Sibling Allogeneic Stem Cell Transplantation Research Articles

Analysis of therapeutic effects of allogeneic hematopoietic stem cell transplantation in 12 patients with DEK-NUP214 fusion gene positive acute myeloid leukemia

Twelve DEK-NUP214 fusion gene-positive patients with acute myeloid leukemia and on allo-HSCT treatment at the Hematology Hospital of the Chinese Academy of Medical Sciences from November 2016 to August 2022 were included in the study, and their clinical data were retrospectively analyzed. The patients comprised five men and seven women with a median age of 34 (16-52) years. At the time of diagnosis, all the patients were positive for the DEK-NUP214 fusion gene. Chromosome karyotyping analysis showed t (6;9) (p23;q34) translocation in 10 patients (two patients did not undergo chromosome karyotyping analysis), FLT3-ITD mutation was detected in 11 patients, and high expression of WT1 was observed in 11 patients. Nine patients had their primary disease in the first complete remission state before transplantation, one patient had no disease remission, and two patients were in a recurrent state. All patients received myeloablative pretreatment, five patients received sibling allogeneic hematopoietic stem cell transplantation, and seven patients received haploid hematopoietic stem cell transplantation. The median number of mononuclear cells in the transplant was 10.87 (7.09-17.89) ×10(8)/kg, and the number of CD34(+) cells was 3.29 (2.53-6.10) ×10(6)/kg. All patients achieved blood reconstruction, with a median time of 14 (10-20) days for neutrophil implantation and 15 (9-27) days for platelet implantation. The 1 year transplant-related mortality rate after transplantation was 21.2%. The cumulative recurrence rates 1 and 3 years after transplantation were 25.0% and 50.0%, respectively. The leukemia free survival rates were (65.6±14.0) % and (65.6±14.0) %, respectively. The overall survival rates were (72.2±13.8) % and (72.2±13.8) %, respectively.

Efficacy of Triple Prophylaxis for Prevention of Graft-Versus-Host Disease in Matched Sibling Allogeneic Peripheral Blood Hematopoietic Stem Cell Transplantation in Pediatric Patients

BACKGROUND: Graft-versus-host disease (GVHD) continues to compromise the overall success of allogenic hematopoietic stem cell transplantation. It is the most important cause of morbidity and non-relapse mortality after allogeneic hematopoietic stem cell transplantation for malignant disease. In adults, post-transplant cyclophosphamide (Cy-PT) has been shown to be a feasible, economically accessible, and effective strategy to reduce the incidence of GVHD in matched sibling hematopoietic stem cell transplantation in combination with a calcineurin inhibitor plus mycophenolate mofetil (MMF). AIM: Demonstrate the clinical benefit of Cy-PT plus a calcineurin inhibitor combined with MMF for GVHD prophylaxis in HLA-matched, related peripheral blood stem cell transplants in pediatric patients with malignant hematologic neoplasms compared to standard therapy in historical controls. METHODS: A retrospective study was conducted on 22 pediatric patients with malignant hematologic neoplasms who underwent HLA-matched related peripheral blood allogenic stem cell transplantation (alloSCT) between July 2012 and December 2022. A comparison was made between two groups, one with triple prophylaxis using Cy-PT, cyclosporine (CsA), and MMF, and a historical cohort that received standard GVHD prophylaxis based on CsA and methotrexate (MTX). Patients were identified from a hospital registry. Descriptive and inferential statistics will be reported, using SPSS version 25 for analysis. RESULTS: Twenty-two patients received HLA-matched alloSCT from first-degree relatives genotypically identical in HLA-A, HLA-B, and HLA-DRB1 alleles. The demographic characteristics of both groups are summarized in the table. No patient experienced primary graft failure, sinusoidal obstructive syndrome, or hemorrhagic cystitis. Acute GVHD grade II-IV did not develop in patients who received Cy-PT, whereas in the CsA/MTX prophylaxis group, 1 (9%) grade IV patient was observed who died due to this cause before day 100. Two patients (18%) developed Moderate/Severe GVHD in the CsA/MTX group, and 1 (9%) had moderate GVHD in the Cy-PT group. Two-year overall survival was similar between the two groups (Cy-PT 53% and CsA/MTX 67%), as was event-free survival (PTCy 48% vs. CsA/MTX 61%). CONCLUSION: Peripheral blood represents a feasible option in our setting due to rapid graft engraftment, short hospital stays, and low incidence of primary graft failure, but with a higher incidence of GVHD as reported in the literature. We explored the efficacy and safety of triple prophylaxis for HLA-matched alloSCTs from peripheral blood using Cy-PT + CsA + MMF in a small group of patients, with outcomes slightly better than standard prophylaxis. These preliminary results motivate us to continue with this new regimen.

A retrospective comparative cohort study on the routine pre-engraftment use of granulocyte colony-stimulating factor in allogeneic hematopoietic stem cell transplantation

Objective: Myeloid growth factors have been often used in allogeneic hematopoietic stem cell transplantation settings. There are some controversies about increased graft versus host disease, relapse, and delayed platelet engraftment with those growth factors in the pre-engraftment period. In this study, we aimed to compare the transplantation outcomes of allogeneic hematopoietic stem cell transplantation recipients according to their myeloid growth factor support status.
 Materials and Methods: Sixty-seven adult acute myeloid leukemia/myelodysplastic syndrome and acute lymphoblastic leukemia patients who underwent allogeneic peripheral blood stem cell transplantation from HLA-identical matched sibling donors were analyzed retrospectively. All-cause mortality at day 100, day 180, and at 1-year were the primary outcome measures. Secondary outcome measures were the engraftment kinetics, length of hospital stay, and graft-versus-host disease incidences.
 Results: Growth factor supported group was younger (p=0.001), and the first complete remission status at transplantation was seen more compared to the unsupported group (p=0.04). Myeloablative conditioning was used more in growth factor supported group (p=0.004). Faster neutrophil engraftment (p=0.008) and delayed platelet engraftment (p=0.022) were seen in growth factor supported group. Graft-versus-host disease, relapse incidences, and all-cause mortality at day 100, day 180, and at 1-year were not different between groups. Steroid-resistant graft-versus-host disease was the only factor related with relapse (OR: 0.196, p=0.043).
 Conclusion: This real-life study shows colony-stimulating-factors are safe in HLA-identical sibling allogeneic hematopoietic stem cell transplantation. Further prospective randomized controlled studies for different stem cell sources, different donors, and different conditioning and graft-versus-host disease prophylaxis regimens are mandatory.

Prophylaxis with ATLG Significantly Improves Chronic Graft-Versus-Host Disease / Relapse-Free Survival and Quality of Life after a Myeloablative HLA Identical Sibling Transplant for Acute Leukemia Patients in Complete Remission. Long-Term Follow-up of the Randomized ATG Familystudy

IntroductionChronic GVHD is a major complication after allogeneic stem cell transplantation (HSCT) affecting both survival and quality of life (QoL). Several strategies are currently used to limit the incidence and severity of GVHD. All but one prospective randomized studies demonstrated in the unrelated and related settings a significant reduction of cGVHD when anti-T cell lymphocyte globulin (ATLG) or anti-thymocyte globulin (ATG) is added to the standard GVHD prophylaxis (cyclosporine and methotrexate) with significant improvement of survival free from relapse and cGVHD (cGRFS), similar overall survival and no increase of relapse risk. In the setting of sibling transplants, the ATGfamilystudy demonstrated that in acute leukemia patients in complete remission the addition of ATLG (Grafalon, NEOVII) at the dose of 10 mg/kg per day from day -3 to day -1 to the standard GVHD prophylaxis within a myeloablative conditioning regimen resulted in a significant reduction of cGVHD (68.7% vs 32.2% at two years), especially of the extensive form (52.4% vs 7.6%) without a significant increase of relapse, infection and non relapse mortality (NRM). Overall survival resulted similar in the two arms while cGRFS was significantly improved (37% vs 16.7%). The risk of relapse is claimed as the major concern for a broader adoption of ATLG in the GVHD prophylaxis and a longer follow-up is strongly claimed by the scientific community to definitely unravel the issue of disease recurrence after in vivo T cell depletion with ATLG.MethodsWe updated the follow-up of the trial NCT 00612875 (Kröger et al. NEJM 2016) and analyzed data of QoL. The primary endpoint was the CI of cGVHD. CI of cGVHD, NRM, relapse, overall survival, disease-free survival and chronic GVHD and relapse-free survival (cGRFS) were analysed. The trial included also quality of life (QoL) questionnaires (EORTC QLQ-30 and HDC29 ) before and after SCT. The QLQ-C30 includes a global QoL scale, 5 functional scales (physical, role, emotional, cognitive and social function) and 9 symptom scales (fatigue, nausea-vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial problems).ResultsOut of 155 patients analyzed for safety and efficacy in the randomized study 119 were still alive at study end after 2 years and 114 provided any follow-up data. The median observation time was 5.2 and 6.0 years, in the experimental and control arm, respectively, with a maximum follow-up time >10 years in both groups.The CI of cGVHD overall was 31.3% (95% CI: 22.6% - 43.3%) in the ATLG arm vs 69.1% (95% CI: 59.1% - 80.7%) in the control arm (p <0.001); the CI of relapse was 36.6% (95% CI: 27.5% - 48.7%) and 23.9% (95% CI: 15.8% - 36.2%, p = 0.09). 5-ys overall survival, disease-free survival and cGRFS in the experimental and control arm were 61.8% and 67.1% (p=0.564), 53.6% and 61.7% (p=0.364), 40.4% and 18.1% (p = 0.001), respectively.Patients who received ATLG showed significantly greater improvement of global health status / QoL over time compared to non-ATLG (p=0.02), with a difference between the two arms of 2.8 ± 3.9 points (marginal mean ± SEM) at day 100 and increasing to 10.5 ± 5.3 points at month 24 in favour of ATG. Patients in the ATG arm showed also a significant superiority in 4 of the 5 functional scales as well as for several symptom scales scores such as appetite loss, insomnia, nausea-vomiting and dyspnea. For the QLQ-HDC29, significant treatment effects favoring ATG were observed for side-effects on gastrointestinal effects and impact on family, impact of family, urinary frequency, helping to distinguish what is important in life.ConclusionsThis long-term follow-up of the ATGfamilystudy confirmed a significant benefit of ATLG in reducing chronic GVHD without significant increase of relapse in patients with acute leukemia undergoing HLA-identical sibling allogeneic peripheral stem cell transplantation resulting in a significant benefit in chronic GVHD/relapse-free survival with a significant improved quality of life. DisclosuresBonifazi:Neovii: Honoraria. Solano:Neovii: Honoraria. Bethge:Neovii GmbH: Honoraria, Research Funding; Miltenyi Biotech GmbH: Consultancy, Honoraria, Research Funding. Kroeger:Neovii: Honoraria, Research Funding.

Comparative Outcome of Reduced Intensity and Myeloablative Preparative Regimen in HLA Identical Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Patients Older Than 50 Years of Age with Acute Myeloblastic Leukaemia: A Retrospective Survey from the Acute Leukemia Working Party (ALWP) of the European Group for Blood and Marrow Transplantation (EBMT).

Results of reduced intensity preparative regimen (RIC) hematopoietic stem cell transplantation (HSCT) in the HLA identical HSCT setting have not been compared to myeloablative HSCT (MA) in patients with AML over 50 years of age. With this aim, outcomes of 315 RIC were compared with 407 MA HSCT recipients from 182 transplant centers. The majority of RIC was fludarabine-based regimen associated to Busulfan (BU) (53%) or low dose TBI (24%). Multivariate analyses of outcomes were used adjusting for differences between both groups. The median follow-up was 13 months. Cytogenetics, FAB classification, WBC count at diagnosis and status of the disease at transplant were not statistically different between the two groups. However, RIC patients were older (median 57 years versus 54 years), transplanted more recently, and more frequently with peripheral blood allogeneic stem cells as compared to MA recipients. In multivariate analysis, Incidence of grade II-IV acute GvHD (aGvHD) was significantly lower after RIC: 22% compared to 31% after MA HSCT (p=0.003) but not Grade III-IV (8% versus 12%, respectively)(p=0.12). the risk of chronic GVHD was lower following RIC (RR=0.69; 95% CI,=0.51 to 0.94, p=0.02). Transplant-related mortality was significantly decreased(18% versus 32%) (p<10−4; RR=0.48, CI= 0.33 to 0.68), and relapse incidence was significantly higher (41% versus 24%) (p=0.0003; RR=1.78, CI=1.3 to 2.43) after RIC transplantation. Leukaemia-free survival (LFS) was not statistically different between the two groups. These results may set the grounds for prospective trials comparing RIC with other strategies of treatment in elderly AML.

The impact of chimerism on DNA-based human identification from skin surface cells of post-allogenic hematopoietic stem cell transplantation (HCST) patients

The use of biological traces recovered from touched or handled items increased with the advance of the forensic analysis system. Thus, DNA profiles obtained from touch DNA became a useful tool in forensic investigation. However, a chimeric person with more than one chromosomal population can be challenging for a forensic analyst. We investigated the genetic profile in blood, buccal swab, and skin swabs from twenty-four recipients aged 21–63 years who underwent a matched sibling allogeneic hematopoietic stem cell transplantation with no sign of skin graft versus host disease. Autosomal short tandem repeats genotyping was performed to evaluate chimerism status at 15 loci along with gender marker Amelogenin. According to our results, donor chimerism was detected in all recipient's blood samples, while in buccal swabs, five recipients showed no presence of donor-derived cells in their genotype. Epithelial cells swabbed from hand fingertips were not devoid of donor-derived cells since all recipients showed high chimerism (39.69%–96.66%) in their genotypes. A significant change in chimerism was seen among various types of biological samples (p<0.05). No correlations were observed between chimerism and recipient age, gender, or time after transplant (p> 0.05). The loci D21S11, D8S1179, and FGA were the most informative, whereas D13S317, Vwa, and TOPX were the least informative STR markers. We concluded that touch DNA from a person who has undergone a successful allogeneic HSCTs should not be considered as reliable evidence for human identifications. Therefore, necessary precautions must be taken to avoid false identification and miscarriage of justice.

Phase II Clinical Trial Evaluating the Standardization of CD3+ T-Cell Dose for Patients Receiving Allogeneic Peripheral Blood Stem Cell Transplants (PBSCT) from Matched Related Donors

<h3>Introduction</h3> Seminal studies of peripheral blood versus bone marrow grafts have elucidated the crucial role of CD3+ T-cells in mediating engraftment, immune reconstitution, disease control, and graft versus host disease (GVHD). An optimal dose-response relationship between the T-cell dose in the graft and outcomes is yet to be defined. Therefore, we performed a phase II clinical trial to evaluate whether T-cell dose standardization would adequately support engraftment and immune reconstitution while mitigating the risk of GVHD. <h3>Methods</h3> We conducted a clinical trial of dose standardization of T-cells between December 2014 and May 2018. Eligible adult patients (pts) with hematologic malignancies undergoing peripheral blood matched sibling allogeneic stem cell transplant were enrolled. Standardized T-cell dose was targeted 15-20 × 10e7. Tacrolimus and methotrexate were utilized for GVHD prophylaxis. The primary endpoint was to determine the incidence of grade II-IV acute GVHD. Secondary endpoints included overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM), and time to engraftment. Chronic GVHD was captured using conventional criteria. <h3>Results</h3> 17 pts were included in the study. Peripheral blood stem cell (PBSCT) graft from matched sibling donors was used in all pts. The mean age was 52 years (20-68 years). 53% pts were female and 82% were Caucasian. The median T-cell dose was 19.1 × 10e7 (range 9.1-21.8 × 10e7). Indications for PBSCT included AML/MDS (70.6%), ALL (17.6%), NHL and MPN (11.8 %). 35% pts received myeloablative and 65% received reduced-intensity conditioning. 59% had age-adjusted HCT-CI scores ≥3. 16 pts received tacrolimus and methotrexate for GVHD prophylaxis, with 1 patient receiving tacrolimus and mycophenolate. All pts successfully engrafted. The median time to engraftment was 15 days for neutrophils (range 10-20), and 12 days for platelets (range 9-22). The cumulative incidence of grade II-IV and grade III-IV acute GVHD at 1 year was 27% (95%-CI: 7-52) and 22.5 (95%-CI: 4.7-48.4) (no grade IV) and that of chronic GVHD was 47% (22-69) (N=8, all extensive by conventional criteria). 18% pts reactivated CMV (median - 40 days, range 33-50). 47% pts were alive in remission after a median follow-up of 18.1 months (3.3-52.2). The cumulative incidence of relapse at 1 year was 23.5% (95% CI: 7-46) (Figure 1). The 1 year PFS was 53% (95% CI: 28-73), and the OS was 65% (95% CI: 37-82). <h3>Conclusion</h3> Administration of a lower standardized T-cell dose is feasible, and when used in combination with standard immune suppression did not negatively affect outcomes. This study paves the way for a larger trial to evaluate the optimal T-cell dose and immune suppressive therapy to strike a favorable GVHD/GVL balance. Such a strategy could be used as a platform for additional interventions aimed towards improving the outcome of PBSCT for hematologic malignancies.

Combination of HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation With Unrelated Cord Blood Unit in Patients Aged 35 to 50 Years With Severe Aplastic Anemia: Preliminary Summary of a Single-Arm Trial

This study reports a single-arm trial in the interim phase in 4 patients with median age of 40.5 years who have undergone combined HLA-matched sibling donor (MSD) stem cell graft and an unrelated cord blood (UCB) unit for the treatment of severe aplastic anemia (SAA). The median time was 10 days for neutrophil engraftment (9-18 days) and 17 days for platelets (12-24 days). Median follow-up of 22 months (ranging from 16 to 29 months) showed survival of the 4 patients with complete hematological response. Acute graft-vs-host disease (GVHD) (grade II) occurred only in 1 patient, yet chronic GVHD was free. One patient showed a pattern of transient MSD graft followed by dominant UCB chimerism, and another 1 achieved mixed chimerism in the first 6 months after allogeneic hematopoietic stem cell transplantation (allo-HSCT) then evolved to a stable MSD graft. The other 2 patients sustained a full MSD graft during the post-HSCT period. Nevertheless, none of the patients developed primary and secondary graft failure up to the final follow-up. Although this is a small cohort, the dual transplantation combining HLA-matched sibling allogeneic hematopoietic stem cell transplantation with unrelated cord blood unit may deserve further exploration for treatment of SAA patients aged 35 to 50 years old.

Transfusion support for matched sibling allogeneic hematopoietic stem cell transplantation (1993-2010): factors that predict intensity and time to transfusion independence.

Patients undergoing allogeneic hematopoietic stem cell transplant require variable, often extensive transfusion support. Identification of factors that predict urgent, intensive, or special needs should improve management of these patients. This is a retrospective study of red blood cell (RBC) and platelet transfusion support provided for sequential matched sibling donor allogeneic transplants conducted at the Clinical Center, National Institutes of Health, from 1993 through 2010. Factors potentially important for predicting quantity of RBC and platelet transfusions, and time to transfusion independence through Day 200 following hematopoietic stem cell transplantation were evaluated. Subjects (n = 800) received 10,591 RBC and 10,199 platelet transfusions. Multivariable analysis demonstrated that the need for RBC pretransplant, CD34+ dose, transplant year, diagnostic category, and ABO match were significantly independently associated with quantity of RBC transfusions during Days 0 through 30. Only pretransplant need for RBCs, CD34+ dose, and transplant year had significance during Days 0 through 100. Similar analyses for quantity of platelet transfusions demonstrated that for both Days 0 through 30 and 0 through 100 significant factors were need for platelet support before transplant, CD34+ dose, transplant year, and transplant regimen. Of note, long term, during Days 101 through 200, only CD34+ dose remained significant for quantity of RBC and platelet transfusions. Analysis of time to transfusion independence demonstrated that patients with ABO major mismatches required longer to achieve freedom from RBC transfusion support compared to identical matches or those with minor mismatches. Patient-specific factors including CD34+ dose and ABO match of the graft should be given particular consideration by transfusion services when planning support of patients receiving allogeneic hematopoietic stem cell transplant.

Distinct Biomarker Profiles in Ex Vivo T Cell Depletion Graft Manipulation Strategies: CD34+ Selection versus CD3+/19+ Depletion in Matched Sibling Allogeneic Peripheral Blood Stem Cell Transplantation

Various approaches have been developed for ex vivo T cell depletion in allogeneic stem cell transplantation to prevent graft-versus-host disease (GVHD). Direct comparisons of T cell depletion strategies have not been well studied, however. We evaluated cellular and plasma biomarkers in 2 different graft manipulation strategies, CD3+CD19+ cell depletion (CD3/19D) versus CD34+ selection (CD34S), and their associations with clinical outcomes. Identical conditions, including the myeloablative preparative regimen, HLA-identical sibling donor, GVHD prophylaxis, and graft source, were used in the 2 cohorts. Major clinical outcomes were similar in the 2 groups in terms of overall survival, nonrelapse mortality, and cumulative incidence of relapse; however, the cumulative incidence of acute GVHD trended to be higher in the CD3/19D cohort compared with the CD34S cohort. A distinct biomarker profile was noted in the CD3/19D cohort: higher levels of ST2, impaired Helios− FoxP3+Treg reconstitution, and rapid reconstitution of naïve, Th2, and Th17 CD4 cells in the early post-transplantation period. In vitro graft replication studies confirmed that CD3/19D disproportionately depleted Tregs and other CD4 subset repertoires in the graft. This study confirms the utility of biomarker monitoring, which can be directly correlated with biological consequences and possible future therapeutic indications.

Role of thymoglobulin in matched sibling allogeneic hematopoietic stem cell transplantation with busulfan and fludarabine conditioning in myeloid malignanicies.

In vivo T-cell depletion using anti-thymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantation (HSCT) for prophylaxis of GvHD. We investigated the influence of thymoglobulin dose (an ATG) on GvHD following matched sibling donor (MSD) HSCT with a busulfan and fludarabine preparative regimen. Medical records of 180 patients who received MSD HSCT with a conditioning regimen of busulfan, fludarabine, and ATG (BuFluATG) were reviewed retrospectively. The median age was 53 years (range 18-68). Initial diagnoses were acute myeloid leukemia (73.3%) and myelodysplastic syndrome (26.7%). Forty-four and 68 patients (24.4 and 37.7%) experienced acute and chronic GvHD of any grade, respectively. High-dose (⩾4.5 mg/kg) ATG was independently associated with decreased risk of acute GvHD (hazard ratio=0.36, 95% confidence interval (CI): 0.15-0.84, P=0.019) compared to low-dose ATG (<4.5 mg/kg). Although ATG dose was associated with the risk of acute GvHD, it was not associated with the risk of chronic GvHD in our study. A higher dose (⩾4.5 mg/kg) of ATG decreases the risk of acute GvHD but had no significant impact on disease-free survival in MSD HSCT patients conditioned with BuFluATG. The optimal dose of ATG should be further investigated in a large prospective study context.

Effect of Antithymocyte Globulin Source on Outcomes of HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Severe Aplastic Anemia

We wanted to evaluate efficacy of porcine antithymocyte globulin (ATG) in HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation (MSD-HSCT) for patients with severe aplastic anemia (SAA). The clinical data of 113 SAA patients who received MSD-HSCT from January 2005 to November 2016 were analyzed retrospectively. Of these, 58 patients received rabbit ATG as a part of conditioning regimen (R-ATG group), whereas the other 55 patients received porcine ATG (P-ATG group). Patient baseline characteristics and donor conditions of the 2 groups were similar, except patients were older and more received peripheral blood stem cell transplantation in the P-ATG group. All patients engrafted in 2 groups. There were significant differences in the incidence of acute (20.7% ± 5.3% versus 43.4% ± 7.0%, P = .015) and chronic graft-versus- host disease (GVHD; 20.1% ± 5.8% versus 46.0% ± 7.9%, P = .003) between the R-ATG and P-ATG groups. However, there were no significant differences in terms of 3-year overall survival (93.1% ± 3.3% versus 84.4% ± 5.7%, P = .235), grades III to IV acute GVHD (3.4% ± 2.4% versus 12.3% ± 4.7%, P = .098), moderate to severe chronic GVHD (12.6% ± 4.9% versus 11.5% ± 4.9%, P = .905), or graft rejection (7.4% ± 3.6% versus 5.5% ± 3.1%, P = .852). There was also no significant difference with regard to the incidence of severe bacterial infection (P = .075), invasive fungal disease (P = .701), or cytomeglovirus viremia (P = .770). P-ATG showed satisfactory efficacy and safety compared with R-ATG in the setting of MSD-HSCT for SAA patients. P-ATG could be a potential alternative preparation for R-ATG, further offering the advantage of lower costs.

ID3012 Evaluation of HLA-identical sibling allogenic peripheral blood stem cell transplantation for acute myelogenous leukemia at BTH, Vietnam

Background: the purposes of this study were to assess the efficacy of HLA-identical sibling allogenic peripheral blood stem cell transplantation in the treatment for acute myelogenous leukemia (AML) at Blood transfusion and hematology hospital at Ho Chi Minh city.&#x0D; &#x0D; Methods: retrospective study, case series.&#x0D; &#x0D; Results: from June 2005 to September 2016, there were 47 AML patients included 24 males and 23 females, with median age was 36 years old. Engraftment was achieved in 47 patients (100%). The median number of transfused CD34+ cells was 7.5 x 106/kg. The median time for neutrophil engraftment and platelet engraftment were 11 ± 2.8 days and 12.5 ± 10.1 days respectively. Oral mucositis occurred in 38 patients (80.9%), febrile neutropenia in 42 patients (89.4%), acute graft-versus-host disease (aGvHD) in 14 patients (29.8%), chronic graft-versus-host disease (cGvHD) in 10 patients (21.3%), and VOD in 6 patients (12.8%). Transplant-related mortality (TRM) was 4 patients (8.5%). Median follow-up time was 52.26 months. Patients remained alive were 27 (57.4%). The 5-year overall survival (OS) and disease-free survival (DFS) were 55% and 54% respectively.&#x0D; &#x0D; Conclusion: HLA-identical sibling allogeneic blood stem cell transplantation can reconstruct hematopoiesis quickly and is a favorable therapeutic method for AML patients. Further development and improvement of hematopoietic stem cell transplantation techniques along with graduated and individualized therapy are expected to provide better outcomes and improved quality of life for AML patients.

Rabbit ATG Plus Cyclophosphamide with or without Fludarabine Is Superior Conditioning Regimen for Patients with Severe Aplastic Anemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Objective: To compare rabbit antithymocyte globulin (ATG) containing conditioning regimen (group A) with horse antilymphocyte globulin (ALG)-based regimen (group B) for sibling allogeneic hematopoietic stem cell transplant (HSCT) outcome, disease free survival, rejection and complications in severe aplastic anemia patients.Methods: We analysed 205 aplastic anemia patients undergoing allogeneic HSCT from HLA matched sibling donors from July 2001 to April 2016. Group A (n=169) received conditioning with ATG plus Cyclophosphamide (CY) 200 mg/Kg with Fludarabine (Flu) 120mg/m2 (n=100) or without Flu (n=69), whereas group B comprised of CY plus ALG (n=36). The stem cell source was bone marrow (43.9%); PBSC (8.3%) and bone marrow plus PBSC (47.8%). Cyclosporin (CsA) was given as GVHD prophylaxis in 129 patients, while methotrexate (MTX) was added to CsA in 76 cases. Chi-square test was used to compare categorical variables. Kaplan Meier survival curves with log rank test was applied to compare the groups for survival analysis.Results: Overall survival was 78.7% in Group A compared to 69.4% in group B (p=0.23). Patients in group A had significantly better disease free survival (DFS) (75.1%) than group B (55.6%) (p=0.018). The incidence of acute GVHD was 18.3% in Group A compared to 22.2% in Group 2 (p=0.64), while chronic GVHD was significantly higher in Group 2 (22.2%) as compared to Group A (9.5%) (p= 0.04). Likewise frequency of Mucositis was high in Group B (30.5%) compared to Group A (10.7%) (p = 0.006). Moreover, patients receiving ALG-based conditioning had more frequent infections (86%) compared to ATG-based group (67.4%) (p=0.03). There was no significant difference within group A with respect to use of fludarabine as part of conditioning.Conclusion: Rabbit ATG containing conditioning regimen is associated with less complications and better survival in patients with severe aplastic anemia undergoing allogeneic HSCT. DisclosuresNo relevant conflicts of interest to declare.

Cyclosporine (CsA) Pharmacogenetics Post HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Myeloid Leukemia: Value of CYP3A4 Gene Polymorphism

Cyclosporine (CsA) Pharmacogenetics Post HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Myeloid Leukemia: Value of CYP3A4 Gene Polymorphism

Impact of the GSTA1 Gene Polymorphism on Clinical Outcomes of HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Myeloid Leukemia

Impact of the GSTA1 Gene Polymorphism on Clinical Outcomes of HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Myeloid Leukemia

A Successful Second Stem Cell Transplantation in Fanconi Anemia: A Case Report

ObjectiveThe aim was to describe a case of successful second stem cell transplantation in Fanconi anemia (FA). MethodsA 7.5-year-old boy with FA was admitted for stem cell transplantation. The first matched sibling allogeneic bone marrow transplantation was done in January 2005. Until August 2008, the patient's blood count had been decreasing and the patient depended on transfusions, and anti-A Ab was detected (donor blood GP is A RH+). Therefore, the second matched sibling allogeneic peripheral blood stem cell transplantation was performed on November 27, 2008 with anti-thymocyte globulin alone as a second transplant conditioning. ResultThe child has been disease-free for 5 years. ConclusionAnti–thymocyte globulin alone as a second transplant conditioning may give first transplant failure FA patients the opportunity for a long-term disease-free survival.

Engraftment in Sibling Allogeneic Stem Cell Transplant Recipients Following the Change in Bone Marrow Collection Devices

Engraftment in Sibling Allogeneic Stem Cell Transplant Recipients Following the Change in Bone Marrow Collection Devices

Impact of Donor and Recipient Sex on Outcomes of HLA-Identical Sibling Allogeneic Hematopoietic Stem Cell Transplantation

Background: hematopoietic cell transplantation (HCT) is well established as therapy for hematologic malignancies as well as many non-malignant disorders. Donor selection is an important way to decrease the risks after HSCS and is therefore a key component of the clinical practice of transplantation. There are many criteria proved or hypothesized to affect outcomes after SCT and one of these, sex is the most controversial. Some investigators have found an increased risk of acute or chronic graft-versus-host disease (GVHD) associated with donor sex. Transplantation of stem cells from a female donor to a male recipient is a special circumstance in which donor T cells specific for minor H antigens, encoded by genes on the recipient Y-chromosome that are polymorphic to their X-chromosome homologues, may make a contribution to GVHD and GVL activity.Objective: investigate the effect of donor and recipient sex mismatch on outcomes of HLA-identical sibling allogeneic stem cell transplantation.Methods: this study was carried on 82 patients selected from patients who had underwent a myelo-ablative preparative regimen for a hematologic malignancy and received HSC transplant from an HLA-identical sibling being divided into 2 groups: 1st one with a female donor to a male recipient and 2nd one include otherwise. Both groups will be subjected to HLA tissue typing, CBC, Bone marrow aspirate evaluation, PT & PTT, blood culture when needed, SGPT, SGOT, ALP, blood urea, s.creatinine, urine analysis, pulmonary function tests, chest x-ray, echocardiography ECG, CMV-, EBV-, VZV-, Toxoplasma- antibodies (IgG , IgM), HBs-Ag, HBs-Ab, and HCV-Ab.Results: after variables controlling for patient and donor, there was an increased risk of acute GVHD in patients who received grafts from female donor being 18% for patients receiving grafts from female compared with 8% for recipients of male grafts. Donor sex was also an important influence on risk of developing chronic GVHD with cumulative incidences of chronic GVHD 9.7% for patients receiving transplants from male donors grafts compared to 24.3% for recipients of female donor grafts.Conclusion: we found that male recipients of grafts from female donors had a significantly higher probability for acute and chronic GVHD than male recipients with male donors or female recipients with female donors and despite the beneficial GVL effect observed in male recipients with female donors, these patients had significantly reduced survival compared with all patient/donor sex combinations, suggesting that other variables, particularly GVHD, contribute to transplantation-related mortality.

Oral Valganciclovir As Preemptive Therapy for Cytomegalovirus Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients

▪Introduction: Cytomegalovirus (CMV) infection remains one of the most important complications after allogeneic hematopoietic stem cell transplantation (AlloHSCT). Preemptive therapy with oral VGC or intravenous ganciclovir has replaced universal prophylaxis. We investigated the effect of oral VGC as preemptive therapy on CMV reactivation or infection in AlloHSCT.Patient & Methods: We retrospectively studied 30 consecutive adult recipients of HLA-identical sibling allogeneic peripheral blood stem cell transplant from June 2011 through June 2014 to analyze the safety and efficacy of preemptive therapy for the treatment of CMV infection. Among 30 patients we studied the results of 13 patients with CMV DNA positivity. All 13 recipients and their donors were seropositive for CMV Ig G status. Their diagnosis of pretransplantation were as 8 acute myeloid leukemia (61 %) and 5 acute lymphocytic leukemia (39 %). Median age was 39 years (range 21-54). There were 9 men and 4 women (Table-1). The patients received no prophylaxis against CMV. Blood/serum samples from all patients were routinely monitored for CMV-DNA using PCR twice weekly. We iniciated pre-emptive therapy for CMV as the viral load was above and equal to 500 copies/ml in two consecutive samples. VGC was given twice daily 900 mg for 2 weeks, and maintened at a dose daily 900 mg until viral load is undetectable.Results: The PCR test was persistently negative in 17 patients (57 %) and positive at least once in 13 (43%)patients. All patients with CMV reactivations were on immunsupressive treatment. CMV infection was cleared in most patients within 2 weeks, but for those with stable or increasing CMV levels, the induction period was continued. Twelve patients were treated with oral VGC on an outpatient basis and they all became CMV negative after the first week of treatment. Only one patient received intravenous ganciclovir and he was also CMV negative after the first week of treatment. While no positivity was identified in any of the patients who received VGC on day 21, clinically unimportant low titer CMV positivity was noted in three of these patients. VGC was continued at same dose and no positivity was detected after 2-3 weeks. We were obligated interrupt VGC in only four patients for serious side effects namely neutropenia and thrombocytopenia. We did not observe CMV-related mortality.Conclusions: We concluded that VGC therapy could be safely used at outpatient clinics, with frequent monitorization to prevent severe myelotoxicity. In conclusion, based on our findings, oral VGC is effective and safe in the pre-emptive treatment of CMV disease following allo-HSCT. Therefore, preemptive strategy by oral VGC appears preferable to the prevention of CMV disease in alloHSCT with its advantage of effectiveness and usage in outpatient clinic condition.Table- 1:Management and outcome of the patient characteristics with CMV-reactivationPatients with CMV reactivation/Total number of patient13/30Median age, years (range)39 (21-54)Gender Male Female9 4Diagnosis AML ALL8 5CMV serologic status Donor+/Recipient +13Preperative regimen Bu-Cy CY-TBI Flu/Amsc(FLAMSA)8 4 1GVHD propylaxis CSA+MTX CSA+MTX+MM12 1GVHD prior to CMV reactivation Acute chronic without GVHD7 1 5Prednisolone treatment at the time of starting VCG Yes No8 5IST at the time of starting VGC Yes No13 0Median duration of CMV reactivation (day)44 (8-330)Viral load before antivial treament (copies/ml)1153 (78-12800)Treatment VGC (900 mg, twice daily for induction) GC (5 mg/kg, twice daily for induction) VGC+GC9 (70 %) 1 (7 %) 3 (23 %)Total treatment duration (day)24 (10-51)CMV DNA at the end of the treatment Conversion to negative Persistently positive (low titer < 50 copies/ml)10 (77 %) 3 (23 %)Serious side effects Interruption of therapy due to neutropenia Interruption of therapy due to thrombocytopenia Reactivation3 (23 %) 1 (7 %) 2 (15 %)Abbreviations: AML: acute myeloid leukemia, ALL: acute lymphoblastic leukemia, CMV: cytomegalovirus,GVHD: graft-versus host disease, CSA: cylosporine, MTX: methotrexate, MMF: mycophenolate mofetil, PDN:prednizolone, IST: Immunosupressive treatment, VGC: valganciclovir, GC: ganciclovir, Bu: Busulfan, Cy: cylophosphamide, TBI: total body irradiation DisclosuresNo relevant conflicts of interest to declare.