bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of Salvage Autologous Versus Allogeneic Hematopoietic Cell Transplantation for Multiple Myeloma Relapsed After Initial Autologous Hematopoietic Cell Transplantation
Authors: Byrne Michael T. , Dai Yunfeng , Moreb Jan , Wirk Baldeep 
Published: October 2019

Abstract
Abstract 4464

BACKGROUND:
Standard therapy for multiple myeloma (MM) includes initial autologous hematopoietic cell transplantation (autoHCT1) but this is not curative and most patients will relapse. Data on salvage autoHCT2 or allogeneic HCT (alloHCT2) are limited and the optimal salvage strategy is unknown.

METHODS:
Retrospective review of MM patients over 18 years of age who relapsed after autoHCT1 and underwent salvage autoHCT2 or alloHCT2 between 1995–2011 at our institution. Tandem auto-autoHCT or auto-alloHCT were excluded. Disease response was defined by the International Myeloma Working Group criteria and assessed 100 days after HCT2.

RESULTS:
Patient characteristics of autoHCT2 (N=27) and alloHCT2 (N=19) (Table 1) were not significantly different except the alloHCT2 median age was significantly lower (54 years) than for autoHCT2 (62 years) and more alloHCT2 patients had KPS 70% or more. Median followup of both groups was 57 months. Complete and very good partial remission (CR/VGPR) improved from 7% to 56% after autoHCT2 and from 26% to 37% after alloHCT2. Of 15 patients with progressive disease (PD) who had autoHCT2, 5 achieved CR/VGPR with 7 PR. Nonrelapse mortality (NRM) at 1 year was 3.7% for autoHCT2 and 5.3% for alloHCT2 (p=.901). Median progression free survival (PFS) and overall survival (OS) for autoHCT2 (19 months, 23 months) and alloHCT2 (6 months, 19 months) were not significantly different (p=0.156 and p=0.255). On multivariate analysis, time from autoHCT1 to relapse less than 1year vs. 1year or more (HR 24.81 [95% CI 2.4–249.9]) and no maintenance therapy vs. given after autoHCT2 (HR 12.19 [95% CI 2.5–249.9] impacted OS after autoHCT2. On multivariate analysis, only time from autoHCT1 to relapse less than 1 year vs. 1 year or more (HR 18.55 [95% CI 2.28–150.57]) impacted PFS after autoHCT2. For alloHCT2, no factors impacted NRM, PFS or OS including chemosensitivity, acute/chronic GVHD, donor lymphocyte infusion, antithymocyte globulin, reduced intensity vs. myeloablative conditioning, matched sibling or unrelated donor, time from autoHCT1 to relapse less than 1 year vs. 1 year or more. For those with relapse from autoHCT1 less than 1 year vs. 1 year or more undergoing autoHCT2, median OS was 15 months (0–53) vs. not yet reached (p=0.003) and median PFS was 5 months (0–49) vs. not yet reached. (p=0.002) Major causes of death for alloHCT2 were PD (n= 5), GVHD (n=3), while for autoHCT2, PD (n=10), infection (n=3).

CONCLUSIONS:
Salvage autoHCT2 and alloHCT2 are both feasible for patients with post autoHCT1 MM relapse. Relpase 1 year or more from autoHCT1 predicts for better PFS and OS in the autoHCT2 group. Those with progressive disease can also be salvaged by autoHCT2. Maintenance therapy after autoHCT2 is beneficial and should routinely be used.

Disclosures:
No relevant conflicts of interest to declare.
Prognostic Value for Survival of Serum Ferritin Levels Over Time After Allogeneic Hematopoietic Cell Transplantation
Authors: Nakamae Mika , Nakamae Hirohisa , Koh Hideo , Nakane Takahiko , Nishimoto Mitsutaka , Hirose Asao , Hino Masayuki 
Published: October 2019

Abstract
Abstract 4466
A significant association between iron overload prior to allogeneic hematopoietic cell transplantation (HCT) and worse prognosis following HCT has been reported. In most previous reports, the serum ferritin level before HCT was used as a surrogate marker of iron load. However, serum ferritin level is known to be increased by acute inflammation, including that due to infection, and/or active hematological diseases. The prognostic value of serum ferritin level has not been evaluated taking into consideration the influence of acute inflammation. In addition, little is known about changes in serum ferritin levels following HCT or the prognostic value for survival after HCT, particularly in the late period post HCT.
Here we comprehensively evaluated the impact of serum ferritin level after HCT as well as pre HCT on survival. We retrospectively studied 204 evaluable patients who had undergone HCT in our institute between February in 2004 and December in 2011, and who had available serum ferritin data pre HCT (median age 46, males 114 and females 90). The median follow-up period among surviving patients was 1023 days. We analyzed the impact of serum ferritin level pre HCT on overall survival after adjusting for various positive and negative acute phase reactants including haptoglobin, fibrinogen, CRP and serum albumin levels in multivariate analysis. On univariate analysis, serum ferritin level pre HCT significantly affected overall survival (ferritin per 100 ng/ml, HR: 1.003, p=0.008) and overall survival significantly worsened as serum ferritin level pre HCT increased (p for trend =0.01). However, after adjustment for haptoglobin or serum albumin levels, the relationship between serum ferritin pre HCT and survival was no longer statistically significant.

Disclosures:
No relevant conflicts of interest to declare.
Anti-HLA Antibodies in Allogeneic Hematopoietic Stem Cell Transplantation From HLA-Mismatched Unrelated Donors
Authors: Koclega Anna , Markiewicz Miroslaw , Siekiera Urszula , Dobrowolska Alicja , Mizia Sylwia , Dzierzak-Mietla Monika , Zielinska Patrycja , Sobczyk-Kruszelnicka Malgorzata , Kyrcz-Krzemien Slawomira 
Published: October 2019

Abstract
Abstract 4475

Introduction:
Anti-HLA Antibodies (Abs) are considered an important factor in solid organ transplants and transfusion medicine, but role of humoral arm of immunological response to HLA antigens in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unknown. Large polymorphism and immunogenicity of HLA-antigens and heterogeneity of anti-HLA Abs warrant the need of such investigation. The purpose of this study was to define presence and profiles of anti-HLA Abs detected before or after allo-HSCT from HLA-mismatched unrelated donors and their impact on allo-HSCT results.

Material and methods:
35 HLA-mismatched donor/recipient pairs entered the study. Indication for allo-HSCT was: ALL (7pts), AML(18pts), CML(5pts), SAA(2pts), CLL(1pt), MDS(1pt) and PNH (1pt). Preparative regimen was myeloablative in 33pts (94.3%) and reduced in 2pts (5.7%). Standard GVHD prophylaxis consisted of cyclosporine, methotrexate and pre-transplant anti-thymocyte globulin (34pts) or Alemtuzumab (1pt). HLA A, B, C, DR, DQ alleles were PCR-typed. 21(60%) pts had mismatch of single HLA-antigen: A-4(11.4%), B-1(2.8%), C-13(37%), DQ-3(8,5%); 10(28.5%) pts had mismatch of single HLA-allele: A-3(8.5%), B(11.4%), DQ-3(8.5%); 4 pts had double antigenic (A+C and A+DQ) or combined antigenic/allelic (A/B and C/A) HLA mismatches. Anti-HLA A, B, C, DR, DQ, DP Abs were identified in sera collected before start of the conditioning treatment and +30 days, +100 days and 1 year after allo-HSCT with use of automated DynaChip assay utilizing microchips bearing purified class I and class II HLA antigens.

Results:
Anti-HLA Abs pre-formed before allo-HSCT were detected in 17(48.5%) pts: against class I, II or both in 6(35%), 4(24%) and 7(41%) pts. Anti-HLA Abs were detected after allo-HSCT in 25(71.4%) pts, against class I, II or both in 9(36%), 3(12%) and 13(52%) pts, respectively. In 7 pts anti-HLA Abs were not detected neither before nor after allo-HSCT. Anti-HLA Abs directed against the mismatched HLA antigens were observed in 4 pts before and in 10 pts after allo-HSCT, no anti-HLA Abs specific against mismatched alleles were detected. Allo-HSCT results obtained in studied subgroups are presented in the Table below:

Conclusions:
Our preliminary results indicate that anti-HLA Abs are present pre- or post-transplant in mismatched allo-HSCT recipients and may be potentially responsible for the occurrence of complications, what needs to be further investigated and analyzed.

Disclosures:
No relevant conflicts of interest to declare.
Effect of Antithymocyte Globulin Dosage for Prophylactic Gvhd On Epstein-Barr Virus Reactivation and Diseases in Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Yu Guo-pan , Liu Qifa , SUN Jing , Xuan Li , Wu Meiqing , Liu Xiaodan , Xu Dan , Meng Fan Yi , Zhou Hongsheng , Huang Fen 
Published: October 2019

Abstract
Abstract 4486

Background:
Antithymocyte globulin (ATG) is one of the main risk factors for Epstein-Barr virus (EBV) reactivation and disease in allogeneic hematopoietic stem cell transplantation (allo-HSCT), however, whether there is a correlation between ATG dose and EBV reactivation is unsure. Aim of this single-center prospective study is to explore the relationship between ATG dose and EBV reactivation in allo-HSCT.

Methods:
Ninety-nine patients with hematologic malignancies underwent allo-HSCT and administration of ATG for graft versus host disease (GVHD) prophylaxis were enrolled in this study in Nanfang hospital from February 2008 to February 2012. Sixty-one patients were unrelated donor transplants, thirty-eight were HLA-mismatched related donor transplants. GVHD prophylactic regimen was cyclosporine A+Methotrexate+ATG. According to donors' HLA matching, we chose three dosage groups of prophylactic ATG: low dose group with ATG dose of 5.0∼6.0mg/kg (n=28), medium dose group with ATG dose of 7.0∼8.0mg/kg (n=55), and high dose group with ATG doses of ≥10mg/kg (n=16). The levels EBV-DNA in plasma were regularly monitored by quantitative real-time polymerase chain reaction (RQ-PCR).

Results:
With a median follow-up of 21 (range, 1–50) months post allo-HSCT, the cumulative incidence of EBV viremia and EBV-associated diseases was 17.6% (5/28) and 17.6% (5/28) in low dose group, respectively, with 32.7% (18/55) and 29.1% (16/55) in medium dose group, respectively, with 50.0% (8/16) and 31.3% (5/16) in high dose group, respectively. There were statistical significances of the incidence (χ2□□9.555, P=0.008). Logistic regression models showed that ATG prophylaxis was one of the main risk factors for EBV infection (RR=16.728, P=0.000) while bivariate correlation analysis presented that the incidence of EBV reactivation was positively correlated with ATG prophylaxis dosage (rpearman = 0.452, P = 0.000). The cumulative incidence of high degree (II∼IV°) aGVHD was 35.7% (10/28) in low dose group, with 39.6% (21/53) in total and 50.0% (6/12) in relapsed leukemia with HLA-mismatched related transplantation in medium dose group, with 68.8% (11/16) in high dose group. There were not statistical significances of the incidence (χ2□□6.971, P=0.137).

Conclusion:
EBV reactivation might be positively correlated with ATG prophylaxis dosage. According to donors' HLA matching, reducing ATG prophylaxis dose appropriately could prevent EBV reactivation in allo-HSCT without increasing high degree aGVHD.

Disclosures:
No relevant conflicts of interest to declare.
Impact of Pretransplant Donor and Recipient Cytomegalovirus Serostatus On Outcome for Multiple Myeloma Patients Undergoing Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation
Authors: El-Cheikh Jean , Devillier Raynier , Crocchiolo Roberto , Furst Sabine , Calmels Boris , Faucher Catherine , Stoppa Anne Marie , Granata Angela , Oudin Claire , Ladaique Patrick , Lemarie Claude , Venton Geoffroy , Bouabdallah Reda , Zandotti Christine , Berger Pierre , Chabannon Christian , Blaise Didier 
Published: October 2019

Abstract
Abstract 4496

Purpose:
To investigate the impact of pre-transplant CMV serostatus of donor or recipient on outcome of patients undergoing allogeneic hematopoietic stem cell transplantation (Allo-SCT) for Multiple Myeloma (MM).

Patients and methods:
We retrospectively followed 99 consecutive patients who underwent reduced-intensity conditioning (RIC) Allo-SCT for MM in our cancer centre at Marseille between January 2000 and January 2012. Based upon CMV serostatus, patients were classified as low risk (donor [D]-/recipient [R]-) 17 patients (17.1%), intermediate risk (D+/R) 14 patients (14.1%), or high risk – either (D-/R+) 31 patients (31.3%) or (D+/R+), 37 patients (37.3%).

Results:
Cumulative incidence of CMV reactivation was 39% with a median time of 61 days (26–318). Three patients (3%) developed CMV disease. Two factors were associated with CMV reactivation: CMV serostatus group (low: 0% vs intermediate: 29% vs high: 50%; p=0.001) and the presence of grade II–IV acute GvHD (Hazard Ratio: HR=2.1 [1.1–3.9]). Thirty-six of the 39 patients (92%) with CMV reactivation did not present positive detection of CMV after a 21-day median duration preemptive treatment with ganciclovir. Cumulative incidence of day 100 grade II–IV acute GvHD, 1-year chronic GvHD and day 100 transplantation related mortality (TRM) were 37%, 36% and 9%, respectively. CMV reactivation and serostatus were not associated with increased GvHD and TRM or short survival. Only the presence of acute GvHD as a time dependent variable was significantly associated with increased TRM (p=0.005). Two-year overall and progression free survival were 56% and 34%, respectively.

Conclusion:
Donor and recipient CMV serostatus and acute GvHD are independent factors for increased CMV reactivation in high-risk MM patients undergoing RIC Allo-SCT. However, we did not find any influence of CMV reactivation on post transplantation outcome. CMV monitoring and pre-emptive treatment strategy could in part explain these results. Novel prophylactic measures such as immunotherapy and drug prophylaxis need to be considered in this specific group of patients, warranting further prospective studies.

Legend:
CR, complete remission; VGPR, very good partial remission; PR, partial remission, PD, progressive disease; Flu, fludarabine; Bu, busulfan; ATG, antithymocyte globulin; CR, complete remission; VGPR, very good partial remission; PR, partial remission, PD, progressive disease; MRD, matched related donor; URD, unrelated donor; GVHD, graft versus host disease; CSA, cyclosporine A; MMF, mycophenolate mofetyl.

Disclosures:
No relevant conflicts of interest to declare.
Inhibition of the Renin Angiotensin System During Autologous Stem Cell Transplant Does Not Impact Time to Engraftment □s€
Authors: Kumar Anita J. , Carver Joseph R , Frey Noelle V. 
Published: October 2019

Abstract
Abstract 4502

Background:
The renin angiotensin system modulates hematopoiesis via local effects in the bone marrow. Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) may adversely impact hematopoiesis and time to engraftment in patients undergoing stem cell transplant (SCT). Our study assesses whether the use of ACEi or ARBs delays time to engraftment in patients with multiple myeloma undergoing a melphalan based autologous SCT.

Methods:
A retrospective review of 58 patients who underwent autologous SCT with a melphalan 200 mg/m2 conditioning regimen for multiple myeloma between January 1 and December 31, 2010 was performed. Neutrophil engraftment was defined as an absolute neutrophil count greater than or equal to 500 cells/uL that persisted for at least three days. Platelet engraftment was defined as achieving platelets of at least 20,000 cells/uL that persisted for at least three days. Time to engraftment was defined as number of days from Day 0 of SCT to the first day of platelet or neutrophil engraftment.

Results:
Of 58 evaluable patients, 47 underwent autologous SCT without an ACEi or ARB (control group), and 11 patients were given an ACEi or ARB (treatment group). Mean time to neutrophil engraftment was 11.5 days in the control group, and 11.3 days in treatment group (p=0.6). Mean time to platelet engraftment in control group was 13.5 days and 15.1 days in treatment group (p=0.2). There was no statistically significant difference between groups in time to neutropenic fever and length of hospital stay.

Conclusion:
Our study demonstrates no significant difference in time to engraftment, incidence of neutropenic fever, or length of hospital stay between patients receiving ACEi or ARBS compared to control subjects. We demonstrate that use of low to moderate dose ACEi or ARB is not associated with prolonged time to engraftment and is safe to use in patients undergoing autologous SCT for multiple myeloma.

Disclosures:
No relevant conflicts of interest to declare.
Combined Transplantation of Bone Marrow and Umbilical Cord Blood of Same Sibling in Twenty Three Children with Beta-Thalassemia Major
Authors: Xuedong Wu , Chunfu Li , Feng Xiaoqin , He Yuelin , Zhou Xiaohui , Liu Qifa 
Published: October 2019

Abstract
Abstract 4506

Objective:
To investigate the effect of transplantation using bone marrow plus umbilical cord blood from same sibling in children with β-thalassemia major (TM).

Methods:
Twenty three TM patients undergoing transplantation of bone marrow and umbilical cord blood of same sibling aged from 4.0 to 12 years, 13 boys and 10 girls, were recruited at the Department of Pediatrics, Nanfang Hospital, Southern Medical University from January 2005 to June 2012. The patients were classified into three classes, class¢ñ to class ¢ò 22 cases and class ¢ó 1 case. Donors ranged 1–4 years received 10 Ìg/kg per day of subcutaneous granulocyte colony-stimulating factor (G-CSF) for 5 consecutive days. Bone marrow was harvested on the fifth day. Bone marrow and umbilical cord blood of the same sibling then were transfused into the patient.

Results:
Recovery of hematopoiesis was gained in all patients 4 weeks following transplantation. Seventeen patients suffered from infection of different degree. Six patients developed mild venous occlusive disease. Four patients developed grade¢ñacute graft-versus-host disease (GVHD), and one developed grade¢ñchronic GVHD. Of twenty three patients, twenty survived, three died of whom, one died of lung infection and heart failure 32 days following transplantation, one died of organ failue on 47days after transplantation, and the other one died of lung fugal infection 22 months after transplantation.

Conclusion:
Combined transplantation of granulocyte colony-stimulating factor primed bone marrow and umbilical cord blood of same sibling in children with β-thalassemia major is safe and effective with promising results. However, complications should be paid high attention following transplantation.

Disclosures:
No relevant conflicts of interest to declare.
HLA-Haploidentical HSCT with Post-Transplant Cyclophosphamide for Severe Aplastic Anemia
Authors: He Yuelin , Li Chunfu , Wu Xuedong , Zhou Xiaohui , Feng Xiaoqin , Liu Huaying , Liu Qifa 
Published: October 2019

Abstract
Abstract 4510

Objective
To investigate the effect of pretransplantation donor lymphocyte infusion (DLI) and posttransplantation cycolphosphamide (CY) to prevent graft rejection and graft-versus-host disease (GVHD) after bone marrow transplantation plus peripheral blood stem cell transplantation from HLA-haploidentical mismatched related donors.

Methods
Four patients (median age, 11 years; range, 8–15 years) with severe aplastic anemia and all of them had HLA-haploidentical donors more than or equal to 2/8 HLA (HLA-A, B, C and DRB1) mismatched at antigen level. The conditioning regimen consisted of pretransplantation DLI (Lymphocytes, 1×10e7/kg at day -9); 40mg/m2/day of fludarabine (day-6 to -2); 3.2mg/kg/day of Busulfex (day-6 and -5); 10mg/kg/day of Thiotepa (day -4) and 50mg/kg/day of Cy on day -7, 14.5mg/kg on day-3,-2 and 40mg/kg on day +3,+4, respectively. The prophylaxis of acute GVHD consisted of tacrolimus and mycophenolate mofetil. The median follow-up time is 5 (rang: 3–6) months.

Results
The median times to neutrophil (>500/ÌL) and platelet recovery (>20,000/ÌL) were 21 and 23.5 days, respectively. No acute GVHD and Chronic GVHD were, so far, observed for all patients and were survive without SAA.

Conclusion
Posttransplantation cyclophosphamide for the prophylaxis of acute GVHD was safe and effective.

Disclosures:
No relevant conflicts of interest to declare.
Effect of KIR Ligand Mismatched SCT for Infantile ALL with MLL gene Rearrangement: A Report From the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG)
Authors: Miyamura Takako , Hirayama Masahiro , Sugita Kanji , Watanabe Tomoyuki , Ishii Eiichi , Koh Katsuyoshi , Kato Koji , Saito Akiko Moriya , Horibe Keizo , Tsurusawa Masahito , Tomizawa Daisuke 
Published: October 2019

Abstract
Abstract 4543

Introduction:
Acute lymphoblastic leukemia (ALL) in infants with MLL gene rearrangement shows poor prognosis and its treatment strategy has not been established. The MLL03 study in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) consisted of the HLA-identical related bone marrow transplantation (BMT) or unrelated cord blood transplantation (CBT) within 4 months after intensive chemotherapy. However, it has not been elucidated whether the stem cell transplantation (SCT) at the early stage of treatment could improve the prognosis of infantile ALL. Recently, the graft- versus- leukemia (GVL) effect in KIR ligand mismatched SCT has been reported in several hematologic malignancies. The purpose of this study is to clarify the effect of KIR ligand mismatched SCT for infantile ALL.

Subjects and Methods:
Twenty-three of the 63 infants with MLL gene rearranged ALL who were registered in the MLL03 study and undergone SCT from February 2004 to January 2009, were evaluated. The prognosis and SCT-related complications were analyzed in patients with KIR ligand matched (n=18) and mismatched (n=5) SCT.

Results:
Overall survival rate (OS) in the KIR ligand matched group was 58.3% (95% CI, 31.3 – 77.8%), while all of the KIR ligand mismatched group have survived (p=0.10). Event free survival (EFS) was 44.4% (95% CI, 21.5 – 65.1%) in the KIR ligand matched group and 80.0% (95% CI, 20.3 – 96.9%) in the KIR ligand mismatched group (p=0.18). Acute GVHD (grade 2 to 4) was detected in 3 patients in the KIR ligand matched group, and 2 in the KIR ligand mismatched group (p=0.54). Two patients in the KIR ligand matched group and 1 in the KIR ligand mismatched group showed chronic GVHD, but it was all mild. Three patients who relapsed after KIR matched first SCT underwent second SCT with KIR mismatched cord blood, and all have survived without relapse.

Discussion:
Our study suggests the effect of KIR ligand mismatched SCT to prevent relapse and improve prognosis of infantile ALL, although no significant difference was observed because of small number of patients in each group. In addition, serious adverse events including GVHD were not detected in KIR ligand mismatched group. We conclude that NK cell mediated GVL effect associated with KIR ligand mismatch might improve the prognosis of infantile ALL after SCT, and therefore should be evaluated as a front-line treatment strategy to improve the prognosis of infants with MLL gene rearranged ALL.

Disclosures:
No relevant conflicts of interest to declare.