Haploidentical Group Research Articles

Composite GRFS and CRFS Outcomes After Adult Alternative Donor HCT.

There is no consensus on the best choice of an alternative donor (umbilical cord blood [UCB], haploidentical, one-antigen mismatched [7/8]-bone marrow [BM], or 7/8-peripheral blood [PB]) for hematopoietic cell transplantation (HCT) for patients lacking an HLA-matched related or unrelated donor. We report composite end points of graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) and chronic GVHD (cGVHD)-free relapse-free survival (CRFS) in 2,198 patients who underwent UCB (n = 838), haploidentical (n = 159), 7/8-BM (n = 241), or 7/8-PB (n = 960) HCT. All groups were divided by myeloablative conditioning (MAC) intensity or reduced intensity conditioning (RIC), except haploidentical group in which most received RIC. To account for multiple testing, P < .0071 in multivariable analysis and P < .00025 in direct pairwise comparisons were considered statistically significant. In multivariable analysis, haploidentical group had the best GRFS, CRFS, and overall survival (OS). In the direct pairwise comparison of other groups, among those who received MAC, there was no difference in GRFS or CRFS among UCB, 7/8-BM, and 7/8-PB with serotherapy (alemtuzumab or antithymocyte globulin) groups. In contrast, the 7/8-PB without serotherapy group had significantly inferior GRFS, higher cGVHD, and a trend toward worse CRFS (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.69; P = .002) than the 7/8-BM group and higher cGVHD and trend toward inferior CRFS (HR, 1.36; 95% CI, 1.14 to 1.63; P = .0006) than the UCB group. Among patients with RIC, all groups had significantly inferior GRFS and CRFS compared with the haploidentical group. Recognizing the limitations of a registry retrospective analysis and the possibility of center selection bias in choosing donors, our data support the use of UCB, 7/8-BM, or 7/8-PB (with serotherapy) grafts for patients undergoing MAC HCT and haploidentical grafts for patients undergoing RIC HCT. The haploidentical group had the best GRFS, CRFS, and OS of all groups.

PS1530 POST‐TRANSPLANT CYCLOPHOSPHAMIDE IN HLA MATCHED AND HAPLOIDENTICAL TRANSPLANT RECIPIENTS RECEIVING MYELOABLATIVE TIMED SEQUENTIAL BUSULFAN CONDITIONING REGIMEN: RESULTS OF A PHASE II STUDY

Background:Timed sequential busulfan with fludarabine (Bu‐Flu) is a promising myeloablative regimen for patients undergoing matched sibling (MSD) or unrelated (MUD) donor transplant (HCT), which is well tolerated and yields low non‐relapse mortality (NRM) in older patients and those with significant comorbidities. [Popat et al, Lancet Haematology 2018]. However, this concept was not tested in the haploidentical setting. Also, whether this approach can be used with post‐transplant cyclophosphamide (PTCy) in MSD, MUD and haploidentical HCT is unknown.Aims:We started a prospective phase II trial to assess (a) if PTCy could be safely incorporated in our timed sequential Bu‐Flu regimen, and (b) whether this approach could be used in patients undergoing MSD, MUD and haploidentical HCT. The objectives were safety and to obtain preliminary evidence of efficacy.Methods:Patients with hematological malignancies received fixed dose busulfan 80 mg/m2 intravenously (i.v.) either on days −13 and −12 (n = 45), or on days −20 and −13 (n = 10). Then, all patients received fludarabine 40 mg/m2 i.v. on days −6 to −2 followed by busulfan i.v. on days −6 to −2, dosed to achieve target area under the curve (AUC) of 20,000 umol/min for the whole course based on pharmacokinetic studies. Thiotepa 5 mg/kg i.v. was given on day −7 to the haploidentical group. GVHD prophylaxis included PTCy 50 mg/kg i.v. given on days +3 and +4 and tacrolimus starting day +5. Haploidentical and later MUD recipients also received mycophenolate mofetil.Results:We enrolled 55 patients with a median age of 47 years (range, 15–65). Diagnoses were acute myeloid leukemia or myelodysplastic syndrome (n = 30), chronic myeloid leukemia or myeloproliferative disorder (n = 9), acute lymphoblastic leukemia (n = 6), lymphoma (n = 5) and myeloma (n = 5). About half had haploidentical donor (n = 26, 47%), one‐third had MUD (n = 18) and the rest had MSD (n = 11, 20%). Disease risk index was high in 18 (32%), intermediate in 32 (58%), and low in 5 (9%) patients. HCT‐comorbidity index was ≥3 in 22 (40%) patients.45 patients experienced grade 3–5 events within 100 days. These included culture‐negative neutropenic fever (32 events), infections (28 events), gastrointestinal (22 events) – predominantly grade 3 mucositis (13 events), pulmonary (11 events; including 6 episodes of pneumonia) and hepatic (11 events – mostly asymptomatic hyperbilirubinemia; 6 events). Three patients suffered diffuse alveolar hemorrhage, 1 of which was terminal. There were 4 cases of venoocclusive disease, with 1 being fatal.There were no graft failures. The median time to neutrophil engraftment was 17 days (95% CI 13–39) and that of platelets (≥ 20K/μL, n = 49) was 25 days (95% CI 11–167). The rate of grade II‐IV aGVHD was 38% (95% CI 25–51%) and that of grade III‐IV acute GVHD was 9% (95% CI 1–17%) at day 100. Rates of chronic GVHD and extensive chronic GVHD were 10% (95% CI 2–28%) and 8% (95% CI 0–15%), at 1‐year respectively.With a median follow up of 17 months (range, 5–28), 1 year OS was 71% (95% CI 60–84%), NRM was 20% (95% CI 9–31%), and relapse rate was 17% (95% CI 7–27%). One year OS in the MSD was 91% (95% CI 75–100%); it was 72% (95% CI 54–96%) in the MUD group, and 62% (95% CI 45–83%) the haploidentical group; P = 0.11 [Figure].Summary/Conclusion:Myeloablative timed sequential busulfan with fludarabine and PTCy is safe in MSD, MUD and haploidentical HCT. It appears to reduce the incidence of severe acute GVHD and chronic GVHD without an apparent increase in relapse.image

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

Haploidentical allogeneic hematopoietic stem cell transplantation increases the risk of cytomegalovirus infection in adult patients with acute leukemia.

Owing to the shortage of hematopoietic stem cells from matched sibling donors (MSD) and matched unrelated donors (MUD), the number of patients undergoing haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT) has rapidly increased. Despite a comparable overall survival (OS) and leukemia-free survival using this approach, some evidence suggests that haploidentical allo-HSCT recipients have a higher incidence of cytomegalovirus (CMV) infection, though this has not been clearly established. This study retrospectively compared the cumulative incidence of CMV DNAemia, 2-year OS, and leukemia-free survival rates in acute leukemia patients with MSD (n=41), MUD (n=18), and haploidentical donor allografts (n=21). The cumulative incidences of CMV DNAemia at day 180 in the MSD, MUD, and haploidentical groups were 39.0, 55.6, and 85.7%, respectively (P<0.000). As less than 50% of patients in the MSD group were detected to have CMV DNAemia, the median time to CMV DNAemia detection in patients allografted with MSD could not be obtained. However, it was 42 and 29days, respectively, for the MUD and haploidentical groups. Multivariate analysis revealed that haploidentical allo-HSCT (MSD vs. haploidentical: HR: 0.26; 95% CI: 0.09-0.78; P=0.017) and age (HR: 1.03; 95% CI: 1.01-1.06; P=0.011) increased CMV infection. Finally, MSD, MUD, and haploidentical allo-HSCT provided comparable 2-year OS rates (52.1%, 65.5%, and 65.6%; P=0.425) and 2-year leukemia-free survival rates (67.1%, 68.3%, and 80.7%, P=0.837). The CMV incidence was higher for haploidentical allo-HSCT than for MSD and MUD allo-HSCT; this could be explained by graft-versus-host disease prophylaxis by multiple immunosuppressants.

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.

Combination of ATG and Post-Transplant Cyclophosphamide for Gvhd Prophylaxis in Matched and Mismatched Donor Peripheral Blood Stem Cell Transplants for Myeloid Malignancies

Introduction ATG and post-transplant cyclophosphamide (PTCy) have been individually shown to be efficacious in reducing rates of GVHD in HLA matched and mismatched transplants. We adopted a combination regimen of ATG and PTCy for GVHD prophylaxis in HLA matched and mismatched transplants for myeloid malignancies in our centre, to decrease the rates of acute and chronic GVHD. Objectives We assessed the overall and progression free survival, incidence of acute and chronic GVHD, relapse rates and non-relapse mortality with this protocol. Patients and Methods Reduced intensity conditioning protocol consisted of iv Fludarabine, iv Busulphan, and low dose TBI. GVHD prophylaxis was with Thymoglobulin total dose 4.5mg/kg, PTCy total dose 100 mg/kg and cyclosporine. The stem cell source was G-CSF stimulated PBSCs. Results 169 patients (median age 58 y, range 19-74y) with high-risk myeloid malignancies (AML-64.5%, MDS-19%, MPN-12%) were treated with this protocol after obtaining institutional approval. The donor types were as follows-10/10 matched unrelated donor (MUD) in 67, 9/10 mismatched unrelated (MMUD) in 24, 10/10 matched related donor(MRD) in 35 and haplo-identical (HI) donors in 43 patients. The median follow-up in the entire cohort was 12 months. The 1year OS in the MUD, MMUD, MRD and HI groups were 73%, 54%, 74% and 56% respectively and the corresponding 1 year PFS were 66%, 38%, 49% and 51% respectively. The percentage of graft failure (primary and/or secondary) in the 4 groups were 1.5%, 12.5%, 0% and 16.3% respectively. The relapse rates were 21% in MUD, 42% in MMUD, 29% in MRD and 14% in HI groups. The MMUD patients had significantly inferior OS (p=0.03), and PFS (p=0.003), and significantly higher risk of relapse(p=0.009), compared to MUD patients. The overall incidence of grade 3-4 acute GVHD in our patients was 10 % and of moderate/severe NIH stage chronic GVHD was 11.6% which is low compared to conventional GVHD prophylaxis regimes. The percentages for grade 3-4 acute GVHD according to donor type were 16.4% in MUD, 4.2% in MMUD, 5.8% in MRD and 9.3% in HI groups and that of moderate/severe NIH stage chronic GVHD were 7.5%, 8.4%, 11.4% and 16.3% respectively. There were high rates of viral reactivation observed with this dual T lymphocyte suppression strategy. The overall incidences of CMV, and EBV reactivation and BK cystitis were 48%, 33% and 17% respectively. In addition, there were 12 pathologically confirmed cases of post-transplant lympho-proliferative disorder. Conclusion Our experience shows that PT-Cy and ATG can be combined for GVHD prophylaxis in PBSCTs for high risk myeloid malignancies and results in low rates of Gr3-4 acute GVHD and moderate/severe chronic GVHD across different donor types with acceptable relapse rates. High rates of viral re-activation are a concern and need close monitoring.

Spectrum of Infections with a Protocol of Dual T-Lymphocyte Suppression Using ATG and PTCy for Gvhd Prophylaxis in Allogeneic Transplants for High-Risk Hematological Malignancies

Introduction ATG and PTCy have been individually shown to reduce rates of GVHD in allogeneic transplants. We adopted a combination regimen of ATG and PT-Cy for GVHD prophylaxis in allogenic transplants for high risk hematological malignancies in our centre, to decrease the rates of acute and chronic GVHD. Objectives We analysed the spectrum of infections in patients who received this dual T lymphocyte suppression protocol. Patients and methods Reduced intensity conditioning consisted of iv Fludarabine, iv Busulphan, and low dose TBI. GVHD prophylaxis was with Thymoglobulin 4.5mg/kg total dose, PT-Cy 100 mg/kg total dose and cyclosporine. The stem cell source was G-CSF stimulated PBSCs. Results 197 patients (median age 57 y, range 19-74y) with high-risk hematological malignancies were treated with this protocol. The donor types were as follows-10/10 matched unrelated donor (MUD) in 76, 9/10 mismatched unrelated (MMUD) in 26, 10/10 matched related donor(MRD) in 43 and haplo-identical (HI) donors in 52 patients. The median follow-up in the entire cohort was 12 months. The 1year OS in the MUD, MMUD, MRD and HI groups were 75%, 50%, 63.3% and 56.7% respectively. The overall percentages of proven bacterial, viral, and fungal infections were 49%, 62% and 11% respectively (Table 1). The overall incidence of CMV reactivation was 48% and was significantly different among the 4 donor groups (p=0.00). We also observed high rates of EBV reactivation (33%) and BK cystitis (18%). There were 14 pathologically confirmed cases of post-transplant lympho-proliferative disorder (PTLD), of which 1 responded to discontinuation of immune-suppression and the rest needed treatment with Rituximab. There was one death attributed to PTLD. Infections were the primary cause of death in 18 patients (23% of deaths) and a contributory cause of death in an additional 16 patients (20% deaths). The overall incidence of grade 3-4 acute GVHD in our patients was 10.1 % and of moderate/severe NIH stage chronic GVHD was 11.6% which is low compared to conventional GVHD prophylaxis regimes. Only 10% of deaths were attributable to GVHD. Conclusion Our experience shows that dual T lymphocyte suppression with PT-Cy and ATG for GVHD prophylaxis results in low rates of acute and chronic GVHD, but is associated with high rates of infections, especially viral reactivation and PTLD.

Increased Risk of 100-Day and 1-Year Infection-Related Mortality in Haploidentical Stem Cell Transplantation Patients

Introduction:Haploidentical hematopoietic stem cell transplantation (HSCT) is a potentially curative intervention for various malignant and non-malignant hematological conditions. Its use has led to the near universal availability of donors, but major challenges compared to HLA-matched related donor (MRD) and HLA-matched unrelated donor (MUD) transplants still exist. Although the most frequently discussed complication of haploidentical HSCT is graft rejection or severe/fatal graft-versus-host disease (GVHD), infection remains a significant cause of morbidity and mortality compared to other forms of transplant.Methods:This was a retrospective, single institution study that analyzed the outcomes of 187 patients with various hematological diseases who received allogeneic HSCT with haplo donor transplants, MRD transplants, or MUD transplants from 2011-2018. Conditioning regimens included combinations of fludarabine, busulfan, cyclophosphamide, melphalan, antithymocyte globulin, and total body irradiation. GVHD prophylaxis included either the combination of cyclosporine, tacrolimus, and mycophenolate mofetil (MMF) or tacrolimus and methotrexate (MTX). All patients received anti-viral prophylaxis with acyclovir, anti-fungal prophylaxis with either an azole or echinocandin, and anti-bacterial prophylaxis with trimethoprim-sulfamethoxazole or levofloxacin if the absolute neutrophil count (ANC) was <500 cell/mm3. Statistical analysis was performed using the Fisher Exact Probability Test with p-values <0.05 deemed significant.Results:Of the 187 patients who underwent allogeneic HSCT, 45 (24%) of the transplants were from haploidentical donors and 142 (76%) from non-haplo donors (MRD and MUD). Amongst all patients, median time to neutrophil engraftment (ANC >500 cells/mm3) was 16 days (range 13-25 days). Acute GVHD was present in 41% of haploidentical patients and 42% of non-haploidentical patients (p >0.05). Rates of chronic GVHD were also similar between the two groups at 45% in haplo patients and 48% in non-haplo patients (p >0.05). The 100-day infection-related mortality rate following transplant was significantly higher in the haploidentical group at 9% compared to 1% in the non-haploidentical group (p = 0.03, Figure 1). In addition, the 1-year rate of infection-related mortality after transplant was also significantly increased at 16% vs. 4% in the haplo vs. non-haplo groups, respectively (p = 0.01, Figure 2). The proportion of patients who experienced bacterial and fungal infections over this time period was comparable between the two groups (41% vs. 42% for bacterial infections and 18% vs. 12% for fungal infections in haploidentical patients vs. non-haploidentical patients, p >0.05 for both) while the incidence rate of viral infections was significantly higher in the haplo group at 72% vs. 38% in the non-haplo group (p < 0.001). However, all cases of infection-related mortality were due to bacterial and fungal infections rather than viral with 27% of bacterial or fungal infections leading to patient death in haploidentical patients compared to 7% in non-haploidentical patients (p = 0.02, Figure 3).Conclusion:The results of our study showed that compared to non-haplo transplant recipients, patients who underwent haplo transplants had significantly increased risks of 100-day and 1-year mortality secondary to infections. This finding is supported by prior data demonstrating that there is a longer time to immune reconstitution, specifically of the T-cell subset and dendritic cell subgroup, in the haploidentical population (Chang et. al. Journal of Clinical Immunology 2011). Furthermore, our results showed that the increased risk of infection-related mortality is not due to higher rates of acute or chronic GVHD, implying that the risk may be due to haploidentical transplantation itself as opposed to increased amounts of immunosuppressive therapy. While there was a greater incidence rate of viral infections amongst haploidentical patients, no viral infections led to mortality in either transplant group. In contrast, despite similar rates of bacterial and fungal infections between haploidentical and non-haploidentical patients, these infections led to death more often in the haplo population. These findings are important in considering future approaches to infection prophylaxis and treatment in haploidentical transplant recipients. DisclosuresNo relevant conflicts of interest to declare.

Current Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric Acute Lymphocytic Leukemia: Success, Failure and Future Perspectives—A Single-Center Experience, 2008 to 2016

Hematopoietic stem cell transplantation (HSCT) is the only curative option for a subset of patients with high-risk or relapsed acute lymphoblastic leukemia (ALL). Given evolving practices, it is important to continually evaluate outcomes for pediatric ALL following HSCT. Outcomes after HSCT are influenced by the type of donor used as this determines the degree and method of T cell depletion used and, consequently, specific transplant-related morbidities. We retrospectively analyzed HSCT data from our center for transplants performed between January 2008 and May 2016, comparing outcomes among different donor types. One hundred and twenty-four pediatric patients underwent HSCT from a matched sibling donor (MSD; n = 48), an unrelated matched donor (UMD; n = 56), or a haploidentical donor (n = 20). We observed a similar 3-year event-free survival (EFS) for MSD recipients (of .64) and for UMD recipients (.62), but a significantly lower EFS for recipients of haploidentical transplants (.35; P = .01). Relapse was the main cause of HSCT failure and was significantly higher in the haploidentical donor group (.47 versus .19 for MSD and .24 for UMD; P = .02). Treatment-related mortality was evenly distributed among the donor groups (.17, .16, and .15 for the MSD, UMD, and haploidentical groups, respectively). Rates of infection-related mortality were lower than previously reported. Relapse is the main obstacle for successful HSCT in the contemporary era, and this effect is most evident in recipients of haploidentical donor grafts. Newer methods to improve graft-versus-leukemia effect are being evaluated and will need to be incorporated into the management of high-risk patients.

Abstract 2762: The comparison of allogeneic stem cell transplantation outcomes between haploidentical donor and international donor: A retrospective multi-institutional study in Korea

Abstract Introduction: The successful rate of hematopoietic stem cell transplantation (HSCT) from HLA-mismatched donor has been increased according to the development in management of complications including graft versus host disease (GVHD) and infections. Especially, haploidentical HSCT provides an opportunity for all patients who do not have HLA-matched sibling donor. Methods: In this study, we compared HSCT outcomes between haploidentical familiar donor and international donor (donors from Japan, China, Germany, Unites States of America and Taiwan) in acute leukemia patients. We reviewed the overall survival (OS), relapse free survival (RFS) and complications. Results: Total 142 acute leukemia patients performed HSCT from 2000 to 2016; 98 patients underwent haploidentical donor transplantation and 44 patients underwent international donor transplantation. Major variables such as age, sex, disease status and the number of CD34 stem cells were not statistically different between two groups. In survival analysis, there was no significant difference according to the donor-type. 1-year OS rate for haploidentical transplantation group was 44.1% and 52.3% for international transplantation group (p=0.345). 1-year RFS rate was 36.6% versus 40.9%, respectively (p=0.362). In addition, the incidence of complication events was similar between two groups. The acute GVHD in haploidentical group and international group were 42.9% and 43.2% (P=0.97), and the infection event within 30days after transplantation were 49.5% in haploidentical group and 34.1% in international group (p=0.09). The cumulative incidence of chronic GVHD was no significantly different (P=0.34), respectively. Conclusion: These data suggest that HSCT from haploidentital donor shows similar outcomes including survival outcomes and complications with international donor transplantation. Therefore, haploidentitial donor transplantation can be good choice for acute leukemia patients who have no HLA_matched sibling donor. Citation Format: Hyunkyung Park, Yoo Jin Lee, Sang-Jin Shin, Jayoun Lee, Inho Kim, Sung-Soo Yoon, Silvia Park, Hyewon Lee, Joonho Moon, Jun Ho Jang, Youngil Koh. The comparison of allogeneic stem cell transplantation outcomes between haploidentical donor and international donor: A retrospective multi-institutional study in Korea [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2762. doi:10.1158/1538-7445.AM2017-2762

HLA-Haploidentical Donors Seem to be Not Inferior to HLA-Identical Sibling Donors for Hematopoietic Stem Cell Transplantation of Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)?

Background PNH is an acquired clonal disorder of the hemopoietic stem cells for which the only curative treatment is allogeneic hematopietic stem cell transplantation (allo-HSCT). But allo-HSCT is challenging for those who have no HLA-matched donors.Several recent studies have shown that haploidentical HSCT for patients with hematological malignancy can achieved comparable outcomes with HLA-identical sibling transplantation . There are very few reports on the use of haploidentical HSCT for PNH . Is haploidentical HSCT a valid alternative option for patients with PNH?Methods 19 PNH patients received allo-HSCT between Dec 2007 and Oct 2015 at our institution. 12 donors were HLA-haploidentical and 7 were HLA-matched siblings. The patients were aged 8 to 54 years (median 28 years) . Of the 12 haploidentical donors, 6 were siblings, 2 fathers,2 mothers,1 son and 1 daughter. 12 patients with haploidentical donors received a myeloablative conditioning regimen consisting of busulfan, cyclophosphamide and ATG (anti-thymocyte globulin), 7 patients with identical siblings were given a reduced intensity conditioning. G-CSF-mobilized bone marrow and peripheral blood stem cells were transplanted as graft. Prophylaxis for graft-versus-host disease (GVHD) consisting of cyclosporine or tacrolimus + short-term methotrexate + mycophenolate mofetil was used for 12 patients with haploidentical donors, and cyclosporine + short-term methotrexate for 7 with identical siblings.Results All 19 patients were engrafted successfully. The median time of neutrophils (ANC) reached to 0.5×109/L and platelets (PLT) reached to 20×109/L was 12 days and 15 days in haploidentical group , and that to identical group was 11 days and 13 days ,respectively. There were 2 patients developed grade II acute GVHD in haploidentical group while 1 patients with grade IV aGVHD in identical group . Limited chronic GVHD was observed in 2/12 patients in haploidentical group and 1/7 patients in identical group. After a median follow-up time of 22.0 (range 4.0-42.0) months, the 3-year OS probability was 77.8±13.9% and 85.7±13.2% for haploidentical and identical group,respectively (P=0.03). 2 patients died of treatment-related mortality in haploidentical group, including severe pulmonary infection (n=1) and transplant-associated thrombotic microangiopathy (n=1) ,and 1 died of severe aGVHD in identical group. No patients were documented to have a recurrence of a PNH clone after HSCT in both groups.Conclusion This report seemed that long-term outcomes of HLA- haploidentical HSCT in patients with PNH were comparable to that of HLA- matched donor at our institution . Haploidentical HSCT should be considered as a valid alternative option for PNH patients without HLA- matched donors . DisclosuresNo relevant conflicts of interest to declare.

Comparison of Outcomes after Peripheral Blood Haploidentical versus Matched Unrelated Donor Allogeneic Hematopoietic Cell Transplantation in Patients with Acute Myeloid Leukemia: A Retrospective Single-Center Review

Recent studies comparing allogeneic hematopoietic cell transplantation (HCT) using HLA-matched unrelated donors (MUD) versus HLA-haploidentical donors in patients with acute myeloid leukemia (AML) have suggested equivalent outcomes. The graft source used in most studies of haploidentical transplants has been bone marrow. Similar comparisons between MUD and haplo-HCT using peripheral blood as a graft source have not been adequately performed. We reviewed the records of all 52 AML patients who underwent haplo-HCT (using peripheral blood and post-transplantation high-dose cyclophosphamide) between January 2010 and August 2015 at our institution and compared their outcomes with 88 patients who had a MUD transplant in the same time frame and were frequency matched (preanalysis) to the haploidentical group for conditioning intensity. Multivariate analysis found no difference in outcomes between the 2 groups with the exception of slower count recovery after haploidentical allografts (HR, .48; 95% CI, .32 to .74 for platelets, and HR, .47; 95% CI, .32 to .71 for neutrophils; P < .001 for both comparisons). Our retrospective analysis, although limited by the small sample size, suggests largely similar outcomes with peripheral blood haploidentical versus MUD transplants for AML.

Survival after T-Cell Replete Haploidentical Related Donor Transplant Using Post-Transplant Cyclophosphamide Compared with Matched Unrelated Donor (MUD) Transplant for Lymphoid Malignancies

▪Background: The use of haploidentical hematopoietic cell transplantation (HCT) using post- transplant cyclophosphamide (PT-Cy), calcineurin inhibitors (CNI) and mycophenolate as graft-versus-host disease (GVHD) prophylaxis is rapidly increasing in patients (pts) lacking suitable HLA-matched donors. Herein we compare outcomes of haploidentical HCT using this GVHD prophylaxis with 8/8 allele-level MUD HCT.Methods: Included are 917 adult (>18) lymphoma pts who underwent allogeneic HCT between 2008 and 2013. All pts received non-myeloablative or reduced-intensity conditioning regimens. The study cohort was divided into 3 groups; haploidentical (n=185), MUD without (w/o) antithymocyte globulin (ATG; n=491) and MUD with (w/) ATG (n=291). The primary end-point was overall survival (OS). Secondary endpoints included cumulative incidence (Cum-Inc) of acute GVHD, chronic GVHD, non-relapse mortality (NRM), relapse/progression (rel/prog) and progression-free survival (PFS). The study had an 83% power to detect an 11% difference in OS.Results: The baseline characteristics are shown in Table 1. Pts in the haploidentical group received conditioning with Flu/CY/2Gy TBI and PT-Cy + CNI and mycophenolate as GVHD prophylaxis, while the two MUD cohorts received fludarabine-based (+ an alkylator or 2GyTBI) conditioning and CNI-based GVHD prophylaxis. Graft source was bone marrow in 93% of the haploidentical pts and peripheral blood in 94% and 91% of MUD w/o ATG and MUD w/ ATG pts, respectively.The 28-day neutrophil recovery and platelet recovery were 94%, 97%, 97% (p=0.32) and 63%, 89%, 84% (p<0.001) in the haploidentical, MUD w/o ATG and MUD w/ ATG groups respectively. Cum-Inc of grade II-IV acute GVHD at day100 and chronic GVHD at 1 year was 27%, 40% and 49% (p=0.07) and 13%, 51% and 33% (p<0.001) in the haploidentical, MUD w/o ATG and MUD w/ ATG groups, respectively. On multivariate analysis (MVA) higher risk of chronic GVHD was seen in MUD w/o ATG (RR=5.85, 95%CI 3.96-8.64; p<0.0001) and MUD w/ ATG (RR=3.64, 95%CI 2.37-5.59; p<0.0001) groups relative to the haploidentical cohort. The 3 year NRM was 17%, 22% and 26% in the haploidentical, MUD w/o ATG and MUD w/ ATG groups (p=0.08), respectively. On MVA a trend towards higher NRM was noted in MUD w/ ATG cohort, RR 1.54 (95%CI 0.98 - 2.41, p=0.06), relative to the haploidentical group. Among the haploidentical, MUD w/o ATG and MUD w/ ATG cohorts the 3 year Cum-Inc of rel/prog was 36% vs. 28% vs. 36%, PFS was 47% vs. 49% vs. 38% and OS was 60%, 62% and 50% (Figure), respectively. MVA demonstrated no significant difference between the three groups in terms of rel/prog (p=0.27) and PFS (p=0.07). Compared to the haploidentical group, the two MUD groups did not have a significantly different mortality risk (inverse of OS; p>0.05), but compared to MUD w/ ATG, the MUD w/o ATG pts had a reduced mortality risk (RR=0.67; p=0.001). We tested for a transplant center effect on survival and found none.Conclusion: With lower-intensity conditioning regimens the early (up to 3 years) survival outcomes are comparable between conventional MUD transplants (w/ or w/o ATG) and haploidentical HCT with PT-Cy approach. Chronic GVHD was significantly lower with haploidentical HCT. Prospective, randomized confirmation of these findings is necessary before wide spread adoption of haploidentical HCT over MUD transplants in lymphomas. Table 1Haploidentical N=185 (%)MUD w/o ATG N=491 (%)MUD w/ ATG N=241 (%)p-valueAge @ HCT, median (range)55 (18-75)55 (19-74)55 (20-73)0.13Male sex118 (64)301 (61)163 (68)0.25White race149 (81)469 (96)227 (94)<0.001KPS ≥ 90145 (78)311 (63)153 (63)<0.001HCT-CI≥355 (30)175 (36)88 (37)<0.001Histology NHL Hodgkin139 (75) 46 (25)386 (79) 105 (21)193 (80) 48 (20)<0.001Months from diagnosis to HCT, median (range)31 (<1-255)34 (<1-342)32 (4-460)0.19High LDH @ HCT16 (31)31 (33)11 (27)<0.001BM +ve @ HCT6 (12)5 (5)2 (5)0.35Extranodal disease @ HCT18 (35)20 (21)6 (15)0.11Prior lines of therapy, median (range)3 (1-7)3 (1-12)3 (1-8)0.41Remission @ HCT CR PR Refractory Untreated / missing72 (39) 99 (54) 10 (5) 4 (2)215 (44) 215 (44) 55 (11) 6 (1)100 (41) 96 (40) 40 (17) 5 (2)0.02Disease Risk Index Low Intermediate High45 (24) 126 (68) 13 (7)199 (41) 263 (49) 48 (10)75 (31) 129 (54) 37 (15)<0.001Median follow-up, months (range)36 (5-73)35 (4-74)35 (<1-75) [Display omitted] DisclosuresArmand:Infinity: Consultancy, Research Funding; Merck: Consultancy, Research Funding; BMS: Research Funding; Sequenta, Inc.: Research Funding. Smith:Celgene: Consultancy; Pharmacyclics: Consultancy. Sureda:Seattle Genetics Inc.: Research Funding; Takeda: Consultancy, Honoraria, Speakers Bureau.

Similar Incidence of Severe Acute Gvhd and Less Extensive Chronic Gvhd in PBSCT from Unmanipulated Haploidentical Donor Compared with That from Matched Sibling Donor for Patients with Hematologic Malignancies

▪Unmanipulated haploidentical hematopoietic stem cell transplantation (haplo-HCT) resulted in encouraging outcomes for treatment of hematologic malignancies and become an alternative option in case of lacking HLA matched sibling donor (MSD). Transplantation with G-CSF mobilized peripheral blood stem cell (PBSCT) has been a stable transplant setting with MSD. Unmanipulated haploidentical donor (haplo-PBSCT) has been applied in patients with hematologic malignancies. However, the characteristics of graft-versus-host disease (GVHD) in unmanipulated haplo-PBSCT are not clear. Here, we report the results of a cohort study on the clinical features of acute and chronic GVHD in haplo-PBSCT compared with PBSCT from MSD in patients with hematologic malignancies.PATIENTS AND METHODSBetween July, 2007 and June, 2014, 94 patients with hematologic malignancies received haplo-PBSCT and 100 patients received PBSCT from MSD consecutively at our unit (Table 1). The PBSCs were collected on day 5 and 6 after 4 days of rhG-CSF (5 mg.kg¨C1 °¤day¨C1), then were infused on the day of collection. The conditioning regimen consisted of Bu (9.6 mg.kg-1, iv, days -10~-8), Carmustine, (250 mg.m-2, day -5), cytarabine (8 g.m-2, days -7~-6), CY (120mg kg-1, days -4~-3). Antithymoglobulin (ATG, rabbit; 10 mg.kg-1, days -5~-2) was used for haplo-PBSCT. All recipients received cyclosporine A, mycophenolate mofetil, and short-term methotrexate for GVHD prophylaxis. The endpoint of the last follow-up for all surviving patients was July 15, 2015.RESULTSAmong the patients with acute GVHD, there was no difference of the rate of the involved organs between these two groups (skin: 67.4% vs 68.0%, p=1.000; liver: 15.2% vs 20.0%, p=0.742; gut: 33.3% vs 32%, p=1.000). Haplo-PBSCT was associated with higher incidence of acute GVHD grade 2-4 (HR: 3.04, 95% CI: 1.55-5.98, P =0.001) and lower incidence of extensive chronic GVHD (HR: 0.49, 95% CI: 0.24-0.99, P =0.047) compared with MSD PBSCT. There was no difference of the incidence of acute GVHD grade 3-4 between these two groups (haplo-PBSCT, 9.6% vs MSD PBSCT 8.9%, P =1.000). According to NIH criteria, the incidence of severe chronic GVHD was lower in haploidentical group (13.6%) compared with MSD group (40.5%, p=0.041). There was no difference of those for mild and moderate chronic GVHD (mild: 27.3% vs 13.5%, p=0.189; moderate: 59.1% vs 45.9%, p=0.422).CONCLUSIONIn this cohort study, haplo-PBSCT was associated with similar incidence of severe acute GVHD, lower extensive chronic GVHD and lower severe chronic GVHD compared with MSD-PBSCT. It suggested the potential advantage of ATG in improvement of long-term quality of life of the transplant recipients.Table 1Characteristics of patients and donorsHaploidentical donor, n = 94Matched sibling donor, n = 100P valueGender, n (%)Receipt, male73 (77.7)64 (64.0)0.041Donor, male63 (67.0)60 (60.0)0.371AgePatient, y, median27380.055Donor, y, median38390.364Hematologic malignances, n (%)Acute leukemia72 (76.6)61 (61.0)MDS3 (3.2)21 (21.0)0.000CML5 (5.3)10 (10.0)Lymphoma14 (14.9)8 (8.0)Status of disease, n (%)0.000CR142 (44.7)76 (76)CR214 (14.9)5 (5)NR/beyond CR238 (40.4)19 (19)Time to transplant (d)3612990.946Conditioning Regimen, n (%)0.354BuCy60 (63.8)66 (66.0)TBIcy28 (29.8)23 (23.0)FB6 (6.4)11 (11.0)CD34+ in graft (106/kg)5.864.770.057≥4.6051 (54.3)41 (41.0)0.084 DisclosuresNo relevant conflicts of interest to declare.

Comparative Survival of Haploidentical and Matched Related Hematopoietic Stem Cell Transplantation for Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia

PurposeThe role of haploidentical related allogeneic hematopoietic stem cell transplantation (allo-HSCT) for Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia( Ph+ ALL) is still not clear in the imatinib era, and limited data are available from the literature. We aimed to investigate the long-term survival between the haploidentical and matched related transplant in Ph+ ALL patients, and to analyze factors affecting relapse rate in different donor-type with maintenance therapy of imatinib post-transplant. Patients and methods The study population included Ph+ ALL patients receiving allo-HSCT from either haploidentical or matched related donor, and with maintenance therapy of imatinib post-HSCT. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect BCR-ABL transcript levels. Imatinib therapy was initiated if patient neutrophil counts were>1.0 ± 109/L and platelet counts were>50.0 ± 109/L, or if they displayed a high BCR-ABL transcript levels (∼10-2 after initial engraftment) or elevated BCR-ABL transcript levels in two consecutive tests. The imatinib treatment was scheduled for 3-12 months, or BCR-ABL transcript levels were negative at least for three consecutive tests and complete molecular remission was sustained for at least 3 months). Imatinib-resistant defined as: (1) transcript levels of BCR-ABL increased in two consecutive tests at least one-month interval; or (2) detection of point mutations in the BCR-ABL kinase domain (KD) after transplant. Results The total 120 consecutive Ph+ ALL patients received allo-HSCT and maintenance therapy of imatinib post-HSCT in our center between May 2005 to September 2012. Of these, 115 patients receiving a haploidentical (n=81) and matched related (n=34) graft were analyzed. 24 patients were identified as imatinib-resistant during post-transplant period, 13 in haploidentical group and 11 in matched related group. The 5-year cumulative incidence of relapse£¨CIR£©and non-relapse mortality (NRM) among the haploidentical group and matched related group were no different ( 18.2% vs.26.0%, p=0.212; 9.4% vs.7.2%, p=0.687). At a median follow-up of 37.5 months, the 5-year DFS and OS were 72.2% and 81.5% for the haploidentical group, compared with 68.5% and 79.5% for matched related group (p = 0.265, 0.419, respectively). Multivariate analysis showed that RT-PCR-BCR-ABL positive pre-transplant was significant factor for OS in haploidentical transplant (P=0.046). Remission status (>CR1) at HCT was a significant predictor to CIR in matched related group (p=0.020), but it wasn’t a significant factor to impact on CIR in haploidentical transplant group. Imatinib-resistant was a significant factor to affect DFS, OS and CIR in both donor-type groups. Conclusion In the imatinib era, haploidentical HSCT for Ph+ALL achieves identical long-term survival compared with matched related HCT. Remission status (>CR1) at the transplant does not significantly impact on relapse in haploidentical transplant. Imatinib-resistant is a worse predictor to long-term survival and relapse rate in both donor-type group after HCT. DisclosuresNo relevant conflicts of interest to declare.

Survival after T-Cell Replete Haplo-Identical Related Donor Transplant Using Post-Transplant Cyclophosphamide Compared with Matched Unrelated Donor Transplant for Acute Myeloid Leukemia

▪Background: Increasing numbers of haplo-identical transplants are being performed and the most common approach in the United States includes transplantation of an unmanipulated graft with tacrolimus, mycophenolate and post-transplant cyclophosphamide for GVHD prophylaxis. In this analysis we compare the early outcomes after haplo-identical transplantation with this GVHD prophylaxis with that after conventional HLA-matched unrelated donor transplant approaches (MUD).Methods: Included are 2174 patients with AML aged 21-70 years and transplanted between 2008 and 2012. Cox regression models were built for recipients of myeloablative (N=1245 MUD compared with N=104 haplo-identical) and reduced intensity (N=737 MUD compared with 88 haplo-identical) conditioning transplants. Primary endpoint was 2-year overall survival. With median follow-ups of 2-3 years, surviving patients in all treatment groups were censored at 2-years.Results: Characteristics of recipients of myeloablative transplantation were similar across the two treatment groups except peripheral blood (PB) was the predominant graft with calcineurin inhibitor (CNI) with methotrexate the predominant GVHD prophylaxis for the MUD group compared to predominantly BM grafts with CNI, mycophenolate and post-transplant cyclophosphamide for the haplo-identical group. Most regimens were non-irradiation containing, 74% for MUD and 78% for haplo-identical transplants. Characteristics of recipients of reduced intensity conditioning transplants differed by treatment groups; recipients of MUD transplants were older (median age 62 vs. 57 years), more likely to report performance score 80 or lower, be in first complete remission at transplantation and shorter interval from diagnosis to transplantation. PB was the predominant graft for MUD and BM, for haplo-identical transplants. The conditioning regimen for reduced intensity haplo-identical transplants was uniform (TBI 200 cGy, cyclophosphamide, fludarabine) and for MUD transplants, it was predominantly an alkylating agent and fludarabine (79%). Day-30 cumulative incidence of neutrophil recovery was higher after myeloabative MUD compared with haplo-identical transplants (97% vs. 90%, p=0.01). Neutrophil recovery was not different after MUD and haplo-identical reduced intensity conditioning transplants (96% vs. 93%, p=0.25). Table 1 shows the results of multivariate analysis for non-relapse mortality (NRM), relapse and overall survival. Overall survival is not significantly different after haplo-identical and MUD transplants with either the myeloablative or reduced intensity conditioning approaches. The 2-year survival rates adjusted for age, disease status and interval from diagnosis to transplant after myeloablative MUD and haplo-identical transplantation were 54% (95% CI 51-57) and 47% (95% CI 37-57), respectively (p=0.22). The corresponding 2-year survival rates after reduced intensity conditioning transplantation were 49% (95% CI 45-53) and 53% (95% CI 42-63), p=0.25. We also explored for difference in survival with in vivo T-cell depletion in the myeloablative (HR 0.81, p=0.19) and reduced intensity (HR 1.18, p=0.33) MUD groups compared with the corresponding haplo-identical groups (baseline HR 1.00) and found none. We tested for a transplant center effect on survival and found none.Conclusion: With the available data, 2-year survival rates for AML after myeloablative or reduced intensity conditioning transplants are comparable after conventional MUD transplant approaches and haplo-identical transplant with the post-transplant cyclophosphamide approach. Longer follow-up of haplo-identical transplant recipients as well as confirmation of these findings in a larger population, are needed before wide spread adoption of selecting haplo-identical donors over HLA-matched unrelated donors.TableTransplant Conditioning RegimenOutcomesMyeloablative Hazard RatioReduced intensity Hazard RatioNRMHaplo-identical1.001.00MUD1.07; p=0.822.35; p=0.03RelapseHaplo-identical1.001.00MUD0.88; p=0.400.76; p=0.09SurvivalHaplo-identical1.001.00MUD0.93; p=0.611.13; p=0.46 [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Haploidentical Allogeneic Transplantation Provides Comparable Outcomes to HLA-Matched or Mismatched Unrelated Donor Grafts in Hematological Malignancies

Haploidentical (HAPLO) and unrelated donors (URD) are established cell sources for patients (pts) who lack HLA-matched siblings. Limited data are available comparing transplant (TP) outcomes using cells from HAPLO vs URD donors. We performed a retrospective analysis of sequential pts (n=54) undergoing HAPLO transplants with post-transplant cyclophosphamide (Cy). A control group of HLA 7/8 or 8/8 matched URD recipients (n=59) matched by diagnosis, transplant date, and cell source (PBSC or marrow) was identified (Table). Most HAPLO pts received cycles of pre-TP fludarabine (Flu) for lymphodepletion to achieve CD4 <0.2x109/l. HAPLO pts received Flu 30 mg/m2 qd x 5 with Cy 14.5 mg/kg qd x 2, followed by TBI, 200-400 cGy in 1 or 2 fractions (physician discretion). PB (n= 30) or BM (n= 24) was infused from 1st or 2nddegree related HAPLO donors. Post-transplant immunosuppression was Cy 50-60 mg/kg on days +3 and +4, followed by tacrolimus (tacro) and mycophenolate (MMF) starting on day +5. Pts received filgrastim daily starting at day +5. URD recipients were conditioned with a variety of standard myeloablative (n=23) or reduced intensity (n=36) regimens, and received PB (n= 40) or BM (n= 19), with daily filgrastim starting on day +9. GvHD prophylaxis was tacro and short-course methotrexate (n= 53) or tacro/MMF (n=6). CD3+ and CD15+ cell chimerisms were assessed at 4 week intervals commencing at day +28. Bone marrow staging and CD34+ cell chimerism were assessed at day +84. GvHD was staged per standard guidelines. Analysis of categorical variables was performed using the Fisher’s exact test. Non-parametric analysis of median values was used for continuous variables. Survival was assessed using the log-rank test. Informed consent for analysis of transplant outcome data was obtained before transplantation for all patients and donors.Engraftment kinetics in the HAPLO cohort was slightly slower compared to the URD cohort, ANC >0.5x109/l at a median of 16 days (range: 13-45) vs 13 days (range: 9-25, p<0.001); PLT >20x109/l median 24 days (range: 13-109) vs 15 days (range: 8-216, p= 0.02). ANC and PLT recoveries were faster for URD PB compared to BM recipients. However, engraftment kinetics did not differ for HAPLO PB or BM recipients, (ANC median days 16.5 vs. 16, p=0.38; PLT median 24 vs 26 days p=0.80). HAPLO donor CD3 engraftment was robust, with 44 of 48 (92%) HAPLO compared to 37 of 52 (71%) URD recipients achieving >95% CD3+ chimerism at day +28 (p=0.01). Engraftment failure defined by failure to achieve ANC recovery and day +28 donor CD3 chimerism >5% was reported in 4 (7.4%) HAPLO and 2 (3%) URD recipients (p=0.42).The cumulative incidence of grade II-IV aGVHD by day 100 was similar for both groups (61% vs 47%, p=0.19). The cumulative incidences of cGVHD in the HAPLO vs URD cohorts were comparable (39% vs 36%, p=0.84) and the incidence of moderate or severe cGVHD was 15% and 22%, respectively (p=0.34). At time of analysis, relapse occurred for 37% HAPLO pts (n=20) compared to 33% (n=20) in the URD group (p=0.84). 23 pts died (43%) in the HAPLO group: 12 from relapse, 5 from infection, 6 from other causes. In the URD group, 23 (39%) died: 13 from relapse, 3 from infection, 7 from other causes. The one-yr survival probabilities were 56% HAPLO and 66% URD, with median OS probabilities 18 mo and 22 mo (p=0.85). OS was lower for recipients of 7/8 vs 8/8 matched URD grafts, but the difference was not significant (not shown).These results show similar outcomes after HAPLO and URD transplant for engraftment, GvHD, relapse and OS. Almost all HAPLO pts achieved full donor CD3+ chimerism by day +28. In conclusion, HAPLO transplant with post transplant Cy is an option for pts lacking HLA matched siblings; prospective studies are needed to validate these findings. [Display omitted] ; [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Comparable Immune Reconstitution Achieved Following Unmanipulated HLA-Mismatched/Haploidentical Transplantation and HLA-Identical Sibling Transplantation

AbstractAbstract 2312Unmanipulated human leukocyte antigen (HLA)-mismatched/haploidentical trasnplantation is an established treatment for patients without HLA-matched related or unrelated donors. In contrast to HLA-matched transplant, intensified immnological suppression, including antithymocyte globulin was used to overcome the HLA barrier. However, it is currently unclear how this radically different transplantation strategy affect immunological recovery. To investigate the immune reconstituion following unmanipulated human leukocyte antigen (HLA)-mismatched/haploidentical trasnplantation and HLA-matched transplantation. Seventy-five patients underwent transplantation from either HLA-identical siblings (25 cases) or haploidentical donors (50 cases) were enrolled in this prospective study. Recovery of T-, B-, monocytes, and dendritic cell subsets, proliferative of T lymphocytes in vitro response to mitogens, were investigated. Our results showed that in the first 90 days after grafting, counts of the following T cell subsets were signifcantly lower in haploidentical transplant recipients than those of HLA-matched transplant recipients: total CD4+ T cells, and their CD45RA positive (naïve), CD45RO (memory) subpopulation. After this interval, increases in CD4+, CD4+ naïve, and CD4+ memory T cell counts were observed in surviving subjects, by 1 year after transplantation, there were no differences in the numbers of recovered CD4+, CD4+ naïve, and CD4+ memory T cells between patients receiving haploidentical transplant and those receiving HLA-identical transplantation. In contrast, total counts of CD8+ T cells declined after conditioning and were significantly reduced by day 30 post-haploidentical transplantation. Thereafter, absolute of CD8+ T cell numbers expanded dramatically, and were signifciantly higher than that of HLA-identical recipients since day 90 post transplantation time point (Figure). CD3+ cells, CD8+ naïve, and CD8+ memory T cells were comparable by 90 days after transplantation, although lower numbers of these cells were found in haploidentical group prior day 90 after grafting. Furthermore, the ratio of CD4/CD8 T cells was significantly inverted in both groups untill 1 year after transplantation. While monocytes recovered promptly and reached normal levels by day 15 after haploidentical transplantation, though they also declined slightly by the 1 year time point, at which CD4+ T cell counts rebounded. These results indciate that quantitative CD4+ T-cell recovery is delayed after haploidentical transplantation, they also suggest that compensatory expansion of cytotoxic T lymphocytes and monocytes may accompany CD4+ T lymphopenia. Subsets of DC, including myeloid DC 1 (MDC1), MDC2 and plasmacytoid DC (pDC), in haploidentical recipients on day 15, and day 30 post allografting were significantly lower than those in HLA-matched recipients. No sigificant difference in the counts of B cells at any time point after transplantation in haploidentical recipients and HLA-matched recipients were found. On day 15 after transplantation, the expression of CD28 on CD8+ T cells was sigificantly lower in patients receiving haploidentical transplantation, then increased promptly and signifcantly higher than those receiving HLA-matched transplant on day 30, and 90, after this two time point the expression of CD28 were comparable between two groups. Moreover, the expression of CD28 on CD4+ T cells was also signifcantly higher than those receiving HLA-matched transplant on day 30, and 90. While only at days 30 post transplant, the expession of CD80 on pDC were signifcantly higher in patients receiving haploidentical transplant and than those receiving HLA-identical transplantation. The ability of the patient-derived T cells to produce IFN-Ã and IL-4 by day 30 after transplantation was similar in in patients without aGVHD between haploidentical transplant recipients and HLA-matched recipients. Our results suggest that comparable immune reconstitution could be achieved folloing hapolidentical transplantation and HLA-matched transplantation, this is related to the similar transplant outcomes. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Allogeneic Hematopoietic Stem Cell Transplantation for Treatment of Philadephia Chromosome Negative Acute Lymphoblastic Leukemia.

Abstract 4338 ObjectiveTo explore the optimum donor selection of allogeneic hematopoietic stem cell transplantation (allo-HSCT) applied in patients with Philadephia chromosome-negative acute lymphoblastic leukemia(Ph- ALL) and investigate its relevant prognostic factors. MethodsA total of 48 adult patients with Ph- ALL who had admitted to our hospital and been treated by allo-HSCT from February 2002 to May 2008 were followed up until July 2008. They were divided into match related donor(MRD -HSCT) group, match unrelated donor(MUD-HSCT) and Haploidentical (Haplo-HSCT) group. Clinical characteristics of these groups were retrospectively analyzed. Survival data were analyzed by the Kaplan-Meier method and the prognostic factors were analyzed with the COX regression model. ResultsOf all the 48 cases, 5-year overall survival(OS) was 45.4±8.1%, disease free survival(DFS) was 40.7±7.9%.The 5-year OS and DFS of MRD –HSCT subgroup, MUD-HSCT subgroup and Haplo-HSCT subgroup were 50%±14.4%,53.2%±13.2%, 31.3%±13.6%(p=0.048) and 44.7%±13.3%,41.4%±13.6%,32.1±14.2%(p=0.167), respectively. Haplo-HSCT subgroup 5-year OS lower than other two subgroups, which showed statistical significance. GradeIIto‡W acute graft versus host disease(aGVHD) [p=0.001,RR=6.980] and white blood cell at diagnosis higher than 30×109 /L[p=0.028, RR=2.679]were the risk factor of OS in multiple covariate analysis model. The HSCT type was not independent risk factor of OS. ConclusionMUD-HSCT and MRD-HSCT have similar efficacy in adult Ph- ALL. Haplo-HSCT can be a distinct option in High-risk adult Ph- ALL patients without a MRD and MUD. Disclosures:No relevant conflicts of interest to declare.

HLA, MLR, P and Lewis antigens and living donor renal transplantation in a single centre in the Middle East.

One hundred and fifty-one living donor renal transplants performed in a single centre in Kuwait were analysed for graft survival in relation to HLA matching, mixed lymphocyte reaction (MLR), P and Lewis antigens. There was a significant difference in graft survival (P = .05) but only at 3, 4 and 5 years between HLA identical (97%, 94%, 94%) and haploidentical combinations (83%, 81% and 79%), respectively. The zero haplotype matched combinations were not significantly different in graft survival from the identical or haploidentical groups. Compatibility or incompatibility for P or Lewis antigens did not influence graft survival. The MLR was significant (P = .05) with the MLR negative recipients having 100% graft survival at 4 years compared to 84% in the MLR positive group. In conclusion with an overall actuarial graft survival of 84% at 6 years none of the factors examined 'dramatically' influenced graft survival. The 'Centre Effect' is the main factor influencing graft survival in our Centre.