bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imatinib Plasma Levels and Its Correlation with Response in Chronic-Phase Chronic Myeloid Leukemia: Experience of One Centre.
Authors: Gutierrez J. Valentin Garcia. , Odriozola Jesús , Herrera Pilar , Lopez Javier , Calbacho Maria , Jimenez-Rolando Marta , Blanchard Maria , Chinea Anabelle , Tenorio Maria , García-Laraña Jose 
Published: October 2019

Abstract
Abstract 4284

Introduction
Imatinib (IM), 400 mg/d. induces durable responses in chronic myeloid leukaemia (CML) in chronic phase (CP). However, although IM-biodisponibility is fairly good, its plasma levels are variable and can not be predicted. Recently, these plasma concentrations have been related both to the dose being administrated and to the cytogenetic and molecular responses. Thus, Imatinib pharmacokinetics could be an issue towards treatment optimisation in CML patients. Recent studies suggest that therapeutic IM plasma levels should be above 1040 ng/dl.

Aims
To evaluate the association between IM dose and throughout plasma levels with different clinical outcomes.

Results
In this study, we looked for an association between plasma concentrations and clinical outcomes in 16/86 CML chronic phase patients who did not achieve optimal responses following the European Leukemia Net guidelines (ELN) (table 1). Patients with optimal responses and treated with the same standard doses were also analysed as a control group. Patients receiving doses above 400 mg showed throughout plasma levels considered as appropriate. In 7 of 16 patients (47.5%) not achieving optimal responses (ELN criteria), plasma levels were below the supposed therapeutic ranges. We have found no evidence for a correlation between clinical risk factors at diagnosis and the measurement of optimal plasma levels.

Conclusions
IM plasma levels are well correlated with IM dose administrated in the patients studied. In almost 50% of patients who did not achieve optimal responses, IM plasma levels were under the ranges considered therapeutic. Probably these are the patients who may benefit of a dose increase. Obviously, to learn more about the practical value of these measurements a longer follow up with a larger number of patients is needed.

Disclosures:
No relevant conflicts of interest to declare.
The Age of Mexican Patients with Chronic Myeloid Leukemia (CML) Ph+ Is Quite Younger Than the Reported in USA and European Series.
Authors: Vargas-Viveros Pablo , Monroy Rafael Hurtado , Cervera Eduardo , Best Carlos , Aguayo Alvaro , Candelaria Myrna 
Published: October 2019

Abstract
Abstract 4291
CML accounts for approximately 15 percent of the cases of leukemia in adults. It has an annual incidence of 1 to 2 cases per 100000, with a slight male predominance. The median age at presentation is about 60 years and the incidence increases as a function of age, as reported in North American, Australian and European series. However, in our country we found a younger age at diagnosis. Herein we report our analysis of the age distribution of the patients included in the Mexican Cooperative Leukemia Group. We analyzed 356 patients with diagnosis of CML Ph+, from January 2001 to December 2008. The data analysis showed a median age at diagnosis of 37 years (range 16 to 64 years), with a male: female ratio of 1.1:1. There is a clear difference of age between Mexican patients with CML and those reported in the referred series (37 vs. 60 years) highlighting a geographical and/or ethnical pattern that may play a role as prognostic factor and response to treatment. Moreover, challenge the multistep theory of carcinogenesis in CML, inspired by the observation that cancer incidence increases as a higher order function of age, explained by an increasing somatic mutations rate with age. Further analysis and long term observation is required.

Disclosures:
No relevant conflicts of interest to declare.
Renal Transplantation for End-Stage Renal Disease Following Bone Marrow Transplantation: A 10-Year Outcomes Review.
Authors: Williams Shelly , Braden Amy , Vasudev Brahm , Palmer Jeanne , Cohen Eric 
Published: October 2019

Abstract
Abstract 4294

Background
The incidence of hematopoietic stem cell transplantations (HSCTs) in the US is increasing dramatically each year. Nephrotoxic agents used in these patients often lead to kidney injury that can be severe and progress to end-stage renal disease (ESRD) requiring long term dialysis or kidney transplant. Kidney transplantation is the best method of renal replacement therapy and maintenance immunosuppression is the mainstay to prevent graft rejection. Immune tolerance is of substantial interest because it obviates the need for long-term immunosuppression.

Methods
We performed a retrospective analysis of nine patients that developed ESRD after HSCT at the Medical College of Wisconsin. Chart review was performed to obtain demographic information and details of the transplants, patient and transplant outcomes, and various renal and HSCT related parameters.

Results
A total of nine patients were reviewed. Patient age at the time of HSCT ranged from 25-40 years. ESRD was caused by bone marrow transplant nephropathy (BMT-Np) in seven patients, HUS/TTP in one patient, and anti-TBM nephritis in one patient. Six patients received their kidney from a living related donor (LRD), whereas two patients received living unrelated renal transplants (LURRTx), and one recipient received a deceased donor transplant. Three of the six LRD recipients had same-donor renal and hematopoietic stem cell (HSC) transplants and did not require post-transplant maintenance immunosuppression. Of the two LURRTx recipients, no maintenance immunosuppression was required for the patient receiving same-donor organs. The deceased donor transplant recipient continues to be on immunosuppression. Follow-up ranges from 12-23 years post HSCT and 3-12 years post-renal transplant. Seven of the nine patients have functioning bone marrow and kidney transplants. Their serum creatinine ranges from 0.77 to 1.7 mg/dL. One patient died 24 months post-renal transplant from metastatic vaginal squamous cell cancer and had a functioning bone marrow and kidney at the time of death. Another patient was lost to follow-up and died of unknown cause, although her renal function 34 months post transplant was excellent off maintenance immunosupression.

Conclusions
Based on our case series, we conclude that the long-term outcome of renal allografts in patients who have received a renal transplant after HSCT is excellent. The overall requirement for immunosuppressive medications in this population is reduced.

Disclosures:
No relevant conflicts of interest to declare.
Clinical Implications of Pulmonary Function Tests in Allogeneic Stem Cell Recipients.
Authors: Ho Moon Joon , Kang Byung Woog , Kim Shi Nae , Lee Soo Jung , Kim Yun Jeong , Suh Jang Soo , Lee Kun Soo , Cho Yoon Young , Park Jae Hoo , Sohn Sang Kyun 
Published: October 2019

Abstract
Abstract 4297
Pulmonary dysfunction is one of major causes of morbidity and mortality in the allogeneic stem cell recipients. From Jun 2002 to Oct 2008, we retrospectively analyzed pulmonary functions (PF) in 116 consecutive patients who received allogeneic stem cell transplantation (SCT) and survived at least 3 months after transplantation. Pulmonary function test was performed at baseline, 3 months, 6 months, 1 year, and annually thereafter. Ventilatory capacity was measured by forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and FEV1/FVC ratio. Lung volume measurements included total lung capacity (TLC), residual volume (RV), and RV/TLC ratio. Diffusion capacity for carbon monoxide (DLCO) was determined with correction for hemoglobin concentration. Of the 116 patients, 63 patients were followed more than 1 year. The patients with acute graft-versus-host disease (GVHD; p=0.011), chronic GVHD (p=0.009), or CMV infection (p=0.410) showed a decline of FEV1 and FEV1/FVC after 1 year of transplantation. TLC and RV/TLC also showed an increasing tendency after 1 year of transplantation which reflected abnormal ventilatory pulmonary function. Conditioning intensity, unrelated donor type, stem cell dose did not adversely affect the pulmonary function. We calculated the lung function score (defined as FEV1 score plus DLCO score; NIH chronic GVHD consensus Project, 2003) at 1 year of transplant and compared it from that of baseline to identify the factors affecting late pulmonary dysfunction. In the multivariate analysis, extensive cGVHD (OR=3.692, 95% CI=1.154-11.818; p=0.028) and previous CMV infection (OR=5.356, 95% CI=1.311-21.882; p=0.019) negatively affected on late pulmonary function. In addition, the patients with early decline of FEV1 more than 10% at 3 months compared to baseline showed a higher incidence of cGVHD during follow-up (p=0.016). In conclusion, patients who had extensive cGVHD or CMV infection had a higher possibility of late pulmonary dysfunction and decline of FEV1 at 3 months of transplantation reflected the development of cGVHD.

Disclosures:
No relevant conflicts of interest to declare.
Low Relapse without Excessive Transplant-Related Mortality Following Allogeneic Stem Cell Transplantation in Patients with High Risk Secondary Acute Myeloblastic Leukaemia and Myelodysplastic Syndromes, Long-Term Outcomes in a Single Centre Experience.
Authors: El-cheikh Jean , Castagna Luca , Furst Sabine , Faucher Catherine , Esterni Benjamin , Ladaique Patrick , Charbonier Aude , Chabannon Christian , Vey Norbert , Blaise Didier 
Published: October 2019

Abstract
Abstract 4308
Allogenic stem cell transplantation (Allo-SCT) as a therapy for secondary acute myeloid leukaemia (sAML) and myelodisplastic syndromes (MDS) is the most powerful treatment option. However, (Allo-SCT) is also complicated by a high risk for treatment-related morbidity and mortality.
We analysed retrospectively the data of 70 patients transplanted at our institution from June 1995 to december 2008, 44 patients (63%) with sAML and 26 patients (37%) with MDS was treated with (Allo-SCT); median age at diagnosis was 41 years, (15-70), and the median age of 42, 5 years (16-70) at transplantation; The conditioning regimen was myeloablative combining (cyclophosphamide and TBI) in 16 patients (23%) and 54 patients (77%) was with a reduced intensity conditioning (RIC) regimens combining fludarabine, busulfan, and antithymocyte globulin; 11 patients (16%) were infused with bone marrow (BM), 55 patients (79%) peripherical blood stem cells (PBSC), and 4 patients (5%) cord blood cells; in 49 cases (70%) donor was a HLA identical sibling and in 21 (30%) was a matched unrelated donor;
41 patients (59%) carried high risk cytogenetic features, like (7q-, 5q-, > 3 alterations), while was normal in 24 patients (34%), and in 5 patients (7%) was unknown. Disease status at transplantation was as follow: CR in 24 patients (34%), 34 patients (49%) was refractory or in progression after treatment, and 12 patients (17%) was with a stable disease.
With a median follow-up of 55 months (3-150), 30 patients (43%) are alive, the overall survival OS at 2 years and 5 years was 48 % and 39% respectively, and after ten years of follow up, OS was 30%, 95%CI [17.8-50.8]. We observed also that 26 % of refractory patients and 54% of patients in CR are alive at five years of transplantation.
The probability of progression after transplantation at five and ten years was 31% with 95%CI [20.-46.5].
2 years and 5 years treatment related mortality (TRM) was 23% and 26% respectively, and no modification at ten year, 95%CI [14.3-37.3]. TRM occurred in 16 patients (23%). Cause of death was; infections in 5 patients (7%), GvHD in 3 patients (4%), GvHD and infection in 3 patients (4%), multi organ failure (MOF) in 5 patients (7%). In multivariate analysis; OS, PFS or TRM, were not influenced by donor type (HLA id sibling vs others), conditioning regimen (RIC vs MAC), and stem cell source (bone marrow vs PBSC).
Allogenic stem cell transplantation can be considered as a good option for the treatment of patients with high risk sAML and MDS when compared with the remission rate at five years of the other nonallogeneic SCT therapies.

Disclosures:
No relevant conflicts of interest to declare.
Early Neurologic Complications After Allogeneic Hematopoietic Stem Cell Transplantation in Children.
Authors: Koh Kyung Nam , Park Meerim , Bae Keun Wook , Kang Hyoung Jin , Im Ho Joon , Moon Hyung Nam , Seo Jong Jin 
Published: October 2019

Abstract
Abstract 4314

Backgrounds
Neurologic complications after allogeneic hematopoietic stem cell transplantation (HSCT) have not been clearly described, especially in children.

Methods
We analyzed the medical records of 194 consecutive children (median: 7.2 years, range: 6 months-18.4 years) who underwent allogeneic HSCT for malignant or non-malignant hematologic disorders at Asan Medical Center between 1998 and 2009.

Results
Donors were matched siblings in 64, unrelated volunteers in 127 and haploidentical mothers in 3. Twenty-eight children (14%, 95% confidence interval[CI]: 9-19) developed neurologic complications within the first 6 months of HSCT. Calcineurin inhibitor associated-neurotoxicity was the most common neurologic complication (n=14), followed by cerebrovascular events (n=6), thrombotic microangiopathy-associated abnormalities (n=2), hypoxic-ischemic brain injury (n=2), CNS infection (n=1), metabolic encephalopathy (n=1), and events of undetermined cause (n=2). Univariate analysis showed that transplant from unrelated donor, peripheral blood grafts and occurrence of acute GVHD (>grade 1) were associated with significant increased risk of neurologic complications. In multivariate analysis, development of acute GVHD (>grade 1) was identified as an independent risk factor for early neurologic complications. Survival at 1-year was significantly inferior in patients who developed neurologic complications within 6 months of transplant (42% [95% CI: 23-61] versus 82% [95% CI: 76-88], p<0.0001).

Conclusion
Neurologic complications are significant clinical problems among children receiving HSCT, contributing to early death after transplant. Immediate diagnostic efforts to detect neurologic events are required in patients with clinically suspicious symptoms.

Disclosures:
No relevant conflicts of interest to declare.
Peripheral Blood Chimerism Can Replace Marrow Chimerism Analyses Following Adult Allogeneic Stem Cell Transplant.
Authors: Rauwerdink Cocav , Tsongalis Gregory J , Hill John M. , Meehan Kenneth R 
Published: October 2019

Abstract
Abstract 4316
Chimerism defines the amount of donor versus recipient hematopoiesis following allogeneic stem cell transplant (SCT). PCR-based analyses of short tandem repeats (STRs) are commonly used and are accurate and applicable to allogeneic transplant recipients. These analyses are performed on peripheral blood and marrow aspirates, but it is not known if it is necessary to analyze both. We performed a retrospective analysis of 42 consecutive adult allogeneic SCT recipients at our institution with available chimerism studies. PCR and capillary electropheresis of microsatellite loci were performed at 30, 60, and 90 days after SCT on both unfractionated blood and unfractionated marrow aspirate. Full donor chimerism (FDC) was defined as 95% or greater donor chimerism. PCR analyses of STRs for chimerism performed on unfractionated blood did not differ from results obtained on unfractionated marrow aspirate at 30, 60, or 90 days post transplant (P<0.0001). Peripheral blood PCR-based chimerism analyses provide similar information as marrow aspirate analyses. Using peripheral blood alone saves the expense of an additional analysis on marrow aspirate and prevents an uncomfortable procedure. These findings provide unique results suggesting larger studies in the adult population are needed to further delineate the role of chimerism analyses following allogeneic SCT.

Disclosures:
Meehan: Berlex Pharmaceuticals: Research Funding.
Life-Threatening Complications Suspected Due to Clinical Pharmacokinetic Interaction Between Cyclosporine A and Triazole Antifungal Agents in Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) Recipients.
Authors: Yang Ting , Fu Danhui , Hu Jianda , Zheng Xiaoyun , Luo Xiaofeng , Qiu Hongqiang , Wu Xuemei , Chen Ruling , Chen Zhizhe 
Published: October 2019

Abstract
Abstract 4319

Background
It is well documented that the co-medication with the triazole antifungal agents is associated with a flattening of the CSA blood concentration profile via the cytochrome P450 3A4 dependent metabolic pathway in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Then it raises the question if the therapeutic monitoring of CsA trough levels is sufficient enough to reflect the drug exposure and to assess the transplant-related complications such as transplant rejection and drug toxicity.

Objectives
To evaluate the tolerability, toxicity and clinical outcome of the co-administration of CSA and triazole antifungal agents in allo-HSCT recipients.

Patients and methods
A retrospective review of the medical records of 104 consecutive patients undergoing allo-HSCT for hematologic malignancies at our transplant center over past 5 years was conducted. The causality of administration of CSA in combination with triazole in 12 cases with life-threatening complications experiencing supratherapeutic trough levels of CSA were identified and analyzed.

Results
In all these 12 patients, the CSA trough levels remained highly than therapeutic range even after gradual tapering of CSA dosage. Shortly after the engraftment, 6 patients (50 %) developed acute graft-versus-host disease (aGVHD) and non-infectious pulmonary complication, and 2 patient (16.66 %) acute graft rejection. Which indicates the trough plasma concentration might be inadequately reflect CSA absorption profile. Whereas, 4 (33.33 %) patients were evaluated with neurological complications, 1 (8.33%) patient cardiovascular complication accompanied by acute renal failure and liver dysfunction, that might be ascribed to CSA-related adverse effects. 10 (83.33 %) out of the 12 patients eventually died, 2 (16.66 %) patient are still alive after graft rejecting. The major causes of death were GVHD related pulmonary injury with fungi infection

Conclusion
Although preemptive CSA dosage reduction and the close monitoring of its whole blood trough levels may minimize the drug-toxicity when co-administration with triazole antifungal agents, the different clinical spectrum and different disease evolution post transplant in this group warn that in the set of hematopoietic cell transplantation with CSA as immunosuppression agent the individual variables influence the drug-exposure and drug-toxicity. Thereof, as clinicians we should not be mislead by trough plasma concentrations as a routine therapeutic drug monitoring in terms of CSA exposure related efficacy or toxicity, especially when CSA in combination with triazole.

Disclosures:
No relevant conflicts of interest to declare.
Preliminary Experience of the Pakistani Network for the Cure and Prevention of Thalassaemia Supported by the Cure2Children Foundation.
Authors: Faulkner Lawrence B. , Shamsi Tahir , Ansari Saqib , Farzana Tasneem , Khalid Sadaf , Clemente Luigi , Yaqub Naila , Zafar Tahira , Kamran Rashid , Iqbal Yasir , Sodani Pietro , Gallucci Cristiano , Erer Buket , Lucarelli Guido 
Published: October 2019

Abstract
Abstract 4331
Since May 2008, the Cure2Children Foundation has supported both financially and professionally a network of centers in Pakistan for stem cell transplantation applied to the cure of thalassemia major, a very prevalent disease with more than 60.000 registered cases in that country. The methodology employed consists of matched-related standard bone marrow transplantation after myeloablative chemotherapy as currently employed at the Mediaterranean Institute of Hematology for younger patients with transfusion-dependent thalassermia (thiotepa 10 mg/kg, busulfan 14 mg/kg and cyclophosphamide 200 mg/kg) followed by GVHD/rejection prophylaxis with prednisone/methotrexate/cyclosporin. Management standards for central venous access, severe pancytopenia, immunosuppression, hospital infection control, and other relevant issues have been addressed by local training as well as with web-based data management and videoconferencing. A total of 15 transplants have been performed to date, 7 at an established center (National Institute of Blood Diseases, Karachi), and 8 at newly developed services (5 at the Pakistan Institute of Medical Sciences, Islamabad, and 3 at Shifa International Hospital, Islamabad).

Patient characteristics
Median age 3.4 years (range 0.9 to 6.2), 7 males and 8 females.

Results
At a median follow up of 135 days (range 17-336), actuarial thalassemia-free survival is 79% and overall survival 93%. So far two patients had a graft failure and are alive and well after autologous reconstitution. One patient died for an intracranial bleed, one developed grade 3 acute GVHD (which responded promptly to steroid therapy), 4 had subclinical CMV activation and one developed pulmonary tuberculosis (currently on treatment and doing well). No case of chronic GVHD has been observed so far.

Conclusions
These preliminary results are comparable to those obtained in western centers, detailed updated clinical and cost analysis will be presented. We believe that this ongoing experience might contribute to extend access to allogeneic transplantation for the cure of low-risk thalassemia children in limited resource settings.

Disclosures:
No relevant conflicts of interest to declare.
HY Disparity Influences Outcomes of HLA-Matched Unrelated Allo-HSCT.
Authors: Markiewicz Miroslaw , Siekiera Urszula , Mietla Monika Dzierzak , Karolczyk Agnieszka , Kruzel Tomasz , Helbig Grzegorz , Krzemien Slawomira Kyrcz 
Published: October 2019

Abstract
Abstract 4337

Introduction
Donor and recipient sex is an important factor that may influence outcomes of HLA-identical allogeneic hematopoietic stem cell transplantation. The rationale of this study was to evaluate the impact of sex-related HY antigen mismatch on results of allo-HSCT from HLA-matched unrelated donors.

Patients and Methods
92 patients treated with 10/10 HLA alleles-matched unrelated allo-HSCT performed in Hematology and BMT center in Katowice in years 2004-2006 entered the study. HY genotyping was performed in the Regional Blood Center with use of Dynal Minor Histocompatibility Antigen Typing Kit. Only immunogenic HY disparities were analysed.

Results
The estimated probability of immunogenic HY mismatches corrected by the frequency of restrictive HLA molecules was 34%. When HY was mismatched in GVH direction (female donor, male recipient), the incidence of cGVHD was increased (66% vs 38%, p=0.02), the relapse rate was decreased (6% vs 23%, p=0.046) and DFS tended to improve (79% vs 44%, p=0.067).

Conclusions
The sex-related HY antigen mismatches in GVH direction influence the results of allo-HSCT from HLA-matched unrelated donors. Results of this study may help to understand why sex difference between the donor and the recipient plays role in the allo-HSCT.

Disclosures:
No relevant conflicts of interest to declare.