ALBERT

Description: Introduction: Allogeneic hematopoietic cell transplant (allo-HCT) is a curative treatment option for patients with acute lymphoblastic leukemia (ALL). Both total body irradiation(TBI)-based and chemotherapy only (non-TBI) transplant conditioning regimens have been utilized. But the optimal conditioning regimen for all-HCT in ALL remains unclear. We performed a systematic review to assess the totality of evidence pertaining to the efficacy of TBI-based vs- non-TBI conditioning regimens. Methods: We searched PubMed and Embase databases for all studies comparing TBI-based vs. non-TBI conditioning regimens in patients who received allo-HCT for ALL. Two authors independently reviewed all references for inclusion and extracted data related to overall survival (OS), progression free survival (PFS), non-relapse mortality (NRM), relapse, acute- and chronic graft-versus-host disease (GVHD) whenever available. We restricted inclusion criteria to studies published only as peer-reviewed manuscripts which included ALL only patients (both T-ALL and B-ALL) who received a myeloablative conditioning; pediatric only studies were excluded. We also assessed outcomes in subgroups of patients 16 years of age and older which were majority of the included studies. Results: Seven studies were included in the final analysis that met our inclusion criteria. The quality assessment rating for each study was good based on its study type. The results for all patients in these observational studies revealed that TBI-based regimen was significantly favorable (all p.05) the risks of NRM (RR=1.09, 95% CI [0.75, 1.58], 6 studies, 4251 patients), grade II-IV acute GVHD (RR=1.11, 95% CI [0.90, 1.36], 5 studies, 4725 patients) or grade III-IV acute GVHD (RR=1.20, 95% CI [0.89, 1.63], 2 studies, 3248 patients). However, TBI-based regimen increased the risk of chronic GVHD (RR=1.12, 95% CI [1.02, 1.23], 5 studies, 4219 patients). Subgroup comparison of patients 16 years of age and older (range 16-70) showed similar results as shown in Table 1a-d. Conclusion: This meta-analysis represents evidence supporting the use of TBI-based conditioning regimens for allo-HCT in patients with ALL as it offers significantly lower risk of relapse and better survival yet acceptable NRM as compared to non-TBI regimens. Disclosures Nishihori: Karyopharm: Research Funding; Novartis: Research Funding. Shah:Celgene/Juno: Honoraria; Kite/Gilead: Honoraria; Incyte: Research Funding; Jazz Pharmaceuticals: Research Funding; Pharmacyclics: Honoraria; Adaptive Biotechnologies: Honoraria; Spectrum/Astrotech: Honoraria; Novartis: Honoraria; AstraZeneca: Honoraria. Bejanyan:Kiadis Pharma: Other: advisory board.

Description: Abstract 2015 Allogeneic hematopoietic stem cell transplantation (AlloSCT) remains the only curative option for MDS. Several retrospective studies evaluated the impact of various prognostic factors (i.e. cytogenetic risk group, WHO classification, ferritin level etc.) on post-transplant outcomes of pts with MDS, however comprehensive analyses including a cytogenetic abnormalities detected by SNP array (SNP-A) karyotyping method have not been performed. We have analyzed prognostic factors of post-AlloSCT outcomes among 74 pts with MDS (2000–2010) including the predictive value of SNP-A abnormalities. Cox proportional hazards analysis was used to identify univariable prognostic factors for acute GVHD (aGVHD), chronic GVHD (cGVHD), disease relapse, relapse free (RFS) and overall survival (OS). Multivariable prognostic factors were identified by stepwise Cox proportional hazards analysis. The median time from MDS diagnosis to transplant for all pts was 6 mos (range, 0.2– 141 mos). The median age at transplant was 51 yrs; 32% of the pts had a hematopoietic cell transplant co-morbidity index (HCT-CI) score ≥ 3; 69% had ≥1 prior chemotherapies; and only 30% were in remission prior to their transplant. 27 pts (37%) had RAEB-2, 11 (15%) had RAEB-1, and 9 (12%) had treatment-related MDS. 42 pts (58%) belonged to an intermediate-2 or higher IPSS risk category. 23 pts (31%) had adverse karyotype (complex or monosomy 7) detected by metaphase cytogenetics (MC). SNP abnormalities were identified in 58% of patients; 79% of all patients with SNP abnormalities had lesions not previously detected by traditional cytogenetic techniques. Median pre-transplant ferritin level was 1127 (range, 9–5201). 73% of the pts received myeloablative conditioning. In 61% of cases stem cells were harvested from the bone marrow. Matched related donors accounted for half of the cases. Twelve pts (16%) died within 100 days of transplant and 39 pts (53%) within the median follow up of 36 mos (range, 5–114). MDS relapse occurred in 22 pts (30%). The rates of grade II-IV aGVHD and extensive cGVHD were 49% and 24% respectively. Disease relapse was the most common cause of death (31%) followed by aGVHD (18%) and cGVHD (13%). In univariate analysis, aGVHD was associated with myeloablative (p

Description: Background: In recent years, genomic studies have uncovered a number of driver gene mutations in acute myeloid leukemia (AML). There is great interest in leveraging residual disease detection methods including next-generation sequencing (NGS) to predict outcomes, especially in the setting of allogeneic hematopoietic cell transplantation (HCT). One study showed measurable minimal residual disease (MRD) at the time of HCT increases the risk of relapse in patients who received a reduced-intensity conditioning (RIC) regimen (Hourigan et al. 2019). In this study, we evaluate the prognostic impact of somatic mutation clearance using NGS prior to HCT in patients with AML. Methods: We identified a total of 139 patients with AML who underwent HCT at the Moffitt Cancer Center (2013-2018). Using European LeukemiaNet (ELN) criteria, patients were included if at the time of HCT they were adverse risk in complete remission (CR)1, intermediate risk in CR1, favorable risk in CR1 if indication for transplant present, or favorable risk in CR2 with at least one time point when NGS was performed before and after HCT. We utilized clinical data captured by BMT Research and Analysis Information Network (BRAIN). Molecular testing via NGS included 54-gene TruSight Myeloid panel tested on Illumina sequencers with a lower limit of detection of 5%. Positive persistent detectable disease (PDD) was defined as presence of detectable mutations on NGS at HCT. Univariate and multivariate analyses were conducted using log-rank and Cox regression, respectively. Kaplan-Meier analysis was used to estimate overall survival (OS) and relapse free survival (RFS) from the time of diagnosis. Cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were calculated by the Fine and Gray model. Results: Of the 139 patients (74 males/65 females), 59% were PDD positive at HCT and 41% PDD negative at HCT. Median age at HCT was 59 years. More patients were in ELN-defined adverse risk (46.8%) in comparison to intermediate risk (35.3%) or favorable risk (18%). In both cohorts, majority of the patients had 1 line of therapy prior to HCT. Overall, 57.6% of patients received myeloablative conditioning regimen (MAC) with the remaining receiving RIC. More patients received MAC in both PDD positive at HCT and PPD negative at HCT groups (Table 1). There were 35 patients (25.2%) who relapsed after HCT, and 17 had NGS available at diagnosis, at the time of HCT, and at relapse. The mutation frequencies and changes over time are shown in Figure 1. Univariate analysis showed inferior OS in patients who are PDD positive at HCT compared to PDD negative at HCT (HR 1.98, 95% CI 1.06-3.72, p=0.032). After adjusting for ELN risk and PDD status, the patients who received more than 1 line of therapy prior to HCT had significantly worse OS (p=0.005). Patients with negative PDD at HCT had a significantly better OS at 2-year compared to PDD positive at HCT patients, 78.7% vs. 62.4% (p=0.029) with a median follow up of 29.9 months (Figure 2A). The RFS at 2-year were 72.6% for PDD negative at HCT patients and 51.8% for PDD positive at HCT patients (p=0.090). There was no difference in NRM or CIR between these two groups (p=0.605 and p=0.136, respectively). Further subgroup analysis did not find a significant difference between PDD status and different types of conditioning regimen (Figure 2B). Conclusions: In this study, we report that clearance of somatic gene mutations in AML patients prior to HCT confers better outcomes compared to those with measurable PDD at HCT. There is a survival advantage in patients who received fewer lines of treatment prior to HCT. Larger cohort and greater depth of NGS coverage is needed to better clarify the impact of conditioning regimen in this population. Disclosures Talati: Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Daiichi-Sankyo: Honoraria; Astellas: Honoraria, Speakers Bureau; Pfizer: Honoraria; Celgene: Honoraria; Agios: Honoraria. Bejanyan:Kiadis Pharma: Other: advisory board. Komrokji:JAZZ: Consultancy; Agios: Consultancy; Incyte: Consultancy; DSI: Consultancy; pfizer: Consultancy; celgene: Consultancy; Novartis: Speakers Bureau; JAZZ: Speakers Bureau. Kuykendall:Janssen: Consultancy; Incyte: Honoraria, Speakers Bureau; Abbvie: Honoraria; Celgene: Honoraria. Lancet:Daiichi Sankyo: Consultancy, Other: fees for non-CME/CE services ; Agios, Biopath, Biosight, Boehringer Inglheim, Celator, Celgene, Janssen, Jazz Pharmaceuticals, Karyopharm, Novartis: Consultancy; Pfizer: Consultancy, Research Funding. List:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Nishihori:Novartis: Research Funding; Karyopharm: Research Funding. Sallman:Abbvie: Speakers Bureau; Novartis: Speakers Bureau; Jazz: Research Funding; Incyte: Speakers Bureau; Celyad: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding, Speakers Bureau. Sweet:Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau; Pfizer: Consultancy; Incyte: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Agios: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Stemline: Consultancy; Jazz: Speakers Bureau.

Description: Background: Hospital services can be significantly reduced over the weekend. This was associated with higher mortality among patients with serious medical conditions in previous studies. It is unknown whether weekend admissions affect outcomes of AML patients, as delay in treatment or delay in obtainment of procedures (such as triple-lumen catheter [TLC] placement requisite for anthracycline delivery) may occur for weekend admissions. We investigated quality of care and clinical outcomes of newly-diagnosed AML patients treated with induction chemotherapy and hospitalized on weekends vs. weekdays. Methods: We conducted a retrospective review of all AML patients treated with cytarabinebased induction chemotherapy at Cleveland Clinic from 1994–2008. Data on known prognostic factors (age, WBC at diagnosis, cytogenetic risk groups [as defined by CALGB 8461] and AML etiology [de novo vs. secondary AML]) were collected and controlled for in multivariable analyses. Quality measures included time to TLC placement; time to induction chemotherapy (TTI); length of stay (LOS); early death (within 15 days of chemotherapy initiation); and 30-day mortality. Weekend admissions were defined as starting Friday, 5pm through Monday, 12am. Factors associated with quality of care and outcomes were assessed by the routines of linear, categorical, and survival analyses. Results: In all, 422 patients were identified. Median age was 61 years (range:17–81) and 47% were female. Median baseline WBC was 9.9/mcL (range:0.4–550); 4.7% had acute promyelocytic leukemia, and 30% had secondary AML. Cytogenetics risk distribution was: favorable (11.6%); intermediate (41.2%); adverse (24.2%); unknown/no growth (23%). In all, 24.4% (n=103) were admitted on the weekend. The complete remission (CR) rate was 66.6%; Median times to TLC was 2 days (range:0–27); TTI was 2 days (range:0–22); and LOS was 32 days (4–91). Early death rate was 3.1%, and 30-day mortality 10.4%. Compared to younger (

Description: Immune Reconstitution After Umbilical Cord Blood Versus Peripheral Blood Progenitor Cell Transplantation In Adults Following Myeloablative Conditioning Introduction: We report on the tempo of immune reconstitution after myeloablative umbilical cord blood transplantation (UCBT, n=61) compared with allogeneic peripheral blood progenitor cells transplantation (PBPCT, n=59). Methods: All patients 18 years or older who underwent first allogeneic transplantation after myeloablative conditioning for hematological malignancies between Jan, 2004 and Dec, 2013 and were alive at 1-year post transplant were included. Patients who received T-cell depletion or antithymocyte globulin were excluded. Results: Overall, the most common diagnosis was acute (83.6% vs 61%) or chronic (3.3% vs. 10.2%) leukemia in UCBT and PBPCT groups, respectively, p=0.07. Median age of UCBT group was 37.2 years vs. 45 years in PBPCT group, p

Description: Areas of loss of heterozygosity (LOH) can be precisely delineated using single nucleotide polymorphism arrays (SNP-A) allowing for detection of submicroscopic chromosomal defects and segmental somatic uniparental disomy (UPD) not revealed by metaphase cytogenetic analysis (MC). This study focused on aberration of chromosome 17. We analyzed marrow specimens in 1162 MDS/AML by MC and found 39 patients whose karyotype involved monosomy 17. All had a complex karyotype, aggressive histomorphologic features (1/39 low risk, 26/39 advanced MDS/sAML, 2/39 MDS/MPD, and 10/39 pAML) with a median survival of 3 months. In addition to loss of chromosome 17, 35/39 patients also showed either −5/del(5q) (N=10), −7/del(7q) (N=2), or both (N=23). To better delineate the boundaries of LOH on 17th chromosome, we analyzed a subset of 532 patients by SNP-A and identified 43/532 samples with an abnormal chromosome 17; 28 had interstitial deletions and 15 had somatic UPD. In 17/19 samples with monosomy 17 by MC, SNP-A revealed a deletion in 17p or 17q, indicating incomplete loss of chromosome 17 material. SNP-A yielded a total of 11 additional lesions on 17q not detected by MC. We were able to define two commonly deleted regions (CDR1 and CDR2). CDR1 (bp 6,828,482 to 8,075,871; 1.25 Mb) encompassed around 90 genes, including TP53, and was present in 11/14 samples with del17p. CDR2 (bp 25,320,435 to 27,355,332; 2Mb) was detected in 7/14 patients and encompassed approximately 33 genes, including NF1. Overall, the frequency of UPD17 was high: 17p UPD was detected in 7 and 17q in 8 samples analyzed. In all cases with 17p UPD, the region of UPD overlapped with CDR1. CDR2 overlapped with the region of 17q UPD in 4/8 samples. In analogy to monosomy 17, 18/21patients with LOH 17p (7 UPD, 14 losses) had a complex karyotype, 21/21 had aggressive histomorphologic features (1/21 RCMD, 3/21 RCMD-RS, 6/21 RAEB-1/2, 3/21 pAML, 8/21sAML) and a poor prognosis with a median survival of 2.6 months. Moreover, in 13/14 patients with del(17p) by SNP-A, −5/del(5q) (N=1) or both −5/del(5q) and −7/del(7q) (N=12) were present. One patient did not show deletions of chromosomes 5 or 7, but had del (4)(q26) and del(6)(q23.2). No patient had del(17p) as the sole abnormality. Strong association between 17p UPD and abnormalities of chromosomes 5 and/or 7 was also noted: of 7 patients with 17p UPD, 3 had 5/del(5q), 1 showed −7/del(7q), and 3 had −5/del(5q) and −7/del(7q). We hypothesized that LOH within the 17p CDR1 that includes TP53 might be associated with a distinct clinical phenotype and point toward pathogenic TP53 mutations. Overall, 18 instances of 17p LOH included the TP53 locus. When TP53 exons 5–9 were screened for mutations in patients with 17p LOH, we found biallelic TP53 mutations in 5/6 patients with somatic 17p UPD and in 6/8 patients with 17p deletions. We detected 10 missense mutations and 1 insertion. All missense mutations were located in the DNA-binding domain of TP53 (4/10 in exon 5: C141Y, V172F, C176Y, H179Q; 2/10 exon 6: H193N, H193R; 1/10 exon 7: R249G and 3/10 exon 8: V272L, V272M, R273H). Our study demonstrates that LOH of 17p in myeloid malignancies should prompt consideration of TP53 mutation. TP53 mutation is linked with an aggressive clinical phenotype and is highly associated with partial or complete loss of chromosomes 5 and/or 7. To our knowledge this is the first report of biallelic TP53 mutations due to UPD17p in myeloid malignancies, and indicates that both heterozygous and homozygous mutations can be encountered and comprise part of the pathologic continuum of the selection process of malignant myeloid clones.

Description: Matching at HLA-C has been shown to influence outcomes and has been incorporated in selection of unrelated adult donors. In contrast, selection of UCB grafts has historically considered HLA-A and B at antigen and DRB1 at allele level resolution. Recent data in single, myeloablative pediatric UCB transplantation demonstrated that antigen level matching at HLA-C was associated with lower NRM and improved survival in patients receiving better HLA-matched units. Whether or not these same principles apply in the setting of double UCB (dUCB) transplantation has not been addressed. Thus, we retrospectively studied whether HLA-C matching would influence outcomes in 490 patients with hematological malignancies at two centers undergoing myeloablative and reduced intensity dUCB transplantation. We considered the worst HLA-matching of the 2 donor units with 316 (64%) patients receiving at least one 4/6 matched unit and 144 (29%) one or two 5/6 units, and 30 (6%) receiving two 6/6 HLA-matched units. Patients were scored considering the number of HLA-C antigen matches as 0-1 (23%), 2 (40%), 3 (18%), and 4 (19%), of 4 possible matches. The median age was 47 yrs. (range, 2-72), 59% were male, 285 (58%) had acute leukemia, 291 (59%) were CMV seropositive, 319 (66%) received RIC regimen, and 400 (82%) had CsA/MMF immunosuppression. In the overall study population, we observed no significant influence of HLA-C matching on the risk of death, treatment failure, non-relapse death, relapse, GVHD and hematopoietic recovery. However, we recognized an interaction between conventional HLA-matching at A, B, and DRB1 and number of matches at HLA-C in the survival endpoints. Thus, we analyzed two groups based on conventional HLA-matching at A, B and DRB1: those receiving at least one 4/6 HLA-matched unit (4/6 & 4-6/6; n=316) or those receiving ≥ 5-6/6 matched unit (5/6 & 5-6/6; n=174). In the ≥5/6 UCB transplants, there was no significant influence of HLA-C matching on the risk of death, treatment failure, non-relapse death, and relapse. However, in 4/6 & 4-6/6 transplants, better matching at HLA-C was associated with lower risk of death, treatment failure, and non-relapse death (Table), but there remained no association with risk of relapse. These data contrast with those reported with single UCB grafts and suggest that with 4/6 HLA-matched UCB units, additional matching at HLA-C reduces treatment failure and improves survival, and should be included in the match strategy. In better matched (≥5/6) dUCB grafts further matching at HLA-C offers no additional benefit. Table 1.Table shows multivariate analysis results in 316 patient who received 4/6 & 4-6/6 dUCB graftsMatching at HLA CNOverall mortalityTreatment failureNon-relapse deathRelapseGrade II-IV acute GVHDRelative Risk (95% CI)PRelative Risk (95% CI)PRelative Risk (95% CI)PRelative Risk (95% CI)PRelative Risk (95% CI)P4/4331.01.01.01.01.03/4521.70.121.50.163.00.100.90.781.10.83(0.8-3.5)(0.8-2.8)(0.8-10.9)(0.4-1.9)(0.4-3.2)2/41362.30.011.70.065.4

Description: Allo-HCT is curative for hematological malignancies that are refractory to conventional chemotherapy. However, GVHD, CMV reactivation and relapse are common complications that either impair immune recovery (IR) or are secondary to the profound immune deficiency associated with these complications. We reasoned that patients who lacked these and survived beyond 1 year 'behaved' as if they had reconstituted functionally. To address this hypothesis we analyzed T, B and NK IR in 423 allo-HCT patients with hematologic malignancy without TRM in the first year. Patients who lacked GVHD, CMV reactivation and relapse were assigned to the "successful" IR group (n=115), while those who had any of these were assigned to the "suboptimal" IR group (n=308). Because some "successful" patients were CMV seronegative (CMV-) and thus at low risk for CMV viremia, we further divided this group into "successful-CMV+" (n=50) and "successful-CMV-" (n=65). In terms of 5-year DFS, "successful-CMV+" patients had the best outcome followed by "successful-CMV-" and "suboptimal" patients (90% [95% CI: 76-96%] vs 57% [36-72%] vs 43% [37-49%], p1480/ul) by D+60 as compared to that in "successful-CMV-" and "suboptimal" patients (57% vs. 13% vs. 24%, p=0.0005 and p=0.0025, respectively). This was primarily driven by faster CD3+CD8+ recovery to normal levels (64% vs. 15% vs. 26%, p=0.0004 and p=0.0016, respectively). These findings were durable over one year, with the "successful-CMV+" patients having significantly higher absolute numbers of CD3+CD8+ T cells at nearly every time point compared to the other two groups. Similarly, a significantly higher proportion of patients reached the normal range for B cells in the "successful-CMV+" and "successful-CMV-" groups relative to "suboptimal" IR group. After antigen encounter, naïve T cells differentiate into effector memory (EM) and central memory (CM) cells with some of the EM cells reacquiring CD45RA (EMRA); therefore, we evaluated the three groups for recovery of these T cell subpopulations. "Successful-CMV+" patients had significantly higher numbers of CD4+ and CD8+ EM and EMRA cells at nearly all time points compared to the other groups. Using a multivariate mixed model and taking time since transplant, donor stem cell source and recipient age into consideration, patients in "successful-CMV+" IR group showed higher ALC as well as higher absolute numbers of CD3, CD4EM, CD4EMRA, CD8EM, CD8EMRA, and NKG2C+CD57+ relative to the other group, Table 1). Together, these data define the phenotypic profile of the successful IR with the unexpected findings of better survival in CMV+ seropositive patients who are able to control CMV reactivation (and without GVHD or relapse). These results highlight the intriguing relationship between CMV and the human immune system and further suggest that strategies to control CMV reactivation (drugs, cellular therapy or vaccination) may have an unexpected impact on transplant outcomes. Table 1. Multivariable Regression Analysis on Lymphocyte Recovery Between Patient Groups. Linear mixed model was used on log transformed absolute counts at multiple time points with covariates of group, time since transplant, stem cell source, and recipient age. Regression coefficients reflect the "average" effect over time adjusted for stem cell source and recipient age. Lymphocyte Subsets Successful CMV+ vs Successful CMV- Non-Successful vs Successful CMV + Suboptimal vs Successful CMV- Coefficient P value Coefficient P value Coefficient P value ALC 0.29 0.014 -0.32 0.001 -0.04 0.664 CD19 0.09 0.77 -0.96 0.0001 -0.88 〈 0.0001 CD3 0.47 0.004 -0.38 0.006 0.09 0.454 CD3CD4 0.17 0.269 -0.33 0.014 -0.16 0.169 CD4 Naive -0.01 0.96 -0.25 0.22 -0.26 0.131 CD4CM 0.09 0.59 -0.25 0.099 -0.15 0.228 CD4EMRA 0.84

Description: Abstract 1094 Poster Board I-116 T cell large granular lymphocyte leukemia (T-LGL) is a rare lymphoproliferative disorder marked by clonal expansion of cytotoxic T lymphocytes (CTL). T-LGL may be a result of clonal outgrowth from initially polyclonal CTL responses seen in the context of viral infections, autoimmune conditions, or tumor surveillance. Similar to classic autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis or aplastic anemia, immunogenetic predisposition to T-LGL is suggested by association with certain immunogenetic polymorphisms including human leukocyte antigen (HLA) and killer immunoglobulin receptor (KIR). In addition to KIR-ligand/KIR interactions, the quality of CTL may be determined by the binding between the major histocompatibility complex class I chain-related gene A (MICA) and its ligand NKG2A. Over fifty five MICA alleles have been documented to date. A number of autoimmune and oncologic conditions such as systemic lupus erythematosus, rheumatoid arthritis, psoriasis, Crohn's disease, cervical cancer, or oral squamous cell carcinoma were all reported to be associated with MICA polymorphism. We hypothesized that specific MICA polymorphisms may be associated with exaggerated CTL responses in T-LGL and may therefore impact clinical features of the disease such as immune cytopenias. We have collected a large well annotated cohort of patients with T-LGL (n=86). HLA, MICA, and KIR alleles were resolved by established molecular techniques. Diagnosis of T-LGL was established by flow cytometry, T cell receptor γ chain rearrangement, Vβ typing, and assessment of peripheral blood smear. Categorical and survival methods of data analysis were used to examine the association between MICA, HLA, and KIR polymorphisms with type and degree of cytopenias, LGL T cell count, response to therapy, splenomegaly, and overall survival. Caucasians accounted for 96.5% of the study cohort (median age, 64 years; 55% males). Neutropenia, anemia, and thrombocytopenia were found in 63.4%, 50%, and 23.5% of the patients, respectively. Bicytopenia and pancytopenia were found in 26% and 13% of subjects, respectively. Median LGL T cell count was 1800 cells/μL (range, 280-20,580 cells/μL). Splenomegaly was found in 47% of patients. Compared to healthy controls (2N=308), our cohort was overrepresented by MICA*A5.1 (population frequency, 0.59 in T-LGL vs. 0.37 in controls, p

Description: Despite continued improvement in outcomes after allo-HCT, acute (aGVHD) and chronic GVHD (cGVHD) remain major causes of morbidity and transplant related mortality (TRM). UCB has emerged as an important alternative donor source with clinical outcomes similar to those after HCT with 8/8 allele matched unrelated and related donor. While prior studies have indicated differences in risks and natural history of GVHD between hematopoietic stem cell (HSC) sources, we sought to provide a more detailed analysis taking advantage of the homogeneity in grading criteria, treatment plans, and graft selection criteria at a single center. To identify incidence and risk factors for acute and chronic GVHD, we retrospectively studied 1180 adult (≥18 years, n=801) and pediatric (n=379) recipients of single (sUCB, n=295), double (dUCB, n=416) UCB and MRD (n=469) allografts transplanted between 2000-2012. We estimated cumulative incidence of aGVHD and cGVHD with non-GVHD deaths modeled as competing risks. Analysis of risk factors for GVHD was performed separately in the three cohorts. sUCB, dUCB, and MRD differed in age (median 8, 44, 47 years, respectively), gender (54%, 63%, 62% males), conditioning (myeloablative in 80%, 40%, 55%; ATG was used in 60%, 23%, 16%), CsA/MMF GVHD prophylaxis (66%, 99%, 48%), total nucleated cells (median 0.5, 0.4, 7.7 x 108 cells/kg), CD34 dose (median 0.5, 0.5, 5.4 x 106 cells/kg), and CD3 dose (median 0.2, 0.1, 3.6 x 108 cells/kg). sUCB transplants had lower incidence of grade II-IV aGVHD (26%), grade III-IV aGVHD (7%) and cGVHD (7%) as compared to dUCB (56% aGVHD II-IV; 21% aGVHD III-IV; 26% cGVHD) and MRD (37% aGVHD II-IV; 16% aGVHD III-IV; 40% cGVHD) (all p