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Background. For patients with B cell acute lymphocytic leukemia (B-ALL) who underwent allogeneic stem cell transplantation (allo-SCT), many variables have been demonstrated to be associated with leukemia relapse. In this study, we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT. Methods. A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People's Hospital from December 2010 to December 2015 were enrolled in this retrospective study. We aimed to evaluate the factors associated with transplant outcomes after allo-SCT, and establish a risk score to identify patients with different probabilities of relapse. The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables. Results. All patients achieved neutrophil engraftment, and 95.4% of patients achieved platelet engraftment. The 5-year cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), and non-relapse mortality were 20.7%, 70.4%, 65.6%, and 13.9%, respectively. Multivariate analysis showed that patients with positive post-transplantation minimal residual disease (MRD), transplanted beyond the first complete remission (≥CR2), and without chronic graft-versus-host disease (cGVHD) had higher CIR (P

Background: The dose of certain cell types in allografts affects engraftment kinetics and clinical outcomes after allogeneic stem cell transplantation (SCT). Hence, the present study investigated the association of cell compositions in allografts with outcomes after unmanipulated haploidentical SCT (haplo-SCT) for patients with acquired severe aplastic anemia (SAA). Methods: A total of 131 patients with SAA who underwent haplo-SCT were retrospectively enrolled. Cell subsets in allografts were determined using flow cytometry. To analyze the association of cellular compositions and outcomes, Mann–Whitney U nonparametric tests were conducted for patient age, sex, weight, human leukocyte antigen mismatched loci, ABO-matched status, patient ABO blood type, donor-recipient sex match, donor-recipient relationship, and each graft component. Multivariate analysis was performed using logistic regression to determine independent influence factors involving dichotomous variables selected from the univariate analysis. Results: A total of 126 patients (97.7%) achieved neutrophil engraftment, and 121 patients (95.7%) achieved platelet engraftment. At 100 days after transplantation, the cumulative incidence of II–IV acute graft-versus-host disease (GVHD) was 32.6%. After a median follow-up of 842 (range: 124–4110) days for surviving patients, the cumulative incidence of total chronic GVHD at 3 years after transplantation was 33.7%. The probability of overall survival at 3 years was 83.0%. Multivariate analysis showed that higher total doses of CD14+ (P = 0.018) and CD34+ cells (P < 0.001) were associated with a successful platelet engraftment. A successful platelet was associated with superior survival (P < 0.001). No correlation of other cell components with outcomes was observed. Conclusions: These results provide evidence and explain that higher doses of CD34+ and CD14+ cells in haploidentical allografts positively affect platelet engraftment, contributing to superior survival for patients with SAA. Key words: Aplastic Anemia; CD14+ Monocyte; CD34+ Cell; Haplo-Stem Cell Transplantation; Outcome

Background: Several studies have shown that detection of minimal residual disease (MRD) in acute myeloid leukemia (AML) is an independent prognostic factor. This study aimed to evaluate the significance of dynamic MRD pretransplantation on outcome of AML patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: We retrospectively analyzed 145 consecutive AML patients undergoing allo-HSCT in complete remission status between June 2013 and June 2016. MRD was determined with multiparameter flow cytometry after the first and second courses of chemotherapy and pre-HSCT. Results: In matched sibling donor transplantation (MSDT) settings, patients with positive MRD had higher cumulative incidence of relapse (CIR) than those without MRD after the first (32.3 ± 9.7% vs. 7.7 ± 3.1%, χ2 = 3.661, P = 0.055) or second course of chemotherapy (57.1 ± 3.6% vs. 12.5 ± 2.7%, χ2 = 8.759, P = 0.003) or pre-HSCT (50.0 ± 9.7% vs. 23.0 ± 3.2%, χ2 = 5.547, P = 0.019). In haploidentical SCT (haplo-SCT) settings, the MRD status at those timepoints had no significant impact on clinical outcomes. However, patients with persistent positive MRD from chemotherapy to pre-HSCT had higher CIR than those without persistent positive MRD both in MSDT and haplo-SCT settings. Patients with persistent positive MRD underwent MSDT had the highest relapse incidence, followed by those with persistent positive MRD underwent haplo-SCT, those without persistent MRD underwent haplo-SCT, and those without persistent MRD underwent MSDT (66.7 ± 9.2% vs. 38.5 ± 6.0% vs. 18.8 ± 8.7% vs. 12.0 ± 1.0%, χ2 = 20.763, P < 0.001). Multivariate analysis showed that persistent positive MRD before transplantation was associated with higher CIR (hazard ratio [HR] = 1.69, 95% confidence interval [CI]: 1.200–2.382, P = 0.003), worse leukemia-free survival (HR = 1.812, 95% CI: 1.168–2.812, P = 0.008), and overall survival (HR = 2.354, 95% CI: 1.528–3.627, P < 0.001). Conclusion: Our results suggest that persistent positive MRD before transplantation, rather than positive MRD at single timepoint, could predict poor outcome both in MSDT and haplo-SCT settings. Key words: Allogeneic Stem Cell Transplantation; Flow Cytometry; Haploidentical Allograft; Human Leukocyte Antigen-Matched Sibling Donor Transplantation; Minimal Residual Disease

Background: Antihypertensive drugs have been linked to new-onset osteoporotic fracture (NOF), and different classes of antihypertensive drugs may alter the risk for the development of NOF; however, the classic effect of different antihypertensive drugs on the development of NOF in the elderly has not been well studied during long-term follow-up. Methods: In this study, we investigated the association between different classic antihypertensives and the development of NOF in the elderly. This was a longitudinal cohort study performed using data from claim forms submitted to the Taiwan Bureau of National Health Insurance in Central Taiwan, China including case patients with NOF aged 65–80 years from January 2002 to December 2012 and non-NOF controls. Prescriptions for antihypertensives before the index date were retrieved from a prescription database. We estimated the hazard ratios (HR s) of NOF associated with antihypertensive use. Non-NOF controls served as the reference group. Results: A total of 128 patients with NOF were identified from among 1144 patients with hypertension during the study period. The risk of NOF after adjusting age, sex, comorbidities, and concurrent medications was higher among the users of angiotensin-converting enzyme (ACE) inhibitors (HR, 1.64; 95% confidence interval [CI], 1.01–2.66) than among nonusers. Patients who took calcium channel blockers (CCBs) (HR, 0.70; 95% CI, 0.49–0.99) were at a lower risk of developing NOF than nonusers. Loop diuretics, thiazide diuretics, angiotensin receptor blocker, beta-blocker, and alpha-blocker were not associated with the risk of NOF. Conclusions: Elderly with hypertension who take CCBs are at a lower risk of NOF and that the use of ACE inhibitors was associated with a significantly increased risk of developing NOF during the 11-year follow-up.

The dose of certain cell types in allografts affects engraftment kinetics and clinical outcomes after allogeneic stem cell transplantation (SCT). Hence, the present study investigated the association of cell compositions in allografts with outcomes after unmanipulated haploidentical SCT (haplo-SCT) for patients with acquired severe aplastic anemia (SAA).A total of 131 patients with SAA who underwent haplo-SCT were retrospectively enrolled. Cell subsets in allografts were determined using flow cytometry. To analyze the association of cellular compositions and outcomes, Mann-Whitney U nonparametric tests were conducted for patient age, sex, weight, human leukocyte antigen mismatched loci, ABO-matched status, patient ABO blood type, donor-recipient sex match, donor-recipient relationship, and each graft component. Multivariate analysis was performed using logistic regression to determine independent influence factors involving dichotomous variables selected from the univariate analysis.A total of 126 patients (97.7%) achieved neutrophil engraftment, and 121 patients (95.7%) achieved platelet engraftment. At 100 days after transplantation, the cumulative incidence of II-IV acute graft-versus-host disease (GVHD) was 32.6%. After a median follow-up of 842 (range: 124-4110) days for surviving patients, the cumulative incidence of total chronic GVHD at 3 years after transplantation was 33.7%. The probability of overall survival at 3 years was 83.0%. Multivariate analysis showed that higher total doses of CD14These results provide evidence and explain that higher doses of CD34

In bone marrow transplant patients, the microenvironment in bone marrow is damaged after chemotherapy or radiotherapy. Subsequent to allogenic hematopoietic stem cell transplantation in patients with clinically successful engraftments, the source of mesenchymal stem cells (MSCs) remains controversial. To further verify the stimulatory effect of the simultaneous transplantation of cells from second donors on engraftment success for hematopoietic stem cell transplantation in support of donor MSCs engraftments, the aim of this study is to monitor the dynamics of the engraftment of bone marrow-derived MSCs in patients after transplantation with mismatched-sex hematopoietic stem and third-party cells.In this study, the hematopoietic stem cells from 32 clinical donors of different sexes that resulted in successful engraftments were selected for transplantation and were classified into three groups for research purposes: group A consisted of 14 cases of transplantation with bone marrow and recruited peripheral hematopoietic stem cell transplantation, group B contained 8 cases of simultaneous re-transfusion of MSCs from the second donor, and group C contained 10 cases of simultaneous re-transfusion of umbilical blood from the second donor. The bone marrow from 32 patients with successful engraftments of hematopoietic transplantation were selected and sub-cultured with MSCs. Flow cytometry (FCM) was used to measure the expression of surface antigens on MSCs. Denaturing high-performance liquid chromatography (DHPLC) in combination with polymerase chain reaction amplification of short tandem repeats (STRPCR) was used to measure the engraftment status of fifth-generation MSCs in patients. Fluorescence in situ hybridization (FISH) revealed the sex origin of the fifth-generation MSCs in 32 patients. Dynamic examinations were performed on patients receiving donor transplantations.The progenies of fifth-generation MSCs were successfully cultured in 32 cases. The results of FCM demonstrated that the expression levels of CD14+ and CD45+ cells were lower than 0.04% in the fifth-generation MSCs. The analysis using DHPLC and FISH showed similar results. One patient from group B also received a temporary transplantation of MSCs from the donor. The MSCs in the remaining 31 patients all originated from the patients themselves.After transplantation, the MSCs present in patients originated from the host. In patients transplanted with MSCs from a second donor, the phenomenon of temporary chimerization of MSCs was observed.

Chronic graft-versus-host disease (GVHD), the commonest long-term complication after allogeneic hematopoietic stem cell transplantation (HSCT), has a negative impact on patients' health related quality of life (HRQoL). This study was designed to investigate the HRQoL in patients with chronic GVHD in China.Two hundred and sixty-four patients with chronic GVHD who were ≥ 24 months post-HSCT and had been in continuous complete remission since HSCT were enrolled in this retrospective study. HRQoL was evaluated using an SF-36 questionnaire. Multivariate analysis was used to identify the factors that affect HRQoL in patients with chronic GVHD.HRQoL in patients categorized as having mild and moderate chronic GVHD was significantly better than in those in the severe category. In the moderate chronic GVHD category, markedly poorer HRQoL was observed in patients with both multiple organ involvement and more severe organ impairment than in those without these factors. According to multivariate analysis, chronic GVHD severity had the greatest significant negative impact on patients' HRQoL; whereas being female was associated with a negative impact on psychological health.Chronic GVHD severity strongly correlates with negative impacts on patients' HRQoL.

Umbilical cord blood (UCB) has grown substantially as an alternative source of hematopoietic stem cells for unrelated donor transplantation in both adult and pediatric patients. Our aim was to assess the leukemia-free survival (LFS) and some primary results, such as hematologic recovery, risk of graft-versus-host disease (GVHD), relapse, and long-term survival, after unrelated cord blood transplantation compared with the outcomes of transplantations from other unrelated graft source.The clinical outcomes of 112 consecutive patients with acute leukemia who received umbilical cord blood (UCBT) as a primary unrelated stem cell source (n = 38), bone marrow (UBMT n = 28, transplanted before January 2003), or peripheral blood stem cells (UPBSCT n = 46, transplanted after January 2003) between July 2000 and July 2008 were analyzed.Except that the patients were much younger in the UCBT group (median age, 10.5 years in UCBT, 30 years in UPBSCT, and 20 years in UBMT), other pre-transplant parameters, such as gender, diagnosis, and the phase of disease, were comparable. All patients received myeloablative regimens, primarily including BUCY; however, there was less anti-thymocyte globulin (ATG) used for the UBMT patients (2/38 in UCBT, 0/46 in UPBSCT, and 8/28 in UBMT did not use ATG, P = 0.000). Significant delays in engraftment occurred after UCBT for both neutrophil cells and platelets. The cumulative allo-engraftment rates were also significantly lower (87.8% vs. 97.8% vs. 100% for WBC, P = 0.000; 73.0% vs. 97.5% vs. 89.5% for PLT, P = 0.000) for UCBT. The incidence of Grade 2-4 and 3-4 acute graft versus host disease (aGVHD) was much higher in the UBMT group but did not differ among the other groups (51% and 13.2%, 40.2% and 10.5%, and 77.4% and 41.2%, respectively, for UCBT, UPBSCT, and UBMT, P = 0.000). The occurrence of extensive chronic GVHD (cGVHD) was significantly decreased for recipients of UCBT (4%) compared with that of UPBSCT (39.1%) and UBMT (49.1%, P = 0.000), although the rates of whole cGVHD were not significantly different (30.3%, 63.1%, and 60.1% for UCBT, UPBSCT, and UBMT, respectively). The patients had a similar rate of CMV infection (21/38, 28/46, and 22/28 for UCBT, UPBSCT, and UBMT, respectively), while the HC occurrence was lower after UCBT (7/38, 16/46, and 14/28 for UCBT, UPBSCT, and UBMT, respectively). As of August 2012, there was no apparent difference in 5-year overall survival (OS), LFS, or the relapse rate for each graft source (52.5%, 52.6%, and 20.8% in UCBT; 48.7%, 46.4%, and 27.9% in UPBSCT; and 46.4%, 42.9%, and 16.0% in UBMT).These data support the use of UCB donors as an alternative allogeneic donor.

The occurrence of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rare but severe. We examine the role of pre-HSCT chemotherapeutic exposure, pre-HSCT comorbidities, and transplant-related complications in the development of BOS after allo-HSCT.A nested case-control study was designed. Cases with BOS and controls matched for the year of allo-HSCT and length of the follow-up were identified from a cohort of 1646 patients who underwent allo-HSCT for treatment of hematologic malignancies between 2006 and 2011. Antithymocyte globulin was used in the partial matched related and unrelated matched donor HSCT, or patients with severe aplastic anemia.Thirty-six patients suffered from BOS; the mean age at the time of presentation was (32.7 ± 12.4) years, and the mean time to presentation was (474 ± 350) days post-HSCT. A pre-HSCT cyclophosphamide dose of ≥ 3.2 g/m(2)(OR = 8.74, P = 0.025), chronic graft-versus-host disease (moderate to severe) (OR = 12.02, P = 0.000), and conditioning regimens without antithymocyte globulin (OR = 2.79, P = 0.031) were independently associated with BOS.We found that higher pre-HSCT cyclophosphamide exposure, a conditioning regimen without antithymocyte globulin, and moderate to severe chronic graft-versus-host disease are significantly and independently associated with BOS. Based on these results, we can identify patients who are at a higher risk of developing BOS after allo-HSCT, select a more appropriate therapeutic strategy, and improve the outcome of HSCT recipients.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for many hematological diseases, but there are many complications following allo-HSCT, among which neurological complications (NC) are one of the most commonly described ones. However, little is known about idiopathic inflammatory demyelinating diseases (IIDDs) of the central nervous system (CNS) in patients following allo-HSCT.A nested case-control study was conducted in a large cohort of 1365 patients, who underwent allo-HSCT at the Institute of Hematology and Peking University People's Hospital, between January 2004 and December 2009, 36 patients of whom developed CNS IIDDs. Kaplan-Meier method, univariate and multivariate Cox regression were applied in our statistical analysis using SPSS 16.0.The cumulative incidence of all cases of IIDDs at 6 years posttransplantation was 3.6%. Thirty-five patients (97.2%) suffered IIDDs after transplantation, 16 patients (44.4%) between day 0 to day 100 post-transplantation, 10 patients (27.8%) between day 100 to 1 year post-transplantation, and 9 patients (25.0%) 1 year post-transplantation. Multivariate regression analysis identified donor type (P = 0.031), infection (P = 0.009), and acute lymphatic leukemia (P = 0.017) as independent risk factors for posttransplantation IIDDs. The median survival time of patients with IIDDs was 514 days after transplantation (95%CI: 223 - 805). Survival at 6 years was significantly lower in patients who developed the diseases compared to those who did not (26.6% vs. 73.5%, P0.001). Of the 36 patients experiencing IIDDs, 58.3% (n = 21) died. The causes of death were graft-versus-host disease (GVHD) (n = 4), underlying disease relapse (n = 3), infections (n = 12), and other causes (n = 2).IIDDs is an uncommon but serious complication of allo-HSCT, especially in patients with a primary diagnosis of acute lymphatic leukemia, mismatched transplants, and infections. Our study results indicate that patients with IIDDs tend toward a poor prognosis following allo-HSCT.

Chimerism analysis is an important tool for the surveillance of post-transplant engraftment. It offers the possibility of identifying impending graft rejection and recurrence of underlying malignant or non-malignant disease. Here we investigated the quantitative chimerism kinetics of 21 relapsed leukemia patients after allogeneic hematopoietic stem cell transplantation (HSCT).A panel of 29 selected sequence polymorphism (SP) markers was screened by real-time polymerase chain reaction (RT-PCR) to obtain the informative marker for every leukemia patient. Quantitative chimerism analysis of bone marrow (BM) samples of 21 relapsed patients and 20 patients in stable remission was performed longitudinally. The chimerisms of BM and peripheral blood (PB) samples of 14 patients at relapse were compared.Twenty-one patients experienced leukemia relapse at a median of 135 days (range, 30 - 720 days) after transplantation. High recipient chimerism in BM was found in all patients at relapse, and increased recipient chimerism in BM samples was observed in 90% (19/21) of patients before relapse. With 0.5% recipient DNA as the cut-off, median time between the detection of increased recipient chimerism and relapse was 45 days (range, 0 - 120 days), with 76% of patients showing increased recipient chimerism at least 1 month prior to relapse. Median percentage of recipient DNA in 20 stable remission patients was 0.28%, 0.04%, 0.05%, 0.05%, 0.08%, and 0.05% at 1, 2, 3, 6, 9, and 12 months, respectively, after transplantation. This was concordant with other specific fusion transcripts and fluorescent in situ hybridization examination. The recipient chimerisms in BM were significantly higher than those in PB at relapse (P = 0.001).This SP-based RT-PCR assay is a reliable method for chimerism analysis. Chimerism kinetics in BM can be used as a marker of impending leukemia relapse, especially when no other specific marker is available. Based on our findings, we recommend examining not only PB samples but also BM samples in HSCT patients.

Intensive treatment such as autologous peripheral blood stem cell (PBSC) transplantation is an important therapeutic strategy in many hematologic malignancies. A number of factors have been reported to impact PBSC mobilization, but the predictive factors varied from one study to another. This retrospective study assessed our current mobilization and collection protocols, and explored the factors predictive of PBSC mobilization in patients with hematologic malignancies.Data of 64 consecutive patients with hematologic malignancies (multiple myeloma, n = 22; acute leukemia, n = 27; lymphoma, n = 15) who underwent PBSC mobilization for over 1 year were analyzed. Four patients with response to treatment of near complete remission or better were administered granulocyte colony-stimulating factor (G-CSF) to mobilize PBSCs. Sixty patients received G-CSF followed by chemotherapy mobilizing regimens. Poor mobilization (PM) was defined as when ≤ 2.0'10(6) CD34(+) cells/kg body weight were collected within three leukapheresis procedures.The incidence of PM at the first mobilization attempt was 19% (12/64). The PM group was older than the non-PM group (median age, 51 vs. 40 years; P = 0.013). In univariate analysis, there were no significant differences in gender, diagnosis, and body weight between the PM and non-PM groups. A combination of chemotherapy and G-CSF was more effective than G-CSF alone as a mobilizing regimen (P = 0.019). Grade III or IV hematopoietic toxicity of chemotherapy had no significant effect on the mobilization efficacy. Supportive care and the incidence of febrile neutropenia were not significantly different between the two groups. In multivariate analysis, age (odds ratio (OR), 9.536; P = 0.002) and number of previous chemotherapy courses (OR 3.132; P = 0.024) were two independent negative predictive factors for CD34(+) cell yield. PM patients could be managed well by remobilization.Older age and a heavy load of previous chemotherapy are the negative risk factors for PBSC mobilization.

Both human hereditary spherocytosis (HS) and chronic myelogenous leukemia (CML) are life threatening. Herein we have reported the case of a woman with a combined disorder of HS and CML who underwent the matched sibling allogeneic stem cell transplantation. The complete donor erythroid cells were obtained. The red blood cell counts significantly improved throughout life comparing with pre-hematopoietic stem cell transplantation (HSCT). Reticulocyte counts normalized, and BCR-ABL was cleared away. The total bilirubin level was also corrected in this recipient. Our case is a rare example with a combined disorder of HS and CML following allogeneic stem cell transplantation. HS was not a contraindication for patient in the matched sibling transplant setting.

Analysis of changes in recipient and donor hematopoietic cell origin is extremely useful to monitor the effect of hematopoietic stem cell transplantation (HSCT) and sequential adoptive immunotherapy by donor lymphocyte infusions. We developed a sensitive, reliable and rapid real-time PCR method based on sequence polymorphism systems to quantitatively assess the hematopoietic chimerism after HSCT.A panel of 29 selected sequence polymorphism (SP) markers was screened by real-time PCR in 101 HSCT patients with leukemia and other hematological diseases. The chimerism kinetics of bone marrow samples of 8 HSCT patients in remission and relapse situations were followed longitudinally.Recipient genotype discrimination was possible in 97.0% (98 of 101) with a mean number of 2.5 (1-7) informative markers per recipient/donor pair. Using serial dilutions of plasmids containing specific SP markers, the linear correlation (r) of 0.99, the slope between -3.2 and -3.7 and the sensitivity of 0.1% were proved reproducible. By this method, it was possible to very accurately detect autologous signals in the range from 0.1% to 30%. The accuracy of the method in the very important range of autologous signals below 5% was extraordinarily high (standard deviation1.85%), which might significantly improve detection accuracy of changes in autologous signals early in the post-transplantation course of follow-up. The main advantage of the real-time PCR method over short tandem repeat PCR chimerism assays is the absence of PCR competition and plateau biases, with demonstrated greater sensitivity and linearity. Finally, we prospectively analyzed bone marrow samples of 8 patients who received allografts and presented the chimerism kinetics of remission and relapse situations that illustrated the sensitivity level and the promising clinical application of this method.This SP-based real-time PCR assay provides a rapid, sensitive, and accurate quantitative assessment of mixed chimerism that can be useful in predicting graft rejection and early relapse.

The cause of late-onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains obscure. In clinical practice, some LOHC patients respond to immunosuppression. The aim of this study was to determine the immune pathogenesis of LOHC post allo-HSCT.With the diagnosis of LOHC, patients were given initial treatment consisting of fluid hydration, alkalization and forced diuresis, and empirical anti-viral therapy for 10 - 14 days or until a week after the virus became negative. The nonresponders were applied corticosteroid. Seven to ten days later, patients' response was evaluated. Along with treatment, CD19(+) B lymphocyte subsets were measured at various study points.From October 2009 to March 2010, we found 28 cases of LOHC occurred in 25 patients who underwent allo-HSCT in our hospital. Except that three cases were not treated according to the protocol, the other 25 cases were divided into three groups: anti-virus responders (Group A, n = 6), corticosteroid responders (Group B1, n = 16), corticosteroid and anti-virus nonresponders (Group C, n = 3) according to their clinical response. Percentages of CD19(+)CD5(+) B lymphocytes were not significantly different among three groups at onset of LOCH. However, in Group B1 after the first anti-virus phase, percentages of CD19(+)CD5(+) lymphocytes significantly increased comparing with those at onset (P = 0.022), and then significantly decreased at PR (P = 0.003) and CR (P = 0.002) with corticosteroid treatment. But significant change was not observed in Groups A and C.The immune etiology seems to be involved in the development of LOHC and the proportion of CD19(+)CD5(+) lymphocytes may serve as a cellular biomarker to predict the response to corticosteroid in LOHC.

Relapse happens frequently after allogeneic hematopoietic cell transplantation (allo-HCT) in the patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL). Detection of the minimal residual disease (MRD) before and after allo-HCT is associated with higher relapse rate. Early administration of imatinib after allo-HCT may prevent recurrent Ph(+) ALL. The aim of this study was to evaluate the safety and efficacy of imatinib in preventing hematological relapse when imatinib was administrated in the first 90 days after allo-HCT.Patients with Ph(+) ALL that underwent allo-HCT were enrolled in a prospective study. A TaqMan-based real-time quantitative polymerase chain reaction (RQ-PCR) technique was used to detect the MRD (bcr-abl transcript levels). Imatinib therapy was initiated prior to 90 days after allo-HCT if the patient's absolute neutrophil count (ANC) was above 1.0 × 10(9)/L (without granulocyte colony-stimulating factor (G-CSF) administration) and the platelet count was greater than 50.0 × 10(9)/L, or if the bcr-abl transcript levels were elevated in two consecutive tests, or if the bcr-abl transcript levels were ≥ 10(-2) after the initial engraftment. The initial daily dose of imatinib was 400 mg/d for adults and 260 mg/m(2) for children (younger than 17 years). Imatinib was administered for at least 1 month and the bcr-abl TaqMan results were negative for 3 consecutive tests, or complete molecular remission (CR(mol)) was sustained for at least 3 months.From May 2005 to October 2008, 29 patients were enrolled in this study, of whom, 19 patients were male and 10 were female. The median age of the enrolled patients was 33 years (range 6 - 50 years). Imatinib therapy was started at a median time of 60 days (range 20 - 122 days) post HCT (only one patient started Imatinib therapy at 122nd day after HCT). Twenty-five adult patients could tolerate a dose of 300 - 400 mg/d of imatinib, and three children tolerated a dose of 260 mg×m(-2)×d(-1). Sixty-eight percent of the patients experienced various adverse events during imatinib therapy, hematological toxicity being the most common adverse event. The median duration of imatinib treatment was 3 months (range 7 days-18 months). During the median follow-up of 24 months (range 16.0 - 54.5 months), 3 out of 27 patients that could be evaluated for efficacy died from relapse. The 3-year probability of relapse for the evaluated patients was (11.3 ± 0.61)%. The relapse rates among the subgroup of positive and negative bcr-abl patients before allo-HCT were 13.6% and 0, respectively (P0.05). The relapse rates among the subgroups of bcr-abl positive and negative patients after allo-HCT were 20.0% and 5.9%, respectively (P0.05). The relapse rates among the patients in first complete remission (CR(1)) and second complete remission/non-remission (CR(2)/NR) before transplantation were 0 and 31.4%, respectively (P0.05). The 3-year probability of overall survival (OS) and disease-free survival (DFS) for the all enrolled patients were (75.3 ± 8.1)%. The 3-year probabilities for OS and DFS among the subgroup of patients in CR(1) and CR(2)/NR before transplantation were (87.7 ± 8.2)% and (54.6 ± 15.0)%, respectively (P0.05).Administration of imatinib at a dose of 300 - 400 mg/d in the first 90 days after allo-HCT is feasible in Ph(+) ALL patients. With this treatment, bcr-abl positive patients before or after transplantation do not have a higher relapse rate after allo-HCT compared with the bcr-abl negative patients. Because of lower relapse rate and better OS and DFS, we recommend that Ph(+) ALL patients receive allo-HCT in CR₁.

Despite its widespread use in the management of HIV-related cytomegalovirus (CMV) infection, there have been surprisingly few reports of the use of valganciclovir (VGC) in the post-allotransplant setting. So far, no multi-center, non-crossover trial data have been available with the use of this drug as the primary pre-emptive. The present study evaluated the efficacy and safety of VGC for preemptive therapy of CMV infection after allogeneic hematopoietic stem cell transplantation (HSCT).From January to April 2007, VGC was adopted in eleven centers in mainland China for pre-emptive therapy of CMV infection in consecutive patients undergoing allogeneic HSCT. Allogeneic HSCT recipients were followed weekly via CMV pp65 antigenemia assay or real-time quantitative polymerase chain reaction (PCR) for detection of CMV-DNA. Patients with a positive assay were treated with VGC, 900 mg P.O. twice a day for 14 days followed by 900 mg P.O. once a day for 14 days after a negative result or the CMV-DNA load was lower.A total of 54 patients (15 siblings, 28 mismatched related donors, 11 unrelated donors) had a positive assay treated with oral VGC. The seroconversion rate was 89% (48/54) as confirmed by a negative assay; six patients failed oral VGC. No significant toxicity was encountered. No case of CMV disease was diagnosed in the responding patients with a median follow-up of 5.3 months after the drug administration.Pre-emptive therapy of CMV viraemia with oral VGC is safe and effective in allogeneic HSCT.

Background The pathophysiology of late-onset hemorrhagic cystitis (LOHC) is currently not well understood. The aim of this study was to analyze the alloimmune aetiology in the pathogenesis of LOHC post allogeneic hematopoietic stem cell transplantation (HSCT). Methods A retrospective study was performed on the medical records of 11 patients with immune-related LOHC post allogeneic HSCT. The clinical characteristics, therapy, and outcomes of these patients were analyzed. Results The median time of onset was 42 days after HSCT (range 16-150 days) and the median duration of HC was 43 days (range 29-47 days). All patients presented with prolonged HC for more than 35 days. Nine patients with evidence of cytomegalovirus (CMV) reactivation did not respond to anti-viral therapy even with CMV clearance in the urine post-therapy. Eleven patients with refractory HC received a low dose of corticosteroids and all patients went into complete remission. Conclusion Our data suggest that alloimmune injury is involved in the pathogenesis of HC in at least some patients and that specific therapy might improve the clinical outcome of hemorrhagic cystitis.

BACKGROUND The definite pathogenesis of hemorrhagic cystitis (HC) after allogenic hematopoietic stem cell transplantation (allo-HSCT) has not been well elucidated. The role of cytomegalovirus (CMV) reactivation and graft-versus-host disease (GVHD) in the development of HC remains obscure. This study determined the incidence and risk factors for HC after allo-HSCT and analyzed its association with CMV reactivation and GVHD. METHODS We retrospectively studied 250 patients at high risk for CMV disease who underwent allo-HSCT all based on busulfan/cyclophosphamide (BU/CY) myloablative regimens. The incidence, etiology, risk factors and clinical management of HC were investigated. RESULTS HC developed within 180 days of transplant in 72 patients, with an overall incidence of 28.8% and an incidence of 12.6% in patients with HLA-matched related donors (MRD), 34.38% in those with HLA-matched unrelated donors (MUD), 49.45% in those with mismatched related donors (MMRD). CMV-viremia significantly increased the incidence of later onset HC (LOHC); however, only 9 out of 15 patients with CMV viruria actually developed LOHC. Multiple regression analysis identified grade II - IV acute GVHD (RR = 2.75; 95% CI 1.63 +/- 4.66; P < 0.01) and grafts from MUD or MMRD (RR = 2.60; 95% CI 1.52 +/- 5.20; P < 0.01) as independent risk factors for HC. Event sequence analysis indicated a majority of HC episodes began around GVHD initiation. CONCLUSIONS CMV-viremia is a high risk factor for LOHC. Our data also showed a correlation between acute GVHD and HC, which suggested that alloimmunity may be involved in the pathogenesis of HC.

Background Allogeneic stem cell transplantation is a potential curative approach in patients with multiple myeloma. The very high transplant related mortality associated with standard allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative treatment modality. The challenge for clinical investigators is to reduce the incidence of post-transplant complications for patients receiving autologous hematopoietic stem cell transplantion for multiple myeloma. In this study the toxicity and efficacy of modified myeloablative conditioning regimen followed by allogeneic stem cell transplantation was investigated in patients with multiple myeloma. Methods The conditioning regimen consisted of hydroxyurea, cytarabine, busulfan, cyclophosphamide, and semustine. Ten patients underwent allogeneic transplantation among them hydroxyurea (40 mg/kg) was administered twice on day-10 and cytarabine (2 g/m(2)) was given on day-9, busulfan was administered orally in four divided doses daily for 3 days (days-8 to -6). The dose of busulfan was 12 mg/kg in the protocol followed by cyclophosphamide intravenously over 1 hour on days-5 and -4 (1.8 g/m(2)), and with semustine (Me-CCNU) 250 mg/m(2) on day -3. Results Chimerism data were available on all patients and all patients achieved full donor chimerism without graft failure. Six patients had not acute graft-versus-host disease (GVHD, 36.4%; 95% CI: 13.9% - 38.6%). Two patients (18.2%) developed grade I acute GVHD (95% CI: 10.9% - 35.9%) and grade II acute GVHD occurred in one patient (9.1%; 95% CI: 8.4% - 32.3%). Severe grade IVa GVHD was seen in one patient, who died from acute GVHD. The incidence of chronic GVHD was 22.2% (95% CI: 11.7% - 36.7%), among them one died of severe grade IV GVHD and one developed multiorgan failure on day +170; the treatment-related mortality was 22.0% (95% CI: 10.3% - 34.1%). The overall 4-year survival rate was 67.8% (95% CI: 16.3% - 46.7%). The estimated 4-year progression-free survival rate was 58.5% (95% CI: 13.7% - 41.8%). The 4-year complete remission was 72.7% (95% CI: 27.8% - 49.6%). One patient relapsed after 4 months and achived the complete remission after receiving the donor lymphocyte infusion. Conclusions Modified conditioning regimen busulfan-cyclophosphamide with peripheral blood stem cells + bone marrow cells transplantation result in a low incidence of severe GVHD with a relatively low treatment-related mortality, high complete remission rates and a long-term survival.

Many patients requiring allogeneic hematopoietic stem cell transplantation (HSCT) do not have an human leukocyte antigen (HLA)-matched donor. Alternative donors, such as HLA mismatched family donors, are associated with higher rates of graft rejection and acute graft versus host disease (aGVHD) if T cells are not first depleted. We developed a new technique for HLA mismatched allogeneic HSCT using G-CSF primed bone marrow plus G-CSF-mobilized peripheral blood stem cells without ex vivo T cell depletion.In this study, 58 patients, including 33 with high-risk or advanced leukemia, were transplanted with cells from an HLA-haploidentical family donor with 1 - 3 mismatched loci. After conditioning, patients received G-CSF-primed bone marrow grafts that had not been depleted ex vivo of T cells, in combination with G-CSF-mobilized peripheral blood stem cells, as well as GVHD prophylaxis.All patients achieved sustained, full donor-type engraftment. The incidence of grade II-IV aGVHD was 37.9%, including 3 patients with grade III-IV aGVHD. The development of aGVHD was not associated with the extent of HLA disparity. Chronic GVHD was observed in 30 of 51 evaluable patients (65.4%). Fourteen patients died among whom 7 died of recurrent disease and 7 of transplant-related complications. Forty-four of the 58 patients survived, and 42 remained disease free at the time of a median follow-up of 12 months (3.5 to 39.5 months). The 2-year probabilities of disease-free survival were 74.8% and 69.3% for standard- and high-risk patients, respectively.We developed a new method to use bone marrow from haploidentical family donors without ex vivo T cell depletion, in combination with G-PBSCs, as a source of stem cells even in cases of HLA mismatched transplantation.