bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toxicity and Early Response after Single Daily Dose of Intravenous Busulfan and Melphalan as Conditioning Regimen for Autologous Stem Cell Transplantation in Patients with Multiple Myeloma.
Authors: Blanes Margarita , de la Rubia Javier , Lahuerta Juan J. , Gonzalez Juan D. , Ribas Paz , Solano Carlos , Sanz Miguel A. 
Published: October 2019

Abstract
Introduction: Conditioning regimen with oral busulfan (BU) and melphalan (MEL) for patients with multiple myeloma (MM) undergoing autologous transplant (ASCT) has been associated with a high incidence of liver complications, especially severe sinusoidal occlusive syndrome (SOS).
Material and methods: We conducted the current study to assess the toxicity profile and outcomes associated with ASCT after intravenous (iv) BU-based conditioning in 45 patients (24 M/21 F; median age 60 years, range 34–71) with MM. Front-line chemotherapy consisted of VBMCP/VBAD (31cases), VAD (8 cases), and other regimens (6 cases). At transplant, 8 patients were in complete response (2 with negative immunofixation) 24 in partial response, 13 with other responses (6 with minor response, 5 had progressive disease, 1 stable disease, and 1 patient no evaluated). Median interval from diagnosis to transplant was 11 months (range 5–80). Conditioning regimen consisted of iv BU (3.2 mg/kg in a single daily dose, days −5 to −3) and MEL (140 mg/m2, day −2). In 39 patients this was the first ASCT and the remaining 6 had relapsed after a previous ASCT conditioned with MEL-based regimens.
Results: Median number of CD34+ cells administered was 2.9 x10^6/kg (range 1–5.8). Hematopoietic recovery was fast with median (range) time to 0.5 PMN and 20 platelets x10^9/L of 12 (11–46) and 13 (9–64) days, respectively. The toxicity profile was favourable. Particularly, no case of SOS, commonly seen with the oral BU, has been reported. Mucositis was the non-hematopoietic toxicity most frequently seen (42 cases). Other toxicities observed were uncommon (gastrointestinal toxicity, 6 cases, increase of liver enzymes, 3 cases and mild cardiac failure, 1 case). Fever was observed in 38 patients: fever of unknown origin in 21 cases, microbiologically documented infection in 13 cases and clinically documented infection in the remaining 4 cases. Only 2 patients (4%) died due to transplant-related toxicity (one patient to pneumonia, day 51; the other patient to sepsis to Acinetobacter baumani, day 54). With a median follow-up of 18 months, 41 patients had been evaluated for response: 19 are in complete response (9 with negative immunofixation), 16 in partial response, 2 with minor response, 2 had progressive disease, and 2 transplant-related deaths. The 18 months actuarial overall and progression-free survival rates are 95±3% and 70±10%, respectively. Interestingly, in 19 patients significant improvement response was observed after transplant.
Conclusions: These preliminary results show that iv BU-containing regimen for MM is associated with an acceptable toxicity profile and with a high anti-myeloma effect.
Detection of Herpesvirus and Adenovirus Infections in Patients Undergoing Stem Cell Transplantation: Looking Below the Tip of the Iceberg with the Microarray Technology.
Authors: Ditzen Anette , Stichling Markus , Mueller Rene , Rutzka Anke , Hille Kristine , Illmer Thomas , Bornhaeuser Martin , Ehninger Gerhard , Jacobs Enno , Ehricht Ralf , Rohayem Jacques 
Published: October 2019

Abstract
Infections with herpesvirus and adenovirus is a major cause of morbidity and mortality in patients undergoing stem cell transplantation (SCT). In those patients, the frequency of herpesvirus and adenovirus co-infections as well as their contribution to the infectious burden remain so far unclear. In this study, we have postulated that co-infections with herpesviruses and adenoviruses are frequent in the 100 days following SCT, contributing significantly to the infectious burden. To address this issue, 615 blood samples collected from patients undergoing SCT (n=35) were retrospectively tested by quantitative real-time PCR for the presence of HSV 1/2, VZV, EBV, CMV, HHV6 A/B, and adenovirus. Infections with a single virus were detected in 46.1% (283/615) of the samples, whereas co-infections with two or three viruses were detected in 9.9% (61/615) and 2.1% (13/615) of the samples, respectively. Interestingly, about 50% of the patients (17/35) displayed a co-infection with two or more viruses, with [CMV+HHV6 A/B], and [EBV + HHV6 A/B +adenovirus] being most frequently detected, respectively. Comparison of viral loads indicated that the infectious burden increases proportionally to the number of viruses detected. Moreover, a DNA-microarray allowing simultaneous detection of HSV 1/2, VZV, EBV, CMV, HHV6 A/B, and adenovirus was developed. The assay displayed a high diagnostic accuracy, being an attractive device for routine assessment of the infectious burden in immunocompromised patients after SCT.
Bacterial, Viral and Fungal Infections in Patients after Allogeneic Stem Cell or Bone Marrow Transplantation - A Comparison between Patients with Related and Patients with HLA-Matched Non-Related Stem Cell Donors.
Authors: Rieger Christina T. , Tischer Johanna , Ostermann Helmut 
Published: October 2019

Abstract
Bacterial, viral and fungal pathogens frequently cause severe, life-threatening infections in immunocompromised patients after allogeneic stem cell transplantation (SCT). We investigated whether patients with related stem cell donors (group A) developed infections less frequently than patients with HLA-matched, non-related donors (group B). Fifty-nine consecutive patients treated at our transplantation unit between April 2004 and January 2005 were included into the analysis. We documented demographic and clinical characteristics at baseline, treatment, clinical course, microbiological examinations, clinical and radiological signs of infection and mortality. Of the total 59 patients analyzed, 22 received stem cells from related and 37 from HLA-matched non-related donors. Both groups were well balanced regarding age and weight. 50% of the patients in group A and 60% in group B were male. Most frequent diagnoses were acute myeloid leukemia (30 of 59 patients [50.8%]; group A: 68.2%; group B: 40.5%), multiple myeloma (15.2%), acute lymphoblastic leukemia (11.9%) and chronic myeloid leukemia (10.2%). Bone marrow was more often the stem cell source in group A (45.5%/ 10 patients) than in group B (10.8%/ 4 patients), peripheral stem cell transplantation respectively was predominant in the unrelated group (86.5%/ 32 patients) versus the family donor group (54.5%/ 12 patients), cord blood was used as unrelated stem cell source in1 patient (2.7%). Clinically documented infections occurred in 6% in group A and in 14% in group B. Pulmonary infiltrates were observed more frequently in group A (11 patients/ 50%) than in group B (16 patients/ 43.2%). The predominant findings were atypical infiltrates (total 16 patients), followed by signs of fungal (total 7 patients) and bacterial pulmonary infiltration (total 4 patients). Microbiologically documented infections were detected in all patients. The average number of pathogens was equal in both groups. Detected pathogens were HHV-6 (48 patients), coagulase-negative Staphylocci (17 patients), EBV (14 patients) and CMV (11 patients). Three fungal infections were detected by microbiological approaches in group A (2 × Candida albicans, 1 × Pitysporum ovale) compared to nine fungal infections in group B (5 × Candida albicans, 1 × Candida glabrata, 1 × Candida parapsilosis, 2 × Geotrichum capitatum). Two years after transplantation, 55.9% of patients were alive (group A: 68.2%; group B: 48.6%). Patients with AML had a two-year survival of 50% (group A: 53.3%; group B: 46.7%). In our study, we observed no clear relation between frequency of infection and donor type, yet there was a trend towards more invasive fungal infections in the unrelated group (13% group A vs. 24% group B).
Bloodstream Infection after Reduced-Intensity Umbilical Cord Blood Transplantation Versus Other Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Takagi Shinsuke , Ishiwata Kazuya , Tsuji Masanori , Yamamoto Hisashi , Kato Daisuke , Matsuhashi Yoshiko , Kusumi Eiji , Seo Sachiko , Matsuno Naofumi , Matsumura Tomoko , Uchida Naoyuki , Masuoka Kazuhiro , Wake Atsushi , Miyakoshi Shigesaburo , Yoneyama Akiko , Matsuzaki Michio , Taniguchi Shuichi 
Published: October 2019

Abstract
Blood stream infection (BSI) is a major cause of transplant-related mortality (TRM) following allogeneic hematopoietic stem cell transplantation, and to overcome it, reduced-intensity preparative regimens were developed in recent years. However, little information has been reported on BSI after reduced-intensity cord blood transplantation (RI-CBT). To clarify the characteristics of BSI after RI-CBT, we compared the incidence of microbiologically documented BSI before day 100 between RI-CBT and reduced-intensity non-cord blood allogeneic hematopoietic stem cell transplant (RI-non-CBT) recipients in Toranomon hospital, Japan. RI-non-CBT group includes related bone marrow (rBM), related peripheral blood stem cell (rPBSC) and unrelated bone marrow (uBM) transplantation. We retrospectively reviewed the first events of BSI in 211 consecutive adult patients between Jan 2004 and July 2006. One hundred and fifteen patients received RI-CBT and 96 patients received RI-non-CBT (4 from rBM, 34 from rPBSC and 58 from uBM). The median ages of patients in both groups were 55 years. All of the preparative regimens were fludarabine-based and prophylaxis against GVHD was tacrolimus alone in most of the RI-CBT recipients and combination of calcinurin inhibitor and short-term methotrexate in most of the RI-non-CBT recipients. The median time to achieve neutrophil engraftment was delayed in RI-CBT group (day 20 vs. day15). The cumulative incidence of engraftment at day 60 was 73.0% in RI-CBT group versus 90.6% in RI-non-CBT group. The cumulative incidence of BSI was 39.3% at day 100 and RI-CBT group tended to have more BSI compared to RI-non-CBT group (46.1% vs. 31.3%, p=0.0122), particularly at the early points after transplantation. Median day of positive culture for bacteremia was earlier (day 9 vs. day 14) in RI-CBT group. In spite of reduced-intensity preparative regimen, RI-CBT in adults is associated with higher rates of BSI at early time points after transplantation.
Birth Order Does Not Affect Outcome in HLA-Identical Sibling Transplantation.
Authors: Copelan Edward , Sobecks Ronald , Dean Robert , Rybicki Lisa , Brown Stacey , Kalaycio Matt , Pohlman Brad , Sweetenham John William , Andresen Steven , Bolwell Brian 
Published: October 2019

Abstract
Fetomaternal and transmaternal sibling microchimerism might result in tolerance of hematopoietic stem-cell donors to recipients who were born before them. A single clinical study comparing first-born recipients and first-born donors provided evidence that birth order can have a significant impact on survival and on the incidence of acute graft-versus-host disease (GVHD) and relapse in HLA-identical sibling transplantation. In order to determine whether birth order might exert a consistent, biologically important effect, we compared survival and the incidence of acute GVHD, chronic GVHD, and relapse in recipients of HLA-identical transplants from sibling donors older than themselves to recipients with younger sibling donors. From 11/84 through 11/06, 410 first HLA-identical sibling transplants were performed. Patients were categorized by whether the sibling donor was older (n=187) or younger (n=223) than the recipient. As expected, the two groups differed with respect to patient age (P<0.001). The groups were similar with respect to gender, diagnosis, interval from diagnosis to transplant, extent of prior treatment, preparative regimen, stem-cell source, donor to patient gender, and CD34+ cell dose. Outcomes were estimated using the Kaplan-Meier Method and compared between the birth order groups using the log rank test. The incidence of acute GVHD, ≥ grade II acute GVHD, chronic GVHD, extensive chronic GVHD, relapse, survival, and disease-free survival were similar (0.39≤P≤0.85) between the two groups. The incidence of acute GVHD and survival in the two groups is shown below:
Figure Figure Figure Figure
After adjustment for differences between the two groups, multivariable assessment of sibling birth order was not prognostic for survival (P=.32). Only older (P=0.029) and male donor/female recipient (P=.017) were independent prognostic adverse factors. In this large study of the HLA-identical sibling transplantation, no impact of birth order on the incidence of GVHD, relapse incidence, or survival was detected. Although (because of different methodologies) not directly contradictory to a previous study of birth order, the present results suggest that further study of the impact of birth order on outcome of HLA-identical sibling transplantation is needed. Suggestions that birth order be integrated into donor-selection algorithms or that matched unrelated donors might be preferred to high-risk HLA identical siblings are premature.
Rituximab Reduces the Incidence of Acute Graft Versus Host Disease and Delays CD3+CD4+ Lymphocyte Recovery.
Authors: Christopeit Maximilian , Schuette Vincent , Behre Gerhard 
Published: October 2019

Abstract
The monoclonal antibody Rituximab has been successfully used to treat steroidrefractory chronic graft versus host disease (cGvH) after allogeneic stem cell transplantation (SCT). We hypothesized that Rituximab might reduce the incidence of aGvH. We found that patients conditioned with a regimen containing Rituximab experienced significantly less aGvH when compared to a regimen without Rituximab (23.1% versus 66.7%, p = 0.032). Furthermore did we find that the recovery of CD3+CD4+ lymphocytes was delayed following administration of Rituximab. As expected, patients were devoid of CD19+CD20+ B lymphocytes after administration of Rituximab; interestingly, both the recovery of CD3+CD8+ lymphocytes and CD16+CD56+ NK cells did not differ between patients receiving Rituximab and Rituximab-naíve patients. Furthermore, our data revealed a significant correlation of the transplants CD34+ HSC content with the occurrence of aGvH (p = 0.031) but only a trend towards a correlation of CD3+ cells with the occurrence of aGvH (p = 0.274). Taken together, our data establish a mechanism of how Rituximab might reduce the incidence of aGvH next to depleting host and perhaps donor antigen presenting cells. It remains to be elucidated whether this effect translates to a graft versus tumor effect and to survival as well.
ASBMT Risk Group and CD 34+ Dose Predicted for the Development of aGVHD in Allogeneic MRD Transplants When the Donors Who Received a Combined Mobilization and In Vivo TCD Regimen Using rhg-CFS and Dexamethasone.
Authors: Ashraf Khaleel K. , Tilden Arabella B. , Li Yufeng , Gupta Sameer , Lamb Lawrence S. , Salzman Donna E. , Lopez Richard , Vaughan William P. 
Published: October 2019

Abstract
We looked at factors affecting the development of acute and chronic GVHD in a cohort of 118 patients who underwent allogeneic matched sibling transplantation between 09/1998 to 05/2006 at the UAB BMT program. Donors were mobilized with rhg-CSF (10–16mcg/kg/day x4) and received dexamethasone 10mg/m2/day x3 days to effect in vivo T cell depletion (TCD). Total CD3 and CD34 cell dose were divided in to 4 quartiles (See table below). We then analyzed the influence of CD3+ and CD34+ dose quartiles on aGVHD, cGVHD, engraftment, TRM and relapse. (see table) Acute GVHD: Univariate Logistic regression indicated that the development of aGVHD is negatively associated with quartiles (q25–q50) interval of CD3 dose (p=0.0418). However this relationship was not independent of risk factor and CD34 dose. After using Multivariable Logistic regression analysis with adjustments for age, race and sex, we found that ASBMT risk factor and CD34 quartiles dose are strong predictors of aGVHD: patients who had high risk are about three times more likely to have aGVHD (OR=2.829, 95% CI 1.142–7.020, p=0.0250). The higher the CD34 dose also predisposed to higher incidence of aGVHD (p=0.0432). Median Survival: Patients who received the CD3 (P=0.00141) and CD34 (P=0.0270) in the q25–q50 quartile did better with improved median survival. Relapse and CD 3 quartiles: Using the - 2 log (LR) test shows the relapse free interval was longer if the CD3 dose is between q25 and q50 (p=0.0058); there was no relation between CD34 and relapse. TRM: Not associated with CD3 or CD 34 dose. WBC engraftment: Multivariable analysis indicated that the relationship is mainly an age effect. After adjusted for risk factor, GVHD status, CD3 or CD34 dose, the engraftment day is still significantly related to age at BMT (p=0.0252). No associations are observed for the relationship between engraftment day and GVHD risk. cGVHD: Neither CD34 dose (p=0.5339) nor CD3 (p=0.4209) dose were statistically associated with incidence and severity of cGVHD. To summarize, higher CD34 dose and higher risk ASBMT category predicted for higher incidence of aGVHD; neither CD3 nor CD 34 dose predicted for the development of cGVHD. Age was the single most important predictor of WBC engraftment.
CD3+ and CD34 Quartiles Quartile <25 25–50 50–75 >75 CD3 X10E8 <2.5 2.53–3.60 3.60–5.30 >5.30 CD34 X10E6 <4.92 4.92–7.79 7.79–11.2 >11.2
Hematopoietic Stem Cell Gene Therapy for Wiskott-Aldrich Syndrome.
Authors: Boztug Kaan , Dewey Ricardo A. , Diez Ines Avedillo , Manfred Schmidt , Kerstin Schwarzwaelder , Jana Diestelhorst , Sonja Naundorf , Klaus Kuehlke , Irina Kondratenko , Laszlo Marodi , von Kalle Christof , Welte Karl , Klein Christoph 
Published: October 2019

Abstract
Wiskott Aldrich Syndrome (WAS) is a fatal primary immunodeficiency disorder caused by mutations in the cytoskeletal adaptor molecule WASP. We here report on our preliminary experience in two patients undergoing hematopoietic stem cell gene therapy upon retroviral WASP gene transfer. Both patients suffered from severe WAS and were treated with 8x10e6 and 7x10e6 /kg body weight transduced CD34 cells, respectively. Follow-up time is 9 and 10 months. Both patients show evidence of gene marking and WAS protein expression in multiple hematopoietic lineages. In particular, WASP-transgenic T and NK cells show a relative increase over time (up to 70% WASP-expressing cells). Both patients show a polyclonal pattern of hematopoiesis, as determined by LAM-PCR. No morphological or cytogenetic abnormalities were observed in the bone marrow. While one patient continues to suffer from autoimmune cytopenia, the other patient has had a marked clinical benefit. This interim analysis documents that hematopoietic gene therapy for WAS is feasible without undue short term toxicity. A longer follow-up period will be required to comprehensively evaluate the clinical and molecular outcome in these patients and to monitor for potential unwanted side-effects.
Prognostic Value of BCR-ABL Transcript Amount for Early Relapse Detection in Chronic Myeloid Leukemia Patients Treated with Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Solarska Iwona , Majewski Miroslaw , Nasilowska-Adamska Barbara , Zaucha Jan M. , Rzepecki Piotr , Calbecka Malgorzata , Sulek Kazimierz , Hellmann Andrzej , Marianska Bozena , Warzocha Krzysztof 
Published: October 2019

Abstract
The detection of BCR-ABL mRNA following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with relapse but not absolutely predictive. Early molecular relapse can be detected using real-time quantitative PCR (RQ-PCR) assay, which provides an accurate and reliable method of BCR-ABL expression evaluation. Using this method we analyzed 66 CML patients 3 months to 12 years (median 50 months) after allo-HSCT, who had BCR-ABL transcript measured in peripheral blood or bone marrow samples every 3, 6 and 12 months after allo-HSCT. The patients were analyzed at monthly intervals in the case of rising BCR-ABL transcript level. The median age at diagnosis and median age at time of allo-HSCT were 38 years (range, 16–55). Fifty three patients were in the first chronic phase, and 13 were in the second chronic phase. The median time from diagnosis to allo-HSCT was 8 months (range, 2.5–59). Eighty two percent of patients received allo-HSCT from HLA-identical siblings and 18% from unrelated donors. Transplant conditioning and GvHD prophylaxis were performed according to standard protocols. Quantification of BCR-ABL mRNA transcript was performed according to ‘Europe Against Cancer’ protocol. The median number of assays per patient was 6 (range, 3–16). According to the amount of BCR-ABL transcript after allo-HSCT, patients were allocated into 3 categories, including 35 patients with stable/low level of BCR-ABL transcript (below 0.005%), 11 patients with fluctuating-low level of BCR-ABL (0.005%–0.01%), and 18 patients with high level of BCR-ABL transcript (0.01%–0.1%). We found strong correlation between the amount of BCR-ABL transcript after allo-HSCT and probability of molecular relapse (6% vs. 9% vs. 28%, respectively) as well as relapse-free survival (median time to relapse: 134 months vs. 106 vs. 89, respectively). In the group of patients with high level of BCR-ABL transcript cytogenetic relapse was observed in 75%. In one case BCR-ABL level spontaneously fall down to a low-lewel expression within 6 months. One patient received donor lymphocyte infusion without response, and then was successfully treated with imatinib. RQ-PCR is valuable method to quantitate BCR-ABL expression in CML patients after allo-HSCT, allows monitoring the kinetics of BCR-ABL mRNA transcript amount and is useful in prediction of the hematologic relapse. RQ-PCR can successfully distinguish the group of patients with high risk of relapse from two groups without need for additional therapy (persistent disease/lack of disease).
Haematopoietic Stem Cell Transplantation - An Experience from Developing World.
Authors: Ullah Khalil , Ahmed Parvez , Raza Shahid , Mahmood Tariq , Khan Badshah 
Published: October 2019

Abstract
One hundred and fifty four patients received allogeneic stem cell transplant from HLA matched siblings for various haematological disorders at Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan from July 2001 to Sep 2006. Indications for transplant included aplastic anaemia (n=66), b-thalassaemia major (n=40), CML (n=33), acute leukaemia (n=8) and misc disorders (n=7). One hundred and twenty patients were male and thirty four were female. Median age of patient cohort was 14 yrs (range 1 ¼ −54 yrs). Pre-transplant infection surveillance was carried out and strict prophylaxis against infection was observed. The mean mononuclear cell dose was 4.2 x 109/kg of recipient. Post transplant complications encountered in our patients were: acute GvHD (grade II-IV) 28.5%, chronic GvHD 15.5%, haemorrhagic cystitis 9.7%, VOD liver 5.1%, acute renal failure 3.2%, bacterial infections 51.2%, fungal infections 15.0%, CMV infection 4%, herpes zoster 4%, tuberculosis 2.6%, pneumocytitis jirovici infection 0.6%, malaria 0.6% patient, graft rejection 5.2% patients and relapse in 4%patients. Certain unexpected rare post transplant complications were also observed in our patients. These included hickman catheter embolization, GB syndrome, deep vein thrombosis, haemorrhagic pericarditis with clots leading to cardiac temponade, idiopathic polycythemia, dengue fever and status epilepticus. Mortality was observed in 27.2% patients. Major causes of mortality were GvHD, VOD, relapse, intracranial haemorrhage, acute renal failure, pseudomonas septicemia, tuberculosis, disseminated aspergillosis and CMV infection. At five years, the overall survival (OS) and disease free survival (DFS) was 72.5% & 70.7% respectively.