bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes After a Sequential Clofarabine/Arac-C Chemotherapy Followed By Reduced-Intensity Conditioning (RIC) and Allogeneic Stem Cell Transplantation (allo-SCT) In Pediatrics Patients With JMML Or Primary/Relapsed Refractory AML: A Pilot Study
Authors: Audrey Grain , Sirvent Anne , Strullu Marion , Mechinaud Francoise , Mohty Mohamad , Chevallier Patrice , Guillaume Thierry , Rialland Fanny 
Published: October 2019

Abstract

Introduction
The FLAMSA sequential treatment with chemotherapy followed by reduced-intensity conditioning (RIC) for allogeneic stem cell transplantation (allo-SCT) has been introduced few years ago for adult refractory acute myeloid leukemia (AML) showing high activity and relatively good survivals in this particular setting (Schmid, Blood, 2006). There is no study at our knowledge reporting the results of the sequential approach in pediatric refractory AML patients. Here we report our own experience in 6 children using a debulking chemotherapy combining clofarabine and Ara-C followed by RIC before allo-SCT.

Patients and Methods
These preliminary results included 3 males and 3 females with a median age of 7 years (range: 4-11). All cases had received a sequential regimen before allo-SCT at the CHU of Nantes (n=5) or at the CHU of Montpellier (n=1) for primary refractory AML (n=1), refractory relapsed AML (n=3), slow responder relapsed AML (n=1) and blastic JMML (n=1). Sequential regimen consisted of 1) clofarabine 30 mg/m²/d days-13 to -9, Ara-C 1g/m²/d days-13 to-9 followed by RIC combining cyclophosphamide 60 mg/kg/d day-5, iv Busulfan 3.2 mg/Kg/d days -4 to -3 and ATG 2.5 mg/Kg/d days -3 to -2 in 5 patients and 2) clofarabine 30 mg/m²/d days-13 to -9, Ara-C 1g/m²/d days-13 to-9 followed by RIC total body irradiation 4 grays day-5, cyclophosphamide 40 mg/Kg/d days -4 to -3, and ATG 2.5 mg/Kg/d days -3 to -2 in 1 patient. One patient received a graft from a sibling donor while the five other patients received a graft from an unrelated donor (10/10 n=3; 9/10 n=2). All patients received PBSC as stem cells graft. Ciclosporine alone was used in case of related donor while ciclosporin+MMF were used in case of an unrelated donor.

Results
Engraftment was observed in 4 patients (67%) and 3 patients out of the 5 refractory cases achieved complete remission (CR) after transplant. The 2 patients who had an autologous reconstitution, relapsed and died rapidly. Considering the 4 patients achieving full engraftment and CR, only one relapsed at day+60 and died of relapse. The three other patients are alive in CR at +12, +35 and +51 months post-transplant.

Conclusion
To our knowledge, this is the first report of a sequential allo-SCT approach for refractory pediatric AML patients. Although the number of patients is limited in our cohort, the results showed here are very encouraging as half of the patients are alive in CR with full engraftment. These results have to be confirmed prospectively.

Disclosures:
No relevant conflicts of interest to declare.
Factors Affecting Unit Predominance In Double Umbilical Cord Blood Transplantation
Authors: Santos Fernanda NC , Hitomi Yokoyama Ana Paula , Kondo Andrea Tiemi , Macedo Erika Maria , Conti Fabiana Mendes , Sakashita Araci M. , Kutner Jose Mauro 
Published: October 2019

Abstract

Background
Umbilical cord blood transplantation is seen as an alternative source of hematopoietic support for patients who lack suitable HLA-matched donors. Disadvantages of this method include the relatively low cellularity, late engraftment and consequently restrictive use to pediatric patients, due to the low number of hematopoietic progenitors. Transplantation of two cord blood units has been seen as a strategy to overcome the low yield, often leading to the long-term establishment of hematopoiesis supported by a single cord blood unit. Predictive factors of the predominant unit are still unclear. Total nucleated cell count, CD34+, CD3+ dose were independent factors associated with unit predominance, although this is still a controversial issue.

Methods
This retrospective study included 21 patients with hematologic malignancies and immunodeficiencies who underwent double unit cord blood transplantation. We analysed HLA mismatch, ABO group, total nucleated cell count (TNC), CD34+ dose and post-thaw viability and their correlation with the prevalent unit. Transplantations were performed from 2007 to 2013. Six patients were excluded due to incomplete information and another three died before engraftment.

Results
Median NC and CD34+ doses were similar between engrafted and non-engrafted units. Nine transplantations (60%) resulted in engraftment of the higher TNC unit. TNC dose in the predominant units varied between 2.02-3.05x107/kg (median dose: 2.651x107/kg), and in the non-engrafted units between 1.69x107/kg-4.39x107/kg (median dose: 2.44x107/kg), which was not statistically significant (p= 0.65). Sixty percent of the transplantations (9 patients) also resulted in engraftment of the unit with higher CD 34+ (median dose: 2.05x106/kg), compared to 40% (6 patients) in which the lower dose unit prevailed (median dose: 1.95 x106), also not statistically significant (p= 0.861). As for ABO, 26% of the units were ABO matched with the recipient, while the majority was HLA mismatched (93%).

Conclusion
Multiple factors related to the unit and patient influence UCB predominance. In the sample studied, no particular variant played a specific role, probably due to the limited sample size. Current evidence suggests that immunologic-related mechanisms (CD34+ and CD3+ dose) are involved, yet further studies are necessary for a better understanding of which factors lead to unit engraftment.

Disclosures:
No relevant conflicts of interest to declare.
Enteral Versus Parenteral Nutritional Support Post Allogeneic Haematopoietic Cell Transplantation – Results Of a Randomized Controlled Trial
Authors: Kennedy Glen A , Andersen Sarah , Banks Merrilyn 
Published: October 2019

Abstract

Background / Aims
Nutritional support post allogeneic haematopoietic progenitor cell transplantation (HPCT) has proven efficacy in preventing malnutrition post-HPCT with resultant improved patient outcomes. However, there is no consensus as to the most efficacious approach to supplemental feeding post-allogeneic HPCT, leading to wide variation in clinical practice with respect to use of enteral (EN) vs. parenteral (PN) feeding, especially in adult units. We aimed to determine the tolerability and efficacy of EN vs.PN in adult patients undertaking allogeneic HPCT.

Methods
Prospective randomized controlled study in adult patients >18yrs of age undertaking allogeneic HPCT with either myeloablative or reduced intensity conditioning (RIC). Informed consent was obtained before commencing conditioning, with patients randomized to receive either EN or PN after commencing HPCT conditioning if they could not maintain adequate oral nutritional intake, defined as maintaining >60% of daily caloric requirements orally. Patients with severe gastro-intestinal toxicity, including severe mucositis, were excluded from randomisation. The primary endpoint was tolerance of route of supplemental nutritional support, defined as <30% of patients needing to change to the alternative route of support for any reason.

Results
In total 38 patients were enrolled onto the study, including 9 patients (24%) undertaking myeloablative and 29 patients (76%) RIC HPCT. Only 19 patients (50%) required nutritional support post-HPCT. Of these 19 patients, only 9 (47%) were able to be randomized between EN (n=5) and PN (n=4), with 10 patients excluded from randomization due to presence of severe gastrointestinal toxicity in 7 (37%), markedly deranged liver function in 1 (5%), and withdrawal of consent in 2 (11%). The 5 patients randomized to EN met on average 74% of their goal nutrition and 100% required changing to PN due to (gastro-intestinal) intolerance. The 4 patients receiving PN met on average 91% of requirements, with none requiring change to EN.

Conclusions
For adult patients undertaking myeloablative or RIC allogeneic HPCT, supplemental feeding with EN commencing at failure to maintain adequate oral nutritional intake is not feasible, due to the presence of significant gastrointestinal toxicity in these patients at this time. Further study is required to determine whether prophylactic nasogastric tube placement would improve the feasibility and tolerance of EN in this patient population.

Disclosures:
No relevant conflicts of interest to declare.
Hypogammaglobulinemia In Children Undergoing SCT: An Immunoglobulin Isotype Class Switch Arrest?
Authors: Lindqvist Henric , Remberger Mats , Sundberg Berit , Uzunel Mehmet , Winiarski Jacek , Sundin Mikael 
Published: October 2019

Abstract
Treatment-requiring hypogammaglobulinemia is common early after allogeneic hematopoietic stem cell transplantation (SCT) in children. Usually, it resolves but in several children it persists, demanding long-term immunoglobulin (Ig) G replacement therapy. By IgG replacement, the morbidity risk may not be reduced, but infectious complications are decreased.
Here we studied clinical events, Ig and immune cell recovery, IgG2m allotypes and dynamics of cytokines important for B-lymphocytes and Ig production in 84 children undergoing SCT. The aim was to identify risk factors for ≥3 months IgG replacement need as well as studying the biology behind the hypogammaglobulinemia seen post-SCT. Clinical data were collected from charts. Interleukin (IL)-4, -5, -6, -7 and -10, BAFF and APRIL were analyzed in patient sera pre- and post-SCT. Donors and patients were IGHG2 genotyped. Uni- and multivariate statistic analyzes were applied.
As many as 48% of the children needed ≥3 months IgG replacement. These were commonly younger (<5 years) and had acute GvHD grade II-IV. However, children with ≥3 months IgG replacement had better overall survival (88 vs. 69%, P=0.036). Significantly lower Ig levels post-SCT, but equal immune cell recovery were seen when comparing the ≥3 vs. <3 months IgG replacement groups. Significantly higher rates of mixed chimerism in CD3 and C33 populations was seen in the <3 months IgG replacement group. IGHG2 genotyping showed no significant frequencies between the groups. Pre-SCT IL-6 and -7 and post-SCT BAFF and APRIL levels were significantly higher in the ≥3 months IgG replacement group. This suggests an unfavorable cytokine milieu for graft-derived immune recovery with possibly later Ig isotype class switch arrest. Age <5 years (OR 8.16, 95% CI 2.62-25.4, P<0.001), acute GvHD grade II-IV (OR 5.61, 95% CI 1.78-17.6, P=0.038) and pre-SCT IL-6 levels >50 pg/mL (OR 8.03, 95% CI 1.26-51.0, P=0.024) were identified as significant risk factors for ≥3 months IgG replacement need.
To conclude, requiring ≥3 months IgG replacement does not need to be unfavorable and could be an effect of deteriorated cytokine signaling resulting in impaired Ig production. Further prospective studies investigating post-SCT hypogammaglobulinemia with and without IgG replacement are warranted.

Disclosures:
No relevant conflicts of interest to declare.
Prolonged Thrombocytopenia Is Associated With Increases Of CD8+ CX3CR1+ Cells In The Bone Marrow After Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Zhang Xiaohui , Wang Guoxiang , Zhu Honghu , Liu Yanrong , Liu Daihong , Xu Lanping , Han Wei , Chen Huan , Chen Yuhong , Wang Feng-Rong , Liu Kaiyan , Huang Xiaojun 
Published: October 2019

Abstract
Prolonged thrombocytopenia is a common complication after allogeneic hematopoietic stem cell transplantation(allo-HSCT),which is associated with a high mortality and poor prognosis. The aim of this study was to assess the impact of the CD8+CX3CR1+ T cells on the development and maturation of megakaryocytes in patients with the prolonged thrombocytopenia after allo-HSCT in order to identify the risk factors related to thrombocytopenia after allo-HSCT.
The changes in CD8+ T cells and their homing receptors CX3CR1, CXCR4 and VLA-4 in bone marrow of patients( N=89) with and without (N=94 ) prolonged thrombocytopenia following allo-HSCT and the impact of activated CD8+ T cells on apoptosis and ploidy of megakaryocytes in vitro ware determined. The percentage of CD8+CX3CR1+ T cells was significantly higher in prolonged thrombocytopenia patients than control (P<0.001).The increase in CD8+ T cells was not observed in peripheral blood. Patients with prolonged thrombocytopenia exhibited a marked increase in the number of low ploidy(≤8) megakaryocytes compared to those without(P<0.05). Depletion of CD8+ T cells increased apoptosis of megakaryocytes (P<0.05), which was corrected by reconstitution of CD8+ T cells (P<0.05). We demonstrated that prolonged thrombocytopenia is associated with increased expression of CX3CR1 and recruitment of CD8+ T cells into the bone marrow. Activated CD8+ T cells suppress apoptosis of megakaryocytes in vitro. Our findings shed light on the prolonged thrombocytopenia is associated with increases of CD8+ CX3CR1+ cells in the bone marrow after allo-HSCT patients.

Disclosures:
No relevant conflicts of interest to declare.
Engraftment Syndrome (ES) After Autologous Stem Cell Transplantation (SCT): Analysis Of Diagnostic Criteria and Risk Factors
Authors: Gerivaz Rita , Costa Fatima , Schuh Juliana , Monteiro Luis P , Ferreira Gilda , Sousa, MD Aida B. 
Published: October 2019

Abstract
ES is increasingly recognized as an important complication of autologous SCT. There is no consensus over diagnostic criteria (leading to variations in reported incidence from 7 to 55%) nor over risk factors. In order to better characterize this syndrome and its potential severity, we reviewed 380 consecutive autologous SCT (in 304 patients [pts]) performed in our center from 1/2006 to 8/2012.

Methods
During this period ES was diagnosed according to the Maiolino criteria (MC): non infectious fever beginning 24h pre-engraftment + pulmonary infiltrates or rash or diarrhea. We retrospectively reviewed all cases according to the Spitzer criteria (SC): 3 major criteria within 96h of engraftment (non infectious fever, rash, pulmonary infiltrates) or 2 major + 2 minor criteria (hepatic and renal disfunction, weight gain, encephalopathy). The following risk factors for ES were evaluated: sex, underlying disease, mobilization regimen (G-CSF with or without chemotherapy), conditioning regimen, number of reinfused CD34+ cells/kg, cryopreservation duration, time to engraftment and bacteremia rate. The following outcomes were analyzed: days on antibiotics, number of platelet transfusions, in-hospital days, and transplant related mortality (TRM).

Results
ES was diagnosed in 29 SCT (8%) in 27 pts (2 tandem SCT had ES in both) by MC. Only 8 of these fullfilled the SC. Most cases (83%) required corticosteroids and improved; 1 death was attributed to ES. By multivariate analysis the single risk factor for ES was a diagnosis of non Hodgkin’s lymphoma as opposed to Hodgkin’s (15% vs 3.7%, p=0.04); none of the remaining risk factors was statistically significant. Pts with ES spent more days on antibiotics (median 12 vs 10, p=0.008) and in the hospital (23 vs 19, p<0.000) and there was a trend to a higher TRM at d+30 (3.7 vs 1.3%) and d+100 (7.4 vs 4.2%).

Conclusions
We were able to confirm in our series that ES prolongs antibiotic duration and hospitalization and may increase the risk of death. Although ES is a complex entity with a difficult diagnosis, its prompt recognition is critical, as timely institution of corticosteroids diminishes the risk of multiorgan failure, avoids unnecessary use of antimicrobials, and reduces hospital days and costs. The SC are more stringent but too insensitive. We believe that, until prospective studies validate clearer diagnostic recommendations, transplant teams are best served by the MC.

Disclosures:
No relevant conflicts of interest to declare.
Imatinib Mesylate Versus Allogeneic Hematopoietic Stem Cell Transplantation For Patients With Chronic Myeloid Leukemia In Chronic Phase
Authors: Xiaoli Liu , Gao Guanlun , Zhou Xuan , Xu Na , Xiao Yajuan , Cao Rui , Yin Changxin , Zhou Hongsheng , Wei Yongqiang , Zhang Yu , Xu Dan , Xu Bing , Feng Ru , Liu Qifa , Sun Jing , Meng Fanyi 
Published: October 2019

Abstract

Background and Objective
Following the introduction of the tyrosine kinase inhibitor (TKI) imatinib in treatment of chronic myeloid leukemia (CML) patients, the allogeneic hematopoietic stem cell transplantation (allo-HSCT) scene in CML has changed dramatically. This retrospective cohort study was designed to compare medical outcomes of Imatinib mesylate and allo-HSCT for patients with CML in chronic phase.

Patients and Methods
From February 2002 to February 2012, 198 patients treated consecutively at the Nanfang Hospital,Southern Medical University were assigned to two groups according to treatment with imatinib or allo-HSCT. One hundred fifteen cases of imatinib group were given imatinib at an initial dose of 400mg daily and the dose was then adjusted according to the patient´s blood and therapy response. All the patients were evaluated for hematologic, cytogenetic and molecular response every 1-3months. Eighty-three cases of allo-HSCT group received myeloablative preconditioning regimen, and methotrexate (MTX) and cyclosporine A (CsA) were used for graft-versus-host disease(GVHD), parts combined with mycophenolate mofetil (MMF) and antihuman thymocyte globulin(ATG). The primary end points of the study were complete cytogenetic response (CCyR), relapse rate, overall survival (OS) and progression-free survival (PFS) after therapy.

Results
In total, 59 (68.9%) patients treated over 12 months achieved a CCyR after 12 months in imatinib group, while 67 (95.7%) patients in allo-HSCT group. The relapse rates were 14.8% (n=17) in imatinib group and 10.8% (n=9) in allo-HSCT group (P=0.456). Ten-year cumulative OS rates were 93.9% in imatinib group and 77.1% in allo-HSCT group(P=0.015) and ten- year cumulative PFS rates of two groups were 86.1% vs.88.0%(P=0.508). For Sokal rating stratified analysis, the ten-year OS rates of two groups were 96.4% vs.68.0% (P = 0.049) for high-risk patients,92.6% vs. 57.1% (P = 0.019) for intermediate-risk patients , while the ten-year PFS rates of two groups were 89.3% vs. 88.0% for high-risk patients (P = 0.942), 70.4% vs. 85.7% for intermediate-risk patients (P = 0.405).The ten-year OS rates and PFS rates were not significant difference for low-risk patients. The cumulative OS rates of two groups were 94.7% vs. 73.5%(P=0.019)for the patients who were not less than 30 years old,and the cumulative PFS rates of two groups were 84.2% vs. 94.1% respectively (P=0.147).

Conclusion
Imatinib mesylate treatment is superior to allogeneic hematopoietic stem cell transplantation for patients with chronic myeloid leukemia in chronic phase.

Disclosures:
No relevant conflicts of interest to declare.
Outcome Of Hematopoietic Cell Transplantation (HCT) In Pediatric Patients With Non-Hodgkin Lymphoma (NHL): Single Institution Results From Saudi Arabia
Authors: Belgaumi Asim F , Sumaili Hassan A , Al-Kofide Amani A , Ayas Mouhab , El-Solh Hassan , Al-Ahmari Ali , Al-Jefri Abdallah , Anas Mohammed , Mohamed Amal , Al-Seraihy Amal 
Published: October 2019

Abstract
Although HCT is an accepted component of the treatment strategy for relapsed/refractory pediatric NHL, only few studies have reported on the outcome for these patients. Most have reported on small numbers of patients, with survivals ranging from 27% to 75%.
Clinical data were retrospectively retrieved for patients with NHL who had undergone HCT. Pre-HCT information, including pathologic diagnosis, response to first- and second-line therapy and pre-HCT disease status were collected, in addition to details of the transplant process and patient and disease outcome.
Between 1996 and 2012, 28 pediatric patients with NHL underwent HCT. Primary diagnosis for these patients included Burkitt lymphoma (n=13), Large B-cell lymphoma (n=4), T-Lymphoblastic lymphoma (n=4), NK/T cell lymphoma/leukemia (n=3), Peripheral T-cell lymphoma (n=2), B-lymphoblastic lymphoma ((n=1) and anaplastic large cell lymphoma (n=1). The median age at HCT was 7.65 years (mean 8.2; range 1-14.3). Twenty had suffered a relapse of their disease, while five had primary progression; three patients with NK/T lymphomas underwent HCT as part of their first-line therapy. Fourteen patients had autologous (autoHCT) and 14 had allogeneic HCT (alloHCT). Among alloHCT, 11 had matched-related grafts while 3 had unrelated umbilical cord blood (UCB) grafts. At the time of HCT, 23 patients were in CR (CR1=7, CR2=15, CR3=1), and 5 had partial responses. HCT conditioning was myeloablative for all patients; in 18 patients, it was TBI-based. Fourteen patients suffered recurrence of their lymphoma post HCT at a median of 1.17 months from HCT (mean 6.2; range 0.63-42); 4 died in CR due to transplant-related toxicity, of these 3 were post alloHCT and one post autoHCT. Three patients have developed secondary malignancies (SMN; 2 post alloHCT and 1 post autoHCT). 10 patients were alive at last follow-up, all of whom were in CR. The 5-year estimated OS from SCT is 38.7%, with and EFS of 26%. There was no difference in 5-year OS or EFS among patients who received alloHCT v. autoHCT (OS 28.6% v. 49%; p=0.53, EFS 14.3% v. 37.5%; p=0.25) and among patients who did or did not receive TBI (OS 33.3% v. 48%; p=0.37, EFS 27.8% v. 18.8%; p=0.66). OS/EFS for patients with Burkitt lymphoma was 23.1%. Of the three patients with NK/T cell lymphoma two remain alive in CR 13.7 and 5.1 years after HCT.
The outcome of relapsed/refractory non-Hodgkin lymphoma of childhood remains suboptimal. In addition to a high post-HCT relapse rate of 50%, HCT-related toxic mortality and SMN contribute to the poor outcome for this cohort of patients.

Disclosures:
No relevant conflicts of interest to declare.