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.

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.

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.

[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.

[Comparison of clinical implications of p16 deletion in childhood and adult B-lineage acute lymphoblastic leukemia].

OBJECTIVE: To investigate and compare the clinical implications of p16 deletion in childhood and adult B-lineage acute lymphoblastic leukemia (B-ALL). METHODS: A total of 129 cases of de novo childhood (73 cases) and adult (56 cases) B-ALL were examined genetically and immunologically using G-banding techniqhe, interphase fluorescence in situ hybridization (I-FISH) and immunophenotyping by flow cytometry, and their clinical data were retrospectively analyzed. RESULTS: Of 73 childhood cases, the prevalences of homozygous deletion, hemizygous deletion and no deletion of p16 were 24.7% (18 cases), 6.8% (5 cases) and 68.5% (50 cases) respectively, and of 56 adult cases, the incidences as of 14.3% (8 cases), 8.9% (5 cases) and 76.8% (43 cases) respectively. The incidence of p16 deletion between the two groups had no significant difference (P = 0.338). In both groups, patients with or without p16 deletion had no significant difference in terms of white blood cells (WBC) count at diagnosis, BM blast percentage, chromosome karyotype, extra-infiltration and CR1 rate. Of note, there were 2 cases, each in childhood and adult, showed no deletion at the time of diagnosis, their p16 deletions occurred at relapse. The deletion of p16 was associated with poor overall survival and event-free survival (EFS) in both childhood and adults. According to the standard of NCI risk stratification, we divided patients of two groups into standard and high risk category respectively, and performed further analysis. The significance of different risk category in children and adults was disparity. The overall survival (OS) rates of deletion and no deletion of p16 were 45.3% and 79.8% (P = 0.006) in children, and 7.7% and 22.6% (P = 0.002) in adults, respectively. EFS rates of deletion and no deletion of p16 were 33.5% and 58.1% (P = 0.008) in children, and 0 and 10.9% (P < 0.01) in adults, respectively. Of the standard risk category in children, OS rates of deletion and no deletion of p16 were 46.8% and 89.3% (P = 0.015) respectively, and EFS rates of deletion and no deletion of p16 as of 40.9% and 82.1% (P = 0.007) respectively. Of the high risk category in children, OS rates of deletion and no deletion of p16 were 41.7% and 67.4% (P = 0.193) respectively, and EFS rates of deletion and no deletion of p16 were 25.0% and 25.6% (P = 0.305) respectively. Of the standard risk category in adults, OS rates of deletion and no deletion of p16 were 20.0% and 46.9% (P = 0.092) respectively, and EFS rates of deletion and no deletion of p16 were 0 and 25.0% (P = 0.062) respectively. Of the high risk category in adults, OS rates of deletion and no deletion of p16 were 0 and 12.4% (P < 0.001) respectively, and EFS rate of deletion and no deletion of p16 was 0 and 4.8%(P < 0.001), respectively. CONCLUSION: This study indicated that deletion of p16 was associated with poor prognosis in both childhood and adult B-ALL, which highlighted an important significance to define the status of p16 in both childhood and adult B-ALL for predicting prognosis and guiding clinical intervention.

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.

[Detection of the JAK2 gene mutation in familial myeloproliferative neoplasm and its clinical significance].

OBJECTIVE: To comprehend the abnormalities of JAK2, c-mp, EPOR, MPW515L/K and TET2 genes in patients with familial myeloproliferative neoplasm (MPN) and their relatives, and to explore mechanism of MPN pathogenesis. METHODS: The complete blood counts of 2 brothers diagnosed with MPN in out hospital and their family members (15 persons in together) were performed, and bone marrow (BM) examinations in patients with abnormal blood count were performed PCR, DNA sequencing were used to evaluate the expression of related genes. RESULTS: The elder brother was diagnosed with essential thrombocythemia (ET), the younger one was polycythemia vera (PV), and others had no clinical manifestation. The third MPN patient was diagnosed based on the blood count and BM examination. The PCR and sequencing results showed that there was JAK2V617F mutation in 3 patients, the elder brother was homozygous, the younger and their father were heterozygous. There were no BCR/ABL fusion gene and c-mp, EPOR, MPW515L/K, TET2 gene mutation in any member. By sequencing the full-length cDNA of familia JAK2 gene, we found that G380A heterozygous mutation was detected in 2 patients, which changed glycine at 127 into aspartic acid, C489T mutation was detected in 13 patients, G2490A mutation in 14, but both of them were synonymous mutations. CONCLUSIONS: JAK2V617F is one of the important indicators to diagnose MPN. The JAK2V617F mutation of this family involves two generations. For newly diagnosed MPN patients, their family members should consider screening, so some familial patients can be diagnosed as early as possible. Gene mutation besides JAK2V627F can be detected by sequencing the full-length of JAK2 gene.

[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.

[Multiprobe fluorescence in situ hybridization panel in detection of the common cytogenetic abnormalities of acute myeloid leukemia].

AIM: To evaluate the value of multiprobe Fluorescence in situ hybridization (FISH) panel in detection of the common cytogenetic abnormalities in acute myeloidleukemia( AML). And to investigate its association with clinical diagnosis, chemotherapy and prognosis. METHODS: Using the multiprobe AML/MDS panel designed to detect upto eight different FISH probes, which was for AML1/ETO transfusion gene, PML-RARα transfusion gene, CBFß/MYH11 transfusion gene, MLL breakapart, P53 deletion,Del(5q), Del(7q), Del(20q), 40 cases of AML were investigated. The conventional karyotype analysis and the in-formation about the treatment responses were also used for assessing. RESULTS: 22 of the 40 AML cases were found to carry 7 types of cytogenetic abnormalities by multiprobe FISH panel including AML1/ETO transfusion gene, PML-RARa transfusion gene, MLL breakapart, P53 deletion, Del (5q), Del7q and trisomy 8. However conventional karyotype analysis only discovered 11 cases with the corresponding cytogenetic abnormalities, the positive ratio was 57.5% in multiprobe FISH panel higher than that in karyotype analysis (27.50%). Patiens with AML1/ETO or PML-RARa transfusion gene are easily to reach CR in the first induction chemotherapy, while the Del(7q), MLL breakapart, complex cytogenetic abnormalities may indicate poor prognosis. CONCLUSION: Mutiprobe FISH panel is more rapid, accurate and effective for detecting the common cytogenetic abnormalities in AML, compared with the conventional karyotype analysis and common FISH analysis.

Analysis of efficacy and cost-effectiveness of high-dose arabinoside versus daunorubicin chemotherapy in older adult patients with acute myeloid leukemia by cytogenetic risk profile: retrospective review from China.

High-dose arabinoside (HiDAC) and daunorubicin (DNR)-based chemotherapy are the primary consolidation treatment options for older adults (50-60 years old) with acute myeloid leukemia in China. We analyzed the event-free survival (EFS) and hospital treatment charges of older adult patients with different cytogenetic risk profiles. In patients with a better/intermediate risk profile, the average total treatment cost of HiDAC was similar to that of DNR (P = 0.11). A 5-year follow-up of patients with better/intermediate cytogenetic risk profiles revealed that the median EFS of patients who received HiDAC was significantly longer than for patients who received the DNR-based regimen (27 vs. 20 months, P = 0.03). Average cost per year of life saved was 18,746.84 USD for HiDAC, compared to 32,733.37 USD for DNR. In contrast, for patients with a poor cytogenetic risk profile, the average total treatment cost for HiDAC was higher than for DNR (P < 0.005). In addition, the median EFS in the HiDAC protocol group was significantly lower than in the DNR group (11 vs. 20 months, P = 0.003). Meanwhile, in this risk group, the average cost per year of life saved was 103,237.70 USD compared to 32,277.93 USD, respectively, in the HiDAC and DNR regimens. We conclude that HiDAC is a more efficacious and cost-effective consolidation treatment regimen in the better/intermediate risk group, while the DNR-based regimen is more cost-effective in the poor risk group.

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.

Simultaneous analysis of telomere length and cell surface antigen in leukemia by multicolor Flow-FISH.

This study was purposed to explore the feasibility of simultaneous analysis of telomere length and cell surface antigen by multicolor Flow-FISH to assess minimal residual disease (MRD) in leukemia. The telomere length in 34 leukemia patients versus 20 normal controls was compared by using Flow-FISH, and the relationship between telomere length and therapeutic effect and prognosis was analyzed preliminarily. As for those patients with follow-up samples, the changes of telomere length combined with surface antigen in different courses of disease were observed by multicolor Flow-FISH. The results indicated that the telomere length of de novo patients was significantly shorter than that of controls except the patients in chronic myeloid leukemia-chronic phase (CML-CP). The shorter telomere, the lower complete remission (CR) rates were observed in acute leukemia cases and the shorter duration of CP before onset of blast phase (BP) occurred in CML cases. The acute leukemia patients showed longer telomere and fewer cells expressed the related antigen after CR. The telomere length of cases with continued CR remained at normal level during remission, and there was no increased expression of the specific antigen. However, the telomere of relapsed cases shortened again after relapse with elevated specific antigen expression. In the relapsed cases, the telomere of related antigen positive cells shortened ahead of telomere length change of the whole cells and morphologic change of bone marrow cells. It is concluded that analysis of telomere length by flow-FISH manifests the significance for monitoring disease conditions, estimating prognosis and guiding therapy in all kinds of leukemia. The simultaneous analysis of telomere length and cell surface antigen by multicolor flow-FISH may monitor abnormal clone or clonal evolution to predict recurrence more sensitively and specifically, and may provide a promising and widely applicable method for monitoring MRD in leukemia.

[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.

Association between acute graft versus host disease and lung injury after allogeneic haematopoietic stem cell transplantation.

OBJECTIVE: To investigate the characteristics of chest high-resolution computed tomography (HRCT) and pathogenesis of acute graft versus host disease (acute GVHD)-induced lung injury after allogeneic haematopoietic stem cell transplantation (allo-HSCT). METHODS: A study of 47 patients with acute GVHD of grades II-IV describes the clinical manifestations and characteristics of chest HRCT of acute GVHD-induced lung injury. Detection of serum interferon gamma (IFNgamma) and tumour necrosis factor alpha (TNFalpha) were performed before the treatment for acute GVHD. Transbronchial biopsy was performed in four patients whose chest HRCT did not recover completely after treatment for acute GVHD. Pulmonary function was measured in patients who survived more than 6 months in every 3 months. RESULTS: Chest HRCT scans were performed in 47 cases and 20 cases showed abnormal in which 17 cases were suspected of acute GVHD-induced lung injury. In 17 patients with acute GVHD-induced lung injury, HRCT revealed diffused interstitial infiltrate in five cases, diffused interstitial and alveolar infiltrate in seven cases, diffused interstitial and segmental lobar alveolar infiltrate in five cases accompanied by bilateral pleural effusion and hydropericardium in nine patients. There was no statistical significance between the levels of serum IFNgamma and TNFalpha in cases with and without lung injury, but the levels of serum IFNgamma and TNFalpha in patients were significantly higher than the healthy group (IFNgamma: p=0.000, TNFalpha: p=0.000). The histopathology of the lung tissue was characterized by disorganization, epithelial cell damage, interstitial fibroplasias and interstitial T lymphocyte or macrophage infiltrate. Forty-seven cases all attained the treatment for acute GVHD, and the total effective rate and the rate of completely remission (CR) were 74.47 and 55.32%, respectively. The total effective rate and the rate of CR in the treatment for acute GVHD-induced lung injury were 94.12 and 58.82%, respectively. The effective rate of treatment for acute GVHD-induced lung injury positively correlated with that for acute GVHD (r=0.771, p=0.001). Three cases in nine cases with lung injury and three cases in 15 cases without lung injury who survived more than 6 months developed late-onset non-infectious lung injury. Eleven patients of 24 patients who survived more than 6 months had abnormal pulmonary function, including seven patients in nine patients with acute GVHD-induced lung injury and four patients in 15 patients without acute GVHD-induced lung injury. There was no difference in the incidence of late-onset non-infectious lung injury, but significance in the incidence of abnormal pulmonary function between cases with and without lung injury (p=0.033, cross-tabs). CONCLUSIONS: These results suggested that the lung might be one of the target organs of acute GVHD and participation of T lymphocyte, macrophage and cytokines such as IFNgamma and TNFalpha might play a role in the pathogenesis of acute GVHD-induced lung injury. Acute GVHD-induced lung injury may progress to late-onset non-infectious lung injury.

[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.

[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.

[Effects of graft compositions on hematopoietic reconstitution and graft-versus-host disease in related donor peripheral blood stem cell transplantation].

OBJECTIVE: To explore the effects of graft composition on hematopoietic reconstitution and graft-versus-host disease (GVHD) in HLA-identical related donor peripheral blood stem cell transplantation (PBSCT) for hematological malignancies. METHODS: The relationship between the number of graft composition and their hematopoietic reconstitution and GVHD in 107 patients with hematological malignancies undergoing HLA-identical related donor PBSCT was retrospectively analyzed. RESULTS: None of the graft composition numbers had correlation with the time of neutrophil reconstitution. There was a negative correlation between the number of mononuclear cells (MNCs) or CD34+ cells and the time of platelet reconstitution (P < 0.05) with the absolute correlation coefficients below 0.4, and so did between the number of CD34+ or CD34+ CD38- cells and the development of acute GVHD (P < 0.05) and their absolute correlation coefficients. Each lymphocyte subset number had no correlation with acute GVHD. There was a positive correlation between the number of CD25+ CD4+, CD3+ or CD4+ CD3+ cells or CD4+ /CD8+ ratio and the development of chronic GVHD (P < 0.05). And the correlation coefficients all exceeded 0.4, more over, CD25+ CD4+ cells number reached up to 0.78. CD34+, CD34+ CD38- cells number had no correlation with chronic GVHD. CONCLUSION: In HLA-identical related donor PBSCT, further increasing infused MNC, CD34+, CD34+ CD38- cells can no more accelerated hematopoietic reconstitution after these cells attained their threshold values, otherwise the incidence of cGVHD might increase due to the increase of the accompanied lymphocytes.