bluuebunny/crossref_metadata_2025_split huggingface dataset:
Daily C - Reactive Protein (CRP) Levels Allow Early Identification of Patients with Severe Complications after Melphalan (MEL) and Autologous Stem Cell Transplantation (ASCT) for Multiple Myeloma (MM).
Authors: Anaissie Elias J. , Grazziutti Monica L. , Fassas Athanasios , Dong Li , Miceli Miceli H. , Van Rhee Frits , Hollmig Klaus A. , Talamo Giampaolo , Tricot Guido J. , Barlogie Bart 
Published: April 2020

Abstract
Background: CRP is an acute-phase reactant that increases rapidly in response to inflammation (including infection).
Objective: to assess the value of daily CRP level as a predictor of severe complications [pneumonia, bacteremia or severe mucositis (Grades 3–4, NCI Common Toxicity Criteria)] after MEL-ASCT for MM.
Patients and Methods: 199 MM patients (pts) who received a MEL-ASCT and had daily CRP levels on days 0–21 after ASCT.
Results: Median age was 58 years (32 – 77) and 60% were males. Mucositis was present in 89% of pts and was severe in 20%; bacteremia and pneumonia developed in 23 % and 13 % of pts respectively.Daily CRP levels (days 0-21): All pts with severe complications had higher daily CRP levels vs. those with mild or no complications (p&lt; 0.0001). Higher CRP levels were observed among pts with pneumonia (p&lt; 0.0001 vs. no pneumonia), bacteremia (p&lt; 0.0001 vs. no bacteremia) and severe mucositis (p=0.002 vs. mild (grades 1–2) and no mucositis). When present among pts with mild mucositis, infection was associated with a higher CRP level (p&lt; 0.0001 vs. no infection). CRP peak levels: Comparable CRP peak levels were observed among pts with various complications: pneumonia (n=27), bacteremia (n=46) or severe mucositis (n=41) [Mean and range in mg/dl: 16.6 (3.63 – 35.3); 17.18 (1.29 – 36.9); 17.81 (4.8 – 36.01) respectively; p= 0.95]. The presence of infection among pts with mild mucositis significantly increased CRP peak [mean and range 15.73 (1.29 – 36.9) vs. 11.59 (1.31 – 35.06) respectively, p= 0.0028].Rate of CRP increase: A significantly faster rate of CRP increase was observed among pts with severe complication vs. those with mild or no complications: mean and range of increase: 2.39 mg/dl/day (0.30 – 9.86) vs. 1.9 mg/dl/day (0.15 – 7.83). A model predictive of severe complications based on rate of CRP increase per day was developed based on the following formula:
p = exp(−0.6630 + 0.1837 * CRP slope (mg /dl/day))
1+ exp (−0.6630 + 0.1873 * CRP slope (mg/dl/day))
This model will now be prospectively validated.
Conclusions: Daily CRP levels provide an early identification of MM pts with severe complications after MEL-ASCT. Higher CRP levels correlate with severe mucositis and/or infection. Among pts with mild mucositis, a rapidly increasing and/or a high CRP level suggest the presence of severe infection.
Evaluation of Aprepitant for Treatment of Acute and Delayed Chemotherapy-Induced Nausea and Vomiting in Patients Undergoing Autologous Stem Cell Transplantation.
Authors: Barnett Chad M. , Oholendt Michael S. , Popat Uday , Carrum George , Heslop Helen E. 
Published: April 2020

Abstract
Autologous stem cell transplant (ASCT) requires therapy with very highly emetogenic chemotherapy regimens. Nausea and emesis are a major issue for patients undergoing ASCT. Aprepitant, a selective substance-P/neurokinin 1 (NK1) receptor antagonist, has been approved by the U.S. Food and Drug Administration for treatment of acute and delayed CINV in combination with a corticosteroid and 5-HT3 receptor antagonist. Due to little patient data in this area, a retrospective chart review was performed which evaluated 41 ASCT patients that had received standard therapy (control group, n=25) compared to aprepitant in addition to standard therapy (aprepitant group, n=16). Patients who underwent an ASCT and were greater than 18 years of age were eligible for inclusion in the study. Patients who underwent an allogeneic stem cell transplant were excluded. All data was collected from the hospital’s computerized nurse charting system. Episodes of nausea and emesis were collected from nursing notes while data for rescue medications was collected from the charted medications. Conditioning regimens given during the study included high dose (HD) melphalan, BEAM (carmustine, etoposide, cytarabine, and melphalan) or R-BEAM (rituximab, carmustine, etoposide, cytarabine, and melphalan). All patients evaluated in the aprepitant group had received aprepitant 125 mg orally once daily on the first day of chemotherapy administration and 80 mg orally once daily the following 2 days in the HD melphalan group (Day -1 through Day 0) and the following 5 days in the BEAM group (Day-6 through Day -1). Although aprepitant dosing was consistent, dosing was determined by the individual physician and prescribed on a patient-specific basis. The primary endpoint was the number of episodes of nausea and emesis after chemotherapy, while the secondary endpoint was the number of rescue medications that were used for nausea and emesis. For the primary endpoint of the study, the mean number of nausea episodes per patient was reduced in the aprepitant group compared to the control group in the acute phase (1.7 versus 2.2, p=0.51) and delayed phase (5.3 versus 5.6, p=0.83). Emetic episodes per patient were decreased in the aprepitant group compared to the control group in both the acute (0.06 versus 0.9, p=0.21) and delayed phases (0.9 versus 2.4, p=0.17). Use of rescue medication per patient was decreased in the aprepitant group compared to the control group in the acute phase (2.3 versus 3.6, p=0.40) but not in the delayed phases (8.1 versus 8.1, p=0.99). None of the results of this study were statistically significant, although the reduced number of emetic episodes with aprepitant may be clinically significant. The results of this study warrant consideration for a prospective evaluation of this therapy in ASCT patients to greater clarify the use of aprepitant in these patients.
Conditioning with Fludarabine (Flu)-Alkylator Is More Effective Cytoreduction Than Cyclophosphamide-Total Body Irradiation (Cy/TBI) for Refractory, Progressive Chronic Lymphatic Leukemia (CLL).
Authors: Grigg Andrew C. , Szer Jeffrey , Artz Andrew , Kline Justin , van Besien Koen 
Published: April 2020

Abstract
Allografting is becoming a more frequent therapeutic consideration for symptomatic CLL. The most frequently used preparative regimen historically has been Cy/TBI but flu-based conditioning is a recently reported alternative. Two cases in which Cy/TBI failed to impact on high pre-transplant peripheral blood (PB) lymphocyte counts prompted us to compare the outcome of stem cell allografts after TBI and non-TBI-based conditioning in 11 patients (pts) from two institutions. All pts had flu-refractory CLL. Five pts received flu 25mg/m2 with either melphalan 120mg/m2 (n=4) or Cy 120mg/kg; the other six received Cy 120mg/kg with fractionated TBI 12Gy. The two groups were comparable for age (median 50 yr overall; range 42–57), number of prior therapies (4; 2–6), extent of marrow involvement pre-transplant (90%; 65–99%) and incidence of cytogenetic abnormalities (abnormal in 8/9 evaluable). PB stem cells were used in 10 pts and marrow in one, with cyclosporine/methotrexate as GVHD prophylaxis in 8 and Campath/tacrolimus in 3. All patients receiving flu-alkylator conditioning had substantial initial cytoreduction with disappearance of PB lymphocytosis (including 2 with &gt;30x109/L pre-transplant), reduction in marrow infiltration to 25%, 15% and &lt;5% at days 30, 60 and 100 respectively. Three of 5 remain in complete remission (CR) at 12, 35 and 49 months; one relapsed at one year and one died of GVHD with minimal disease at 5 months. In contrast, 5 of 6 pts had no significant initial marrow cytoreduction, 2 of whom maintained PB lymphocyte counts &gt;300 and 30x109/L during the first month. Median marrow CLL involvement was 93%, 80% and 77% at days 30, 60 and 100 post transplant in this group. Two pts subsequently experienced late onset cytoreduction in the context of chronic GVHD but have yet to achieve CR; three died of progressive disease and one of GVHD. In vitro studies in one patient demonstrated resistance of CLL cells to irradiation. These preliminary data demonstrate that advanced CLL may be resistant to TBI and despite prior resistance to single agent flu, a combination of melphalan and flu may be the optimal cytoreductive regimen in this context.
Low Incidence of Acute Graft-VS.-Host Disease (GVHD) Using Tacrolimus (TAC) and Mycophenolate Mofetil (MMF) after Matched Sibling Donor (MSD) Non-Myeloablative Stem-Cell Transplants (NST) Conditioned with Fludarabine (FLU) and Low-Dose Total Body Irradiation (TBI).
Authors: Nieto Yago , Patton Nigel , Hawkins Timothy , Spearing Ruth , Bearman Scott I. , Rabinovitch Rachel , Zeng Chan , Baron Anna , McSweeney Peter A. 
Published: April 2020

Abstract
Randomized studies after conventional allografting showed that in combination with methotrexate TAC was superior to cyclosporine for prevention of acute GVHD. Using the Seattle conditioning regimen of FLU/low-dose TBI we evaluated TAC/MMF as a substitute for cyclosporine/MMF as post-grafting immunosuppression after MSD PBPC NST. Thirty-two patients (median age 57, range 32–68 years), who were poor candidates for a conventional myeloablative transplant, were enrolled. Patient diagnoses included lymphoma (N=12) (7 follicular, 2 transformed, 1 mantle-cell, 1 diffuse large cell, 1 NK), myeloma (N=12), high-grade MDS (N=5), AML (N=2), Hodgkin’s (N=1). Patients were conditioned with FLU (30 mg/m2/d x 3), TBI (200 cGy), were infused donor PBPCs on day 0, and received GVHD prophylaxis with TAC (0.06 mg/kg PO b.i.d. from day −3), targeting initially 10–20 ng/mL, and MMF (15 mg/kg PO b.i.d., from day 0 to +27, discontinued without taper). TAC was tapered from day +100 to +180 and from day +35 to +56, in those patients with indolent (N=25) and aggressive malignancies (N=7), respectively. Regimen toxicities and myelosuppression were mild, allowing 75% of patients to have entirely outpatient transplantations. One patient (3%) experienced a non-fatal graft rejection. The % patients with mixed/donor T-cell chimerism were as follows: 1 month: 77%/23%, 3 mo: 86%/14%, and 1 yr: 20%/80%. Five patients (15.6%) experienced stage II–IV acute GVHD, presenting at median day +61. Eleven patients (34%) experienced chronic GVHD (1 limited, 10 extensive) at median onset day +190. In 6 of those patients (22%), chronic CVHD was not elicited by immunosuppression withdrawal or DLI upon tumor progression. Day+100 transplant-related mortality (TRM) was 0%. Overall TRM was 9%, with 3 deaths from GVHD-related multiorgan failure on days +105, +343, and +354, respectively. At median follow-up of 19 (2–41) months, 20 patients (62.5%) were alive, 17 patients (53%) remained progression-free, 13 of them (41%) in complete remission. Median progression-free and overall survival times were 21 and 33 months, respectively.
Conclusion: TAC/MMF after a MSD NST provides effective acute GVHD prophylaxis, and is associated with an excellent early safety profile. As compared to reported outcomes with cyclosporine/MMF, acute GVHD incidence appeared lower and onset was delayed.
Efficacy of Fluconazole Prophylaxis for Autologous Peripheral Blood Stem Cell Transplantation: Results of a Prospective, Randomized, Controlled, Multicenter, Open Label Study.
Authors: Walsh Tracey L. , Bachier Carlos , Shaughnessy Paul , Freytes Cesar O. , Callander Natalie , LeMaistre C. Fred , Grimley Michael , Bradshaw Patrick 
Published: April 2020

Abstract
Infection is the leading cause of morbidity and mortality among hematopoietic stem cell transplant (HSCT) recipients. Fungal infection is particularly a threat because of difficulty in both diagnosis and treatment. The frequency of fungal infection is largely dependent on the mode of transplantation and duration of neutropenia. While fluconazole prophylaxis in allogeneic and autologous BMT is well studied, a trial in autologous PBSCT is lacking.
Methods: The Texas Stem Cell Transplant Consortium initiated a phase III randomized study to evaluate the efficacy of fluconazole for prophylaxis of invasive fungal infections (IFI) following autologous PBSCT with an initial planned enrollment of 150 patients. Patients were randomized to receive either no prophylaxis or fluconazole 400mg/day (or 12mg/kg if &lt;18 years of age) beginning on the day of stem cell re-infusion. The prophylaxis phase continued until the post-nadir absolute neutrophil count (ANC) reached 1000/μL or until the patient developed an IFI according to criteria developed by the IFI Cooperative Group of the EORTC. Primary endpoints measured included the comparative incidence of proven, probable or possible IFI through engraftment and through day 100 post-transplantation and IFI-related mortality through day 100. Overall survival and the comparative incidence of superficial fungal infection were also analyzed.
Results: Thirty patients have been enrolled to date (16 fluconazole, 14 without prophylaxis). The median stem cell dose received was 3.5 million CD34+ cells/kg for patients randomized to fluconazole versus 6.2 million CD34+ cells/kg for those that did not receive antifungal prophylaxis. The median duration of neutropenia, defined as an ANC &lt;1000/μL, was 7.5 days versus 7 days with a median duration of fever ≥100.5°F of 2 days and 2.5 days respectively. Superficial fungal infection developed in none of the patients that received fluconazole versus 31.3% of patients that did not receive antifungal prophylaxis. Additionally, the incidence of proven IFI was 0% in the fluconazole group versus 18.8% in those that did not receive prophylaxis and mortality due to proven IFI was 0% and 16.7% respectively. Although the small numbers do not allow for statistical comparison, the study was terminated early as a result of the high incidence of IFI and IFI-related mortality in the patients randomized to receive no anti-fungal prophylaxis.
Conclusion: Results of this study suggest that fluconazole prophylaxis should be provided as standard of care in patients following autologous PBSCT.
Cytomegalovirus Infection after Unrelated Cord Blood Transplantation (CBT) for Adults with Hematological Diseases.
Authors: Myojo Tomohiro , Matsumura Tomoko , Narimatsu Hiroto , Masuoka Kazuhiro , Inokuchi Chiho , Kami Masahiro , Miura Yuji , Kato Daisuke , Kusumi Eiji , Yuji Koichiro , Wake Atsushi , Ueyama Junichi , Miyakoshi Shigesaburo , Yoneyama Akiko , Matsuzaki Michio , Morinaga Shinichi , Taniguchi Shuichi 
Published: April 2020

Abstract
Backgrounds: Cytomegalovirus (CMV) infection is a major complication after allogeneic transplantation; however clinical significance of CMV reactivation after cord blood transplantation remains unclear.
Objective: We retrospectively investigated the incidence of CMV antigenemia, and CMV diseases, and its prognosis in adult patients who underwent reduced-intensity cord blood transplantation (RI-CBT)
Patients/ Methods: We reviewed medical records of 77 patients who received RICBT at Toranomon Hospital between January 2002 and March 2004. Median age of the patients was 55 years (range 17–79). Underlying diseases were chemorefractory hematologic diseases (n=76) and severe aplastic anemia (n=4). Conditioning regimen comprised fludarabine (125 mg/m2), melphalan (80 mg/m2), and TBI 4-8Gy. GVHD prophylaxis was cyclosporine (n=69) or tacrolimus (n=11). Median total nucleated cells and CD34+ cells was 2.4×106 cells/kg (0.39–4.3), and 0.81×105 cells/kg (0.05–5.7) respectively. HLA disparity was 6/6 (n=3), 5/6 (n=12), 4/6 (n=63), and 3/6 (n=2). All patients were monitored CMV-antigenemia weekly and received pre-emptive gancyclovir or foscarnet.
Results
CMV antigenemia tested positive in 47 patients on a median of day 32 (range, 12–55) after RICBT. The cumulative incidence of CMV reactivation at day 100 was 0.70. Seven and 29 patients were treated with preemptive ganciclovir and foscarnet, respectively. Adverse events of them were myelosuppression in 3 patients given ganciclovir, and mild hyponatremia in a patient given foscarnet. CMV diseases developed in 15 patients on a median of day 39 (range 15–92); enterocolitis (n=13), pneumonia (n=1), and encephalitis (n=1). Seven of 15 patients were resolved with antiviral treatment, and the other patients were fatal with CMV infection. Univariate analysis showed any risk factors for CMV reactivation.
Discussion
CMV reactivation and diseases develop early after cord blood transplantation. Opitimal strategy for preventing CMV disease should be established in RICBT.
Reduced Intensity Conditioning Regimen for Allografting Following Autografting Is Feasible and Has a Strong Anti Multiple Myeloma Activity.
Authors: Carella A.M. , Beltrami Germana , Corsetti Maria T. , Scalzulli Potito , Cascavilla Nicola , Carella Michele , Nati Sandro , Greco Mario M. , Musto Pellegrino 
Published: April 2020

Abstract
The development of reduced intensity conditioning regimens (RICT) has renewed interest in allografting for patients with multiple myeloma (MM). Taking advantage of this new approach, we firstly postulated that combining maximal tumor reduction achieved with autografting and the benefits of RICT, we could achieve more cures of multiple myeloma (MM) with acceptable toxicity. Sixteen patients, 51 years of age (range, 36–63) with previously treated stage III MM were given melphalan 140 mg/m2 and autologous peripheral blood progenitor cells (PBPC) reinfusion. The regimen-related toxicities were moderate with a median of 8 and 11 days of neutropenia and thrombocitopenia, respectively. Forty-six to 156 days later (median, 79 days), the patients received fludarabine 30 mg/m2/d x 3 days plus 2 Gy TBI and HLA-identical donor mobilized PBPC. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. Donor lymphocyte infusions were given to eight patients with stable mixed chimerism or progressive disease who did not show signs of aGVHD. Engraftment occurred in 14 patients (87%). Ten patients (62%) are alive with 9 of them in continuous complete remission 11–36 months (median, 30 months) after transplants. All remitters patients achieved full chimerism and developed GVHD. Grade II–III acute GVHD occurred in 7 patients (43%) but no patient died of aGVHD. Three patients (18%) developed extensive chronic GVHD requiring intensive therapy. Six patients died; five of them of progressive disease and one of progressive disease combined with extensive cGVHD and interstitial pneumonitis. In conclusion, this 2-step approach is feasible and demonstrated to have a strong antimyeloma activity with reduced deaths due to acute toxicities.
Reduced-Intensity Stem Cell Transplantation (RIST) for Non-Hodgkin Lymphoma (NHL): A Single-Institute Experience of 52 Patients.
Authors: Sugimoto Kyoko , Onishi Yasushi , Kusumoto Shigeru , Kim Sung-Won , Kami Masahiro , Mori Shin-ichiro , Heike Yuji , Takaue Yoichi , Tobinai Kensei , Tanosaki Ryuji 
Published: April 2020

Abstract
Since allogeneic hematopoietic stem cell transplantation (HSCT) is reported to have a high mortality rate for advanced lymphoma patients, less toxic technique has been expected. We evaluated the safety and preliminary efficacy of RIST in patients with advanced NHL on the basis of the WHO classification. We retrospectively reviewed the medical records of 52 patients with NHL who underwent RIST from February 2000 to April 2004 at National Cancer Center Hospital. The median age of the patients at the time of RIST was 50 years (range, 26 to 67 years). Eighteen patients had indolent B-cell lymphoma (follicular 16, lymphoplasmacytic 1, chronic lymphocytic leukemia 1), 11 had aggressive B-cell lymphoma (diffuse large B cell 8, mediastinal large B cell 2, mantle cell 1), and 23 had T-cell and NK-cell lymphoma (adult T-cell leukemia/lymphoma 12, peripheral T-cell, unspecified 8, extranodal NK/T-cell 1, enteropathy-type T-cell 1, anaplastic large cell 1). The median number of prior chemotherapy regimens was 3 (range, 1–8), and 17 (33%) patients had experienced autologous HSCT before RIST. Thirty (58%) patients had progressive/refractory disease at the time of transplantation. The RIST regimens were fludarabine- (n=47) and cladribine-based (n=5), of whom 9 patients received additional anti-thymocyte globulin. Stem cell sources were related peripheral blood (n=36), unrelated bone marrow (n=8), and unrelated cord blood (n=8). GVHD prophylaxis was cyclosporin alone (n=36) or cyclosporin and short-term methotrexate (n=16). The median duration of follow-up after transplantation was 309 days (range, 2 to 1492 days). Except for one patient who died early on day 2, all patients showed sustained engraftment. Acute GVHD gradeII–IV developed in 32 patients (62%), gradeIII–IV developed in 12 (23%) and chronic GVHD developed in 29 (56%). The day-100 TRM rate was 6%, including sepsis (n=2) and liver failure (n=1). The estimated one-year overall-survival and estimated progression-free survival rates were 75% and 63%, respectively, for all patients; 94% and 94% for indolent B cell, 76% and 58% for T or NK cell and 42% and 21% for aggressive B cell, as shown in Figures 1 and 2. (P = 0.0037 and, 0.0004 by log-rank test). In our analysis, GVHD did not clearly affect the clinical response or survival. Sustained engraftment and the low TRM rate indicate that RIST is feasible in patients with relapsed or refractory NHL. Although this is a preliminary study with a heterogeneous population and a short follow-up, the results suggest that RIST might be a promising procedure in relapsed or refractory NHL, especially in indolent B-, T- and NK-NHL. Further large-scale prospective studies are warranted.
Allogeneic Hematopoietic Stem Cell Transplantation with Nonmyeloablative Conditioning in Patients with Myeloid Leukemias: Results of a Prospective Study of the Latin American Cooperative Onco Hematology Group (LACOHG).
Authors: Ruiz-Arguelles Guillermo J. , Gómez-Almaguer David , Gómez-Rangel José D. , Vela-Ojeda Jorge , Kardus Amado , Cantú-Rodríguez Olga G. , Jaime-Pérez José C. , González-Llano Oscar , Herrera-Garza José L. 
Published: April 2020

Abstract
Using a nonmyeloablative stem cell transplantation (NST) program previously shown to be effective in individuals receiving allografts in México, 29 patients with either acute myelogenous leukemia (AML, n = 12) or chronic myeloid leukemia (CML, n = 17) from the Latin American Cooperative Onco Hematology Group (LACOHG) were prospectively given allogeneic bone marrow allografts. Patients received a modified NST conditioning regimen consisting of oral busulphan 4 mg/kg on Days −6 and −5, IV cyclophosphamide 350 mg/m2 on Days −4, −3, and −2, IV fludarabine 30 mg/m2 on Days −4, −3, and −2, oral cyclosporine A 5 mg/kg twice daily starting on Day −1 (continuing until Day 180), and IV methotrexate 5 mg/m2 on Days +1, +3, +5, and +11. Median patient age was 43 years (range, 10–63). All patients engrafted; median time to achieve an absolute neutrophil count &gt;0.5 x 109/L was 14 days (range, 0–21), whereas the median time to achieve a platelet count &gt;20 x 109/L was 12 days (range, 0–21). Follow-up periods ranged between 39 and 519 days (median, 249). In patients with CML, the median overall post-transplant survival has not been reached, whereas the 519-day overall survival was 88%, and the 100-day mortality was 0%. In patients with AML, the median overall post-transplant survival has not been reached, the 459-day overall survival was 66%, and the 100-day mortality was 8%. The results from this multicenter, multinational study complement and further support the efficacy of our NST preparative regimen. The initial experience obtained from individuals with CML and AML receiving allografts in 2 institutions in México has now been extended into other Latin American countries, and the results are acceptable.