Efficacy and Safety of Allogeneic Hematopoietic Stem Cell Transplantation with Decitabine-containing Regimen in Myelodysplastic Syndromes and Myelodysplastic Syndromes Transformed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with decitabine (Dec)-conditioning regimen in the treatment of myelodysplastic syndrome (MDS) and MDS transformed acute myeloid leukemia (MDS-AML).@*METHODS@#The characteristics and efficacy data of 93 patients with MDS and MDS-AML who received allo-HSCT in our center from April 2013 to November 2021 were retrospectively analyzed. All patients were administered by myeloablative conditioning regimen containing Dec (25 mg/m2 /d×3 d).@*RESULTS@#Among the 93 patients, 63 males and 30 females, were diagnosed as MDS（n ＝77）, MDS-AML（n ＝16）. The incidence of I/II grade regimen-related toxicity (RRT) was 39.8%, and III grade RRT was only found in 1 patient (1%). Neutrophil engraftment was successful in 91 (97.8%) patients after a median neutrophil engraftment time of 14 (9-27) days; Successful platelet engraftment was achieved in 87 (93.5%) patients, with a median engraftment time of 18 (9-290) days. The incidence of acute graft versus host disease（aGVHD） and grade III-IV aGVHD was 44.2% and 16.2%, respectively. The incidence of chronic graft versus host disease（cGVHD） and moderate-to-severe cGVHD was 59.5% and 37.1%, respectively. Of the 93 patients, 54 (58%) developed posttransplant infections, among which lung infection (32.3%) and bloodstream infection (12.9%) were the most common. The median follow-up after transplantation was 45 (0.1-108) months. The 5-year overall survival (OS) rate, disease-free survival (DFS) rate, treatment-related mortality, and cumulative incidence of relapse were 72.7%, 68.4%, 25.1%, and 6.5%, respectively. And the 1-year graft-versus-host disease/relapse-free survival rate was 49.3%. The patients in different group of relative high-risk prognostic scoring or low-risk prognostic scoring, with or without poor-risk mutation(s), with mutations number ≥3 or <3 had similar 5-year OS rate (more than 70%). Multivariate analysis showed that the incidence of grade III-IV aGVHD was the independent risk factor affecting OS（P =0.008）and DFS (P =0.019).@*CONCLUSION@#Allo-HSCT with Dec-conditioning regimen is feasible and effective in the treatment of patients with MDS and MDS-AML, especially those in high prognostic risk and with poor-risk mutations.

A multicenter retrospective study on the real-world outcomes of autologous vs. allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphoma in China / 中华医学杂志(英文版)

BACKGROUND@#There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China.@*METHODS@#From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n  = 72) or allo-HSCT (n  = 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups.@*RESULTS@#Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P = 0.001), chemotherapy-resistant disease (41% vs. 8%, P = 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2-143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300).@*CONCLUSIONS@#Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.

Analysis of Factors Influencing Autologous Peripheral Blood Stem Cells Mobilization in Patients with Lymphoma and Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To analyze the factors influencing the mobilization of autologous peripheral blood stem cells (auto-PBSCs) in patients with lymphoma and multiple myeloma, and provide reference for optimizing the autologous stem cell mobilization regimen.@*METHODS@#Clinical data of 33 multiple myeloma and lymphoma patients received auto-PBSCs mobilization in our center from January 2015 to December 2018 were collected, the correlation of mobilization failure rate with gender, age, courses of chemotherapy before mobilization, does of recombinant human granulocyte colony stimulating factor (rhG-CSF), type of disease, and chemotherapy regimen were retrospectively analyzed.@*RESULTS@#Type of disease and course of pre-mobilization chemotherapy could affect the mobilization failure rate (P0.05).@*CONCLUSION@#Multi-course chemotherapy before collection and lymphoma patients are poor factors negatively impacting on auto-PBSCs mobilization.

Clinical research of severe aplastic anemia with pulmonary invasive fungal infection after transplantation / 解放军医学杂志

Objective To study the clinical characteristics of pulmonary invasive fungal infection (IFI) in patients with severe aplastic anemia (SAA) after allogeneic hematopoietic stem cells transplantation (allo-HSCT).Methods The clinical data of 30 SAA patients received allo-HSCT in 307 Hospital of PLA from Jan.2012 to Jan.2015 were analyzed retrospectively.All the SAA patients accepted combined bone marrow with peripheral blood stem cells transplantation,and then the clinical features and outcome of pulmonary IFI after transplantation were analyzed.Results Six (20％) of the 30 SAA patients were complicated by IFI after transplantation,including 4 males and 2 females with average age of 18.3(6-42) years.All the 6 patients showed characteristic imaging changes in pulmonary,of which 3 cases were definitely diagnosed by bronchoscopy or sputum fungal culture,and the other 3 cases by imaging and clinical manifestation.Four cases were cured and 2 cases died after first-line antifungal therapy,the total mortality was 33.3％.Conclusion High incidence of complicated IFI in SAA patients after allo-HSCT may lead to the high mortality,it's necessary to give an empiric antifungal therapy as earlier as possible.

Clinical study of decitabine-intensified conditioning regimen prior to hematopoieticstem cell transplantation in the treatment of refractory/relapse acute myeloid leukemia / 军事医学

Objective To observe the treatment results of 44 consecutive patients with refractory/relapse acute myeloid leukemia( AML) not in remission who received allogeneic hematopoietic stem cell transplantation ( allo-HSCT ) following decitabine (DAC)-intensified conditioning regimen (18) and idarubicin(IDA)-intensified conditioning regimen (26). Methods We conducted a retrospective study to evaluate the outcome of 44 consecutive patients with refractory/relapse AML not in remission who received allo-HSCT from 2009 July to 2016 May.Eighteen of them were given DAC-intensified conditioning regimen and 26 of them were given IDA-intensified conditioning regimen prior to allo-HSCT.The effects of DAC and IDA intensified conditioning regimen on the patients ' engraftment, transplant-related mortality, survival and occurrence of graft versus host disease(GVHD)were analyzed.Results and Conclusion In the DAC group, 7(38.9％) patients had acute GVHD (aGVHD).Among them,2 patients had grade Ⅰ aGVHD,5 patients had grade Ⅱ aGVHD.In the IDA group, 16(61.5％)patients had aGVHD.Among them,9 patients had grade Ⅰ aGVHD, 6 patients had grade Ⅱ aGVHD and 1 patient had grade ⅢaGVHD.In the IDA group, 9 of 26(34.6％) patients experienced leukemia relapse , all of them died due to the lack of effective therapies .In the DAC group, 4 of 18(22.2％) patients experienced leukemia relapse, 2 of them got long-term survival throughout salvage therapies .For the DAC group and IDA group , the 1-year probabilities of overall survival (OS) and leukemia-free survival (LFS) were 65.0％ versus 57.7％ (P=0.602) and 53.5％versus 57.7％(P=0.910), respectively.DAC-intensified conditioning regimen before allo-HSCT in the treatment of refractory/relapse AML is safe and effective.

Relationship between NK Cell Reconstitution and aGVHD after Allo-HSCT / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between NK cell count/activity and acute graft-versus-host disease (aGVHD) in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>A total of 26 patients who had undergone allo-HSCT from January to July 2015 were enrolled in this study. The NK cell count/activity in the peripheral blood of recipients on day 30 after allo-HSCT were monitored by using 4-color flow cytometry. The incidence of aGVHD in patients was evaluated by clinical manifestation combinating with related pathologic indicators, and the relationship between NK cell count/activity and aGVHD were analyzed.</p><p><b>RESULTS</b>In the aGVHD group and the no-aGVHD group, the NK cell count and activity on days 30 after allo-HSCT were 655±216 cells/µl vs 1169±372 cells/µl(P=0.002) and 7.3±3.6% vs 9.0±3.6% (P=0.008). In the II-IV grade aGVHD group and the 0-I grade aGVHD group, the NK cell count/activity were 617±220 cells/µl vs 1081±399 cells/µl (P=0.001) and 4.2±1.7% vs 8.3±3.5%(P=0.001). As compared with the 0-I grade aGVHD group, patients in the II-IV grade aGVHD group had higher relapse rate (57% vs 5%)(P=0.010) , lower 1-year progression-free survival(PFS) rate (43% vs 84%)(P=0.010).</p><p><b>CONCLUSION</b>NK cell count/activity on day 30 after allo-HSCT were closely relates with aGVHD, which may be a potential marker for aGVHD and can provide a new target for aGVHD therapy.</p>

Clinical Features and Prognosis of t(8;21) AML Patients in China: A Multicenter Retrospective Study / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To summarize the clinical characteristics of peripheral blood, immune phenotypes, fusion genes and cytogenetics of patients with t(8;21) acute myeloid leukemia(AML) through the retrospective analysis of 586 patients with t(8;21) AML from 15 blood disease research centers in Northern area of China.</p><p><b>METHODS</b>The factors affecting prognosis of patients with t(8;21) AML were investigated by using univariate and multivariate COX regression.</p><p><b>RESULTS</b>The immune type of t(8;21) AML patients was mainly with HLA-DR, CD117, CD34, MPO, CD38, CD13and CD33(>95%), part of them with CD19and CD56; the most common accompanied mutation of t(8;21) AML patients was C-KIT mutation (37.8%); in addition to t(8;21) ectopic, the most common chromosomal abnormality was sex chromosome deletions (38.9%). The univariate analysis revealed a significant survival superiority of OS and PFS in t(8;21) AML patients of WBC≤3.5×10/L without C-KIT mutation, the newly diagnosed ones achieved HSCT(P<0.05), only survival superiority on OS in t(8;21) AML patients with extramedullary infiltration and CD19 positive; the results of multivariate analysis showed a significant survival superiority on OS and PFS in t(8;21) AML patients with WBC≤3.5×10/L(P<0.05).</p><p><b>CONCLUSION</b>The clinical features of t(8;21) AML patients in China are similar to those in other countries, WBC≤3.5×10/L is a good prognostic factor while the C-KIT mutation is a poor one in t(8;21) AML patients.</p>

Analysis of Risk Factors for Cytomegalovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the incidence of cytomegalovirus infection and related risk factors after allogeneic hematopoietic cell transplantation and to develop a rational strategy for the preemptive treatment of CMV infection.</p><p><b>METHODS</b>The clinical data of 398 patients undergoing allogeneic hematopoietic cell transplantation from December 2011 to December 2014 were analyzed retrospectively by using a Kaplan Meier analysis and Logistics model.</p><p><b>RESULTS</b>Out of 398 patients 233 developed post-transplant CMV infection (58.5%). Univariate analysis showed that HLA mismatch, ATG administration, acute graft versus host disease (aGVHD), using prednisone ≥ 1 mg/kg body weight or equivalent were associated with increase of CMV infection. Multivariate analysis showed that HLA mismatch (HR = 2.765, P = 0.000), ATG administration (HR = 3.866, P = 0.000), using prednisone ≥ 1 mg/kg body weight or equivalent (HR = 4.767, P = 0.000) also were associated with increase of CMV infection.</p><p><b>CONCLUSION</b>HLA mismatch, ATG administration, using prednisone ≥ 1 mg/kg are risk factors for CMV reaction.</p>

Establishment of Humanized Mouse Model by Using Transplantation of Mobilized Peripheral Blood Stem Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the hematopoietic reconstitution in immunodeficiency NPG(TM) mice after transplantation of G-CSF-mobilized peripheral blood CD34(+) hemopoietic stem cells.</p><p><b>METHODS</b>CD34(+) cells were isolated from peripheral blood stem cells (PBSC) by magnetic activated cell sorting (MACS), and then were transplanted into NPG(TM) mice irradiated with sublethal dose of X ray by marrow cavity transplantation. The hemogram of mice after transplantation for 2, 4 weeks was observed; human cell populations (CD45(+), CD19(+)) in the peripheral blood of mice were dynamically analyzed by flow cytometry (FCM) at 4, 6, 8, 10 and 12 weeks after transplantation. Until the planned harvest at the 12 week after transplantation, the CD45(+), CD19(+) level in bone marrow, liver, spleen from each mouse were detected by flow cytometry; the expression of human Alu gene in the bone marrow cell of mouse was detected by PCR.</p><p><b>RESULTS</b>The purity of CD34(+) cells accounted for 96.3%; after irradiation, the nucleated cells and megalokaryocytes in the marrow cavity of NPG mice were reduced significantly or were lost, and reached the myeloablative effect. At week 4 after transplantation, components of blood cells in peripheral blood of transplanted mice were recovered to the level before irradiation; all the mice survived, human CD45(+), CD19(+) cells were found by FCM in the peripheral blood of all the surviving mice in transplantation group at week 4, 6, 8, 10, 12 after the transplantation; at the 12th week, the human Alu gene could be detected in the bone marrow of all the mice in transplantation group.</p><p><b>CONCLUSION</b>The human-mouse chimeric model is successfully established in irradiation-induced NPG mouse by transplantation of CD34(+) HSC from G-CSF-mobilized peripheral blood via marrow cavity.</p>

Construction of mouse VCAM-1 expression vector and establishment of stably transfected MSC line C3H10T1/2 / 中国实验血液学杂志

This study was aimed to construct the mouse VCAM-1 expression vector, to establish the stably transfected MSC line and to investigate the effect of VCAM-1-modified mesenchymal stem cells (MSC) on the immunological characteristics of MSC. The cDNA of murine VCAM-1 gene was amplified by RT-PCR from the total RNA isolated from the mouse spleen; then the cDNA was inserted into the retrovirus vector PMSCVmigr-1; the recombinant plasmid was confirmed by restriction endonuclease experiments and sequencing, then designated as PMSCVmigr-1-mVCAM-1; the recombinant plasmid PMSCVmigr-1-mVCAM-1 was transfected into 293 cells by lipofecamin and the supernatant was collected to transfect MSC cell line (C3H10T1/2). Moreover, VCAM-1 expression on MSC was evaluated by FACS. Furthermore, the inhibitory effect of VCAM-1-MSC on lymphocytic transformation was tested by (3)H-TdR incorporation assay. The results indicated that the successful construction of recombinant retroviral expression plasmid of mouse VCAM-1 was confirmed by digesting and sequancing. After transfection of MSC with retroviral supernaptant, the high expression of VCAM-1 on MSC could be detected by flow cytometry. The MSC high expressing VCAM-1 could significantly inhibit the proliferation of Con A-inducing lymphocytes in dose-depentent marrer. It is concluded that recombinant retroviral encoding VCAM-1 (PMSCVmigr-1-mVCAM-1) has been successfully constructed and mouse VCAM-1 has been stably expressed in C3H10T1/2. MSC over-expressing VCAM-1 show more potent immunosuppressive effect on cellular immune reaction in vitro. Our data laid a foundation for the subsequent studying the effect of VCAM-1 transfecting into MSC on immune related disease study.

Effectiveness of allogeneic peripheral blood stem cell transplantation in 23 patients with myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the outcome of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) for myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>Twenty-three patients with MDS received G-CSF mobilized HLA-identical sibling allo-PBSCT. The numbers of mononuclear cells (MNC) and CD34+ cells were 8. 25 (4.50 -22.36) x 10(8)/kg and 5.59 (1.57 - 12.22) x 10(6)/kg respectively. CsA and shorten course MTX were used for graft-versus-host disease (GVHD) prophylaxis and MMF was given on + 1 d - +28 d posttransplantation.</p><p><b>RESULTS</b>Among 23 patients, 22 achieved hematopoietic recovery. The median time of ANC > 1.0 x 10(9)/L and BPC > 50 x 10(9)/L were + 13 (+ 11 - +17) days and + 30 (+13 + 102) days respectively. Two patients died of transplant related complications and three died of disease relapse, while 18 patients survived. Kaplan-Meier analysis showed disease free survival and relapse rate were (77.8 +/- 8.7)% and (14.4 +/- 7.5)% respectively.</p><p><b>CONCLUSION</b>Allo-PBSCT is an effective treatment for MDS patients.</p>

Clinical study on anti-leukemia effect mediated by dentritic cells / 中国实验血液学杂志

Immunotherapy of tumor is extensively attentioned as an important part of combined therapy of tumor in recent years. Dendritic cell (DC) is the most powerful antigen presenting cell (APC) by now which not only activates auto-immunity to attack tumor cells, but also does help to enhance antitumor effect for allogenic bodies. To explore the feasibility and safety of clinical therapy application of peripheral blood derived DC cultured ex vivo, and analyze the influence of DC-inducing-immunotherapy upon long-term survival of ANLL patients accepted autologous bone marrow transplantation, peripheral blood mononuclear cells (PBMNC) of 13 ANLL patients after autologous bone marrow transplantation were collected by using CS3000Plus. DC immunotherapy was administered after cultivation of PBMNC ex vivo for 2 weeks, desease-free survival time was observed after therapy for long time follow-up. The results showed that no any severe adverse event associated with DC therapy was observed, the survival analysis of Kaplan-Meier suggested that five year survival rate was 75.52% in DC group while 45.71% in non-DC group. DC group surpassed non-DC group in accumulative survival rate. It is concluded that the ex vivo cultivation and clinical therapy application of DC derived from peripheral blood are feasible and safe, DC immunotherapy in patients with acute non-lymphocytic leukemia after autologous bone marrow transplantation prolongs desease-free survival time and enhances long-term survival rate.

Selected CD34+ cell autologous transplantation for advanced malignant tumors / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To determine the clinical results of selected CD34(+) cell autologous transplantation in advanced malignant tumors.</p><p><b>METHODS</b>After pretreatment, fifteen patients aged 12 - 70 (49.5) years with various Stage III or IV malignant tumors were given the sorted CD34(+) cells collected by magnetic-activated cell sorting (Clini MACS, Milteny Biotech, Germany).</p><p><b>RESULTS</b>Peripheral blood progenitor cells (PBPC) from the patients were mobilized by chemotherapy and G-CSF 5 micro g/kg per day. CD34(+) cells gave 2.0 - 5 log depletion after cell sorting, with a median yield of CD34(+) selected cells of 2.4 (0.15 - 12.03) x 10(6)/kg. It gave a median recovery of 64 (52 - 81.4)% and median purity of 98.2 (83.2 - 99.7)%. The median time of neutrophil recovery > 1.0 x 10(9)/L and platelet recovery > 20 x 10(9)/L post-transplantation were 14 (8 - 26) days and 13 (11 - 35) days, respectively. On follow-up of 2 - 33 (11) months, the event-free survival rate was 53.3% (8/15) and the overall survival rate was 66.7% (10/15).</p><p><b>CONCLUSION</b>Transplantation of autologous selected PBPC CD34(+) cells gives prompt and stable engraftment. Selected CD34(+) cell transplantation, being a safe approach, may improve the clinical outcome even in patients with advanced malignant tumors.</p>

Cytomegalovirus infection and disease in allogeneic hematopoietic stem cells transplantation / 军事医学科学院院刊

Objective: To investigate the incidence of CMV infection(CMV-I) and CMV related diseases (CMV-D) after allogeneic hematopoietic stem cells transplantation in 70 consecutive allogeneic hematopoietic stem cells transplantation(allo-HSCT) patients and to search for the optimal prophylactic strategy.Methods: Blood samples were monitored using the CMV pp65 antigenemia assay.Of the 70 patients observed,30 patients with chronic myeloid leukemia［CML:CP(27),AP(2),BC(1)］,12 with acute myeloblastic leukemia(AML),10 with acute lymphoblastic leukemia(ALL)and other cases were NHL(3), AA(5), MDS(7), SCLC with pancytopenia (1),CLL(1), and MF (1). Sixty six patients received HLA - identical siblings transplantation and four received tranplants from their HLA- haploidentical donors. Seventy cases included allo-PBPCT (64 cases) , allo-BMT (4 cases) and allo-PB+BMT (2). Before transplantation, all patients and donors received CMV serological examination except 4 pairs of donors/recepients. All 66 patients (3 cases were CMV IgM positive) and 64/66 donors were CMV IgG positive. Results：After transplantation, 64/70 patients developed CMV viremia during monitoring period. Forty three of 70 patients developed CMV-D.Thirty five of them suffered from CMV-associated interstitial pneumonia(CMV-IP). The high peak levels of CMV antigenemia were associated with development of CMV disease　. Close correlation was found between acute graft vs host disease(GVHD) and CMV disease. The patients were followed up for 2 to 24 months. The patients who received preemptive therapy(group A)had significantly better outcome than CMV disease group(group B, P=0.0001). Conclusions: The results suggest that CMV antigenemia has high predictive value for subsequent CMV disease and CMV pp65 antigenemia -guided early therapy has particular advantage for avoiding morbidity and mortality caused by CMV disease.