Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients with CMML.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.

Hematopoietic Stem Cell Transplantation Activity in China 2020-2021 During the SARS-CoV-2 Pandemic: A Report From the Chinese Blood and Marrow Transplantation Registry Group.

Between 2020 and 2021, 31,525 hematopoietic stem cell transplantations (HSCTs) were reported to the Chinese Blood and Marrow Transplantation Registry Group throughout mainland China. In this report, we describe the activity and current trends for HSCT in China during the SARS-CoV-2 pandemic. In 2020, a total of 13,415 cases of HSCT were reported from 166 transplantation teams, and 75% (10,042 cases) were allogeneic HSCTs. In 2021, a total of 18,110 cases of HSCT were reported from 174 transplantation teams, and 70% (12,744 cases) were allogeneic HSCTs. Haploidentical donor (HID) transplantation accounted for 63% (7977 cases) of allogeneic HSCTs in 2021. The most common indications for allogeneic HSCT for malignant disease were acute myeloid leukemia (37%) and acute lymphoblastic leukemia (23%), and the largest proportion of nonmalignant disease comprised aplastic anemia (13%). The peripheral blood stem cell source accounted for 41% of HIDs and 75% of matched sibling donors. The BuCy-based regimen (57%) was the most popular conditioning regimen for allogeneic HSCT, followed by the BuFlu-based regimen (28%) and total body irradiation-based regimen (11%). This survey provides comprehensive information about the current activities and might benefit clinical physicians' decision planning for HSCT.

Atorvastatin ameliorated myocardial fibrosis in db/db mice by inhibiting oxidative stress and modulating macrophage polarization.

BACKGROUND: People with diabetes mellitus (DM) suffer from multiple chronic complications due to sustained hyperglycemia, especially diabetic cardiomyopathy (DCM). Oxidative stress and inflammatory cells play crucial roles in the occurrence and progression of myocardial remodeling. Macrophages polarize to two distinct phenotypes: M1 and M2, and such plasticity in phenotypes provide macrophages various biological functions. AIM: To investigate the effect of atorvastatin on cardiac function of DCM in db/db mice and its underlying mechanisms. METHODS: DCM mouse models were established and randomly divided into DM, atorvastatin, and metformin groups. C57BL/6 mice were used as the control. Cardiac function was evaluated by echocardiography. Hematoxylin and eosin and Masson staining was used to examine the morphology and collagen fibers in myocardial tissues. The expression of transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α (TNF-α), interleukin-1 ß (IL-1ß),M1 macrophages (iNOS+), and M2 macrophages (CD206+) were demonstrated by immunohistochemistry and immunofluorescence staining. The levels of TGF-ß1, IL-1ß, and TNF-α were detected by ELISA and real-time quantitative polymerase chain reaction. Malondialdehyde (MDA) concentrations and superoxide dismutase (SOD) ac-tivities were also measured. RESULTS: Treatment with atorvastatin alleviated cardiac dysfunction and decreased db/db mice. The broken myocardial fibers and deposition of collagen in the myocardial interstitium were relieved especially by atorvastatin treatment. Atorvastatin also reduced the levels of serum lactate dehydrogenase, creatine kinase isoenzyme, and troponin; lowered the levels of TGF-ß1, TNF-α and IL-1ß in serum and myocardium; decreased the concentration of MDA and increased SOD activity in myocardium of db/db mice; inhibited M1 macrophages; and promoted M2 macrophages. CONCLUSION: Administration of atorvastatin attenuates myocardial fibrosis in db/db mice, which may be associated with the antioxidative stress and anti-inflammatory effects of atorvastatin on diabetic myocardium through modulating macrophage polarization.

Reactivation of γ-globin expression using a minicircle DNA system to treat ß-thalassemia.

Reactivation of fetal hemoglobin by editing the B-cell lymphoma/leukemia 11A (BCL11A) erythroid enhancer is an effective gene therapy for ß-thalassemia. Using the CRISPR/Cas9 system, fetal γ-globin expression can be robustly reactivated to mitigate the clinical course of ß-thalassemia. In our study, we found that the transfection efficiencies of CD34+ hematopoietic stem/progenitor cells (HSPCs) were significantly and negatively correlated with the length of plasmids and greatly affected by the linearization of plasmids. Furthermore, the transgene expression of minicircles (MC) without plasmid backbone sequences was better both in vitro and in vivo compared with conventional plasmids. Thus, MC DNA was used to deliver the cassette of Staphylococcus aureus Cas9 (SaCas9) into HSPCs, and a single-guide RNA targeting the erythroid enhancer region of BCL11A was selected. After electroporation with MC DNA, an evident efficiency of gene editing and reactivation of γ-globin expression in erythroblasts derived from unsorted HSPCs was acquired. No significant off-target effects were found by deep sequencing. Furthermore, fragments derived from lentiviral vectors, but not MC DNA, were highly enriched in promoter, exon, intron, distal-intergenic, and cancer-associated genes, indicating that MC DNA provided a relatively safe and efficient vector for delivering transgenes. The developed MC DNA vector provided a potential approach for the delivery of SaCas9 cassette and the reactivation of γ-globin expression for ameliorating syndromes of ß-thalassemia.

Basiliximab for steroid-refractory acute graft-versus-host disease: A real-world analysis.

Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR-aGVHD patients treated with basiliximab in a real-world setting. Nine hundred and forty SR-aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second-line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval [CI] 76.5%-82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%-29.6%) and 64.3% (95% CI 61.2%-67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III-IV aGVHD, and high-risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real-world data suggest that basiliximab is safe and effective for treating SR-aGVHD.

Hematopoietic stem cell transplantation activity in China 2019: a report from the Chinese Blood and Marrow Transplantation Registry Group.

Between 2008 and 2019, 58,914 hematopoietic stem cell transplantations (HSCTs) were reported to the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) throughout China. In this report, we focus on 2019 data and describe current trends in HSCT in China. There was continued growth in transplant activity in China, with a rapid increase in haploidentical HSCT. In 2019, a total of 12,323 cases of HSCT were reported from 149 transplant teams, 78% (9597 cases) were allogeneic HSCTs. Haploidentical donor (HID) HSCT accounted for 60% (5771 cases) of allogeneic HSCT. The most common indications for allogeneic HSCT for malignant disease were acute myeloid leukemia (AML) (37%) and acute lymphoblastic leukemia (ALL) (24%), and the largest proportion of non-malignant diseases comprised aplastic anemia (AA) (13%). Multiple stem cell source composed 70% of HID and 28% of MSD, which was typical in China. The BuCy based regimen (59%) was the most popular conditioning regimen for allogeneic HSCT, followed by the BuFlu based regimen (23%) and TBI-based regimen (12%). This survey clearly shows comprehensive information about the current state and recent trends for HSCT in China. Further efforts should be made to obtain detailed information.

Optimizing conditioning regimen with low-dose irradiation or busulfan enables the outcome of transplantation from a 6-7/8 HLA-matched donor comparable to that from an 8/8 HLA-matched unrelated donor in severe aplastic anemia patients under 40 years.

With the dramatic improvements in outcomes following alternative donor hematopoietic stem cell transplantation (HSCT), interest in the use of alternative donors in severe aplastic anemia (SAA) is increasing. We conducted a multicenter prospective study to explore the efficiency and safety of upfront HSCT from a 6-8/8 HLA-matched unrelated donor (MUD) or 6-7/8 HLA-matched related donor (MRD) in acquired SAA patients under 40 years. Between August 2014 and July 2017, 115 patients were enrolled, including 48 (41.7%) patients receiving grafts from an 8/8 MUD, 25 (21.7%) from a 6-7/8 MRD, and 42 (36.5%) from a 6-7/8 MUD. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was higher in the 6-7/8 MUD group than in the 8/8 MUD group (42.9% vs. 12.8%, P=0.001). The corresponding incidence in the 6-7/8 MRD group was comparable to that in the 8/8 MUD group (21.7% vs. 12.8%, P=0.332). There was no significant difference in the incidence of chronic GVHD (24.3%, 13.6%, and 17.9%, P=0.676), graft failure (2.4%, 8.0%, and 6.3%, P=0.551), overall survival (85.7%, 96.0%, and 87.5%, P=0.424), and failure-free survival (83.3%, 88.0%, and 83.3%, P=0.885) among the three groups (6-7/8 MUD, 6-7/8 MRD, and 8/8 MUD). In multivariate analysis, conditioning regimen without low-dose irradiation or busulfan was associated with an inferior failure-free survival (HR=2.973, P=0.042). In conclusion, after an intensified conditioning regimen with additional low-dose irradiation or busulfan, the outcome of HSCT from a 6-7/8 MRD or 6-7/8 MUD is comparable to that from an 8/8 MUD.

[Establishment of A Mixed Chimeric Mouse Model of Allogeneic Bone Marrow Transplantation and Its Influencing Factors].

OBJECTIVE: To establish a mouse mixed chimerism (MC) model of nonmyeloablative allogeneic bone marrow transplantation(allo-BMT) and explore its affecting factors. METHODS: The MC model was established by nonmyeloablative allo-BMT followed by high-dose post-transplant cyclophosphamide (PTCY). 123 mice in the experiments was retrospectively analyzed, and the factors related with the chimerism were explored with the univariate and multivariate logistic regression analysis. A multivariate linear regression was performed by R project to obtain a mathematical model for predicting the chimeric level with relevant affecting factors. RESULTS: The model presented mixed chimerism on day 14 after transplantation, and was characterized by a donor lymphocyte infusion (DLI) which significantly promoted donor engraftment on day 15, but transfplantation of PBS in control group was failed. Among 123 mice, 47 (38.21%) mice were MC, while 76 (61.79%) mice were non-MC in 123 mice, respectively; univariate analysis showed that the baseline body weight of mice (P=0.001, 17.84±1.19 g vs 18.50±0.94 g), total body irradiation(TBI，P=0.048) and the using of cyclophosphamide (P=0.16) were affected the chimeric state of mice, while the number of infusing cells and the time of detection showed no significant effects. Multivariate regression analysis showed that under certain conditions, the body weight of mice on day 0 was an independent factor affecting chimeric levels (OR=0.493, 95% CI 0.307-0.791, P=0.003). Through R project multiple linear regression, the math model was achieved, which was chimerism=6.09-12×weight(g)+80.03×TBI(Gy)-4.4×cell-counts (× 107) +0.38×CTX (mg/kg), R2=0.5841, P<0.001. CONCLUSION: The experiment presents a method for establishing a mixed chimeric mice model after non-myeloablative bone marrow transplantation and constructs a mathematical model with relevant factors affected chimerism status.

Long noncoding RNA HBBP1 enhances γ-globin expression through the ETS transcription factor ELK1.

ß-Thalassemia is an autosomal recessive genetic disease caused by defects in the production of adult hemoglobin (HbA, α2ß2), which leads to an imbalance between α- and non-α-globin chains. Reactivation of γ-globin expression is an effective strategy to treat ß-thalassemia patients. Previously, it was demonstrated that hemoglobin subunit beta pseudogene 1 (HBBP1) is associated with elevated fetal hemoglobin (HbF, α2γ2) in ß-thalassemia patients. However, the mechanism underlying HBBP1-mediated HbF production is unknown. In this study, using bioinformatics analysis, we found that HBBP1 is involved in γ-globin production, and then preliminarily confirmed this finding in K562 cells. When HBBP1 was overexpressed, γ-globin expression was increased at the transcript and protein levels in HUDEP-2 cells. Next, we found that ETS transcription factor ELK1 (ELK1) binds to the HBBP1 proximal promoter and significantly promotes its activity. Moreover, the synthesis of γ-globin was enhanced when ELK1 was overexpressed in HUDEP-2 cells. Surprisingly, ELK1 also directly bound to and activated the γ-globin proximal promoter. Furthermore, we found that HBBP1 and ELK1 can interact with each other in HUDEP-2 cells. Collectively, these findings suggest that HBBP1 can induce γ-globin by enhancing ELK1 expression, providing some clues for γ-globin reactivation in ß-thalassemia.

Preconditioning with fludarabine, busulfan and cytarabine versus standard BuCy2 for patients with acute myeloid leukemia: a prospective, randomized phase II study.

To compare the efficacy and toxicity of a novel regimen called FBA, consisting of fludarabine, busulfan, and cytarabine, with the standard BuCy2 regimen for younger adult patients with acute myeloid leukemia, we conducted a prospective randomized phase II study. Patients in complete remission were randomly assigned to receive either the FBA (n = 56) or the BuCy2 regimen (n = 55). The difference in 100-day transplant-related mortality (TRM) was not statistically significant between the two arms (1.79% for FBA versus 5.45% for BuCy2, P = 0.260), as were the cumulative incidences of relapse, TRM, overall survival (OS) and event-free survival (EFS) at 3 years. However, the 100-day cumulative incidences of grades II-IV and III-IV acute graft-versus-host disease (aGVHD) were lower in the FBA group [(8.93% versus 21.86%, P = 0.032) (1.79% versus 9.09%, P = 0.025)]. The 3-year GVHD and relapse-free survival (GRFS) was 31.20% for the FBA group and 14.96% for the BuCy2 group (P = 0.004). The incidences of diarrhea and severe oral mucositis within the first 30 days post-transplantation were lower in the FBA group [(28.57% versus 65.45%; P < 0.001) (51.79% versus 70.91%; P = 0.039)]. In conclusion, allogenic transplantation with the FBA regimen achieved similar TRM, relapse rate, OS and EFS, as that with the BuCy2 regimen but with less frequent and less severe complications in early stage after transplantation and a trend toward higher GRFS.

Microarray profiling and co-expression network analysis of the lncRNAs and mRNAs associated with acute leukemia in adults.

Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are common types of acute leukemia in adults and cause low survival rate and poor outcome after 5 years despite high rates of complete remission (CR) with modern chemotherapeutic regimens. To understand the distinct mechanisms in leukemogenesis for ALL and AML and to identify markers for diagnosis and treatment, lncRNA and mRNA expression profiles of AML and ALL patients and healthy controls were generated using microarray analysis. For comparison, the differentially expressed mRNA functions were annotated using gene ontology (GO) and pathway analysis. The microarray revealed that 1011 lncRNAs and 2656 mRNAs differed in AML patients and 6069 lncRNAs and 5338 mRNAs differed in ALL patients from those in healthy controls. The GO terms and KEGG pathway annotation data revealed that the olfactory receptor activity, G-protein coupled receptor activity and olfactory transduction-related genes were significantly associated with AML and ALL. Co-expression network analysis indicated that 108 lncRNAs and 85 mRNAs were included in the co-expression network. This study is the first to explore genome-wide lncRNA expression and co-expression with mRNA patterns in AML and ALL using microarray technology and could provide basic information for new biomarkers or treatment targets to alleviate AML and ALL.

Up-regulation of P2X7 receptors mediating proliferation of Schwann cells after sciatic nerve injury.

Peripheral nerve injury (PNI) is a common disease, which results in a partial or total loss of motor, sensory and autonomic functions, leading to a decrease in quality of life. Schwann cells play a vital role in maintaining the peripheral nervous system and in injury and repair. Using immunohistochemistry, Western blot, calcium assay and bromodeoxyuridine (BrdU) proliferation assay, the present study clearly demonstrated that P2X7 receptors (R) were expressed in myelinating and non-myelinating Schwann cells in longitudinal sections of sciatic nerves. After sciatic nerve injury (SNI), P2X7R expression in Schwann cells of injured sciatic nerves was significantly up-regulated during the early days of SNI. Double immunofluorescence of proliferating cell nuclear antigen (PCNA) and P2X7R implied that P2X7R may be involved in proliferation of Schwann cells. Further experiments on primary cultures of Schwann cells showed that P2X7R are functionally expressed in Schwann cells of rat sciatic nerves; ATP via P2X7R can promote Schwann cell proliferation, possibly via the MAPK/ERK intracellular signalling pathway. Other possible roles of P2X7R on Schwann cells are discussed.

Characteristics of acute myeloid leukemia with myelodysplasia-related changes: A retrospective analysis in a cohort of Chinese patients.

We retrospectively analyzed 449 patients with AML under the WHO classification of AML 2008 and probed implications of this classification in diagnosis and treatment of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) among them. The clinical presentations, biological features, treatments, and prognosis of patients diagnosed with AML-MRC were analyzed and compared with those of AML not otherwise specified (AML-NOS). In all patients, 115 (25.6%) were diagnosed as AML-MRC including 64 males and 51 females with median onset age of 48 years (range from 17 to 78). Their complete remission (CR) rate was 60.9% and relapse rate was 57.1%. The observed median overall survival (OS) and disease-free survival (DFS) were 10 and 5 months, respectively, which was significantly shorter than those of AML-NOS patients (P < 0.05). The prognosis of AML-MRC patients with myelodysplastic syndrome (MDS)-related cytogenetics sole was similar to those with history of MDS or myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Patients with MDS-related cytogenetic abnormalities and/or history of MDS or MDS/MPN predisposed significantly shortened CR, OS, and DFS than AML-MRC patients with only multilineage dysplasia (MLD) and AML-NOS patients (P < 0.05). Multivariate analysis showed that age, cytogenetics, and history of MDS or MDS/MPN were independent prognostic factors. Patient diagnosed as AML-MRC presented distinctive clinical and biological features. Presence of MLD does not change the prognosis.

Allogeneic peripheral blood stem cell transplantation is a promising and safe choice for the treatment of refractory/relapsed acute myelogenous leukemia, even with a higher leukemia burden.

The prognosis of patients with refractory/relapsed acute myelogenous leukemia (rAML) is poor. Recent studies have shown that more transplant centers are choosing allogeneic peripheral blood stem cell transplantation (allo-PBSCT) for recipients, even with a higher leukemia burden. The purpose of the present study is to evaluate the outcome of rAML patients undergoing allo-PBSCT and to determine whether the disease status can predict the post-transplantation survival. The outcome of 58 patients (median age, 34 years; range, 14 to 52) with rAML who underwent allo-PBSCT in our institution from January 2000 until September 2011 was retrospectively studied. Thirty-three patients had complete remission (CR) before PBSCT, whereas 25 patients had no remission. Donors were matched related (31 patients) and unrelated (27 patients). Reduced-intensity conditioning was used for 18 patients with rAML, and myeloablative conditioning was used for others. Sixty-six consecutive non-rAML patients (median age, 33 years; range, 15 to 51) who received an allo-PBSCT at the same period were used as a control. Full donor-type engraftment was achieved in all patients. After a median follow-up of 61 months, the 5-year overall survival of rAML patients was 54.21% ± 7.06%, which was lower than non-rAML patients (71.82% ± 6.4%, P = .0386). However, the 5-year event-free survival for rAML and non-rAML patients had no statistical significance (53.54% ± 6.87% versus 62.07% ± 6.78%, P = .2626). The 5-year overall survival between rAML patients who had CR and no remission before PBSCT was 56.06% ± 9.2% and 51.85% ± 10.83%, respectively (P = .6408). These data demonstrate that allo-PBSCT is a promising and safe choice for the treatment of rAML, and the results were partially due to the rapid tapering of immunosuppressants in the early stage after PBSCT and prophylactic donor lymphocyte infusion. Meanwhile, the patients who did not achieve CR before PBSCT could also benefit from allo-PBSCT.

[Clinical and laboratory characteristics of hematological diseases associated with eosinophilia].

OBJECTIVE: To analyze the clinical and laboratory characteristics of hematological diseases associated with eosinophilia. METHODS: Karyotype analysis was performed by direct method and/or short-time culture of bone marrow cells for R-banding. Fluorescence in situ hybridization (FISH) was performed using PDGFRα, PDGFRß and FGFR1 break-apart probes. RESULTS: The clinical and hematological findings of 44 patients were diagnosed as hematological diseases associated with eosinophilia. Abnormal karyotypes were detected in 6 cases (13.64%) with karyotyping. The efficiency of the detection of abnormal clone was markedly increased to 29.55% (13/44) with FISH techniques, including 7 cases with FIP1L1-PDGFRα (F/P, 15.91%), 3(6.82%) PDGFRα rearrangement, 2 (4.55%) aberrant PDGFRß gene and 1(2.27%) FGFR1 rearrangement. Patients being PDGFRα, PDGFRß or FGFR1 positive (13 cases) or negative (31 cases) showed predominant difference in clinical and laboratory features. The incidence of gut involvement, the absolute count of eosinophils in peripheral blood and the percentage of immature eosinophils in bone marrow were significantly increased in positive patients (P < 0.05). CONCLUSIONS: The hematological diseases associated with eosinophilia are characterized by unique clinical and laboratory features. Karyotyping should be a routine approach to detect the abnormal clone in these diseases. Screening for PDGFRα, PDGFRß and FGFR1 gene with FISH can provide more genetic information.

[Prognostic significance of EBMT score for chronic myeloid leukemia patients in allogeneic stem cell transplantation].

OBJECTIVE: To analyze the risk factors of allogeneic stem cell transplantation (allo-SCT) for chronic myeloid leukemia (CML) in an attempt to avoid transplant risks. METHODS: A total of 121 CML patients received allo-SCT were analyzed retrospectively. The risk analysis was based on the EBMT score (gratwohl score) which included donor type, age of patients, disease status before transplantation, donor/recipient sex match and time interval between diagnosis to allo-SCT. Patients were divided into 3 risk groups based on their EBMT score: low risk (score 0-2), intermediate risk (3-4) and high-risk (5). RESULTS: The median follow-up duration was 37 (1 - 126) months. The estimated 5-year overall survival (5 y-OS), non-relapse mortality (5 y-NRM) and relapse rate (5 y-RR) were (56.8 ± 5.0)%, (35.6 ± 4.9)% and (12.9 ± 3.7)%, respectively. The 5y-OS, NRM and RR were (66.0 ± 6.1)%, (28.8 ± 6.0)% and (7.8 ± 3.3)% in the low risk group being significantly superior to both intermediate-risk \[(47.2 ± 8.7)%, (43.6 ± 8.5)% and (18.7 ± 8.1)%\] and high-risk group \[(16.8 ± 15.2)%, (66.7 ± 25.5)% and (50.0 ± 25.0)%\] (P = 0.0015, 0.045 and 0.0053 for OS, NRM and RR respectively). CONCLUSION: The EBMT risk score can effectively predict the overall outcome, relapse and transplant-related mortality of allo-SCT for CML patients.

[Relationship between the absolute lymphocyte count before or after autologous hematopoietic stem cell transplantation and the prognosis in patients with non-Hodgkin's lymphoma].

OBJECTIVE: To evaluate the relationship of the absolute lymphocyte count (ALC) before or after autologous hematopoietic stem cell transplantation (AHSCT), and the infused CD34(+) count with the relapse, disease-free survival (DFS), overall survival (OS) in non-Hodgkin's lymphoma (NHL) patients. METHODS: A retrospective analysis of the relationship of the absolute lymphocyte count before (ALC-Pro) or 15 days after (ALC-15) the AHSCT, and the infused CD34(+) cell count with the relapse, DFS, OS of NHL. RESULTS: ALC-Pro and ALC-15 were related to NHL relapse. The patients with high levels of ALC-Pro and ALC-15 had lower relapse rate. By Kaplan-Meier curve and COX multi-variable regression analysis, it was found that both ALC-Pro and ALC-15 were factors associated with the DFS. Patients infused high levels of CD34(+) cells had longer DFS. Patients with high levels of ALC-Pro, ALC-15, CD34(+) counts had longer OS. CONCLUSION: ALC-Pro, ALC-15 and CD34(+) counts were significant in predicting relapse, DFS and OS for patients with NHL.

[Clinical and laboratory study of myleodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) with PDGFRß abnormalities].

OBJECTIVE: To explore the clinical and laboratory characteristics of myleodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) with PDGFRß abnormalities. METHODS: Chromosome specimens were prepared directly and/or short-time culture of bone marrow cells. Karyotyping was performed with R-binding technique. Fluorescence in situ hybridization (FISH) was performed using PDGFRß, PDGFRα, FGFR1 break-apart probes and whole chromosome 5 and 12 painting probes, respectively. The expression of JAK2 V617F was measured with quantitative PCR. RESULTS: The clinical and hematological findings of 27 patients were compatible with diagnosis of MDS/MPN. PDGFRß rearrangement was detected in 4 patients with D-FISH, and 2 of which were confirmed as t(5;12) by chromosome painting. PDGFRα, FGFR1 and JAK2 V617F mutation were not detected in these 4 PDGFRß positive MDS/MPN patients with. CONCLUSIONS: PDGFRß gene rearrangement may be detected in some MDS/MPN patients. FISH is a convenient and reliable approach to detect PDGFRß gene.

[Reduced intensity conditioning regimen for related and unrelated allogeneic peripheral blood hematopoietic stem cell transplantation in chronic myeloid leukemia.].

OBJECTIVE: To evaluate the overall efficacy and transplant-related mortality (TRM) of related and unrelated allogeneic peripheral blood hematopoietic stem cell transplantation (allo-PBSCT) in chronic myeloid leukemia (CML) patients conditioned with fludarabine-busulfan (FB) reduced intensity regimen. METHODS: Forty-four patients received FB (Flud 30 mgxm(-2)xd(-1) x 5 d, BU 4 mgxkg(-1)xd(-1) x 3 d) conditioning followed by allo-PBSCT. Of them, 29 patients were transplanted with related donor and 15 unrelated donor (URD). All patients received mycophenolate mofetil (MMF), CsA and MTX for acute GVHD (aGVHD) prophylaxis. 5 mg/kg rabbit-antithymocyte globulin (ATG-Fresenius) was incorporated in 15 URD recipients. RESULTS: All patients were successfully engrafted. The median times to ANC above 0.5 x 10(9)/L in related (RG) and unrelated groups (URG) were 13.7 (9 - 18) d and 13.6 (12 - 17) d, and PLT above 20 x 10(9)/L were 15.3 (9 - 20) d and 14.7 (10 - 26) d, respectively. Two patients in RG. 1 in URG developed graft rejection 5 - 8 months after transplantation. One of the two patients in RG received second transplantation and engrafted. The cumulative incidence of aGVHD and cGVHD were 13.8% (4/29) and 46.4% (13/28) in RG, and were 33.3% (5/15) and 57.1% (8/14) in URG respectively. Two patients in RG relapsed after transplantation, and obtained CR again after donor stem cell infusion (DSI). Median time of follow-up was 34.7 (2 - 73) months. Thirty-four patients were alive and 10 died. The main causes of death were IP, GVHD, graft rejection and infection. The 5-year overall survival (OS) probability was 77.0%, and the disease-free-survival (DFS) was 73.9%, of which, 79.0% and 74.1% were in RG, and 73.3% and 73.3% in URG, respectively. CONCLUSIONS: Fludarabine-busulfan based reduced intensity conditioning for allo-PBSCT with either related or unrelated donors is a safe, less toxic and curative approach to CML.