bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Pre/Post Fluoro-Deoxyglucose Positive Emission Tomography (PET) Does Not Predict Outcome of Patients Undergoing Hematopoietic Stem Cell Transplantation in Hodgkins Disease and Non-Hodgkins Lymphoma.
Authors: Palmer Jeanne , Goggins Timothy , Broadwater Gloria , Chao Nelson J. , Chute John , Coleman R. E. , Sullivan Keith M , Long Gwynn , Gasparetto Cristina , Beaven Anne , Rizzieri David 
Published: April 2020

Abstract
This study was designed to investigate the predictive value of early pre/post stem cell transplant (SCT) FDG-PET on outcomes in non hodgkins (NHL) or Hodgkins lymphoma (HL). We analyzed patients who received SCT for treatment of relapsed or refractory NHL or HL at Duke Medical Center between the years of 1996–2007. Patients who had either a FDG-PET scan following salvage chemo- or radio- therapy and within 14 weeks of transplantation (pre-PET)or a FDG PET scan within 6–14 weeks following transplantation (post-PET) were included in the analysis. PET was determined to be positive or negative based on chart review of radiology reports. Survival times are estimated using Kaplan- Meier method. Hazard ratios (HR) are from univariate Cox proportional hazards models. Overall survival (OS) was measured from the time of transplant until death, and for those patients still alive, it was censored at the last follow up date. Disease free survival (DFS) was measured from the time of transplant until first progression or death, whichever occurred first, and was censored at the date of last follow up for those alive without progression. A total of 102 patients were identified with PET in the appropriate time period. Median age was 48.5 (18–78); 71 patients had NHL, 31 patients had HL. Ninety-eight (96%) of the patients had chemosensitive disease, and had a documented PR (62) or CR (36) prior to transplant. The median DFS and OS of this population was 55 and 73 mo respectively. Median time to follow up was 38 mo (1.5 – 145 mo). Of the 75 pre-PET scans, 32 (43%) were positive; of the 78 post-PET scans, 22 (28%) were positive. At the time of this analysis, 28 (27%) of the patients had died from disease progression. There were 8 (10.6%) pre-PET, and 7 (9%) post- PET readings that were not clear. Our analysis revealed that neither pre-PET nor post-PET results were predictive of DFS (HR 1.73 p=0.16, HR 1.97 p = 0.052) or OS (HR 1.92 p=0.13; HR1.65 p=0.21). Further, for the patients who had measurable disease at the entry to SCT, post-PET was not predictive for DFS (HR 1.62, p=0.29) or OS (HR 1.59 p=0.35). Exclusion of unclear PET readings did not have any effect on these results. In subset analysis, post- PET did predict DFS in patients with NHL (HR 2.6 p=0.034). Our results suggest that early pre/post SCT PET analysis is not beneficial in this algorithm for predicting overall survival in these patients. Negative post-PET may predict DFS in patients with aggressive NHL, however, did not predict OS in this group. Our analysis indicates that other methods of determining risk of relapse and transplant outcome are needed.
HIV Status Does Not Affect the Outcome of Autologous Stem Cell Transplantation (ASCT) for B Cell Non Hodgkin Lymphoma (NHL).
Authors: Krishnan Amrita , Zaia John , Alvarnas Joseph , Kogut Neil , Spielberger Ricardo , Wardlow Michelle , Tsai Nicole , Paris Tanya , Forman Stephen J 
Published: April 2020

Abstract
Randomized trials have demonstrated superior progression free (PFS)and overall survival (OS) with autologous stem cell transplant (ASCT) for patients with relapsed chemosensitive non-Hodgkin lymphoma (NHL) compared with conventional dose salvage chemotherapy. More recent trials have proven that ASCT is also feasible in pts with AIDS associated NHL (ARL). However, the impact of the HIV infection on long term outcome is unknown. We therefore, undertook a retrospective case control analysis of ASCT for high risk B cell NHL in HIV positive (HIV Pos) and HIV negative (HIV Neg) pts. Twenty-nine pts with ARL who underwent ASCT between 1998 and 2007 were matched with HIV Neg controls. Pts were matched for gender, time from NHL dx to ASCT, age at ASCT, dz status at ASCT, number of prior regimens, conditioning regimen (chemo vs. FTBI). Histology was matched as closely as possible with the exception that there were more high-grade NHL pts in the HIV Pos group.
Patient HIV Pos HIV Neg P value* (* P value by Fishers exact test or Wilson signed rank sum test) Age at ASCT 42 (11–68) 48(21–65) .06 HISTOLOGY Large cell 19 25 Burkitts 10 0 Follicular gr 3 0 3 Marginal zone 0 1 Disease status 1CR/PR 16 16 IF 2 2 1.0 Relapse 11 11 Prior regimens 2(1–4) 2(1–4) .33 Conditioning - - FTBI 4 4 1.0 Non TBI 25 25
Median followup for HIV Pos pts is 46.7 months and 43.3 months for HIV neg controls (NS). Pts engrafted WBC at a median of 10 days (HIV Pos) and 11 days (HIV Neg) (NS) respectively. Non-relapse mortality (NRM) was 8% (95% CI 2–26) in HIV Pos pts and 4% (95%CI 0.7–25)in HIV Neg controls (NS). Two year PFS for the HIV Pos cohort was 76% (95% CI 62–85) and 56% (95% CI 45–66) for the controls (NS). OS was also similar at 75% (95% CI 61–85) versus 75% (95% CI 60–85)respectively{ see figure }. In conclusion, despite the inclusion of more poor risk pts by histology in the HIV Pos cohort, our series demonstrated matching OS for HIV Pos and HIV Neg pts undergoing ASCT for NHL The equivalent NRM also provides further evidence that HIV status does not affect the outcome of ASCT for NHL and therefore, should be considered a standard approach for select pts with ARL.
Figure Figure
Hemorrhagic Cystitis and BK Virus Infection in Children after Hematopoietic Stem Cell Transplantation.
Authors: Gruhn Bernd , Maier Loreen , Egerer Renate , Fuchs Dietlinde , Zintl Felix , Beck James 
Published: April 2020

Abstract
Hemorrhagic cystitis (HC) is a serious complication after hematopoietic stem cell transplantation (HSCT). The pathogenesis of HC in adults is not fully understood and may be influenced by BK virus infection, type of transplant, conditioning regimen, stem cell source, and graft-versus-host disease. Little is known about the development of HC in children after HCST, especially about the association with BK virus infection. Therefore, we retrospectively analyzed the incidence, risk factors and BK virus association of HC in 165 consecutive children (median age, 12 years) who underwent peripheral blood stem cell (n=97; T-cell depleted: n=48) or bone marrow transplantation (n=68) between 1/2000 and 12/2006 in a single center. Fifty nine patients received autologous HSCT and 106 patients underwent allogeneic HSCT. Nineteen of the 165 patients (11.5%) developed HC after a median of 33 days (range, 1–98 days). All 19 patients with HC underwent allogeneic HSCT and showed BK viruria after transplantation. An acute graft-versus-host disease was significantly more frequent in children with HC (P &lt; .001). Significant risk factors in univariate binary logistic analyses were age &gt; 12 years (OR, 3.275; P &lt; .031), use of busulfan (OR, 3.514; P &lt; .013), use of busulfan and cyclophosphamide in combination (OR, 4.935; P &lt; .002), and an unrelated donor (OR, 3.309; P &lt; .043). Independent risk factors in multivariate binary logistic analyses were age &gt; 12 years and the combination of busulfan and cyclophosphamide. We suggest that cyclophosphamide is toxic to the urinary bladder and busulfan enhances this effect. Furthermore, we analyzed the BK virus load in urine by real-time polymerase chain reaction. We found in patients without HC a significantly increased number of BK virus copies in urine in children older than 12 years (P &lt; .009) and in children who received antithymocyte globulin (P &lt; .001). In addition, BK virus load in urine was significantly increased in children who suffered from HC. Thirteen of 14 children with HC had a BK virus load in urine &gt;107 copies/mL (P &lt; .001). We observed in individual BK virus profiles an increase of BK virus copies in urine before the onset of HC. We conclude that HC in children is a disease of multiple etiologies. Allogeneic HSCT, the combination of busulfan and cyclophosphamide, age &gt; 12 years, and an unrelated donor are risk factors for the development of HC in childhood. Increased BK virus load in urine of more than 107 copies/mL may lead to HC. Therefore, it is useful to quantify BK virus in urine in those children with above mentioned risk factors to initiate early treatment or to prevent the development of HC.
Association of Mannose Binding Lectin (MBL-2) Deficiency with Pulmonary Infection after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT).
Authors: Chung Dick , Ding Lily , Amigues Isabelle , Kadeishvili Katuna , Lo Theresa , Pamer Eric , Kalambakas Stacey , Buchbinder Aby , Papanicolaou Genovefa 
Published: April 2020

Abstract
Background: Low MBL2 concentration and MBL2 genotype variants have been associated with an increased risk of infection in various clinical settings. Pulmonary infection is a major complication of HSCT. We examined the relationship of MBL genotypes with post-engraftment bacterial (B-PNA) and fungal (F-PNA) pneumonia
Methods: Retrospective review of 236 non-consecutive, non-selected patients who underwent HSCT at MSKCC from 1/1/2000–4/30/2007. Microbiologically confirmed infections and pneumonias were recorded. Antifungal prophylaxis consisted of fluconazole 400 mg daily. Patients at high risk for mold infection received mold-active prophylaxis. After 1/1/2006 voriconazole was the first line anti-mold prophylaxis. Genotype was determined by PR-Melting Curve Analysis on blood or buccal swab specimens. MBL genotype was classified as wild-type: A/A (MBL-sufficient, MBL-S) or variant-type: A/O, O/O (MBL deficient, MBL-D). Patients were followed for up to 2 years. Statistical analysis: Fisher’s Exact test was used to compare the incidence rate between MBL-S and MBL-D patients. Multivariate logistical regression models were used to investigate the relationship between bacterial or fungal pneumonia and MBL genotype, matched related donor (MRD), myeloablative conditioning (MC) peripheral blood as stem cell source (PBSC), acute GVHD grade 2–4 (aGVHD). The results from Maximum Likelihood Estimates were summarized.
Results: Transplant characteristics: 80% MC, 76% PBSC, 48.6% MRD. Incidence of aGVHD: 22.4%. MBL genotypes: One-hundred and forty-two (60%) patients were homozygous for wild-type MBL2 (AA), 85(36%) were heterozygous (A/0) and 9 (3.8%) were homozygous for variant genotypes (OO). Transplant characteristics, rates of GVHD, relapse-free and overall survival were similar between MBL-D and MBL-S. There was higher incidence of overall bacterial infections in MBL-D compared to MBL-S pts (47.87% vs 36.62%, p=0.1049). MBL-D had a higher incidence of B-PNA (12.7% vs 4.9%, p=0.048). In multivariate logistic regression analysis, MBL-D(p=0.04) and aGVHD(p=0.06) were likely associated with B-PNA. Rates of overall fungal infections and F-PNA were similar [among MBL-D and MBL-S pts (12.77% vs 9.86%, p=0.5277) and (8.51% vs 7.75%, p=0.1049) respectively]. In multivariate logistic regression analysis only aGVHD was statistically significantly associated with F-PNA p=0.0002.
Conclusions: 1) MBL-D genotype was likely associated with increased risk of bacterial pneumonia. 2) MBL-D and aGVHD were risk factors for B-PNA. 3) Further analyses are in progress to evaluate the effect of MBL-D on fungal pneumonia in patients who received mold prophylaxis versus patients who did not receive mold prophylaxis. 4) Prospective studies are needed to assess the relative contribution of MBL-D genotype on the risk of pulmonary infection in HSCT.
Improved Overall Survival in Patients Recovering with High Gamma/Delta T Cells after Allogeneic Haematopoietic Stem Cell Transplantation.
Authors: Kordelas Lambros , Junge Matthias , Trenschel Rudolf , Elmaagacli Ahmet H , Beelen Dietrich W 
Published: April 2020

Abstract
T-cells play a crucial role in the Graft-versus-Leukemia (GvL)-effect, since T-cells depleted grafts are associated with a higher relapse risk. Unfortunately, the GvL-effect is often associated with Graft-versus-Host-Disease (GvHD). T-cells can be divided into two phenotypic sub-groups by the expression of specific alpha/beta- and gamma/delta T-cell receptors. Gamma/delta-T-cells might provide a useful source for T-cell-immunotherapy since they may exert a GvL-effect without inducing a GvHD-risk.
Only few studies have been carried out investigating the possible impact of gamma/delta-T-cell recovery following allogeneic hematopoietic stem cell transplantation (HSCT). A recent prospective study (Godder et al., BMT 2007) indicates a survival advantage for patients (pts) recovering with higher gamma/delta-T-cell numbers following HSCT. The data presented here emerge from a single-centre analysis evaluating the possible impact of higher gamma/delta-T-cell numbers following HSCT in pts with hematologic malignancies. We included all patients who had at least three consecutive analyses of alpha/beta- and gamma/delta-T-cell numbers within the first year after HSCT. This cohort of 107 patients includes the following haematological malignancies: AML (n=40), CML (n=19), ALL (n=13), MDS (n=11), OMF (n=9), NHL (n=7), and other diseases (n=8). Median patient age was 41 years (range 16 – 67 years). Median donor age was 38 years (range 18 – 70 years). HSCT was performed with related donors in 37 pts (35%) and with unrelated donors in 70 pts (65%).
We defined the threshold for “high” gamma/delta-T-cell recovery as three ore more absolute gamma/delta-T-cell numbers above the absolute median gamma/delta-T number in the peripheral blood within the first 12 months after HSCT. According to this threshold 29 pts (27%) recovered with “high” gamma/delta-T-cells. These pts achieved a significantly higher overall survival with lower gamma/delta-T-cell numbers (log-rank p .029). This resulted from a lower relapse risk and a lower risk for acute GvHD. In multivariate analysis including other prognostic factors of overall survival (patient age, disease status, donor type, grades of acute GvHD and relapse), the beneficial effect of “high” gamma/delta-T-cell recovery could be confirmed. In contrast, recovery of alpha/beta T-cell numbers in peripheral blood had no significant influence on HSCT endpoints and were further not associated with the recovery of gamma/delta T-cells.
This analysis supports the hypothesis of a beneficial effect of high gamma/delta-T-cells recovery following HSCT regarding overall survival. Further analyses and research are warranted to determine more accurately the importance of increased recovery of gamma/delta-T-cells to possibly develop new therapeutic options in HSCT as e.g. graft engineering.
Rituximab Prophylaxis of EBV Reactivation after Alternative Donor Transplants Following Anti-Thymocyte Globulin-Based Conditioning Regimens.
Authors: Bacigalupo Andrea , Dominietto Alida , Soracco Monica , Raiola Anna Maria , Van Lint Maria Teresa , Lamparelli Teresa , Ibatici Adalberto , Gualandi Francesca , Frassoni Francesco , Tedone Elisabetta 
Published: April 2020

Abstract
Background. Reactivation of Epstein Barr Virus (EBV) frequently occurs after allogeneic stem cell transplantation (ASCT) and EBV-induced lymphoproliferative disease is a potentially fatal complication.
Aim of the study. Prevent EBV reactivation and EBV-induced post-transplant lymphoproliferative disease (LPD) after ASCT from alternative donors following anti-thymocyte globulin (ATG)-based conditioning regimen.
Methods. In 2004, we initiated a pilot study with Rituximab given prophylactically on day +5 after an alternative donor transplant. We treated 68 patients with a fixed dose of 200 mg of Rituximab on day+5 and compared their outcome with a concurrent group of 77 controls who did not receive EBV prophylaxis. The two groups were comparable for patient and disease-associated variables, and all 145 patients received ATG as part of the conditioning regimen.
Results. Rituximab on day +5 was well tolerated without any serious adverse event. Patients receiving rituximab had a significantly lower rate of EBV reactivation 41% vs 78% (p=0.0001), a lower number of EBV copies at reactivation (3 vs 10, p=0.04), a lower viral load expressed as maximum number of EBV copies (79 vs 1321,p=0.001) and a significantly lower proportion of patients with EBV copies exceeding 1000 (10% vs 44% p=0.001). Time to neutrophil and platelet engraftment was not different between the 2 groups. In the group treated with Rituximab, there was a trend for a lower incidence of acute GvHD grade II-IV (21 vs 34%, p=0.07) and grade III-IV (2 vs 8%,p=0.07), and for a reduced transplant related mortality (28 vs 39% p=0.1). Actuarial survival at 1-year was better for the Rituximab group (67 vs 50% p=0.09), but this did reach statistical significance.
Conclusions. The use of Rituximab on day +5 after ASCT from alternative donors was safe and feasible. It did significantly lower the number of EBV copies at reactivation and the number of patients with an EBV load greater than 1000, at higher risk for EBV-related LPD. Thus, this approach may reduce the need of preemptive treatment or adoptive immunotherapy for EBV reactivation after an alternative donor transplant and may warrants further investigation.
Aberrant Intracellular Retention of Mutated Receptor Tyrosine Kinase FLT3 in Human Leukemic Cells as a Potential Mechanism Supporting the Pathogenesis of Acute Myeloid Leukaemia.
Authors: Koch Sina , Ryser Martin , Jacobi Angela , Brenner Sebastian , Bornhaeuser Martin , Ehninger Gerhard , Thiede Christian 
Published: April 2020

Abstract
The exact regulation of FLT3 expression, a type III receptor tyrosine kinase (RTK), contributes to controlled proliferation and differentiation of blood cells at different stages during hematopoiesis. Activating mutations of FLT3 are found in AML, ALL and MDS and contribute to their pathogenesis, but it is unknown how mutant FLT3 deregulates hematopoiesis. It has been reported that murine mutant FLT3 signal transduction, namely with the most frequent Internal Tandem Duplication (ITD), differs from FLT3 wild type signalling. One possible mechanism for a different signalling quality leading to pathogenic effects observed in leukaemia, might be an aberrant intracellular trafficking of mutant FLT3, like shown for the other mutated type III RTKs PDGFR and KIT, which are aberrantly localized in human cancer. The localization of mutant FLT3-ITD as well as wild type FLT3 was investigated in retrovirally transduced COS7 cells, human leukemic cells and cell lines and primary CD34+ hematopoietic stem cells, enriched by MACS technique with an anti-CD34 antibody. Subcellular distribution of FLT3 was determined by confocal laser scanning microscopy. Internalization kinetics was studied by fluorescently labelling the ligand (FL) and time lapse imaging. The effects on signal transduction were investigated by Western blot analysis of protein phosphorylation for FLT3 and downstream targets (ERK, STAT5, PIM1). FLT3 localized to the plasma membrane, whereas mutant FLT3- ITD accumulated in the trans Golgi network (TGN), and not as previously speculated in the Endoplasmic Reticulum. FL was not internalized in FLT3-ITD expressing cells, while internalization in FLT3 expressing cells started at around 4 min. This observation is consistent with the non-surface localization of FLT3-ITD. Inhibition of Golgi specific glycosylation by Swainsonine led to TGN retention of FLT3. The STAT5 pathway was FL-independently activated only by FLT3-ITD. TGN accumulation of human FLT3- ITD, possibly caused by immature glycosylation, and the lack of FL internalization might support FL-independent autonomous signalling. The TGN environment may provide interactions with additional/different substrate(s), altering subsequent signalling quality (as shown here for STAT5) and thereby favouring uncontrolled proliferation of undifferentiated cells.
Newly-Diagnosed Versus Non-Initial Episodes of Thrombotic Thrombocytopenic Purpura: A Comparison of Presenting Clinical Characteristics and Response to Treatment.
Authors: Alvarez-Larrán Alberto , Río-Garma Julio del , Muncunill Josep , de la Rubia Javier , Hernández-Jodrá Manuel , Pujol Misericordia , González-Porras José , Mateo José , Rodríguez-Vicente Pilar , Viejo Aurora , Peña Francisco , Contreras Enric , Pereira Arturo 
Published: April 2020

Abstract
The remission rate with plasma exchange (PE) in thrombotic thrombocytopenic purpura (TTP) exceeds the 80%, but the disease relapses in up to 20–30% of the cases. Clinical characteristics and response to treatment of relapsed TTP is not well defined. The objective of the present study was to analyze the presenting clinical and biological features of relapsed TTP as compared with de novo TTP in a series of 102 TTP episodes (70 de novo and 32 relapses) followed prospectively and treated by daily PE and corticosteroids according to a homogeneous protocol. In comparison with de novo TTP, relapsed TTP episodes showed a higher Hb level (122 g/L versus 91 g/L, p&lt;0.001) and lower serum LDH (2.2 versus 4.5 fold above the upper limit of normality, p&lt;0.001). Neurological symptoms and fever were less frequent in patients with relapsed TTP than in patients with de novo TTP. There were no statistically significant differences in the percentage of patients with a severe deficit of ADAMTS13 activity (72% in de novo TTP versus 81% in relapsed TTP, p not significant) or the presence of inhibitory autoantibodies (87% versus 81%, p not significant). Patients with relapsed TTP needed fewer PE sessions (5 versus 10, p= 0.02) and a smaller volume of plasma (221 ml/kg versus 468 ml/kg, p=0.004) to achieve remission than those with de novo TTP. There were no significant differences in the rate of recrudescence under treatment, the need for complementary treatments (e.g. rituximab or splenectomy) or the frequency of refractoriness to PE therapy. In conclusion, relapsed TTP presents with a milder clinical and biological profile and responds easier to PE than de novo TTP.