bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Chimerism and Other Transplant Variables on Allogeneic Transplant Outcome after Reduced Intensity Conditioning (RIC) Regimens.
Authors: Corbella Veronica Ortiz , Lê Quoc-Hung , Nicolini Franck E. , Thiébaut Anne , Thomas Xavier , Chelgoum Youcef , Ducastelle Sophie , Mollet Isabelle , Dubois Valérie , Michallet Mauricette 
Published: October 2019

Abstract
RIC regimens followed by allogeneic hematopoietic stem cell transplantation (HSCT) were evaluated in patients with hematologic malignancies who were not candidates for conventional transplantation because of age or medical co-morbidities. In this kind of transplantation, the analysis of chimerism kinetics remains fundamental. The main aims of this study were to evaluate and compare the impact of pre- and post-transplant variables and chimerism on transplantation outcome. Chimerism status was evaluated in total blood (TB) and in purified CD3+ cells using quantitative PCR (STR/SNP) for all. We analysed donor type and kinetics chimerism of 52 patients (32 M - 20 F) who had undergone allogeneic HSCT after RIC for hematological malignancies. Median age was 40 years (range 25–67 years). Diagnosis were multiple myeloma: 16, acute myeloid leukemia: 13, myelodysplasia: 6, chronic lymphocytic leukemia: 5, Non Hodgkin’s lymphoma: 5, acute lymphoblastic leukemia: 1, chronic myeloid leukemia: 2 and primitive myelofibrosis: 4. Conditioning regimens were Fludarabine + Busulfan in 33 patients, Fludarabine + 2 Gys total body irradiation 15, Cyclophasphamide 3 (2 alone/one with Busulfan) and one other chemotherapy. Stem cell source was PB in all except one who received cord blood. Fourty-eight were identical sibling and 4 unrelated donor transplantations. At transplant, 17 patients were in CR, 21 PR and 14 in evolutive diseases. All patients except one engrafted. Twenty-five developed aGVHD ≥ Grade II (16 Grade III-IV). At the last follow-up 22 patients died (9 disease progression and 13 of transplant related mortality, 30 were alive (18 developed chronic graft vs Host disease (cGVHD) 12 extensive/6 limited cGHVD). Among 52 patients, only 49 had a long-term chimerism documentation of CD3 subpopulation (43 TB and CD3+ cells): 15 (14 TB) were full donor chimerism (FDC) throughout the follow-up, and 34 remained mixed chimerism (MC). Among these 34 (29 TB) MC patients at the latest follow-up, 7 (5 TB) remained in MC, 2 (5 TB) converted to recipient profile and 25 (19 TB) converted to donor profile. Univariate analysis demonstrated the close correlation between chimerism status evaluated on PB CD3+ cells only at any time post-transplant and the onset of aGVHD (p = 0.0391) but not cGVHD. Multivariate analysis according to linear regression method did not find any impact of the following variables on chimerism kinetics after RIC transplant: disease status before transplant, age, sex, type of RIC regimen, number of days of ATG, aGVHD (p ≥ 0.11). In conclusion, this study underlines the tight correlation that exists between chimerism status and kinetics on CD3+ PB subpopulations after RIC transplant and acute GVHD development that impacts on transplant outcome.
Novel Tyrosine Kinase Inhibitor Therapy (NTKI) Prior to Allogeneic Stem Cell Transplantation (ASCT) in Patients with Chronic Myeloid Leukemia (CML): No Evidence for Increased Transplant-Related Toxicity.
Authors: Jabbour Elias , Cortes Jorge , Kantarjian Hagop , Giralt Sergio , Giles Francis , Andersson Borje S. , Champlin Richard , de Lima Marcos 
Published: October 2019

Introduction: Patients undergoing ASCT for CML are increasingly likely to have received a NTKI after failing imatinib mesylate. It is unknown whether the use of these NTKIs prior to ASCT increases transplant-related toxicity.
Methods: We retrospectively analyzed the outcome of 12 patients with CML (1 in chronic phase, 6 in accelerated phase, and 5 in blastic phase) who received dasatinib (n=2), nilotinib (n=7), or both (n=3) prior to ASCT.
Results: Median age was 41 years (range, 18–59 years). The median time on treatment was 134 days (range, 30–285 days), and the median time from the end of NTKI therapy to ASCT was 34 days (range, 7–130 days). Preparative regimen was ablative in 8 patients and non-ablative in 4. Stem cell source was a matched related donor in 7 patients, a matched unrelated donor in 3, a haplo-identical donor in 1, and unrelated cord blood in 1. All patients engrafted within 13 days. There was no significant early transplant-related toxicity: gastro-intestinal toxicities of grade 3 were encountered in 2 patients. One patient had secondary graft failure 6 months after the first ASCT that required a second ASCT. Acute graft-versus-host disease (GVHD) of grade 2 was observed in 7 patients (58%) and chronic GVHD in 6 (50%). Nine patients achieved a molecular response: four complete and five major (Q-PCR< 0.05%). Three patients had disease progression by day 30 post ASCT. Two patients have relapsed after 6 and 18 months. After a median follow-up of 10 months (range, 3–22 months), 7 patients are alive in molecular response and 5 patients died, 4 of disease progression and one of extensive chronic GVHD.
Conclusion: Previous treatment with NTKI did not increase transplant-related toxicity in this preliminary experience. Further follow-up and larger number of patients will be necessary to confirm these observations.
Defibrotide for the Treatment of Hepatic Veno-Occlusive Disease in Children.
Authors: Uygun Vedat , Tezcan Gulsun , Hazar Volkan , Yesilipek Akif 
Published: October 2019

Abstract
Veno-occlusive disease (VOD) of the liver is a major complication of allogeneic or autologous stem cell transplantation (HSCT), particularly after busulfan-based conditioning regimens. Clinically, VOD is characterized by fluid retention, weight gain, hyperbilirubinemia and painful hepatomegaly. Efficacy and safety of defibrotide for the treatment of VOD, especially in pediatric patients, has not been adequately confirmed or the results are still preliminary. This retrospective report describes experience with defibrotide in children with hepatic veno-occlusive disease (HVOD) following HSCT in a single institution.
Materials and Method: Children who had undergone HSCT between April 2005–June 2006 and who received defibrotide for the treatment of HVOD during their admission were identified. Demographic data and clinical information of these patients were abstracted from their health records.
Results: Eight children (median age: 4.5 years; range: 1–14 years) who underwent HSCT during the study period received defibrotide for the treatment of HVOD; 5 were boys and 3 were girls. Three patients underwent HSCT for hematologic malignancies, 2 for neuroblastoma, 1 for hemoglobinopathy, 1 for severe combined immunodeficiency (SCID) and 1 for fanconi aplastic anemia. Conditioning regimens included busulfan (16 mg/kg) in four, melphelan (140 mg/m2) in two and total body irradiation in 1 patient as being risk factors for HVOD. Two patients with neuroblastoma had undergone autologous HSCT, three patients had been transplanted from matched sibling donor and the other three were either unrelated donor or unrelated cord blood transplantation. HVOD was diagnosed on transplant day +4 to +19 (median: +12 ). The median initial defibrotide dose was 31.5 mg/kg/day (25–46 mg/kg/day). The median duration of defibrotide therapy was 27 days (1–46 days). Defibrotide was discontinued due to clinical improvement (5), gastrointestinal hemorrhage (2), death (1). Two patients in whom defibrotide was discontinued because of gastrointestinal hemorrhage died. The primary cause of death in these two children was: progressive HVOD and multiorgan failue following sepsis.
As a result of this experience and under the light of literature, we believed that defibrotide is an effective treatment for children with HVOD and should be instituted in each children without delay in the event of at least one of the criteria for HVOD is established. But it is necessary to carry out further studies in larger group of patients with longer follow-up to validate the efficacy and safety of defibrotide.
The Impact of Alemtuzumab as a Component of Conditioning Regimens on Transplantation Outcomes in a Setting of CMV-Seropositive Recipient and Donor.
Authors: Ahn Byung Min , Sohn Sang Kyun , Kim Jong Kwang , Chae Yee Soo , Cho Yoon Young , Moon Joon Ho , Yang Deok Hwan , Lee Je-Jung , Kim Yeo-Kyeoung , Kim Hyeoung-Joon 
Published: October 2019

Abstract
Background: Graft-versus-host disease (GVHD) is one of the main issues for allogenic stem cell transplantation (SCT). Previous studies demostrated that in vivo administration of alemtuzumab (an anti-CD52 antibody) was effective to decrease the incidence of GVHD after allogenic SCT. However, due to delayed immune reconstruction, graft failure or infection is concerned. We investigated the impact of in vivo administration of alemtuzumab on the post-transplantation outcomes.
Patients and methods: Thirty-five patients entered a pilot study employing allogenic SCT with alemtuzumab-containing conditioning regimen in two centers (KNUH, CNUH). We evaluated the clinical outcomes, complications and their relationship with dose of alemtuzumab.
Results: The median dose of alemtuzumab was 50mg (range, 20–75) which was not adjusted on body weight and surface. All recipients (9 BM, 26 PB) and donors were CMV-seropositive before transplantion. The median survival was 14.03 months and 2 year survival rate was 47.0%. The probability of nonrelapse mortality at 90 days and 1 year was 11.4% and 22.8%, respectively. The cumulative incidence of grade II-IV acute GVHD at day 90 was 37.1%. The overall incidence of chronic GVHD was 20.8% and the incidence of extensive chronic GVHD was only 8.3%. The cumulative incidence of CMV antigenemia was 70.2%, which has been well controlled with preemptive ganciclovir treatment, and two patients with CMV antigenemia developed into CMV disease. The febrile episode was 37.1% but the duration was relatively short (median, 3 days). There were no differenecies in engraft (P = 0.573), acute and chronic GVHD (P = 0.359, P = 0.335, respectively), relapse (P = 0.849), mortality (P = 0.229), CMV antigenemia (P = 0.227) or overall survival (P = 0.51) between two groups (treated with ≥50mg of alemtuzumab vs. <50mg).
Conclusion: Our study has shown that alemtuzumab is effective for GVHD prevention but correlated with high incidence of CMV antigenemia regardless of its dose. As CMV antigenemia was easily controllable with preemptive ganciclovir, the conditioning regimen containing alemtuzumab seems hopeful especially in a setting of CMV-seropositive recipient and donor with a high risk of GVHD.
Comparative Analysis of Clinical Outcomes between Unrelated Donor Peripheral Blood Stem Cell Transplantation and Bone Marrow Transplantation for Leukemia.
Authors: Fan Zhiping , Liu Qifa , Yang Kai , Sun Jing , Xu Dan , Zhang Yu , Wei Yong-qiang , Ye Chang-xiong , Jiang Qianli , Meng Fan-yi 
Published: October 2019

Abstract
Objective To evaluate hematopoietic reconstitution, immune reconstitution, infection, incidence of graft-versus-host disease (GVHD) and other complications between unrelated donor peripheral blood stem cell (PBSC) transplantation and bone marrow (BM) transplantation.
Methods The clinical results in 21 patients receiving a PBSC graft mobilized by granulocyte colony stimulating factor (G-CSF) from unrelated donors were compared to 32 patients receiving unrelated BM transplants.
Results The PBSC graft contained significantly more nucleated cells (P=0.000), and resulted in a significantly shorter time-to-neutrophil (12.43±3.67 versus 16.16±2.99 days) and platelet engraftment (14.67±6.19 versus 21.23±8.25 days), compared to the BM group (P=0.000, 0.003, respectively). T cell reconstitution between the two groups differed little after transplantation. The incidences of early-stage infection were 42.86% and 53.13% (not significant [NS]) in the PBSC and BM groups, respectively. Probabilities of acute graft-versus-host disease (aGVHD) were 61.90% and 71.88% (NS), of grades III to IV aGVHD 23.81% and 15.63% (NS) and of chronic GVHD 47.06% and 43.48% (NS) in the PBSC and BM groups, respectively. The probabilities of relapse were 6.90% and 12.50% (NS) in the PBSC and BM groups, respectively. The 2-year disease free survival (DFS) rates of the two groups were (50.14±12.00) % and (59.81±8.99) %( NS), respectively.
Conclusion G-CSF-mobilized PBSCs engraft rapidly in unrelated donor recipients compared to conventional BM, but T cell reconstitution and the incidence of infection between the two groups differed little. There were no significant differences of the incidence and severity of aGVHD and cGVHD, and 2-year DFS rates between the two groups.
Therapeutic CSF Primed Donor Lymphocyte Infusion Using Cells Reserved at the Time of Transplantation for Patients with Relapsed Hematologic Malignancies after allo-PBSCT.
Authors: Sohn Sang Kyun , Cho YoonYoung , Kim JongGwang , Chae YeeSoo 
Published: October 2019

Abstract
Background
Reharvesting leukocytes from donors for a donor lymphocyte infusion (DLI) is inconvenient and occasionally impossible in case of unrelated donors. The effect of a growth factor-primed DLI is known to be comparable to that of nonprimed DLI for patients with relapsed disease. We reserved some portion of PBSCs harvested at the time of transplantation for the purpose of future DLI for relaping disease.
Method
In total, ninety nine patients (43 high risk, 46 standard disease) with hematologic malignancies who were treated by allo-PBSCT were allocated on an intent-to-treat basis. The dose of CD34+ cells with a range of 2–6*106/kg was transplanted, and additional PBSCs were cryopreserved.
Result
PBSC harvest for transplantation allowed to reserve extra cells in 35 (67.3%) high risk patients and in low risk 25 (55.6%) patients. Among 29 patients (29.9%) who relapsed after allogeneic PBSCT, 19 (65.5%) patients were treated with mainly cytarabine-based chemotherapy followed by cryopreserved PBSC infusion. The median dose of CD3+ and CD34+ cells for the primed DLI was 1.43*108/kg and 4.75*106/kg, respectively. Six (24.9%) out of 19 relapsed patients exhibited a complete response after the primed DLI, and their 1-year survival rate was 36%. The new development or progression of graft-versus-host disease after the primed DLI was observed in 16 (82%) patients. Overall, the survival at 1 year after the primed DLI was 21%.
Conclusion
The induction of a graft-versus-leukemia effect through a primed DLI, using additional PBSCs reserved at the time of transplantation, would appear to be feasible for patients with relapsed hematologic malignancies. Furthermore, this approach seem to be more convenient for donors.
Risk Factors for Predicting CMV Infection in Allogeneic-PBSCT Setting: MNC Dose, Campath Use, and Acute GVHD Grade ≥II.
Authors: Ahn Byung Min , Moon Joon Ho , Cho Yoon Young , Chae Yee Soo , Kim Jong Gwang , Sohn Sang Kyun 
Published: October 2019

Abstract
Risk factors for predicting CMV infection in allogeneic-PBSCT setting: MNC dose, Campath use, and acute GVHD grade ≥II
Background: CMV infection remains an important complication of allogeneic stem cell transplantation (SCT). Campath-1H (anti-CD52) antibodies have been widely used in vivo for T-cell depletion following conventional and reduced intensity conditioning regimens and associated with a significant reduction in GVHD but at the cost of impaired immune reconstitution. We studied the risk factors, for the development of CMV infection after allogeneic SCT, including the use of Campath-1H.
Methods: From Sep. 1998 to May 2006, 122 patients who received allogeneic peripheral blood stem cell transplantation were enrolled. CMV infection was routinely sought by at least weekly screening for CMV related matrix protein pp65 antigenemia after engraftment (WBC>1,500/uL) was achieved. CMV antigenemia was treated with ganciclovir 5mg/kg twice daily i.v. as preemptive therapy for at least 10 days.
Results: The overall incidence of CMV infection was 56/122 (45.9%) cases with a median onset of 44 days post transplants. Risk factors for CMV infection in the multivariate analysis were acute graft-versus-host disease (GVHD) grade II-IV (p=0.015), use of Campath-1H in conditioning therapy (p=0.012), and mononuclear cell (MNC) doses in the transplants (p=0.010). Among conditioning therapies, the use of Campath-1H was associated with increased incidence of CMV infection (75.0%) compared with conventional conditioning therapy (40.9%)(p<0.01) and relatively early occurrence of CMV infection, median 22 days post transplant (p=0.016).
Conclusion:The incidence of CMV infection was strongly associated with acute GVHD, MNC doses, and especially Campath-1H use in an allogeneic PBSCT setting.
Multivariate Analysis for the Incidence of CMV infection RR 95% CI P-value Conditioning: use of Campath-1H 5.112 1.429–18.285 0.012 Acute GVHD, grade II-IV 2.696 1.209–6.010 0.015 Stem cell dose: MNC(×10^8/kg) 1.149 1.034–1.276 0.010 Stem cell dose: MNC ≥10 vs. MNC<10 2.613 1.165–5.859 0.020
Mesenchymal Stem Cells for Treatment of Severe Acute Graft-Versus-Host Disease.
Authors: Le Blanc Katarina , Frassoni Francesco , Ball Lynne , Lanino Edoardo , Sundberg Berit , Lonnies Lena , Roelofs Helene , Dini Giorgio , Bacigalupo Andrea , Locatelli Franco , Fibbe Willem F. , Ringden Olle 
Published: October 2019

Abstract
Mesenchymal stem cells (MSC) from adult bone marrow have the capacity to differentiate into several mesenchymal tissues and inhibit T-cell alloreactivity in vitro. Within the EBMT MSC expansion consortium we have used MSC to treat grades III–IV acute graft-versus-host disease (GvHD) in 40 patients. The MSC dose was median 1.0 (range 0.4–9) 10^6 cells/kg body weight of the recipient. No side-effects were seen after MSC infusions. Nineteen patients received one dose, 19 patients received two doses, two patients received three and five doses respectively. MSC donors were in five cases HLA-identical sibling donors, 19 haploidentical donors and 41 third-party HLA-mismatched donors. Among the 40 patients treated for severe acute GvHD, 19 had complete responses, nine showed improvement, seven patients did not respond, four had stable disease and one patient was not evaluated due to short follow-up. Twenty-one patients are alive between six weeks up to 3.5 years after transplantation. Nine of these patients have extensive chronic GvHD. One patient with ALL has recurrent leukaemia and one patient has denovo AML of recipient origin.
We conclude that MSC have immunomodulatory and tissue repairing effects and should be further explored as treatment of severe acute GvHD in prospective randomized trials.
Double Umbilical Cord Blood Transplant Patients Have a Higher Risk of HHV-6 Infection.
Authors: Chen Sharon F. , DeFor Todd , Thomas Avis J. , Baker K. Scott 
Published: October 2019

Abstract
By age 2 years, 90% of children will have had primary infection with human herpesvirus 6 (HHV-6), which then becomes latent. HHV-6 can subsequently reactivate and cause disease in an immunosuppressed person. To investigate the effect of high-dose acyclovir as a prophylaxis against HHV-6 infection and to investigate the risk factors for having a positive HHV-6 quantitative polymerase chain reaction (PCR) assay, we identified a cohort of hematopoietic cell transplant (HCT) patients who had clinical indications for obtaining a HHV-6 PCR assay from 2003–2005 and evaluated their prospectively collected data. A total of 442 patients, including children and adults, obtained a hematopoietic cell transplantation from 2003–2005. Of this cohort, 137 were tested for HHV-6 with a PCR assay (median age 19 years; range 0.3–68 years). A positive HHV-6 PCR assay was found in 38 of the patients. The cell source included single (n=26) or double umbilical cord blood (UCBT, n=67), bone marrow (BM, n=25) and peripheral blood (PB, n=19). The median age was not significantly different for patients who tested positive compared to those patients who tested negative for HHV-6. About 50% of the patients received high-dose acyclovir. There was no significant difference in the cumulative incidence of a positive HHV-6 PCR assay by post-transplant day 100 in patients who received high-dose acyclovir (1500mg/m2/day) compared to those who did not receive high-dose acyclovir (p=0.8). Double umbilical cord blood transplant patients had 6 times higher risk of a positive HHV-6 PCR assay compared to BM or PB transplant patients, after adjusting for the transplant conditioning regimen (Hazard ratio=6.2, 95%CI 1.79–21.35, p=0.004). Compared to single UCBT patients, double UCBT patients still had 2 times higher risk of a positive HHV-6 PCR assay (95%CI 1.1– 7.4, p=0.03). For double UCBT, a significantly higher rate of positive HHV-6 PCR assay was found for those patients who received a myeloablative conditioning regimen compared to a non-myeloablative regimen (p=0.01). The use of Fludarabine was not significantly different between myeloablative and non-myeloablative conditioning regimens in those patients who received a double UCBT. In summary, we did not find statistical evidence that high-dose acyclovir was an effective prophylaxis against HHV-6 infection, though the analysis may be hampered by low power. We did find that double umbilical cord blood transplant patients are at high risk of having a positive HHV-6 PCR assay compared to BM, PB and single UCBT patients. The underlying reason for this increased risk is unclear and further investigation will be clinically valuable.
Immune Reconstruction Inflammatory Syndrome (IRIS) with Invasive Aspergillosis (IA) in Patients (pts) with Hematological Cancer (Hem-Ca): Clinical and Research Implications.
Authors: Miceli Marisa , Grazziutti Monica , Woods Gail , Krishna Somashekar , Kiwan Elias , Rahman Mazher , Barlogie Bart , Anaissie Elias , Syed Nayyar 
Published: October 2019

Abstract
Background: Assessing IA outcome with conventional criteria is difficult particularly when clinical and radiological worsening coincides with neutrophil recovery. This worsening is assumed to be related to immune reconstitution (IRIS). Because it is not possible to distinguish between pts whose worsening is transient from those who have progressive IA, clinical and radiological deterioration usually prompts invasive diagnostic procedures and therapeutic modifications including investigational agents, surgery, others. Galactomannan (GM) is an Aspergillus-specific polysaccharide released during aspergillosis and detected by the serum GM test. This FDA-approved test is an accepted diagnostic marker for aspergillosis and preliminary data suggest a correlation between GM index (GMI) and outcome.
Purpose: using GMI, to distinguish response from progressive IA among patients with IRIS.
Patients and Methods: patients at risk for IA (11/03–2/06) underwent GMI screening during periods at risk. The clinical and laboratory findings of pts with ≥ 2 (+) GMI (optical density ≥ 0.5) were reviewed.
Results: 30 pts had GMI (+) aspergillosis of the respiratory tract [myeloma 92%; median age: 59 years (27–75); 15 males]. Invasive aspergillosis developed following stem cell transplantation [autologous (11), allogeneic (1)], or conventional chemotherapy (18). 12 of 25 (48%) neutropenic pts (<1000/ml) developed transient clinical and radiological worsening coinciding with neutrophil recovery, suggesting an IRIS. This deterioration coincided with rapidly declining GMI in 7 pts, all of whom survived with complete resolution of IA and without therapeutic modifications while the remaining 5 pts had persistently elevated GMI and rapidly died of IA.
Conclusion: These data establish the presence of IRIS among Hem-Ca pts with IA who suffer clinical and radiologic deterioration coinciding with neutrophil recovery. IRIS is common and occurs among both responders and non-responders. Declining GMI values implies IRIS with response and obviates the need for invasive procedures and / or therapy modification while persistent GMI elevation is indicative of IRIS with progressive infection. Serial GMI testing should be performed to guide management and evaluate pts prior to therapy with investigational antifungal agents.