Decrease post-transplant relapse using donor-derived expanded NK-cells.

In this phase I/II clinical trial, we investigated the safety and efficacy of high doses of mb-IL21 ex vivo expanded donor-derived NK cells to decrease relapse in 25 patients with myeloid malignancies receiving haploidentical stem-cell transplantation (HSCT). Three doses of donor NK cells (1 × 105-1 × 108 cells/kg/dose) were administered on days -2, +7, and +28. Results were compared with an independent contemporaneously treated case-matched cohort of 160 patients from the CIBMTR database.After a median follow-up of 24 months, the 2-year relapse rate was 4% vs. 38% (p = 0.014), and disease-free survival (DFS) was 66% vs. 44% (p = 0.1) in the cases and controls, respectively. Only one relapse occurred in the study group, in a patient with the high level of donor-specific anti-HLA antibodies (DSA) presented before transplantation. The 2-year relapse and DFS in patients without DSA was 0% vs. 40% and 72% vs. 44%, respectively with HR for DFS in controls of 2.64 (p = 0.029). NK cells in recipient blood were increased at day +30 in a dose-dependent manner compared with historical controls, and had a proliferating, mature, highly cytotoxic, NKG2C+/KIR+ phenotype.Administration of donor-derived expanded NK cells after haploidentical transplantation was safe, associated with NK cell-dominant immune reconstitution early post-transplant, preserved T-cell reconstitution, and improved relapse and DFS. TRIAL REGISTRATION: NCT01904136 ( https://clinicaltrials.gov/ct2/show/NCT01904136 ).

Comparable Outcomes of Matched Sibling Donor and Matched Unrelated Donor Stem Cell Transplantation in Children With Acute Leukemia in Argentina.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is an effective mode of consolidation therapy for children with high-risk acute leukemia. In high-income countries, match sibling donor (MSD) and match unrelated donor (MUD) HSCT have similar outcomes, but data are scarce in upper-middle-income countries. Our objective was to compare MSD and MUD HSCT outcomes for children with acute leukemia in Argentina. PATIENTS AND METHODS: This was a single-institution retrospective cohort study. We included children with acute leukemia who underwent HSCT with either MSD or MUD between 2014 and 2019. RESULTS: The study included 45 patients who received MSD (n=27) or MUD (n=18) for acute leukemia. Event-free survival was not significantly different between MSD (62.3±10.7%) versus MUD (54.2±15.0%; P=0.54) at 5 years. Similarly, there was no significant difference in 5-year overall survival between MSD (71.9±9.8%) versus MUD (65.1±13.5%; P=0.38). The cumulative incidence of treatment-related mortality (P=0.31), cumulative incidence of relapse (P=0.99), and proportion with acute-graft-versus-host disease (P=0.76) and chronic-graft-versus-host disease (P=0.68) were also not significantly different. CONCLUSIONS: In Argentina, we did not show significant differences in outcomes between MSD and MUD HSCT for children with high-risk leukemia. Future work should focus on strategies to reduce the relapse risk in children with high-risk leukemia in upper-middle-income countries.

Association Between Donor-Recipient Biological Relationship and Allograft Outcomes After Living Donor Kidney Transplant.

Importance: The proportion of living donor kidney transplants from donors unrelated to their recipients is increasing in the US. Objective: To examine the association between donor-recipient biological relationship and allograft survival after living donor kidney transplant. Design, Setting, and Participants: This retrospective cohort study used Organ Procurement and Transplantation Network data on US adult living donor kidney transplants (n = 86 154) performed from January 1, 2000, to December 31, 2014, excluding cases in which recipients previously received a kidney transplant (n = 10 342) or key data were missing (n = 2832). Last follow-up was March 20, 2020. Exposures: Donor-recipient biological relationship. Main Outcomes and Measures: The primary outcome was death-censored allograft failure. Univariate and multivariable time-to-event analyses were performed for death-censored allograft failure for the overall cohort, then separately for recipients with and without primary diagnoses of cystic kidney disease and for transplants from African American and non-African American donors. Results: Among the 72 980 transplant donor and recipients included in the study (median donor age, 41 years; interquartile range [IQR], 32-50 years; 43 990 [60%] female; 50 014 [69%] White), 43 174 (59%) donors and recipients were biologically related and 29 806 (41%) were unrelated. Donors related to their recipients were younger (median [IQR] age, 39 [31-48] vs 44 [35-52] years) and less likely to be female (24 848 [58%] vs 19 142 [64%]) or White (26 933 [62%] vs 23 081 [77%]). Recipients related to their donors were younger (median [IQR] age, 48 [34-58] vs 50 [40-58] years), more likely to be female (18 035 [42%] vs 10 530 [35%]), and less likely to have cystic kidney disease (2530 [6%] vs 4600 [15%]). Related pairs had fewer HLA mismatches overall (median [IQR], 3 [2-3] vs 5 [4-5]). After adjustment for HLA mismatches, donor and recipient characteristics, and transplant era, donor-recipient biological relationship was associated with higher death-censored allograft failure (hazard ratio, 1.05; 95% CI, 1.01-1.10; P = .03). When stratified by primary disease, this association persisted only for recipients without cystic kidney disease. When stratified by donor race, this association persisted only for transplants from African American donors. Conclusions and Relevance: In this cohort study, living donor kidney transplants from donors biologically related to their recipients had higher rates of allograft failure than transplants from donors unrelated to their recipients after HLA matching was accounted for. Further study is needed to determine which genetic or socioenvironmental factors are associated with this finding.

Changes in Hematopoietic Cell Transplantation Practices in Response to COVID-19: A Survey from the Worldwide Network for Blood & Marrow Transplantation.

SARS-CoV-2 has spread rapidly worldwide, but the full impact of the COVID-19 pandemic on the field of hematopoietic cell transplantation (HCT) remains unknown. To understand this better, an 18-item online survey was disseminated by the Worldwide Network for Blood & Marrow Transplantation with questions exploring SARS-CoV-2 testing algorithms, mobilization, and cryopreservation strategies and COVID-19 infections in allogeneic related and autologous hematopoietic progenitor cell (HPC) donors. The aim of this survey was to assess the impact of the outbreak on policies relating to HPC mobilization, collection, and processing with respect to changes in daily routine. A total of 91 individual responses from distinct centers in 6 continents were available for analysis. In these centers, the majority (72%) of allogeneic related and autologous donors are routinely tested for SARS-CoV-2 before HPC collection, and 80% of centers implement cryopreservation of allogeneic HPC grafts before commencing conditioning regimens in patients. Five related and 14 autologous donors who tested positive for COVID-19 did not experience any unexpected adverse events or reactions during growth factor administration (eg, hyperinflammatory syndrome). These data are limited by the small number of survey respondents but nonetheless suggest that centers are following the recommendations of appropriate scientific organizations and provide some preliminary data to suggest areas of further study.

Multimedia resources to support the recruitment of committed hematopoietic stem cell donors: Perspectives of the most-needed donors.

BACKGROUND: Recruitment of committed unrelated hematopoietic stem cell donors from the most-needed demographics remains a challenge for donor recruitment organizations worldwide. Multimedia resources are gaining attention as a modality to support recruitment efforts; however, there is a lack of guidance for the development of such tools. This qualitative study explores the perspectives of eligible stem cell donors on an educational whiteboard video about stem cell donation, generating insights into how whiteboard videos and related multimedia may be optimized for donor recruitment. STUDY DESIGN AND METHODS: Eight semistructured focus groups were conducted with 38 potential donors from the most-needed demographics (young, male, and non-Caucasian) after they had watched a 3.5-minute whiteboard video explaining key concepts in stem cell donation (https://youtu.be/V4fVBtxnWfM). Constructivist grounded theory was used to identify themes and to develop a framework for understanding participants' preferred features of recruitment multimedia. RESULTS: Participants identified a range of features contributing to the effectiveness of recruitment multimedia, adding that the whiteboard video is an effective, integrated, and readily accessible format for supporting donor recruitment. Topics that participants felt are important to address include knowledge gaps regarding donation procedures, concerns about donor safety, and the particular need for specific donor demographics. Suggested avenues for improvement include the addition of donor/recipient/patient personal experiences, attention-grabbing hooks, and a call to action including opportunities for further learning. CONCLUSIONS: Several considerations were generated to inform the development of future multimedia for donor education/recruitment and are relevant to donor recruitment organizations worldwide.

Role of HLA-DP Expression in Graft-Versus-Host Disease After Unrelated Donor Transplantation.

PURPOSE: The main aim of this study was to evaluate the significance of HLA-DPB1 expression in acute graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) from HLA-A, -B, -C, -DRB1, -DQB1-matched and -mismatched unrelated donors. PATIENTS AND METHODS: Between January 1, 2017, and January 10, 2019, we assessed 19,136 patients who received HCT from an HLA-A, -B, -C, -DRB1, -DQB1-matched or -mismatched unrelated donor performed in Australia, the European Union, Japan, North America, and the United Kingdom between 1988 and 2016. Among transplant recipients with one HLA-DPB1 mismatch, the patient's mismatched HLA-DPB1 allotype was defined as low or high expression. Multivariable regression models were used to assess risks of GVHD associated with high expression relative to low expression HLA-DPB1 mismatches. The effect of increasing numbers of HLA-DPB1 mismatches on clinical outcome was assessed in HLA-mismatched transplant recipients. RESULTS: In HLA-A, -B, -C, -DRB1,-DQB1-matched transplant recipients, donor mismatching against one high-expression patient HLA-DPB1 increased moderate (odds ratio [OR], 1.36; P = .001) and severe acute GVHD (OR, 1.32; P = .0016) relative to low-expression patient mismatches, regardless of the expression level of the donor's mismatched HLA-DPB1. Among transplant recipients with one HLA-A, -B, -C, -DRB1, or -DQB1 mismatch, the odds of acute GVHD increased with increasing numbers of HLA-DPB1 mismatches (OR, 1.23 for one; OR, 1.40 for two mismatches relative to zero mismatches for moderate GVHD; OR, 1.19 for one; OR, 1.40 for two mismatches relative to zero for severe GVHD), but not with the level of expression of the patient's mismatched HLA-DPB1 allotype. CONCLUSION: The level of expression of patient HLA-DPB1 mismatches informs the risk of GVHD after HLA-A, -B, -C, -DRB1, -DQB1-matched unrelated HCT, and the total number of HLA-DPB1 mismatches informs the risk of GVHD after HLA-mismatched unrelated HCT. Prospective consideration of HLA-DPB1 may help to lower GVHD risks after transplantation.

Hemophagocytic Lymphohistiocytosis and Graft Failure Following Unrelated Umbilical Cord Blood Transplantation in Children.

Hemophagocytic lymphohistiocytosis (HLH) following hematopoietic stem cell transplantation is closely correlated with graft failure and poor prognosis. Because of its rarity, the incidence, risk factors, and optimal treatment strategy are unclear. We analyzed data from cases of HLH following umbilical cord blood transplantation (UCBT) performed for pediatric patients at our center. Among 66 UCBT recipients, 5 developed HLH and imminent graft failure. The median time of diagnosis of HLH was 22 (range, 19 to 30) days after UCBT, and the cumulative incidence of HLH was 7.6% (95% confidence interval, 2.8-15.7) at day 60. In univariate analysis, the cumulative incidence of HLH was significantly higher in patients with infused CD34 cells <1.0×10/kg than in patients with higher CD34 cells. Patients with preengraftment infection showed a trend toward higher incidence of HLH compared with patients without any infection. All 5 patients with HLH received corticosteroids and low-dose etoposide (VP-16), with or without high-dose intravenous immunoglobulin. Following these treatments, successful engraftment was observed in 2 patients. Corticosteroids and low-dose VP-16 may be worthy of a trial before attempting salvage hematopoietic stem cell transplantation. Further analyses are required to identify risk factors and to develop methods for prophylaxis, diagnosis, and treatment of HLH.

Excellent outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome: a PIDTC report.

Wiskott-Aldrich syndrome (WAS) is an X-linked disease caused by mutations in the WAS gene, leading to thrombocytopenia, eczema, recurrent infections, autoimmune disease, and malignancy. Hematopoietic cell transplantation (HCT) is the primary curative approach, with the goal of correcting the underlying immunodeficiency and thrombocytopenia. HCT outcomes have improved over time, particularly for patients with HLA-matched sibling and unrelated donors. We report the outcomes of 129 patients with WAS who underwent HCT at 29 Primary Immune Deficiency Treatment Consortium centers from 2005 through 2015. Median age at HCT was 1.2 years. Most patients (65%) received myeloablative busulfan-based conditioning. With a median follow-up of 4.5 years, the 5-year overall survival (OS) was 91%. Superior 5-year OS was observed in patients <5 vs ≥5 years of age at the time of HCT (94% vs 66%; overall P = .0008). OS was excellent regardless of donor type, even in cord blood recipients (90%). Conditioning intensity did not affect OS, but was associated with donor T-cell and myeloid engraftment after HCT. Specifically, patients who received fludarabine/melphalan-based reduced-intensity regimens were more likely to have donor myeloid chimerism <50% early after HCT. In addition, higher platelet counts were observed among recipients who achieved full (>95%) vs low-level (5%-49%) donor myeloid engraftment. In summary, HCT outcomes for WAS have improved since 2005, compared with prior reports. HCT at a younger age continues to be associated with superior outcomes supporting the recommendation for early HCT. High-level donor myeloid engraftment is important for platelet reconstitution after either myeloablative or busulfan-containing reduced intensity conditioning. (This trial was registered at www.clinicaltrials.gov as #NCT02064933.).

ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia.

Overcoming graft-versus-host disease (GvHD) without increasing relapse and severe infections is a major challenge after allogeneic hematopoietic stem-cell transplantation (HSCT). ATIR101 is a haploidentical, naïve cell-enriched T-cell product, depleted of recipient-alloreactive T cells to minimize the risk of GvHD and provide graft-versus-infection and -leukemia activity. Safety and efficacy of ATIR101 administered after T-cell-depleted haploidentical HSCT (TCD-haplo + ATIR101) without posttransplant immunosuppressors were evaluated in a Phase 2, multicenter study of 23 patients with acute leukemia and compared with an observational cohort undergoing TCD-haplo alone (n = 35), matched unrelated donor (MUD; n = 64), mismatched unrelated donor (MMUD; n = 37), and umbilical cord blood (UCB; n = 22) HSCT. The primary endpoint, 6-month non-relapse mortality (NRM), was 13% with TCD-haplo + ATIR101. One year post HSCT, TCD-haplo + ATIR101 resulted in lower NRM versus TCD-haplo alone (P = 0.008). GvHD-free, relapse-free survival (GRFS) was higher with TCD-haplo + ATIR101 versus MMUD and UCB (both P < 0.03; 1-year rates: 56.5%, 27.0%, and 22.7%, respectively) and was not statistically different from MUD (1 year: 40.6%). ATIR101 grafts with high third-party reactivity were associated with fewer clinically relevant viral infections. Results suggest that haploidentical, selective donor-cell depletion may eliminate requirements for posttransplant immunosuppressors without increasing GvHD risk, with similar GRFS to MUD. Following these results, a randomized Phase 3 trial versus posttransplant cyclophosphamide had been initiated.

Cutaneous graft-versus-host disease incidence is similar in haploidentical and matched unrelated hematopoietic transplant recipients: A retrospective cohort study.

BACKGROUND: Cutaneous graft-versus-host disease (GVHD) is common after hematopoietic cell transplants. Haploidentical transplants (Haplo) have historically higher rates of GVHD with overall outcomes improved with the use of posttransplant cyclophosphamide. Specific cutaneous outcomes have not been explored in haploidentical versus matched unrelated donor (MUD) transplants. OBJECTIVE: We sought to examine the incidence of GVHD in MUD and Haplo transplants. METHODS: This is a retrospective cohort study of patients' records that received MUD or Haplo transplants between 2010 and 2015 with determination of GVHD severity and features by one investigator. RESULTS: The Haplo cohort included more minorities (22.7% vs 6.8%; P < .001). The incidence of acute cutaneous GVHD was similar (Haplo 47.7% [95% confidence interval {CI} 37.0-58.6%] vs MUD 42.6% [95% CI 37.9-47.3%]; P = .41). Chronic GVHD was also similar (Haplo 17.1% [95% CI 9.9-26.6%] vs MUD 12.8% [95% CI 9.9-16.3%]; P = .31). The Haplo group had lower rates of sclerosis (13.3% [95% CI 1.7-4.05%] vs 50.9% [95% CI 37.3-64.4%]; P = .0095). Other secondary outcomes showed no difference. LIMITATIONS: Severity of GVHD was determined retrospectively and not all patients were seen by a dermatologist. CONCLUSIONS: No difference was observed between rates or severity of acute or chronic GVHD. Sclerosis was less common in the Haplo group.

Haploidentical transplantation might have superior graft-versus-leukemia effect than HLA-matched sibling transplantation for high-risk acute myeloid leukemia in first complete remission: a prospective multicentre cohort study.

This study aimed to investigate graft-versus-leukemia (GVL) of haploidentical donor (HID) compared with HLA-matched sibling donor (MSD) for high-risk acute myeloid leukemia (H-AML) in first complete remission (CR1). One hundred and eighty-nine patients with H-AML in CR1 were enrolled in this multicentre prospective cohort study. Patients were assigned to groups transplanted with HID (n = 83) or MSD (n = 106) based on donor availability (biological randomization). The primary endpoint was the incidence of MRD positivity posttransplantation (post-MRD+). All post-MRD+ patients received preemptive interventions. The cumulative incidences of post-MRD+ were 18 and 42% in HID and MSD groups, respectively, (p < 0.001). Fifty-two patients received preemptive DLI, including 13 (16%) in HID and 39 cases (37%) in MSD groups (p = 0.001). Among HID and MSD groups, the 3-year cumulative incidence of relapse were 14 and 24% (p = 0.101); the 3-year cumulative incidence of treatment-related mortality were 15 and 10% (p = 0.368); the 3-year overall survival rates were 72 and 68% (p = 0.687); the 3-year disease-free-survival were 71 and 66% (p = 0.579); the 3-year graft-versus-host disease and relapse free survival were 63 and 43% (p = 0.035), respectively. HID might have a stronger GVL than MSD in H-AML patients. HID transplantation as postremission therapy should be recommended as one of the optimal choices for H-AML patients in CR1.

Allogeneic hematopoietic stem cell transplantation from unrelated donors is associated with higher infection rates in children with acute lymphoblastic leukemia-A prospective international multicenter trial on behalf of the BFM-SG and the EBMT-PDWP.

Severe infections (SI) significantly impact on non-relapse mortality after hematopoietic stem cell transplantation (HSCT). We assessed 432 children and adolescents with acute lymphoblastic leukemia (ALL) after total body irradiation based myeloablative HSCT within the multicenter ALL-BFM-SCT 2003 trial for SI grade 3 or higher according to common terminology criteria for adverse events. A total 172 patients experienced at least one SI. Transplantation from matched unrelated donors (MUD) was associated with any type of SI in the pre-engraftment period (hazard ratio [HR]: 2.57; P < .001), and with any SI between day +30 and + 100 (HR: 2.91; P = .011). Bacterial (HR: 2.24; P = .041) and fungal infections (HR: 4.06; P = .057) occurred more often in the pre-engraftment phase and viral infections more often before day +30 (HR: 2.66; P = .007) or between day +30 and + 100 (HR: 3.89; P = .002) after HSCT from MUD as compared to matched sibling donors. Chronic GvHD was an independent risk factor for any type of SI after day +100 (HR: 2.57; P < .002). We conclude that allogeneic HSCT from MUD in children and adolescents with pediatric ALL is associated with higher infection rates, which seems attributable to an intensified GvHD prophylaxis including serotherapy and methotrexate.

Discovery of donor genotype associated with long-term survival of patients with hematopoietic stem cell transplantation in refractory acute myeloid leukemia.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been the only treatment option for acute myeloid leukemia (AML) refractory to induction chemotherapy, with only 10-20% of patients achieving long-term survival. Certain donor genotypes may confer leukemia-clearing effects after allo-HSCT. We performed whole-exome sequencing of five pairs of the germ lines in AML patients who achieved long-term remission after allo-HSCT and in their donors, and found two significant variants: EGFR c.2982C > T and CDH11 c.945G > A. To validate the protective effects of these leukemia-clearing genotypes (LCGs), AML patients who received allo-HSCT in a complete-remission status were also analyzed. Twenty-two of 96 donors (22.9%) had LCGs in their genomes, and overall survival was significantly longer in patients who received allo-HSCT from donors with germ-line LCGs (hazard ratio=0.47, 95% confidence interval=0.24-0.94, p = .033). These findings indicate that donor germ-line LCGs have phenotypically leukemia-clearing effects and are biomarkers for predicting clinical outcomes in allogeneic transplantation in AML patients.

The incidence, risk factors and outcomes of early bloodstream infection in patients with malignant hematologic disease after unrelated cord blood transplantation: a retrospective study.

BACKGROUND: Bloodstream infection (BSI) is one of the major causes of morbidity and mortality for patients undergoing hematopoietic stem cell transplantation (HSCT). The unrelated cord blood transplantation (UCBT) can provided opportunities for patients without suitable donors for bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT), while few studies have addressed BSI after UCBT. The aim of this study was to analyse the incidence and risk factors of BSI, causative organisms, microbial resistance, and its impact on the clinical outcomes and survival of patients. METHODS: There are 336 patients, were divided into two groups depending on whether developing BSI. Demographic characteristics, laboratory data, and clinical outcome were compared between different groups. The risk factors of BSI was examined using logistic regression and the survival was examined using the Kaplan-Meier method and log-rank test. RESULTS: Ninety-two patients (27.4%) developed early BSI with 101 pathogenic bacteria isolated, and the median day of developing initial BSI was 4.5 d. Gram-negative bacteria were the most common isolate (60, 59.4%), followed by Gram-positive bacteria (40, 39.6%) and fungi (1, 1.0%). Thirty-seven (36.6%) isolates were documented as having multiple drug resistance (MDR). Myeloid malignancies, conditioning regimens including total body irradiation (TBI), and prolonged neutropenia were identified as the independent risk factors for early BSI. The 3-year OS was 59.9% versus 69.2% in the BSI group and no-BSI group (P = 0.0574), respectively. The 3-year OS of the MDR group was significantly lower than that of the non-BSI group (51.1% versus 69.2%, p = 0.013). CONCLUSIONS: Our data indicate that the incidence of early BSI after UCBT was high, especially in patients with myeloid disease and a conditioning regimen including TBI and prolonged neutropenia. Early BSI with MDR after UCBT had a negative impact on long-term survival.

Is the use of unrelated donor transplantation leveling off in Europe? The 2016 European Society for Blood and Marrow Transplant activity survey report.

Hematopoietic cell transplantation (HCT) is an established procedure for acquired and congenital disorders of the hematopoietic system. In 2016, there was a tendency for continued activity in this field with 43,636 HCT in 39,313 patients [16,507 allogeneic (42%), 22,806 autologous (58%)] reported by 679 centers in 49 countries in 2016. The main indications were myeloid malignancies 9547 (24%; 96% allogeneic), lymphoid malignancies 25,618 (65%; 20% allogeneic), solid tumors 1516 (4%; 2% allogeneic), and non-malignant disorders 2459 (6%; 85% allogeneic). There was a remarkable leveling off in the use of unrelated donor HCT being replaced by haploidentical HCT. Continued growth in allogeneic HCT for marrow failure, AML, and MPN was seen, whereas MDS appears stable. Allogeneic HCT for lymphoid malignancies vary in trend with increases for NHL and decreases for Hodgkin lymphoma and myeloma. Trends in CLL are not clear, with recent increases after a decrease in activity. In autologous HCT, the use in myeloma continues to expand but is stable in Hodgkin lymphoma. There is a notable increase in autologous HCT for autoimmune disease. These data reflect the most recent advances in the field, in which some trends and changes are likely to be related to development of non-transplant technologies.

Comparison of Autologous and Unrelated Transplants for Cytogenetically Normal Acute Myelogenous Leukemia.

Allogeneic stem cell transplantation (SCT) from an HLA-matched sibling donor (MSD) is a postremission treatment that offers a potential cure for adults with cytogenetically normal (CN) acute myelogenous leukemia (AML) in first complete remission (CR1). The best alternative in the absence of an MSD remains unclear, however. The aim of this study was to retrospectively compare the outcomes of autologous peripheral blood stem cell transplantation (auto-PBSCT; n = 177) and allogeneic bone marrow transplantation (BMT) from an HLA-matched unrelated donor (MUD; n = 173) in adult patients with CN-AML/CR1. Both the multivariate analysis (hazard ratio [HR], 1.18; 95% confidence interval [CI], 0.71 to 1.97; P = .53) and propensity score models (HR, 1.40; 95% CI, 0.80 to 2.43; P = .24) indicated that the leukemia-free survival (LFS) rate of auto-PBSCT was not significantly different from that of MUD-BMT. These results suggest that in the absence of an available MSD, auto-PBSCT remains a viable alternative as postremission therapy in patients with CN-AML/CR1.

Comparing outcomes of matched related donor and matched unrelated donor hematopoietic cell transplants in adults with B-Cell acute lymphoblastic leukemia.

BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) using human leukocyte antigen (HLA)-matched related donors (RDs) and allogeneic HCT using HLA-matched unrelated donors (URDs) produce similar outcomes for patients with acute myelogenous leukemia, whereas the donor source has been reported to be a predictor of outcomes in myelodysplastic syndrome. METHODS: Post-HCT outcomes for 1458 acute lymphoblastic leukemia patients from 2000 to 2011 were analyzed, and RD and URD transplants were compared. RESULTS: The median age was 37 years (range, 18-69 years). In the multivariate analysis, HLA 8/8 allele-matched URD recipients had similar transplant-related mortality (TRM) and all-cause mortality in comparison with RD recipients (hazard ratios [HRs], 1.16 [95% confidence interval (CI), 0.91-1.48] and 1.01 [95% CI, 0.85-1.19], respectively); 7/8 URD recipients had a greater risk of TRM and all-cause mortality in comparison with RD recipients (HRs, 1.92 [95% CI, 1.47-2.52] and 1.29 [95% CI, 1.05-1.58], respectively). The risk of TRM and all-cause mortality was also greater for 7/8 URD recipients versus 8/8 URD recipients. Compared with RD recipients, both 8/8 and 7/8 URD recipients had a lower risk of relapse (HRs, 0.77 [95% CI, 0.62-0.97] and 0.75 [95% CI, 0.56-1.00], respectively). Both 8/8 and 7/8 URD recipients had a greater risk of acute graft-versus-host disease (GVHD; HRs, 2.18 [95% CI, 1.76-2.70] and 2.65 [95% CI, 2.06-3.42], respectively) and chronic GVHD (HRs, 1.28 [95% CI, 1.06-1.55] and 1.46 [95% CI, 1.14-1.88], respectively) in comparison with RD recipients. CONCLUSIONS: In the absence of RD transplantation, 8/8 URD transplantation is a viable alternative with similar survival outcomes, whereas 7/8 URD transplantation is associated with poorer overall survival. Cancer 2017;123:3346-55. © 2017 American Cancer Society.

Annual Data for Kidney Transplant Services in Kuwait (2015).

OBJECTIVES: Renal transplant services have been provided by the Hamed Al-Essa Organ Transplant Center in Ibn Sina Hospital since 1979 for Kuwaitis and non-Kuwaiti citizens residing in Kuwait. We aimed to monitor the activity and outcome of annual renal transplants in 2015. MATERIALS AND METHODS: Data on transplant patients were collected from hospital records from January 1, 2015, through December 31, 2015, at Ibn Sina Hospital. RESULTS: Eighty-one patients underwent a renal transplant in Kuwait in 2015; 46 patients (56.8%) were male and 35 (43.2%) were female. Of these 81 patients, 24 (29.6%) received a kidney from a deceased donor, 19 (23.5%) received a kidney from a living-unrelated donor, and 38 (46.9%) received a kidney from a living-related donor. Thirty-four patients (41.98%) who were highly sensitized immunologically underwent successful desensitization before transplant according the local protocol; 13 (38.2%) of these patients were male and 21 (61.8%) were female. Two patients (2.47%) experienced acute rejection within the first week after transplant. One diabetic female patient underwent a successful simultaneous deceased-donor kidney and pancreas transplant. Seventy-nine patients who underwent a transplant outside of Kuwait in 2015 were added to the follow-up list; 62 (78%) of these patients were male and 17 (22%) were female. Of these 79 patients, 31 patients (39%) received a kidney from a living-related donor, 45 (57%) received a kidney from a living-unrelated donor, and 3 (4%) received a kidney from a deceased donor. In addition, 303 patients were assessed for fitness for kidney transplant; 204 (67.3%) of these patients were male and 99 (32.7%) were female. Eight (2.6%) patients were not placed on the waiting list for a kidney transplant for medical reasons. CONCLUSIONS: A total of 81 patients underwent a renal transplant in Kuwait in 2015, only 2 (2.47%) of whom experienced acute rejection in the first week after transplant.

Identification of a 10/10 matched donor for patients with an uncommon haplotype is unlikely.

BACKGROUND: Despite over 6 million subjects contributing to the National Marrow Donor Program human leukocyte antigen (HLA) haplotype frequency reference data (HFD), haplotypes cannot be predicted from the HLA assignments of some patients searching for an unrelated donor (URD) in the Be The Match Registry®. We aimed to determine the incidence of these patient searches and whether haplotypes lacking from the HFD can be found among the low-resolution typed URD pool. MATERIALS AND METHODS: New NMDP searches with uncommon patient haplotypes (UPH), defined as a lack of haplotype pairs in any single ethnic group in the HFD based upon HLA-A˜C˜B˜DRB1˜DQB1, were identified. Each search had up to 20 potential 10/10 or 8/8 URDs typed to determine the likelihood of an allele match. RESULTS: The incidence of patient searches without haplotype pairs in a single ethnic group in the HFD was 1.2% (N=144 out of 12,172) and a majority of these patients (117; 81%) had one uncommon haplotype previously uncharacterized in the HFD. Non-White patients had the highest incidence of UPH. Importantly, no patients with UPH had a 10/10 URD identified. The transplant rate among UPH patients was 15%, and a majority of these patients utilized cord blood units as their transplant stem cell source. CONCLUSION: Therefore, the HLA HFD that informs the HapLogic matching algorithm is thorough as UPH patient searches were infrequent. Since such patients are highly unlikely to have a fully 10/10 matched URD identified, this study supports the identification of alternative stem cell sources including cord blood or a mismatched URD early in the search process.

Adult to adult right lobe living donor liver transplantation: does biological relationship matter?

The influence of the biological relationship between the donor and the recipient is rarely discussed in living donor liver transplantation (LDLT), although it is believed to be an important risk factor in other types of organ transplantations. A total of 272 consecutive patients undergoing adult to adult right lobe LDLT were retrospectively analyzed and stratified into a nonbiologically related (NBR) group (69 patients) and a biologically related (BR) group (203 patients). The preoperative data and postoperative outcomes of both recipients and donors were evaluated.More than two-thirds of the recipients had histories of HBV infection, and hepatocellular carcinoma (HCC) was the main reason for the patients undergoing LDLT in both groups. The percentage of female donors in the NBR group was more than the percentage in the BR group (P = 0.000). There were no differences between the groups in postoperative laboratory testing or daily immunosuppression dose, and the complication rates in both the recipient and donor surgeries showed no significant differences. For patients with benign diseases, the cumulative 1-, 3-, 5-, and 10-year survival rate were 92.9% in the 4 periods in the NBR group and 89.1%, 87.6%, 83.7%, and 83.7%, respectively, in BR group, while for the patients diagnosed as HCC, if patients exceeding the Milan criteria were involved, the 5-year survival rate was 41.2%, compared to 82% for patients within the Milan criteria, which was nearly the same as for those with the benign disease. In conclusion, our findings suggested that the biological relationship between the donor and the recipient in adult to adult LDLT was not associated with the short- and long-term outcomes of recipients diagnosed with benign liver diseases and early stage HCC. Moreover, the criteria for patients diagnosed with HCC to undergo LDLT should be restrictively selected.