Incidence and Risk Factors for Vzv Infection after Allogeneic Hematopoietic Cell Transplantation in 1,045 Patients: Younger Age Less Than or Equal to 45, Occurrence of Cgvhd By NIH Consensus Criteria, and No T-Cell Depletion

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1921-1921
Author(s):  
Sita D. Bhella ◽  
Elizabeth Shin ◽  
Marc Poch Martell ◽  
Jieun Uhm ◽  
Fotios V. Michelis ◽  
...  
Keyword(s):  
Risk Factors ◽  
T Cell ◽  
Risk Score ◽  
Research Funding ◽  
Univariate Analysis ◽  
High Risk Group ◽  
Cell Depletion ◽  
T Cell Depletion ◽  
Younger Age ◽  
Nih Consensus Criteria

Abstract Introduction: Varicella zoster (VZV) infection is a common complication post allogeneic hematopoietic stem cell transplantation (HCT) associated with significant morbidity, such as post herpetic neuralgia and secondary bacterial infection. Strategies to diminish the incidence of VZV infection include the use of prophylactic antivirals with some controversy. Our previous studies have explored risk factors associated with the incidence of VZV infection in 192 patients (Kim, Transplant Infectious Diseases, 2007). We attempted to determine the incidence of VZV infection and to explore risk factors leading to the development of VZV infection in an extended cohort of 1,045 patients receiving alloHCT. Methods: A retrospective single center study was conducted at Princess Margaret Cancer Centre, Toronto, Canada. Medical record review was performed for 1,045 consecutive patients who had undergone an alloHCT from 2001 to 2013. VZV infection was determined by clinical features and/or microbiologic determination. The incidence of VZV infection was calculated using cumulative incidence method considering death and relapse as competing risks. Univariate and multivariate analyses were conducted using EZR to identify the risk factors for VZV infection. Results: Out of 1,045 patients, 142 cases were identified with VZV infection (13.6%) with 14.4% of VZV incidence at 5 years (95% CI, 12.3-16.8%). The median days to the diagnosis of VZV post allogeneic transplantation was 231 days (range, 27-1488 days). 86.6% of patients were diagnosed as having VZV within 2 years post transplantation. 52.1% of those who developed VZV developed post-herpetic neuralgia, while 14.8% developed disseminated VZV. A univariate analysis was conducted including the following risk factors: aGVHD grade 2-4, aGVHD grade 3-4, occurrence of cGVHD, cGVHD severity by NIH consensus criteria, diagnosis (lymphoid v. others), T-cell depletion for GVHD prophylaxis, donor (related v. unrelated), HLA (matched v. mismatched) and donor type (matched related v. matched unrelated v. mismatched). Risk factors that were significant on univariate analysis were cGVHD occurrence by NIH criteria (p<0.001, HR 3.441), progressive type onset of GVHD (p=0.001, HR 1.89,), and age (p=0.006, HR 0.98,). T cell depletion (p=0.002, HR 0.67) and matched related donor (p=0.005, HR 1.86) were also significant. Multivariate analysis confirmed that age (p=0.007, HR 0.98), occurrence of cGVHD by NIH consensus criteria (p<0.001, HR 3.07), and T-cell depletion (p=0.032, HR 0.55) were significant risk factors. ROC analysis was performed which revealed an age less than or equal to 45 to be a categorical risk factor for VZV infection. A risk score model was generated assigning a score to each risk factor. A score of 1 was assigned to younger patient with age less than or equal to 45, occurrence of cGVHD by NIH consensus criteria, and no T-cell depletion. Total score was calculated with risk score 0 (n=82, 10%), risk score 1 (n=264, 31%), risk score 2 (n=334, 40%), risk score 3 (n=163, 19%)(843 patients were used for risk score analysis from 845 patients due to missing information). Three risk groups were created: low (score 0-1, n=346, 41%), intermediate (score 2, n=334, 40%) and high (score 3, n=163, 19%). This risk score group could stratify the patients according to VZV infection (p<0.0001): 5.9% in low vs. 14.3% in intermediate vs. 25.8% in high-risk group for VZV infection at 5 yrs. Conclusions: The incidence of VZV infection was substantial at 14.4% at 5 yrs. The occurrence of cGVHD by NIH consensus criteria increases the risk of VZV infection. Of interest, younger age was also associated with increasing risk of VZV infection, while T-cell depletion was protective from VZV infection. Strategies to prevent VZV infection should be considered in the high risk group of patients for VZV infection. Further study is strongly warranted to confirm these risk factors in other cohorts. Figure 1. Figure 1. Disclosures Lipton: Pfizer: Consultancy, Research Funding; Teva: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Novartis Pharmaceuticals: Consultancy, Research Funding. Kim:Novartis Pharmaceuticals: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding.

scholarly journals Comprehensive Analysis of Systemic Immunosuppression (SIS) Duration after Allogeneic Hematopoietic Stem Cell Transplant: Risk Score Model Provides Stratification of Patients According to Probability of SIS Discontinuation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3403-3403
Author(s):  
Maria Rhida Bautista ◽  
Arjun Law ◽  
Wilson Lam ◽  
Fotios V. Michelis ◽  
Santhosh Thyagu ◽  
...  
Keyword(s):  
T Cell ◽  
Risk Score ◽  
Predictive Factors ◽  
Research Funding ◽  
Cell Depletion ◽  
T Cell Depletion ◽  
Time Points ◽  
Allogeneic Hct ◽  
Related Donor ◽  
Score Model

Abstract BACKGROUND: Systemic immunosuppression (SIS) is the standard treatment for significant acute and chronic graft versus host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). Previous studies have shown that 30-70% of patients require immunosuppressive treatment for GVHD for more than 2 years. Prolonged SIS increases the risk of infections, recurrence of malignancy and multi-organ complications including endocrine dysfunction, hypertension, myopathy and ocular complications. This study aimed to evaluate the predictive factors associated with increased likelihood of SIS discontinuation from 3 different time points: from the day of transplant in all patients, from the day of treatment of acute GVHD (aGVHD) and from the day of treatment of chronic GVHD (cGVHD). METHODS: A retrospective review was conducted in 674 consecutive patients who underwent allogeneic HCT at Princess Margaret Cancer Centre from 2004 to 2013. Analyses were done using cumulative incidence method considering competing risks for SIS discontinuation. The incidence of SIS discontinuation was calculated from 3 time points: from the day of transplant in all patients, from the day of treatment of aGVHD and from the day of treatment of cGVHD. Univariate and multivariate analyses were conducted to identify the predictive factors for SIS discontinuation and hazard ratio (HR) with 95% confidence interval (CI) was calculated using Fine-Gray model. Risk score models were generated based on the results from the multivariate analysis with respect to the 3 time points. Each predictive factor was weighted according to the HR. Risk score models are presented in the Table below: for each risk score model, the patients were divided into 3 risk groups based on the scores. The cumulative incidence of SIS discontinuation was compared according to the risk group for each risk score model as shown in the Figure below. RESULTS: With a median follow-up duration of 3.5 years, the probability of SIS cessation at 3 years was 30.7% (27.0-34.5%) in all patients (n=674), 25.4% (21.2-29.8%) in patients treated for aGVHD (n=457) and 34.6% (29.1-40.3%) in patients treated for cGVHD (n=347). Multivariate analysis confirmed the following predictive factors associated with increased likelihood of SIS discontinuation. In all patients (n=654): age >50 years (vs ≤ 50 yrs; p<0.001, HR 1.83), bone marrow (BM) as a source of stem cells (vs peripheral blood [PBSC]; p=0.002, HR 1.78), T-cell depletion (vs no T-cell depletion; p<0.001, HR 1.98), matched related donor (vs others; p<0.001, HR 1.81) and HLA match (vs partially mismatched HLA; p=0.026, HR 2.58). In patients treated for aGVHD (n=457): age>50 (vs ≤ 50 yrs; p<0.001, HR 1.77), BM (vs PBSC; p<0.001, HR 2.38), matched related donor (vs others; p=0.025, HR 1.55) and aGVHD grade 0-2 (vs grade 3/4 aGVHD; p<0.001, HR 1.77). In patients treated for cGVHD (n=347): age >50 (vs ≤ 50 yrs; p=0.002, HR 1.83), BM (vs PBSC; p=0.004, HR 2.13), Grade 0-2 aGVHD (vs grade 3/4 aGVHD; p=0.003, HR 2.32), cGVHD grade (mild vs moderate vs severe; p<0.001, HR 2.02) and classical subtype (vs overlap syndrome; p=0.028, HR 1.52). The risk score model stratified the patients into low, intermediate and high risk groups: for all patients, SIS discontinuation at 3 years was 52.5% (37.9-65.2%), 30.7% (26.5-35.0%) and 17% (8.6-27.7%) respectively (p<0.0001); in patients treated for aGVHD, SIS discontinuation at 3 years was 70.6% (39.0-87.9%), 29.2% (24.0-34.5%) and 2.7% (0.5-8.6%) respectively (p<0.001); in patients treated for cGVHD, SIS discontinuation at 3 years was 62.8% (48.4-74.3%), 36.4% (29.8-43.0%) and 5.7% (1.0-17.1%) respectively (p<0.001). CONCLUSIONS: Older age, bone marrow as a source of stem cells, T-cell depletion, matched related donor and a full matched donor increase the likelihood of discontinuation of SIS after allogeneic HCT. In addition, the severity of aGVHD and cGVHD significantly affects the chance of SIS discontinuation. The proposed risk score stratifies patients into well-defined groups according to the chance of SIS discontinuation. Further studies in a larger number of patients are strongly recommended to validate this finding. Prospective validation is also warranted to confirm the utility of the risk score as a clinical tool for estimation of likelihood of SIS discontinuation in patients after allogeneic HCT. Figure. Figure. Disclosures Lipton: Pfizer: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding.

Higher Infused CD34+ Cell Dose Improves Survival In Patients Undergoing In Vivo T-Cell Depleted, but Not T-Cell Replete Peripheral Blood Hematopoietic Cell Transplant

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1272-1272
Author(s):  
Abraham S Kanate ◽  
Salman Osman ◽  
Aaron Cumpston ◽  
Gerry Hobbs ◽  
Sonia Leadmon ◽  
...  
Keyword(s):  
T Cell ◽  
Peripheral Blood ◽  
Univariate Analysis ◽  
Cell Depletion ◽  
Cell Transplant ◽  
Cellular Composition ◽  
T Cell Depletion ◽  
Cell Dose ◽  
Cd8 Cell

Abstract Abstract 1272 Introduction: Allogeneic hematopoietic cell transplant (HCT) remains a potentially curative modality for various hematological disorders. The cellular composition of the infused allograft has important ramifications for transplantation outcomes, for example higher infused CD34+ cell doses have previously been shown to be is associated with early engraftment, improved survival and possibly increased acute graft-versus-host disease (GVHD) following HCT. The influence of cellular composition of infused allograft on transplant outcomes has been the subject of many previous studies. There is paucity of data on the impact of cellular composition of allograft on transplant outcomes of patients undergoing HCT with in vivo T-cell depletion (TCD) compared to patients receiving T-cell replete allografts. We report here a comparative analysis of the impact of CD34+, CD3+, CD4+ and CD8+ cell doses and survival outcomes of allogeneic, peripheral blood HCT patients receiving in vivo T-cell depletion with alemtuzumab or anti thymocyte globulin (TCD group) versus patients who underwent T-cell replete HCT (non-TCD group). Methods: The study cohort includes 150 consecutive patients who underwent allogeneic HCT between January 2003 through December 2009. All patients received peripheral blood allografts from matched sibling or unrelated donors (URD). In vivo T-cell depletion consisted of alemtuzumab 40mg in two divided doses on days -4 and -1 (n=39) or Thymoglobulin at a total dose of 6 mg/kg for ablative and reduced intensity conditioning (RIC) transplants and 7.5 mg/kg total dose for non myeloablative allografts (n=51). 4 patients received Atgam at 30mg/kg on days -5, -4 and -3. Impact of CD34+, CD3+, CD4+ and CD8+ cell doses divided into two groups; >/= 50th and < 50th percentile on overall survival (OS), progression free survival (PFS) and non relapse mortality (NRM) was initially measured by univariate analysis. Multivariate logistic regression analysis was constructed for variables showing significance on univariate analysis (p<0.1). Cellular components of allografts was done by standard flow cytometric techniques. Results: Of the 150 patients, 94 (62.7%) were males. Median age was 49 (range 17–69). Baseline diagnosis included acute leukemia and myelodysplastic syndrome (n=88; 58.6%), chronic myeloid leukemia (n=19; 12.7%), non-Hodgkin lymphoma (n=27; 18%) and others (10.7%). There were 95 patients (63.3%) in the TCD group and 55 (36.7%) in the non-TCD group. The baseline characteristics of the TCD group and non-TCD group were well matched except that significantly more patients in the TCD group had high risk disease (86.3% vs. 61.8%, p = 0.0005) and received allografts from unrelated donors (62.1% vs. 29.1%, p < 0.001). Median doses of the infused cellular components in the allograft were; CD 34+ = 5.8 × 106/Kg (range 1.2 – 16), CD3+ = 30.8 × 107 (4.5 – 100.8), CD4+ = 18.6 × 107 (1.9 – 63) and CD8+ = 11.3 × 107 (0.8 – 52.4). Median follow-up time for surviving patients was 3 years. In the TCD group, multivariate analysis showed that CD34+ cell doses >/= 5.8 × 106 was associated with improved OS (p=0.0085; CI 0.28–0.83), PFS (p=0.03; CI 0.31–0.93) and NRM (p=0.02; CI 0.21–0.89). Multivariate analysis also showed that CD3+ cell dose >/= 30.8×107 improved OS (p=0.03; CI 0.25–0.92), but not PFS (p=0.14; CI 0.16–1.31) and NRM (p=0.15; CI 0.23–1.26). No association was noted between CD4+ and CD8+ cell doses and OS, PFS and NRM (p>0.05), in the TCD group. In the non-TCD group, univariate analysis of CD34+, CD3+, CD4+ and CD8+ cell doses failed to show any statistical significance for NRM, OS and PFS (p>0.1). Conclusion: Our limited, retrospective analysis of 150 peripheral blood allogeneic HCT shows improved OS, PFS and NRM in patients receiving CD34+ cell dose >/= 5.8×106/Kg and improved OS with CD3+ dose >/= 30.8×107/Kg, limited only to the TCD group. No such association was seen in the non-TCD group. We hypothesize that higher CD34+ in TCD transplants probably improved survival by rapid engraftment and by robust immune reconstitution thereby reducing infectious complication otherwise associated with TCD. Disclosures: Abraham: Genentech: Membership on an entity's Board of Directors or advisory committees. Hamadani:Celgene: Honoraria, Speakers Bureau; Otsuka: Research Funding, Speakers Bureau.

Incidence, Risk Factors and Allogeneic Stem Cell Transplant Outcomes In Chronic Sclerotic Gvhd: T-Cell Depletion Is Preventive and Peripheral Blood Stem Cellis a Risk Factor, But Not HLA-Mismatch With No Adverse Impact On Transplant Outcomes

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3293-3293
Author(s):  
Jieun Uhm ◽  
Nada Hamad ◽  
Mohamed Shanavas ◽  
Fotios V. Michelis ◽  
Vikas Gupta ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Stem Cell ◽  
T Cell ◽  
Peripheral Blood ◽  
Causes Of Death ◽  
Cell Depletion ◽  
Prognostic Impact ◽  
T Cell Depletion ◽  
Transplant Outcomes

Abstract Introduction Chronic graft versus host disease GVHD) is one of the major complications of allogeneic hematopoietic stem cell transplantation (HSCT) and is associated with significant morbidity and poor quality of life. A few studies reported the incidence of sclerotic GVHD to range between 15.5% and 52.9% among patients with chronic GVHD (cGVHD). However, the risk factors and clinical markers associated with sclerotic GVHD (SclGVHD) are yet to be identified which led us to review the incidence of and risk factors for SclGVHD at our institution. Methods and patients We retrospectively reviewed 756 patients who underwent HSCT between 2000 and 2012 at the Princess Margaret Cancer Centre, Toronto Canada. We identified patients who were diagnosed with cGVHD, re-classified this using the National Institute of Health consensus criteria (NCC) and identified those who developed SclGVHD. We evaluated HSCT outcomes including overall survival (OS), non-relapse mortality (NRM), relapse and duration of immunosuppressive therapy (IST). The Kaplan-Meier method was used for OS and the cumulative incidences of SclGVHD, cGVHD, NRM, relapse and IST cessation were calculated considering completing risks. Univariable and mulrivariable analyses were done using the Gray’s and Fine-Gray methods and EZR software. Results Of the 756 patients, 502 had cGVHD by NCC and among these 96 (19.1%) had SclGVHD. The median time to onset of SclGVHD was 540 days (range 481-577). Only 7 (7.3%) patients had SclGVHD as the first manifestation of cGVHD, while the remainig 89 (92.7%) had preceding other organ involvment. The cumulative incidence of SclGVHD was 22.6% at 5 years (95% CI 18.6-26.8). A univariable model identified 2 risk factors for SclGVHD: T-cell depletion (TCD) (4.0% in TCD vs 25.9% in non-TCD; p<0.001) and peripheral blood stem cells (PBSC) (26.5% in PBSC vs 10.2% in bone marrow, p<0.001). Acute GVHD and mismatched or unrelated donors did not increase the risk of SclGVHD in univariable analysis. Multivariate analysis confirmed that the 2 factors identified in the univariable model were independent risk factors for SclGVHD: TCD (p=0.001; HR 0.14, 95% CI, 0.05-0.46) and PBSC (p=0.001; HR 2.96, 95% CI, 1.52-5.74). OS at 7 years after HSCT was significantly better in the SclGVHD group (87.5%) than in the non-SclGVHD group (58.4%) (p<0.001). However, once the time-dependent variable of SclGVHD was taken into account, the favorable prognostic impact of SclGVHD on OS became borderline (p=0.06, HR 0.55 [95% CI 0.29-1.04]). In view of the OS results we attempted to ascertain the clinical course of SclGVHD by evaluating its impact on duration of IST and causes of death in patients who develop it. As shown in Figure 1, those with SclGVHD seem to have a longer IST duration (median 70.5 months) compared to those without SclGVHD (median 62.0 months). However, there was no difference in the rates of IST cessation at 7 years (57.4% vs 51.3%; p=0.312). The SclGVHD group showed a significantly lower NRM rate at 7 years; 6.0% vs 24.0% in the non-SclGVHD group (p<0.001). Similarly, the SclGVHD group showed a lower incidence of relapse at 7 years; 10.2% vs 19.8% in the non-SclGVHD group (p=0.01). Conclusion The incidence of SclGVHD at 5 years is significant at 22.6%. Two risk factors for SclGVHD were identified: PBSC and non-TCD. HLA-mismatch was not identified as a risk factor. SclGVHD does not appear to have an adverse effect on OS, NRM or relapse. SclGVHD was associated with longer IST duration but the IST cessation rates at 7 years were similar in the groups with and without SclGVHD. Stacked incidences IST cessation and causes of death based on the development of chronic sclerotic GVHD Disclosures: No relevant conflicts of interest to declare.

Decreased Incidence of GvHD after Reduced Intensity Conditioning and a Fixed T-CELL Dose in Hematological Malingnancy Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5889-5889 ◽  
Author(s):  
Audrey Simon ◽  
Eddy Roosnek ◽  
Yordanka Tirefort ◽  
Yan Beauverd ◽  
Carole Dantin ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Disease Risk ◽  
Risk Index ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Cell Depletion ◽  
Unrelated Donor ◽  
T Cell Depletion ◽  
Two Factors

Abstract Introduction: To decrease graft versus host disease (GvHD), the Geneva transplantation team has performed allogeneic hematopoietic stem cell (alloHSCT) with reduced intensity conditioning (RIC) and T cell depletion (TCD) to treat hematological malignancies for older or non fit for myeloablative conditioning patients. This is a new approach of engineering stem cell products that lowers the risk of GvHD while preserving graft versus leukemia (GvL) as much as possible. Patient and methods: We report a retrospective study of 73 patients who received alloHSCT with RIC and TCD between 2001-2013. The median age was 59 years (21-70), 60% were male. Disease at transplant time was acute leukaemia for 45%, Hodgkin lymphoma and non-Hodgkin lymphoma for 24%, myelodysplastic disorders for 13%, myeloproliferative disorders for 9,3 % and multiple myeloma for 8%. Source of stem cell was peripheral in 96% of the cases. 41% of the donors were matched related donor, 37% matched unrelated donor, 19% mismatched unrelated donor and 3% mistmatched related donor. The conditioning regimen consisted on fludarabine with busulfan or melphalan and ATG. Extensive T-cell depletion was done using Campath in the bag followed by washing procedures to remove free antibody. Fixed number of CD3+ T-cell addback was given on d+1 to preserve GvL with minimal residual disease (MRD) assessment and early donor lymphocyte infusions (DLI) given if MRD positive. Doses of DLI were preserved and frozen at the time of stem cell harvest. GvHD prophylaxis was with ciclosporine and mycophenolate mofetil. Results: With a median follow up of 5 (0.5-11) years, the 5-year overall survival (OS), disease free survival (DFS), current disease free survival, relapse rate and non relapse mortality (NRM) were 41.7% (95%CI 30.7-53.7%), 38.8% (95%CI 28.8-50.8%), 39,5% (95%CI 27.7-51.7%), 45.3% (95%CI 32.7-57.2%) and 15.8% (95%CI 8.3-25.4%) respectively. The main cause of death was relapse 38.7 % followed by GvHD 17% and infection 1.3%. In this cohort, the cumulative incidence (CI) of acute GvHD was 15.1% (95% CI: 8.0-24.3%) as well as for acute GvHD grade II-IV. CI of chronic GvHD was 14.7% (95%CI:7.2-23.6%) with extensive chronic GvHD CI being 5.9% (95% CI: 1.9-13.4%). Five patients received DLI for relapses, 27 for mixed chimerism and 8 for both causes. The average number of DLI was 2. Twenty-eight patients entered CR, 4 PR and 13 did not respond to DLI. In univariate analysis, two factors GvHD before DLI and GvHD after first DLI have a tendency for favorable impact on OS respectively p=0.093 and 0.071. For DFS, two factors are significant: disease risk index and GvHD after first DLI respectively p=0.013 and 0.044. For NRM disease risk index is the only factor which is statistically significant p=0.005. For relapse no factors were significant. Discussion: Our study showed a lower rate of acute and chronic GvHD as compared to other studies with unmanipulated stem cells. However, we describe a high rate of relapse incidence and relapse mortality. We have found in univariate analysis two factors statistically significant for DFS GvHD before and after first DLI. Our cohort is a heterogeneous group with different diseases at different stages, which can explain those results. It’s a monocentric study and small number of patient can be a limit for this work. Of note, since 2009 we have changed our strategy introducing a day +100 preemptive DLI infusion in the absence of GvHD, with escalading doses of lymphocytes every 8 weeks up to 5x 107 CD3/kg in the absence of GvHD to improve response. We don’t have enough patients and follow up to draw any conclusion regarding this new strategy. To improve the outcomes, the selection of patients who may receive partial T-cell depletion should be refined, avoiding transplanting patients with high risk of relapse with this strategy. To help decision making, the revised disease risk index as presented by Armand et al. (Blood 2014;123:3664) may be useful. Disclosures No relevant conflicts of interest to declare.

Impact of Donor-Recipient Histocompatibility and CMV-Mismatch on Outcome of Allogeneic Stem Cell Transplantation for AML and MDS: A Retrospective Registry Study of the German Stem Cell Transplant Registry (DRST) of the German Working Group for Blood and Marrow Transplantation (DAG-KBT)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2304-2304 ◽  
Author(s):  
Francis A. Ayuk ◽  
Dietrich W. Beelen ◽  
Martin Bornhäuser ◽  
Matthias Stelljes ◽  
Tajana Zabelina ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Research Funding ◽  
Cox Regression ◽  
Negative Impact ◽  
Cell Depletion ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
T Cell Depletion ◽  
Cox Regression Analysis

Abstract Introduction Allogeneic stem cell transplantation (allo-SCT) is a curative treatment for several hematological diseases. Donor-recipient histo-incompatibility is associated with poorer outcome. Transplant outcome of CMV positive patients is reported to be poorer, if the unrelated donor is CMV negative (CMV-mismatch). Recent developments in transplant strategies including high resolution HLA-typing, toxicity-reduced conditioning regimens, CMV-monitoring, and improved supportive care have made transplants from HLA- as well as CMV- mismatched unrelated donors more feasible. We present a retrospective registry analysis from a large, and recent cohort of patients transplanted under these conditions. Patients and methods: We report data from adult recipients of allo-SCT treated between 2005 and 2013 in 10 transplant centers across Germany. Inclusion criteria were: 1.) consecutive patients from each center with AML or MDS as reported to the German Stem Cell Transplant Registry (DRST), 2) age >/= 18 years, 3) availability of high-resolution typing for HLA-A, -B, C, DRB1 and DQB1 in case of unrelated donor. Patients with ex-vivo T cell depletion were excluded. 3215 patients with AML (n = 2648) or MDS (n = 567) were included in the study. Donors were matched related (MRD, n =872), matched unrelated (MUD, n = 1553) or mismatched unrelated (9/10 MMUD, n= 620; 8/10 MMUD n = 137; <8/10 MMUD n = 33). Remission status at transplant was CR (49%), not in CR (40%) or untreated (11%). The vast majority of patients (96%) received peripheral blood stem cell grafts. Conditioning was reduced intensity (51%) or myeloablative (49%) according to EBMT criteria. ATG (56%) or alemtuzumab (8%) were used for in vivo T cell depletion. Median patient age was 56 (18-79) years. Median donor age was 38 (12-80) years. Median follow-up was 54 months (34-81 months). Primary endpoint was overall survival (OS) at 3 years. Results: Kaplan-Meier estimates for OS at 3 years was similar after transplants from MRD = 55% (95%CI 51-59%) compared to MUD = 53% (95%CI 51-59%), p = 0.26. OS at 3 years was worse for 9/10 MMUD with 45% (95% CI 41-49%, p<0.001), for 8/10 MMUD with 35% (95% CI: 27%-43%, p < 0.001) and for <8/10 MMUD with 29% (95% CI 13%-45%, p = 0.005) (figure 1). In recipients of unrelated donor transplants, multivariate cox regression analysis revealed significant negative impact of increasing patient age, increasing donor age, sex-mismatch (male patient/female donor), CMV-mismatch (patient pos/ donor neg), diagnosis of AML or sAML compared to MDS, lack of complete remission at transplant, abnormal cytogenetics and HLA-mismatching (table 1a). In a subgroup analysis restricted to patients transplanted from unrelated donors after myeloablative conditioning and T cell depletion, 3 years OS was better after 10/10 MUD: 60% (55-65%) compared to 9/10 MMUD: 49% (41-57%), p = 0.02. This was also true after reduced intensity conditioning and T cell depletion with ATG, with 3 year OS after 10/10 MUD: 49% (45-53) compared to 9/10 MMUD: 37% (31-43%), p = 0.001. Excluding HLA-DQB1-mismatches and HLA-C0303/0304-mismatches from the 9/10 MMUD group did not significantly alter results. Acknowledging the negative impact of both HLA and CMV-mismatching, we sought to determine which of these two parameters is of higher relevance for donor selection. For this purpose subgroup analyses were performed including only CMV-positive patients who received transplants from an unrelated donor (10/10 MUD or 9/10 MMUD). HLA-DQB1-mismatches and HLA-C0303/0304-mismatches were excluded. For this subgroup of n = 1167 patients multivariate cox regression analysis revealed better outcome after 10/10 MUD from CMV neg. donors compared to 9/10 MMUD from a CMV pos. donors (RR: 1.31, p = 0.04, table 1b and figure 2). Restricting the analysis only to patients who received T cell depletion with ATG did not significantly alter these findings. Conclusions: In this large multicenter cohort of recently transplanted patients, we find similar survival outcomes for matched related and fully matched unrelated donor transplants. We confirm the negative impact of HLA-mismatching on survival outcome, irrespective of conditioning intensity. Our results show that though CMV-mismatching is associated with poorer outcome, its relevance is secondary to HLA-mismatching. Acknowledgments: This work was supported by a research grant of the DKMS-Stiftung to FA and WB. Disclosures Stelljes: Pfizer: Consultancy. Kobbe:Jansen: Honoraria, Other: travel support; Celgene: Honoraria, Other: travel support, Research Funding. Kröger:Sanofi: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.

BK Virus-Associated Hemorrhagic Cystitis Following Allogeneic Hematopoietic Stem Cell Transplantation; Incidence and Risk Factors

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5759-5759
Author(s):  
Feras Alfraih ◽  
Amjad Alhussaini ◽  
Farhan Anjum ◽  
Ghuzayel Mubarak Aldawsari ◽  
Fahad Alsharif ◽  
...  
Keyword(s):  
Risk Factors ◽  
T Cell ◽  
Acute Gvhd ◽  
Hemorrhagic Cystitis ◽  
Conditioning Regimen ◽  
Bk Virus ◽  
Cell Depletion ◽  
T Cell Depletion ◽  
Factors Associated ◽  
Gvhd Prophylaxis

Abstract Introduction : Hemorrhagic cystitis (HC) is one of common complications after allogeneic hematopoietic SCT (HSCT) with reported incidence varying from 7 to 70%. Several reports have shown that BK is strongly associated with HC (BK-HC) following HSCT. We conducted an institutional retrospective study to analyze the incidence and clinical factors associated with BK-HC following HSCT. Methods : A total of 517 consecutive patients above the age of 14 years receiving HSCT from 2009 and June 2015 were included in this retrospective analysis and evaluated for HC and urinary BK. HC was defined as documented hematuria of any grade and BK viruria was defined as positive at any level by BKV quantitative PCR testing in urine. Patients were stratified, based on hematuria and urinary BK virus, into the following groups (a) BK virus positive hemorrhagic cystitis (BK+HC), (b) BK virus negative hemorrhagic cystitis (BK-HC) and (c) Non-hemorrhagic cystitis (HC-). Screening for microscopic hematuria was performed only for patients with any kind of urinary symptoms. Results: 479 patients (92.6%) were matched related donor and 308 (60%) were male with a median age of 24 (range 14 to 66). Diagnoses were AML for 195 (38%), ALL for 183 (35%) and bone marrow failure for 44 (8.5%). Conditioning regimen was cyclophosphamide based in 427 (82.6%) patients (97%) versus others in 90 (17.4%) patients. GVHD prophylaxis was CSA/MTX for 456 (88.4%) however, T cell depletion was used in 13%. Peripheral blood stem cells were used for 56% of patients. With a median follow-up of 60 months for survivors (range 2 to 116.5 months), 43 (8%) patients showed BK+HC, 264 (51%) BK- HC while 209 (41%) did not have any hematuria (HC- group). Median time from transplantation to BK+ HC was 67 days (range 7 to 1261 days). Univariate analysis for risk factors of BK+ HC showed male, use of T-cell depletion and AML diagnosis were statistically significant factors. Other factors like age, conditioning regimen, GVHD prophylaxis, stem cell source, mismatched and remission status were not statistically significant. BK+ HC group was associated with higher incidence of other infections like CMV viremia (p=0.01) and fungal infection (p<0.01). Incidence of acute GVHD was 62.8% in BK+ HC group, 43% in HC- BK and 33.3% in HC- group (p=<0.01), suggesting higher incidence of acute GVHD in BK+ HC group. There was no difference in incidence of chronic GVHD. Conclusion: Hematuria following allogeneic bone marrow transplantation occurs in almost half of patients (51%) while BK associated HC develops in 8% of patients. Factors associated with BK+ HC were male gender, use of T-cell depletion and AML diagnosis. BK+HC is usually associated with other infections like CMV viremia and fungal infections. Further studies are needed to minimize or prevent BK+ HC following HSCT especially in high risk group. Disclosures No relevant conflicts of interest to declare.

scholarly journals Classification of Donor KIR-Genotype Information to Predict Outcome after Unrelated Hematopoietic Stell Cell Transplantation: The Jury Is Still out

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2162-2162
Author(s):  
Johannes Schetelig ◽  
Henning Baldauf ◽  
Carolin Massalski ◽  
Sandra Frank ◽  
Jürgen Sauter ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Cell Transplantation ◽  
Research Funding ◽  
Nk Cell ◽  
Disease Risk ◽  
Cell Depletion ◽  
Unrelated Donor ◽  
T Cell Depletion ◽  
Travel Grant

Abstract Introduction: A series of studies suggest that harnessing natural killer (NK) cell reactivity by killer cell immunoglobulin-like receptor (KIR) genotype based unrelated donor selection could further improve outcome after allogeneic hematopoietic cell transplantation (alloHCT). A Receptor-Ligand model has been proposed for donor selection which aims at augmenting NK cell activation while minimizing inhibition. Information on education of KIR2DS1-positive NK cells (Venstrom et al, NEJM 2012) and the predicted Receptor-Ligand interaction of KIR3DL1-positive NK cells is utilized for this algorithm. By combining this information donors can be classified as KIR-advantageous or disadvantageous. Patients with donors, characterized by activating KIR2DS1 and weak/non-inhibiting KIR3DL1, experienced less relapse and improved survival compared to patients with donors, characterized by lacking an activating KIR2DS1 but presence of strong-inhibiting KIR3DL1. This study aimed at validating this predictor in an independent cohort of patients. Methods: Donor samples were retrieved from the Collaborative Biobank (Dresden, Germany) and mapped to patient outcome data extracted from the German Registry for Stem Cell transplantation. KIR typing was performed using a high resolution amplicon-based next generation sequencing method. KIR typing at the allele level was based on sequencing of exons 3, 4, 5, 7, 8, and 9. The patient population was restricted to patients with AML or MDS. Donor and patient mapping was cross-checked by HLA-typing of the donor sample. The impact of the predictor on overall survival was tested in a Cox regression model adjusted for patient age, a modified disease risk index, performance status, donor age, HLA-match, sex match, CMV match, conditioning intensity, type of T-cell depletion and graft type. Results: Clinical data from 2314 patients were analyzed. The median age at alloHCT was 59.4 years (range, 18.1 to 79.6 years). The indication for alloHCT was AML for 80% of patients and MDS for 20% of patients. Disease risk was assessed as low, intermediate, high or very high in 1%, 52%, 42%, and 5%, respectively. Patient and donor were 10/10 matched in 78% of pairs, whereas a one locus mismatch was reported for 21% of pairs. Myeloablative, reduced-intensity and non-myeloablative conditioning regimens were used in 29%, 67%, and 4% of patients, respectively. ATG was administered in 77% and alemtuzumab in 3% of patients. Twenty percent of patients received no T-cell depletion. In total, 535 patients experienced relapse and 945 patients died. This number of events translated into a power of the confirmatory analysis for the predictor of KIR2DS1 and KIR3DL1 of 67%. Two-year overall and event-free survival for the whole cohort was 51% (95%-CI 48% to 53%) and 44% (95%-CI 42% to 47%) and the 2-year incidence of relapse and non-relapse mortality was 28% (95%-CI 26% to 30%) for both endpoints. In univariate analysis, overall survival (54% versus 56%) and the cumulative incidence of relapse of patients with a KIR-advantageous donor were comparable to patients with KIR-disadvantageous donors. The adjusted hazard ratio from the multivariable Cox regression model for the comparison of patients with KIR-advantageous versus KIR-disadvantageous donors was 0.99 (Wald-test, p=0.95) for overall survival and 1.12 (Wald-test, p=0.41) for relapse incidence. When evaluated separately, the two components of the predictor (degree of inhibition by KIR3DL1 & presence of activating KIR2DS1) did not have an impact on overall survival or the incidence of relapse (see Figure). Also, evaluation of the combined predictor in subsets of patients by disease, type of T-cell depletion and HLA-compatibility did not allow prediction of these outcomes. Conclusions: Relapse incidence and overall survival after unrelated donor alloHCT could not be predicted using information on activating KIR2DS1 and inhibiting KIR3DL1 donor genes in an independent cohort of predominantly Caucasian patients. The predictor had been developed in a cohort of patients with AML who were younger and predominantly had received myeloablative conditioning based on total-body irradiation, ATG was administered less often, but donors often were only partially HLA-compatible. The different outcome in the current analysis thus points at potential interactions between NK-cell mediated allo-reactivity and procedural variations of alloHCT. Figure Figure. Disclosures Schetelig: Sanofi: Consultancy, Research Funding; Janssen: Consultancy, Honoraria; Roche: Honoraria; Abbvie: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding. Stelljes:Novartis: Honoraria; MSD: Consultancy; Pfizer: Consultancy, Honoraria, Research Funding; JAZZ: Honoraria; Amgen: Honoraria. Ayuk:Therakos (Mallinckrodt): Honoraria; Novartis: Honoraria; Celgene: Consultancy; Gilead: Consultancy. Bethge:Neovii GmbH: Honoraria, Research Funding; Miltenyi Biotec GmbH: Consultancy, Honoraria, Research Funding. Bug:Neovii: Other: Travel Grant; Novartis Pharma: Honoraria, Research Funding; Janssen: Other: Travel Grant; Celgene: Honoraria; Amgen: Honoraria; Astellas Pharma: Other: Travel Grant; Jazz Pharmaceuticals: Other: Travel Grant. Kobbe:Roche: Honoraria, Research Funding; Celgene: Honoraria, Other: Travel Support, Research Funding; Amgen: Honoraria, Research Funding. Beelen:Medac: Consultancy, Other: Travel Support. Fleischhauer:GENDX: Research Funding.

scholarly journals Analysis of risk factors for the development of GVHD after T cell-depleted allogeneic BMT: Effect of HLA disparity, ABO incompatibility, and method of T-cell depletion

2001 ◽  
Vol 7 (11) ◽  
pp. 620-630 ◽  
Author(s):  
Carolyn A Keever-Taylor ◽  
Christopher Bredeson ◽  
Fausto R Loberiza ◽  
James T Casper ◽  
Colleen Lawton ◽  
...  
Keyword(s):  
Risk Factors ◽  
T Cell ◽  
Cell Depletion ◽  
T Cell Depletion ◽  
Allogeneic Bmt ◽  
Abo Incompatibility

scholarly journals Impact of Donor-Derived CD34+ Infused Cell Dose on Outcomes of Patients Undergoing Allo-HCT Following Reduced Intensity Regimen for Myelofibrosis:a Study from the Chronic Malignancies Working Party of the EBMT

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3338-3338
Author(s):  
Tomasz Czerw ◽  
Vittoria Malpassuti ◽  
Simona Iacobelli ◽  
Linda Koster ◽  
Nicolaus Kröger ◽  
...  
Keyword(s):  
T Cell ◽  
Research Funding ◽  
Independent Predictor ◽  
Cell Depletion ◽  
Study Group ◽  
T Cell Depletion ◽  
Cd34 Cells ◽  
Donor Type ◽  
Higher Doses

Introduction: Cellular composition of grafts is believed to be one of the significant determinants of outcomes of reduced-intensity conditioning (RIC) allogenic hematopoietic cell transplantation (allo-HCT). However, inconsistent results of the influence of CD34+ cells dose on the incidence of graft-versus-host disease (GVHD), disease control and survival have been reported in studies published thus far. Allo-HCT remains the only potentially curative treatment modality for eligible patients with myelofibrosis (MF). As patients with this diagnosis were underrepresented or not included in the above mentioned analyses, this EBMT registry study aimed to determine impact of CD34+ cell counts on allo-HCT results in this population. Methods: Six hundred and fifty seven patients with primary or secondary MF transplanted with use of peripheral blood (PB) as a source of stem cells after RIC regimen (Fludarabine/Melphalan, N=536 (82%); Fludarabine/Busulphan, N=121 (18%)) between 2000 and 2016 were included. Stem cell donor type was HLA-identical sibling (MSD; N=249, 38%) or unrelated (UD; N=408, 62%). Use of ex vivo T-cell depletion and post-transplant cyclophosphamide to prevent GVHD were the exclusion criteria. Median patient age was 58 (range, 22-76) years. In-vivo T-cell depletion was used in 526 (80%) of cases. Median transplanted CD34+ dose was 6.6 (2-29) x 10^6 per kg of recipient body weight. Median follow-up was 46 (2-194) months. Patient and transplant characteristics are summarized in Table 1. Results: We did not observe any impact of CD34+ cells dose on outcome variables in the whole study group. However, in an analysis adjusted for donor type, among patients transplanted from a MSD, the 2yr overall survival (OS) probability was 77% for those transplanted with higher doses of CD34+ cells (defined as >7.0 x 10^6/kg) compared to 60% for lower CD34+ counts (below 7.0 x 10^6/kg), P=0.007 (Figure 1). The corresponding probabilities of 2yr non-relapse mortality (NRM) were 16% and 29% (P=0.04), respectively (Figure 2). In multivariate analysis, for patients transplanted from a MSD, higher CD34+ dose was an independent predictor for better survival (HR 0.56; P=0.01) and lower risk of NRM (HR 0.54; P=0.02). We did not find any association between CD34+ counts with probability of engraftment, the incidence of acute (aGVHD) and chronic (cGVHD) nor disease relapse. The effect of cell dose was not seen in the UD cohort. Factors associated independently with an unfavorable outcome in the whole study group were: older patient age and transplantation from CMV seronegative donors to seropositive recipients for OS and NRM and use of an UD and female donor for NRM. Allo-HCT from UD was also an independent predictor for higher incidence of aGVHD and lower probability of engraftment. Use of in vivo T-cell depletion was a protective factor for aGVHD. It was in turn associated with higher risk of relapse. Conclusions: Our analysis suggests a potential survival benefit for MF patients treated with RIC PB-allo-HCT from MSD with higher doses of CD34+ cells (threshold > 7.0 x 10^6/kg). We suggest that this factor should be taken into consideration when planning and performing hematopoietic cell apheresis. Disclosures Kröger: Celgene: Honoraria, Research Funding; DKMS: Research Funding; JAZZ: Honoraria; Medac: Honoraria; Neovii: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Riemser: Research Funding; Sanofi-Aventis: Research Funding. Robin:Novartis Neovii: Research Funding. Chevallier:Daiichi Sankyo: Honoraria; Jazz Pharmaceuticals: Honoraria; Incyte: Consultancy, Honoraria. Mielke:Bellicum: Consultancy, Honoraria, Other: Travel (via institution); EBMT/EHA: Other: Travel support; Miltenyi: Consultancy, Honoraria, Other: Travel and speakers fee (via institution), Speakers Bureau; IACH: Other: Travel support; Jazz Pharma: Honoraria, Other: Travel support, Speakers Bureau; ISCT: Other: Travel support; GILEAD: Consultancy, Honoraria, Other: travel (via institution), Speakers Bureau; Celgene: Honoraria, Other: Travel support (via institution), Speakers Bureau; DGHO: Other: Travel support; Kiadis Pharma: Consultancy, Honoraria, Other: Travel support (via institution), Speakers Bureau. Snowden:Janssen: Honoraria; Mallinckrodt: Honoraria; Kiadis: Membership on an entity's Board of Directors or advisory committees; IDMC: Honoraria; Jazz: Honoraria; Gilead: Honoraria. Blaise:Sanofi: Honoraria; Pierre Fabre medicaments: Honoraria; Molmed: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria. Hernandez Boluda:Incyte: Other: Travel expenses paid. McLornan:Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Novartis: Honoraria.

scholarly journals Haploidentical Allogeneic Stem Cell Transplantation in Sickle Cell Disease: A Systematic Review and Meta-Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 424-424
Author(s):  
Mesire Aydin ◽  
Elisabeth Dovern ◽  
Mariska M.G. Leeflang ◽  
Josu de la Fuente ◽  
Adetola A. Kassim ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Research Funding ◽  
Graft Failure ◽  
Meta Analysis ◽  
Cell Depletion ◽  
T Cell Depletion ◽  
Related Mortality

Abstract Background Allogeneic hematopoietic stem cell transplantation (SCT) is the only established curative treatment option for patients with sickle cell disease (SCD). Transplantations with an HLA-identical matched sibling donor (MSD) have resulted in excellent disease-free survival of &gt;90% and overall survival (OS) of &gt;95%. However, lack of HLA-identical siblings is a limiting factor. The chance of finding a potential matched unrelated donor is low for patients with a non-Western ethnic background (&lt; 20%). Haploidentical related donors are a promising pool of donors potentially extending SCT as a curative treatment to a larger group of SCD patients with no other meaningful treatment options. Myeloablative conditioning regimens (MAC) are not recommended for adult SCD patients, as cumulative SCD-related organ damage renders these patients susceptible to increased toxicity and higher risk of transplant-related mortality. Using reduced-intensity conditioning (RIC) or non-myeloablative conditioning (NMC) in both adult and pediatric patients has resulted in decreased transplant-related toxicity and mortality. However, while successful in hematologic malignancies, NMC has been associated with significant risk of graft failure in hemoglobinopathies. In the present study, we aimed to systematically review (1) the outcomes of haploidentical SCT (Haplo-SCT), (2) the effects of conditioning intensity and modes of T-cell depletion on Haplo-SCT outcomes and (3) comparative outcomes between matched sibling donor SCT (MSD-SCT) and Haplo-SCT in selected studies. Methods A comprehensive search was performed in MEDLINE/PubMed and Embase up to May 2021. Data was extracted by two reviewers independently and the Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of the studies. Only studies reporting at least one of the outcomes: graft failure, OS, transplant-related mortality, and acute/chronic graft-versus-host disease (GvHD) were included. Fourteen studies met the inclusion criteria. To have an overview of the results of Haplo-SCT, we divided the included studies in four groups according to the conditioning intensity (MAC versus NMC/RIC) and the T-cell depletion method (in vivo (post-transplant cyclophosphamide (PTCy)) vs. in vitro). Results All included studies were observational cohort studies. A subgroup meta-analysis of the results of Haplo-SCT showed relatively low overall pooled proportions of graft failure (7%, 95% CI: 2 - 20), acute (4%, 95% CI: 2 - 12) and chronic (11%, 95% CI: 7 - 16) GvHD. Overall survival was high (91%, 95% CI: 85 - 94). Graft failure in MAC-in vitro, MAC-in vivo, NMC/RIC-in vitro and NMC/RIC-in vivo groups was 4% (95% CI: 1 - 14), 0% (95% CI: 0 - 100), 25% (95% CI: 10 - 51) and 11% (95% CI: 3 - 36) respectively (Figure 1). OS was 100% and 93% for MAC and NMC/RIC groups with PTCy (in vivo T-cell depletion) respectively. In patients with in vitro T-cell depletion, OS was 87% and 81% in MAC and NMC/RIC groups respectively (Figure 2). Based on a comparative meta-analysis of the three studies that included both haploidentical and MSD transplantation, graft failure was significantly higher in the haploidentical group than in the MSD group (odds ratio 5.3, 95% CI: 1.0 - 27.6). Overall survival, transplant-related mortality and acute/chronic GvHD were not significantly different between the groups. Conclusions This systematic review shows that modifications in the intensity of the conditioning regimen and improved T-cell depletion approaches in Haplo-SCT in SCD have led to reduced transplantation-related toxicity while keeping graft failure rates low. Both in vitro and in vivo (PTCy) T-cell depletions result in very low transplantation-related mortality, though in vitro T-cell depletion is associated with a higher incidence of viral reactivations and other infectious complications. Haploidentical stem cell transplantation is becoming a viable alternative curative option for SCD, extending the availability of allogeneic SCT as a treatment option to many more transplant eligible SCD patients. Novel immunosuppression (immunoablation) and improvement in supportive care have allowed the use of RIC or NMC regimens, resulting in low risk of transplantation-related complications and improvement in engraftment rates. Figure 1 Figure 1. Disclosures Biemond: Global Blood Therapeutics: Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; CSL Behring: Honoraria; Sanquin: Research Funding; Novo Nordisk: Honoraria; Celgene: Honoraria. Nur: Celgene: Speakers Bureau; Roche: Speakers Bureau; Novartis: Research Funding, Speakers Bureau.

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