Peripheral Hematopoietic Stem Cell Transplantation Research Articles

Infused autograft lymphocyte to monocyte ratio predicts survival in classical Hodgkin lymphoma.

The infused autograft lymphocyte to monocyte ratio (A-LMR) as a surrogate marker of host immunity (ie, absolute lymphocyte count) and CD14+ HLA-DRlow/neg immunosuppressive monocytes (ie, absolute monocyte count) is a prognostic factor for patients with diffuse large B-cell lymphoma after autologous peripheral hematopoietic stem cell transplantation (APHSCT). Thus, we set out to investigate if A-LMR can also affect survival post-APHSCT in classical Hodgkin lymphoma. From 1994 to 2012, 183 patients with classical Hodgkin lymphoma who underwent APHSCT were studied. The patients were randomly divided into a training set (n=122) and a validation set (n=61). The receiver operating characteristic and area under the curve identified an A-LMR ≥1 as the best cut-off value and validated by the k-fold cross-validation in the training set. Multivariate analysis showed A-LMR to be an independent prognostic factor for survival in the training set. Patients with an A-LMR ≥1.0 experienced a superior overall survival (OS) versus patients with an A-LMR <1.0 (median OS not reached versus 40.4 months, 5-year OS rates of 86% [95% CI 72–93] versus 43% [95% CI 28–58], P<0.0001, respectively) in the training set. In the validation set, an A-LMR ≥1 showed a median OS of not reached versus 41.4 months for an A-LMR <1, 5-year OS rates of 90% (95% CI 73–97) versus 48% (95% CI 28–68; P<0.0001). A-LMR provides a platform to engineer an autograft versus tumor effect to improve clinical outcomes in patients with classical Hodgkin lymphoma undergoing APHSCT.

Engineered dendritic cells from cord blood and adult blood accelerate effector T cell immune reconstitution against HCMV

Human cytomegalovirus (HCMV) harmfully impacts survival after peripheral blood hematopoietic stem cell transplantation (PB-HSCT). Delayed immune reconstitution after cord blood (CB)-HSCT leads to even higher HCMV-related morbidity and mortality. Towards a feasible dendritic cell therapy to accelerate de novo immunity against HCMV, we validated a tricistronic integrase-defective lentiviral vector (coexpressing GM-CSF, IFN-α, and HCMV pp65 antigen) capable to directly induce self-differentiation of PB and CB monocytes into dendritic cells processing pp65 (“SmyleDCpp65”). In vitro, SmyleDCpp65 resisted HCMV infection, activated CD4+ and CD8+ T cells and expanded functional pp65-specific memory cytotoxic T lymphocytes (CTLs). CD34+ cells obtained from PB and CB were transplanted into irradiated NOD.Rag1−/−.IL2γc−/− mice. Donor-derived SmyleDCpp65 administration after PB-HSCT stimulated peripheral immune effects: lymph node remodeling, expansion of polyclonal effector memory CD8+ T cells in blood, spleen and bone marrow, and pp65-reactive CTL and IgG responses. SmyleDCpp65 administration after CB-HSCT significantly stimulated thymopoiesis. Expanded frequencies of CD4+/CD8+ T cell precursors containing increased levels of T-cell receptor excision circles in thymus correlated with peripheral expansion of effector memory CTL responses against pp65. The comparative in vivo modeling for PB and CB-HSCT provided dynamic and spatial information regarding human T and B cell reconstitution. In vivo potency supports future clinical development of SmyleDCpp65.

Infused Autograft Lymphocyte to Monocyte Ratio and Survival in Classical Hodgkin Lymphoma

Infused autograft absolute lymphocyte count (A-ALC) is a prognostic factor for survival post-autologous peripheral hematopoietic stem cell transplantation (APHSCT) for lymphoma. Myeloid-derived suppressor cells (MDSCs) affect tumor growth by suppression of host anti-tumor immunity. Thus, we set out to investigate if the infused autograft lymphocyte /monocyte ratio (A-LMR), as a biomarker of host immunity (i.e., lymphocytes) and MDSCs (i.e., monocytes), affects survival post-APHSCT in patients with classical Hodgkin lymphoma (cHL). Only patients that collected their stem cells through the peripheral blood were included in the study. From 1994 to 2012, 183 cHL patients qualified for the study. The 183 patients were randomly divided into a training set (n = 122) and a validation set (n = 61). Receiver operating characteristic and area under the curve (AUC) identified an A-LMR ≥ 1 as the best cut-off value (AUC = 0.8, p < 0.01) and validated by the k-fold cross-validation (AUC = 0.8) in the training set. Multivariate analysis showed A-LMR to be an independent prognostic factor for survival in the training set. Patients with an A-LMR ≥ 1.0 experienced a superior overall survival (OS) versus patients with an A-LMR < 1.0 (median OS was not reached vs 40.4 months, 5-year OS rates of 86% (95 CI, 72%-93%) vs 43% (95 CI, 28-58 %), p < 0.0001, respectively) in the training set. In the validation set, an A-LMR ≥ 1 showed a median OS of not reached vs 41.8 months for an A-LMR < 1, 5 year OS rates of 90% (95 CI, 73%-97%) vs 48% (95 CI, 29-68%), p < 0.0001, respectively. A-LMR provides a platform to engineer an immunocompetent autograft to improve clinical outcomes in cHL patients undergoing APHSCT. DisclosuresNo relevant conflicts of interest to declare.

Clinical features and risk factors analysis of acute graft-versus-host disease in patients with related HLA-haploidentical non T cell-depleted in vitro peripheral hematopoietic stem cell transplantation

To study the clinical features of acute graft-versus-host disease (aGVHD) and its risk factors for the related HLA-haploidentical non T cell-depleted in vitro peripheral hematopoietic stem cell transplantation (RHNT-PBSCT). From July 2002 to December 2012, 104 patients who underwent the RHNT-PBSCT were enrolled to analyze the incidences, location and its risk factors of aGVHD, compared with those of the 103 patients who received the HLA-matched sibling non T cell-depleted in vitro PBSCT (MSNT-PBSCT) in the same period. (1)The cumulative incidence of aGVHD in the RHNT-PBSCT group was significantly higher than the MSNT-PBSCT group [(56.2±4.7)% vs (34±3.6)%, P<0.05], but the cumulative incidences of II-IV and III-IVgrade aGVHD had no significant difference between the two groups[(39.5±2.9)% vs (21.2±5.4)%, P>0.05; (12.6±4.1)% vs (10.8±2.4)%, P>0.05]. (2)The cumulative incidence of cutaneous aGVHD was significantly higher in RHNT-PBSCT group than that in MSNT-PBSCT group [(42.3±3.2)% vs (17.5±2.3)%, P<0.05]. The cumulative incidences of liver and gastrointestinal aGVHD between the two groups had no significant difference [(7.7±2.1)% vs (12.6±3.4)%, P>0.05; (16.3±4.5)% vs (10.3±2.5)%, P>0.05]. (3)The 3-year disease free survival (DFS) and overall survival(OS) of RHNT-PBSCT group and MSNT-PBSCT group were (63±5.5)%, (65.2±4.7)% and (74.2±5.4)%, (77.4±5)% respectively, without significance (P=0.078, P=0.052). (4)aGVHD occurrence with HLA haplotype (P=0.003) and matched loci (P=0.002) were significantly correlated by univariate analysis. Multivariate analysis showed that only the HLA typing is a risk factor for aGVHD (HR=1.891, P=0.03). Although the incidence of total aGVHD in RHNT-PBSCT protocol is higher than that in MSNT-PBSCT, but there was no significance in severe aGVHD and cutaneous aGVHD was the common type, which indicates that RHNT-PBSCT protocol is feasible.

Infused Autograft Lymphocyte to Monocyte Ratio and Survival in Diffuse Large B Cell Lymphoma

Infused autograft absolute lymphocyte count is a prognostic factor for survival after autologous peripheral hematopoietic stem cell transplantation (APHSCT) for diffuse large B cell lymphoma (DLBCL). CD14+ HLA-DRlow/neg immunosuppressive monocytes affect tumor growth by suppressing host antitumor immunity. Thus, we set out to investigate if the infused autograft lymphocyte to monocyte ratio (A-LMR), as a biomarker of host immunity (ie, lymphocytes) and immunosuppression (ie, monocytes), affects survival after APHSCT. From 1994 to 2012, 379 DLBCL patients who underwent APHSCT were studied. The 379 patients were randomly divided into a training set (n = 253) and a validation set (n = 126). Receiver operating characteristic and area under the curve identified an A-LMR ≥1 as the best cut-off value, which was validated by the k-fold cross-validation in the training set. Multivariate analysis showed A-LMR to be an independent prognostic factor for survival in the training set. Patients with an A-LMR ≥ 1.0 experienced superior overall survival (OS) compared with patients with an A-LMR <1.0 (median OS: 167.2 versus 17.6 months; 5-year OS: 73% [95% confidence interval (CI), 63% to 80%] versus 30% [95% CI, 2% to 38%], P < .0001, respectively) in the training set. In the validation set, an A-LMR ≥ 1 showed a median OS of 181.2 months versus 19.5 months for an A-LMR <1, and 5-year OS rates of 67% (95% CI, 52% to 79%) versus 35% (95% CI, 25% to 47%), P < .0001, respectively. The A-LMR provides a platform to engineer immunocompetent autograft to improve clinical outcomes in DLBCL patients undergoing APHSCT.

Outcome and prognosis in acute myeloid leukemia patients treated with related peripheral blood hematopoietic stem cell transplantation

This study was purposed to evaluate the outcome of acute myeloid leukemia patients treated with related peripheral blood hematopoietic stem cell transplantation (PBHSCT) and analyse the potential prognostic factors. A total of 64 acute myeloid leukemia patients treated with related peripheral allo-HSCT from march 2008 to august 2012 in our hospital were enrolled in the analysis. All the patients received either HLA-matched related or mismatched related donor mobilized peripheral blood stem cells. All the patients were followed up and evaluated for overall survival (OS), leukemia-free survival (LFS) and relapse rate (RR) , and the potential prognostic factors well analyzed. The results showed that the 3 year OS , LFS and RR were 61.9%, 52% and 39.1% respectively. Univarite analysis demonstrated that the disease status before transplantation (P < 0.01) , donor type (P < 0.01), white blood cell count at initial diagnosis (P < 0.05) are related with outcome, and severe aGVHD has some influence on the outcome (P > 0.05) . Multivariate analysis indicated the status of disease before transplantation, donor type, severe aGVHD are the most important prognostic factors. It is concluded that the related PBHSCT is effective treatment method for AML patients, recurrence is the main reason for the failure after transplantation, disease status before transplantation, donor type, and severe aGVHD are independent prognostic factors.

Role of antioxidant in protecting the biological function of hematopoietic stem cells

In peripheral blood hematopoietic stem cell transplantation (PBHSCT) , the mobilization and circulating of bone marrow hematopoietic stem cells in blood with higher oxygen concentration all increase reactive oxygen species(ROS) production, which has negative effect on the biological function of BMHSC. In order to investigate the protective effect of antioxidant on hematopoietic stem cells (HSC), the ascorbic acid 2-phosphate (AA2P), an ascorbic acid derivative of vitamin C, was added in HSC culturing by imitating oxygen conditions which BMHSC experienced in peripheral blood stem cell transplantation. The protective effect of above-mentioned culture methods on the biologic functions of BMHSC was evaluated by vitro amplification assay, committed division assay, reactive oxygen species (ROS) measurement, CD34(+) HSC engraftment. The results showed that the ROS level in HSC from in vitro cultures was much higher than that freshly separated BMHSC, and the amplified AC133(+)CD34(+) HSC, BFU-E, CFU-GM, CFU-GEMM colonies, migration rate and severe combined immunodeficiency (SCID)-repopulating cells (SRC) were all much more than HSC cultured without AA2P. It is concluded that antioxidant intervention may be an effective methods for protecting the biological function of PBHSC and improving the therapeutic effect of PBHSCT.

Post-Transplantation B Cell Activating Factor and B Cell Recovery before Onset of Chronic Graft-versus-Host Disease

Excessive levels of B cell activating factor (BAFF) are found in patients with active chronic graft-versus-host disease (cGVHD). In mice, BAFF has been shown to be essential for B cell recovery after myeloablation. To assess how BAFF levels relate to transplantation factors and subsequent development of cGVHD, we prospectively monitored 412 patients in the first year after allogeneic peripheral blood or bone marrow hematopoietic stem cell transplantation (HSCT) and censored data at time of cGVHD onset. In patients who did not develop cGVHD, we affirmed a temporal pattern of gradually decreasing BAFF levels as B cell numbers increase after myeloablative conditioning. In contrast, after reduced-intensity conditioning, BAFF levels remained high throughout the first post-HSCT year, suggesting that the degree of myeloablation resulted in delayed B cell recovery associated with persistence of higher BAFF levels. Given that high BAFF/B cell ratios have been associated with active cGVHD, we examined differences in early BAFF/B cell ratios and found significantly different BAFF/B cell ratios at 3 months post-HSCT only after myeloablative conditioning in patients who subsequently developed cGVHD. In addition to HSCT conditioning type, the use of sirolimus was significantly associated with higher BAFF levels after HSCT, and this also was potentially related to lower B cell numbers. Taken together, our results are important for interpreting BAFF measurements in cGVHD biomarker studies.

Development of model for analysing respective collections of intended hematopoietic stem cells and harvests of unintended mature cells in apheresis for autologous hematopoietic stem cell collection

Hematopoietic stem cells (HSCs) required to perform peripheral hematopoietic autologous stem cell transplantation (APBSCT) can be collected by processing several blood volumes (BVs) in leukapheresis sessions. However, this may cause granulocyte harvest in graft and decrease in patient's platelet blood level. Both consequences may induce disturbances in patient. One apheresis team's current purpose is to improve HSC collection by increasing HSC collection and prevent increase in granulocyte and platelet harvests. Before improving HSC collection it seemed important to know more about the way to harvest these types of cells. The purpose of our study was to develop a simple model for analysing respective collections of intended CD34+ cells among HSC (designated here as HSC) and harvests of unintended platelets or granulocytes among mature cells (designated here as mature cells) considering the number of BVs processed and factors likely to influence cell collection or harvest. For this, we processed 1, 2 and 3 BVs in 59 leukapheresis sessions and analysed corresponding collections and harvests with a referent device (COBE Spectra). First we analysed the amounts of HSC collected and mature cells harvested and second the evolution of the respective shares of HSC and mature cells collected or harvested throughout the BV processes. HSC collections and mature cell harvests increased globally (p<0.0001) and their respective shares remained stable throughout the BV processes (p non-significant). We analysed the role of intrinsic (patient's features) and extrinsic (features before starting leukapheresis sessions) factors in collections and harvests, which showed that only pre-leukapheresis blood levels (CD34+cells and platelets) influenced both cell collections and harvests (CD34+cells and platelets) (p<0.001) and shares of HSC collections and mature unintended cells harvests (p<0.001) throughout the BV processes. Altogether, our results suggested that the main factors likely to influence intended HSC collections or unintended mature cell harvests were pre-leukapheresis blood cell levels. Our model was meant to assist apheresis teams in analysing shares of HSC collected and mature cells harvested with new devices or with new types of HSC mobilization.

Clinical observation and long-time follow-up of patients with malignant lymphoma treated with autologous peripheral blood hematopoietic stem cell transplantation

This study was purposed to evaluate the efficacy of autologous peripheral blood hematopoietic stem cell transplantation (auto-PBHSCT) for patients with malignant lymphoma. From January 1992 to June 2012, 32 malignant lymphoma (ML) patients were treated with auto-PBHSCT in our hospital. There were 56 cases of non-Hodgkins lymphoma (NHL) and 16 cases of Hodgkin's lymphoma(HD). The preconditioning regimens of total body irradiation (TBI) plus cyclophosphamide combined with etoposide/pharmorubicin were used in 50 patients, and the BEAM (BCNU+etoposide+Ara-C+melphalan) were used in the other 22 patients. The average number of CD34(+) cells was (6.6 ± 4.9) ×10(6)/kg. The results showed that transplanted cells were engrafted and hematopoiesis was reconstituted in all patients. The median time of neutrophilic granulocyte recovery up to ≥ 0.5×10(9)/L was 12 ± 4.4 days, and the platelet recovery up to ≥ 20×10(9)/L was 14 ± 4.9 days . The transplantation related mortality was 4.2%. The patients were followed up for 6-217 months. The median follow-up time was 63.5 months. 1-year OS rate was 92.3 ± 3.2%. 3-years OS rate was 81.4 ± 4.9%. 5-years OS rate was 77.6 ± 5.3%. 10-years OS rate was 68.9 ± 6.8%. It is concluded that auto-PBHSCT is effective for malignant lymphoma, and long time follow-up shows that the OS rate is still high. Furthermore, the safety of auto-PBHSCT can also be received. Before transplantation the patients with CR can get higher OS rate.

Lack Of Advantage Of Peripheral Blood Hematopoietic Stem Cell Transplantation Over Bone Marrow From HLA Matched Related Donors After Myeloablative Conditioning For Hematologic Malignancies

Although bone marrow (BM) and peripheral blood mobilized hematopoietic stem cells (PBSC) are widely used as graft sources in patients undergoing hematopoietic stem cell transplantation (HSCT), the graft of choice for each subset of patients remains to be determined. Several studies have, prospectively and retrospectively, addressed this question with inconsistent results. While the increased incidence of chronic graft versus host disease (cGVHD) in PBSC recipients has been unanimously found, data regarding disease free survival (DFS), overall survival (OS) and acute graft versus host disease (aGVHD) incidence have been controversial, mainly for patients with high risk disease. We retrospectively compared the clinical outcomes of 334 patients with acute leukemia and chronic myeloid malignancies receiving related BMT or PBSCT after myeloablative conditioning regimen, treated at seven transplantation centers in Brazil from 2008 to 2009.Median OS was 2.85 and 2.39 years (HR 1.19; 95% CI, 0.84 to 1.68, p=0.34), and DFS was 2.48 and 2.18 years for BM and PBSC recipients respectively (HR 1.07; 95% CI, 0.77 to 1.48, p=0.70). For patients with high risk disease, median OS was 2.1 and 1.72 years (HR 1.18; 95% CI, 0.73 to 1.91, p=0.50) and DFS was 0.46 and 0.58 years (HR 1.04; 95% CI, 0.66 to 1.64, p=0.86) for BMT and PBSCT respectively. Additionally, in agreement with previous reports, the cumulative incidence of chronic GVHD at three years was 53.7% and 79.8% (HR 1.93; 95% CI 1.38 to 2.69, p< 0.001) for BM and PBSC respectively (Figure 1). On the other hand, aGVHD incidence / severity, cumulative incidence of relapse and non relapse mortality (NRM) were not different between BM or PBSC recipients. The same being true when only patients with high risk disease were evaluated. [Display omitted] In conclusion, in our cohort, there was no OS or DFS benefit for patients receiving PBSC when compared to BM recipients, even when only high risk patients were analyzed. Disclosures:No relevant conflicts of interest to declare.

Long-term results of autologous peripheral blood hematopoietic stem cell transplantation in patients with peripheral arterial diseases

Long-term results of autologous peripheral blood hematopoietic stem cell transplantation in patients with peripheral arterial diseases

Long-term follow-up of autologous stem cell transplantation for severe paediatric systemic lupus erythematosus

This study attempts to evaluate the outcome of autologous peripheral blood hematopoietic stem cell transplantation (auto-PBHSCT) in patients with severe paediatric systemic lupus erythematosus (SLE). Five patients (n = 2 females, n = 3 males) with severe or refractory paediatric SLE received autologous peripheral blood CD34+ cell transplants between July 2005 and February 2009. The patients ranged in age from 6 to 14 years, and the course of disease extended over a period from 5 to 90 months. All of the patients received conventional therapy for 3 to 87 months. After their discharge from the hospital, the patients continued to maintain their regular follow-up visits and basic quality of life. The patients exhibited decreased immune function after the auto-PBHSCT. The CD4+ and CD19+ cells were significantly reduced. Viremia occurred in four patients 2 months after the transplantation. All of the patients went into clinical remission in 3-6 months. The severity of encephalopathy, nephritis and organ damage declined in varying degrees. The disease recurred in patient 2 at 9 months and in patient 4 at 12 months after the transplantation. Because the disease was relatively mild, we were able to administer small doses of glucocorticoids that were sufficient to control the course of the disease. Macrophage activation syndrome occurred in patient 3 at 18 months after the transplantation. At the end of the follow-up period, three of the five patients were completely off their medications. Another two patients sustained small doses of glucocorticoids. The developmental levels of these patients were comparable to those of normal children at the end of the follow-up. The quality of life improved significantly. The auto-PBHSCT is effective for severe and refractory paediatric SLE. The incidence of lethal infection and other adverse reactions is low. Long-term remission can be achieved. A milder form of the disease may have recurred after the transplantation.

AB0498 Transient improvement of severe and rapidly progressive dysphagia with autologous peripheral blood hematopoietic stem cell transplantation in a patient with long standing dermatomyositis refractory to standard therapy

BackgroundAutologous hematopoietic stem cell transplantation (HSCT) has become a significant treatment option for severe autoimmune diseases. Dermatomyositis (DM) and Polymyositis (PM) belong to inflammatory myopathies, autoimmune diseases in which the...

Day 100 peripheral blood absolute monocyte/lymphocyte count prognostic score and survival in diffuse large B-cell lymphoma post-autologous peripheral blood hematopoietic stem cell transplantation.

7041 Background: Prognostic factors for diffuse large B-cell lymphoma (DLBCL) at day 100 post-autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) have not been evaluated. We previously reported that absolute monocyte (AMC)/lymphocyte count (ALC) prognostic score (AMLCPS) at diagnosis of DLBCL patients is a prognostic factor of survival, stratifying patients into three risk groups: low- (AMC&lt;630/μL and ALC&gt;1000/μL), intermediate- (AMC ≥ 630/μL or ALC ≤ 1000/μL) and high-risk (AMC ≥ 630/μL and ALC ≤ 1000/μL) (Leukemia 25: 1502-9, 2011). Therefore, we evaluated day 100 AMLCPS as a prognostic factor of survival by landmark analysis from day 100 post-APBHSCT in DLBCL patients. Methods: DLBCL patients that achieved complete response by day 100 post-APBHSCT qualified for the study. From 2000 to 2007, 134 consecutive DLBCL patients were evaluated. Overall survival (OS) and progression free survival (PFS) were calculated using Kaplan-Meier analysis. Results: The median follow up from day 100 for the cohort was 5.5 years (range: 0.17-12.17 years) and for living patients (N=93) was 6.9 years (range: 2.5-12.17 years). Day 100 AMLCPS was able to stratify patients into three risk groups low-, intermediate-, and high-risk for OS [low: median OS = not reached, 5-year survival rate = 94% (95%CI 83.3%-98.1%); intermediate: median OS = not reached, 5-year survival rate = 70% (95%CI 58.0%-79.8%); high: median OS = 2.2 years, 5-year survival rate = 13% (95%CI 3.4%-40.5%); p&lt;0.0001] and PFS [low: median PFS = not reached, 5-year progression free rate = 87% (95%CI 74.5%-94.3%); intermediate: median PFS = 10.9 years, 5-year progression free rate = 67% (95%CI 55.4%-77.5%); high: median PFS = 1 year, 5-year progression free rate = 13% (95%CI 3.4%-40.5%); p&lt;0.0001]. The day 100 AMLCPS was balanced in relation to the International Prognostic Index (IPI; p=0.22), infused CD34+ stem cells (p=0.92), and disease status pre-APBHSCT (complete remission versus partial response; p=0.11). Conclusions: The day 100 AMLCPS is a simple biomarker that can help identify DLBCL patients post-APBHSCT with poor clinical outcomes.

Day 100 Peripheral Blood Absolute Lymphocyte/Monocyte Ratio and Survival in Classical Hodgkin's Lymphoma Postautologous Peripheral Blood Hematopoietic Stem Cell Transplantation

Day 100 prognostic factors of postautologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) to predict clinical outcome in classical Hodgkin lymphoma (cHL) patients have not been evaluated. Thus, we studied if the day 100 peripheral blood absolute lymphocyte/monocyte ratio (Day 100 ALC/AMC) affects clinical outcomes by landmark analysis from day 100 post-APBHSCT. Only cHL patients achieving a complete remission at day 100 post-APBHSCT were studied. From 2000 to 2010, 131 cHL consecutive patients qualified for the study. The median followup from day 100 was 4.1 years (range: 0.2–12.3 years). Patients with a Day 100 ALC/AMC ≥ 1.3 experienced superior overall survival (OS) and progression-free survival (PFS) compared with Day 100 ALC/AMC < 1.3 (from day 100: OS, median not reached versus 2.8 years; 5 years OS rates of 93% (95% CI, 83%–97%) versus 35% (95% CI, 19%–51%), resp., P < 0.0001; from day 100: PFS, median not reached versus 1.2 years; 5 years PFS rates of 79% (95% CI, 69%–86%) versus 27% (95% CI, 14%–45%), resp., P < 0.0001). Day ALC/AMC ratio was an independent predictor for OS and PFS. Thus, Day 100 ALC/AMC ratio is a simple biomarker that can help to assess clinical outcomes from day 100 post-APBHSCT in cHL patients.

The changes of the coagulation indicators in the process of lymphoma patients with autologous blood stem cell transplantation

Objective To explore the inflnence of autologous peripheral blood hematopoietic stem cell transplantation (auto-HSCT) for lymphoma process on the quality of patients blood coagulation.Methods Plasma samples were collected before the conditioning and on day 0,7,14,28,35 follow auto-HSCT from 20 patients.The following parameters were measured:prothrombin time (PT),activated partial thromboplastin time (APTT),fibrinogen (FIB) and D-dimer(D-Di).Results Compared with the values before conditioning,a significant rise in the FIB values was detected on day 7 and day 14 after auto-HSCT,no essentially change in the FIB values was detected on day 21 and day 28 and day 35 after auto-HSCT.Other coagulation parameters investigated(PT.APTT.D-Di) remained essentially unchanged.All of the patients not concurrent thrombotic disease.Conclusion Lymphoma patients with autologous peripheral blood hematopoietic stem cell transplantation appear abnormality in coagulant function.Clinical doctors should concern. Key words: Lymphoma; Hematopoietic stem cell transplantation; Transplantation,autologous; Fibrinogen; Prothrombin time

Mumps virus encephalomyelitis in a 19-year old male patient with an undefined severe combined immunodeficiency post-haematopoietic bone marrow transplantation: A rare fatal complication

We describe a rare case of fatal mumps encephalomyelitis occurring in 19-year old male following matched unrelated donor peripheral blood haematopoietic stem cell transplantation (HSCT). The indication for HSCT was for an undefined form of severe combined immunodeficiency (SCID). Molecular typing of the mumps viral RNA isolated from neural tissue indicated that the infection was acquired at the time of a mumps outbreak in England and Wales that occurred between 2004 and 2006. This case highlights the importance of considering mumps in the differential diagnosis of central nervous system infection in highly immunosuppressed patients.

Day 100 Absolute Monocyte/Lymphocyte Prognostic Score and Survival Post Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation in Diffuse Large B-Cell Lymphoma

Day 100 prognostic factors post-autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) to predict clinical outcomes in diffuse large B-cell lymphoma (DLBCL) patients have not been studied. Thus, we retrospectively examined if day 100 absolute monocyte/lymphocyte prognostic score (AMLPS-100) affects clinical outcomes by landmark analysis from day 100 post-APBHSCT in DLBCL. Only DLBCL patients in complete remission at day 100 post-APBHSCT were evaluated. From 2000 to 2007, 134 consecutive DLBCL patients are qualified for the study. Patients with a day 100 absolute monocyte count (AMC-100) ≥ 630 cells/μL and day 100 absolute lymphocyte count (ALC-100) ≤ 1000 cells/μL experienced inferior overall survival (OS) and progression free survival (PFS). On multivariate analysis, the AMC-100 and ALC-100 remained independent predictors of OS and PFS. Combining both values into the AMLPS-100, the 5-year OS rates for low, intermediate, and high AMLPS-100 risk groups were 94% (95% CI, 83.0% - 98.1%), 70% (95% CI, 58.6% - 80.1%), and 13% (95% CI, 3.4% - 40.5%), respectively; and the 5-year PFS rates were 87% (95% CI, 74.0% - 94.1%), 68% (95% CI, 56.0% - 77.8%), and 13% (95% CI, 3.4% - 40.5%), respectively. The AMLPS-100 is a simple biomarker score that can stratify clinical outcomes from day 100 post-APBHSCT in DLBCL patients.

The Use of Hematopoietic Stem Cell Transplant in Mitochondrial Neurogastrointestinal Encephalopathy Disease

Purpose: There have been few successful treatments of gastrointestinal diseases using hematopoietic stem cell transplantation (HSCT). However, with a growing body of evidence that it delivers a successful cure for mitochondrial neurogastrointestinal encephalopathy disease (MNGIE) we present a case of this progressive motility disease that highlights the curative potential of the treatment and its common side effects. A 25 y/o woman with a history of IDDM and hypertriglyceridemia presented with progressive ascending numbness, tingling and weakness with associated bilateral ptosis and external ophthalmoplegia. Her gut symptoms included dysphagia, postprandial abdominal pain, profound emesis and sitophobia leading to cachexia for one year. Her labs were notable for hyperglycemia, but her electrolytes and CBC were normal. A motility work up was significant for diminished esophageal peristalsis but no evidence for GERD. She had a normal gastric emptying study. An MRI of the brain revealed confluent white matter changes. The diagnosis of MNGIE was confirmed by TYMP genetic testing and the absence of thymidine phosphorylase activity (<10%) with serum thymidine elevation. She received a minimal residual disease allogenic peripheral HSCT from two siblings who were carriers of the disease. However, the siblings produced enough of the critical enzyme to be asymptomatic and deemed to be suitable donors for her transplant. Despite a post transplant course complicated by sepsis, esophagitis, and GVHD of the skin and gastrointestinal tract she had biochemically verified improvement in her thymidine phosphorylase activity and subsequent gastrointestinal and neurological symptoms. MNGIE is an autosomal recessive disease defined by an underlying nuclear loss-of-function mutation in a phosphorylation gene leading to a deregulation of deoxyribonucleotide pools with subsequent instability and toxicity to mitochondrial DNA in various tissues (notably GI tract, brain, peripheral nerves, autonomic nerves, spleen, bladder, and lungs). The mean age of death in these patients is 37.6 years. In addition to supportive and symptomatic therapy, reducing thymidine and deoxyuridine levels via dialysis, and enzyme replacement therapy via platelet transfusions are under investigation. The therapeutic effects are transient and subclinical, respectively. Based on the success of treatments for different inborn errors of metabolism, less than 200 HSCT have been performed for MNGIE worldwide, with a nearly complete biochemical correction of the underlying deficiency with long-term clinical improvement. Ongoing attempts at refining the process of HSCT will help guide multidisciplinary teams on a sustainable treatment for MNGIE.