bluuebunny/crossref_metadata_2025_split huggingface dataset:
BEAC or BEAM Chemotherapy Followed by Autologous Stem Cell Transplantation in Non-Hodgkin’s Lymphoma Patients: Comparative Analysis on Efficacy and Toxicity.
Authors: Koo Ja Eun , Kim Shin , Ko Ock Bae , Lee Danbi , Chong Young Pill , Kang Yoon-Koo , Huh Jooryung , Suh Cheolwon 
Published: April 2020

Abstract
Background: Non-Hodgkin’s lymphoma (NHL) is the major indication of high dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT). However, little is known on the comparative efficacy and toxicity of various HDC regimens.
Aims: This study aimed to compare the efficacy and toxicity of BEAC and BEAM regimen.
Methods: Between April 1994 and February 2005, 97 NHL patients were received HDC with BEAC (N=69) or BEAM (N=28) followed by ASCT at Asan Medical Center. We matched one patient received BEAM with two patients received BEAC who has same International Prognostic Index (IPI). Thus total 84 patients (56 in BEAC group and 28 in BEAM group) were analyzed.
Results: Of 84 patients, 55 (65.5%) were male, 29 (34.5%) were female and median age was 40.5 (15–65) years. Baseline characteristics such as age, sex, disease status at ASCT, histology, stage at ASCT, IPI were not different between two groups. Time to neutrophil engraftment (WBC&gt;0.5′109/mm3) was significantly longer in BEAC group (14.5days) than in BEAM group (11.0days, p=0.002). Total amount of RBC transfusion was more in BEAC group than in BEAM group (6.5 units vs. 3.7 units, p=0.037). Time to platelet engraftment (platelet&gt;20′109/mm3) and total amount of platelet transfusion were different between two groups. Patients received BEAM had more frequent WHO grade ≥ 2 diarrhea than those received BEAC (46.4% vs. 19.6%, p=0.010). But, other clinically important toxicity such as mucositis, nausea/vomiting, bleeding were not different between two groups. In addition, neutropenic fever and documented infection were not different between two groups. Two year overall survival (OS) rate was 30% in BEAC group and 66% in BEAM group. Two year event free survival (EFS) rate was 34% in BEAC group and 61% in BEAM group. Both OS and EFS was significantly superior in BEAM group than in BEAC group (p=0.049, p=0.032, respectively).
Summary/Conclusions: BEAM appears to be a superior HDC regimen in the aspect of OS and EFS than BEAC while regimen related toxicity is similar except more frequent diarrhea in BEAM.
Pegfilgastrim after Allogeneic Transplantation - A Alternative to Daily Filgastrim?.
Authors: Wolschke Christine , Zabelina Tatjana , Heinzelmann Marion , Dahlke Joachim , Kroeger Nicolaus M. , Zander Axel R. 
Published: April 2020

Abstract
Long time of aplasie after allogeneic Stem cell- or Bone marrow-transplantation increase the risk of infections complications. Studies showed the positive effect of daily filgastrim to reduce the duration of aplastic time. The use of the Pegfilgastrim promise a simple handle with a single doses after transplantation.
Between December 2004 and July 2005 we observed 19 patients with different diseases after SCT or BMT.
All patients received a single doses subcutaneous injection of 6 mg pegfilgastrim on day 5 after transplantation. The median leucocytes engraftment was on day 16 after transplantation. The incidence of neutropenic infections was 84 percent with fever unknown origin, 21 percent with catheter induced infections and 10 percent with fungal pneumonia. Side effects of the cytokines had not been observed. The median hospitalisation was 33 days. In compared with the daily doses of Filgastrim 5 mg/kg/day was the duration to leucocytes engraftment and the infections profile similar. The use of the single injection doses of 6 mg pegfilgastrim shows a safe and comfortable profile for patients after allogenic transplantation.
Age 17 – 61 years, median 47 years Sex 11 male, 8 female Diseases 8 acute myeloid leukaemia, 1 acute lymphatic leukaemia, 1 chronic myeloid leukaemia, 1 Thalassaemia, 1 non hodgkin lymphoma, 1 osteomyelofibrosis, 5 multiple myeloma, 1 myelodysplastic syndrom Conditioning regime 7 normal conditioning, 12 reduce intensity conditioning Type of transplantation 12 MUD-PBSCT, 5 MMUD-PBSCT, 2 MUD-BMT CD34+ count median 7,9 x 10 6 /kg KG Engraftment of leucocytes median 16 days (10–25 days) Infection disease 16 FUO (84%), 2 fungal-pneumonia (10%), 4 sepsis of catheter (21%) Duration of hospitalisation median 33 days (17 – 47 days)
Treosulfan + Fludarabine +/− Thymoglobulin - An Effective Low Toxicity Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in Chronic Myeloid Leukemia.
Authors: Holowiecki Jerzy , Giebel Sebastian , Wojnar Jerzy , Krawczyk-Kulis Malgorzata , Wylezol Iwona , Markiewicz Miroslaw , Kruzel Tomasz , Holowiecka-Goral Aleksandra , Kopera Malgorzata 
Published: April 2020

Abstract
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only treatment of proved long-term efficacy in chronic myeloid leukemia (CML). However, high procedure-related toxicity observed after oral busulfan- or TBI-based conditioning limits its applicability and deteriorates outcome. Between 2003–2005 a phase II study was conducted to evaluate the feasibility of a new preparetive regimen consisting of Treosulfan (a soluble alkylyting agent) 14 g/m2/d. on days -6, -5, -4, Fludarabine 30 mg/m2/d on days -5, -4, -3, -2, -1, and, in case of unrelated donor transplants (URD-HSCT), anti-thymocyte globulin (Thymoglobulin) at a total dose of 6 mg/kg. Results were compared to those from the historical control group of CML patients treated with oral Busulfan (16 mg/kg) + Cyclophosphamide (120 mg/kg) (BuCy) in the same institution between 2000–2003. 35 patients (age 35, range 16–52 years) with CML in the 1st chronic phase (n=33) or in 2nd chronic phase (n=2) were included in the study. Median interval from diagnosis to alloHSCT equaled 10 (6–144) months. 22 (63%) patients were given transplant from an unrelated donor, 13 (37%) - from an HLA identical sibling. Bone marrow was used a source of stem cells in 29 patients, peripheral blood - in 6 cases. GVHD prophylaxis consisted of Cyclosporin A and short-course Methotrexate. All patients engrafted after a period of absolute agranulocytosis. Median time to neutrophil recovery &gt;0.5 G/L was 24 (10–42) days, and to PLT &gt;50 G/L - 21 (13–38) days. 1/35 patient experienced grade 3 mucositis; no severe (grade 3–4) neutropenic infection nor VOD was observed. The incidence of grade II acute GVHD was 17%, grade III–IV - 3%. The cumulative incidence of non-relapse mortality (NRM) at 2 years equaled 14% (4/35). Causes of death were: EBV-LPD, late neuroinfection, late fungal infection, acute GVHD.
At 2 years the probability of the overall survival and hematological relapse-free survival equaled 86% (+/−7%) and 83% (+/−7%). Respective rates for the control BuCy group (n=78) were significantly lower: 55% (+/−6%), p=0.02, and 54% (+/−6%), p=0.03. Seven patients in the Treosulfan+Fludarabine group required immunosuppression taper and additional interferone or imatinib treatment because of incomplete donor chimerism or molecular/cytogenetic relapse after initial response.
We conclude that Treosulfan+Fludarabine+/−Thymoglobulin myeloablative conditioning is associated with low organ toxicity, low incidence of acute GVHD and NRM. The regimen is feasible for CML patients and appears superior in comparison with BuCy.
Reduced Intensity Conditioning Unrelated Transplant Plus Cyclosporine and MMF as GVHD Prophylaxis: Results of a Prospective Study.
Authors: Perez-Simon J.A. , Martino R. , de la Camara R. , de Oteiza J. Perez , Moraleda J.M. , Diez-Campelo M. , Sureda A. , Alegre A. , Sierra J. , Miguel J.F. San 
Published: April 2020

Abstract
Some studies have suggested that mycophenolate mofetil (MMF) offers a similar efficacy in terms of GVHD prophylaxis as compared to methotrexate (MTX) but a faster engraftment and a lower incidence of mucositis.
We have analyzed the results of fludarabine (150 mg/m2) and melphalan (140 mg/m2) or busulphan (10 mg/m2) plus Cyclosporine (CsA) and MMF instead of MTX as GVHD prophylaxis in a series of 30 patients undergoing unrelated allogeneic transplantation. Median age was 44 years (18–60). Patients younger than 40 were required to have a previous comorbid condition (8 had a previous autologous transplant; 2 had proven fungal infection; 1 had severe altered lung capacity). Twelve patients were diagnosed with AML, 4 had ALL, 4 MDS, 2 CML, 3 CLL, 3 NHL, 2 MM/WM. Disease status at transplant was 1st or 2nd CR in 12 patients, &gt;2nd CR or PR in 11 patients while the remaining patients had active disease at the time of transplant (relapse, refractory, untreated diasease). Median day to reach &gt; 0,5 x 109 granulocytes / L was +17 and to reach &gt; 20 x 109 platelets / L was +13. At a median follow up of 445 days among patients alive, projected overall survival (OS) and event free survival at 3 years are 47% and 30%, respectively. Overall TRM was 32%. Cumulative incidence of grades 2–4 and 3–4 aGVHD was 67% and 33%, respectively while cumulative incidence of extensive cGVHD was 70%. Gut was the organ most severely involved in aGVHD in 10 out of 16 patients while liver was involved in only 3 cases. Interestingly, among patients who developed aGVHD, incidence of skin (80%) and liver (22%) involvement were similar to that observed in a similar series of patients receiving related donor transplant using the same RIC plus CsA and MTX instead of MMF while the incidence of gut involvement was significantly higher (64% vs 42%).
In conclusion, the RIC used in the current study plus CsA and MMF offers promising results in high risk patients. In terms of GVHD prophylaxis, MMF shows a good efficacy at skin and liver but poor at the gastrointestinal tract.
Prolonged Administration of Aprepitant Does Not Increase Toxicity in Patients Undergoing High Dose Chemotherapy and Autologous Stem Cell Transplant.
Authors: Junagadhwalla Mehnaz , Chilton Joanne , Gentile Teresa 
Published: April 2020

Abstract
Aprepitant is a neurokinin-1 receptor antagonist used for the prevention of chemotherapy induced nausea and vomiting (CINV) with highly emetogenic chemotherapy. The recommended dose for the prevention of CINV is 125 mg orally on day of treatment, followed by 80 mg orally on days 2 and 3. It is known that aprepitant inhibits cytochrome P450 3A4, therefore elevating plasma concentrations of various drugs, including certain chemotherapy drugs such as etoposide. Given the highly emetogenic nature and length of conditioning regimens used in Bone Marrow Transplant (BMT) patients, we elected to treat patients for a longer period of time with aprepitant. Twenty-five patients received aprepitant for an average of 7.6 days, with an initial dose of 125 mg p.o. on day 1 and 80 mg p.o. on subsequent days. Eleven patients were women and the remaining fourteen were men. The youngest transplanted patient was 20 and the oldest was 68 years old. Engraftment was defined as
an absolute neutrophil count (ANC) greater than 1000 x 3 days and number of days until platelet transfusion independence.
The mean day to ANC recovery was 12.3 and the mean day of platelet transfusion independence was 13. This data was based on 24 patients, as one male patient died day +10 secondary to RSV bronchiolitis prior to engraftment. The incidence of mucositis, neutropenic fevers, pulmonary toxicities, and other complications did not differ compared with previously established data. We conclude that aprepitant can be used safely without adding significant toxicity to therapy with high dose chemotherapy in autologous stem cell transplant patients. A randomized prospective trial should be considered to evaluate the efficacy in reducing CINV and to further evaluate toxicity.
Survival Benefit of Asymptomatic Cytomegalovirus Reactivation and Early Lymphocyte Recovery after HLA-Identical Allogeneic Peripheral Blood Stem Cell Transplantation.
Authors: Kim Dong Hwan , Sohn Sang Kyun , Baek Jin Ho , Kim Jong Gwang , Lee Kyu Bo , Park Jae-Hoo 
Published: April 2020

Abstract
Background: Cytomegalovirus (CMV) reactivation (CMV-R) is associated with increased morbidity after allogeneic stem cell transplantation (SCT). However, after the introduction of ganciclovir preemptive therapy, CMV-R can be successfully controlled if the recipient’s immunity recovers. Although many investigations have already focused on CMV-R as a risk factor, data related to the impact of asymptomatic CMV-R on transplant outcomes is scarce. Accordingly, the present study analyzed the differences in the transplant outcomes the immune reconstitution according to the CMV-R after allogeneic PBSCT.
Method: A total of 76 patients undergoing allogeneic peripheral blood stem cell transplantation (PBSCT) were included in the current study. The transplant outcomes and immune reconstitution after 3, 6, and 12 months were analyzed according to the occurrence of CMV-R in 33 patients.
Result: The analysis revealed a favorable prognosis for the group with CMV-R compared to those without CMV-R: p=0.0037 for OS, p=0.0204 for NRM, and p=0.05 for the risk of relapse. CMV-R was also found to correlate to the lymphoid reconstitution (p=0.024). In multivariate analyses, CMV-R was found to be a favorable prognostic factor in terms of OS (p=0.010, hazard ratio [HR] 2.948) and NRM (p=0.05, HR 2.665), along with a higher transplant CD34+ cell dose (p=0.003 for OS, p=0.002 for NRM), standard risk (p=0.023 for OS), and acute GVHD grade 0~2 (p=0.007 for NRM).
Conclusion: In a PBSCT setting, CMV-R did not seem to be a poor prognostic factor in terms of OS and NRM, possibly due to the accelerated lymphoid immune reconstitution associated with CMV-R.
Figure. Survival curve for overall survival (A) and lymphoid immune reconstitution according to CMV reactivation (B) Figure. Survival curve for overall survival (A) and lymphoid immune reconstitution according to CMV reactivation (B)
Heterophilic and Homophilic Interactions of Junctional Adhesion Molecule-C (JAM-C) Mediate Different Intercellular Adhesive Interactions.
Authors: Chavakis Triantafyllos , Orlova Valeria , Song Kaimei , Andrei-Selmer Cornelia L. , Santoso Sentot 
Published: April 2020

Abstract
Junctional adhesion molecules (JAM) are a new subfamily of the Ig superfamily. We recently identified that the third member of this family, JAM-C, expressed on endothelial, epithelial cells and platelets (i) undergoes a heterophilic interaction with leukocyte β2-integrin Mac-1 (CD11b/CD18) (J Exp Med. 2002; 196:679–91) and (ii) that endothelial JAM-C is predominantly localized within tight junctions and mediates neutrophil transendothelial migration in a Mac-1-dependent manner in vitro and in vivo (J Biol Chem. 2004, 279:55602–8). Here, we characterized JAM-C to undergo a homophilic interaction that participates in tumor cell-endothelial cell interactions. As assessed in a purified system, recombinant soluble JAM-C in fluid phase bound to immobilized JAM-C; moreover, JAM-C-transfected CHO cells adhered to immobilized JAM-C. The homophilic interaction of JAM-C was mediated by the isolated amino-terminal Ig-domain (D1) but not the carboxy-terminal Ig-domain (D2) of the molecule. Dimerization of JAM-A is dependent on the sequence RVE in the aminoterminal Ig-domain. This motif is conserved in JAM-C (R64I65E66) and a single amino acid mutation in this motif (E66R) abolished the homophilic interaction of JAM-C. The lung carcinoma cell line NCI-H522 was found to be positive for JAM-C expression. NCI-H522 cells adhered to immobilized JAM-C, as well as to JAM-C-transfected CHO cells, but not to mock-transfected CHO cells or to CHO cells transfected with the JAM-C mutant (E66R). Adhesion of NCI-H522 cells to JAM-C protein or JAM-C-transfected CHO cells was abolished in the presence of soluble JAM-C or the isolated D1. Furthermore, the adhesion of NCI-H522 cells to endothelial cells was significantly blocked by soluble JAM-C or the isolated D1. Thus, JAM-C undergoes a homophilic interaction via the R64I65E66 motif on the membrane-distal Ig-domain of the molecule. The homophilic interaction of JAM-C can mediate tumor cell-endothelial cell interactions and may thereby be involved in the process of tumor cell metastasis. Together, the heterophilic and homophilic interactions of JAM-C mediate distinct adhesive interactions.
Micafungin Is Extremely Effective Against Fungal Infections Complicating Hematological Malignancies: Report of a Multicenter Study by N-FISH (Niigata Fungal Infection Study Group in Hematology).
Authors: Aoki Sadao , Takizawa Jun , Seki Yoshinobu , Takai Kazue , Nikkuni Koji , Maruyama Souichi , Nomoto Nobuhiko , Tsukada Nobuhiro , Aizawa Yoshifusa 
Published: April 2020

Abstract
[Background]Micafungin (MCFG) is a candin antifungal agent, and was marketed in Dec. 2002 in Japan and in Apr. 2005 in the United States. The Niigata Fungal Infection Study Group in Hematology (N-FISH) performed a multicenter prospective study to clarify the therapeutic effects of MCFG on deep fungal infections complicating hematological malignancies.
[Methods]A total of 36 pts. who had been treated in centers belonging to N-FISH between Oct. 2003 and Apr. 2005 were included in this study. They consisted of 14 men and 22 women with a mean age of 53.5 years: 14 pts. with AML, 10 pts. with malignant lymphoma, 6 pts. with ALL, and 6 pts with other diseases. They had a proven fungal infection, or were suspected of having a fungal infection because of fever unresponsive to antimicrobial agents or from laboratory data. Three of them had a proven infection, and 33 were suspected of having a fungal infection. Three of these 33 pts. failed to respond to fluconazole. As a rule, MCFG was administered for more than 14 days until infectious symptoms improved or disappeared. When MCFG was judged ineffective because of the worsening of clinical symptoms despite the administration of MCFG, or when the administration of MCFG was judged difficult because of adverse effects, the drug was discontinued or replaced by other drugs. Two pts. orally received amphotericin B syrup singly.
[Results]The mean dose of MCFG was 2.6 mg/kg (1.5–4.2 mg/kg), and the mean duration of administration was 15.9 days (5–85 days). Complete or partial response was achieved in 31 (86.1%) of the 36 pts., who showed improvements in infectious symptoms. In 4 pts, MCFG was discontinued because of insufficient effects. There were no breakthrough fungal infections within 7 days after the completion of MCFG therapy. Of the 36 pts., 31 (86.1%) and 24 (66.7%) survived 1 and 3 months after MCFG therapy, respectively. The cause of death was exacerbation of the primary disease, and not exacerbation or the onset of a fungal infection. Eight adverse events occurred in 7 pts.: hypoglycemia in 1, liver dysfunction in 3, eosinophilia in 1, kidney dysfunction in 2, and hypokalemia in 1. In 1 of the 3 pts. with liver dysfunction (grade 3), MCFG therapy was discontinued, with rapid improvement of the liver dysfunction. All other adverse events were mild, allowing continued MCFG therapy.
[Conclusion]This multicenter study demonstrated the effectiveness and safety of MCFG therapy for deep fungal infections complicating hematological malignancies. The results suggest that MCFG should be promptly used for fever associated with a fungal infection complicating hematological malignancies.
Hemophagocytic Syndrome (HPS) after Autologous Peripheral Stem Cell Tansplantation (APSCT) for Multiple Myeloma (MM)- Successful Treatment with High Dosages of Intravenous Immunoglobulin (IVIG).
Authors: Ostronoff Mauricio , Domingues Mariana Coutinho , Ostronoff Fabiana , Calixto Rodolfo , Florencio Rodrigo , Souto Ana Patricia , Sucupira Alexandre , Matias Kleber , Tagliari Clemente 
Published: April 2020

Abstract
HPS is characterized by activation of histiocytes with prominent hemophagocytosis in bone marrow and reticulo-endothelial system, resulting in cytopenias. Reactive HPS (R-HPS) is known to be associated with infection, malignancies and autoimmune disorders. We report a case of R-HPS with massive life-threatening gastro-intestinal (GI) tract bleeding after APSCT for MM which responded to high dosages of IVIG. In May 2005, a 54-year old female diagnosed with MM stage III A, achieved CR after 4 cycles of VAD. APSCT conditioning consisted of L-PAM 140mg/m2. 2x106 CD34+ cells/kg were infused. G-CSF 10μg/kg was started on D0. Pt was placed on cefepime and vancomycin (D+4) and amphotericin B (D+7) for FUO and discontinued after neutrophil recovered (D+10). During aplasia, she received 2 packed RBC and 4 PLT transfusions (irradiated and filtrated). On D+12 G-CSF was discontinued. Four days after thrombocytopenia aggravated (PLT 3000/mm3) and she presented with fever (39°C) and disseminated petechiae. Other coagulation tests were normal. A complete search for infection was negative- cultures (urine and blood) and thoracic, abdominal and sinus CT scan. Pt was again placed on cefepime, vancomycin and amphotericin B without defervescence. In the following 3 days, hypovolemic shock due to profuse GI tract bleeding occurred. Upper endoscopy showed diffuse petechiae and bleeding. Bone marrow (BM) aspirate was performed and revealed 3% histiocytes with hemophagocytic activity. R-HPS was diagnosed. Massive RBC and PLT transfusions were started (4x/day) without response. Search for HSV, EBV, HIV, CMV, auto-immune disease and malignancy were negative. She was on prophylactic acyclovir. On D+21 pt received IVIG 1g/kg/day for 2 days and dexamethasone 40mg for 4 days. Hemorrhage resolved and PLT counts improved. However, on D+30 PLT counts dropped again (PLT 24000/mm3) and BM aspirate showed persistent hemophagocytosis with 4% of histiocytes. A new course of IVIG was given and repeated once a week for 2 weeks when it was no longer needed. BM aspirate on D+39 was normal, with no evidence of hemophagocytosis and there was no recurrence of R-HPS. In this case platelet was the more affected cell lineage resulting in severe and life-threatening hemorrhagic syndrome. The immune mechanism of HPS is not clear, but a defect in immune regulation has been hypothesized. R-HPS after auto-BMT is rare event and appears to be associated with hematological and immunological recovery. We believe that IVIG was effective and its known mechanism of action is compatible with current knowledge of HPS pathophysiology. IVIG might be an effective treatment for R-HPS secondary to auto-BMT.