (ANLL), 9 elderly patients with acute lymphoblastic leukemia (ALL) and 10 healthy blood donors. Polymerase chain reaction (PCR) coupled with single-strand conformation polymorphism (SSCP) was performed to detect T cell receptor (TCR) V gamma I-J gamma gene rearrangement. RESULTS: In the 34 elderly ANLL patients, 47.1% (16/34) were found with TCRV gamma I-J gamma gene rearrangement, showing a higher rate of the rearrangement than in younger ANLL patients (P<0.025). TCRV gamma I-J gamma gene rearrangement was identified in 7 (77.8%) of the 9 elderly patients with ALL, and 3 of the identified cases had oligoclonal/ subclonal rearrangement, suggesting a higher rate of oligoclonal/subclonal rearrangement in elderly ALL patients than in younger ALL patients (P<0.01). None of the blood donors was found with TCRV gamma I-J gamma gene rearrangement. The complete remission rate was lower in the elderly ANLL patient with TCRV gamma I-J gamma gene rearrangement than in those without (P<0.05). CONCLUSION: The detection of TCRV gamma I-J gamma gene rearrangement can be of value in assessing the therapeutic effect and making prognostic prediction in elderly patients with acute leukemia.

[Effects of allogeneic hematopoietic stem cell transplantation with very-high-dose conditioning regimen for refractory leukemia].

OBJECTIVE: To explore the regimen-related toxicity (RRT) and therapeutic effects of very-high-dose conditioning regimen combined with induction of graft-versus-leukemia (GVL) effects in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for refractory leukemia with unattainable complete remission (CR) before transplantation. METHODS: Eighteen patients who failed to obtain CR before transplantation received very-high-dose conditioning regimen protocol (experimental group), and 62 patients with acute leukemia with CR or with chronic myeloid leukemia in the chronic phase before transplantation received total body irradiation plus cyclophosphamide (CTX) or modified BuCY (hydroxyurea, busulfan, Ara-C, CTX) protocol (control group). In patients with refractory leukemia who did not develop graft-versus-host disease (GVHD) 30 d after the transplantation, GVL was induced by rapid reduction of the dosage of cyclosporin A or by donor lymphocytic infusion. The incidence and mortality of RRT and the rates of CR, GVHD and leukemia relapse after transplantation were investigated. Kaplan-Meier survival analysis model was used to estimate the disease-free survival (DFS) rate at 3 years post-transplantation. RESULTS: Except for one patient in the experimental group and two in the control group who died of transplantation- related complications, all the other patients obtained hematopoietic reconstitution. The total incidence of RRT was 100% in both groups, involving most frequently the stomach and intestines at the rate as high as 83.3% in the experimental group and 85.5% in the control group. RRT involving the oral cavity occurred in 44.4% and 62.9%, and that involving the bladder in 16.7% and 33.9% of the cases in the experimental group and control group, respectively, all similar between the groups (P=0.823, 0.172 and 0.244, respectively). The RRT mortality was 0 and 5% in the experimental and control groups, respectively (P=0.341). With the exception of one patient who died of infection, all the other patients treated with very-high-dose conditioning regimen obtained CR. The incidences of acute/chronic GVHD were 58.8%/92.6% and 40.0%/55.8%, respectively, in the experimental and control groups. The incidence of leukemia relapse was 11.8% and 18.3%, and DFS at 3 years after transplantation was (61.2+/-12.3)% and (65.0+/-7.4)% (P=0.6311) in the two groups, respectively. CONCLUSION: Consecutive very-high-dose conditioning regimen combined with GVL induction after transplantation can increase the rate of CR and DFS, without increasing RRT incidence and mortality in allo-HSCT for the refractory leukemia with unattainable CR pre-transplantation.