Search

Background: The aim of this study is to evaluate the prognostic impact of myeloid-derived suppressor cells (MDSCs) in multiple myeloma (MM) in the context of autologous stem cell transplantation (ASCT)., Methods: Peripheral blood samples were collected for measuring monocytic (M-) MDSCs (CD14 pos HLA-DR low/neg ) and early-stage (E-) MDSCs (Lin neg HLA-DR neg CD33 pos CD11b pos ) before and after ASCT. Clinical outcomes following ASCT differed according to the frequency of each MDSC phenotype., Results: In the pre-ASCT analyses, lower M-MDSCs (

Background: Effective treatment options for patients with chronic myeloid leukemia (CML) or Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) who have the threonine to isoleucine mutation at codon 315 (T315I) are few. The objective of this study was to compare overall survival (OS) between patients with CML and those with Ph+ ALL who received treatment with ponatinib versus allogeneic stem cell transplantation (allo-SCT)., Methods: A post hoc, retrospective, indirect comparison of OS among patients who received single-agent ponatinib in the Ponatinib Ph+ ALL and CML Evaluation (PACE) trial with those who underwent allo-SCT as reported to the European Bone Marrow Transplant registry, stratified by CML disease phase and Ph+ ALL, was conducted. Kaplan-Meier survival curves and multivariate Cox proportional-hazards models were used to compare OS between intervention groups, adjusting for time from diagnosis to intervention, age, sex, and geographic region; 24-month and 48-month OS rates and median OS were reported., Results: After adjustment for potential confounders, 24-month and 48-month OS rates were significantly higher in patients with chronic-phase CML (CP-CML) who received ponatinib compared with those who underwent allo-SCT (24 months: 84% vs 60.5%, respectively; P = .004; 48 months: 72.7% vs 55.8%, respectively; P = .013), with a hazard ratio (HR) of 0.37 (95% confidence interval [CI], 0.16-0.84; P = .017). In patients who had accelerated-phase CML, OS rates were not significantly different between the groups (HR, 0.90; 95% CI, 0.20-4.10; P = .889). In patients who had blast-crisis CML and those with Ph+ ALL, ponatinib was associated with shorter OS compared with allo-SCT (blast-crisis CML: HR, 2.29 [95% CI, 1.08-4.82; P = .030]; Ph+ ALL: HR, 2.77 [95% CI, 0.73-10.56; P = .146])., Conclusions: Although allo-SCT remains an important treatment option for patients with T315I-positive advanced CML and Ph+ ALL, ponatinib represents a valuable alternative for patients with T315I-positive CP-CML. Cancer 2017;123:2875-80. © 2017 American Cancer Society., (© 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.)

Background/aims: The aim of this study was to identify the role of BCR-ABL1 transcript level as a predictor for post-transplant relapse and outcome in patients who underwent allogeneic stem cell transplantation (SCT) for chronic phase (CP) chronic myeloid leukemia (CML)., Methods: Of 101 patients receiving allograft in CML CP, 85 had available quantitative reverse transcriptase polymerase chain reaction data at post-transplant 3 months. These patients were divided into two groups according to molecular response (MR 4.5 ), defined as a BCR-ABL1 transcript level ≤ 0.0032% on the international scale, at 3 months based on receiver operating characteristic curve analysis of relapse., Results: The 4-year overall survival and event-free survival (EFS) were 80.6% and 57.3%, respectively, and the cumulative incidence of relapse at 4 years was 29.6% after a median follow-up of 126.4 months. We performed multivariate analyses including potential variables to evaluate the early predictive role of MR 4.5 at 3 months and found that MR 4.5 at 3 months was associated with a higher EFS ( p = 0.028) and showed a trend for a lower relapse rate ( p = 0.089)., Conclusions: our results imply that frequent molecular monitoring and immune suppressive therapy modulation are required for patients without reduction of BCR-ABL1 transcripts to this level after SCT., Competing Interests: No potential conflict of interest relevant to this article was reported.

CD161 is a type II transmembrane glycoprotein with characteristics of the C-type lectin superfamily, which has recently been shown to promote T cell expansion. In this study, the role of T cells expressing CD161 as a predictor for the occurrence of acute graft-versus-host disease (aGVHD) after allogeneic stem cell transplantation (SCT) was investigated. Sixty-one patients who underwent first allogeneic SCT were enrolled. At engraftment, the expression of CD3, CD4, CD8, CD161, CD16, and CD56 was analyzed by flow cytometry. After adjusting for potential variables by univariate analysis, we performed a multivariate analysis, which revealed a low frequency of CD8(+)CD161(+) cells (P = .034) and a high ratio of CD4(+)CD161(+) to CD8(+)CD161(+) cells (P = .001) were associated with the occurrence of aGVHD with a grade of ≥ II. Moreover, the frequency of CD8(+)CD161(+) T cells was negatively correlated with aGVHD grade. A separate analysis for visceral aGVHD showed similar results, with a low frequency of CD8(+)CD161(+) T cells (P = .031) or a high ratio of CD4(+)CD161(+) to CD8(+)CD161(+)cells (P < .001), indicating a high risk. Also, the predictive role of serum IL-17 levels for the occurrence of aGVHD was identified, and RORγT was more highly expressed in CD4(+)CD161(+) T cells than in CD8(+)CD161(+) T cells after allogeneic SCT (P = .032). Although our study was limited by the heterogeneity and small number of patients, these results suggest that the CD8(+) subset of CD161(+) T cells may have regulatory effects and that they provide a basis for predicting the occurrence of aGVHD after allogeneic SCT., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

We analyzed the outcome of stem cell transplantation (SCT) for 59 acute myeloid leukemia (AML) patients with t(8;21). The 5-year overall and disease-free survival (OS and DFS) were 70.2 and 68.4%, respectively. The 5-year cumulative incidence of relapse (CIR) and nonrelapse mortality were 16.9 and 13.6%, respectively. OS and DFS in the reduced-intensity conditioning (RIC)-SCT group (70.4%) were not different from in the autologous SCT (ASCT) group (72.4 and 69.0%, respectively). Age was a factor affecting OS (p = 0.007) and DFS (p = 0.008) in the ASCT group, but not in the RIC-SCT group. In the ASCT group, lack of the X chromosome (-X) and an age of >50 years were associated with inferior survival; however, these differences disappeared in the RIC-SCT group. CIR was significantly higher in patients with -X than in those without -X only in the ASCT group (p = 0.038), i.e. not in the RIC-SCT group. ASCT and RIC-SCT are equally effective for the intensification of postremission treatment of AML patients with t(8;21). The subgroups with advanced age or -X should be preferentially considered for RIC-SCT, rather than ASCT. Further investigations with randomized prospective trials of a sizeable study population are warranted.

Background: In unrelated donor allogeneic stem cell transplantation (URD-SCT), most studies reported that peripheral blood stem cells (PBSC) resulted in higher incidence of acute and/or chronic graft-versus-host disease (GVHD) without survival benefits compared with bone marrow (BM). To overcome these shortcomings of PBSC, we have used a risk-adapted GVHD prophylaxis for patients that received HLA-matched URD-SCT, which was adding low-dose rabbit antithymocyte globulin (Thymoglobulin(®) , 1.25 mg/kg for 2 d) to conditioning in the transplants with PBSC and not BM., Methods: To determine whether this strategy is effective, we analyzed 115 adult patients with acute myeloid leukemia who received HLA-matched URD-SCT with PBSC (n = 70) or BM (n = 45) using our risk-adapted GVHD prophylaxis strategy., Results: The PBSC group showed faster neutrophil (11 d vs. 13 d; P < 0.01) and platelet (12 d vs. 18 d; P < 0.01) engraftment compared with the BM group. No difference was observed in the incidence of acute GVHD grade II-IV at 100 d (54.3% vs. 64.4%; P = 0.38) and chronic GVHD at 4 yr (65.1% vs. 60.0%; P = 0.83). Other outcomes including the incidence of relapse (30.8% vs. 31.2%; P = 0.53), non-relapse mortality (13.5% vs. 6.9%; P = 0.24), disease-free survival (55.7% vs. 61.9%; P = 0.68), and overall survival (62.2% vs. 63.2%; P = 0.96) at 4 yr were not significantly different., Conclusion: Our risk-adapted GVHD prophylaxis strategy resulted in similar transplant outcomes including comparable incidence of GVHD between the PBSC and BM groups in HLA-matched URD-SCT., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The role of reduced-intensity conditioning (RIC) in adult acute lymphoblastic leukemia (ALL) remains unclear because of the small sample size, short follow-up duration, various regimens for conditioning and graft-versus-host disease (GVHD) prophylaxis, and the heterogeneity of selection criteria for transplantation. We compared long-term outcomes of 60 consecutive RIC transplants (fludarabine plus melphalan) with 120 myeloablative conditioning (MAC) transplants (total body irradiation plus cyclophosphamide) for adult high-risk ALL in first or second complete remission. All transplants received a uniform strategy of pretransplant chemotherapy and GVHD prophylaxis. Compared to MAC transplants, RIC transplants had older age (46 years vs. 33 years, P < 0.001) and higher proportions of transplantation using peripheral blood (93.3% vs. 13.3%; P < 0.001) but otherwise showed similar characteristics. After a median follow-up of 67 months, RIC transplants showed comparable nonrelapse mortality (21.2% vs. 24.3%) and disease-free survival (50.8% vs. 54.9%) to MAC transplants, although relapse risk was higher (34.2% vs. 26.4%; HR, 2.07; P = 0.019) in multivariate analysis. Other independent factors associated with better outcomes were the presence of chronic GVHD and transplantation in first complete remission. Interestingly, the negative impact of RIC on relapse risk was seen only for Philadelphia-positive ALL transplants (32.7% vs. 19.6%; HR, 3.46; P = 0.020), while no difference was found between RIC and MAC for Philadelphia-negative ALL transplants (35.0% vs. 32.1%; HR, 1.39; P = 0.429). RIC can be considered as a reasonable choice for providing a sufficient long-term graft-versus-leukemia effect for adult high-risk ALL patients ineligible for MAC., (Copyright © 2013 Wiley Periodicals, Inc.)

We investigated the effects of environmental enrichment (EE) on the function of transplanted adipose stem cells (ASCs) and the combined effect of EE and ASC transplantation on neurobehavioral function in an animal model of chronic hypoxic-ischemic (HI) brain injury. HI brain damage was induced in 7-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min). At 6 weeks of age, the mice were randomly injected with either ASCs or PBS into the striatum and were randomly assigned to either EE or standard cages (SC), comprising ASC-EE (n=18), ASC-SC (n=19), PBS-EE (n=12), PBS-SC (n=17), and untreated controls (n=23). Rotarod, forelimb-use asymmetry, and grip strength tests were performed to evaluate neurobehavioral function. The fate of transplanted cells and the levels of endogenous neurogenesis, astrocyte activation, and paracrine factors were also measured. As a result, EE and ASC transplantation synergistically improved rotarod latency, forelimb-use asymmetry, and grip strength compared to those of the other groups. The number of engrafted ASCs and βIII-tubulin(+) neurons derived from the transplanted ASCs was significantly higher in mice in EE than those in SC. EE and ASC transplantation also synergistically increased BrdU(+)βIII-tubulin(+) neurons, GFAP(+) astrocytic density, and fibroblast growth factor 2 (FGF2) level but not the level of CS-56(+) glial scarring in the striatum. In conclusion, EE and ASC transplantation synergistically improved neurobehavioral functions. The underlying mechanisms of this synergism included enhanced repair processes such as higher engraftment of the transplanted ASCs, increased endogenous neurogenesis and astrocytic activation coupled with upregulation of FGF2.

Objective: The aim of this study was to determine the optimum conditioning intensity for allogeneic stem cell transplantation (SCT) in young (age ≤50), lower-risk (INT-1 by IPSS) Myelodysplastic syndrome (MDS) patients without significant comorbidities (hematopoietic cell transplantation-comorbidity index score ≤3)., Methods: Transplant outcomes from 46 consecutive patients were retrospectively analyzed according to the conditioning intensity: reduced-intensity conditioning (RIC; n = 14), intensified RIC by adding low-dose total body irradiation (iRIC; n = 15), and myeloablative conditioning (MAC; n = 17)., Results: After a median follow-up of 73.7 months, RIC had a better 4-yr overall survival (OS) (92.9%) compared with the iRIC (64.2%) or MAC (70.6%). Multivariate analysis showed that RIC was associated with improved OS compared with the MAC [relative risk (RR) of 0.08, P = 0.022] because of a lower transplant-related mortality (TRM) (RR, 0.08, P = 0.035). iRIC failed to show survival benefits over the MAC (RR of 0.77, P = 0.689) because of similarly high TRM (RR of 0.41, P = 0.480). Cumulative incidence of acute and chronic graft-versus-host disease (GVHD) after RIC was higher, but GVHD-specific survival was significantly better (RIC 100% vs. iRIC 45.7% vs. MAC, P = 0.018). Relapse rate was not different among the three groups, but in the RIC group, azacitidine was available and useful for inducing remission in two patients., Conclusion: This study shows that RIC improved OS by directly lowering TRM and indirectly giving an additional chance for relapsed MDS in the era of hypomethylating treatment. RIC-SCT should be considered for relative healthy lower-risk MDS patients., (© 2011 John Wiley & Sons A/S.)

Purpose: We intended to determine whether transplanted neural precursors, derived from mouse embryonic stem (ES) cells, can migrate and differentiate into mature neurons and glial cells in damaged brains and improve functional deficits caused by global cerebral ischemic injury in adolescent rats., Methods: Global ischemia was induced using the four-vessel occlusion method. ES cells that display enhanced expression of yellow fluorescent protein were co-cultured in N2 supplemented media with PA6 cells that had stromal derived inducing activity. Neural precursor cells were directly transplanted bilaterally into hippocampal C3 areas 2 weeks after induction of global ischemia. Assessments of the Morris water-maze test at eight weeks and, the Open field activity levels at two, four, six and eight weeks after transplantation were carried out according to standard methods., Results: From neural precursors, we were able to generate neural lineages, including neurons and glial cells in vitro. Eight weeks following transplantation, cellular migration as well as generation of neural cells including neurons, astrocytes, and oligodendrocytes developed from the grafted ES cell-derived neural precursors were observed. Cell-transplanted animals exhibited enhanced functional recovery on sensorimotor and behavioral tests, compared to vehicle-treated control animals., Conclusion: Therefore, transplantation of mouse ES cell-derived neural precursor cells shows promise for improving recovery after global ischemia in adolescent rats., (Copyright 2009 Elsevier B.V. All rights reserved.)

Cell therapy using human embryonic stem cells (hESCs) is a promising therapeutic option for Parkinson's disease (PD), an incurable neurodegenerative disease. A prerequisite for clinical application of hESCs for PD is an efficient and strict differentiation of hESCs into midbrain dopamine (mDA) neuron-like cells, which would be directly translated into high effectiveness of the therapy with minimum risk of undesirable side effects. Due to fruitful efforts from many laboratories, a variety of strategies for improving efficiency of dopaminergic differentiation from hESCs have been developed, mostly by optimizing culture conditions, genetic modification, and modulating intracellular signaling pathways. The rapid advances in the fields of dopaminergic differentiation of hESCs, prevention of tumor formation, and establishment of safe human induced pluripotent stem cells (hiPSCs) would open the door to highly effective, tumor-free, and immune rejection-free cell therapy for PD in the near future., ((c) 2009 Wiley-Liss, Inc.)

In this study, we demonstrate that embryonic stem cells can be engineered to differentiate into high percentages of serotonergic and dopaminergic neurons. In vitro, these cells release serotonin and dopamine in response to membrane depolarization. Upon engraftment into the medial prefrontal cortex in rats, the homolog of the human anterior cingulate cortex, the cells assumed neuronal morphologies, expressed monoaminergic-specific proteins, and seemed to functionally integrate, as assessed by the upregulation of the immediate-early gene, cfos. Furthermore, the transplanted animals performed in a manner similar to that of animals that received the antidepressant, citalopram, when administered the forced swim test, a validated model of human depression. These results suggest that transplantation of customized stem cells might perhaps be useful in the study treatment of psychiatric disorders.

To test the in vivo effect of a high yield of dopaminergic (DA) neurons (90% of total neurons) which had been generated from a genetically modified mouse embryonic stem cell line, N2, the cells were transplanted into a rat model of Parkinson's disease (PD). The PD animals grafted with N2-derived cells showed significant behavior improvements compared with sham controls from 2 weeks posttransplantation, whereas animals with naïve D3-derived cells ( approximately 28% DA neurons of total neurons) showed only a modest recovery. Furthermore, hyperactivity observed in the subthalamic nucleus, pedunculopontine nucleus, and substantia nigra pars reticulata of PD rat models was dramatically reduced by the grafting of N2-derived cells. The number of DA neurons in the striatum which originated from N2 grafting was much higher compared to that from D3 grafting, and the neurons efficiently released DA in the brain, showing a good correlation with behavioral recovery.

The objective of this study was to compare how cyclophosphamide (CY) and oral busulfan (BU) therapies, each in combination with total body irradiation (TBI), affect the outcome of stem cell transplantation in patients with advanced myelodysplastic syndrome. This study was conducted with 31 patients who received bone marrow from an HLA-matched sibling and underwent treatment with BU-TBI (n = 18) or CY-TBI (n = 13). The incidence of acute graft-versus-host disease (GVHD) grades II to IV was higher, but not significantly, in the BU-TBI group (58.8%) than in the CY-TBI group (30.8%). However, the incidences of chronic extensive GVHD were significantly different (41.7% [CY-TBI] versus 80.0% [BU-TBI], P = .04). Trends after BU-TBI conditioning indicated a lower 3-year probability of disease-free survival (DFS) (38.1% versus 53.9%, P = .4), lower relapse rates (28.5% versus 36.4%, P = .8), and higher nonrelapse mortality rates (46.7% versus 15.4%, P = .2). After adjusting for the International Prognostic Scoring System risk group and the cytogenetic risk group, DFS in the CY-TBI group (relative risk, 9.0; 95% confidence interval, 1.5-52.5; P = .015) was found to be significantly increased compared with the BU-TBI group. Approaches to minimize transplantation-related toxicity should be pursued, and efforts other than the potentiation of the conditioning regimen should be made to reduce the likelihood of posttransplantation relapse.

Background: Haploidentical transplantation has become a popular modality of treatment for acute myeloid leukemia (AML) patients lacking donors with matching HLA. We attempted to assess the success rate and ramifications of full haplotype mismatch transplantation., Methods: Four patients received stem cell transplantation from their full haplotype mismatched family donors. The conditioning regimen included total-body irradiation, intravenous busulfan, antithymocyte globulin, and fludarabine. Megadose CD34+ stem cell transplants were performed, in a dosage range between 10.9 x 10(6)/kg and 20.6 x10(6)/kg. Neither GvHD prophylaxis nor post-transplant G-CSF were administered. We monitored patients' bone marrow cellularity and peripheral blood chimerism using real-time PCR., Results: All patients evidenced stable engraftment. The most frequent side effect was severe mucositis, but all patients recovered successfully, without early death. No patients exhibited acute GvHD. Two refractory patients relapsed soon after transplantation. The other 2 patients have remained in good clinical condition, with a follow-up duration of 1-4 months., Conclusion: Using a newly-developed conditioning regimen, we were able to circumvent GvHD and graft failure, which are the main limitations associated with full haplotype mismatch transplantation. According to our analysis of the relevant literature, it appears that this is the first report of such a conditioning regimen.

For cell replacement therapy of neurodegenerative diseases such as Parkinson's disease (PD), methods for efficiently generating midbrain dopaminergic (DA) neurons from embryonic stem (ES) cells have been investigated. Two aspects of DA neuron generation are considered: genetic modification and manipulation of culture conditions. A transcription factor known as critical for development of DA neurons, Nurr1, was introduced into ES cells to see how they facilitate the generation of DA neurons from ES cells. Also, two culture procedures, the 5-stage method and stromal cell-derived inducing activity (SDIA) method, were used for ES cell differentiation. Using the 5-stage method, we and others previously demonstrated that Nurr1-overexpressing ES cells, under treatment of signaling molecules such as SHH and FGF8 followed by treatment of ascorbic acid, can differentiate into DA neurons with a high efficiency (> 60% of TH+/Tuj1+ neurons). Furthermore, using the SDIA method with treatment of signaling molecules, we found that Nurr1-overexpressing ES cells can differentiate to DA neurons with the highest efficiency ever reported (approximately 90% of TH+/Tuj1+ neurons). Importantly, our semi-quantitative and real-time PCR analyses demonstrate that all known DA marker genes (e.g., TH, AADC and DAT) were up-regulated in Nurr1- overexpressing ES cells when compared to the na ve ES cells. These cells produced increased dopamine compared to na ve D3 cells after differentiation. In the in vivo context after transplantation, the genetically modified ES cells also showed the highly increased dopaminergic neuronal phenotypes. Thus, the combination of genetic engineering and appropriate culture conditions provides a useful tool to generate a good cell source from ES cells for cell replacement therapy of degenerative diseases such as PD.

Fourteen adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) were studied to evaluate the role of imatinib prior to allogeneic stem cell transplantation (SCT). Of these, 12 patients were in complete hematologic response (CHR), and 2 were refractory. Imatinib was administered as an interim schedule after each chemotherapy course. After the first imatinib cycle, 11 patients remained in sustained CHR with a decrease in the BCR-ABL/ABL ratios (0.89 logs), and one refractory patient achieved CHR. Meanwhile, 2 patients were resistant to imatinib. Ten patients receiving a second imatinib cycle following consolidation showed sustained CHR, including 2 molecular CR, with a further decrease in the BCR-ABL/ABL ratios (0.19 logs). Twelve patients underwent SCT in a favorable status, and of these, 11 are still alive in a leukemia-free status at 9 to 28+ months after SCT. First-line imatinib interim therapy appears to be a useful strategy to bridge the time to SCT for patients with Ph+ ALL.

Background: The NIH protocol for non‐myeloablative (NMA) conditioning allogeneic stem cell transplantation (alloSCT) with alemtuzumab and low‐dose total body irradiation corrected the abnormal sickle cell disease (SCD) phenotype without the risk of graft‐versus‐host disease. However, alloSCT using NMA conditioning had been rarely applied to β‐thalassemia major (β‐TM) patients. Methods: To avoid prolonged immunosuppression, we developed a two‐stage strategy. Mixed donor chimerism was initially achieved using the protocol developed by the NIH protocol. Thereafter, we facilitated donor chimerism using the optional reinforced stem cell (SC) infusion in cases requiring protracted immunosuppression or experiencing impending graft failure. Results: In this study, β‐TM (n = 9) and SCD (n = 4) patients were equally effectively treated with eradicating the abnormal hemoglobin phenotype. Five patients, including four β‐TM, achieved stable mixed chimerism without receiving optional reinforced SC infusion. All patients that received optional reinforced infusion achieved complete (n = 4) or mixed chimerism (n = 1). The overall survival rate and event‐free survival at 4 years were 91.7% (95% CI; 53.9‐98.8) in both groups, with a thalassemia‐free survival rate in β‐TM patients of 87.5% (95% CI; 38.7‐98.1). Conclusion: This study is the first to report successful NMA conditioning alloSCT to achieve stable mixed chimerism correcting the abnormal hemoglobin phenotype in adult β‐TM patients. [ABSTRACT FROM AUTHOR]

In 27% of diffuse large B cell lymphoma (DLBCL) cases, bone marrow (BM), assessed by BM biopsy, is involved. BM involvement, an extranodal site involvement, affects the International Prognostic Index (IPI) score adversely. However, chromosomal abnormalities are neither included as a prognostic factor nor are they considered in the IPI risk classification category. We retrospectively analyzed 600 DLBCL patients at diagnosis for BM involvement (by both BM biopsy immunohistochemistry [BMI] with karyotyping and 18-fluorodeoxyglucose-positron emission tomography [FDG-PET] high uptake [BMP]). The BM-involved DLBCL patients identified by both BMI and BMP showed significantly inferior survival outcomes. Chromosomal abnormalities, especially complex karyotype (CK) of the involved BM, are related to much worse survival outcomes due to the inadequate treatment response including frontline auto-hematopoietic stem cell transplantation (HSCT). Therefore, CK population should either be considered for more aggressive treatment modalities, such as frontline allo-HSCT, or those further clinical trials are explored for alternative or novel treatment approaches. Furthermore, if the FDG-PET shows high possibility of marrow involvement, bilateral BM biopsy with cytogenetic evaluation should be incorporated into the routine workup for newly diagnosed DLBCL patients. This is to look for other markers of poor-risk factors, such as CK or further genetic mutations. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore if measurement of pretransplant circulating CD161-expressing cells, in addition to clinical risk factors, could predict mucositis and infections in patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT). To determine if CD161-expressing cells are likely to predict early complications, namely, mucositis (≥grade 3), infections, and cytomegalovirus (CMV) reactivation, we prospectively examined CD161-expressing cells (CD3+CD4+CD161+ and CD3+CD8+CD161+) in peripheral blood samples from 108 patients with MM undergoing ASCT. After adjusting for factors identified by univariate analysis that predicted mucositis (≥grade 3), infection before engraftment, and CMV reactivation, multivariate analyses revealed that the low proportion of CD3+CD4+CD161+ cells in peripheral blood was an independent predictor of mucositis (≥grade 3) (P=0.020), infections before engraftment (P=0.014), and CMV reactivation (P=0.010). In addition, we found that female sex and decreased glomerular filtration rate were independent factors for predicting mucositis. Female sex and severe pulmonary comorbidity were independent factors for predicting infection before engraftment. We found that the proportion of circulating CD3+CD4+CD161+ cells is useful for predicting the occurrence of early complications, including mucositis and infections, after ASCT in patients with MM. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to evaluate the long-term outcomes of allogeneic stem cell transplantation ( SCT) in patients with paroxysmal nocturnal hemoglobinuria ( PNH) with or without aplastic anemia ( AA). Method A total of 33 patients with PNH clones who underwent allogeneic SCT were analyzed. Results After a median follow-up of 57 months (range, 6.0-151.3), the 5-year estimated overall survival rate was 87.9±5.7%. Four patients died of transplant-related mortality ( TRM). With the exception of one patient with early TRM, 32 patients were engrafted. Two patients who had developed delayed GF received a second transplant and recovered. The cumulative incidences of acute graft-vs-host disease ( GVHD) (≥grade II) and chronic GVHD (≥moderate) were 27.3±7.9% and 18.7±7.0%, respectively. Twenty-one patients receiving SCT with reduced-intensity conditioning ( RIC) had available follow-up data for PNH cell population for the first 6 months post-transplant. Analysis of these data revealed that the PNH clones disappeared within approximately 2 months. Conclusion RIC regimen was sufficient to eradicate PNH clones with sustained donor-type engraftment after allogeneic SCT. Therefore, application of allogeneic SCT with RIC should be considered in patients with PNH, in accordance with the severity of the underlying bone marrow failure. [ABSTRACT FROM AUTHOR]

Background: The risk of developing tuberculosis (TB) in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is expected to be relatively high in an intermediate TB burden country. This single-center retrospective study was conducted to investigate risk factors and the incidence of TB after allogeneic HSCT. Methods: From January 2004 to March 2011, 845 adult patients were enrolled. Starting April 2009, patients were given isoniazid (INH) prophylaxis based on interferon-γ release assay results. The incidence of TB was analyzed before and after April 2009, and compared it with that of the general population in Korea. Results: TB was diagnosed in 21 (2.49%) of the 845 allogeneic HSCT patients. The median time to the development of TB was 386 days after transplantation (range, 49–886). Compared with the general population, the standardized incidence ratio of TB was 9.10 (95% CI; 5.59–14.79). Extensive chronic graft-versus-host disease (GVHD) was associated with the development of TB (P = 0.003). Acute GVHD, conditioning regimen with total body irradiation and conditioning intensity were not significantly related. INH prophylaxis did not reduce the incidence of TB (P = 0.548). Among 21 TB patients, one patient had INH prophylaxis. Conclusion: Allogeneic HSCT recipients especially those who suffer from extensive chronic GVHD are at a high risk of developing TB. INH prophylaxis did not statistically change the incidence of TB, however, further well-designed prospective studies are needed. [ABSTRACT FROM AUTHOR]

Background Few studies have been performed to identify factors that are associated with an increased risk of infections during the neutropenic period in patients undergoing allogeneic stem cell transplantation (allo- SCT). The aim of this study was to identify the host immune cells responsible for infections before engraftment. Methods A total of 282 patients who underwent allo- SCT were enrolled. Peripheral blood samples were collected before conditioning therapy. Expression of CD161-expressing T cells, natural killer cells, and immature myeloid cells was analyzed by flow cytometry. Microbially and clinically defined infections and fevers of unknown origin as proposed by the Immunocompromised Host Society were included in this study. Results The median age was 45 years (range, 16-68 years). Patients had various hematologic disorders and were transplanted from human leukocyte antigen ( HLA)-matched siblings, unrelated donors, and familial HLA-mismatched donors. In univariate analysis, younger age and a familial HLA-mismatched donor were risk factors for the occurrence of infections. After adjusting for potential variables in univariate analysis, multivariate analyses revealed that a lower frequency of CD3+ CD4+ CD161+ cells was significantly associated with the occurrence of neutropenic infections. An age of 35 years or younger and allografting from familial HLA-mismatched donors showed a trend toward higher infection rates. Conclusion Our data indicated that a lower frequency of CD3+ CD4+ CD161+ T cells in peripheral blood before conditioning therapy was associated with a higher incidence of infection during the neutropenic period. These results suggest that recipient innate T cells with expression of C-type lectin CD161 can guard against infections before engraftment. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the impact of the response to induction therapy on the long-term prognosis of multiple myeloma (MM) after autologous stem cell transplantation (ASCT) in the era of novel agents (NAs). A total of 171 patients who were newly diagnosed with MM and underwent early ASCT were analyzed. One hundred ten had a NA-based induction therapy, and 61 patients had a non-NA-based induction therapy. After a median follow-up of 45.4 months, the 4-year overall survival (OS) and progression-free survival (PFS) from transplantation were 60.5 and 25.5 %, respectively, for the NA-based induction group and 54.6 and 15.6 %, respectively, for the non-NA-based induction group. Multivariate analyses revealed that the patients who had NA-based induction had a significantly shorter OS ( P < 0.001) and PFS ( P < 0.001) when at least a partial response (PR) was not achieved. In patients who did not receive NAs before ASCT, lack of at least a PR to induction therapy was not associated with a survival disadvantage. These findings suggest that, unlike pretransplantation induction before NAs, patients who do not respond to induction treatment using NAs may not derive a benefit from ASCT. The relevance of induction failure differs for corticosteroid- and NA-based induction. [ABSTRACT FROM AUTHOR]

The aim of this study was to estimate the prognostic factors for the outcomes of chronic myeloid leukemia (CML) patients receiving allogeneic stem cell transplantation (SCT) in chronic phase (CP) in the era of tyrosine kinase inhibitors (TKIs). Ninety-seven patients who underwent allogeneic SCT in CP were analyzed. Forty-seven were TKI-naïve at the time of transplant, and 50 received TKI(s) treatment before transplantation. After a median follow-up of 115.8 months, the 4-year overall survival and event-free survival were 80.4 and 58.8%, respectively. Multivariate analysis showed that there were no differences in survival outcomes based on prior TKI therapy. Older age was a prognostic factor for higher treatment-related mortality (TRM), and the type of graft source and younger age were associated with relapse, but prior TKI therapy and disease status at the time of transplant were not associated with either TRM or relapse. Additionally, a major molecular response at 1 month and an MR4.5 at 3 months were important predictors of favorable long-term outcomes. This study demonstrates the prognostic factors for the outcomes of allogeneic SCT in CP CML and shows that survival outcomes were not affected by the administration of long-term multi-TKI treatment prior to transplantation. [ABSTRACT FROM AUTHOR]

The major limitation of autologous stem cell transplantation (auto- SCT) in non- Hodgkin lymphoma ( NHL) is relapse. Although autologous graft contamination may be a potential cause, prior purging of the autograft remains controversial. Therefore, we retrospectively analysed 56 consecutive patients with NHL receiving auto- SCT at complete ( n = 41) or partial remission ( n = 15). Among them, 24 patients underwent autograft manipulation with positive selection of CD34+ cells using a Clini MACS device (purged group). Twenty-five patients had received ≥2 previous chemotherapy regimens before auto- SCT. After a median follow-up of 41·4 months, transplant-related mortality was observed only in unpurged group ( n = 2; 3·6%). The 3-year overall survival (91·7% vs. 56·1%, P = 0·009) and progression-free survival (78·7% vs. 53·1%, P = 0·034) favoured CD34+ purification. While neutrophil recovery was similar, platelet recovery was delayed in the purged group. Cytomegalovirus reactivation was predominantly observed in the purged group, although no other clinically unmanageable infectious complications occurred. Although this study has the inevitable limitations of heterogeneity in previous treatment and NHL subtypes, and a small number of patients analysed, the high survival rate in the purged group may suggest the need for prospective randomized trials to determine the role of CD34+ purification in auto- SCT for NHL. [ABSTRACT FROM AUTHOR]

Antithymocyte globulin (ATG) is the drug of choice for immunosuppressive therapy (IST) in patients with severe aplastic anemia (SAA) ineligible for allogeneic stem cell transplantation. Recently, rabbit ATG with cyclosporine A has been used as a first-line IST regimen in patients with SAA because of unavailability of horse ATG. We retrospectively analyzed adult SAA patients who were treated with horse ATG ( n = 46) or rabbit ATG ( n = 53) between Feb 2001 and May 2010 to compare hematologic response and survival. Overall response rates at 3, 6, 12, and 18 months were similar in both the horse and rabbit ATG groups: 28.3 versus 35.8 % ( P = 0.421), 39.1 versus 45.3 % ( P = 0.537), 45.7 versus 49.1 % ( P = 0.735), and 47.8 versus 50.9 % ( P = 0.757), respectively. The complete response (CR) rate at 6 months in the horse ATG was significantly superior in comparison with the rabbit ATG (13.0 versus 1.9 %, P = 0.031). But CR rates became similar in both groups after 6 months: 17.4 versus 11.3 % ( P = 0.387) at 12 months and 21.7 versus 22.6 % ( P = 0.914) at 18 months. Lymphocyte depletion after ATG was more profound and protracted in the rabbit ATG group compared to the horse ATG group. Overall survival ( P = 0.460) and failure-free survival ( P = 0.911) were not significantly different between the two groups. Our retrospective study demonstrated that the efficacy of first-line IST with rabbit ATG is similar to that with horse ATG. However, the time from treatment to CR was longer with rabbit ATG than with horse ATG, partly due to more profound and protracted lymphocyte depletion. [ABSTRACT FROM AUTHOR]

IL-17 is involved in inducing and mediating pro-inflammatory responses. The association of IL-17 with tumor growth or graft-versus-host disease (GVHD) has become a subject of controversy. We hypothesized that serum IL-17 (sIL-17) levels during the peri-transplant period may affect alloreactive responses after allogeneic stem cell transplantation (SCT). sIL-17 levels of 95 patients with leukemia who had undergone myeloablative allogeneic SCT were measured using ELISA before conditioning and on day 0, +7, and +14 after transplantation. With a median follow-up of 17 months, the overall survival, disease-free survival, non-relapse mortality, and relapse incidence were 70.9%, 66.3%, 10.3%, and 23.4%, respectively. Ten patients relapsed within 180 days (early relapse, 10.5%) post-transplant. The cumulative incidence of acute GVHD over grade II and chronic GVHD was 55.8% and 69.0%, respectively. Analyses using repeated measures of ANOVA and mean values of sIL-17 revealed that patients relapsed within 180 days had higher sIL-17 levels, whereas no association existed between sIL-17 levels and other clinical outcomes, including acute GVHD. Receiver operating characteristic curve analyses also revealed that sIL-17 levels were available for the prediction of early relapse and that patients with higher sIL-17 levels at each time point had a significantly higher early relapse. Multivariate analyses and subgroup analyses with only standard disease status suggest the association of sIL-17 levels with subsequent early relapse independent of disease status at transplantation. This study is the first one demonstrating the early change in sIL-17 during the peri-transplant period and the association with early relapse in humans. [ABSTRACT FROM AUTHOR]

This study analyzed the results of stem cell transplant (SCT) in elderly patients with acute myeloid leukemia (AML) who achieved complete remission (CR) with a gemtuzumab ozogamicin (GO)-containing regimen in order to identify the impact of the drug as a remission induction regimen on the outcome of SCT. Patients who achieved CR with GO proceeded to reduced-intensity conditioning or autologous SCT after one or two cycles of consolidation chemotherapy. With a median follow-up of 53.5 months ( n - 17), probabilities of overall survival (OS) and disease-free survival (DFS) at 3 years were 58.2 ± 12.1% and 47.1 ± 12.1%, respectively, and the cumulative incidences of relapse and non-relapse mortality were 35.3 ± 12.1%, and 17.7 ± 9.5%, respectively. Patients with high bone marrow CD33 expression at the time of diagnosis showed significantly higher OS and DFS (70.7%, p == 0.008 and 57.1%, p == 0.008, respectively) than those with low expression. The intensification of post-remission treatment using SCT in elderly patients with AML who achieve CR on GO appears to be an effective and feasible treatment modality. [ABSTRACT FROM AUTHOR]

Although reduced-intensity conditioning (RIC) has been increasingly used in patients with myelodysplastic syndrome (MDS) to reduce transplant-related mortality, a high relapse rate in RIC remains an unresolved problem. Considering the additive antileukemic effect of low-dose total body irradiation (TBI), we evaluated the feasibility of combining RIC regimens with low-dose TBI in de novo MDS. The RIC regimen combined with low-dose TBI in this study consisted of fludarabine (150 mg/m2), intravenous busulfan (6.4 mg/kg), and TBI (400 cGy). Antithymocyte globulin was used to overcome HLA mismatching. A total of 31 subjects were recruited with a median age of 39 years (range 19-63). The patients received transplants from siblings (n = 20) or unrelated donors (n = 11). All patients rapidly achieved full-donor chimerism. At a median follow-up for survivors of 35 months (range 6.0-54.9), the 3-year overall survival, event-free survival, transplantation-related mortality, and relapse rates were 67.6, 63.2, 20.5 and 11.4%, respectively. The 3-year cumulative incidence of acute (grades II-IV) and chronic extensive graft-versus-host disease in patients who survived at least 100 days was 39.2 and 44.6%, respectively. These results suggest that an RIC combined with low-dose TBI may be a feasible therapeutic approach for treating de novo MDS. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Copyright of Stem Cells is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Relapse is a major concern with reduced-intensity conditioning. We analyzed 257 patients with acute myeloid leukemia (AML) who received allogeneic stem cell transplantation (SCT) and fulfilled the following criteria: intermediate- or poor-risk disease by National Comprehensive Cancer Network guidelines (2017, version 3), in first complete remission (CR1) at SCT, received either myeloablative conditioning (MAC; busulfan plus cyclophosphamide or cyclophosphamide plus total body irradiation) or reduced-intensity conditioning (RIC; FluBu2TBI400) peripheral blood SCT from 8/8 matched sibling or unrelated donor, and having bone marrow Wilms tumor gene 1 (WT1) expression results before transplant. We and other groups serially published a predictive value for pretransplant WT1 expression in patients with AML to identify patients at higher risk of relapse. Among the total 257 patients, 191 (74.3%) and 66 (25.7%) patients received MAC and RIC transplants, respectively. WT1 ≥250 copies/104 ABL was defined as WT1high. WT1high before SCT was found to be an independent prognostic factor for inferior overall survival (OS), disease-free survival (DFS), and higher cumulative incidence of relapse (CIR). There were 201 patients with WT1 low expression based upon pretransplant analysis. There was no significant difference in OS, DFS, CIR, and nonrelapse mortality between MAC and RIC patients. To conclude, post-transplant survival or relapse was not different by conditioning intensity in AML CR1 patients whose WT1 level was below 250 copies per 104 ABL at transplantation. [ABSTRACT FROM AUTHOR]

The incidence of Philadelphia chromosome positivity (Ph + ) in adults with acute myeloid leukemia (AML) is very low. Ph + AML is considered to be high risk for failure to attain remission or for early relapse after standard chemotherapy. Because of the low incidence of the disease, it has been difficult to determine the best treatment, including the effects of tyrosine kinase inhibitors. We retrospectively analyzed 29 patients with Ph + AML (median age, 45 years; range, 18 to 80) managed at our center between 2002 and 2016. Two patients were not treated at all, 3 received repeated low-dose cytarabine, and 24 were treated with 3 + 7 standard induction chemotherapy. All 27 treated patients also received interim imatinib 400 mg orally until the day of the next chemotherapy cycle began or as conditioning for allogeneic hematopoietic cell transplantation (HCT), which was performed in 17 patients. Of the 29 patients with Ph + AML, 7 (24.1%) had additional inv(16), 3 of whom had therapy-related AML. In the 7 with inv(16), the median age was younger (31 versus 44 years, P  = .083) and the complete remission (CR) rate was relatively higher (85.7% versus 54.5%, P  = .214) than in those without inv(16). Among the 27 treated patients, 20 (74.1%) achieved CR after standard chemotherapy with interim imatinib and 2 (7.4%) achieved CR after low-dose cytarabine with interim imatinib. After a median follow-up of 65.5 months (range, 13.4 to 156.6), the 5-year overall survival (OS) among all 27 treated patients was 43.1%. For the 17 patients who underwent HCT the 5-year OS of 17 patients (10 in subgroup without inv(16) and 7 in subgroup with inv(16)) treated with allogeneic HCT was 69.3%. All 7 with inv(16) were still alive at the end of the study. In contrast, all patients not treated with HCT died within a median of 6.25 months (range, .2 to 18.2). Interim imatinib combined with chemotherapy yielded an acceptable remission rate in adult patients with Ph + AML. Allogeneic HCT as a postremission therapy provided long-term disease control in two-thirds of those who underwent the transplant. We also demonstrated that inv(16) was related to a favorable outcome in Ph + AML, including therapy-related AML. [ABSTRACT FROM AUTHOR]

The role of autologous hematopoietic cell transplantation (auto-HCT) for postremission therapy of acute myeloid leukemia is yet to be elucidated. We retrospectively analyzed 240 patients treated with auto-HCT in first remission. All patients were treated with standard induction chemotherapy, and CD34 +  stem cells were collected at each cycle of consolidation. Stem cells were infused after total body irradiation (1200 cGy), cytarabine (9 g/m 2 ), and melphalan (100 mg/m 2 ). Estimated 5-year overall survival, disease-free survival (DFS), cumulative incidence of relapse (CIR), and nonrelapse mortality were 58.4%, 55.3%, 38.8%, and 5.9%, respectively. We identified that poor-risk karyotype showed very poor outcome after auto-HCT, and then analyzed 85 patients with good to intermediate-risk molecular cytogenetics with available molecular study results and markers for minimal residual disease (MRD) such as WT1 and core-binding factor (CBF) associated MRD (ie, AML1/ETO and CBFβ/MYH11 ). Our data identified that old age, pre-HCT markers for MRD, and high post-HCT WT1 , high dose of CD34 +  stem cell (≥4.5 × 10 6 /kg) infusion, and c-kit or FLT3 -ITD mutations were associated with higher relapse rate and poor DFS. Using pre-HCT parameters, except for post-HCT WT1 , multivariate analysis revealed that patients with young age (<40 years old), no adverse mutations, and limited dose of CD34 +  stem cells might be good candidate for auto-HCT (3-year DFS and CIR were 83.4% and 16.6%, respectively). Young patients with good- to intermediate-risk molecular cytogenetics may benefit from auto-HCT if stem cell dose is limited. [ABSTRACT FROM AUTHOR]

Eighty adult patients with acute myeloid leukemia (AML) received peripheral blood T cell–replete HLA haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Disease status at transplantation was either first or second complete remission (CR, n = 69) or relapse/refractory (n = 11). Identical transplant-related procedures with conditioning regimen consisting of fractionated 800 cGy total body irradiation (TBI), fludarabine (30 mg/m 2 /day for 5 days), busulfan (3.2 mg/kg/day for 2 days), and antithymocyte globulin (1.25 mg/kg/day on days −4 to −1) and graft-versus-host disease (GVHD) prophylaxis with tacrolimus and methotrexate were used in all patients. Recovery of neutrophil (median, 11 days) and platelet (median, 10 days) counts was achieved in all patients with full donor chimerism (≥99%), and no delayed engraftment failure was observed. The cumulative incidence of grades III to IV acute GVHD and moderate to severe chronic GVHD was 11.2% and 26.3%, respectively. A donor CD8 + and CD4 + T cell dose above the median value was significantly associated with the incidences of grades II to IV acute GHVD and moderate to severe chronic GVHD, respectively. After a median follow-up of 28 months for survivors, the 2-year cumulative incidences of relapse (n = 20) and nonrelapse mortality (n = 10) were 26.6% and 12.2%, respectively. Although all but 1 patient in relapse/refractory status died, the 2-year overall and progression-free survival of patients in first CR was 82.5% and 75.1%, respectively. We suggest the strategy of fractionated 800 cGy TBI-based conditioning with unmanipulated peripheral blood stem cell grafts seems feasible with favorable outcomes for adult patients with AML undergoing haplo-HSCT in CR. [ABSTRACT FROM AUTHOR]

To weigh the pros and cons of familial-mismatched/haploidentical transplantation (FMT) in patients with high-risk acute myelogenous leukemia, we assessed outcomes of 23 patients who underwent FMT, using reduced-intensity conditioning with total body irradiation 800 cGy/busulfan/fludarabine/antithymocyte globulin without ex vivo T cell depletion, compared to 33 patients who underwent well-matched unrelated donor transplantation (WM-UDT) and 13 who underwent partially matched unrelated donor transplantation (PM-UDT) during the same period. The FMT patients had not only a similar pattern of engraftment and immune reconstitution as the WM-UDT and PM-UDT patients but also comparable incidences and severity of acute and chronic graft-versus-host disease. The FMT patients did not experience any form of engraftment failure. However, the cumulative incidence of cytomegalovirus DNAemia was significantly higher in the FMT group compared with the other groups (P = .036). After a median follow-up of 28 months, overall survival, disease-free survival, relapse, and nonrelapse mortality were 83%, 74%, 20%, and 7%, respectively, for WM-UDT; 51%, 51%, 31%, and 18% for PM-UDT; and 66%, 64%, 26%, and 10% for FMT. This demonstrates a trend for favorable survival outcomes of WM-UDT over FMT and of FMT over PM-UDT. However, we found no significant statistical differences in survival according to donor type. These data need to be interpreted cautiously because of limited power calculations due to the small number of each donor group. This pilot study suggests the feasibility of FMT using our novel regimen with careful evaluation of CMV DNAemia compared with WM-UDT and PM-UDT. Further trials with larger numbers of patients, comparing FMT directly with transplantation with other donor types, are needed. [Copyright &y& Elsevier]

The impact of National Institutes of Health consensus criteria (NCC) graft-versus-host disease (GVHD) on survival has rarely been investigated in a large cohort of patients with GVHD presenting before and after day 100 posttransplantation. We retrospectively investigated 775 patients who underwent allogeneic stem cell transplantation and assessed the GVHD effects on survival by the time-dependent covariates in Cox proportional hazards regression models. Using the NCC, the patients were classified into 4 groups: (1) no GVHD (n = 251); (2) acute GVHD (aGVHD) only (n = 199), including 26 patients with late aGVHD; (3) classic chronic GVHD (cGVHD; n = 232); and (4) overlap syndrome (OS; n = 93). Multivariate analyses showed that classic cGVHD (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.27-0.77) and OS (HR, 0.52; 95% CI, 0.28-0.96) were associated with significantly decreased risk of relapse, whereas aGVHD only was not associated with relapse rate (HR, 1.11; 95% CI, 0.76-1.63). All aGVHD events, including the period of aGVHD in patients who developed cGVHD after aGVHD, also did not affect the risk of relapse (HR, 0.74; 95% CI, 0.49-1.12). All types of GVHD were significantly associated with higher nonrelapse mortality in common. Finally, patients with aGVHD only had significantly lower overall survival and disease-free survival compared with those without GVHD, in contrast to favorable survival outcomes in patients with cGVHD without previous aGVHD. This study demonstrates that NCC GVHD type is associated with different graft-versus-tumor effects. Further studies are needed to investigate risk factors, pathogenesis, and biomarkers for each type of NCC GVHD. [ABSTRACT FROM AUTHOR]

B cell activating factor (BAFF), also known as B cell survival and activation factor, is associated with autoimmune disease and chronic graft-versus-host disease (cGVHD). T cells are known to be modulated by soluble BAFF (sBAFF). Considering the possible association of sBAFF with T cell as well as B cell function, sBAFF during the peritransplantation period may affect the development of acute GVHD (aGVHD). To test this hypothesis, we evaluated 45 patients who had undergone myeloablative (MA) allogeneic stem cell transplantation (SCT) for hematologic malignancy. Serum sBAFF levels were measured before conditioning and on day 0, day +7, and day +14. Thirty-three of the 45 patients (cumulative incidence, 73%) developed aGVHD between 16 days and 98 days posttransplantation. Repeated-measures analysis of variance revealed significantly lower sBAFF levels during the peritransplantation period in patients with aGVHD than in those without aGVHD (P =.001). Receiver operating characteristic curve analysis revealed that sBAFF levels at every time point were available for the prediction of aGVHD development, and that patients with a sBAFF level >43pg/mL at each time point (which could ensure 75% sensitivity and 73%-82% specificity for the prediction of aGVHD at every time point) had a significantly lower cumulative incidence of aGVHD. This study is the first to demonstrate that sBAFF level during the peritransplantation period not only may be predictive of aGVHD, but also may have a protective effect against aGVHD in humans. Further investigation is needed to confirm our findings. [Copyright &y& Elsevier]

Abstract: The aim of the present study was to identify graft-versus-leukemia effects and the factors that affect outcome in 201 adults with acute lymphobalstic leukemia who received myeloablative allogeneic stem cell transplantation from matched sibling or unrelated donors (1995-2004). One hundred seventy-eight (88.6%) of these patients had high-risk criteria, and 151 (75.1%) patients were transplanted in first complete remission (CR). All patients received unmodified stem cell grafts (185 bone marrow and 16 peripheral blood) following total- body irradiation-containing myeloablative preparations. Graft-versus-host disease (GVHD) prophylaxis was uniformly attempted by administering calcineurin inhibitor plus methotrexate. After a median follow-up of 63 months (range: 25+ to 139+ months) for surviving transplants, disease-free survival at 5 years was 47.8% for all patients and 60.3% for patients in the first CR. No difference in transplantation outcome was observed between sibling and unrelated transplants in the first CR. The most powerful predictive factor affecting transplantation outcome was disease status at transplantation (the first CR versus beyond the first CR, P < .001). Chronic GVHD (cGVHD), especially limited type, was also found to have a significant antileukemic effect. Interestingly, the influence of cGVHD on relapse risk was prominent in patients with chromosomal translocations or normal cytogenetics. [Copyright &y& Elsevier]