Matched Unrelated Donor Transplantation Research Articles

Characteristics of Graft-Versus-Host Disease (GvHD) After Post-Transplantation Cyclophosphamide Versus Conventional GvHD Prophylaxis

Post-transplantation cyclophosphamide (PTCy) has been shown to effectively control graft-versus-host disease (GvHD) in haploidentical (Haplo) transplantations. In this retrospective registry study, we compared GvHD organ distribution, severity, and outcomes in patients with GvHD occurring after Haplo transplantation with PTCy GvHD prophylaxis (Haplo/PTCy) versus HLA-matched unrelated donor transplantation with conventional prophylaxis (MUD/conventional). We evaluated 2 cohorts: patients with grade 2 to 4 acute GvHD (aGvHD) including 264 and 1163 recipients of Haplo and MUD transplants; and patients with any chronic GvHD (cGvHD) including 206 and 1018 recipients of Haplo and MUD transplants, respectively. In comparison with MUD/conventional transplantation ± antithymocyte globulin (ATG), grade 3-4 aGvHD (28% versus 39%, P=.001), stage 3-4 lower gastrointestinal (GI) tract aGvHD (14% versus 21%, P=.01), and chronic GI GvHD (21% versus 31%, P=.006) were less common after Haplo/PTCy transplantation. In patients with grade 2-4 aGvHD, cGvHD rate after Haplo/PTCY was also lower (hazard ratio [HR]=.4, P < .001) in comparison with MUD/conventional transplantation without ATG in the nonmyeloablative conditioning setting. Irrespective of the use of ATG, non-relapse mortality rate was lower (HR=.6, P=.01) after Haplo/PTCy transplantation, except for transplants that were from a female donor into a male recipient. In patients with cGvHD, irrespective of ATG use, Haplo/PTCy transplantation had lower non-relapse mortality rates (HR=.6, P=.04). Mortality rate was higher (HR=1.6, P=.03) during, but not after (HR=.9, P=.6) the first 6 months after cGvHD diagnosis. Our results suggest that PTCy-based GvHD prophylaxis mitigates the development of GI GvHD and may translate into lower GvHD-related non-relapse mortality rate.

Matched Unrelated Hematopoietic Stem Cell Transplant in Juvenile-Onset Krabbe's Disease

Background: Krabbe's disease is a neurodegenerative condition caused by a deficiency of a lysosomal enzyme, galactocerebrosidase (GALC), found mainly in the brain. There are four variants based on the age of onset: Infantile, late infantile, juvenile, and adult. Hematopoietic stem cell transplants can be curative as the GALC-positive donor cells migrate to the brain and provide GALC, thus correcting the deficiency. However, this is most effective when performed in the asymptomatic or mildly symptomatic phase. Maximum experience is in infantile-onset disease. The types of transplants usually used are matched sibling donor transplant or umbilical cord blood transplant. Clinical Description: A 5-year-old girl, the only child of a nonconsanguineous marriage, presented with complaints of frequent falls and progressive visual deterioration for 2 months. After evaluation, the clinical phenotype was ascertained to be that of a juvenile-onset (&gt;5 years) neurodegenerative disorder with neuro-axis involvement of the brain (predominantly, white motor involvement-because of gait abnormalities and visual involvement) and absence of organomegaly or any other systemic involvement. Krabbe's disease was suspected. Supportive evidence was found on neuroimaging and confirmed by a homozygous mutation in the GALC gene that was consistent with Krabbe's disease. Management: The patient was treated with a matched unrelated bone marrow transplant, a modality that is generally not used in the management of Krabbe's disease. The clinical, neurophysiological, and neuroradiological profiles are compared during a 2-year follow-up. Currently, 2 years' posttransplant, she has not deteriorated further neurologically, and though legally blind is attending a special school for the visually impaired and performing most activities of daily living independently. Conclusion: Early matched unrelated donor transplant can be beneficial in juvenile-onset Krabbe's disease.

Defibrotide Prophylaxis of Sinusoidal Obstruction Syndrome in Adults Treated With Inotuzumab Ozogamicin Prior to Hematopoietic Stem Cell Transplantation.

Sinusoidal Obstruction Syndrome (SOS) is a life threatening HSCT complication and it can rapidly evolve in Multiple Organ Dysfunction Syndrome, with a mortality exceeding 80%. Early treatment with defibrotide is the leading factor for efficacy. Its prophylactic use is recommended in the pediatric setting, but its value isn’t validated for adults, although factors for individual risk assessment are debated. We here present a real-world experience of Defibrotide prophylaxis in adults at very high risk of SOS. We treated with prophylactic Defibrotide and Ursodeoxycholic Acid seven patients receiving allogeneic HSCT for high risk B-ALL, previously treated with single agent Inotuzomab-Ozogamicin. They all had other high risk factors for SOS such as previous hepatotoxicity, previous allo-HSCT, double alkylating conditioning. All patients received Treosulfan-Fludarabine conditioning, Thiotepa was added in 4 patients and 4GyTBI in 2 patients. GvHD prophylaxis included post-transplant cyclophosphamide, rapamycin and mycophenolate. Donor source was PBSC. Five patients received family MMRD transplant, 1 patient a MRD transplant and 1 patient a MUD transplant. Non-severe gastrointestinal bleeding occurred in two patients requiring defibrotide temporarily discontinuation. SOS occurred in 3/7 cases within 21 days after HSCT and no late-onset SOS were diagnosed. SOS caused death in all cases. All three patients were characterized by a common pattern of very high risk factors by prior HSCT, they all received a myeloablative conditioning with Treosulfan-Thiotepa and a MMRD transplant. Defibrotide prophylaxis apparently failed to protect against the development of SOS in those patients treated with a double alkylator-based conditioning regimen, while a possible efficacy for the other high-risk patients is debatable.

Does recipient body mass index inform donor selection for allogeneic haematopoietic cell transplantation?

It is not known whether obesity has a differential effect on allogeneic haematopoietic cell transplantation outcomes with alternative donor types. We report the results of a retrospective registry study examining the effect of obesity [body mass index (BMI)>30] on outcomes with alternative donors (haploidentical related donor with two or more mismatches and receiving post-transplant cyclophosphamide [haplo] and cord blood (CBU)] versus matched unrelated donor (MUD). Adult patients receiving haematopoietic cell transplantation for haematologic malignancy (2013-2017) (N=16 182) using MUD (n=11 801), haplo (n=2894) and CBU (n=1487) were included. The primary outcome was non-relapse mortality (NRM). The analysis demonstrated a significant, non-linear interaction between pretransplant BMI and the three donor groups for NRM: NRM risk was significantly higher with CBU compared to haplo at BMI 25-30 [hazard ratio (HR) 1.66-1.71, p<0.05] and MUD transplants at a BMI of 25-45 (HR, 1.61-3.47, p<0.05). The results demonstrated that NRM and survival outcomes are worse in overweight and obese transplant recipients (BMI≥25) with one alternative donor type over MUD, although obesity does not appear to confer a uniform differential mortality risk with one donor type over the other. BMI may serve as a criterion for selecting a donor among the three (MUD, haplo and CBU) options, if matched sibling donor is not available.

HLA-Haploidentical Family Donors: The New Promise for Childhood Acute Lymphoblastic Leukaemia?

Allogeneic haematopoietic stem cell transplantation (HSCT) is indicated in children with high-risk, relapsed or refractory acute lymphoblastic leukaemia (ALL). HLA-matched grafts from cord blood and stem cell repositories have allowed patients without suitable sibling donors to undergo HSCT. However, challenges in procuring matched unrelated donor (MUD) grafts due to high cost, ethnic disparity and time constraints have led to the exponential rise in the use of stem cells from human leukocyte antigen (HLA)-haploidentical family donors. Whilst HLA-haploidentical HSCT (hHSCT) performed in adult patients with acute leukaemia has produced outcomes similar to MUD transplants, experience in children is limited. Over the last 5 years, more data have emerged on hHSCT in the childhood ALL setting, allowing comparisons with matched donor transplants. The feasibility of hHSCT using adult family donors in childhood ALL may also address the ethical issues related to selection of minor siblings in matched sibling donor transplants. Here, we review hHSCT in paediatric recipients with ALL and highlight the emergence of hHSCT as a promising therapeutic option for patients lacking a suitable matched donor. Recent issues related to conditioning regimens, donor selection and graft-vs.-host disease prophylaxis are discussed. We also identify areas for future research to address transplant-related complications and improve post-transplant disease-free survival.

Impact of donor types on reduced-intensity conditioning allogeneic stem cell transplant for mature lymphoid malignancies.

We retrospectively compared the outcomes of reduced-intensity conditioning (RIC) transplantation from matched related donors (MRD; n = 266), matched unrelated donors (MUD; n = 277), and umbilical cord blood (UCB; n = 513) for mature lymphoid malignancies. The 3-year overall survival rates for the MRD, MUD, and UCB groups were 54%, 59%, and 40%, respectively (P < 0.001). Multivariate analysis showed no differences in survival between the MRD group and the MUD or UCB group. However, survival was significantly affected by the conditioning regimen and graft-versus-host disease (GVHD) prophylaxis in the UCB group, but not in the MRD and MUD groups. Notably, multivariate analysis showed that the risk of overall mortality in the UCB recipients who received the optimal conditioning regimen and GVHD prophylaxis (n = 116) was lower than that in the MRD group (relative risk [RR], 0.69; P = 0.03) and tended to be lower than that in the MUD group (RR, 0.75; P = 0.09). Our results suggest that UCB transplantation performed with the optimal conditioning regimen and GVHD prophylaxis is highly effective. Moreover, UCB is readily available. Thus, UCB transplantation with the optimal conditioning regimen and GVHD prophylaxis is preferable to MUD transplantation when MRD are not available in the setting of RIC transplantation for mature lymphoid malignancies.

Post-Transplant High Dose Cyclophosphamide and Bortezomib As Graft-Versus-Host Disease Prophylaxis Following Allogeneic Hematopoietic Stem Cell Transplantation

Introduction. Prevention of graft-versus-host disease (GvHD) following allogeneic hematopoietic cell transplantation (AHCT) remains a major challenge. The combination of methotrexate (MTX) and a calcineurin inhibitor has been the standard regimen for prophylaxis in patients receiving matched sibling donor (MSD) or matched unrelated donor (MUD) transplants for the past few decades. However, over 50% of patients undergoing AHCT still develop acute or chronic GvHD or even both, causing high rates of morbidity and mortality. Moreover, calcineurin inhibitors also have untoward toxic side effects. High dose post-transplant cyclophosphamide (PTCy), initially introduced for GvHD prevention in the setting of haploidentical transplantation, has now been studied in MSD and MUD transplants. We adopted a novel approach to prevent GvHD using a short course of PTCy and bortezomib. We hypothesized that such combination is safe and effective and omits the need for calcineurin or m-TOR inhibitors.Study Design. We report the outcomes of a prospective cohort of patients who received PTCy and bortezomib for GvHD prevention following MSD or MUD transplants. Twenty-eight patients were treated in a phase I-II trial and their clinical outcomes were previously reported (al-Homsi AS et al, BBMT 2019). Most of the remaining patients were treated on an extension trial. GvHD prevention consisted of PTCy 50 mg/kg IV on day +3 and +4, and bortezomib 1.3mg/m 2 IV 6 hours after transplant and again 72 hours after. Patients receiving MUD transplants also received rabbit ATG (thymoglobulin®) 5mg/kg total IV fractionated on day -4 to -2. All patients received peripheral blood grafts and standard supportive care as per Institutional policy. G-CSF was administered routinely until neutrophil engraftment.Results. Fifty-eight patients are included in this analysis. Median age was 60 (range 22-78) years. Fifty-three percent of patients were male. Underlying malignancies consisted of myeloid and lymphoid malignancies in 79.3% and 20.6%, respectively. Acute myeloid leukemia (50%) and myelodysplastic syndromes (24.1%) were the most common diseases. At transplant, disease risk index was low, intermediate, high and very high in 19.0%, 48.3%, 31.0% and 1.7% of patients, respectively. Median Pretransplant Assessment of Mortality Score (PAM) was 16.7 (5.4-29.4). Grafts were from MSD in 24.1% or MUD in 75.9% of patients. Recipient (R)/Donor (D) CMV status at transplant was as follows: R+/D+: 43%; R+/D-: 21%; R-/D+: 14% and R-/D-: 22%. Conditioning regimens consisted of reduced intensity fludarabine and busulfan in all but 2 patients who were conditioned with myeloablative fludarabine and busulfan. Overall, the regimen was remarkably well tolerated. Median times to neutrophil and platelet engraftment were 16 (13-28) and 26 (15-57) days respectively. No patient experienced primary graft failure. CMV and EBV reactivation rates were 46.6% and 24%. Cumulative incidences of grade II-IV and grade III-IV acute GVHD were 35% (95% CI: 22%-47%) and 15% (95% CI: 7%-25%) at day +120, respectively. Cumulative incidence of chronic GvHD was 14% at 1 year . Overall, 34% of patients required immunosuppression with systemic steroids after day +4 either for grade III-IV acute or chronic GvHD. Disease relapse rate was 26%. One-year cumulative incidence of transplant-related mortality was 14% (95% CI: 6%-25%). Median overall survival was 30.7 (95% CI: 15.7-not yet reached) months. One-year overall survival was 72% (95% CI: 57%-82%). One-year composite GvHD (acute and chronic) free and relapse free survival (GRFS) was 41.6% (95% CI: 28.9%-54%).Conclusion. PTCy and bortezomib combination for GvHD prophylaxis following MSD and MUD transplants is well tolerated and effective. It offers an alternative regimen to calcineurin and m-TOR inhibitor-containing regimens and may be preferred in certain settings including patients with limited resources, poor medication compliance, and with impaired renal function. A comparison of this cohort to a matched control group of patients receiving methotrexate and cyclosporine for GvHD prevention is ongoing. DisclosuresAbdul-Hay: Amgen: Membership on an entity's Board of Directors or advisory committees; Servier: Other: Advisory Board, Speakers Bureau; Jazz: Other: Advisory Board, Speakers Bureau; Abbvie: Consultancy; Takeda: Speakers Bureau. Al-Homsi: Celyad: Other: Advisory Board; Daichii Sanyko: Consultancy. OffLabel Disclosure:Cyclophosphamide and Bortezomib are used for GvHD prevention

Optimizing Donor Selection for Haploidentical Transplantation Utilizing the Four-Group T Cell Epitope (TCE-4) Algorithm for Prediction of HLA-DPB1 Non-Permissive Mismatches

▪An HLA-DPB1 non-permissive mismatch (npmm) has been associated with higher risks of acute graft-versus-host disease and non-relapse mortality after matched unrelated donor transplantation (MUDT) and thus avoiding HLA-DPB1 npmm is important in unrelated donor selection. In contrast, HLA-DPB1 npmm by the 3-group T cell epitope algorithm (TCE-3) has been shown to be protective in the context of haploidentical donor transplantation (HIDT) using post-transplant cyclophosphamide (PTCy) (Solomon et al. BBMT 2018). Additional HLA-DPB1 “permissiveness” models, also based on cross-reactive patterns of alloreactive T cells against HLA-DPB1 alleles, include the TCE-4 (based on 4 TCE groups) and functional distance (FD, based on net difference in distance between key amino acid polymorphisms) algorithms. Lastly, an expression model is based on the surface expression of the recipient mismatched HLA-DPB1 (RDP) allele according to variants of a biallelic SNP. The present analysis had 2 major aims: to 1) determine which HLA-DPB1 permissiveness model (TCE-3, TCE-4, FD, expression) provides the best tool for haploidentical donor selection and 2) analyze the role of vector (GVH vs. HVG direction) on the effect of an HLA-DPB1 npmm. A total of 322 patients with acute leukemia, MDS, lymphoma, CLL or CML, receiving a HIDT-PTCy from a single institution were evaluated with a median follow-up time of 45 months [range 6, 184]. Baseline characteristics included a median age of 50 years [19, 80], 47% non-white, HCT-CI ≥3 in 50%, PBSC graft in 80%, and myeloablative conditioning in 49%. The number of donor-recipient pairs having an HLA-DPB1 npmm according to the TCE-3, TCE-4, FD and expression was 82 (25%), 130 (40%), 54 (17%) and 99 (31%) respectively. In univariate analysis, HLA-DPB1 npmm identified by the TCE-3 and TCE-4 models were statistically associated with improved overall survival (OS) (p=0.041 and p=0.004 respectively), whereas FD risk and RDP expression were not (see figure). For disease-free survival (DFS), only the TCE-4 model showed a statistically significant association (p=0.022). Directionality of the HLA-DP npmm (GVH vs. HVG vector) had no significant impact on survival following HIDT-PTCy, a finding similar to the context of MUDT (Fleischhauer BMT 2017). In multivariate Cox analysis, adjusting for patient/donor age, gender, race, HLA-DR mismatch and transplant year, HLA-DPB1 npmm by the TCE-4 model had the most significant association with improved OS (HR 0.59, p=0.012), with TCE-3 being less predictive (HR 0.65, p=0.07) (see figure). Furthermore, HLA-DPB1 npmm by TCE-4 led to improved DFS (HR 0.69, p=0.046) and trends for lower cumulative incidences of relapse/progression (HR 0.73, p=0.16) and NRM (HR 0.54, p=0.09). In summary, the presence of an HLA-DP npmm in either the GVH or HVG direction continues to be associated with improved survival following HIDT-PTCy in a large single institution retrospective analysis with extended follow-up. Compared to the original TCE-3 model, a TCE-4-predicted HLA-DPB1 npmm is more strongly associated with overall survival. This fact, combined with the larger number of HLA-DPB1 npmm donors identified by the TCE-4 model, suggests that it may be a better selection tool for optimal haploidentical donor identification. [Display omitted] DisclosuresSolh: Partner Therapeutics: Research Funding; Jazz Pharmaceuticals: Consultancy; BMS: Consultancy; ADCT Therapeutics: Consultancy, Research Funding.

Finding the best haematopoietic stem cell transplant regimen for GATA2 haploinsufficiency: how close are we?

Finding the best haematopoietic stem cell transplant regimen for GATA2 haploinsufficiency: how close are we?

An EBMT Analysis of Matched Sibling, Mismatched Family or Matched Unrelated Donors for Allogeneic Stem Cell Transplants in MDS

An EBMT Analysis of Matched Sibling, Mismatched Family or Matched Unrelated Donors for Allogeneic Stem Cell Transplants in MDS

Use of Leflunomide for Treatment of Cytomegalovirus Infection in Recipients of Allogeneic Stem Cell Transplant

Background :Reactivation of cytomegalovirus (CMV) commonly occurs post allogeneic stem cell transplant (ASCT). The incidence is at least 40-50% in India, where most patients and donors are CMV seropositive. Ganciclovir, although the drug of choice, is expensive and associated with significant toxicities. Second line agents like foscarnet and cidofovir are not available in India leaving few therapeutic options. Leflunomide, an anti rheumatoid arthritis drug, acts by inhibiting virion assembly of CMV and has been effective in post renal transplant CMV infections. This drug is inexpensive and has a favourable toxicity profile. There have been only occasional case reports of leflunomide post ASCT. Here we report the efficacy of leflunomide in CMV reactivation in ASCT setting.Methods :All patients who underwent ASCT at our centre between April 2015 and February 2017 were included in this retrospective study. Serologic evaluation for CMV infections was done at baseline for all patients and donors. Conditioning regimens used were either myeloablative [total body irradiation (TBI)-cyclophosphamide (Cy)] or reduced intensity (fludarabine with either melphalan, or Cy or treosulfan +/- 2 gray TBI). Graft versus host disease (GVHD) prophylaxis used was cyclosporine or tacrolimus with methotrexate or mycofenolate mofetil for matched sibling donor (MSD) and matched unrelated donor (MUD) transplants. Post transplant Cy was used for haplo-identical transplants (HIT).Monitoring was done twice weekly using quantitative CMV DNA polymerase chain reaction (QPCR) on peripheral blood post transplant till day +120 or longer if patient was on steroids. Patients who were detected to have a positive QPCR greater than 500 copies/mL at 2 consecutive time points were started on pre-emptive therapy. Ganciclovir was the preferred agent for pre-emptive therapy, however in case of ongoing cytopenias, leflunomide was used. In case of clinical resistance to ganciclovir, leflunomide was added as second line. Leflunomide was started at a loading dose of 100 mg once a day for 3 days followed by daily maintenance dose of 20 mg till clearance of CMV (undetectable CMV DNA on QPCR at 2 consecutive time points) or intolerance. Failure of leflunomide was defined as > 1 log increase in CMV copy number at any time or if another anti CMV agent was added due to CMV disease or non-clearance. Invasive procedures such as broncho-alveolar lavage, colonoscopic biopsies, and liver biopsies were used to detect CMV disease, when clinically suspected.Results :Seventy patients underwent ASCT during this period. This included 47 MSD transplants, 18 HIT and 5 MUD transplants. There were 49 episodes of CMV reactivation in 43 patients (61%). The incidence was highest in HIT with 17 of 18 patients developing reactivation.Leflunomide was used in 24 (49%) of the 49 episodes of CMV reactivations. It was used as 1st line agent in 15 episodes and as 2nd line in 9. The median CMV copy number/ml was 0.82x 103 (range 0 to 13x103) on day of starting leflunomide. The median duration of use was 34 days (range 6 to 85 days). It was used pre-emptively in 20 episodes and as therapeutic (i.e. patient had end organ involvement) in 4. None of the patients had toxicity requiring stopping of the drug. Nine (38%) of the 24 CMV reactivation episodes cleared with leflunomide. When used as a 1st line agent, CMV infection cleared in 7 of the 15 episodes (46%) in comparison to ganciclovir as 1st line with which 12 (52%) of 23 episodes cleared.Seven of the 24 episodes had initial CMV burden more than 2 x 103 copies/mL. Leflunomide failed in all of these, as against clearance in 9 of the 17 episodes which had CMV less than 2 x 103 copies/mL. (p= 0.022). None of the patients who received leflunomide in therapeutic setting cleared CMV (0 of 4), compared to 9 of 20 with pre-emptive leflunomide. (p= NS).Conclusions:This is the largest study of using leflunomide for CMV reactivation in post ASCT setting to our knowledge. Leflunomide has considerable activity against CMV, however it is best used when CMV copies are less than 2000 /mL in pre-emptive setting. In therapeutic setting its role seems limited. A larger prospective study is warranted. DisclosuresNo relevant conflicts of interest to declare.

Comparison of Outcomes Following Allogeneic HCT for Adverse Cytogenetic/Molecular Risk AML Using T-Replete Haploidentical Donors to Optimally Matched Related and Unrelated Donors

Outcomes following allogeneic hematopoietic cell transplantation (allo-HCT) for AML patients characterized as adverse risk by cytogenetic or molecular criteria have historically been unsatisfactory. Relapse of AML is the primary cause of treatment failure in these patients and can affect the majority of patients with long term survival seen in only a minority of transplanted patients. We evaluated all consecutive patients who underwent first allo-HCT for AML classified as adverse risk on cytogenetic and molecular criteria by the European LeukemiaNet (Dohner et al Blood 2017) at our center between Feb 2003 and Feb 2017 in order to compare outcomes between patients transplanted using a T-replete HLA-haploidentical donor (HID) to those transplanted from a conventional matched sibling (MRD) or optimally matched unrelated donor (MUD). Patient characteristics and outcome data were prospectively entered into our institutional database from which they were retrospectively extracted for this analysis. Our institutional algorithm for donor selection prioritized MRD followed by 8/8 HLA matched MUD. HID were used for patients lacking timely access to a fully matched donor. All patients were treated using standardized supportive care algorithms in the outpatient setting. All HID transplants received GVHD prophylaxis using post-transplant cyclophosphamide (100mg/kg), tacrolimus (d+5 to +180) and MMF (d +5 to +35), MRD and MUD patients received GVHD prophylaxis with tacrolimus and methotrexate. A total of 78 patients were analyzed (HID =31, MUD=27 MRD=20) Patient characteristics were: median age=53 (23-73); male 47%; HCT-CI 0-2=45%, >3=55%; DRI Into=20%, High=65%, v High =15%; ELN adverse risk criterion - complex/monosomal karyotype = 81% , Other adverse cytogenetics = 13% , High-risk mutation =6% ; Disease Status at BMT CR1=60%, other=40%; Graft Source PBSC=85%, BM=15%; Regimen Intensity MAC=63%, RIC/NST =37%. Median follow-up of survivors was 42 months. Patient characteristics were not significantly different between HID, MRD and MUD transplants except that BM was more often the graft source in HID (23%) than MRD (0%) and MUD (15%) (p=0.06). For the entire population and patients with HID, MRD and MUD respectively, 3 year cumulative incidences of non-relapse mortality (NRM) were 21%, 19%, 20% 24% and of relapse were 45%, 42%, 50%, 44%. Three year Kaplan-Meier estimates of overall survival(OS) were 41%, 47%, 43%, 33% and disease-free survival (DFS) were 34%, 39%, 30%, 32% respectively (p=NS for all endpoints on pointwise and global comparisons for donor type). Disease-risk index (DRI) was a significant predictor of three year OS (77% for DRI-intermediate vs 34% for High/v.High, p=0.013 and 0.03 on pointwise and global comparison respectively), DFS (68% vs 26%, p=0.004 and 0.009), relapse (9% vs. 54%, p<0.001 and p=0.002 respectively). Regimen intensity (MAC vs RIC/NST), patient age (<55 vs >55), year of transplant (2003-2011vs 2012-2017) were not significant predictors of any outcome parameter. Female gender was associated with a lower 3 yr NRM (14% vs 29%), and higher OS (52%vs 41%) (p=0.059 and 0.058 on global comparison). These data demonstrate that in patients defined as Adverse Risk by the current ELN classification, three year DFS can be achieved in approximately a third of patients with a NRM of approximately 20%. DRI remains predictive even within this adverse risk cohort. HID donors produce equivalent outcomes to those using optimally matched conventional donors and specifically, relapse rate is not higher following HID even within this high-risk population. Thus, HID may be used to facilitate early transplantation. [Display omitted] DisclosuresSolh:ADC Therapeutics: Research Funding; Celgene: Speakers Bureau; Amgen: Speakers Bureau.

Comparison of Biologically Assigned HLA-Identical Versus Haploidentical Related Donor Hematopoietic Stem Cell Transplantation

Comparison of Biologically Assigned HLA-Identical Versus Haploidentical Related Donor Hematopoietic Stem Cell Transplantation

Impact of Donor Type on Long-Term Outcomes of Hematopoietic Cell Transplantation for Adult Acute Lymphoblastic Leukemia during First Remission

Background: Standard therapy for adult patients with high-risk acute lymphoblastic leukemia (ALL) consists of hematopoietic cell transplantation (HCT) including autologous-HCT (AUTO) and allogeneic-HCT from a matched-sibling donor (MSD) or matched unrelated donor (MUD). When a conventional donor is not available, HCT from a partially-mismatched unrelated donor (MMUD), cord blood transplantation (CBT) or a familial haploidentical donor (HID) is considered.Aim: Although HCT outcomes of those alternative strategies are advancing with optimization of pre-conditioning regimens with immunosuppressive agents, there are still subjects to debate. We tried to analyze the long-term HCT outcomes according to the donor types including MMUD, double CBT (DCBT) and AUTO as an alternative choice compared to the conventional donors.Methods: We enrolled 661 adult ALL patients who underwent transplantation from 1995 to 2015 in their first remission (CR1). Patients with acute undifferentiated leukemia (AUL, n=5) and mixed phenotype acute leukemia (MPAL, n=52) in the same department were also enrolled and median age was 33 years old (range, 15-65). Before 2010, our treatment strategy for ALL patients in CR1 was to offer allogeneic or autologous HCT according to the donor availability and the presence of high-risk features. After 2010, DCBT was mainly used for patients who were not available with conventional donors. For myeloablative regimen, we administered cyclophosphamide (120 mg/kg) combined with TBI (1320 cGy), and reduced intensity regimen was applied for elderly or patients with comorbid conditions which consisted of fludarabine (150 mg/m2 in total) and melphalan (140 mg/m2 in total). Conditioning regimen for AUTO was TBI (1200 cGy), ARA-C (9g/m2 in total) and melphalan (100mg/m2 in total), and fludarabine (150mg/m2 in total) was used for DCBT instead of melphalan. Graft-versus-host disease (GVHD) prophylaxis was attempted by administering calcineurin inhibitors (cyclosporine for MSD, tacrolimus for others) plus methotrexate or mycophnolate mofetil (for DCBT). Antithymocyte globulin (ATG) was administered to the patients who received grafts from MMUD.Results: Engraftment was successful in all donor types, but neutrophil and platelet recovery was significantly delayed only after DCBT (median recovery for neutrophil and platelet was 25 and 33.5 days respectively). After median follow-up of 80.4 months (range, 6.5-259.1), 7-year OS for the entire 661 patients was 57.0%. In detail, 7-year OS for MSD, MUD, MMUD, DCBT, and AUTO was 56.9%, 56.8%, 62.6%, 65.1% and 48.6% (p=0.423). MSD, MUD and MMUD showed similar relapse rate (27.5%) and non-relapse mortality (NRM) rate (20.6%), but DCBT showed significantly higher NRM rate (29.6%) and AUTO showed significantly higher relapse rate (41.6%). In contrast, DCBT showed lower relapse rate (7.2%) and AUTO showed lower NRM rate (9.7%). Interestingly, 7-year GVHD and relapse-free survival (GRFS) for MSD, MUD, MMUD, and DCBT was 34.1%, 15.0%, 40.9%, and 50.3%, respectively, which was related with higher incidence of severe chronic GVHD in MUD (27.6%) and MSD (14.1%) compared to DCBT (4.2%, p < 0.001). In high-risk subgroup (n=517) including 233 Philadelphia chromosome (Ph)-positive ALL, 7-year OS for MSD, MUD, MMUD, DCBT, and AUTO was 54.9%, 58.1%, 57.8%, 60.7%, and 33.3%, respectively. But the 7-year GRFS for MSD, MUD, MMUD, and DCBT was 30.7%, 14.5%, 35.3%, and 47.7%, respectively, which revealed lower relapse rate (8.7%) and low severe chronic GVHD (2.6%) of DCBT. Multivariate analysis showed that old age and AUTO was related with poor OS in high-risk ALL patients group, and old age and poor-risk karyotype and MUD transplant without ATG were related with poor GRFS.Conclusion: Our data showed similar transplant outcomes of alternative donors such as DCBT and ATG-applied MMUD compared to conventional donor transplants in ALL patients in CR1. In addition, GRFS was rather superior in patients treated with DCBT. Our long-term transplantation outcome results revealed that DCBT might be a good alternative choice for patients who are not available with conventional allogeneic donors, and AUTO may be considered for selected standard-risk patients with low NRM rate without a risk of GVHD. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Health Disparity in Hematopoietic Cell Transplantation for Sickle Cell Disease: Analyzing the Association of Insurance and Socioeconomic Status Among Children Undergoing Hematopoietic Cell Transplantation

OBJECTIVE: The impact of racial and socioeconomic status (SES) on access to hematopoietic cell transplantation (HCT) are well known. Even when controlled for SES, racial minorities have lower access to HCT than the racial majority groups. Since the majority of patients with sickle cell disease (SCD) in the US are of African descent, HCT for SCD provides a unique opportunity to study the impact of SES on access to HCT in a relatively uniform racial population. The objectives of this study were to explore whether insurance status and SES are associated with the HCT for SCD.METHODS: The clinical database from the SCD program at Children's Healthcare of Atlanta (CHOA), which contains over 3,100 patients, was used to identify SCD patients who have undergone HCT between January 1, 2012 and December 31, 2016 at CHOA. We then identified non-transplanted SCD patients matched for age at transplant, gender, and SCD genotype. Three matched controls were randomly selected for each case except for one older patient who only had two controls. Non-Georgia residents during the year of transplant were excluded; one sickle cell patient who had BMT due to acute lymphoblastic leukemia was also excluded. Among both the transplanted patients and their controls, insurance status was assessed as well as socioeconomic status was estimated based on block-level census data, specifically household income, home value, percent single parent households, percent unemployment, and education level. Conditional logistic regression analysis using backwards elimation was performed to determine the odds of receiving HCT.RESULTS: Of 34 patients with SCD who underwent HCT at CHOA during this time period, 27 (66.7% females and 33.3% males) were Georgia residents. Twenty-five of the 27 patients received a matched-sibling donor transplant and two had matched-unrelated donor transplant. Among the HCT patients, the median age at transplant was 8 ± 4.7 years (range 1-20 yr). Of the 27 HCT patients, 59.3% had Medicaid and 40.7% had Private insurance at the time of transplant. Among the controls, 81.3% were covered by Medicaid insurance, 17.5% with Private insurance, and 1.3% self-pay. Using a conditional logistic regression model, we found insurance status to be a statistically significant factor in predicting whether a patient undergoes HCT. The model showed that those with Private Insurance are 2.96 (95% Confidence Interval: 1.02, 8.54) times more likely to undergo HCT compared to patients with Medicaid and self-pay. No other socioeconomic status variables were associated with receiving HCT.CONCLUSION: The data suggest that there may be health disparities in the application of HCT for SCD and that SCD patients who have private insurance are more likely to undergo HCT than those with Medicaid insurance. Important limitations of this study include absence of information about the availability of matched-sibling donors among the non-transplanted patients. A more detailed analysis of the impact of disease severity on the application of HCT for SCD is warranted. Similarly, these data provide the rationale for a larger study of national trends on the impact of the type of insurance and SES on access to HCT for SCD as well as factors that may be contributing to this health disparity. DisclosuresNo relevant conflicts of interest to declare.

Hematopoietic Stem Cell Transplantation from Full Matched Alternative Donor Has Same Results As Those from Matched Sibling for Patients with Beta-Thalassemia Major —a Large-Cohort Multicenter Study from China

Background: For patients with beta-thalassemia major (TM), the optimization of both blood-transfusion and iron-chelation has resulted in a remarkable improvement in the life expectancy and the gene therapy has showed a good prospect,however, only allogeneic hematopoietic stem cell transplantation (HSCT) currently remains a curative therapy. Although experiences on leukemia proved that HLA matched alternative-donor transplant (MAT), including matched unrelated-donor transplant (MUT)and matched parent-donor transplant MPT), had similar outcomes as matched sibling transplant (MST), a large-cohort multicenter TM-MAT study has not yet been reported.Hence, we designed the current study.Methods: 583 consecutive TM-patients from four pediatric centers in China underwent HSCT between Jan. 2009 and Jun. 2016, with median follow-up time of 46 months (range: 10-105 months). Rate of male to female was 376:207. The median age at transplant was 6 years (rang:1-23years). Of them, 314 patients received MAT consisted of 235 HLA 10/10 (full-match) MAT (F-MAT) and 79 HLA 9/10 (well-match) MAT (W-MAT), and 269 patients received MST adopting bone marrow and/or cord blood. Among MAT, 214 received F-MUT and 60 W-MUT, and 21F-MPT and 19W-MPT. All patients received the NF-08-TM protocol (see Li et al., Blood 2012) briefly composed of Cyclophosphamide (Cy), IV Busulfan (by age-dependent dose adjustment and following Cy), Fludarabine and Thiotepa. Prophylaxis of GVHD consisted of ATG, Cs A, MMF and short MTX.Results: The estimated 5-year overall survival (OS), TM-free survival (TFS), cumulative incidence of graft rejection (GR) and cumulative transplant related mortality (TRM) in total were showed on the Figure. OS and TFS were 93.3%,and 91.8%,and 97.4% and 96.2% in MAT and MST, respectively. GR and TRM were 3.1% and 1.7%, and 6.7% and 2.6% in MAT and MST, respectively. Acute GVHD, chronic GVHD, venous occlusive disease and hemorrhagic cystitis were 18.6%,4.1%, 1.2% and 12.7%, and 9%, 2%, 4.3% and 6.9%, respectively, in MAT and MST.Acute GVHD (18.6% vs. 9%, P=0.001) and cytopenia (18.1% vs. 7.5%, P=0.002) in MAT was more than MST. Although no significant differences were found in comparison of F-MAT with W-MAT in OS (93.4% vs. 92.3%,P=0.487), TFS (89.1% vs. 90.9%,P=0.876), TRM (6.6% vs. 7.7%,P=0.487) and GR (5.6% vs. 4.2%,P=0.545), cytopenia post-transplant in W-MAT was more than F-MAT (27.4% vs. 15.1%, P=0.022).Conclusion: The current large-cohort multicenter TM-MAT prospective study showed that MAT had comparable result as those from MST for TM patients receiving NF-08-TM protocol. Despite similar OS and TFS, F-MAT is superior to W-MAT for TM-patients because the latter has more the complication than the former.Fig. OS, TFS, TRM and GR in 583 HSCTs in patients with beta-thalassemia major [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Who Is a Better Donor for Recipients of Allogeneic Hematopoietic Cell Transplantation: A Young HLA- Haploidenitcal Relative or an Older Fully HLA-Matched Sibling or Unrelated Volunteer?

T-cell Replete HLA-haploidenitcal donor transplantation (HIDT) with post-transplant cyclophosphamide is increasingly considered an acceptable alternative for patients lacking timely access to an optimally matched related (MRDT) or unrelated donor (MUDT). Multiple recent registry and single center studies have shown comparable overall survival and disease free survival rates among the three donor sources with a significantly lower risks of acute and chronic GVHD among HIDT recipients(1). Donor age may also affect outcomes. Many candidates for allogeneic HCT will have access to multiple available donor sources. In this situation, it is unclear whether outcomes can be improved using a younger HID rather than an older MRD or MUD.We analyzed 406 consecutive allogenic HCT recipients, median age of 54 years (range 19, 77) comparing outcomes after a MRDT (n-222) or MUDT (n-91) using a donor ≥ 35 years old to HIDT performed using donors aged ≤ 35 years (n=93). Survival was calculated using the Kaplan-Meier estimator. Univariate analysis with Gray test and log-rank test were used for cumulative incidence and survival respectively. Pointwise comparison at 3 years post HCT was performed using the Wald test. Median follow up for survivors was 51.5 months. Compared to MRDT and MUDT, HIDT recipients had similar median age at time of HCT, hematopoietic cell transplant comorbidity index (HCT-CI), disease risk index (DRI) distribution and donor recipient sex matching. Recipients of HIDT were more likely to have received TBI based Myeloablative conditioning (39% vs 18% and 11% for MUDT and MRDT, p <0.001), bone marrow graft source (33% vs 11% and 2% for MUDT and MRDT, p<0.001) and more likely to be transplanted after 2011 (79% vs 56% and 56% for MUDT and MRDT, p<0.001). The median donor age for HIDT of 27 years (range 15, 34) was significantly younger than MRDT 53 years (range 35, 77) and MUDT 41 (35, 64), p=0.001. The survival estimates and relapse incidence at 1 and 3 years respectively post HCT were: OS (80% and 64% for MRDT, 79 and 54% for MUDT, 79% and 62% for HIDT), DFS (69% and 55% for MRDT, 61% and 44% for MUDT, 66% and 58% for HIDT), TRM (11% and 19% for MRDT, 8% and 16% for MUDT, 12% and 18% for HIDT), and relapse (20% and 26 % for MRDT, 31% and 37% for MUDT, 22% and 24% for HIDT). HIDT recipients had better 3-year relapse rates (p=0.048) and DFS (p=0.042) compared to MUDT with similar overall survival. Recipients of HIDT also had significantly lower incidence of moderate-severe chronic GVHD compared to MRDT and MUDT (23% HIDT vs 45% for MUDT and 38% for MRDT, p=0.01). When limiting the analysis to recipients age ≥ 50 years (n=258), there was no difference in OS, DFS or relapse between the 3 donor sources.Recipients of HIDT from a young donor ≤35 years, have similar overall survival and lower rates of chronic GVHD compared to transplants using MRD or MUD donor ≥ 35 years. Moreover, HIDT recipients have lower relapse and better DFS compared to MUDT. This study suggests that given a situation where a choice between a young Haploidenitcal relative and an older matched unrelated donor is to be made, one can achieve better disease free survival with haploidentical donor and significantly lower rates of chronic GVHD.1. Ciurea SO, Zhang MJ, Bacigalupo AA, Bashey A, Appelbaum FR, Aljitawi OS, et al. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia. Blood. 2015;126(8):1033-40.Figure 1: Kaplan-Meier and Cumulative Incidence Curves for OS, DFS, Relapse, cGVHD, Grade II-IV and III-IV acute GVHD [Display omitted] DisclosuresSolh:ADC Therapeutics: Research Funding; Celgene: Speakers Bureau; Amgen: Speakers Bureau.

Cord Blood Regulatory T Cells for Prevention of Graft Versus Host Disease

Background: Regulatory T-cells (Tregs) are a T-cell subset capable of suppressing effector T-cells (Teffs) and, when given at the time of allogeneic hematopoietic stem cell transplantation (Allo-SCT), have been shown to prevent graft v. host disease (GVHD). We previously demonstrated that cord blood (CB) Tregs can be ex vivo expanded to clinically meaningful doses and prevent GVHD in a xenogenic mouse model. The efficacy of the ex vivo expanded CB Tregs in preventing GVHD was markedly improved with fucosylation, which adds fucose resulting in creation of a siayl-Lewis X moiety found on P-selectin ligand, thereby facilitating trafficking through the endothelium into inflammatory sites. We hypothesized that adoptive therapy with fucosylated Tregs could prevent GVHD even when given at suboptimal Tregs:Teffs ratios. We conducted a Phase I clinical trial to evaluate the clinical safety of fucosylated CB Treg infusion for GVHD prophylaxis (ww.clinicaltrials.gov NCT02423915). We now report on 5 patients who received GVHD prophylaxis with 3rdparty, ex-vivo expanded CB Tregs at a dose level of 1.0 x10e6 cells/ kg (2 un-fucosylated and 3 fucosylated CB Treg products).Patients and methods: A 3rd party CB unit with at least 3/6 HLA matching to the recipient was selected. Treg isolation and expansion was performed as shown previously. When indicated, expanded CB Tregs were incubated with substrate (GDP β-fucose) and fucosyltrasferase-VI (FT6) enzyme (TZ101, Targazyme, Carlsbad, CA) for 30 minutes, washed and infused on day -1. The first 2 patients underwent double cord transplant with Flu/Cy/TBI reduced intensity conditioning and received unfucosylated CB Tregs at a dose of 1 x 10e6/kg. The subsequent 3 patients underwent peripheral blood (PB) matched unrelated donor (MUD) transplant with Fludarabine/ Melphalan myeloablative conditioining and received fucosylated CB Tregs at a dose of 1 x 10e6/kg. All patients received additional pharmacologic GVHD prophylaxis with sirolimus and mycophenolate mofetil. All patients received their designated CB Treg dose. The median proportion of CD4+25+CD127- in the infused Treg product was 96% (94-98%). Expanded CB Treg product showed suppression of T cell proliferation using CFSE assay. For the first 2 patients, the infused graft Teffs dose was at least 12 times more than the CB Tregs and for the subsequent 3 patients, the dose of infused Teffs dose was at least 132 times more than that of the infused fucosylated CB Tregs. No infusion toxicities were observed.Results: All patients receiving fucosylated CB Tregs followed by PB MUD transplants exhibited non-infectious high fevers up to 40οC accompanied by an erythematous rash starting on post-transplant day +5 that lasted for 5-7 days and resolved after steroid administration (IV methylprednisolone 1mg/kg) for 24-96 hours. Skin biopsies were consistent with engraftment syndrome and not GVHD. All 5 patients engrafted at a median of 13 days. The three patients who received fucosylated CB Tregs and one of two patients receiving untreated CB Tregs developed ≥ grade II acute GVHD at a median of day +22 which had completely resolved by day 130 post-transplant. One patient had late onset aGVHD. No cGVHD was documented in any patient. One recipient of non-fucosylated Tregs died on day +40 due to unrelated causes (intracranial bleeding). No GVHD was observed in this patient. PB Flow cytometric analysis revealed an increase in inflammatory T-cell subsets in the first week post-transplant with a concurrent bimodal increase in the Treg populations on day -1 and day +7 (figure 1A). NK and DC but not B cell subsets were significantly increased. A consistent increase in the cell populations secreting IFNү, IL-4 and IL-17 was observed in the post-transplant period and a bi-modal increase in the IL-10 secreting cells was observed on Day -1 and Day +7 consistent with the circulating Treg cells (figure 1B).Conclusions: Our group is the first to show safety of infusing 3rd party, ex-vivo expanded CB Tregs in a PB MUD transplant setting. At a dose level of 1.0 x 10e6 /kg, 3rd party CB Tregs were administered without acute infusional toxicity and no negative impact on engraftment. The cause for the high fevers observed in the fucosylated CB Treg recipients is unclear at this time. We are now enrolling additional patients with unfucosylated Tregs in a PB MUD transplant setting to investigate the mechanisms underlying this phenomenon. [Display omitted] DisclosuresKhoury:Kiromics: Research Funding; Angle: Research Funding; Stemline Therapeutics: Research Funding; Pfizer: Research Funding.

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

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: <30).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. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Probability of Finding a Matched Unrelated Donor for An Asian Indian Patient Who Needs a Stem Cell Transplant.

Abstract 4343In March 2008 we initiated a matched unrelated donor (MUD) bone marrow transplant program. Forty three searches have been performed through the National Marrow Donor Program USA (NMDP) and through the German Registry (DKMS) and completed data is available on 17 patients. High resolution HLA typing for A, B, DRB1, C and DQB1 alleles was done by Histogenetics (USA), NMDP or DKMS. Of the 17 patients for whom the search process was completed we identified a 10/10 matched donor for 7 patients, a 9/10 for 7 patients and an 8/10 for one patient. The 8/10 mismatch was at the C and DQB1 loci. Thus 15 of 17 (88%) had a suitable donor identified. After the preliminary search 2 patients were unlikely to have a donor. Of the15 matched donors, 4 were Caucasian and 11 were Asian. HLA is determined by the racial background of the individual and therefore the probability of finding a high resolution allele matched donor for an Asian Indian would have been low in registries that are predominantly Caucasian. Identification of matches from among the primarily Caucasian donor pool is interesting and may reflect a Caucasoid background in some of the population in the sub continent. In 11 out of the 17 completed searches an Asian donor was identified (61%). The NMDP has 7.5 million donors of which 553,000 are Asian and Pacific Islanders, 141,462 are South Asian, and 36,790 are Southeast Asian. These data exclude Asian donors reported as being from multiple races. Thus there was a 61% probability of finding a matched donor from among the 141,462 South Asian donors registered with the NMDP.Eleven patients have had a MUD transplant (Acute Myeloid Leukemia: 8, Acute Lymphatic Leukemia: 2 and Myelofibrosis: 1): 3 patients died before engraftment, 8 engrafted, 5 remain in remission, 2 have relapsed and one died of sepsis 100 days post transplant. The remaining four patients with matched donors are awaiting transplant.Since identification of a well-matched donor (allele matched at HLA-A, B, C, DRB1) is important for good outcome after MUD transplantation, these early search data for Indian patients suggest the need for a greater number of donors in India to be available and HLA typed in order to increase the probability of finding a suitable match for patients needing a MUD transplant.Number of SearchesDonor 10/10Donor 9/10Donor 8/10No DonorDonor M/FDonor C/ADonor CMV +/-/?Matched donor able to proceed to collection Yes/NoTransplanted187 [39%]7 [39%]1 [6%]3 [17%]12/34/119/5/411/411C- Caucasian A- Asian Disclosures:No relevant conflicts of interest to declare.