bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Prophylaxis with Aerosolized Amphotericin-B Deoxycholate (d-AmB) on Respiratory Tract Invasive Fungal Infections (IFIs) after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT).
Authors: Morello Enrico , Cavattoni Irene M. , Fabris Pietro , Coin Silvia , Amato Barbara , Cassibba Vincenzo , Casini Marco , Pagani Leonardo , Cortelazzo Sergio 
Published: October 2019

Abstract
Background and aims IFIs still pose major challenges in HSCT, and effective prophylaxis remains a matter of debate. The aim of this retrospective study was to evaluate the impact of aerosolized d-AmB on respiratory tract IFIs in a homogeneous cohort of allogeneic HSCT patients, transplanted at our institution. Patients and methods Since 1999, 81 consecutive patients were transplanted from matched related (N=61) or unrelated donor (MUD). Analysis was performed on 74 evaluable patients, in order to monitor the prevalence of respiratory tract IFIs within 40 days after HSCT, according to current guidelines (possible, probable, proven IFIs). Conventional antifungal prophylaxis was based on the association of fluconazole (400 mg/d), plus aerosolized d-AmB (15 mg bid) in 54 out of 74 cases (73%). All the patients were screened before transplant and monitored thereafter with CT or x-rays (paranasal sinuses, thorax), surveillance swabs and galactomannan antigenemia. Chi square test was performed to evaluate correlations between variables.
Results Aerosolised d-AmB was administered to 70 patients for a median time of 15 days (range 1–45). Prolonged administration was not associated with increased severe bacterial infections, nor severe adverse events were observed; only a patient developed moderate bronchial spasm. In 13 pts, aerosolized d-AmB was delivered for less than 7 days, due to worsened clinical conditions, or poor compliance. In this group, proven IFIs were diagnosed in 2 patients (1 mucormycosis and 1 fusariosis), possible aspergillosis in one and probable aspergillosis in another one. A shortened administration (<7 days) of aerosolized d-AmB was associated with an increased risk of IFIs (p=0,002). Overall, 95% of patients did not experience IFIs and nobody died due to IFIs. Nine patients had a pre-transplant nasal swab positive for Aspergillus spp., and 8 of them received Aerosolized d-AmB; subsequent surveillance swabs proved negative. On the other hand, the only patient with positive swab who was not able to receive aerosolized d-AmB due to bronchial spasm developed a possible aspergillosis.
Discussion Despite the low number of patients, prolonged aerosolized d-AmB seems to play a role in preventing respiratory tract IFIs, but a randomised controlled trial is recommended to verify the impact of this prophylaxis in the setting of allogeneic HSCT.
Comparison of Cyclosporine A and Mycophenolate Mofetil vs Cyclosporine A and Methotrexate in Reduced Intensity Conditioning HLA Sibling Allogeneic Stem Cell Transplantation. A Case-Match Single-Center Experience.
Authors: Piñana Jose L. , Valcárcel David , Martino Rodrigo , Parody Rocio , Sureda Anna , Briones Javier , Delgado Julio , Snchez Blanca , Brunet Salut , Sierra Jorge 
Published: October 2019

Abstract
BACKGROUND: Graft-versus-host disease (GVHD) is the major obstacle to successful allogeneic stem cell transplantation (SCT) transplantation. Cyclosporine (Csa) in combination with methotrexate (MTX) is the most commonly used prophylactic regimen. The combination of CsA and Mycophenolate Mofetil (MMF) has recently been introduced. In this case-match study we retrospectively analyzed the introduction of MMF as GVHD prophylaxis in comparison with a short course of MTX in the setting of reduced intensity conditioning allogeneic SCT (Alo-RIC).
PATIENTS AND METHODS: We analyzed 59 Alo-RIC recipients who received an Alo-HSCT from an HLA-identical sibling between April 2000 and June 2006. The median follow-up for the whole group was 473 days (8 to 2139 days). The study group included 40 males and 19 females. Median age was 59 years (range 43 to 72). Diagnoses were acute leukemia/myelodisplastic syndrome) (n=19/22), mutiple myeloma (n= 6), chronic myeloid leukemia (n=5) and non- Hodgkin lymphoma (NHL) (n= 4). GVHD prophylaxis consisted of Csa/MTX (MTX group) in 37 patients and Csa/MMF (MMF group) in 22 patients. The conditioning regimen was based on fludarabine in combination with busulfan (42 recipients) or melfalan (17 cases).
RESULTS: The occurrence of mucositis grade 2–4 was higher in the MTX group than in the MMF group (62% vs 28% p= 0.015). No significant differences were found between MMF vs MTX groups in time to neutrophil recovery (16 +/−3 days vs 15 +/− 2days) (p= 0.5). Median time to the achievement of complete T-cell donor chimerism in the MTX and MMF groups was 79 days (range 19–740) and 76 days (range 24–223) respectively (P=0.4). The 1- year non-relapse mortality was similar in MTX and MMF groups 14% (95% C.L. 6–31%) vs 28% (95% C.L. 13–60%) respectively; P=0.2. Cumulate incidence of acute GVHD for MTX and MMF groups was 49% (95% C.L. 35–68%) and 68% (95% C.L. 51–91%) respectively (P= 0.6). Patients in the MTX group showed a trend to a higher incidence of chronic GVHD than the Csa/MMF group, 55% (95% C.L. 40–74%) vs 42% (95% C.L. 23–75%) (P=0.2). No differences were found between MTX vs MMF groups in 1-year overall survival [78%(64–92%) vs 53%(38–76%); P=0.1] nor in 1-year relapse incidence [37% (95%CI 21–64%) vs 19% (95%CI 10–37%) P=0.1) We conclude that the Csa/MMF combination appears to be equivalent to the standard Csa/MTX aGVHD prophylaxis in Alo-RIC. MMF showed significantly less mucositis.
Incidence and Characteristics of Infections Following Cord Blood Stem Cell Transplantation in Children.
Authors: Lim Y.J. , Lee Y.H. , Koo H.H. , Yoo K.H. , Sung KW , Chung NG , Cho B. , Kim H.K. , Kang H.J. , Shin H.Y. , Ahn H.S. , Kook H. , Hwang T.J. , Moon H.N. , Seo J.J. , Im H.J. , Park S.K. , Ghim Thad T. , Hah J.O. , Lyu C.J. , Park J.E. , Lee K.C. , Lim Y.T. , Lim J.Y. , Kang I.J. 
Published: October 2019

Abstract
Infection is one of the most important causes of morbidity and mortality after hematopoietic stem cell transplantation. We assessed the incidence and characteristics of infections in 163 cord blood stem cell transplantation (CBT) recipients from 13 transplant centers of Korea between October, 1996 and April, 2005. The patients underwent CBT with standardized conditioning, GVHD prophylaxis and supportive care including pre-emptive ganciclovir therapy for cytomegalovirus (CMV) antigenemia. The median time to neutrophil engraftment was 19 days (10–62 days) and to platelet engraftment was 45 days (14–394 days). Within the post-transplant day 0 to day 30, 81.6% of patients (133/163) experienced febrile episodes with 11.7% (19/163) of clinically documented infection (CDI) and 19.6% (32/163) of microbiologically documented infection (MDI). The neutrophil engraftment was delayed in the patients with CDI and MDI rather than without CDI and MDI (day 26.3 vs day 21.5, P=0.03) before day 30. In the time period of day 30 to 100, febrile episodes, CDI and MDI occurred in 54.3% (82/151), 14.6% (42/151) and 13.2% (20/151), respectively. After day 100, 38.5% of patients (45/117) experienced febrile episodes with 17.9% (21/117) of CDI and 7.7% (9/117) of MDI. Although the incidence of febrile episodes before day 30 was significantly higher than after day 30, the incidence of CDI and MDI was comparable. There were no significant differences of infection rate according to the infused cell dose, the degree of HLA disparity, acute GVHD and chronic GVHD. The overall mortality rate after CBT was 40% (65/163). Infection was considered the primary cause of transplant-related mortality and represented 18.4% (106/163) of the causes of death with the median day of 96.5 (1∼1,081 days). The incidence of pre-transplant CMV-seropositivity was 85.5% of the patients (106/123) and CMV antigenemia developed in 52.7% of CMV-seropositive patients compared to 11.8% of CMV-seronegative patients (P=0.002). CMV disease developed in 25.7% of CMV-seropositive patients and 6.7% of CMV-seronegative patients, which showed statistiacally not significant. Pre-transplant conditioning regimens such as antithymocyte globulin did not affect on the incidence of CMV antigenemia or CMV disease. Based on our study, the infection was still the primary cause of mortality after CBT, particularly in patients with delayed neutrophil engraftment. The high prevalence of CMV seropositive patients in Korea was associated with increased incidence of CMV antigenemia, not with CMV disease.
Chimerism Status as a Possible Marker of Incipient Disease Relapse in Patients with AML.
Authors: Horky Ondrej , Mayer Jiri , Borky Marek , Krejci Marta , Pospisilova Sarka , Dvorakova Dana 
Published: October 2019

Abstract
The connection between chimerism status and occurence of relapse in patients undergoing hematopoietic stem cell transplantation remains controversial. One reason for this seems to be employment of different methods with inherrited different sensitivity and related definition of complete donor chimerism (CDC). We compared an application of fragment analysis (FA) of minisatellite, microsatellite or sex specific regions (limit of quantification ∼1%) with real-time quantitative PCR (RQ-PCR) of insertion/deletion and sex polymorphism (limit of quantification ∼0.1%). Long-term data (follow-up 1.8–7.4 years, median 3.3 years) obtained from two groups of AML patients transplanted in our centre are presented. The first group involves 9 patients that experienced relapse (one of them three times) whereas the second one contains 11 individuals in complete remission. Retrospective chimerism analysis of patients in the first group by RQ-PCR allowed prediction of hematological relapse significantly earlier (p=0.016) than quantification by FA, (35–448 days, median 77 days by RQ-PCR vs. 0–154 days, median 35 days by FA). Beside this, in two cases the incipient relapse was detected only by RQ-PCR and not by FA, 118 and 70 days in advance. Moreover, in two patients with fusion gene, there was detection of molecular relapse recorded simultaneously by either increase of autologous hematopoiesis or conversion of CDC to MC in granulocytes, as revealed by analysis of sorted leukocyte subsets. On the other hand, after achievement of CDC within the group of patients in complete remission, the amount of detectable autologous DNA did not repeatedly exceeded the limit of quantification of RQ-PCR. The CDC was not achieved in one case only, whereas lineage-restricted analysis persistently shows MC in T-lymphocytes (1–3% of autologous origin). Our data demonstrate, that assessment of chimerism by RQ-PCR along with analyses within specific leukocyte subsets can provide an early indication of incipient disease relapse of AML and could be used for residual disease monitoring in cases, where another specific marker is not available.
Bone Marrow Transplant Activity - A Country Report from Pakistan.
Authors: Ullah Khalil , Shamsi Tahir S. , Adil Salman N. 
Published: October 2019

Abstract
Bone Marrow transplant activity started in 1999 in Pakistan when Bismillah Taqee Institute of Health Sciences & Blood Diseases Centre started functioning in the southern port city of Karachi, Pakistan. Two years later in year 2001 Armed Forces Bone Marrow Transplant Centre started functioning in the northern part of country, Rawalpindi, Pakistan. In 2004 another transplant centre, started in Aga Khan University Hospital, Karachi, Pakistan. Since the establishment of these transplant centers a total of 349 allogeneic transplants have been carried out for various hematological disorders. The major indications included aplastic anaemia (n=166), β-Thalassaemia major (n=76), chronic myeloid leukaemia (n=57), acute leukaemias (n=37) and misc disorders including MDS, Fanconi anaemia and others (n=13). A total of 22 autologous transplants in lymphomas and multiple myeloma have also been carried out. Since this number is very small, only data of allogeneic transplants is being presented here. Major post transplant complications encountered were neutropenic fever in 92.6% patients with 27% culture positivity (412/1571). Infective complications included bacterial infections (both gram+ive and gram-ive) in 194 patients (56%), fungal infection in 32 patients (10%), CMV infection in 15 patients (5%), herpes infection in 16 patients (5%), tuberculosis in 9 patients (3%) and PCP in 1 patient (0.28%) and malaria in 1 patient (0.28%). So post transplant infections were confirmed in 76.6% (268/349) patients on the basis of clinical assessment, microbiological, virological and histopathological analysis. Non infective post transplant complication included aGvHD (grade II-IV) in 80 patients (23%), cGvHD 46 patients (13.1%), VOD liver in 25 patients (7.2%), haemorrhagic cystitis in 27 patients (7.7%), ARF in 13 patients (3.7%), primary graft failure in 5 patients(1.4%), graft rejection in 17 patients (4.9%) and relapse in 14 patients (4%). Transplant related mortality was observed in 93 patients (26.6%). Infective & non infective causes of mortality included septicemia in 15 patients (4.3%), CMV in 8 patients (2.3%), fungal infections in 8 patients (2.3%), tuberculosis in 2 patient (0.6%). herpes encephalitis in 1 patient (0.3%) VOD in 8 patients (2.3%), aGvHD in 12 patients (3.4%), cGvHD in 7 patients (2.0%), ARF in 8 patients (2.3%) and intracranial haemorrhage in 3 patients (0.9%). Graft related mortality due to graft failure and relapse was observed in 6 patients (1.7%) and 14 patients (4%) respectively. Unrelated accidental death in 1 patient (0.3%). Overall survival was observed in 256 patients (73.3%) and DFS in 250 patients (71.6%). The OS and DFS was 72.7% and 70.9% in BTIHS & BDC patients, whereas OS & DFS was 72.8% and 70.7% respectively in AFBMTC patients. The OS & DFS was 82.6% at AKUH. Disease wise overall survival in aplastic anemia, β-Thalassaemia, CML and acute leukemia was 78.3%, 76.3%, 63.1% and 59.5% respectively.
Two Cases of Chronic Active Epstein-Barr Virus Infection (CAEBV) Successfully Treated with Allogeneic Bone Marrow Transplantation and Induction of Specific Cytotoxic T Lymphocyte (CTL).
Authors: Miyamura Takako , Chayama Kousuke , Wada Tomoaki , Yamaguchi Kazunari , Yamashita Nobuko , Ishida Toshiaki , Washio Kana , Morishita Naoto , Oda Megumi , Morishima Tsuneo 
Published: October 2019

Abstract
Chronic active Epstein-Barr virus infection (CAEBV) is a heterogenous EBV-related disorder, characterized by clonal expansion of EBV-infected T or NK cells. Although CAEBV is a high mortality and morbidity disease with life-threatening complications, effective treatment regimens have not yet been established. The pathogenesis and etiology of CAEBV are not well characterized. The clonal expansion of EBV-associated T or NK cells has been suggested to play important roles in the pathogenesis of CAEBV. It is not clear why EBV-associated abnormal cells cannot be excluded, because of a factor on the virus side or a function on the host side. We report two cases of CAEBV in which allogeneic bone marrow transplantation (BMT) was performed soon after diagnosis. After BMT, the EBV genome titer decreased as cytotoxic T lymphocyte (CTL) activity gradually increased.
Case 1: A five-year-old boy had exhibited prolonged fever, lymphadenopathy, and severe liver dysfunction for more than 6 months. Clonally proliferating EBV-infected T cells and abnormally high titers of EBV-related antibodies were detected. No EBV-specific CTLs were detected. The patient was given a diagnosis of T-cell type CAEBV and he received BMT (the donor was his 1-locus mismatched mother) 6 months after diagnosis. Severe treatment-related toxicity did not occur. After BMT, the EBV genome titer gradually decreased as the CTL activity increased. At 2 months after BMT, the EBV genome titer of the patient was nearly negative.
Case 2: A two-year-old girl had exhibited a persistent fever of unknown etiology and hepatosplenomegaly. Abnormally high titers of EBV-related antibodies were detected and NK cells in her peripheral blood contained a high EBV genome titer. The EBV-specific CTL levels were low. She received BMT from an unrelated donor 3 months after diagnosis. Toxicity other than grade 2 graft-versus-host disease was not detected. After BMT, the EBV genome titers decreased gradually as the CTL activity increased.
Conclusion: These cases suggest that not only high-dose chemotherapy as a preconditioning treatment of BMT, but also that increased CTL activity to eliminate virus-infected cells might be effective. Additional cases should be studied to establish effective treatments.
Non Myeloablative Allogeneic Related Transplant in Patients with Aggressive B Cell Lymphoma: Results of Two Multicenter Spanish Trials. The GELTAMO Group.
Authors: Caballero M.D. , Briones J. , Mateos M.V , Tomás J.F. , Martino R. , de la Serna J. , Díez J.L. , Pérez-Simón J.A. , Sureda A. , Sarrá J. , García-Laraña J. , Ribera J.M. , Sierra J. , Miguel J.F. San 
Published: October 2019

Abstract
Although autologous transplant is the election in poor prognosis patients with Non Hodgkin agressive histologies, some patients relapse, for others collection of progenitor cells is not possible and in some categories as Mantle Cell Lymphoma results after autologous transplant are dismal. From 1999, three prospective multicenter trials with non-myeloablative allogeneic transplant in hematological malignancies have been performed in Spain. Up to now, 36 patients have been registered in these trials. From them,28 (58%)had aDBLCL,1 (3%) a transformed MZL,1 (3%) a BL and 14 (37%) a MCL. The conditioning regimen consisted of fludarabine 30 mg /m2 intravenously (IV) on days −8 to −4 followed by melphalan 70–140 mg/m2 IV on days −3 and−2. The last 25 patients enrolled in the latest trial received rituximab 375mg/ m2;on days −8, −1,+8 and +15 as part of conditioning; filgrastim stimulated peripheral blood stem cells were infused on day 0. GVHD prophylaxis consisted of cyclosporine A (CsA) from day −7 plus short-course methotrexate (MTX) (10mg/m2, days +1, +3, +6), followed by folinic acid rescue. Median age was 51 years (range 27–68);at transplant 5 (13%) of the patients were in CR1, 4 (11%) in a later CR and 29 (76%) had active disease 18 (47%) had sensitive disease and 11 (29%) resistant disease. Days to reach more than 500x 109 granulocytes and more than 20000x109 platelets were +14 (range 10–93) and +12(range 8–18). At a median time of 25 days (range 19–97), 19 patients (50%) developed acute GVHD (13 patients (34%) grade II–IV). At a median time of 107 days(80–267), 68% out of 19 patients at risk developed cGVH being extensive in 11 (39%)Disease was evaluated at day +100 and at that moment 23 patients(65%) were in CR (including 4 / 8 patients transplanted on PGR), 4% in PR and 23% have died due to NRM(Non relapse mortality). With a median follow up of 31 months (range: 6–67 months), 19 patients (50%) are alive, 17 disease free and 19(50%) have died, 10(26%) due to NRM and 8 (21%) due to progression with a proyected NRM at 1 year of 22%. OS and EFS at 5 years of of 43 and 36% respectively. None of the variables analysed influenced on NRM. Regarding efficacy of transplant in different histologies, OS and DFS for MCL were 71% and for BDLCL, 31% and 20% respectively. In this preliminary analysis results in MCL are quite good however for patients with DLBCL should be improved. severe toxicity is still present and to date it should be performed only in the setting of well designed clinical trials.
Unrelated Donor (URD) Searches in African-Americans with Hematologic Malignancies: Paucity of HLA Identical Donors.
Authors: Dew Alexander , Collins-Jones Demetria , Artz Andrew , Rich Elizabeth Shima , Stock Wendy , van Besien Koen 
Published: October 2019

Abstract
Recent analyses have demonstrated the importance of molecular matching in HLA-A, B, C and DRB1 (8/8) for the success of adult URD hematopoetic stem cell transplantation (HSCT). Little is known about the likelihood of identifying an 8/8 HLA identical URD in pts of African-American (AA) descent. From 2/2002 to 5/2007, we performed 51 preliminary (PRLM) URD searches for AA pts using the National Marrow Donor Program (NMDP) and its cooperative international registries. The median age was 38 (range, 1–73), and diseases included AML (n=18), MDS (n=1), ALL (n=1), CLL (n=4), CML (n=4), Hodgkin lymphoma (n=4), NHL (n=4), MM (n=1), severe aplastic anemia (n=4), sickle cell anemia (n=6), and other (n=4). Of the 51 PRLM searches, 13 (25%) pts had at least 1 potential HLA-A, B, and DRB1 (6/6) URD and 37 pts had at least 1 potential URD with a single allele or antigen mismatch at HLA-A, B, or DRB1 (5/6). Of the 13 pts with potential 6/6 donors, 12 proceeded to a formal URD search. After a median formal search duration of 5 months (range 1–39), 3 pts were found to have a high resolution 8/8 HLA identical URD (6% of total AA searches, 25% of formal searches with 6/6), and 2 were found to have an URD with a single allele or antigen mismatch at one of the 8 HLA loci (7/8). Two of the 3 pts with an 8/8 HLA identical URD were transplanted. Twenty-four of the 37 AA pts with a potential 5/6 URD proceeded to formal URD search. The median formal search duration for this group was also 5 months (range 1–29). Eight pts were found to have a high resolution 7/8 HLA URD (33% of formal searches with 5/6), but only 1 went on to HSCT using the 7/8 HLA URD. 275 donors were activated, and 133 were unavailable (48%). These data illustrate the difficulty in locating an appropriate URD in AA pts. In order to allow more AA pts to proceed to HSCT in a timely manner, alternative donor procurement strategies (e.g. haplo-identical or umbilical cord transplantation) should be investigated.
Table 1 URD searches in African-Americans with hematologic malignancies Preliminary search n Formal search 8/8 7/8 <7/8 Transplanted 6/6 13 12 3 2 7 2 5/6 37 24 8 16 1 <5/6 1 Total 51 36 3 10 23 3