Immune reconstitution after single-unit umbilical cord blood transplantation using anti-thymoglobulin and myeloablative conditioning in adults with hematological malignancies.

This study aimed to investigate the kinetics of immune recovery following umbilical cord blood transplantation (UCBT) in adults who received a myeloablative conditioning (MAC) regimen and antithymocyte globulin (ATG). While the immune recovery kinetics has been extensively studied in pediatric UCBT recipients, limited data exist for adults. We conducted a comprehensive analysis of 221 consecutive adult patients who underwent UCBT with MAC and ATG at a single institution. Our objective was to evaluate the influence of patient, disease, and transplant factors, along with acute graft-versus-host disease (aGVHD), on immune reconstitution and overall survival. Our findings confirm a delayed recovery of T cells, while B and NK cell reconstitution exhibited rapid progress, with NK cell counts reaching normal levels within 3 months post-transplantation and B cells within 6 months. Within CD3+ T cells, CD8+ T cells also experienced a delayed recovery (12 months), but to a lesser extent compared to CD4+ T cells (18 months). Delayed immune recovery of T-cell subsets was associated with the development of aGVHD grade II-IV, older age, CMV negativity, and a female donor. Patients with lymphoproliferative diseases showed slower NK cell recovery. Our study demonstrates that adult patients undergoing MAC with ATG and receiving a single unit UCBT for hematologic malignancies experienced rapid reconstitution of NK and B cells. However, T cell recovery, particularly CD4+ T cells, was significantly delayed. To enhance T cell recovery, it may be crucial to consider UCB units with higher cellularity and optimize ATG doses in conditioning.

Cytomegalovirus Reactivations in Allogeneic Hematopoietic Stem Cell Transplantation from HLA-Matched and Haploidentical Donors with Post-Transplantation Cyclophosphamide.

Cytomegalovirus (CMV) reactivations cause significant morbidity in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy) is associated with an increased risk of CMV infections. Data are limited comparing HSCT with PTCy performed from matched sibling donors (MSDs), matched unrelated donors (MUDs), and haploidentical (Haplo) donors. In the present study, we aimed to characterize CMV reactivation and recurrence in patients with hematologic malignancies undergoing HSCT from MSD, MUD, and Haplo donors using PTCy as GVHD prophylaxis in the pre-letermovir era. We also analyzed risk factors of CMV reactivation, including GVHD as a time-dependent variable, on the incidence and mortality associated with CMV infections. We analyzed CMV reactivation in patients undergoing HSCT from 160 MSDs, 124 MUDs, and 82 Haplo donors from a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus, and mycophenolate mofetil was given irrespective of donor type. Overall, 46% of patients had at least 1 CMV reactivation. The 1-year cumulative incidence of CMV infection was 39% for MSD, 44% for MUD, and 62% for Haplo donors (P < .001), with 96% of reactivations occurring before day +100. Multivariate analysis identified factors associated with the first CMV reactivation, including Haplo donor, positive recipient CMV serology, older patient age, and grade II-IV acute GVHD. The 1-year cumulative incidence of second reactivation from HSCT was 13%. Recipient CMV seropositivity, older patient age, and grade II-IV acute GVHD, but not type of donor, were identified as adverse factors for second CMV reactivation in multivariate analysis. The 1-year cumulative incidence of a third reactivation post HSCT was 4.4%. Ten cases of CMV disease were recorded, with no attributable deaths. Nevertheless, the risk for nonrelapse mortality was greater for patients who experienced CMV reactivation in multivariate time-dependent Cox model analysis. CMV reactivation is frequent in HSCT with PTCy in patients not receiving letermovir prophylaxis. Identified risk factors include the use of a Haplo donor, recipient CMV seropositivity, and grade II-IV acute GVHD. The prevalence of recurrent CMV reactivations is a noteworthy issue, especially after acute GVHD, warranting trials of secondary prophylaxis strategies.

Reduced Incidence of Neurologic Complications after Allogeneic Hematopoietic Stem Cell Transplantation with Calcineurin-Free Graft-versus-Host Disease Prophylaxis.

Calcineurin inhibitors (CNIs), including cyclosporine and tacrolimus, are frequently associated with neurologic complications after allogeneic hematopoietic stem cell transplantation (HSCT). However, there is a lack of studies comparing the incidence and characteristics of neurologic complications in patients undergoing HSCT based on CNI-free or CNI-based GVHD prophylaxis. This retrospective single-center study analyzed the neurologic complications in 2 cohorts of patients undergoing HSCT with either CNI-based GVHD prophylaxis (n = 523) or CNI-free prophylaxis with post-transplantation cyclophosphamide, sirolimus, and mycophenolate mofetil (n = 371). The latter cohort included older patients and received more reduced-intensity conditioning and transplants from matched unrelated and haploidentical donors. The 2-year cumulative incidence of neurologic complications was significantly lower in the CNI-free cohort (6.9% versus 11.9%; P = .016), and GVHD prophylaxis was the sole statistically significant variable in multivariate analysis (hazard ratio, 2.2; 95% confidence interval [CI], .25 to 3.13; P = .0017). The distribution of neurologic types was similar in the 2 cohorts, with encephalopathy the most prevalent complication, except for headaches and myopathy, which decreased equally from 15% in the CNI-based cohort to 4% in the CNI-free cohort. Neurologic complications had negative impacts on mortality and survival rates, with a significantly higher 2-year cumulative incidence of nonrelapse mortality (NRM) (44% [95% CI, 34% to 54%] versus 16% [95% CI, 13% to 18%]; P < .0001) and inferior overall survival (66% [95% CI, 62% to 69%] versus 46% [95% CI, 37% to 58%]; P < .0001) in patients with neurologic complications. This study suggests that CNI-free GVHD prophylaxis with post-transplantation cyclophosphamide, sirolimus, and mycophenolate mofetil may reduce not only the incidence of GVHD incidence, but also the rates of neurologic complications and NRM, leading to improved survival outcomes in patients undergoing HSCT.

Transfusion Burden in Allogeneic Hematopoietic Stem Cell Transplantation over Time: Experience from a Single Institution.

INTRODUCTION: Transfusion plays a main role in supportive treatment for patients who receive an allogeneic hematopoietic stem cell transplantation (HSCT). In this study, we compare the transfusion requirements of patients undergoing different modalities of HSCT according to different time periods. The objective is to assess the evolution of HSCT transfusion requirements over time, from a single institution. METHODS: The clinical charts and transfusion records of patients who underwent HSCT of different modalities at La Fe University Hospital during a twelve-year period were reviewed (2009-2020). For analysis, we divided the overall time into three periods: 1 from 2009 to 2012, 2 from 2013 to 2016 and 3 from 2017 to 2020. The study included 855 consecutive adult HSCT: 358 HLA-matched related donors (MRD), 134 HLA-matched unrelated donors (MUD), 223 umbilical cord blood transplantation (UCBT) and 140 haploidentical transplants (Haplo-HSCT). RESULTS: There were no significant differences in RBC and PLT requirements or transfusion independence among the three time periods for MUD and Haplo-HSCT. However, the transfusion burden increased significantly for MRD HSCT during the 2017-2020 period. CONCLUSION: despite HSCT modalities having evolved and changed over time, overall transfusion requirements have not significantly decreased and continue to be a cornerstone of transplantation-supportive care.

Impact of Post-Transplantation Cyclophosphamide on Transfusion Requirements in HLA-Matched Sibling Peripheral Blood Stem Cell Transplantation.

Post-transplantation cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis is being increasingly used in allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched related donors (MRDs); however, information regarding the transfusion needs in this setting is lacking. This study compared RBC and platelet units transfused and time to transfusion independence according to the GVHD prophylaxis regimen in MRD HSCT. We performed a matched-pair analysis comparing the transfusion requirements and the clinical outcomes of patients who underwent MRD peripheral blood HSCT using PTCy between January 2017 and June 2021 (n = 100) with historical MRD HSCTs using standard cyclosporine A (CsA)-based prophylaxis (n = 100). Neutrophil engraftment was significantly delayed in the PTCy group compared with the CsA group (16 days versus 13 days; P = .003). PTCy was associated with increased RBC (median, 5 units versus 4 units; P = .04) and platelet (median, 6 units versus 3 units; P = .01) transfusion requirements during the first 30 days after transplantation. The proportion of patients requiring platelet transfusion during days 31 to 90 after transplantation was also higher in the PTCy group (55% versus 25%; P < .0001). In multivariate analysis, PTCy was associated with delayed RBC and platelet transfusion independence (hazard ratio, .61 [P = .007] and .51 [P < .0001], respectively). The cumulative incidence (CuI) of BK polyomavirus-associated hemorrhagic cystitis grade ≥2 at 100 days was higher in the PTCy group (34% versus 12%; P < .0001); however, the PTCy group had lower rates of grade II-IV acute GVHD (100-day CuI, 57% versus 23%; P < .0001) and moderate to severe chronic GVHD (1-year CuI, 49% versus 28%; P = .003), as well as better 2-year overall survival (74% versus 56%; P = .01). Our study shows that although PTCy increases the transfusion burden in MRD HSCT, it is associated with a low incidence of severe GVHD and with encouraging survival outcomes.

T Cell-Depleted Peripheral Blood versus Unmanipulated Bone Marrow in Matched Sibling Transplantation for Aplastic Anemia.

Bone marrow (BM) is the recommended stem cell source for hematopoietic stem cell transplantation (HSCT) from matched sibling donors (MSDs) in patients with severe aplastic anemia (SAA) for its superior survival and graft-versus-host disease (GVHD) outcomes compared to recipients of unmanipulated peripheral blood (PB) HSCT. Nevertheless, no studies comparing BM with ex vivo T cell-depleted (TCD) PB have been reported to date. The aim of the present study was to compare the transplantation outcomes of MSD HSCT recipients with SAA using PB (with partial ex vivo TCD targeted cell dose grafts) with those of MSD HSCT recipients with SAA using unmanipulated BM. We performed a matched-pair analysis of MSD-HSCT using TCD PB in a single institution with unmanipulated BM MSD-HSCT in the United States between 2013 and 2019 reported to the Center for International Blood and Marrow Transplant Research. We compared 23 recipients of TCD PB HSCT for SAA (cases) and 69 recipients of unmanipulated BM grafts (controls) matched for age, Karnofsky Performance Status, Hematopoietic Cell Transplantation-Specific Comorbidity Index, time from diagnosis to transplantation, and recipient cytomegalovirus serostatus. We found significantly faster neutrophil and platelet recovery in the TCD PB cohort (P < .001 and P = .03, respectively), as well as a lower incidence of grade II-IV acute GVHD (0% versus 17%; P = .05) and similar overall survival (96% versus 97% at 3 years; P = .8). Our study shows that TCD PB can be considered a safe source for MSD-HSCT in patients with SAA, with potential advantages in engraftment and GVHD that could challenge the standard with BM. These findings provide a basis for future research in a prospective controlled clinical trial.

Acute hemolytic reaction by anti-Wra: Case report and review of the hemovigilance database of a tertiary care hospital.

Wra is the most common LIA in white population. The incidence of Wra antigen in Spanish population has been estimated to be 1 in 785 in blood donors, while anti-Wra was found in 2.7 % and 3.6 % of healthy donors and transfused patients respectively. Severe, even fatal hemolytic transfusion reactions and hemolytic disease of the newborn caused by anti-Wra have been reported. Since the reagent red blood cells used for antibody screening usually lack Wra antigen, the anti-Wra is not detected and hemolytic reaction could occur if transfusion is performed by type and screen approach. We report an acute hemolytic reaction due to anti-Wra in a patient with negative antibody screening. We have also reviewed the records of the hospital hemovigilance database in order to collect the previous hemolytic cases due to anti-Wra. During a 21-year period 461,539 red blood cell units have been transfused to 81,614 patients in our hospital. Alloimmnunization was detected in 3840 patients (0.83 %) and anti-Wra was detected in 22 patients (1/3709), 10 of whom had other alloantibodies, and only in 1 occasion (this case) has been implicated in mild hemolytic acute transfusion reaction. In our experience, the risk of fatal hemolytic reaction due to LIA in hospitals with blood services using the type and screen policy is extremely low.

Extracorporeal photopheresis vs standard therapies for steroid-refractory chronic graft-vs-host disease: Pharmacoeconomic assessment of hospital resource use in Spain.

BACKGROUND: This study assessed pharmacoeconomic costs associated with extracorporeal photopheresis (ECP) compared with other available second-line therapies for chronic graft-vs-host disease (cGvHD) in a tertiary Spanish institution. METHODS: Patients (≥18 years) diagnosed with steroid-refractory cGvHD were eligible. Data were collected retrospectively from index date until 1 year or relapse. Patients were distributed in two cohorts (ECP vs non-ECP), matched by age (≤ or > 40), hematopoietic stem cell transplant (HLA-identical sibling donor or other) and number of previous immunosuppressive lines (1, 2, or ≥ 3). Costs were assigned using the 2016 diagnosis-related group (DRG) system: DRG 579 (€22 383) overnight stay due to major complication (ie, sepsis, pneumonia, parenteral nutrition, or respiratory failure), and DRG 875 (€5154) if no major complication. The primary endpoint was healthcare resource utilization per patient. RESULTS: Forty patients (n = 20 per cohort) were included. Median age was 49, and 37.5% were female. Mean total cost per patient was €25 319 (95% CI: €17 049-€33 590) across the two cohorts, with a slightly lower mean cost per ECP-treated patient (€23 120) compared with the non-ECP cohort (€27 519; P = .597). Twenty-seven inpatient hospitalizations occurred among ECP-treated patients, vs 33 in the non-ECP cohort. Day hospital and external consultations were more frequent in the ECP cohort. However, fewer inpatient admissions included DRG 579 compared with the non-ECP cohort (44% vs 58%). Inpatient length of stay was slightly shorter in the ECP cohort (30 vs 49 days; P = .298). CONCLUSIONS: ECP treatment may yield economic savings in Spain through resource savings and moving costs toward outpatient care.

Adoptive transfer of ex vivo expanded SARS-CoV-2-specific cytotoxic lymphocytes: A viable strategy for COVID-19 immunosuppressed patients?

Cellular and humoral response to acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is on focus of research. We evaluate herein the feasibility of expanding virus-specific T cells (VST) against SARS-CoV-2 ex vivo through a standard protocol proven effective for other viruses. The experiment was performed in three different donors' scenarios: (a) SARS-CoV-2 asymptomatic infection/negative serology, (b) SARS-CoV-2 symptomatic infection/positive serology, and (c) no history of SARS-CoV-2 infection/negative serology. We were able to obtain an expanded VST product from donors 1 and 2 (1.6x and 1.8x increase of baseline VST count, respectively) consisting in CD3 + cells (80.3% and 62.7%, respectively) with CD4 + dominance (60% in both donors). Higher numbers of VST were obtained from the donor 2 as compared to donor 1. T-cell clonality test showed oligoclonal reproducible peaks on a polyclonal background for both donors. In contrast, VST could be neither expanded nor primed in a donor without evidence of prior infection. This proof-of-concept study supports the feasibility of expanding ex vivo SARS-CoV-2-specific VST from blood of convalescent donors. The results raise the question of whether the selection of seropositive donors may be a strategy to obtain cell lines enriched in their SARS-CoV-2-specificity for future adoptive transfer to immunosuppressed patients.

Central Nervous System Involvement in Epstein-Barr Virus-Related Post-Transplant Lymphoproliferative Disorders after Allogeneic Hematopoietic Stem Cell Transplantation.

Central nervous system (CNS) involvement in Epstein-Barr virus-related post-transplant lymphoproliferative disorders (EBV-PTLDs) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is poorly defined. We analyzed the incidence, clinical and pathological characteristics, and impact on outcomes of EBV-PTLDs with CNS involvement (CNS-PTLDs) in 1009 consecutive adult patients undergoing allo-HSCT at a single-center institution. Four hundred eighty-two patients received matched sibling donor (MSD) transplants, 388 umbilical cord blood transplants (UCBTs), 56 matched unrelated donor (MUD) transplants, and 83 haploidentical transplants. We detected 25 cases of biopsy-proven EBV-PTLDs. Of these, nine patients (36%) had CNS-PTLDs: six after UCBT (67%), one after MSD transplantation (11%), one after MUD transplantation (11%), and one after haploidentical transplantation (11%). The 5-year cumulative incidence risk of CNS-PTLDs was 0.9%. Median time from transplant to CNS-PTLDs was 187 days, and all patients had neurological symptoms at diagnosis. Six out of the nine cases (67%) occurred with systemic involvement, and three cases (33%) had isolated CNS involvement. The most frequent histological subtype was monomorphic EBV-PTLD, and laboratory characteristics were similar to EBV-PTLDs without CNS involvement. We observed statistical differences in the rate of positive EBV DNA detection in plasma between isolated CNS-PTLDs (detection in one out of three, 33%) and the rest of the EBV-PTLDs (100%) (P = .01). Treatment strategies included chemotherapy, radiotherapy, and T cell therapy. However, seven out of nine patients died due to progression of the CNS-PTLDs at a median time of 17 days (range, 8 to 163) from diagnosis. The 5-years overall survival in patients who developed CNS-PTLDs was 22% (95% confidence interval [CI], 7% to 75%) and 5-year treatment-related mortality was 78% (95% CI, 51% to 100%), with no statistically significant differences between CNS-PTLDs and the rest of the EBV-PTLDs. In conclusion, despite advances in EBV monitoring and treatment strategies, CNS-PTLDs remain an uncommon but serious complication after allo-HSCT, with very poor prognosis.

Ex vivo T-cell depletion vs post-transplant cyclophosphamide, sirolimus, and mycophenolate mofetil as graft-vs-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: To compare the efficacy and safety of CD34+ selected ex vivo T-cell depletion (TCD) vs post-transplant cyclophosphamide, sirolimus, and mycophenolate mofetil (PTCy-Sir-MMF) as graft-vs-host disease (GVHD) prophylaxis. METHODS: We retrospectively included patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with either TCD (n = 38) or PTCy-Sir-MMF (n = 91). RESULTS: Cumulative incidence of neutrophil and platelet recovery was 92% vs 99% (P = .06) and 89% vs 97% (P = .3) in TCD and PTCy-Sir-MMF, respectively. Cumulative incidences of aGHVD grade II-IV, III-IV, and moderate to severe cGVHD were 11% vs 19% (P = .2), 3% vs 2% (P = .9), and 3% vs 36% (P < .001) in TCD and PTCy-Sir-MMF, respectively. The 2-year non-relapse mortality, relapse, disease-free and overall survival were 25% vs 8% (P = .01), 20% vs 16% (P = .2), 55% vs 76% (P = .004), 57% vs 83% (P = .004) for TCD and PTCy-Sir-MMF, respectively. Cumulative incidence of cytomegalovirus and Epstein-Barr infection requiring therapy was 76% vs 40% (P < .001) and 32% vs 0% (P < .001) in TCD and PTCy-Sir-MMF, respectively. PTCy-Sir-MMF platform showed faster T-cell reconstitution. CONCLUSIONS: PTCy-Sir-MMF provides better survival outcomes but is associated with higher risk of cGVHD compared to TCD.

Pure red cell aplasia after major or bidirectional ABO incompatible hematopoietic stem cell transplantation: to treat or not to treat, that is the question.

Pure red cell aplasia (PRCA) is a complication related to major or bidirectional ABO mismatched hematopoietic stem cell transplantation. This disorder is characterized by anemia, reticulocytopenia, and the absence or virtual absence of erythroid progenitors, other causes such as infections, hemolysis, disease relapse, or drug toxicity having been excluded. Patients with PRCA may become RBC transfusion dependent for long periods, suffering an important long-term iron overload, alloimmunization, and transfusion reactions. The persistence of recipient isoagglutinins against donor ABO antigens produced by host residual plasmatic cells has been considered as the immunological cause of the prolonged erythroid aplasia. PRCA behaves in many cases as a self-limited condition and resolution may occur spontaneously within weeks, months, and even years. Many different therapeutic approaches have been reported for posttransplant PRCA as plasmapheresis, high doses of erythropoietin, donor lymphocyte infusions, anti-thymocyte globulin, Rituximab and steroids, among others. However, to date there is no standard of care and the question if patients with PRCA should be treated and at which point remains. The objective of this article is to review the natural evolution of PRCA, and the treatments that have been used over time focusing on their suitability and efficacy.

Allogeneic hematopoietic stem cell transplant recipients in Spain: Human leukocyte antigen characteristics and diversity by high-resolution analysis.

There are many studies on the polymorphism of the HLA system in healthy donor populations, such as registries of unrelated bone marrow donors. Investigations on the characterization of the HLA complex in hematopoietic stem cell transplant (HSCT) patients, however, are scarce, at least in the Spanish population. This study presents a large-scale analysis of allelic diversity and HLA distribution at a high-resolution level in 2886 patients undergoing HSCT in Spanish centres of the "Grupo Español de Trasplante Hematopoyético y Terapia Celular" during a period of 11 years. Allelic diversity analysis identified 67 HLA-A, 133 HLA-B, 60 HLA-C, 63 HLA-DRB1, 24 HLA-DQB1 and 27 HLA-DPB1 different alleles. Rare alleles were detected among which 33 alleles had not been reported in the European catalog of common and well-documented HLA alleles. Regarding the distribution of five genes-haplotypes, it was observed that the five most frequent extended haplotypes found in our population were between the most common in other Spanish populations, both in patients and in healthy subjects. However, some particular haplotypes were also detected. Bilocus associations HLA-C ~ B and -DRB1 ~ DQB1 were analyzed in order to predict the probability of finding 10/10 matched donors in registries. We found HLA-B alleles showing a great diversity of combinations with HLA-C alleles and unusual associations involving a negative predicting factor. In the field of adoptive therapies, our work supports the necessity to expand further research of TCR-engineered cells, adoptive transfer of virus-specific T-cells and vaccines to target HLA alleles other than A*02:01. HLA alleles such as A*01:01, A*03:01, A*24:02, B*44:03, B*07:02 or B*51:01, might be considered new targets due to its high frequency in our population.

A case of megaloblastic anemia simulating a cold autoimmune hemolytic anemia.

CONCLUSIONS: We report a case of pernicious anemia in which the first diagnosis suspicion was cold autoimmune hemolytic anemia (cAIHA) due to the presence of cold autoantibodies. A 47-year-old woman with a medical history of autoimmune thyroid disease came to the hospital with a clinical and serologic presentation of AIHA. However, because of determination of vitamin B12 (VB12) deficiency, she was finally diagnosed with megaloblastic anemia. In the acute period, the patient received short-term corticosteroid therapy and later VB12. The patient's hemoglobin level and general condition showed improvement.

Partial T Cell-Depleted Peripheral Blood Stem Cell Transplantation from HLA-Identical Sibling Donors for Patients with Severe Aplastic Anemia.

We analyzed the outcomes of 26 consecutive patients with acquired severe aplastic anemia (SAA) undergoing peripheral blood stem cell transplantation (PBSCT) with partial ex vivo T cell depletion with a targeted T cell dose from HLA-identical sibling donors. The median patient age was 37 years (range, 3 to 63 years). Four patients with uncontrolled pneumonia at the time of transplantation died, on days +1, +2, +21, and +26. All evaluable patients engrafted, with a median time to neutrophil recovery of 11 days (range, 10 to 14 days) and a median time to platelet recovery of 19 days (range, 8 to 53 days). Two patients had transient grade I acute graft-versus-host disease (GVHD) with skin involvement, but no patients developed grade II-IV acute GVHD. Two patients had mild skin chronic GVHD, and 1 patient had moderate chronic GVHD with ocular involvement. No relapse was observed after a median follow-up of 114 months (range, 4 to 233 months). The overall cumulative incidence of TRM at 10 years was 19%, whereas it was 5% for those with a Karnofsky Performance Status (KPS) score >60 at the time of transplantation. Disease-free survival, overall survival, and GVHD and relapse-free survival at 10 years were 81%, 81%, and 80%, respectively, for all patients and 95%, 95%, and 90%, respectively, for patients with a KPS score >60 at transplantation. Our data indicate that PBSCT with partial ex vivo T cell-depleted targeted cell dose grafts from an HLA-identical sibling donor is a feasible, safe, and effective approach to reduce GVHD and cure patients with SAA.

Comparison of transfusion requirements in adult patients undergoing Haploidentical or single-unit umbilical cord blood stem cell transplantation.

OBJECTIVES: Umbilical cord blood transplantation (UCBT) and haploidentical hematopoietic stem cell transplantation (haplo-HSCT) modalities have been developed to offset the lack of matched donors. In this study, we compare the transfusion requirements of patients undergoing UCBT and haplo-HSCT in a single institution with the aim of providing additional information for clinicians to choose the most adequate alternative graft for HSCT. METHODS: The study reviewed 67 and 46 patients undergoing UCBT and haplo-HSCT, respectively. RESULTS: There were no significant differences for RBC and PLT requirements according to the transplantation modality. Median time to RBC transfusion independence was 35 and 25.5 days in patients who received an UCBT and haplo-HSCT, respectively (P = 0.38), while median time to platelet transfusion independence was 31 days for UCBT patients and 23 for haplo-HSCT patients (P < 0.001). Days until neutrophils > 0.5 × 109 /L were the only variable that significantly influenced RBC and PLT requirements for both transplantation modalities. Cumulative incidence of RBC and PLT transfusion independence at 90 days after transplantation was similar for both UCBT and haplo-HSCT. CONCLUSIONS: Both transplantation platforms require prolonged and intensive supportive RBC and PLT transfusion therapy. Both transplantation platforms require prolonged and intensive supportive RBC and PLT transfusion therapy.

Incidence and outcome of invasive fungal disease after front-line intensive chemotherapy in patients with acute myeloid leukemia: impact of antifungal prophylaxis.

Few reports analyze the incidence and clinical outcome of invasive fungal disease (IFD) in patients with newly diagnosed acute myeloid leukemia (AML) undergoing intensive chemotherapy, and thus the impact of different antifungal prophylactic regimens remains unclear. We analyze the incidence and clinical outcome of IFD in a large series of adult AML patients undergoing front-line intensive induction and consolidation chemotherapy between 2004 and 2015 in a single institution. Three antifungal prophylaxis regimens were given (2004-2005 oral fluconazole, 2006-2012 intravenous itraconazole, and 2013-2015 voriconazole). Overall, 285 patients and 589 intensive chemotherapy episodes were assessed (47%) (induction courses 47% and consolidation 53%). The median age was 51 years (range, 17-65). We observed 56 (10%) episodes of IFD. According to the EORTC 2008 criteria, IFD was classified as possible (29, 52%), probable (17, 30%), and proven (10, 18%). Possible/probable/proven IFD rate was significantly lower during HiDAC consolidation as compared to any anthracycline-containing chemotherapy courses (2% vs. 11%, P = 0.001), and under voriconazole prophylaxis as compared to itraconazole and fluconazole (6% vs. 11% vs. 15%, P = 0.007), and the multivariate analysis showed that they were independent risk factors. Patients under voriconazole prophylaxis had shorter hospitalization duration and less frequent use of empirical or directed antifungal therapy. In conclusion, IFD was a frequent complication during upfront intensive chemotherapy courses for adult AML patients. This retrospective study shows that voriconazole prophylaxis was feasible and associated with a lower risk of IFD compared with intravenous itraconazole or oral fluconazole schedules.