Matched Unrelated Donor Transplantation Research Articles

Chronic Graft Versus Host Disease Burden and Relapse Rates Are Lower with Comparable Overall Survival and Graft Versus Host Disease Free, Relapse Free Survival Following Adult Umbilical Cord Blood Compared to Matched Sibling Peripheral Blood Stem Cell Transplantation

Abstract Background: Although matched related donors (MRD) are the preferred source of stem cells for allogeneic hematopoietic cell transplantation, umbilical cord blood (UCB) is a well-established donor source in patients without a MRD or matched unrelated donor (MUD). Prior studies (Eapen et al, Lancet Oncology 2010; Rocha et al, NEJM 2004) have shown similar overall survival and relapse rates after umbilical cord blood transplant (UCBT), and our group (Gutman et al, BMT 2016) has shown lower chronic graft-versus-host-disease (GVHD) when compared to MUD transplant. Based on these data, our preferred donor source is MRD followed by UCB. Here, we evaluate our data comparing transplant outcomes in UCBT recipients versus MRD recipients. Methods: We compared outcomes in all consecutive adult patients undergoing first MRD transplant versus first double UCBT from January 2010 to December 2017. Patient selection, graft-versus-host disease prophylaxis and transfusions were per institutional standards. Graft-versus-host-disease free, relapse free survival (GRFS) was defined by events that includedgrade 3-4 acute GVHD, moderate to severe chronic GVHD, relapse or any death. Results: Of the 296 patients studied, 187 underwent UCBT and 109 received MRD transplant. Graft failure occurred in 6 (3%) UCBT recipients (5 of whom received reduced intensity conditioning) and did not occur in any MRD transplant recipients. While the incidence of grade 2-4 acute GVHD was higher in UCBT recipients (p= 0.006), grade 3-4 acute GVHD was comparable (p= 0.36) between the two groups. Any chronic GVHD (p= 0.0000001) and moderate to severe chronic GVHD (p= 0.00011) was significantly higher in MRD transplant recipients (figure 1a and 1b). There were significantly lower disease relapses in UCBT recipients (n= 51, 27% versus n= 46, 42%; p= 0.0036) compared to MRD transplant recipients. Transplant related mortality was higher in UCBT recipients (n= 33, 42% versus n= 11, 23% in MRD transplant recipients; p= 0.03). There was no difference in GRFS (p=0.15, figure 1c) and overall survival (OS) in the 2 study cohorts (p=0.31, figure 1d). Conclusions: UCBT recipients as compared to MRD recipients had lower chronic GVHD and lower relapse rates with no difference in OS and the composite endpoint of GRFS. Based on these results, UCB remains an appropriate alternative donor source for hematopoietic cell transplantation and might result in improved quality of life by virtue of lower incidence of chronic GVHD in long-term transplant survivors. Disclosures Haverkos: Viracta Therapeutics: Membership on an entity's Board of Directors or advisory committees. Pollyea:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Argenx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Curis: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Celyad: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Research Funding. Kamdar:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Mark:Janssen, Takeda, Celgene, Amgen: Consultancy; BMS, Celgene: Research Funding; Celgene: Honoraria.

Durability Results of Non-Myeloablative (NMA) Allogeneic Stem Cell Transplantation (alloSCT) for Relapsed Follicular Lymphoma: 17- Year Experience

Abstract Purpose: We have previously reported the outcomes of NMA alloSCT in 47 patients with relapsed/chemosensitive follicular lymphoma (FL) who received a matched sibling donor (MSD) after FCR conditioning (Khouri, Blood 2008;111:5530). In subsequent trials, eligibility was expanded to include transplants from matched unrelated donors (MUDs) using a 90yttrium ibritumomab tiuxetan (90YIT)-based regimen (Khouri, Blood 2012 ;119:6373) or, more recently, BFR (bendamustine, fludarabine, rituximab; Khouri, Blood 20014;124:2306) conditioning. Herein we report on long-term outcomes in 98 FL patients treated on these 3 consecutive trials between 1999-2017. Methods: The BFR regimen (N=20) consisted of bendamustine 130 mg/m2 IV daily on days -5 to - 3 prior to transplantation, thus substituting for the cyclophosphamide in the FCR regimen (N=47) . The dose and schedule of fludarabine (30 mg/m2 IV daily x3) and rituximab (375 mg/m2 IV on day -13 and 1000 mg/m2 on days -6, +1, and +8) were similar in both regimens. 90YIT-regimens (N=31) : A diagnostic dose of 111In-ibritumomab was administered on day-14, followed by a fixed dose of 0.4 mCi/kg 90YIT on day -7; FC or BF chemo was then administered at the same dose and schedule (days -5 to -3) as described above. Tacrolimus and methotrexate was used for GVHD prophylaxis. In addition, thymoglobulin of 1 mg/kg was given on days -2, -1 in patients receiving a MUD transplant. Results: Median age was 53 years (range, 29-71) and 24 patients (24%) were >60 years. Twenty-eight patients (29%) had a HCT-CI of ≥ 3. The median prior number of treatments was 3 (range, 2-9); 51 patients (52%) had rituximab-chemo induction at diagnosis. Seventy-one patients (72%) relapsed within 2 years of their induction treatment and median duration of last remission prior to alloSCT was < 1 year in 61% of patients. At transplant, 82 patients (84%) had chemosensitive disease (46% CR, 38% PR); 16% had refractory disease; 22% were PET+; and 20% had elevated serum LDH. Seventy patients (71%) had a transplant from a MSD and 28 (29%) from MUDs; 15 (15%) transplants had female-to-male donors, and 42 (43%) were ABO-mismatched. In addition, CMV was reactive in 80% of patients/ and or donors. Most patients (94%) had alloSCT from peripheral blood. Median number of CD34-positive cells infused was 4.9 x 106/kg. A significant difference in ANC recovery between the 3 conditioning regimens was observed. Neutrophil counts recovered to > 0.5 x 109/L a median of 0 days (range 0-16) for the BFR groups vs. 10 days (range, 0-17) and 11 days (range, 5-17) for the FCR and 90YIT-regimen groups, respectively (p<0.0001). This difference was consistent for each transplant type. With a median follow-up time for all patients of 98 months (range, 3-208 months), the overall survival (OS) and progression-free-survival (PFS) rates at 98 months were 82% (95%CI, 73-89) and 74% (95% CI, 64-82), respectively (Figure 1) . The cumulative incidence (CI) of grade II-IV and III-IV acute GVHD was 22% and 9%, respectively. The CI of chronic GVHD was 38%. Treatment-related mortality at 1 year was 9%. Patient demographic, disease characteristics, and transplant characteristics and their correlation with outcomes were evaluated. Disease status of > 1st relapse, >2 prior chemotherapies, duration of last remission prior to alloSCT < 1 year, ≥ 3 comorbidities, elevated LDH, acute II-IV GVHD, chronic extensive GVHD were associated with inferior OS. By multivariable analysis (MVA), duration of last remission prior to alloSCT (<1year) [HR 6.48 (1.28, 32.69); p=0.024]) and acute II-IV GVHD [HR 8.61 (2.99, 24.83); p<0.001] were associated with inferior OS. No significant prognostic factors on MVA for PFS, or risk for acute or chronic GVHD were noted for this cohort of patients. Conclusions: Nonmyeloablative allogeneic transplant can induce complete responses lasting over a decade in most patients with relapsed FL. Our initial findings published in 2008 were thus confirmed in a larger number of patients including those who received MUD transplants. BFR conditioning has been associated with significantly lesser myelosuppression and a faster neutrophil recovery than other regimens used, validating our initial observation in earlier reports. Disclosures Jabbour: Novartis: Research Funding; Pfizer: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Abbvie: Research Funding; Takeda: Consultancy, Research Funding. Oran:AROG pharmaceuticals: Research Funding; ASTEX: Research Funding; Celgene: Consultancy, Research Funding. Champlin:Otsuka: Research Funding; Sanofi: Research Funding.

Impact of T-cell depletion strategies on outcomes following hematopoietic stem cell transplantation for idiopathic aplastic anemia: A study on behalf of the European blood and marrow transplant severe aplastic anemia working party.

We retrospectively analyzed the outcomes of 1837 adults and children with severe aplastic anemia (SAA) who underwent matched sibling donor (MSD) and matched unrelated donor (MUD) hemopoietic stem cell transplantation (HSCT) between 2000 and 2013. Patients were grouped by transplant conditioning containing either anti-thymocyte globulin (ATG) (n = 1283), alemtuzumab (n = 261), or no serotherapy (NS) (n = 293). The risks of chronic GvHD were significantly reduced when ATG or alemtuzumab were compared with NS (P = .021 and .003, respectively). Acute GVHD was significantly reduced in favor of alemtuzumab compared with ATG (P = .012) and NS (P < .001). By multivariate analysis, when compared with ATG, alemtuzumab was associated with a lower risk of developing acute (OR 0.262; 95% CI 0.14-0.47; P < .001) and chronic GVHD (HR 0.58; 95% CI 0.35-0.94; P = .027). OS was significantly better in ATG and alemtuzumab patients compared with NS (P = .010 and .025). Our data shows inclusion of serotherapy in MSD and MUD HSCT for patients with SAA reduces chronic GVHD and provides a survival advantage over patients not receiving serotherapy. Notably, alemtuzumab reduced the risk of acute and chronic GvHD compared with ATG and indicates that alemtuzumab might be the serotherapy of choice for MSD and MUD transplants for SAA.

Is a matched unrelated donor search needed for all allogeneic transplant candidates?

AbstractDonor availability for allogeneic transplantation remains an important factor in determining outcomes of a successful transplant. We examined outcomes of 242 patients treated over 3 years who had a matched unrelated donor (MUD) search at our institution. One hundred sixty patients (66%) had a 10 of 10 MUD identified, and 85 (53%) proceeded to MUD transplantation. White patients and those with common haplotypes were more likely to have a MUD identified (odds ratio [OR], 7.4 [P < .0001]; OR, 41.6 [P < .0001]), and were more likely to proceed to transplantation with a MUD (OR, 11.2 [P < .0001]; OR, 85.1 [P = .002]). In addition, patients who were newly diagnosed/in remission at the time of MUD search had a higher probability of receiving a transplant (OR, 2.01 [P = .013]) and better progression-free survival (PFS; P < .0001). In multivariate analysis for patients who received a transplant, donor type did not influence PFS at 3 years, which was 40% for MUD and 57% for haploidentical transplants, respectively (hazard ratio, 1.2 [P = .50]). In conclusion, race, haplotype frequency, and disease status at the time of MUD search influence the probability of identifying a MUD and receiving a transplant. Patients with a low likelihood of receiving a MUD transplant may proceed to a haploidentical transplant as soon as indicated, as this approach does not appear to compromise transplant outcomes.

Unmanipulated Haploidentical Hematopoietic Stem Cell Transplantation Achieved Outcomes Comparable With Matched Unrelated Donor Transplantation in Young Acquired Severe Aplastic Anemia

Salvage haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is considered in patients with severe aplastic anemia (SAA) if a matched unrelated donor (MUD) is unavailable. However, studies on haplo- and MUD transplantation in SAA are lacking. The present study retrospectively analyzed the outcomes of 89 young SAA patients who underwent unmanipulated alternative HSCT between September 2012 and September 2016 at our single center. Forty-one patients received haploidentical donors and forty-eight patients MUDs for HSCT. Most were heavily transfused and refractory to previous immunotherapy. The median durations for myeloid engraftment in the haplo- and MUD cohorts were 14 (range, 10 to 21) and 13 (range, 10 to 18) days, respectively. Compared with the MUD cohort, haplo-HSCT cohorts had an increased cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV (43.9% ± 7.8% versus 12.5% ± 4.8%, P = .001) and grades III to IV (21.1% ± 6.7% versus 6.6% ± 3.7%, P = .045) and similar limited chronic GVHD (47.7% ± 8.5% versus 38.5% ± 7.3%, P = .129) and extensive chronic GVHD (12.1% ± 6.8% versus 9.1% ± 4.3%, P = .198). The median follow-up time of the surviving patients was 26 months (range, 6 to 45). No significant differences were observed between haplo-HSCT and MUD HSCT cohorts in 3-year overall survival (80.3% ± 5.1% versus 89.6% ± 7.0%, P = .210), disease-free survival (76.4% ± 5.1% versus 89.4% ± 7.7%, P = .127), and GVHD-free failure-free survival (79.0% ± 8.6% versus 71.6% ± 9.3%, P = .976). Thus, haplo-HSCT, as salvage therapy, achieved similar outcomes as MUD HSCT in young SAA patients, thereby rendering it as an effective and safe option for SAA.

282 - Kidney Dysfunction Post-Allogeneic Transplant: High Incidence of TMA and Kidney GvHD

Abstract Introduction: Kidney dysfunction is an important problem in adult recipients of allogeneic stem cell transplantation (HSCT) and independently predicts overall survival and non-relapse mortality. Kidney dysfunction occurs in ~50% of transplant recipients. More than 20% of all survivors of HSCT in long-term follow up develop chronic kidney disease. However, there is currently limited data on the cause and consequences of kidney dysfunction in adult recipients after allogeneic HSCT. Common causes of kidney dysfunction after HSCT include chemotherapy or radiation toxicity, infections, sepsis, hepatic sinusoidal obstruction, drug toxicities due to immunosuppressive medications, thrombotic microangiopathy, as well as acute or graft versus host disease (GvHD). Kidney biopsies are seldom obtained and hence the tissue diagnosis in these patients often remains speculative. Early identification of the causes of kidney dysfunction may help define preventive and therapeutic strategies and improve outcome. Hence, in August 2016, we designed a prospective study at our center to systematically evaluate kidney dysfunction in adult recipients of allogeneic HSCT. Herein we present our initial report of 8 kidney biopsies. Methods: All adult HSCT recipients with kidney dysfunction were evaluated by Nephrologists to determine the need for kidney biopsy. Kidney dysfunction was defined as either (i) acute kidney failure or (ii) proteinuria. Acute kidney failure was defined by the ‘ Kidney Disease: Improving Global Outcomes (KDIGO)‘ criteria. Proteinuria was defined as (i) spot urine albumin to creatinine ratio of ≥1 (equivalent to ≥1 g in 24 hours). Kidney biopsies were done under ultrasound guidance and the tissue specimens were interrogated by light, immunofluorescence and electron microscopy. Results: A total of 8 HSCT recipients (including one patient who had a biopsy prior to Aug 2016) underwent kidney biopsies. The patient and transplant characteristics are summarized in Table 1. Seven of the 8 pts had AML. One patient had NHL in CR2. Four patients received a MUD transplant. Two received MRD transplants. Two received combined haploidentical and single unit cord blood transplant (haplo-cord). Six of the 8 patients received conditioning with fludarabine and melphalan. One patient received additional 400 Gy TBI. One patient received additional azacytidine. Median time to neutrophil engraftment was 13.5 days (range 9-20). Median time to platelet engraftment was 19 days (range 14-76). There were no cases of graft failure. All patients also demonstrated either acute or chronic GvHD of other organs - most commonly skin. All kidney biopsies were performed without complications. Kidney biopsies were done at median 254 days after transplantation (range 126-680). Baseline serum creatinine (mg/dL) prior to transplant was 0.95 (median, range 0.65-1.1, reference range: 0.64-1.27 mg/dL). Creatinine at time of biopsy: 3.0 (median, range 1.53-5.07). Urine albumin/creatinine ratio: 832 (median, range 55-2864, reference range: The kidney biopsy findings are summarized in Table 2. All patients had evidence of endothelial cell injury, either acute or chronic. Three patients had features suggestive of GvHD of the kidney while one patient had BK virus nephropathy. Four of the 8 recipients died; 80 days (median, range 39-124) from the biopsy, 346 days (median, range 178-804) from transplantation. The clinical outcome is summarized in Table 3. Conclusions: Kidney biopsies post-transplant are an important diagnostic tool that should be considered for prolonged kidney dysfunction or proteinuria, particularly in the setting of other post-transplant complications. Our single-center biopsy results highlight the under-recognition of kidney dysfunction complications and complexities observed post-transplant. All kidney biopsies performed were instrumental in treatment planning. Further investigation is needed to define criteria for diagnosis and to understand the pathophysiology. This requires multi-disciplinary engagement as well as a proactive approach for obtaining kidney biopsies. With appropriate transfusion support, percutaneous kidney biopsies were performed safely without complication. Download : Download high-res image (217KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.

The impact of alternative donor types on viral infections in pediatric hematopoietic stem cell transplantation.

Viral infections remain one of the most important complications following allogeneic HSCT. Few reports compare virus infection between different donor types in pediatric patients. We retrospectively analyzed viral infections and the outcome of one hundred and seventy‐one pediatric patients (median 7.38 years) who underwent allogeneic HSCT from matched related donor (MRD, n = 71), 10 of 10 HLA allele‐matched unrelated donors (MUD1; n = 29), 9 of 10 HLA allele‐matched unrelated donors (MUD2; n = 40), and haploidentical donors (n = 31). PCR screening for BK virus, adenovirus, Epstein‐Barr virus, parvovirus B19, human herpesvirus 6, and CMV were performed routinely weekly. Infections between 0‐30, 31‐100, and 101 days‐2 years were identified separately. BK virus and CMV reactivations were significantly low in MRD transplant patients (P = .046 and P < .0001, respectively), but incidences of all virus infections between MUD1, MUD2, and haplo‐HSCT were found statistically not different. The OS was found to be affected by having one or multiple virus infection (P = .04 and P = .0008). Despite antiviral prophylaxis and treatments, post‐transplant viral infections are associated with reduced overall survival. Haplo‐HSCT is comparable with MUD transplantation in the setting of viral infections. A larger study group and prospective studies are needed to confirm this observation.

Применение инфузий T-клеток памяти с целью профилактики вирусных инфекций у пациентов с гемобластозами, перенесших аллогенную трансплантацию гемопоэтических стволовых клеток с деплецией α/β-Т-лимфоцитов

Viral infections are frequent complications in the recipients of the HSCT with TCRαβ and CD19-graft depletion. Adoptive transfer of memory T cells may improve immune response to common pathogens. The work reflects the retrospective safety analysis of using the infusions of CD45RA-depleted donor lymphocytes. Data from 80 patients were analyzed. Up to 3 doses of donor lymphocytes were administered at monthly intervals, escalating to 100 × 103/kg in haploidentical transplants and 300 × 103/kg in MUD transplants. Median follow-up for alive patients was 18 (8–44) months. We did not observe any allergic reactions, septic complications after infusion of donor lymphocytes (DLI). The cumulative incidence of a de novo acute GVHD after DLI was 5% (95% CI: 2–13). In 64% patients (n = 51) was detected CMV in the blood. There were no cases of resistant CMV disease on the background of drug therapy. In patients who received DLI, 70% (n = 56) had documented appearance of virus-specific lymphocytes in peripheral blood (Elispot assay). Thus, the introduction of memory T cells at a dose of 25–100 × 103/kg body weight of the recipient for CD3+ in the case of HSCT from a haploidentical donor and 100–300 × 103/kg for an unrelated HSCT. Infusions of low dose memory T-lymphocytes after transplant engraftment are safe, potentially effective and constitute a simple measure to prevent infections in the setting of alpha/beta T-cell-depleted transplantation.

Low-dose donor memory T-cell infusion after TCR alpha/beta depleted unrelated and haploidentical transplantation: results of a pilot trial.

Recovery of immunity is delayed in recipients of T-depleted grafts. Adoptive transfer of memory T-cells may improve immune response to common pathogens. A cohort of 53 patients with malignant (n = 36) and non-malignant conditions (n = 17) received TCR alpha/beta depleted grafts from haploidentical (n = 25) or MUD (n = 28) donors. Donor lymphocytes were depleted of CD45RA-positive cells. At a median of 48 days after transplantation, patients received DLI at 25 × 103/kg CD3 cells from haploidentical or 100 × 103/kg CD3 from MUD donors. Up to 3 doses of donor lymphocytes were administered at monthly intervals, escalating to 100 × 103/kg in haploidentical transplants and 300 × 103/kg in MUD transplants. At a median follow-up of 23 months, the cumulative incidence of de novo acute GVHD after DLI is 2% (1 of 43), while the rate of reactivation of preexisting aGVHD was 50% (5 of 10). The transplant-related mortality is 6%. The overall survival rates are 80% and 88% in malignant and non-malignant conditions, respectively. Among patients with absent CMV-specific immune reactivity at baseline (n = 31) expansion of CMV-specific T-cells was demonstrated in 20 (64.5%) within 100 days. Infusions of low dose donor memory T-lymphocytes are safe and constitute a simple measure to prevent infections in the setting of alpha/beta T cell-depleted transplantation.

Nicord Single Unit Expanded Umbilical Cord Blood Transplantation: Final Results of a Multicenter Phase I/ II Trial

Background: Delayed or failed engraftment after adult UCBT is a major contributor to the morbidity, mortality and resource utilization associated with this procedure. Increasing the number of hematopoietic stem and progenitor cells within the cord blood graft may overcome this limitation. NiCord, developed and manufactured by Gamida Cell, is an ex vivo-expanded, cryopreserved graft derived from an entire cord blood unit (CBU). In a pilot study, NiCord transplanted with a second, unmanipulated CBU was shown to shorten time to neutrophil engraftment and provide long-term hematopoiesis (Horwitz M, JCI 2014). In another study, NiCord UCBT demonstrated clinical benefit by reducing the incidence of severe infections as well as the duration of hospitalization during the first 100 days following transplantation (Anand S BBMT 2017). With confirmation that NiCord expands both hematopoietic stem and progenitor cells, we conducted a multicenter study using NiCord as a single stem cell graft.Methods: The study objective was to assess safety and efficacy of NiCord as a single, ex vivo expanded stem cell graft. The primary endpoint was to assess the cumulative incidence of NiCord-derived neutrophil engraftment. Thirty-five evaluable patients, median age 44 (13-63) with ALL (n=9), AML (n=16), MDS (n=7), CML (n=2) or Hodgkin lymphoma (n=1) were transplanted at 10 sites in the USA, EU, and Singapore. 79% had intermediate-high risk disease by Disease Risk Index. All patients received myeloablative conditioning with a TBI-based (n=14) or chemotherapy-only (n=21) regimen. Graft vs. host disease (GvHD) prophylaxis consisted of MMF for a minimum of 60 days and tacrolimus or cyclosporine for a minimum of 180 days. HLA matching was 4/6 (n=25), 5/6 (n=8) or 6/6 (n=2).Results: NiCord processing resulted in a median 32-fold (20-52 fold) increase in CD34+ cells relative to that reported by the cord blood bank prior to cryopreservation. This translated to a median CD34+ cell dose of 6.3 x 106/kg (1.4-14.9 x 106/kg). The cumulative incidence of engraftment at day 42 was 94%. Two patients experienced secondary graft failure; one at day 40 due to HHV6 infection, and another at day 260 due to an overwhelming, lethal adenovirus infection. Neutrophil engraftment occurred at a median of 11 days (95% CI: 9-13 days)(Figure 1). Platelet engraftment occurred at a median 34 days (95% CI:32-42 days)(Figure 2). Full donor whole blood chimerism (≥ 95%) was observed in 100% of engrafted patients by day 100 following transplantation. The incidence of grade II-IV and grade III/IV acute GvHD was 48.6% and 12.2%, respectively. Cumulative incidence of all chronic GvHD was 45%, and moderate/severe cGvHD 11.5% at 1 year following transplantation. Median CD3+, CD4+, and CD19+ lymphocyte counts were 286/µl, 183/µl, and 147/µl at day 100, and 479/µl, 290/µl, and 446/µl at 6 months, respectively. The incidence of grade 2-3 bacterial (n=9) or grade 3 fungal (n=0) infections was 23.9% by day 100. With a median follow-up of 13 months (range 1-35 months), the 6-month and 2-year non-relapse mortality was 12.8% and 20.3%, respectively. The cumulative incidence of relapse was 27% at 2 years. The Kaplan-Meier estimate of overall survival at 6 months and 2 years was 80.5% and 50.8%, respectively.Conclusions: The rapid engraftment kinetic coupled with a low graft failure rate and durable hematopoiesis suggests a favorable safety profile of NiCord as a single umbilical cord blood graft. Ex vivo expansion of the CBU resulted in a CD34+ cell dose comparable to adult mobilized peripheral blood stem cell grafts. Compared to a recently reported multi-center phase II study of adult, unmanipulated myeloablative double UCBT (Barker J, Br. J. Haem 2014), NiCord markedly reduced the median time to neutrophil recovery (11 days vs. 22 days) and platelet recovery (34 days vs. 49 days). Transplantation of NiCord appears not to adversely affect cellular immune recovery. Quantitative assessment of neutrophil, T-cell, and B-cell recovery is comparable to that observed following adult matched unrelated donor transplantation. We conclude that UCBT using NiCord has the potential to broaden accessibility to stem cell transplantation and to become a graft of choice for patients without a matched donor. A global randomized phase III study of NiCord vs. standard UCBT is ongoing (NCT02730299). [Display omitted] DisclosuresJagasia:Therakos: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Mallinckrodt: Consultancy. Wagner:Magenta Therapeutics: Research Funding; Novartis: Research Funding. Kuball:Gadeta (www.gadeta.nl): Consultancy, Equity Ownership, Patents & Royalties: on gdT cells and receptors and isolation strategies , Research Funding; Miltenyi: Research Funding. Majhail:Anthem, Inc.: Consultancy; Sanofi: Honoraria. Montesinos:Celgene Corporation: Honoraria, Research Funding. Kurtzberg:Gamida Cell: Research Funding. Sanz:Gamida Cell: Research Funding.

Incidence of Infectious Complications in Children With Acute Lymphoblastic Leukemia Treated With Hematopoietic Stem Cell Transplantation

ObjectiveWe analyzed incidence and profile of infections in children with acute lymphoblastic leukemia (ALL) treated with hematopoietic stem cell transplantation (HSCT) in Polish pediatric HSCT departments, over a 2-year period. Patients and MethodsHospital records of 67 patients, who underwent allogeneic HSCT for ALL, were analyzed retrospectively for microbiologically documented infection: bacterial infection (BI), viral infection (VI), and fungal infection (FI). The majority of patients (40/67; 59.7%) underwent HSCT from matched unrelated donors (MUD). ResultsIn total, 84 BI in 31 patients, 93 VI in 50 patients, and 27 FI in 22 patients were diagnosed. No differences were found in the frequency of occurrence of BI according to the type of transplant (P = .16); the occurrence of VI was statistically more frequent in MUD transplant recipients as compared with matched sibling donors (MSD) and mismatched related donors (MMFD; P = .001) and there was a trend in MUD patients for the higher occurrence of FI in comparison with MSD and MMFD transplants (P = .08). Regarding disease status, the occurrence of BI, VI, and FI was statistically more frequent in children who underwent transplantation in their first complete remission (CR1), rather than those who underwent transplantation in ≥CR2 (P < .05). In conclusion, infectious complications are an important cause of morbidity in children with ALL treated with allogeneic HSCT and the incidence of infections is high in this group of patients.

Post-Transplantation Cyclophosphamide-Based Haploidentical Transplantation as Alternative to Matched Sibling or Unrelated Donor Transplantation for Hodgkin Lymphoma: A Registry Study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation.

Purpose To compare the outcome of patients with Hodgkin lymphoma who received post-transplantation cyclophosphamide-based haploidentical (HAPLO) allogeneic hematopoietic cell transplantation with the outcome of patients who received conventional HLA-matched sibling donor (SIB) and HLA-matched unrelated donor (MUD). Patients and Methods We retrospectively evaluated 709 adult patients with Hodgkin lymphoma who were registered in the European Society for Blood and Marrow Transplantation database who received HAPLO (n = 98), SIB (n = 338), or MUD (n = 273) transplantation. Results Median follow-up of survivors was 29 months. No differences were observed between groups in the incidence of acute graft-versus-host disease (GVHD). HAPLO was associated with a lower risk of chronic GVHD (26%) compared with MUD (41%; P = .04). Cumulative incidence of nonrelapse mortality at 1 year was 17%, 13%, and 21% in HAPLO, SIB, and MUD, respectively, and corresponding 2-year cumulative incidence of relapse or progression was 39%, 49%, and 32%, respectively. On multivariable analysis, relative to SIB, nonrelapse mortality was similar in HAPLO ( P = .26) and higher in MUD ( P = .003), and risk of relapse was lower in both HAPLO ( P = .047) and MUD ( P < .001). Two-year overall survival and progression-free survival were 67% and 43% for HAPLO, 71% and 38% for SIB, and 62% and 45% for MUD, respectively. There were no significant differences in overall survival or progression-free survival between HAPLO and SIB or MUD. The rate of the composite end point of extensive chronic GVHD and relapse-free survival was significantly better for HAPLO (40%) compared with SIB (28%; P = .049) and similar to MUD (38%; P = .59). Conclusion Post-transplantation cyclophosphamide-based HAPLO transplantation results in similar survival outcomes compared with SIB and MUD, which confirms its suitability when no conventional donor is available. Our results also suggest that HAPLO results in a lower risk of chronic GVHD than MUD transplantation.

422 - CMV and BK Virus Reactivation in Post Transplant Cyclophosphamide (PTCY) after Allogeneic MUD, MRD and Haploidentical Transplant

422 - CMV and BK Virus Reactivation in Post Transplant Cyclophosphamide (PTCY) after Allogeneic MUD, MRD and Haploidentical Transplant

Haploidentical Hematopoietic Stem Cell Transplant Compared with Matched Sibling and Unrelated Transplants in Adults with Philadelphia-Negative Acute Lymphoblastic Leukemia in First Complete Remission

Matched-sibling donor (MSD) and matched unrelated donors (MUD) hematopoietic stem-cell transplantation (HSCT) have been recommended for the adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR1). However, it is not defined for this portion of patients whether HLA haploidentical donor (HID) transplants can achieve equivalent outcomes compared to MSD and MUD transplants. From 2009 to 2014, 379 adult patients with Ph-negative ALL in CR1 underwent HID HSCT (n = 159), or MSD HSCT (n = 135), or MUD HSCT (n = 85). Among HID, MSD and MUD transplants, the 100-day incidences of acute graft-versus-host disease (aGVHD) Grade III-IV were 11.0%, 8.4% and 10.6% respectively (P>0.05), and 2-year chronic GVHD (cGVHD) were 38.9%, 28.5% and 35.6% respectively ( P>0.05 ). At 5 years, the incidences of relapse were 19.0%, 24.0% and 23.4% in HID, MSD and MUD transplants respectively (P>0.05). The 5-year transplant related mortality (TRM) of HID was higher than MSD transplants (16.5% vs 10.9%, P = 0.032), and no difference compared with MUD transplants (16.5% vs 18.1%, P > 0.05). However, the 5-year overall survival (OS), disease-free survival (DFS) did not differ among HID, MSD and MUD transplants (OS 70.9%, 72.0%, 65.4% respectively, P > 0.05; DFS 67.3%, 66.0%, 62.0%, respectively, P > 0.05).Our results indicate that outcomes of adult patients with Ph-negative ALL in CR1 from HID transplants are comparable to MSD and MUD transplants. DisclosuresLin:National Natural Science Foundation of China 81400141: Research Funding; National Natural Science Foundation of China 81270647: Research Funding; Science and technology planning project of Guangdong Province 2014B020226004: Research Funding; The project of health collaborative innovation of Guangzhou City 201400000003-4: Research Funding.

Outcomes for Allogeneic Hematopoietic Cell Transplantation for AML and High-Grade MDS in Older Adults in the Era of T-Replete Haploidentical Donor Grafts. a Single Center Multivariate Analysis

Introduction: Outcomes for non-transplant therapy in older adults (age> 60 years) with AML or high-grade MDS have historically been poor. Allogeneic hematopoietic cell transplantation (allo-HCT) may improve these outcomes. However, many older patients will lack suitably HLA-matched sibling donors (MRD). Furthermore, many patients from ethnic minorities will lack an optimally matched unrelated donors (MUD). Additionally, the greater incidence and severity of chronic GVHD typically seen following MUD transplants may be particularly difficult to tolerate in older patients. T-replete haploidentical donor transplants (HAPLO) using post-transplant cyclophosphamide to mitigate alloreactivity may provide a suitable donor option for some older patients. However, no detailed comparison of outcomes after HAPLO to MRD and MUD donors in elderly patients with AML and high-grade MDS have been reported in the modern era..Methods: We analyzed outcomes of patients aged > 60 years with AML or high-grade MDS who received an allo-HCT at our center between 2005 and 2015. Ex-vivo T-cell depleted transplants and cord blood transplants were excluded. Supportive care measures were identical between the three donor groups. Patient characteristics and outcome parameters were extracted from our institutional database where they had been prospectively entered. Kaplan-Meier estimates of overall survival (OS) and disease-free survival (DFS) were calculated and the cumulative incidence method with competing risks was used to calculate rates of non-relapse mortality (NRM) and relapse. Cumulative incidences of acute and chronic GVHD were estimated with death being treated as the competing risk. Cox proportional hazards models, stratified on the three transplant donor groups, were developed using OS, DFS, NRM and relapse as endpoints and other parameters as covariates. GVHD was prospectively documented by a single dedicated nurse using established criteria including NIH consensus criteria for chronic GVHD and rates calculated using the cumulative incidence method.Results: Patient characteristics (n=127, 33 HAPLO, 37 MRD, 57 MUD) were as follows: median age 64 (60-77); male 57%; regimen- myeloablative (24%) non-myeloablative (76%); graft- PBSC (80%) BM (20%); Diagnoses- AML 59%, MDS 41%; DRI- low (2%), intermediate (58%), high (39%), very high (1%); Sorror HCT-comorbidity index 0-2 (46%), >3 (54%); Median HLA mismatches were 5/10 (range 2/10 to 5/10) for HAPLO patients. Estimated rates of OS, DFS, NRM and relapse for the entire group at 2 years were 60%, 49%, 18%, and 33%. When compared to MRD and MUD, HAPLO patients had similar characteristics but were less likely to have myeloablative conditioning (6% vs. 32% and 30% respectively for MRD and MUD, p=0.016) and were more likely to have a BM graft (52% vs. 0% and 21%, p<0.001). Median follow-up of surviving patients following MRD, MUDT and HAPLO transplants were 34m, 26m and 17m. For MRD, MUD, and HAPLO transplants respectively, estimated outcomes are as follows: TRM at 1year: 14%, 14% and 9% and 2yrs 17%, 23%, 9%, Relapse at 1year - 25%, 34%, 22% and 2 yrs -32%, 34%, 33%; OS at 1 yr 72%, 72%, 77% and 2 yrs - 62%, 55% , 67%. DFS at 1 yr - 61%, 52%, 69% and 2 yrs - 51%, 43%, 58% (Fig 1.) (p=NS for all endpoints on pointwise and global comparison). The cumulative incidences of acute GVHD at 180 days were: grade 2-4 - 27%, 37% and 39%; grade 3-4 - 8%, 18% and 15% (p=NS for all) and chronic GVHD at 2 yrs were: moderate to severe - 38%, 35%, 15% (p=0.028 MUD vs HAPLO, p=0.026 MRD vs HAPLO); severe - 12%, 11%, 0% (p=0.030 MUD vs HAPLO, p=0.009 MRD vs HAPLO). On multivariable Cox analysis, donor type was not a significant predictor of OS, DFS, NRM or relapse (Table 1).Conclusions: The results show that in the current era, using predominantly non-myeloablative conditioning regimens, 2 year OS and DFS rates of 60% and 49% with a NRM <20% can be achieved in patients aged >60 years who undergo allo-HCT for AML and high-grade MDS. Outcomes of patients transplanted from HAPLO donors are comparable to those from matched donors although the rate of clinically significant chronic GVHD appears significantly less following HAPLO transplants, which may translate to an improved quality of life. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Transplantation from Matched Unrelated and Haploidentical Donor in Pediatric Severe Aplastic Anemia: Experience with TCR Alpha/Beta and CD19 Depletion As Graft Processing Method

Introduction Hematopoietic stem cell transplantation from non-sibling donors remains the only curative option for severe aplastic anemia patients refractory to ATG/CsA immunosuppression. Although the results of MUD and haploidentical transplantation in SAA have improved significantly, graft-versus host disease (GVHD) remains a serious problem, associated with significant morbidity and mortality. We investigated the role of new method of graft processing - TCR alpha/beta depletion as a way to improve the results of MUD and haploidentical transplants in SAA.Patients and methods Forty two patients with SAA were treated since November 2012 till February 2016. Median age at HSCT was 11(3-22) years, 27 male/15 female. All pts. were refractory/relapsed (36/6) after at least two courses of ATG/CsA, 3 pts. had concurrent severe hemolytic PNH. Time from diagnosis to transplant was 17(143-8,6)/15(99-5,5) months. Donors were unrelated volunteers in 32 cases, haploidentical parents in 10 cases. Preparative regimen included cyclophosphamide 100-150 mg/kg, fludarabine 150mg/kg, ATG and 2-6Gy thoraco-abdominal irradiation, in haplo transplants patients additionaly received thiophosphamide at 10mg/kg. Two patients recieved alemtuzumab instead of ATG because of anaphylaxis. Post-transplant GVHD prophylaxis included Tacro and Mtx on days +1, +3, +6. PBSC grafts were depleted of TCR alpha/beta cells and CD19 cells with CliniMACS device as recommended by the manufacturer. Patients received a median of 10(6,0-23) x106 CD34 per kg, 8(1-39) x104 TCR alpha/beta per kg.Results All patients engrafted with a median of 15 days for WBC and 13,5 days for platelets. In 4 patients after MUD transplantation secondary graft failure (rejection) developed, two of them were successfully retransplanted. Cumulative incidence of aGVHD 2-3 was 9% (95% CI: 3-27%) and 40%(95% CI: 18-85%) in MUD and haplo respectively, 90% patients with aGVHD had only skin involvement. No grade 4 aGVHD detected. Cumulative incidence of grade 3 aGVHD was 3%(95% CI: 0,5-21%) and 10%(95% CI: 2-64%) in MUD and haplo, respectively. Cumulative incidence of cGVHD was 12%(95% CI: 0,5-58%) and 30%(95% CI: 11-77%) in MUD and haplo respectively. A median follow up is 2 years. Seven patients died of viral infection - CMV (2 pts.), viral infection - CMV plus GVHD (2 pts.), microangiopathy (1 pt), 2 pts. died after second transplantation (1 - disseminated toxoplasmosis, 1 - ADV and CMV and GVHD). Event and GVHD-free survival is 73%(95% CI: 57-89%) and 60% (95% CI: 30-90%) in MUD and haplo respectively (pic.1)Overall survival is 86%(95% CI: 74-99%) and 78%(95% CI: 50-100%) respectively for MUD and haploidentical (pic.2). Prolonged stable mixed chimerism in T-cells was detected in recipients of MUD grafts in contrast to haploidentical grafts (pic/3).Conclusion TCR alpha/beta depletion is a robust platform for allogeneic transplantation from MUD and haploidentical donors in severe aplastic anemia. Results should be further improved by additional measures to control viral infections and prevent rejection in MUD transplants. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Integrated In Silico Prediction of Minor Histocompatibility Antigen Peptides in HLA-Matched Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia

Background and Rationale: T-cell responses to minor histocompatibility antigens (mHA) are important drivers of the beneficial graft versus leukemia (GvL) effect and harmful graft versus host disease (GvHD) pathology following HLA-matched allogeneic stem cell transplantation (alloSCT). Despite their importance, Genome Wide Association Studies (GWAS) have failed to elicit a prognostic set of individual mHA associated with the clinically observed GvL and GvH effects of alloSCT [Sato-Otsubo et al. Blood 2015]. This is likely due to a lack of public mHA shared across the global set of donor/recipient pairs (DRPs). Even an optimally frequent single nucleotide polymorphism (SNP) would result in a recipient restricted genetic variant in only 24% of DRPs with a matched unrelated donor (MUD) or 17% of DRPs with a matched related donor (MRD) [Armistead et al. PLoS One 2011]. Moreover, even when DRPs do share a recipient restricted genetic variant, any resulting peptide would have to bind a MHC molecule within the recipient for presentation to T-cells.Methods: To evaluate the role of mHA in alloSCT without requiring public mHA, we developed a bioinformatics pipeline to predict mHA peptides based on SNP differences taking into account peptide/MHC binding estimated by netMHCpan [Nielson et al. Genome Med 2016] and expected GvL vs GvH tissue expression derived from mRNA sequencing data from acute myeloid leukemia (AML) and normal hematopoietic, hepatobiliary, skin, and gastrointestinal tract tissues. In order to understand the distribution of mHA in HLA-matched alloSCT drawn from a diverse pool of DRPs, we applied this analysis to putative DRPs drawn from healthy individuals who underwent whole-exome sequencing as part of the 1000 Genomes Project (n = 1,916) [1000 Genomes Project Consortium et al. Nature 2015]. To evaluate the association of mHA with AML relapse and GvHD incidence following alloSCT, we predicted mHA from SNP data using clinical information from an earlier study [Armistead et al. PLoS One 2011].Results: To determine a baseline for the number of predicted mHA in an alloSCT, we considered every possible pair of samples in the 1000 Genomes data set as a theoretical alloSCT (n = 3,669,140). We determined each sample’s HLA type using PHLAT [Bai et al. BMC Genomics 2014] and then performed mHA predictions for all theoretical transplants with a 10 out of 10 HLA match (n = 10). Within each ethnicity represented in the 1000 Genomes data, the degree of HLA matching was greater than that of all ethnicities pooled, with the lowest HLA diversity in the Finnish, Chinese, and Japanese populations. The number of predicted mHA binding MHC with Kd < 500nM ranged from 6,217 to 13,545 in the 1000 Genomes theoretical HLA-matched DRPs, with mHA contained in genes selectively expressed in AML versus those selectively expressed in GvH target organs numbering 213 to 610 and 367 to 1,135, respectively. HLA-A*02:01 restricted mHA were predicted for 37 actual DRPs in the context of MUD alloSCT and 97 DRPs from MRD alloSCT [Armistead et al. PLoS One 2011]. There were significantly more predicted mHA in MUD transplants (Figure 1). Taking into account both predicted peptide/MHC binding and tissue expression, the number of predicted GvL mHA was significantly associated with remission and the aggregate number of predicted GvH mHA was significantly associated with grade 2-4 GvHD incidence in MUD transplants (Figure 2).Conclusions: Prediction of mHA based on whole-exome sequencing data is feasible and can be used to discover associations of mHA distribution features with clinical outcomes including AML remission and GvHD incidence. Future work in larger datasets will be required to validate these predicted associations and guide development of mHA-directed therapeutics. [Display omitted] [Display omitted] DisclosuresMolldrem:Astellas Pharma: Patents & Royalties.

Antithymocyte Globulin-Based Prophylaxis for Graft Versus Host Disease Compared to Post-Transplant Cyclophosphamide-Based Prophylaxis in Matched Unrelated Donor Transplantation

INTRODUCTIONPost-transplant high-dose cyclophosphamide (PTCy) has shown to prevent graft versus host disease (GvHD) after haploidentical allogeneic hematopoietic cell transplantation (HSCT). Although less extended, its use after matched unrelated donor (MUD) HSCT in combination with additional immunosuppression has been encouraging. The aim of this study was to analyze and compare outcomes of antithymocyte globulin based (ATG) versus PTCy-based GvHD prophylaxis in matched unrelated donor HSCT.MATERIAL AND METHODSWe retrospectively analyzed 51 MUD (8/8 HLA-matched) transplants performed in two Spanish centers: 25 received ATG-based prophylaxis and were performed from 2010 to 2013, and 26 received PTCy-based prophylaxis and were performed from 2013 to 2016.RESULTSCharacteristics of patients and post-HSCT complications are detailed in Table 1. There were no significant differences in age, gender, diagnosis and Disease risk index. For the ATG group, conditioning regimen consisted of fludarabine combined with busulfan (80%) or melphalan (12%), and TBI plus cyclophosphamide (8%). All patients received ATG 2 mg/kg from day -4 to day -2 followed by methotrexate and cyclosporine (CsA). Conditioning regimen for patients from the PTCy group consisted of fludarabine and busulfan (85%) and thiotepa combined with busulfan and fludarabine (15%). GvHD prophylaxis consisted of PTCy 50 mg/kg on days +3 and +4, combined with: CsA plus MMF in 57%, CsA alone in 31%, or tacrolimus plus MMF or sirolimus in 8%, and tacrolimus alone in 4%.With a median follow-up of 58 months for the ATG group and 12 months for the PTCy group, there were no statistically significant differences in overall survival at 18 months (56% vs 85%, p=0.08), in event free survival (56% vs 68%, p=0.5), and in cumulative incidence of relapse (12% vs 18%, p=0.3). Non-relapse mortality at 12 months was significantly higher in the ATG group (32% vs 10%, p = 0.04). The ATG group presented more cases of hepatic toxicity grades I-IV and hemorrhagic cystitis than PTCy group (Table 1). Cumulative incidence of acute GvHD grades II-IV was higher in the ATG group as well as acute GvHD grades III-IV, with no differences in moderate/severe chronic GvHD incidence (Figure A).CONCLUSIONIn our experience, albeit differences in follow-up and limited number of patients, we conclude that PTCy combined with additional immunosuppression after MUD allogeneic HSCT offers lower rates of acute GvHD together with less toxicity and non-relapse mortality compared to ATG-based prophylaxis. Further analysis including larger series and follow-up are needed to confirm these observations. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Low Dose Antithymocyte Globulin (ATG) for Graft-Versus-Host Disease (GVHD) Prophylaxis

ATG appears to reduce the incidence of acute and chronic GVHD after allogeneic hematopoietic stem cell transplantation (HSCT). Potential risks of this strategy include viral reactivation, delayed immune recovery and increased relapse rates. The ideal dosing of rabbit ATG in this context is largely unknown. We therefore hypothesized that low dose ATG would reduce the incidence of acute and chronic GVHD in matched unrelated donor (MUD) transplants without compromising survival and relapse rate. A retrospective analysis was performed of a cohort of high-risk MUD HSCT recipients treated since year 2013, when our practice changed to include rabbit ATG at 3 mg/Kg for all MUD transplants at the Case Medical Center in Cleveland, Ohio. Herein we present the results of this analysis.Methods. 58 MUD transplants were performed between years 2013 and 2016, with a median follow up of 262 days post-transplant. All donor-recipient pairs were matched by high resolution HLA typing at HLA-A, -B, -C, and DRB1, (8/8 matches) with the exception of 4 pairs (7/8 matches. Median age was 56 years (range, 53-64). Underlying diagnoses were AML (n=26), MDS (13), CML (n=5), NHL (n=9), Hodgkin's lymphoma (n=2), Multiple Myeloma (n=1) and myeloproliferative disorders (n=2). Preparative regimens were ablative in 26 cases (45 %) and of reduced intensity in 31 cases (55 %). Graft source was bone marrow (n=5) and peripheral blood (n=53). All but 4 pts received GVHD prophylaxis with tacrolimus, and mini-methotrexate (5 mg/m2 on days +1, +3, +6 and +11), in addition to rabbit ATG 3 mg/Kg divided in two doses on days -2 and -1 pre HSCT. Cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Human Herpes Virus (HHV6) PCR were conducted thrice weekly during the first 100 days after HSCT.Results. The 100-day cumulative incidence of grade II-IV acute GVHD was 41% (95% CI: 29-57; Fig 1), while the cumulative incidence of grade III-IV acute GVHD was 18% (95% CI: 9-35; Fig 2). 1-year cumulative incidence of chronic GVHD was 27% (95% CI: 17-42; Fig 3). At 180 days, the incidence of CMV viremia (defined as more than 1,000 copies/mL) was 25% (95% CI: 16-40), while the incidence of EBV and of HHV6 viremia was 35% (95% CI: 24-51) and 14% (95% CI: 8-27), respectively. There was no instance of EBV-related lymphoproliferative disorder.3-year overall survival estimate is 48% (95% CI: 34-62). Cumulative incidence of Non-relapse mortality (NRM) and relapse at 1 year was 21% (95% CI: 12-37) and 44% (95% CI: 29-65), respectively.Conclusion. Our study shows that low dose rabbit ATG appears to reduce chronic GVHD rates without a major effect on acute GVHD incidence. CMV, EBV and HHV6 reactivation did occur, albeit at rates that are somewhat lower than those historically reported, without EBV-driven lymphoproliferative disorder. [Display omitted] [Display omitted] [Display omitted] DisclosuresCaimi:Genentech: Speakers Bureau; Roche: Research Funding; Novartis: Consultancy; Gilead: Consultancy.

Comparable Survival Outcome with a Faster Engraftment of HSCT from a Haploidentical Donor Compared to Other Donor Types in Pediatric Acquired Aplastic Anemia

Background: Hematopoietic stem cell transplantation (HSCT) remains the preferred frontline curative modality for patients with aplastic anemia in the presence of a matched familial donor (MFD). In the absence of MFD, the general consensus is frontline immunosuppressive therapy followed by HSCT from a matched unrelated donor (MUD) in case of failure or relapse, and recently haploidentical family donor (HFD) is emerging as an alternative donor in aplastic anemia. We evaluated the outcome of HSCT in children and adolescents with acquired severe aplastic anemia (SAA), and compared outcomes of transplantation according to the donor types.Methods:We performed a retrospectively analysis of 61 patients with acquired SAA at a single center between July 1998 and May 2016. Conditioning regimen was a reduced-intensity combination of fludarabine, cyclophosphamide, and rabbit anti-thymocyte globulin in most cases, and low dose total body irradiation was added for haploidentical hematopoietic stem cell transplantation (HHCT). Grafts for HHCT were manipulated by ex vivo T-cell depletion.Results: Of the 61 patients reviewed, total 66 HSCTs were done. The median age at HSCT was 12.5 years (range, 0.7-21.7 years). By donor types, 15 patients received grafts from MFD, 20 from MUD, and 26 from HFD. Grafts for HHCTs were CD3-depleted in 12 patients, CD3/CD19-depleted in 4, and ¥á¥â+ T-cell depleted in 10 patients.Among 61 patients, 59 patients achieved neutrophil engraftment at a median of 11 days (range, 9-18 days). The medians of neutrophil engraftment were 10 days in HFD recipients, 13 days in MFD and 12 days in MUD HSCTs, respectively, and HHCT group had significantly faster neutrophil engraftment than others (Figure 1).There were 9 patients who experienced graft failure (GF) among 61 patients. Of the 35 patients with matched donors, 1 patient failed to achieve primary engraftment, and 3 experienced graft rejection after engraftment. Of the 26 HFD recipients included, neutrophil engraftment was achieved in 25 patients, except 1 patient. Additional 4 HHCT recipients experienced graft rejection within 1 month post-HHCT. Five (1 MUD, 4 HFD) out of 9 patients who experienced GF received a second HSCT and achieved sustained engraftment, another 1 patient was alive without transfusion or further treatment, and the other 3 patients died after GF.A total of 18 patients developed grade II-IV acute GvHD (13 with grade II and 5 with grade III); 9 had received MUD transplant, 7 HFD, and 2 MFD. Seven patients developed chronic GvHD; 4 patients were MUD recipients, and 3 HFD. The cumulative incidence (CI) of grade II-III acute GvHD was 34% (MUD : 45%, HFD : 33.3%, MFD : 16.7%), and 1-year CI of chronic GvHD was 14.4%. There was no statistically significant difference in GvHD occurrence according to the donor types.As for survival results, total four patients died; one HFD recipient died of CMV pneumonia on day +157 of HHCT, and other 3 patients (1 MFD, 1 MUD, 1 HFD) died after GF. Two out of these 3 patients received a second HSCT; one MUD recipient died of acute respiratory distress syndrome and acute renal failure, and another HFD recipient died of pure red cell aplasia. The other MFD recipient died of poor graft function after GF. The overall transplant-related mortality was 7.6%. At a median follow up 45.7 months (range, 1.5-195.2 months), the estimated 5-year overall survival (OS) was 92.7% in 61 patients. There was no statistical difference in OS among HSCTs from three different donor types (MFD : 92.9% vs MUD : 94.4% vs HFD : 91.3% at 5 years, respectively, p value = 0.915) (Figure 2).Conclusions: Our study demonstrated that survival outcomes of HHCT were comparable to HSCT from matched familial or matched unrelated donors in pediatric patients with acquired SAA. HHCT was associated with rapid neutrophil recovery, and tolerable treatment related toxicities in SAA patients. These data suggest that hematopoietic stem cell transplantation from haploidentical family donors is a reasonable therapeutic option for children and adolescents with acquired SAA. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.