Double Cord Research Articles

Does HLA-C Matching Predict the Engrafting Unit in Double Umbilical Cord Blood Transplants?: A Single Institution Retrospective Analysis

▪Background: Lower total CD34+ cell dose and increased HLA-mismatch are known predictors of engraftment failure and higher transplant related mortality (TRM) in cord blood (CB) recipients. To compensate for cell dose, double unit grafts (DUCBT) are commonly used in adult. However, in the majority of patients (pts), only one of the two CB units engrafts. Identification of the factors that predict which unit will engraft remains elusive, although increased recipient-donor HLA-matching and larger CD3+ cell dose have been associated with the predominating unit in a single center retrospective analysis (Ramirez et al, 2012). Historically, CB units are selected by maximizing matching at the HLA-A and -B antigen and -DRB1 allelic level. Evidence supports that matching at HLA-C appears to decrease TRM, and many clinicians incorporate HLA-C antigen matching into unit selection. It is unclear, however, if HLA-C matching predicts the engrafting unit in DUCBT. This study retrospective study evaluates whether HLA-C matching is associated with the “winning” CB unit.Design: Clinical data was reviewed from all pts with a hematologic malignancy receiving a DUCBT at Moffitt Cancer Center between November 13, 2009 and August 29, 2013. Chimerism studies identified the predominating unit (> 65% single unit) between day 21 and day 28. Subsequent chimerism analyses performed at a median of day 100 confirmed unit predominance. Unit selection required intermediate resolution antigen match at HLA-A, -B, -C, and high resolution allele match at -DRB1. Units were a minimum of 4/8 matched to the patient and each other with a minimum cell dose of 1.5 x 107 total nucleated cell dose (TNC) /kg. Serology for donor specific antibodies against both units was negative.Results: Excluding 6 pts who were missing HLA-C typing on one or both CB units, 54 pts with hematologic malignancies (ALL=6, MDS/AML=29, Other=19) received chemotherapy and total body irradiation as part of a myeloablative conditioning (MAC) or reduced intensity conditioning (RIC) with or without thymoglobulin (ATG) followed by a DUCBT (MAC=14, RIC=23, RIC+ATG=17). Median age was 52 (range 22-69) years. Seven pts demonstrated persistent mixed chimerism in the myeloid and/or lymphoid cell lines beyond day 100. A total of 20 pts with available chimerism data received at least one CB unit matched to the recipient at HLA-C, with one patient excluded due to persistent mixed chimerism. Six pts received both CB units matched at HLA-C, but of the 13 pts receiving one matched and one mismatched unit, the HLA-C matched unit was the engrafting unit 69% (9/13) of the time. Comparing similar HLA mispairings, a matched unit engrafted over a mis-matched unit at HLA-A 50% (5/10) of the time, at HLA-B 38% (5/13) of the time, and at HLA-DRB1 50% (3/6) of the time. TNC dose (larger vs smaller with a required difference of at least 0.03 x 107 TNC/kg), order of infusion (first vs second unit), and overall CB unit HLA matching (4/8-8/8), were assessed as potential predictors for engraftment. Of evaluable patients, the CB unit with the larger TNC engrafted 44% (16/36) of the time, and the first unit infused was the engrafting unit 54% (21/39) of the time. In patients with an unequal overall match grade between the CB units, the better HLA-matched CB unit engrafted 64% (14/22) of the time. Survival analysis of all pts revealed that those who received at least one CB unit antigen matched at HLA-C (n=20) had a 100 day and 1 year overall survival (OS) of 85% (95% Confidence Interval(CI): 67–97%) and 55% (95% CI: 33–75), respectively, whereas pts receiving two HLA-C mismatched CB units (n=34), 100 day OS was 62% (95% CI: 45–77) with 1 year OS 44% (95% CI: 28–61) (Fig 1).Conclusion: HLA-C antigen matching appears to help predict the “winning” unit in settings of HLA-match disparity and DUCBT. Confirmation in a larger population of DUCBT recipients is necessary. To date, the effects of HLA matching and other variables influencing engraftment have been predominately evaluated in recipients of single unit transplants and studies in DUCBT have been limited. Further investigation assessing HLA matching as well as donor-donor interactions is best served through a multicenter data resource. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Phase I Trial of Maintenance Sorafenib after Allogeneic Hematopoietic Stem Cell Transplantation for Patients with FLT3-ITD AML

Introduction: The FLT3-ITD mutation is associated with a high relapse rate for patients with AML even after allogeneic hematopoietic stem cell transplantation (HSCT). Sorafenib is an oral tyrosine kinase inhibitor which inhibits the FLT3 tyrosine kinase. Evidence based on FLT3-ligand levels has suggested that the maintenance setting may be the optimal time to administer FLT3 inhibition.Methods: We conducted a phase I trial of maintenance sorafenib after HSCT in patients with FLT3-ITD AML. Patients received a variety of conditioning regimens (12 myeloablative, 10 reduced intensity) and graft sources (19 matched related / unrelated, 1 haploidentical, 1 double umbilical cord blood, 1 mismatched unrelated). All patients were in morphological remission with predominant donor chimerism after HSCT before starting sorafenib. A dose escalation 3+3 cohort design was used to define the maximum tolerated dose (MTD) with an additional 10 patients treated at the MTD. Sorafenib was initiated between days 45 and 120 after HSCT and given continuously for twelve 28-day cycles. The DLT period was the first cycle of treatment.Results: Twenty-two patients with FLT3-ITD AML were enrolled (status at HSCT: CR1=16, CR2=3, refractory=3). The MTD was established at 400 mg BID with one DLT observed (pericardial effusion) which was later deemed unrelated to sorafenib. Two patients died of transplant-related causes and neither was deemed related to sorafenib (idiopathic pneumonia syndrome, cirrhosis from iron overload). Two patients stopped sorafenib after relapse and 5 stopped sorafenib due to attributable toxicities after the DLT period. The most common toxicities observed were skin and GI with dose reductions and interruptions common. There were no significant flares of acute GVHD observed after starting sorafenib and 1-year cumulative incidence of chronic GVHD was 42% (90% CI, 23%, 60%). Effective inhibition of FLT3 as measured by a plasma inhibitory assay was observed at all doses employed. Serial levels of FLT3 ligand were measure in 7 patients. Median level at baseline and prior to any sorafenib administration was 125 pg/ml (range 40-323) and this significantly increased to a median level of 254 pg/ml (range 80-500) (p = 0.016) measured on day 29 of cycle 1.The median follow-up for survivors is 14.5 months (range, 6.6-34.0) after HSCT. One-year progression-free survival is 84% (90% CI, 63%-94%) and one-year overall survival is 95% (90% CI, 79%-99%) (Figure 1). Only one patient who underwent HSCT in CR (n=19) has relapsed.Conclusion: Sorafenib is safe to give as maintenance therapy after HSCT for patients with FLT3-ITD AML and may reduce the rate of relapse. Maintenance sorafenib or other FLT3 inhibitors after HSCT merits further investigation. [Display omitted] DisclosuresChen:Bayer Pharmaceuticals, Inc.: Other, Research Funding. Off Label Use: Sorafenib as maintenance therapy for FLT3-ITD AML.

The Cell Loss after Thawing in Cord Blood Units

Umbilical cord blood (CB) are increasingly used for allogeneic transplantation as an alternative source to bone marrow or peripheral stem cell for patients who lack a human leucocyte antigen (HLA)-matched donor. Cell dose is one of the main determinant factor for selection of the unit and it has been shown to correlate with time and probability of engraftment. Cell doses available for selection of the unit are the ones evaluated before cryopreservation. Processing of the graft either with cryopreservation and/or thawing inevitably lead to cell loss but the data showing to what extent is very limited although this has great importance especially for the units with critical cell counts. To evaluate the extent of the cell loss after thawing and the effect of preservation duration on cell loss and the viability, we retrospectively analyzed our single center experience in a cohort of patients receivingunrelated CBT.Sixty cord blood units used for unrelated CBT in fifty-eight patients in our Pediatric Stem Cell Transplantation Unit were included in the study. One of the patient was transplanted with double cord blood unit and one had recurrent CBT because of previous graft failure.Median number of declared TNC per kilogram of recipient body weight was 16x107/kg (range: 3,16-59,1). After thawing the median TNC dose decreased to 11,1x107/kg (range:1,5-34), with median cell viability at 80%. The median TNC recovery was found as 70%. Median CD 34+ cell count declared by the banks per kilogram body weight of recipient was 6,0x105/kg (range: 0,5-37). The CD 34 cell count of one of the units used in a patient having double cord blood infusion was not available. The CD34 cell count of the other complementary unit was 0,48x105/kg. Since the total cell counts received bu the recipient was given, the CD34 cell count of the patient having double CB infusion was not included in statistical analysis. The median postthawed CD 34 cell count was 3,4 x105/kg (range: 0-21)and median CD34 cell recovery was %58.The storage duration of the CB units in liquid nitrogen was available for 59 units and that was 52±30 months (range:3-130 months). Correlation analysis did not show any significant correlation between CB unit storage duration and viability (r=-0,2 p=0.07). Also any correlation between storage time and also TNC and CD34 cell recovery were not identified.Our study indicated that approximately 30% of cell loss is expectable in cord blood transplantation because of either cryopreservation or thawing. It should be kept in mind while assessing acceptibility of cord blood units with limited cell counts DisclosuresNo relevant conflicts of interest to declare.

OR32: GETTING OUT OF THE PANIC MODE: MATERNAL BLOOD CONTAMINATION IN A CORD BLOOD UNIT FOR DOUBLE CORD HEMATOPOIETIC CELL TRANSPLANTATION

Aim A patient with severe aplastic anemia was scheduled for double cord blood transplant. However the confirmatory typing results revealed the detection of extra class II alleles for one of the cord blood unit (CBU). The aim of our study was to determine if a typing error had occurred or if there was maternal blood contamination. If there was maternal contamination, would there be a risk of GVHD? Should the transplant physicians cancel the scheduled transplant and identify a different CBU?. Method Reverse SSO at HLA-A, B, C, DRB1 and DQB1 loci, SSP and sequencing based typing (SBT) at HLA-DRB1 locus were performed. Chimerism testing was also performed using multiplexed short tandem repeat (STR) to determine the percentage of maternal blood contamination. Results Confirmatory typing at DRB1 by SBT for one of the CBUs was found to be discrepant with NMDP consensus results: DRB1∗04:03, 04:07; our results: DRB1∗01:01, 04:03, 04:07, with HLA-A and B results by SSO being concordant with NMDP. Further allele specific DRB1∗04 SSP testing confirmed the presence of DRB1∗04:03, 04:07. Class II SSO typing indicated the presence of DRB1∗01and DQB1∗05, consistent with DRB1∗01:01 by SBT. Due to the identification of an extra antigen for one of the CBUs, the hematopoietic cell transplant physician canceled the pretransplant work-up and requested further investigation. The back-up segment of this problematic cord, maternal sample and HLA typing were requested through NMDP coordinators. Maternal HLA typing was found to be DRB1∗ 01:01, 04:07. No extra antigens were detected for this CBU at HLA-A and B loci by SSO method, possibly due to the decreased sensitivity of this method. STR test was performed on maternal blood and CBU. The STR results indicated approximately 5% maternal blood contamination in the CBU. The NMDP physician was consulted and indicated that maternal contamination adds no additional GVHD risk because the maternal cells should be all dead. The transplant was performed. The patient is currently doing well with 90 day posttransplant follow up indicating 99.5% engraftment. Conclusion NMDP sources estimate approximately 1% of cord units have maternal blood contamination, and expect a 1–5% chimerism result by STR analysis. The contamination from maternal blood does not appear to increase the risk for GVHD.

Complete Donor T Cell Chimerism Predicts Lower Relapse Incidence after Standard Double Umbilical Cord Blood Reduced-Intensity Conditioning Regimen Allogeneic Transplantation in Adults

Double umbilical cord blood (dUCB) allogeneic transplantation after a low-dose total body irradiation, cyclophosphamide, and fludarabine (TCF)–based reduced-intensity conditioning regimen (RIC) is increasingly used in adults lacking a suitable related or unrelated donor. Currently, there are little data regarding the long-term outcome of CD3+ T cell chimerism (TCC) in this particular setting. Thirty-six adults with various hematological diseases who received dUCB allogeneic transplants conditioned with TCF were included in this retrospective study. Peripheral blood CD3+ TCC was considered until day +100 after transplantation to determine the impact of full versus mixed chimerism on long-term outcomes. Twenty-nine and 7 patients were documented with full and mixed CD3+ TCC, respectively, within the first 100 days after transplantation. With a median follow-up of 36 months, 3 year-overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse (CIR) were 61%, (95% confidence interval [CI], 43% to 75%); 50% (95% CI, 32.5% to 66%), and 28% (95% CI, 16% to 44%), respectively. In univariate analysis, a full CD3+ TCC was associated with a better 3-year DFS: 59% (95% CI, 39% to 75.5%) versus 14% (95% CI, 7% to 46%); hazard ratio (HR), .24 (.09 to .65); P = .005 and a lower CIR: 24% (95% CI, 21.5% to 57%) versus 78% (95% CI, 52% to 99%); HR, .18 (.05 to .50); P = .004. In multivariate analysis, a full CD3+ TCC remained associated with a lower CIR (HR, .17 [.028 to .99]; P = .049). CD3+ TCC has no impact on graft-versus-host disease and nonrelapse mortality in this study. In conclusion, here, full CD3+ TCC was independently associated with a lower risk of relapse in adults receiving a dUCB TCF RIC allogeneic transplantation. This highlights the need to develop immunotherapy approaches allowing for early conversion to full chimerism after this type of transplantation.

Human herpesvirus 6 reactivation before engraftment is strongly predictive of graft failure after double umbilical cord blood allogeneic stem cell transplantation in adults

Our main objective was to determine new factors associated with engraftment and single-unit predominance after double umbilical cord blood (UCB) allogeneic stem-cell transplantation. Engraftment occurred in 78% of cases in this retrospective study including 77 adult patients. Three-year overall survival, disease-free survival, relapse incidence, and nonrelapse mortality were 55 ± 6%, 44 ± 6%, 33 ± 5%, and 23 ± 4%, respectively. In multivariate analysis, Human herpesvirus 6 reactivation during aplasia (hazard ratio [HR] = 2.63; 95% confidence interval [CI]: 1.64-4.17; p < 0.001), younger recipient age (<53 years) (HR = 1.97; 95% CI: 1.16-3.35; p = 0.012), and lower human leukocyte antigen matching between the two units (3 of 6 or 4 of 6) (HR = 2.09; 95% confidence interval: 1.22-3.59; p = 0.013) were the three factors independently associated with graft failure. Also, factors independently predicting the losing UCB unit were younger age of the UCB unit (odds ratio [OR] = 1.01; 95% CI: 1-1.02; p = 0.035), lower CD34(+) cell dose contained in the UCB unit (≤ 0.8 × 10(5)/kg) (OR = 2.55; 95% CI: 1.05-6.16; p = 0.04), and presence of an ABO incompatibility between the UCB unit and the recipient (OR = 2.53; 95% CI: 1.15-5.53; p = 0.02). Thus, Human herpesvirus 6 reactivation during aplasia, lower unit-unit human leukocyte antigen matching, and younger UCB unit age, as new unfavorable predictive factors, may represent new parameters to take into account after double UCB allogeneic stem-cell transplantation in adults. These results need to be confirmed prospectively, as they may influence unit selections and patient outcomes.

Double Umbilical Cord Blood Transplantation after Novel Myeloablative Conditioning Using a Regimen of Fludarabine, Busulfan, and Total Lymphoid Irradiation

We conducted a pilot study evaluating double umbilical cord blood transplantation (dCBT) after myeloablative conditioning with fludarabine and busulfan 3.2 mg/kg i.v. × 4, followed by total lymphoid irradiation at 400 cGy (FluBu4/TLI) for any indicated hematological disorder for patients without a suitable donor. Twenty patients with predominantly high-risk disease underwent dCBT according to protocol. The regimen was well tolerated, with mucositis as the primary observed toxicity (n = 19). The cumulative incidence of neutrophil engraftment was 89% (95% confidence interval [CI], 64% to 97%), with a median time to recovery of 16 days (range, 12 to 31 days). All evaluable patients with neutrophil engraftment achieved complete donor chimerism by day 40. The cumulative incidence of grades III and IV acute graft-versus-host disease (GVHD) at day 100 was 10% (95% CI, 2% to 27%), and the cumulative incidence of chronic GVHD was 35% (95% CI, 16% to 55%) by the end of the study. At 1 year, the cumulative incidence of treatment-related mortality (TRM) was 35% (95% CI, 16% to 55%). The leading cause of nonrelapse mortality was acute GVHD (n = 4), followed by graft failure (n = 2) and chronic GVHD (n = 1). TRM was significantly associated with a pretransplantation hematopoietic cell transplantation–specific comorbidity index score ≥ 3 (P = .005). At 1 year, disease relapse occurred in 6 patients and overall survival was 40% (95% CI, 19% to 60%). We conclude that FluBu4/TLI is an adequate preparative regiment before dCBT, providing high engraftment rates and relatively early neutrophil recovery. The best survival outcomes were seen in patients without significant comorbidities before transplantation, and outcomes are comparable to previously published dCBT studies.

Bilateral facet dislocation of the C2–C3 cervical spine with double level spinal cord transection

A 2-year-old boy was admitted to the emergency department after a low impact motor vehicle accident. He was put on a backboard with cervical neck immobilization. On admission, he was pulseless and unresponsive with multiple abrasion wound noted over his face and trunk. After cardiopulmonary resuscitation and intubation, his vital sign was stabilized. The pupils were 4 mm in diameter and reactive; the Glasgow Coma Scale score was 3. Head computed tomography (CT) revealed an intracranial hemorrhage without obvious mass effect.

Clinical study of unrelated umbilical cord blood transplantation for 25 patients with hematological diseases

This study was purposed to investigate the engraftment, graft-versus-host disease (GVHD), transplantation related mortality (TRM), relapse and survival in hematologic patients received unrelated umbilical cord blood transplantation (UCBT). A total of 25 patients with hematological disease underwent UCBT, including 8 pediatric and 17 young adult patients. Among them 3 cases received single unit of UCBT and 22 cases received double units of UCBT. For donor/recipients human leukocyte antigen (HLA) matching: HLA 6/6 loci matched in 9 cases, HLA 4-5/6 loci matched in 16 cases. There were 19 patients with hematologic malignancies, including 3 cases in the period of disease progression and 6 cases of non-hematologic malignancies. Conditioning regimens were TBI/Cy ± Flu ± ATG or BuCy ± Flu ± ATG for 21 patients and Cy+Flu+ATG for 4 patients. For prophylaxis of acute graft-versus-host disease (aGVHD) the regimen of cyclosporine (CsA) as dominant drug was used. The results showed that among 16 patients (80.0%) achieved engraftment, 20 patients survived for more than 42 d after transplantation. The cumulative neutrophil recovery rate on day 42 after transplant was 64.0%, with a median time of 17.0 d;the cumulative platelet recovery rate on day 100 after transplant was 60.0 %, with a median time of 35.0 d. The cumulative rate of grade II-IV and III-IV aGVHD after transplantation 100 d was 44.0% and 30.7%, respectively. Until the end of the follow-up, the cumulative rate of TRM was 54.3%. For all the patients, overall survival rate was 42.7%. Out of 17 evaluable patients with hematologic malignancies 7 cases (41.2%) survived to date, and only 1 case relapsed, so event-free survival rate was 35.3%. Out of 5 evaluable patients with non-hematologic malignancies, 4 patients survived and 2 patients were in stable engraftment state, 2 cases with autologous hematopoietic recovery. Among 3 cases of hematologic malignancies at advanced stage, only 1 case survived to date. It is concluded that HLA-4-6/6 loci matched UCBT is an effective option to treat hematological diseases. Double cord blood transplantation (dUCBT) can overcome the disadvantage of insufficient cells of single cord blood UCBT to treat overweight children and adult.

Haplo+cord transplantation: Neutrophil and platelet recovery and long-term survival compared to double umbilical cord blood (UCB) transplantation—A case-cohort analysis.

7004 Background: Double UCB (dUCB) SCT can result in long-term survival and low rates of chronic GVHD. Limitations are delayed engraftment and early TRM. We previously reported that co-infusion of ...

T-cell replete haploidentical donor transplantation using post-transplant CY: an emerging standard-of-care option for patients who lack an HLA-identical sibling donor.

Availability of an HLA-identical sibling (MRD) or suitably matched unrelated donor (MUD) has historically been a limiting factor in the application of allogeneic hematopoietic transplantation. Although almost all patients have an HLA-haploidentical family donor, prior attempts at transplantation from such donors using T-cell replete grafts and conventional immunosuppression were associated with unacceptable rates of GVHD, and when stringent ex vivo T-cell depletion was used to control GVHD, rates of graft rejection and post-transplant infections were prohibitive. The recent approach to HLA-haploidentical donor transplantation developed in Baltimore that uses T-cell replete grafts and post-transplant CY (Haplo-post-HCT-CY) to control post-transplant allo-reactivity appears to have overcome many of the obstacles historically associated with haploidentical donor transplantation. In particular, TRM rates of <10% are usual and rapid reconstitution of immunity leads to a low rate of post-transplant infections and no post-tranplant lymphoproliferative disorders (PTLD), consistent with the hypothesis that post-transplant CY selectively depletes proliferating alloreactive T cells responsible for GVHD and graft rejection while preserving resting memory T cells essential for post-transplant immunologic recovery. In parallel trials using similar non-myeloablative conditioning regimens, Haplo-post-HCT-CY produced similar overall survival to double umbilical cord blood transplantation(DUCBT) in adult patients (62% vs 54%), with low rates of TRM (7% vs 24%), severe acute GVHD (0% vs 21%) and chronic GVHD (13% vs 25%). Furthermore, recent non-randomized comparisons adjusted for risk factors show that Haplo-post-HCT-CY achieve at least equivalent outcomes to conventional MRD and MUD transplants. Although most experience has been obtained using BM, emerging data suggest that a G-CSF mobilized PBSC graft can also safely be used for Haplo-post-HCT-CY. Haplo-post-HCT-CY also avoids the graft acquisition costs of DUCBT and MUDs and the cost of cell selection associated with T-depleted grafts. Although randomized comparisons will be forthcoming, Haplo-post-HCT-CY can already be considered a valid standard-of-care in patients who lack conventional donors thus extending the availability of allogeneic transplants to almost all patients. This donor source may also challenge the routine preference for a MUD in patients lacking an MRD.

Blood gas values in clamped and unclamped umbilical cord at birth

AimTo determine the reliability of the cord blood gas analysis on the unclamped cord compared to the standard technique of sampling on double clamped cord. Study designProspective observational study conducted on 46 singleton neonates vaginally delivered at term. Matched pairs of umbilical artery and vein blood samples were collected from unclamped cord within 90s after birth and from the same cord after clamping, with the clamping occurring immediately after the first blood collection. A blood gas analysis was performed on each collected sample. Outcome measuresArterial and venous blood samples were analyzed for pH, PO2, pCO2, SaO2, hemoglobin concentration (ctHb) and base excess (BE). The values were compared between the two groups (clamped vs unclamped) using a Wilcoxon test. ResultsNo significant difference was found in pH, PO2, pCO2, SaO2 and ctHb values on arterial blood between unclamped and clamped cord. The only significant difference was related to BE (p<0.001). For the venous blood, the values of pH, PO2, pCO2 were comparable between unclamped and clamped cord, while the values of SaO2, ctHb and BE were significantly different (p<0.05). ConclusionNo significant difference was found in almost all the arterial blood gas parameters and in the main venous blood gas parameters between unclamped and clamped cord. Sampling of cord blood for gas analysis may be performed on the unclamped cord right after birth without reducing the accuracy of the analysis.

Long-Lasting HHV-6 Reactivation in Long-Term Adult Survivors After Double Umbilical Cord Blood Allogeneic Stem Cell Transplantation

Higher incidence of human herpesvirus 6 (HHV-6) infection has been documented after umbilical cord blood allo-transplant in adults. Here we demonstrate that HHV-6 reactivation persists for a very long time in half of the patients after this type of graft. Long-term immune reconstitution does not explain this event, which remains to be explained.

Design of a cost–effectiveness analysis alongside a randomized trial of transplantation using umbilical cord blood versus HLA-haploidentical related bone marrow in advanced hematologic cancer

BMT CTN 1101 is a Phase III randomized controlled trial evaluating the comparative effectiveness of double unrelated umbilical cord blood (dUCB) versus HLA-haploidentical related donor bone marrow (haplo-BM) donor cell sources for blood or bone marrow transplantation (BMT) in patients with hematologic malignancies. Herein, we present the rationale, design and methods of the first cost-effectiveness analysis to be conducted alongside a BMT trial. Consenting patients will provide health insurance information to allow calculation of direct medical costs from reimbursement records, and will provide out-of-pocket costs, time costs and health-related quality of life measures through an online survey. These outcomes will inform a cost-effectiveness analysis comparing dUCB and haplo-BM donor cell sources from patient, payer and societal perspectives. Novel approaches may significantly change the cost, outcomes or availability of BMT. The results of this analysis will be the first to provide a comprehensive evaluation of the comparative effectiveness of these approaches from multiple perspectives.

Double Umbilical Cord Blood Transplantation after Novel Myeloablative Conditioning Using FluBu4/TLI

We conducted a pilot study evaluating double umbilical cord blood transplantation (dCBT) after myeloablative (MA) conditioning with Fludarabine/Busulfan 3.2mg/kg IV × 4, followed by Total Lymphoid Irradiation at 400cGy (FluBu4/TLI) for any indicated hematological disorder without a suitable donor. Twenty patients with predominantly high-risk disease underwent dCBT according to protocol. The regimen was well tolerated, with mucositis as the primary observed toxicity (n=19). The cumulative incidence of neutrophil engraftment was 89% (95% C.I., 64-97%), with a median time to recovery of 16 days (range: 12-31 days). All evaluable patients with neutrophil engraftment achieved complete donor chimerism by day 40. The cumulative incidence of grade III/IV acute GVHD at day 100 was 10% (95% C.I., 2-27%), and the cumulative incidence of chronic GVHD was 35% (95% C.I. 16-55%) by the end of the study. At one year, the cumulative incidence of treatment related mortality (TRM) was 35% (95% C.I. 16-55%). The leading cause of non-relapse mortality was acute GVHD (n=4), followed by graft failure (n=2), and chronic GVHD (n=1). Treatment-related mortality was significantly associated with a pre-transplant HCT-CI score ≥3 (p=0.005). At one year, disease relapse occurred in six patients, and overall survival was 40% (95% C.I. 19-60%). We conclude that MA FluBu4/TLI is an adequate preparative regiment prior to dCBT, providing high engraftment rates, and relatively early neutrophil recovery. The best survival outcomes were seen in patients without significant comorbidities pre-transplant, and are comparable to previously published dCBT studies.

Outcomes of Double Unit Umbilical Cord Blood Transplantation Using Fludarabine/Busulfan Based Reduced Intensity Conditioning Regimen

Outcomes of Double Unit Umbilical Cord Blood Transplantation Using Fludarabine/Busulfan Based Reduced Intensity Conditioning Regimen

Double Unit Umbilical Cord Blood Transplant for Adults with Acute Leukemia and Myelodysplastic Syndrome Results in Comparable Outcome As Matched Sibling or Unrelated Donor Transplant Only after Myeloablative Conditioning but Not Reduced Intensity Conditio

Double Unit Umbilical Cord Blood Transplant for Adults with Acute Leukemia and Myelodysplastic Syndrome Results in Comparable Outcome As Matched Sibling or Unrelated Donor Transplant Only after Myeloablative Conditioning but Not Reduced Intensity Conditio

Recipient T-Cell Repertoire Diversity after Double Umbilical Cord Transplantation Correlates with Non-Relapse Mortality and Survival

Recipient T-Cell Repertoire Diversity after Double Umbilical Cord Transplantation Correlates with Non-Relapse Mortality and Survival

Maintenance of Naïve T Cells and a Diverse TCR Repertoire Are Critical for Reconstitution of EBV-Specific Immunity after Double Cord Blood Transplantation

Maintenance of Naïve T Cells and a Diverse TCR Repertoire Are Critical for Reconstitution of EBV-Specific Immunity after Double Cord Blood Transplantation

Hemophagocytic Lymphohistiocytosis in Infants: A Single Center Experience from India

There is paucity of outcome data for hemophagocytic lymphohistiocytosis (HLH) in infants from India, especially post stem cell transplant (SCT). We report outcome data of eight infants diagnosed with HLH. Mean age was 7.1 months (range 2–11). Mutation analysis was possible in seven patients. One patient had Griscelli syndrome. In three patients, no known mutation could be identified, while in remaining three homozygous mutations in Perforin, Munc and STX11 gene were identified. All were treated as per HLH 2004 protocol. Four died during induction phase. One patient abandoned therapy. Two underwent SCT, while one is awaiting SCT. First patient is alive and disease-free at 22 months postmatched sibling donor SCT. Second underwent unrelated double cord blood transplant, but died 5 months posttransplant due to renal failure. It is feasible to offer SCT for infants with familial HLH in the developing world although barriers like sepsis and disease refractoriness remain.