Haploidentical Recipients Research Articles

Immunosuppression-Free Status at 1 Year after Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide

The development of chronic graft-versus-host disease (GVHD) in 1-year survivors after matched related or unrelated hematopoietic cell transplantation was shown to be associated with higher nonrelapse mortality (NRM) and worse overall survival (OS). The impact of chronic GVHD requiring immunosuppression (IS) for recipients of haploidentical transplantation (HIDT) with post-transplantation cyclophosphamide (PTCy) who have survived to 1 year post-transplantation has not been studied previously and was investigated for this analysis. A total of 322 adult patients who underwent HIDT at our center were included in this study. The effect of IS-free status on post-transplantation outcomes was assessed. The median follow-up for survivors was 63.9 months (range, 18.3 to 165 months). A total of 163 patients (65%) were IS-free at 1 year post-HIDT. Baseline characteristics of this group were similar to those of patients still requiring IS, except for higher percentages of female donor-male recipient pairs (28% versus 15%; P =.03) and female donors (48% versus 30%; P =.008). Logistic regression to identify patients more likely to be on IS at 1 year post-HIDT identified the use of a female donor as a significant risk factor (odds ratio, 2.11; P = .009). In a Cox regression analysis, patients requiring IS at 1 year post-transplantation had higher NRM (hazard ratio [HR], 4.18; 95% confidence interval [CI], 1.80 to 6.72; P < .001) and showed a trend toward worse disease-free survival (DFS) (HR, 1.59; 95% CI, .95 to 2.66; P =.08), with no impact on OS (HR, 1.44; 95% CI, .90 to 2.31; P = .13) or relapse (HR, .77; 95% CI, .37 to 1.61; P = .49). These results indicate that use of a female donor is a significant risk factor for requiring IS at 1 year post-HIDT. Additionally, chronic GVHD requiring IS at 1-year post-HIDT no significant effect on relapse but is associated with higher NRM and a trend toward worse DFS.

Graft-versus-host disease after an outpatient peripheral blood hematopoietic cell transplant using reduced-intensity conditioning: a single-center LATAM experience

ABSTRACT Background HLA compatibility predicts allogeneic hematopoietic cell transplant (allo-HCT) and graft-versus-host disease (GvHD) outcomes. There is insufficient information regarding GvHD outcomes for outpatient HLA-identical and haploidentical-HCT employing reduced-intensity conditioning (RIC). Research design and methods We compare GvHD outcomes between donor types and report risk factors associated with GvHD. Stem cell source was T-cell replete peripheral blood. GvHD prophylaxis was post-transplant cyclophosphamide (PT-CY), mycophenolic acid, and calcineurin inhibitors for haploidentical (n = 107) and oral cyclosporine (CsA) plus methotrexate i.v. for HLA-identical (n = 89) recipients. Results One hundred and ninety-six HCT transplant patients were included. aGvHD and cGvHD frequency were similar between HCT types. aGvHD severity was comparable, but severe cGvHD was less frequent in the haploidentical group (p = .011). One-hundred-day cumulative incidence (CI) of aGvHD for haploidentical and HLA-identical was 31% and 33% (p = .84); 2-year CI of cGvHD was 32% and 38% (p = .6), respectively. Haploidentical recipients had less steroid-refractory cGvHD (p = .043). Patients with cGvHD had less 2-year relapse (p = .003); both aGvHD and cGvHD conferred higher OS (p = .010 and p = .001), respectively. Male sex was protective for steroid-refractory cGvHD (p = .028). Conclusions Acute and chronic GvHD rates were comparable between HLA-identical and haploidentical transplant groups. cGvHD severity was lower in the haploidentical group.

Clinically Significant CMV Infection in Allogeneic Stem-Cell Transplant Recipients: A Single Center Experience

Introduction: Cytomegalovirus (CMV) infection is one of the major causes of concern in allogeneic stem cell transplantation (allo-HSCT). Here we report the clinically significant CMV infections among allo-HSCT recipients at the National Center for Cancer Care and Research (NCCCR) in Qatar. Methods: A retrospective review of the electronic health records of all malignant hematology patients who underwent allo-HSCT at NCCCR was performed from September 2017 to December 2022. Results: Fifty-one malignant hematology patients have been transplanted during the data collection period. Patient characteristics are summarized in Table 1. The median age was 34 years (range 14-53 years). CMV-serostatus was positive in fifty recipients (98%) and all donors. Thirty-two patients (62.7%) have received matched-related grafts. The most frequent indication for HSCT was acute myeloid leukemia, followed by acute lymphoblastic leukemia. Forty-six patients (92%) underwent myeloablative conditioning therapy. Graft-versus-host disease (GvHD) prophylaxis used in the non-haploidentical group was cyclosporine and short-course methotrexate while haploidentical recipients received cyclosporine, mycophenolate mofetil, and post-transplant cyclophosphamide. Letermovir prophylaxis was accessible for use for high-risk patients from February 2022. CMV-PCR was monitored twice per week for all patients until day +100. The clinically significant CMV infection rate was 51%. The cumulative incidence of CMV infection in haploidentical and non-haploidentical groups was 70% and 30%, respectively (figure 1). The median CMV-PCR viral load was 1783.5 IU/mL (range 133- 9600 IU/mL), with the earliest CMV reactivation on day -1 of transplantation. The clinically significant CMV infection incidence was significantly higher in patients who did not receive letermovir prophylaxis. Preemptive antiviral therapy was initiated to prevent CMV disease in all indicated recipients. Foscarnet was the preferred first-line pre-emptive treatment option for patients during cytopenia. No CMV disease or CMV-related mortality occurred in our population. Conclusion: This is the first report from Qatar to report CMV infection post-allogeneic stem cell transplantation. Future in-depth analysis of our population and treatment responses is needed.

Outcomes of blood and marrow transplantation in children less than 2-years of age

Allogeneic hematopoietic cell transplantation (Allo-HCT) is a curative option for children with various malignant and non-malignant diseases. Most reports studied all age groups amongst children. Herein we analyzed our data in children transplanted at or less than 2-years of age. We reviewed medical charts of 618 patients who underwent 666 transplantation at our center between 1993 and 2015. There were 340 boys and 278 girls. Median age was 0.7 years (range 0.04-2). Stem cell source was bone marrow (BM) in 492 (73.9%), unrelated umbilical cord blood (UCB) in 161 (24.2%) followed by peripheral blood stem cell (PBSC) in 13 (2%) patients. Matched siblings were the most common donors (n=356, 53.5%), followed by unrelated (n=161, 24.2%) with haploidentical family member donors in 29 (4.4%) transplants. Disease groups were categorized as benign hematology (Thalassemia, Fanconi, Aplastic anemia etc.), benign neoplasm (Langerhans cell histiocytosis, Hemophagocytic Lymphohistiocytosis etc.), non-neoplasms (metabolic disorders, immunodeficiency disorders etc.) and Leukemia/lymphomas (myeloid and lymphoid malignancies etc.). Cumulative incidence of acute GvHD (I-IV) was 31.5% (n=210) and grade III-IV GvHD was 8.7% (n=58). At median follow-up of 115.1 months, the cumulative probability of overall survival (OS) at 5 years was 70.0%±1.9%. Our mortality rate was 31.2% (n=193). The five-year OS was significantly better in patients transplanted for benign hematological disorders (P=.001). Patients transplanted using BM/PBSC as source of stem cells fared significantly better compared to those in which CB was used (P<.001). Post-transplant graft failure remains the leading cause requiring further transplants in this age group. In conclusion, the cumulative probability of OS at 5 years was about 70.0% for all with an OS of 61% in our haploidentical recipients. Analyzing our institutional data over time has enabled us to develop tentative strategies to minimize transplant related toxicities in very young children who are candidates for allo-HCT.

Selecting the Best Transplant Donor (HLA-Matched vs. Haploidentical) for Patients with Lymphoid Malignancy Based on Recipient HLA-B-Leader Genotype

Choosing the best donor type for allogeneic transplant (HLA-matched related (MRD) or unrelated (MUD) vs. haploidentical (HAPLO)) is typically based on the timely availability of an HLA-matched donor. There is currently no role for either patient or disease characteristics to facilitate this decision. In the context of HAPLO transplant, our group has previously demonstrated that an M+ recipient HLA-B-leader genotype (either M/T or M/M) is associated with reduced relapse risk and superior survival in patients with lymphoid, but not myeloid, malignancies (Solomon et al. TCT journal 2022). Based on this finding, we hypothesized that recipient HLA-B-leader genotype may be important in donor selection. To this end, we analyzed 352 patients with lymphoid malignancies (ALL[ 166], NHL [111], HL [39] and CLL [36]) receiving a first allogeneic transplant from an MRD [110], MUD [104] or HAPLO [138] donor. GVHD prophylaxis was PTCy-based in all HAPLO recipients, in contrast to MRD and MUD recipients who received conventional prophylaxis with calcineurin inhibitor + methotrexate. M+ or M- (T/T) genotype was seen in 165 (47%) and 187 (53%) respectively. Compared to MUD and MRD, HAPLO recipients tended to be younger (median 46 vs. 49 and 51 years respectively) and less likely to be non-Hispanic white (46% vs. 90% and 71% respectively). There were no differences in baseline characteristics between patients with M+ and M- B-leader genotype. Overall, MRD, MUD and HAPLO recipients had similar overall survival (OS, see figure). In HAPLO recipients, those with an M+ HLA-B-leader demonstrated improved 5-yr OS and DFS when compared to M- recipients (81% vs. 49%, p<0.001 and 70% vs. 42%, p=0.001, respectively), due to decreased relapse risk (18% vs. 48%, p=0.002). In multivariable analysis (MVA), controlling for other relevant variables (e.g. age, race, DRI, conditioning intensity, transplant year), M+ HAPLO transplant recipients had decreased relapsed risk (HR 0.27, p<0.001) leading to improved DFS (HR 0.34, p<0.001) and OS (HR 0.28, p<0.001). In contrast, relapse and DFS did not significantly differ according to recipient HLA-B-leader genotype in MRD or MUD recipients in either univariate or MVA. We then analyzed differences in transplant outcome according to donor type (HAPLO vs. MRD/MUD) and recipient HLA-B-leader genotype (M+ vs. M-). In univariate analysis, M+ HAPLO recipients had superior 5-yr OS and DFS when compared to M+ MRD/MUD recipients (81% vs. 52%, p=0.002 and 70% vs. 47%, p=0.008, respectively). In contrast, M- HAPLO recipients demonstrated inferior 5-yr OS and DFS when compared to M- MRD/MUD recipients (49% vs. 67%, p=0.005 and 42% vs. 57%, p=0.022, respectively) (see figure). This result was confirmed in MVA where M- HAPLO recipients demonstrated inferior OS and DFS compared to M- MRD/MUD recipients (HR 2.83, p<0.001 and HR 2.06, p=0.003 respectively). Conversely, M+ HAPLO recipients showed superior OS and DFS (HR 0.54, p=0.045 and HR 0.57, p=0.036 respectively). In summary, recipient HLA-B-leader genotype predicts relapse risk and survival following PTCy-based HAPLO transplant for lymphoid malignancy, but not MRD/MUD transplant utilizing conventional GVHD prophylaxis. As a result, recipient HLA-B-leader genotype can help guide optimal donor selection for patients with lymphoid malignancies with preference for MRD/MUD or HAPLO donor in the context of recipient M- or M+ HLA-B-leader genotype, respectively. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Allogeneic STEM Cell Transplantation in 45 Patients with Myelodysplastic Syndrome: Single-Center Analysis

Background: Myelodysplastic syndromes (MDS) includes a group of clonal myeloid neoplasms characterized by cytopenias due to ineffective hematopoiesis, abnormal blood and marrow cell morphology, and an increased risk of transformation to acute myelogenous leukemia (AML). Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapeutic option for patients with MDS.Aim: To analyze the clinical features and evolution of the MDS patients who underwent to HCT in our institution.Methods: Between July 2006 to January 2021, forty-five patients with MDS underwent allogeneic HCT at the Institut Català d'Oncologia, Hospital Duran i Reynals in Barcelona. Median age at HCT was 56 years (range 35 - 69 years). Thirty-two patients (64%) were male. The diagnosis of patients according to the 2016 WHO classification was: 22% MDS-MLD, 29% MDS-EB-1, 18% MDS-EB-2, 20% CMML, 4% MDS with isolated del(5q) and 7% unclassifiable MDS. Seven patients (15%) underwent allogeneic HCT after progression to AML. Treatments received before the transplant were: chemotherapy AML-like 11 patients (24%) and Azacitidine 24 patients (53%). Ten patients (23%) underwent HCT upfront.Results: Median time from diagnosis to allogeneic HCT was 5 months (range 2 - 12 months). Donors were: matched related (MRD) 17 (38%), matched unrelated (MUD) 12 (27%) and haploidentical 16 (35%). For HLA-MRD transplants, 12 patients received busulfan and fludarabine, 2 patients received TBI and cyclophosphamide, and 3 received busulfan, cyclophosphamide and thiotepa. All of them received tacrolimus or cyclosporine with methotrexate. For HLA-MUD transplants, 7 patients received busulfan and fludarabine, 1 received busulfan and cyclophosphamide, 2 received fludarabine and melphalan, and 2 received busulfan, cyclophosphamide and thiotepa. Six patients received tacrolimus or cyclosporine with methotrexate, 3 patients received tacrolimus with sirolimus and 3 patients received posttransplant cyclophosphamide . For recipients of haploidentical transplants, 6 patients received fludarabine, busulfan and cyclophosphamide, 4 patients received busulfan, thiotepa and fludarabine, 5 patients received fludarabine, cyclophosphamide and TBI and 1 patient received TBI and cyclophosphamide. All patients received tacrolimus or cyclosporine with mycophenolate and posttransplant cyclophosphamide. Five patients (11%) received myeloablative conditioning and 40 patients (89%) received a reduced intensity conditioning regimen. According to graft soure,5 patients (11%) received bone marrow grafts and 40 patients (89%) received peripheral blood grafts. Grade II-IV acute GVHD at day +100 was observed in 19/41 patients (39%) and chronic GVHD in 15/35 patients (42%). Four patients (8%) presented veno occlusive disease. Cytomegalovirus reactivation was reported in 19/38 (50%), and possible/probable invasive fungal infection was reported in 4/49 (8.2%) patients. Median follow-up from MDS diagnosis was 47 months (range 9 - 252 months). At the time of last follow up, 23 patients (51%) are still alive. Median overall survival (OS) was 20 months (range 2 - 180 months). Median progression-free survival (PFS) after transplant was 17 months (range 3 - 180 months). No significant differences were found in OS between the donor types (P = .234) (Figure 1). However, there was a trend for improved PFS in the MRD group, with 2-year PFS of 88%, 58% and 66% for MRD, MUD, and haploidentical recipients, respectively (P = .084) (Figure 2).Summary/Conclusion: Although statistical power is limited, these data suggests that MRD should be the first choice as donor transplant. MUD and haploidentical donors are an acceptable approach for patients without an HLA-matched donor. [Display omitted] DisclosuresMussetti: GILEAD: Other: Clinical trials participation, Research Funding; TAKEDA: Honoraria; NOVARTIS: Honoraria, Other: Clinical trials participation. Sureda: Roche: Other: Support for attending meetings and/or travel; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bluebird: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy; GSK: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding, Speakers Bureau; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Arnan: Jazz: Other: Participation in clinical trials; Takeda: Other: Participation in clinical trials; BMS/Celgene: Consultancy, Other: Participation in clinical trials; Novartis: Consultancy, Other: Participation in clinical trials; Astellas: Consultancy.

Poster: CT-046: Post-Transplant Cyclophosphamide in HLA-Matched and Haploidentical Transplant Recipients Receiving a Myeloablative Fractionated Busulfan Conditioning Regimen: Results of a Phase II Study

Poster: CT-046: Post-Transplant Cyclophosphamide in HLA-Matched and Haploidentical Transplant Recipients Receiving a Myeloablative Fractionated Busulfan Conditioning Regimen: Results of a Phase II Study

The Presence of Recipient CMV Immunodominant Human Leukocyte Antigen (HLA) Alleles Affect Outcomes after Haploidentical (HI) Hematopoietic Stem Cell Transplantation (HSCT)

CMV reactivation is associated with increased treatment-related mortality (TRM), decreased overall survival (OS), and in some analyses, protection from relapse after HSCT. We previously showed that CMV reactivation was significantly higher in HI versus matched related HSCT recipients receiving an identical preparatory regimen, implicating HLA mismatch as a contributor to reactivation. It is known that specific CMV immunodominant HLA alleles (CMV ID alleles) are associated with more efficient antigen presentation and protection from CMV. We hypothesized that a match at a CMV ID allele in the shared haplotype of the donor and recipient pairs may overcome the disadvantage proffered by HI HSCT with respect to CMV. As a control, we tested whether the presence of a CMV ID allele in either the donor or recipient, as opposed to a match at the CMV ID allele, was the more important impactor of outcomes. This information would potentially impact donor selection and identify HI recipients with greater risk for CMV-related complications.MethodsThis is a retrospective, analysis of 138 HI HSCT recipients at risk for CMV reactivation as defined by the presence of positive CMV serologic status in the recipient, donor, or both. All recipients were treated on the Jefferson 2 step approach in which after conditioning, a fixed T cell dose (2 x 108/kg) is administered (step 1), followed 2-3 days later by cyclophosphamide (CY) for bidirectional tolerization. Two days after CY, patients receive a CD34-selected donor product (step 2). To be included in the analysis, patients had to successfully engraft and be alive for at least 1 month post HSCT. Outcomes related to CMV, 1) reactivation incidence, 2) peak copy number of initial CMV reactivation occurring by d+100, 3) TRM, 4) relapse related mortality (RRM), and 5) OS, were tested in 3 contexts: the presence vs the absence of a CMV ID allele in the recipient or the donor, or the presence or absence of a donor/recipient (R/D) match at the same CMV ID allele. CMV ID alleles were defined as HLA A01:01, A02:01, A24:02, B07:02, B08:01, B35:01 and C07:02. Statistics used: incidence of CMV reactivation=Chi-Square; comparison of peak CMV copy numbers=T-test; assessment of RRM and NRM=cumulative incidence (CI); OS=Kaplan-Meier method.Results:A CMV ID allele was present in 68.1% recipients and 66.7% donors. 41.7% of D/R pairs were matched at the same CMV ID allele. The incidence of CMV reactivation was not associated with a D/R CMV ID allele match or recipient or donor CMV ID allele positivity. Peak CMV levels were lower in the presence of any recipient or donor CMV ID allele, but only approached significance in D/R pairs matched at the same CMV ID allele (p=0.065) with a mean of 8.7 x 10e3 vs 4.1 x10e4 copies/ml by PCR in matched vs non-matched pairs respectively. At 3 years, in recipients who matched their donor at 1 or more CMV ID alleles vs those who had no match, CI of NRM was 28% vs 26% (p=0.48) and 16% vs 32% (p=0.07) for RRM. In recipients with vs without a CMV ID allele CI of NRM was 23% vs 36% (p=0.059) and 20% vs 36% for RRM (p= 0.02) (Figure). In recipients with donors who possessed a CMV ID allele vs not, CI of NRM was 27% vs 28% (p=0.80) and 21% vs 31% for RRM (p= 0.12). OS in recipients who were matched at the same CMV ID allele with their donors or who possessed a CMV ID allele was 51% vs 37% (p=0.062) and 52% vs 27% (p=0.001) respectively as compared to recipients negative for these alleles.Conclusion:This analysis suggests that matching HI D/R pairs at a CMV ID epitope may reduce CMV peak copy number but has no significant effect on post HSCT reactivation. Recipient positivity for a CMV ID allele was strongly associated with improvement in NRM, RRM, and OS. Whether the benefit is specific to improved CMV control or to a more efficient antigen presentation in general by these alleles is unknown, but should be further investigated. This data requires confirmation with multivariate analysis. [Display omitted] DisclosuresWagner:Novartis: Research Funding.

Allogeneic Hematopoietic Stem-Cell Transplantation for GATA2 Deficiency Using a Busulfan-Based Regimen

Background: GATA2 deficiency is an increasingly recognized bone marrow failure syndrome responsible for: MonoMAC, monocytopenia with atypical mycobacterial infection (MAC); DCML, dendritic cell, monocyte and lymphoid cell deficiency; Emberger syndrome with lymphedema and monosomy 7; and familial myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML). GATA2 deficiency can be reversed by hematopoietic stem cell transplantation (HSCT). However, the intensity of conditioning required to ensure engraftment and reverse the myelodysplastic syndrome (MDS) characteristic of the disease remains controversial.Methods: We carried out a prospective study of allogeneic HSCT in 22 patients (mean age 26 years; range 17 to 45 years) with GATA2 deficiency, or the MonoMac syndrome, using a myeloablative, busulfan-based conditioning regimen. All 22 patients had MDS and two had AML. Eleven patients had clonal cytogenetic changes in the bone marrow. There were two matched related donor (MRD) recipients, 13 matched unrelated donor (URD) recipients, and 7 haploidentical related donor recipients. MRD and URD recipients received conditioning with 4 days of busulfan (days -6 to -3) to target an AUC between 3600 and 4800 min*microm/L and 4 days of fludarabine 40 mg/m2/day (days -6 to -3). Haploidentical related donor recipients received low-dose cyclophosphamide for two days (days -6 and -5), fludarabine 30 mg/m2/day for 5 days (days -6 to -2), 2-3 days of busulfan depending upon cytogenetics, along with 200 cGY total body irradiation (TBI) on day -1. MRD and URD recipients received tacrolimus and short course methotrexate for post-transplant graft-versus-host disease (GVHD) prophylaxis, whereas haploidentical recipients received high-dose post-transplant cyclophosphamide (PT/CY) followed by tacrolimus and mycophenolate mofetil for GVHD prophylaxis.Results: Nineteen of the 22 patients are alive with resolution of the clinical phenotype and correction of the bone marrow MDS with eradication of the cytogenetic changes at a median follow-up of 23 months (range, 6 to 48 months) giving an overall disease-free survival of 86 percent. The three deaths all occurred in the URD group. Of the three deaths, one resulted from refractory acute myelogenous leukemia (AML), and two from complications related to treatment for GVHD. There was a 26 percent incidence of grade III-IV acute GVHD (aGVHD) in the MRD and URD groups, and no grade III-IV aGVHD in the haploidentical related donor cohort. Similarly, there was a 46 percent incidence of chronic GVHD (cGVHD) in the MRD and URD cohort, whereas two of the 7 (28 percent) of the haploidentical related donor recipients had cGVHD.Conclusions: Despite overall disease-free survival of 86 percent with eradication of the clonal cytogenetic abnormalities in the bone marrow, GVHD remains a limitation in the MRD and URD cohorts treated with standard post-transplant tacrolimus/methotrexate prophylaxis for GVHD. We are currently de-escalating the busulfan dosing based on the AUC in all cohorts and incorporating PT/CY in the MRD and URD cohorts to decrease toxicity and reduce the incidence of aGVHD and cGVHD. Together with our previous studies using a nonmyeloablative regimen, it appears that when GATA2 deficiency patients are transplanted when they have a hypocellular bone marrow with MDS and without cytogenetic changes, a nonmyeloablative regimen results in reliable engraftment in GATA2 deficiency since the GATA2 deficient marrow has a proliferative disadvantage. However, with clonal progression and unfavorable cytogenetic changes and/or a hypercellular marrow, where the malignant clone has a proliferative advantage, a higher dose regimen results in more reliable engraftment and eradication of the clone. Studies to identify the precise level of conditioning for the stages of the disease are ongoing. DisclosuresNo relevant conflicts of interest to declare.

MCL-075: Allogeneic Stem Cell Transplantation in Mantle Cell Lymphoma (MCL): Outcomes with Haploidentical Donors at the Sidney Kimmel Cancer Center (SKCC)

Background: MCL is an incurable, aggressive B-cell lymphoma. Allogeneic stem cell transplantation (allo-SCT) is often reserved for relapsed/refractory patients, but upfront allo-SCT transplant in younger patients is feasible and produces durable remissions in high-risk disease. Objective: To describe the SKCC experience with allo-SCT transplantation in MCL. Design: Retrospective data review of all consecutive MCL patients who underwent allo-SCT at SKCC between 1999 and 2019. Results: We identified 16 patients with MCL who underwent allo-SCT. Indications: blastoid variant (N=5), physician preference (n=5), relapse after auto-SCT (N=3), high-risk MIPI (N=2), inadequate autologous stem cell collection (N=1). The majority of patients were male (n=11, 69%) and Caucasian (n=14, 88%) with a median age at transplant of 50 years (range 40-69). Donor source was HLA haploidentical (n=8), matched-related (n=4), and matched-unrelated (n=4). The majority of haploidentical recipients were transplanted on our two-step T-cell tolerization approach. Conditioning was chemotherapy-based myeloablative (n=7) and reduced intensity (n=9); 69% were treated on clinical trial. Pretransplant induction regimens were heterogeneous over this span of time. Disease status at transplant: first complete remission (n=5), second complete remission (n=3), first relapse with chemosensitive disease (n=2), first relapse with chemoresistant disease (n=1), primary induction failure with chemosensitive disease (n=2), not evaluated (n=3). Median follow-up of surviving patients is 104 months (range 11-253). At 5 years, probability of overall survival is 52.5% and in haploidentical vs matched recipients is 73% vs 31%, respectively. Transplant-related mortality was 25% in the total cohort, all of which occurred in patients treated >15 years ago. Graft-vs-host disease (GVHD) occurred in 10/16 (63%) patients, with no GVHD-related death. Conclusions: For patients with aggressive MCL treated at SKCC on or off clinical trial, allo-SCT is feasible and effective, with evidence of a graft-vs-lymphoma effect. The increased tolerability of allo-SCT with recent approaches and the favorable outcomes with haploidentical donor source support the use of allo-SCT in high-risk MCL patients. TP53 gene status in this patient cohort is being evaluated to assess the effect of allo-SCT on outcomes and will be reported.

Comparing transplant outcomes in ALL patients after haploidentical with PTCy or matched unrelated donor transplantation

AbstractWe compared outcomes of 1461 adult patients with acute lymphoblastic leukemia (ALL) receiving hematopoietic cell transplantation (HCT) from a haploidentical (n = 487) or matched unrelated donor (MUD; n = 974) between January 2005 and June 2018. Graft-versus-host disease (GVHD) prophylaxis was posttransplant cyclophosphamide (PTCy), calcineurin inhibitor (CNI), and mycophenolate mofetil (MMF) for haploidentical, and CNI with MMF or methotrexate with/without antithymoglobulin for MUDs. Haploidentical recipients were matched (1:2 ratio) with MUD controls for sex, conditioning intensity, disease stage, Philadelphia-chromosome status, and cytogenetic risk. In the myeloablative setting, day +28 neutrophil recovery was similar between haploidentical (87%) and MUD (88%) (P = .11). Corresponding rates after reduced-intensity conditioning (RIC) were 84% and 88% (P = .47). The 3-month incidence of grade II-IV acute GVHD (aGVHD) and 3-year chronic GVHD (cGVHD) was similar after haploidentical compared with MUD: myeloablative conditioning, 33% vs 34% (P = .46) for aGVHD and 29% vs 31% for cGVHD (P = .58); RIC, 31% vs 30% (P = .06) for aGVHD and 24% vs 29% for cGVHD (P = .86). Among patients receiving myeloablative regimens, 3-year probabilities of overall survival were 44% and 51% with haploidentical and MUD (P = .56). Corresponding rates after RIC were 43% and 42% (P = .6). In this large multicenter case-matched retrospective analysis, despite the limitations of a registry-based study (ie, unavailability of key elements such as minimal residual disease testing), our analysis indicated that outcomes of patients with ALL undergoing HCT from a haploidentical donor were comparable with 8 of 8 MUD transplantations.

Matched-Pair Analysis of Transplant from Haploidentical, Unmanipulated Bone Marrow Donor versus HLA Identical Sibling for Patients with Hematologic Malignancies.

A matched-pair analysis of transplant-related outcomes was carried out in 116 of 255 consecutive patients who received transplants from an HLA identical sibling (n=58) or haploidentical related donor (n=58). The 2 patient series were matched with 9 variables: period of transplant, patient and donor age, sex, diagnosis, disease phase, conditioning regimen, donor-recipient sex, and cytomegalovirus (CMV) status combinations. As graft-versus-host disease (GVHD) prophylaxis, all patients received the standard cyclosporine and methotrexate association with the addition of anti-thymocyte globulins, mycophenolate mofetil, and basiliximab in haploidentical, unmanipulated bone marrow recipients. Anti-infectious management, transfusion policy, and supportive care were identical for all patients. By comparing the 2 patient series, no statistically significant difference was observed for the cumulative incidence of advanced acute and extensive chronic GVHD, transplant-related mortality, and relapse. With a median follow-up of 3.5 years, the 5-year disease-free survival was 37% ± 6% and 36% ± 6% for HLA identical sibling and haploidentical recipients, respectively. The results of transplant from HLA identical siblings and haploidentical donors are comparable. Regardless of the HLA matching, other factors known to affect the transplant outcomes, such as donor-recipient age, sex, and CMV status combinations, might drive the search for the best donor.

Letermovir for Primary Cytomegalovirus Prevention in Haploidentical Stem Cell Transplant Recipients

<h3>Introduction</h3> Cytomegalovirus (CMV) continues to be a leading cause of morbidity and mortality among recipients of allogeneic hematopoietic stem cell transplant (HSCT). Marty et al. demonstrated the utility of letermovir for primary prophylaxis. However, a majority of the population in their study (69.4%) received a matched-unrelated or a matched-sibling donor transplant. Therefore, data is limited on optimal CMV prophylaxis among haploidentical recipients. <h3>Objectives</h3> The primary objective of this study was incidence of CMV reactivation prior to and beyond day 100 among haploidentical HSCT recipients who received primary letermovir prophylaxis. Secondary endpoints included median time to reactivation, median time to engraftment, and non-relapse mortality. <h3>Methods</h3> We conducted a single-center retrospective analysis to evaluate the efficacy of letermovir as primary prophylaxis among CMV seropositive haploidentical recipients between May 2018 to December 2019. Patients received letermovir prophylaxis from day 16 to 100. Exclusion criteria included subjects with history of CMV end-organ disease within 6 months of HSCT, history of CMV viremia at any time prior to transplant, received either ganciclovir, valganciclovir, foscarnet, or cidofovir within 7 days of transplant. <h3>Results</h3> We identified 20 haploidentical HSCT recipients, median age 52 years, the majority of which received reduced-intensity conditioning therapy with fludarabine, cyclophosphamide, and total-body irradiation. Graft-versus-host disease prophylaxis included tacrolimus, mycophenolate mofetil, and post-transplant cyclophosphamide. CMV reactivation occurred in 5 patients before day 100 (25%) range (day 20 to 45). Of the remaining 15 patients, an additional 4 (27%) had CMV reactivation after letermovir was discontinued at day 100, range (day 117 to 156). Overall survival at 1 year was 79.2% and non-relapse mortality at 1 year was 12.5%. <h3>Conclusion</h3> Our study demonstrated the efficacy of letermovir as primary prophylaxis among CMV seropositive haploidentical recipients. However, significant CMV reactivation was seen beyond day 100 and future studies need to be conducted on the ideal duration of prophylaxis in this high-risk population.

Early Immune Reconstitution after Haplo-Identical Hematopoietic Stem Cell Transplantation (HCT) with Post-Transplant Cyclophosphamide (PTCY) Does Not Improve Overall Survival Compared to Matched Unrelated Donor HCT Recipients Receiving Thymoglobulin Prophylaxis (ATG)

Recent retrospective studies demonstrated similar overall survival (OS) and relapse rate after allogeneic HCT using matched unrelated or haplo-identical donors. However, differences in graft versus host disease (GVHD) prevention protocols using ATG or PTCY may have influenced the results. In addition, there is little knowledge about immune reconstitution after PTCY compared to ATG. We examined the outcomes of 73 consecutive patients who received allogeneic HCT from 5/2015 to 4/2019 (39 Haplo, 34 MUD). Patient's Characteristics shown in table-1. The two groups matched except for donor age, CD34 dose infused and race. Conditioning regimens shown in table-1. MUD recipients received GVHD prophylaxis with Tacrolimus/ Mycophenolate (Tacro/MMF) in addition to ATG (24 Patients) or PTCY (10 Patients) while Haploidentical patient received Tacro/MMF with PTCY. A panel of immune reconstitution markers collected at day 100 post- transplant for CD3, CD4, CD8, Activated T cell ( HLA- DR3+ CD3+)and NK cells ( CD56+) was obtained for 29 MUD and 28 Haploidentical recipients. We observed pronounced proliferation and recovery in all T cell subsets in Haploidentical patients compared to MUD patients at day 100 as shown in Fig-1. This robust T cell recovery in Haploidentical transplant patients with PTCY was statistically significant for CD3, CD4 and CD8. When Immune reconstitution for Haploidentical patients compared to MUD patients who received PTCY, it maintained its robust effect on T cell proliferation (Fig-2) although it did not reach statistical significance. The overall survival at one-year with median duration of follow up of 22.6 months was 61.5% and 82.3% for Haploidentical and MUD recipients respectively; P=0.14. There were 15 deaths during the first year in the Haploidentical patients (3 = relapse, 5 = severe cytokine release syndrome (CRS), 1=Veno-occlusive disease, 3= infection, 2=GVHD and 1 = primary graft failure). In contrast there were only six deaths in MUD patients (2= relapse, 3= GVHD and 1= infection). There was no deaths in MUD PTCY patients in the first year. There was no primary graft failure in either arm, however secondary graft failure occurred in 2 Haploidentical and 1 MUD patients. Median time to engraftment was 18 days for Haploidentical (range, 12-57) and 11.6 days for MUD (range, 10-18). Acute GVHD grade 2-4 developed in 35% in MUD and 23% in Haploidentical patients. Conclusions: We found robust early immune recovery after Haploidentical HCT compared to MUD HCT. The degree of HLA mismatch with Haploidentical HCT and antigen presentation may have contributed to pronounced T cell proliferation as the same effects was not observed in MUD HCT with PTCY. Despite the early recovery of T cells after Haploidentical HCT the overall survival did not exceed the overall survival with MUD HCT. Severe CRS contributed to the increased mortality seen in Haploidentical HCT patients. Further strategies are needed to decrease treatment related mortality with Haploidentical HCT. Disclosures No relevant conflicts of interest to declare.

Antibody Conditioning Enables MHC-Mismatched Hematopoietic Stem Cell Transplants and Organ Graft Tolerance.

Hematopoietic cell transplantation can correct hematological and immunological disorders by replacing a diseased blood system with a healthy one, but this currently requires depleting a patient's existing hematopoietic system with toxic and non-specific chemotherapy, radiation, or both. Here we report an antibody-based conditioning protocol with reduced toxicity and enhanced specificity for robust hematopoietic stem cell (HSC) transplantation and engraftment in recipient mice. Host pre-treatment with six monoclonal antibodies targeting CD47, Tcells, NK cells, and HSCs followed by donor HSC transplantation enabled stable hematopoietic system reconstitution in recipients with mismatches at half (haploidentical) or all major histocompatibility complex (MHC) genes. This approach allowed tolerance to heart tissue from HSC donor strains in haploidentical recipients, showing potential applications for solid organ transplantation without immune suppression. Fully mismatched chimeric mice developed antibody responses to nominal antigens, showing preserved functional immunity. These findings suggest approaches for transplanting immunologically mismatched HSCs and solid organs with limited toxicity.

PS1558 COMPARISON OF THE INCIDENCE AND OUTCOMES OF TRANSPLANT‐ASSOCIATED THROMBOTIC MICROANGIOPATHY BETWEEN HAPLOIDENTICAL AND MATCHED SIBLING DONOR HEMATOPOIETIC STEM CELL TRANSPLANTATION

Background:Transplant‐associated thrombotic microangiopathy (TA‐TMA) is an early complication of hematopoietic stem cell transplantation (HSCT) that usually occurs within the first 3 months and has a high mortality rate of approximately 50–75%. TA‐TMA is less common in autologous (0–27%) than in allogeneic HSCT (6–76%). We previously reported risk factors and mortality of TA‐TMA with concomitant acute graft versus host disease (aGvHD) (Xiao Liu, Eur J Haematol, 2018). Recently, the use of haploidentical (HID) donors has continued to increase, but no information is available on the incidence and outcomes of TA‐TMA patients after HID allo‐HSCT.Aims:To compare the incidence and outcomes of TA‐TMA in HID recipients with those of matched sibling donor (MSD) transplantation.Methods:In this retrospective, nested case‐control study, 102 consecutive TA‐TMA patients (HID: 87 patients, MSD: 15 patients) were identified from a total of 3726 patients who underwent allo‐HSCT at Peking University People's Hospital between 2009 and 2018. Patients with TA‐TMA and controls were matched for follow‐up time after transplantation (total n = 278). TA‐TMA were diagnosed based on the clinical suspicion of the physician according to the diagnostic criteria for overall TMA (Byung‐Sik Cho, Transplantation, 2010). Upon diagnosis of TA‐TMA, all CNIs were discontinued, and monoclonal antibodies, TPE and other supportive treatments were used as required by the patients’ condition. Cox regression was used to identify independent risk factors associated with the occurrence and outcomes of TMA.Results:The 10‐year cumulative incidence of TA‐TMA occurrence in HID recipients was 3.5%, which was significantly higher than that of the MSD group (Figure 1, p &lt; 0.001). A total of 60.5% of TA‐TMA events occurred in the first 3 months after HSCT. TA‐TMA patients in the HID group were younger, more likely to receive additional anti‐human T‐lymphocyte immunoglobulin during conditioning and had more ABO mismatches and more concomitant aGvHD. The time from transplantation to the TA‐TMA diagnosis was comparable between the two groups (p = 0.365). In the multivariate Cox regression analysis, concomitant aGvHD ≥ grade 3 (HR 2.629, 95%CI 1.363–5.069, p = 0.004), higher doses of corticosteroids administration (HR 1.005, 95%CI 1.002–1.007, p &lt; 0.001), but not the HID/MSD donor type, were each associated with an increased risk of TA‐TMA development in HSCT patients. With a median follow‐up of 374 days, the 1‐week, 1‐month, and 1‐year probabilities of overall survival (OS) of the TA‐TMA patients were 92.6%, 56.9% and 16.5% in the HID patients and 53.3%, 20.0% and 19.3% in the MSD patients, respectively. The main cause of death was disease‐related. Multivariate analysis showed that the only significant predictive factor was the time from HSCT to aGvHD (HR 0.845, 95% CI 0.934–2.661, p = 0.009). HLA mismatch showed no significant correlation with either long‐term OS (p = 0.464) or nonrelapse mortality (p = 0.322).Summary/Conclusion:TA‐TMA is more common in HID than in MSD HSCT. However, HID is not an independent risk factor of the occurrence of TA‐TMA, and OS is comparable between the groups. Further studies on the role of HID in the setting of TA‐TMA are required to confirm these findings.image

Increased risk of 100-day and 1-year infection-related mortality and complications in haploidentical stem cell transplantation.

Background: While haploidentical transplantation has led to the near-universal availability of donors, several challenges for this form of transplant still exist. This study sought to investigate the rates of infection-related mortality and other complications following haploidentical vs nonhaploidentical transplant.Methods: We conducted a retrospective cohort study in adults with various malignant and benign hematological conditions who underwent allogeneic hematopoietic stem cell transplantation from 2011 to 2018. One hundred-day and 1-year overall survival were defined as survival from the time of transplant until 100 days or 1 year later.Results: A total of 187 patients were included in this study, with 45 (24.1%) receiving transplants from haploidentical donors and 142 (75.9%) from nonhaploidentical donors. There were similar rates of acute graft-versus-host disease (GVHD) (40% vs 38% in haploidentical vs nonhaploidentical recipients, P=0.86) and chronic GVHD (44.4% vs 43.7%, P=1). Rates of 100-day and 1-year infection-related mortality were significantly higher in the haploidentical group compared to the nonhaploidentical group (8.9% vs 1.4% at 100 days, P=0.03, and 15.9% vs 3.8% at 1 year, P=0.01). There were also higher rates of cytomegalovirus infections (59.1% vs 23.8%, P<0.01), BK virus-associated hemorrhagic cystitis (40.9% vs 8.4%, P<0.01), and BK viremia (15.9% vs 0.8%, P<0.01) in haploidentical recipients.Conclusions: Despite the use of identical antimicrobial prophylactic and treatment agents, haploidentical recipients were found to have significantly increased rates of 100-day and 1-year infection-related mortality as well as several other infectious complications.

HSCT Engraftment Kinetics: Differences in Chimerism between Haploidentical (HI) and Matched Related (MR) Transplant Recipients (HSCT) after the 2 Step Approach

Cyclophosphamide (CY) toleration has been associated with low rates of graft versus host disease (GVHD) and non-relapse mortality after both HI and MR HSCT. At Jefferson, both recipient types undergo a 2 step approach to HSCT in which after myeloablative (MYA) or reduced intensity (RIC) conditioning, patients receive a fixed dose of 2 x 108/kg donor CD3+ T cells (DLI), followed 2 days later by CY daily x 2 for bidirectional tolerization. A CD34-selected stem cell product containing < 5 x 104/kg untolerized CD3 cells is infused 24 hours after CY. Mycophenolate mofetil and tacrolimus are started on day-1 for GVHD prophylaxis. The consistency of cell doses, conditioning, and GVHD prophylaxis in the approach provides an optimal platform for comparing patient outcomes. Because tolerance induction and sustained engraftment in CY-based HSCT approaches depends on elimination of donor and host alloreactive T cells, we hypothesized that engraftment in this model would be different between HI and MR recipients based on the lower proliferation of alloreactive T cells in major histocompatibility (MHC) MR versus HI donor-recipient pairs.Data for 292 consecutive patients (232 HI, 60 MR) treated on a 2-step trial were evaluated for incorporation into this analysis. To be included, patients were required to be in remission for 3 months post HSCT and have available d+28 and d+90 peripheral blood T cell chimerism data. Seven HI patients with graft rejection, 5/232 with early (2%-all MYA) and 2/232 with late (0.1%-1 MYA and 1 RIC), were not included in the analysis. No MR patients developed graft rejection. Days to ANC > 500 cells x 103/ul, CD3/4 and CD3/8 counts at d+28 and d+90, peak fever after DLI infusion as a rough measure of alloreactivity, and number of patients requiring post HSCT donor lymphocytes for mixed chimerism were also examined. Independent samples T test was used for chimerism and peak fever comparisons.The final study group contained 201 patients treated on a 2 step MYA [12 Gy total body irradiation (TBI)] or RIC (fludarabine/TBI based) regimen. Patients had various hematological malignancies and 6 had aplastic anemia. Data is contained in the table.Mean T cell chimerism was higher in HI versus MR recipients at d+28 and d+90 (p= 0.001 both time points). In 3 MR recipients, donor T cell chimerism was < 70% through d+90. Four (9%) MR versus no HI recipients received post HSCT DLI for mixed chimerism in the absence of recurrent disease. Chimerism differences did not affect time to myeloid engraftment or lymphoid reconstitution. While higher median peak temperatures after DLI were observed in HI versus MR recipients, some patients in the latter population were also highly febrile. Those MR recipients with higher fevers had a higher mean donor engraftment percentage at d+28 than those with lower fevers, but the difference was not significant (96.61% vs 93.95%, p=0.193).The data presented here supports the concept that MHC mismatching in HI HSCT is associated with a higher frequency of alloreactive T cells in the DLI which more efficiently eliminate residual host lymphocytes prior to CY administration resulting in more complete donor lymphoid chimerism. Interestingly, further support for this notion was provided by the MR recipient data where higher fevers, a surrogate for more robust immunologic activation, translated into the more rapid achievement of full donor chimerism. This finding was potentially due to higher alloreactivity between some MR recipient/donor pairs from non-MHC polymorphisms. Persistence of small numbers of host lymphocytes, which have also been rendered tolerant by CY administration, does not, in and of itself, lead to graft failure/rejection. However, concerns that low degree of chimerism might contribute to higher risk of relapse led to administration of post-transplant DLIs to push donor lymphoid chimerism closer to 100%. The impact if any, of delayed complete chimerism on GVHD and relapse requires further evaluation and may dictate changes to the 2 step regimen for the MR group. [Display omitted] DisclosuresPorcu:Innate Pharma: Consultancy.

ICOSL+ Plasmacytoid Dendritic Cells As Biomarker and Inducer of Graft-Versus-Host Disease

Acute graft-versus-host disease (GVHD) remains one of the leading causes of death post allogeneic hematopoietic cell transplantation (HCT). Gastrointestinal GVHD (GI-GVHD), the most fatal type of GVHD, would benefit from additional biomarkers that are therapeutic targets. Using state-of-the-art quantitative proteomics we previously identified and validated an increased CD4+CD146+ T cell population in GI-GVHD patients. This population expressed a Th1 and Th17 phenotype and was induced by Inducible COStimulator (ICOS), a critical costimulatory molecule for the development of pathogenic Th17 (Li W. et al, J. Clin. Invest. Insights, 2016).ICOS binds its ligand, ICOSL, which is expressed on dendritic cells (DCs) that prime naïve T cells to initiate immune responses. This prompted us to examine ICOSL expression on the two blood DCs subsets that can be identified in human peripheral blood: Lineage-HLADR+CD11c+ myeloid DCs (mDCs) and Lineage-HLADR+CD123+ plasmacytoid DCs (pDCs). Using the same cohort of patients aforementioned, the frequency of ICOSL was significantly higher on pDCs in 64 GI-GVHD patients when compared to 22 non-GVHD enteritis patients, 35 skin GVHD patients, and 39 patients without GVHD (Figure 1). The numbers and frequencies of total DCs, mDCs and pDCs were similar between groups.The growth factor fms-related tyrosine kinase 3 ligand (Flt3l) is necessary for the development and differentiation of pDCs, and the transcription factor, Stat3, is required for Flt3l-dependent dendritic cell differentiation in mice. The role of pDCs in acute GVHD is still controversial (tolerogenic or initiator of GVHD depending on the murine model), and confirmatory studies about their functions are necessary before a therapeutic approach based on this mechanism can be contemplated. Based on the patients' data and previous knowledge, we hypothesized that absence of ICOSL signaling in donor DCs would protect against GVHD through Flt3l, Stat3, or both. We first found that knocking out (KO) ICOSL in the donor bone marrow (BM) extended survival compared to wild-type (WT) mice in the major mismatch (B6, H-2b à BALB/c, H-2d) experimental HCT model, while recipients of Stat3KO BM did not show any difference in GVHD mortality (Figure 2A). We also found a significant decrease of Flt3l levels in plasma collected at day 3 from ICOSLKO BM recipients compared to WT mice (Figure 2B). We then analyzed the recipients' infiltrating intestinal immune cells at day 10 post-HCT for the infiltration of pDCs and pathogenic Th17 cells. We found significantly lower frequencies of intestinal pDCs (CD11b-CD11c+B220+CD103+) (Figure 2C), and intestinal T cells coexpressing interferon (IFN)g and IL-17 (Figure 2D) in recipients of ICOSLKO BM compared to recipients of WT BM. Absolute counts of these two populations followed the same trend (data not shown). To confirm these data were not strain-specific, we performed similar analyses in the haplo-identical (B6, H-2b à B6D2F1, H-2d) experimental model showing similar outcomes for pDCs and IFNγ+IL-17+ T cells frequencies and counts in recipients of ICOSLKO BM compared to recipients of WT BM. Importantly, and in contrast to human T cells, CD146 is not expressed on naïve murine T cells and thus cannot be measured in vivo in acute GVHD models. Transcriptome analyses by Nanostring technology (Immunology panels) comparing 14 days post-HCT of sorted pDCs from ICOSLKO BM versus WT haplo-identical recipients showed increased expression of key molecules required for development (Itgax, Nos2, Socs1, Tcf4 and Bst2), costimulation (Cd80, Cd48, Cd74 and Cd86), and function (Tyrobp, Ikbkg, Nod2 and Irf7) of pDCs (Figure 3A). Lastly, we found increased T cell activation markers including Prf1, Il17a, eomes in sorted CD4+ T cells from ICOSLKO BM compared to WT recipients (Figure 3B).We conclude that early quantification of ICOSL+ pDCs frequency may allow identification of patients at risk of GI-GVHD development. Targeting ICOSL may represent a new avenue to treat acute GVHD. [Display omitted] DisclosuresPaczesny:Viracor IBT Laboratories: Patents & Royalties.

An alternative method for custom prime: A case report of successful peripheral blood stem cell harvesting from two low-weight child donors

Allogeneic peripheral blood stem cell (APBSCs) transplantation is an effective treatment for hematological malignancies. However low-weight donor children meet some complications. In the current report, PBSCs were harvested from a 14-month-old child (9.8Kg) for a 6years old sibling recipient suffering from pre-B type of acute lymphoblastic leukemia (ALL) and also 24 months old male child donor (12Kg) for a haploidentical recipient suffering from acute myeloid leukemia (AML-M4EO). The PBSC harvesting was performed using Spectra™ Optia® apheresis software with continuous mononuclear cell (CMNC) procedure. The results were completely promising and both recipients underwent an acceptable transplantation.