Analysis of relapse after transplantation in acute leukemia: A comparative on second allogeneic hematopoietic cell transplantation and donor lymphocyte infusions.
Relapse of acute leukemia (AL) after allogeneic hematopoietic cell transplantation (Allo-HCT) entails a dismal prognosis. In this scenario, donor lymphocyte infusions (DLIs) and second Allo-HCT are two major approaches. We compared outcomes of AL patients treated for relapse with DLI or second Allo-HCT after receiving debulking therapy. In total, 46 patients were included in the study; 30 (65%) had acute myeloid leukemia and 16 (35%) had acute lymphoblastic leukemia. The median age was 38 years (range 4-66). Twenty-seven patients received a second Allo-HCT and 19 patients received DLI. The median follow-up of the cohort was 273 days (range 9-7013). Overall survival (OS), disease-free surviv…
Seasonal Human Coronavirus Respiratory Tract Infection in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation
Abstract Background Little is known about characteristics of seasonal human coronaviruses (HCoVs) (NL63, 229E, OC43, and HKU1) after allogeneic stem cell transplantation (allo-HSCT). Methods This was a collaborative Spanish and European bone marrow transplantation retrospective multicenter study, which included allo-HSCT recipients (adults and children) with upper respiratory tract disease (URTD) and/or lower respiratory tract disease (LRTD) caused by seasonal HCoV diagnosed through multiplex polymerase chain reaction assays from January 2012 to January 2019. Results We included 402 allo-HSCT recipients who developed 449 HCoV URTD/LRTD episodes. Median age of recipients was 46 years (range,…
Community-acquired respiratory virus lower respiratory tract disease in allogeneic stem cell transplantation recipient: Risk factors and mortality from pulmonary virus-bacterial mixed infections.
Abstract Risk factors (RFs) and mortality data of community‐acquired respiratory virus (CARVs) lower respiratory tract disease (LRTD) with concurrent pulmonary co‐infections in the setting of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is scarce. From January 2011 to December 2017, we retrospectively compared the outcome of allo‐HSCT recipients diagnosed of CARVs LRTD mono‐infection (n = 52, group 1), to those with viral, bacterial, or fungal pulmonary CARVs LRTD co‐infections (n = 15, group 2; n = 20, group 3, and n = 11, group 4, respectively), and with those having bacterial pneumonia mono‐infection (n = 19, group 5). Overall survival (OS) at day 60 after bronchoalveol…
Allogeneic Stem Cell Transplantation for Myelodysplastic Syndrome Patients with a 5q Deletion
The deletion (5q) karyotype (del [5q]) in patients with myelodysplastic syndrome (MDS) is the most common karyotypic abnormality in de novo MDS. An increased number of blasts and additional karyotypic abnormalities (del [5q]+) are associated with a poor outcome. We analyzed the outcome of allogeneic hematopoietic cell transplants (HCT) in patients suffering from MDS with only del (5q) or del (5q)+ . A total of 162 patients, of median age 54 years (range, 9 to 73), having MDS and del (5q) abnormalities received HCT from identical siblings (n = 87) or unrelated donors (n = 75). The cumulative incidence of nonrelapse mortality and relapse incidence at 4 years was 29% (95% CI, 22 to 36) and 46%…
Tumor lysis syndrome in patients with acute myeloid leukemia: identification of risk factors and development of a predictive model
Background Despite the prophylactic use of allopurinol, tumor lysis syndrome (TLS)- related morbidity and mortality still occur in a number of patients with acute myeloid leukemia (AML).The aim of this study was: (i) to analyze the incidence and outcome of TLS in a large series of patients with AML receiving hyperhydration and allopurinol, (ii) to identify risk factors for TLS, and (iii) to develop a prognostic scoring system for estimating individual risk of TLS. Design and Methods The study included 772 adult patients with AML receiving induction chemotherapy between 1980 and 2002. TLS was divided into laboratory TLS (LTLS) or clinical TLS (CTLS).The population study was randomly divided …
Kinetics of Torque Teno virus DNA in stools may predict occurrence of acute intestinal graft versus host disease early after allogeneic hematopoietic stem cell transplantation
Torque Teno virus (TTV) DNA load in blood may act as a marker of immune competence after allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). Conflicting data have been reported as to the value of this biomarker for anticipating acute Graft-versus-host disease (aGvHD) occurrence. Here, we hypothesized that quantitation of TTV DNA load in stool specimens early after allo-HSCT could be used to identify patients at high risk of acute intestinal graft-versus-host disease (aIGvHD). In this prospective two-center study we recruited a total of 83 non-consecutive adult patients undergoing allo-HSCT. The study period comprised the first 120 days after allo-HSCT. TTV DNA was quantita…
Assessment of immunodeficiency scoring index performance in enterovirus/rhinovirus respiratory infection after allogeneic hematopoietic stem cell transplantation.
BACKGROUND: Enterovirus/rhinoviruses (EvRh) are the most common cause of respiratory virus infections in recipients of allogeneic stem cell transplantation (allo-HSCT).; OBJECTIVE: We sought to analyze the value of the immunodeficiency scoring index (ISI) in predicting lower respiratory tract disease (LRTD) progression and mortality in a prospective cohort of consecutive adult (> 16 years) allo-HSCT recipients with EvRh infection from December 1 2013 to December 1 2019 at two Spanish transplant centers.; RESULTS: We included 234 allo-HSCT recipients with 383 EvRh episodes. Out of 383 EvRh episodes, 98 (25%) had LRTD. Multivariate logistic regression analysis identified three independent fac…
An investigation of the potential association between gastrointestinal viral and bacterial infection and development of intestinal acute graft versus host disease following allogeneic hematopoietic stem cell transplantation.
It is uncertain whether gastrointestinal (GI) infection caused by viral and bacterial pathogens may predispose to gastrointestinal acute Graft-versus-host disease (aGvHD-GI) in allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). We investigated the potential association between detection of enteropathogenic viruses or bacteria in stools and subsequent occurrence of aGvHD-GI in a cohort of 121 allo-HSCT patients. Eighty-six out of 121 patients (71%) had acute diarrhea and underwent screening for primary GI pathogens by molecular diagnostic methods. One or more GI pathogens were detected in 27 out of the 86 patients with diarrhea (31.3%). Specifically, Clostridioides diffici…
INFECTIOUS COMPLICATIONS AFTER UMBILICAL CORD-BLOOD TRANSPLANTATION FROM UNRELATED DONORS
Umbilical cord-blood (UCB) is a well-recognized alternative source of stem cells for unrelated donor hematopoietic stem cell transplantation (HSCT). As compared with other stem cell sources from adult donors, it has the advantages of immediate availability of cells, absence of risk to the donor and reduced risk of graft-versus-host disease despite donor-recipient HLA disparity. However, the use of UCB is limited by the delayed post-transplant hematologic recovery due, at least in part, to the reduced number of hematopoietic cells in the graft and the delayed or incomplete immune reconstitution. As a result, severe infectious complications continue to be a leading cause of morbidity and mort…
Pulmonary cytomegalovirus (CMV) DNA shedding in allogeneic hematopoietic stem cell transplant recipients: Implications for the diagnosis of CMV pneumonia
Highlights • CMV DNA is frequently detected in BAL fluid specimens from allo-HSCT. • CMV DNA detection in BAL fluids is comparable across pneumonia etiologies. • CMV DNA loads in BAL fluids are comparable across pneumonia etiologies. • CMV DNA load in BAL may predict attributable-pneumonia mortality.
Umbilical cord blood transplantation in adults with advanced hodgkin's disease: high incidence of post-transplant lymphoproliferative disease
We report the outcome of 30 consecutive patients with Hodgkin disease (HD) who underwent single-unit UCBT. Most (90%) patients had failed previous autologous hematopoietic stem cell transplantation. The conditioning regimens were based on combinations of thiotepa, busulfan, cyclophosphamide or fludarabine, and antithymocyte globulin. The cumulative incidence (CI) of myeloid engraftment was 90% [95% confidence interval (C.I.), 74-98%] with a median of 18 d (range, 10-48). CI of acute graft-versus-host disease (GvHD) grades II-IV was 30% (95% C.I., 17-44%), while the incidence of chronic GVHD was 42% (95% C.I., 23-77%). The non-relapse mortality (NRM) at 100 d and 4 yr was 30% (95% C.I., 13-4…
Clinical effectiveness of influenza vaccination after allogeneic hematopoietic stem cell transplantation: A cross-sectional prospective observational study.
Abstract Background Vaccination is the primary method for preventing influenza respiratory virus infection (RVI). Although the influenza vaccine is able to achieve serological responses in some allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, its clinical benefits are still uncertain. Methods In this prospective, cross-sectional study, we retrospectively analyzed the effect of inactivated trivalent influenza vaccination on the prevalence of influenza RVI in a consecutive cohort of 136 allo-HSCT adult recipients who developed 161 RVI over 5 flu seasons (from 2013 to 2018). Respiratory viruses in upper– and/or lower–respiratory tract specimens were tested using multi…
Umbilical Cord Blood Transplantation in Children and Adults
Umbilical cord blood transplantation (UCBT) from unrelated donors is a suitable option of HSCT for patients in whom it is indicated, and a suitable related or unrelated BM or PB donor is not available in due time.
Clinical significance of Pneumocystis jirovecii DNA detection by real-time PCR in hematological patient respiratory specimens
The clinical benefit of instituting a prospective clinical community-acquired respiratory virus surveillance program in allogeneic hematopoietic stem cell transplantation
Highlights • Rapid detection methods used as first diagnostic test for CARVs may delayed the start of antiviral therapy in a significant number of influenza and RSV cases. • Syndromic multiplex RT-PCR-based prospective clinical CARV survey in allo-HCT recipients translates into a lower mortality rate as compared to standard clinical practice based on RSV and influenza virus rapid detection test. • We found that donor/recipient HLA mismatch, CARV LRTD and high-risk ISI were also associated with higher mortality.
Unexpected postmortem diagnosis of Acanthamoeba meningoencephalitis following allogeneic peripheral blood stem cell transplantation.
Meningoencephalitis caused by pathogenic free-living amebas is usually fatal. Only a few cases of Acanthamoeba meningoencephalitis, diagnosed at autopsy, have been reported following hematopoietic stem cell transplantation. We here report a case of Acanthamoeba meningoencephalitis following allogeneic peripheral blood stem cell transplantation with rapidly evolving neurologic symptoms that remained unexplained. Magnetic resonance imaging failed to show brain lesions and cerebrospinal fluid was negative for microbiological cultures. Definite diagnosis was an unexpected autopsy finding. As overall and teaching hospital autopsy rates are declining worldwide, we must emphasize the need of autop…
Detection of plasmid-mediated colistin resistance, mcr-1 gene, in Escherichia coli isolated from high-risk patients with acute leukemia in Spain
Background: Bacterial infections in immunocompromised patients are associated with a high mortality and morbidity rate. In this high-risk group, the presence of multidrug-resistant (MDR) bacteria, particularly bacteria that harbor a transferable antibiotic resistance gene, complicates the management of bacterial infections. In this study, we investigated the presence of the transferable colistin resistance mcr genes in patients with leukemia in Spain. Methods: 217 fecal samples collected in 2013-2015 from 56 patients with acute leukemia and colonized with MDR Enterobacteriaceae strains, were screened on September 2017 for the presence of the colistin resistance mcr genes (mcr-1 to -5) by mu…
Advances in haploidentical stem cell transplantation for hematologic malignancies
One of the most important advances in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the use of alternative donors and cell sources, such as haploidentical transplants (haplo-HSCT) from family donors. Several approaches have been developed to overcome the challenging bidirectional alloreactivity. We discuss these approaches, including ex vivo T-cell-depleted grafts with megadose of CD34(+) cells, not requiring immunosuppression after allogeneic transplantation for graft-versus-host disease (GVHD) prophylaxis, and other strategies using unmanipulated T-cell-replete grafts with intensive immunosuppression or post-transplantation cyclophosphamide to minimize the GVHD. We als…
Dielectric and mechanical assessment of cellulosic insulation during transformer manufacturing
Due to the impact of cellulose of paper insulation on transformer life, it is imperatire to remove moisture from the oil and the solid insulation. Several techniques have been implemented during manufacturing of power transformers to reduce water content in transformers. These drying processes can involve different costs and time, and they can damage the insulation paper. In this work, a drying process has been implemented in the laboratory trying to simulate the most aggressive conditions that can be suffered by the paper in transformer manufacturing in a real industry. Once the moisture content of papers was lower than 0.5%, the effect of the drying process on paper degradation was evalua…
Post-transplant cyclophosphamide and sirolimus based graft-versus-host disease prophylaxis after allogeneic stem cell transplantation for acute myeloid leukemia.
Post-transplant cyclophosphamide (PTCy) has emerged as a promising graft-versus-host disease (GvHD) prophylaxis in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, no studies have reported the efficacy of a GvHD prophylaxis based on PTCy with sirolimus (Sir-PTCy) in patients with acute myeloid leukemia (AML). In this retrospective study, we analyze the use of sirolimus in combination with PTCy, with or without mycophenolate mofetil (MMF), on 242 consecutive adult patients with AML undergoing a myeloablative first allo-HSCT from different donor types, in three European centers between January 2017 and December 2020. Seventy-seven (32%) patients received allo-HSCT from…
Single umbilical cord blood with or without CD34+ cells from a third-party donor in adults with leukemia
We retrospectively compared the clinical outcomes of adults with acute leukemia who received single-unit umbilical cord blood (UCB) transplantation (sUCBT) (n = 135) or stem cell transplant using coinfusion of a UCB graft with CD34+ cells from a third-party donor (Haplo-Cord) (n = 72) at different institutions within the Grupo Espanol de Trasplante Hematopoyetico. In multivariable analysis, patients in the Haplo-Cord group showed more rapid neutrophil (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.5-3.3; P < .001) and platelet recovery (HR, 1.6; 95% CI, 1.2-2.3; P = .015) and lower incidence of chronic graft-versus-host disease (GVHD) (relative risk, 0.5; 95% CI, 0.3-0.8; P = .01)…
Incidence and risk factors of post-engraftment invasive fungal disease in adult allogeneic hematopoietic stem cell transplant recipients receiving oral azoles prophylaxis.
Studies that analyze the epidemiology and risk factors for invasive fungal disease (IFD) after engraftment in alloSCT are few in number. This single-center retrospective study included 404 alloSCT adult recipients surviving > 40 days who engrafted and were discharged without prior IFD. All patients who received >= 20 mg/day of prednisone were assigned to primary oral prophylaxis (itraconazole or low-dose voriconazole). The primary end point was the cumulative incidence (CI) of probable/proven IFD using the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) criteria. The independent prognostic factors after multivariate analyses were used to constr…
Post-transplantation cyclophosphamide after HLA identical compared to haploidentical donor transplant in acute myeloid leukemia: a study on behalf of GETH-TC
Post-transplantation cyclophosphamide (PTCY) effectively prevents graft-versus-host disease (GVHD) after unmanipulated HLA-haploidentical hematopoietic stem cell transplantation (HSCT) and achieves low rates of GVHD in HLA-identical transplantation. To compare the outcomes of haploidentical versus HLA identical HSCT in patients undergoing HSCT for acute myeloid leukemia (AML) using PTCY. We conducted a retrospective study of 229 patients undergoing first HSCT for AML using PTCY with additional immunosuppression, 99 from matched sibling or unrelated donor (MSD/MUD) performed in 3 hospitals and 130 from haploidentical donors (haplo group) performed in 20 hospitals within the Spanish Group of …
Incidence, risk factors, and outcome of pulmonary invasive fungal disease after respiratory virus infection in allogeneic hematopoietic stem cell transplantation recipients
Abstract Background There is growing evidence that community‐acquired respiratory virus (CARV) increases the risk of pulmonary invasive fungal disease (IFD) in the allogeneic hematopoietic stem cell transplantation (allo‐HSCT) setting. To date, there is a lack of knowledge regarding the risk factors (RFs), as well as the most critical period for subsequent onset of IFD after CARV infections in allo‐HSCT recipients. Methods In this prospective longitudinal observational CARV survey, we analyzed the effect of CARV on subsequent IFD development in 287 adult allo‐HSCT recipients diagnosed with 597 CARV episodes from December 2013 to December 2018. Multiplex PCR panel assays were used to test CA…
Prospective Randomized Study Comparing Myeloablative Unrelated Umbilical Cord Blood Transplantation versus HLA-Haploidentical Related Stem Cell Transplantation for Adults with Hematologic Malignancies
In this prospective randomized study, we compared the outcomes of single-unit umbilical cord blood transplantation (UCBT) and unmanipulated haploidentical stem cell transplantation (haplo-SCT) with post-transplantation cyclophosphamide (PTCy) in adults with hematologic malignancies. All patients received a myeloablative conditioning (MAC) regimen consisting of thiotepa, busulfan, and fludarabine, with antithymocyte globulin (ATG) added for UCBT recipients. Nineteen patients were randomized to UCBT and the other 26 to haplo-HSCT. Four patients (15%) allocated to the haplo-HSCT arm lacked a suitable donor and were crossed over to the UCBT arm. Finally, 23 underwent UCBT and 22 underwent haplo…
Umbilical cord blood transplantation from unrelated donors in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia
Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't; There are very few disease-specific studies focusing on outcomes of umbilical cord blood transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia. We report the outcome of 45 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia who underwent myeloablative single unit cord blood transplantation from unrelated donors within the GETH/GITMO cooperative group. Conditioning regimens were based on combinations of thiotepa, busulfan, cyclophospamide or fludarabine, and antithymocyte globulin. At the time of transplantation, 35 patients (78%) were in first complete remission, four (8%) …
Feasibility of thiotepa addition to the fludarabine-busulfan conditioning with tacrolimus/sirolimus as graft vs host disease prophylaxis.
In classical reduced-intensity conditioning (RIC) regimens, including the fludarabine and busulphan (BF) combination, sirolimus and tacrolimus (SIR-TAC) as graft vs host disease (GVHD) prophylaxis has shown acceptable results. The outcomes of SIR-TAC in a more intense RIC regimen as Thiotepa-fludarabine-busulfan (TBF) have been hardly investigated. This retrospective study included all consecutive patients receiving an allogeneic hematopoietic stem cell transplantation for myeloid malignancies (January 2009-2017) conditioned with either TBF or BF and receiving SIR-TAC. Patients receiving TBF presented higher non-relapse mortality (31.6 vs 12.3%,p = .01), along with shorter overall survival …
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 < …
Post-transplant lymphoproliferative disorders after solid organ and hematopoietic stem cell transplantation.
Post-transplant lymphoproliferative disorders (PTLD) are a rare complication after both solid organ (SOT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this single center retrospective study, we compared clinical, biological, and histological features, and outcomes of PTLD after both types of transplant. We identified 82 PTLD (61 after SOT and 21 after allo-HSCT). The presence of B symptoms, Waldeyer ring, spleen, central nervous system, and liver involvement, and advanced Ann-Arbor stage were more frequent in allo-HSCT recipients. PTLD had an earlier onset in allo-HSCT than in SOT cohort (4 vs. 64 months, p .0001). PTLD was EBV-positive in 100% of allo-HSCT, in co…
Significance of increased blastic-appearing cells in bone marrow following myeloablative unrelated cord blood transplantation in adult patients.
An abnormal increase of nonleukemic blastic-appearing lymphocytes in bone marrow (BM) specimens has been reported after unrelated cord blood transplantation (UCBT). This study analyzed the incidence, chronology, biological features, and clinical significance of elevated numbers of these cells in a series of 165 consecutive adult patients demonstrating myeloid engraftment after myeloablative UCBT in a single institution. The patients' BM samples were routinely evaluated by cytomorphology at different time points after UCBT. When ≥5% of blastic-appearing cells were detected by cytomorphology in the BM, samples were also evaluated by multiparametric flow cytometry to characterize these cells. …
Hematopoietic Stem Cell Transplantation in APL
The indication for hematopoietic stem cell transplant (HSCT) in APL has evolved historically from a widespread use in frontline therapy during the pre-ATRA era to a virtual rejection of this indication when patients are treated with modern treatments containing all-trans retinoic acid (ATRA), either in combination with chemotherapy, arsenic trioxide (ATO), or both. This indication has gradually been abandoned and explicitly rejected by the European LeukemiaNet recommendations. The high cure rate obtained using ATRA plus chemotherapy or ATRA plus ATO indicates that there is no role for HSCT for patients who achieve molecular remission at the end of consolidation. The HSCT in first complete r…
Haploidentical Stem Cell Transplantation With Posttransplant Cyclophosphamide Therapy vs Other Donor Transplantations in Adults With Hematologic Cancers A Systematic Review and Meta-analysis
Question What are the outcomes of haploidentical stem cell transplantation with posttransplant cyclophosphamide therapy compared with other transplant types in adults with hematologic cancers? Findings In this meta-analysis of 30 studies including 22974 patients, the use of haploidentical stem cell transplantation with posttransplant cyclophosphamide therapy appeared to show increased all-cause mortality compared with matched related donors, similar all-cause mortality compared with matched unrelated donors, and reduced all-cause mortality compared with mismatched unrelated donors. Relapse appeared to be increased in lymphoma and similar in acute leukemia compared with matched unrelated don…
The effect of timing on community acquired respiratory virus infection mortality during the first year after allogeneic hematopoietic stem cell transplantation: a prospective epidemiological survey.
The effect of timing of community acquired respiratory virus (CARV) infection after allogeneic hematopoietic stem cell transplant (allo-HCT) is an as yet unsettled issue. We evaluate this issue by including all consecutive allo-HCT recipients with molecularly-documented CARV infection during the first year after transplant. The study cohort was drawn from a prospective longitudinal survey of CARV in allo-HCT recipient having respiratory symptoms conducted from December 2013 to December 2018 at two Spanish transplant centers. Respiratory viruses in upper and/or lower respiratory specimens were tested using multiplex PCR panel assays. The study cohort comprised 233 allo-HCT recipients with 37…
Invasive fungal disease in patients undergoing umbilical cord blood transplantation after myeloablative conditioning regimen
OBJECTIVE Characteristics and risk factors (RFs) of invasive fungal disease (IFD) have been little studied in the setting of umbilical cord blood transplantation (UCBT). METHOD We retrospectively included 205 single-unit myeloablative UCBT recipients with a median follow-up of 64 months. RESULTS Fifty-six episodes of IFD were observed in 48 patients (23%) at a median time of 123 days after stem cell infusion. Invasive mold disease (IMD) occurred in 42 cases, 38 of them (90%) caused by invasive aspergillosis whereas invasive yeast disease (IYD) occurred in 14 cases, most of them due to candidemia (n = 12, 86%). The 5-year cumulative incidence of IFD, IMDs, and IYDs was 24% 19%, and 7%, respe…
Impact ofABCsingle nucleotide polymorphisms upon the efficacy and toxicity of induction chemotherapy in acute myeloid leukemia
Anthracycline uptake could be affected by efflux pumps of the ABC family. The influence of 7 SNPs of ABC genes was evaluated in 225 adult de novo acute myeloid leukemia (AML) patients. After multivariate logistic regression there were no significant differences in complete remission, though induction death was associated to ABCB1 triple variant haplotype (p = .020). The ABCB1 triple variant haplotype was related to higher nephrotoxicity (p = .016), as well as this haplotype and the variant allele of ABCB1 rs1128503, rs2032582 to hepatotoxicity (p = .001; p = .049; p .001). Furthermore, the variant allele of ABCC1 rs4148350 was related to severe hepatotoxicity (p = .044), and the variant al…
Cytomegalovirus DNA load monitoring in stool specimens for anticipating the occurrence of intestinal acute graft‐versus‐host disease following allogeneic hematopoietic stem cell transplantation: Is it of any value?
Background Data have been published suggesting a bidirectional interaction between cytomegalovirus (CMV) infection and acute graft-versus-host disease (aGvHD) in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Here, we hypothesized that prospective CMV DNA monitoring in stool specimens may be useful for predicting subsequent occurrence of intestinal aGvHD (IaGvHD). Methods This two-center study enrolled 121 consecutive adult patients undergoing any modality of allo-HSCT. A total of 1,009 stool specimens were collected (a median of 7 specimens/patient; range, 1-18). CMV DNA monitoring in stools and plasma was performed using real-time PCR assays. Results CMV DNA was det…
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 invol…
Infections of the Central Nervous System after Unrelated Donor Umbilical Cord Blood Transplantation or Human Leukocyte Antigen–Matched Sibling Transplantation
We analyzed the incidence, clinical characteristics, prognostic factors, and outcome of central nervous system (CNS) infections in consecutive patients with receiving umbilical cord blood transplantation (UCBT) (n = 343) or HLA-matched sibling donor stem cell transplantation (MST) (n = 366). Thirty-four CNS infections were documented at a median time of 116 days after transplantation (range, 7 to 1161). The cumulative incidence (CI) risk of developing a CNS infection was .6% at day +30, 2.3% at day +90, and 4.9% at 5 years. The 5-year CI of CNS infection was 8.2% after UCBT and 1.7% after MST (P .001). The causative micro-organisms of CNS infections were fungi (35%), virus (32%), Toxoplasm…
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 6…
Sirolimus versus cyclosporine in haploidentical stem cell transplantation with posttransplant cyclophosphamide and mycophenolate mofetil as graft‐versus‐host disease prophylaxis
Sirolimus has emerged as an alternative to calcineurin inhibitors-based (CNI) graft-versus-host disease (GVHD) prophylaxis. This retrospective study compares the outcome of 133 consecutive adult patients with haematological malignancies undergoing haploidentical stem cell transplantation with posttransplant cyclophosphamide (PTCy) and mycophenolate mofetil (MMF), combined with cyclosporine A (PTCy-CsA-MMF,
Bone Marrow-Derived Cells from Male Donors Do Not Contribute to the Endometrial Side Population of the Recipient
Accumulated evidence demonstrates the existence of bone marrow-derived cells origin in the endometria of women undergoing bone marrow transplantation (BMT). In these reports, cells of a bone marrow (BM) origin are able to differentiate into endometrial cells, although their contribution to endometrial regeneration is not yet clear. We have previously demonstrated the functional relevance of side population (SP) cells as the endogenous source of somatic stem cells (SSC) in the human endometrium. The present work aims to understand the presence and contribution of bone marrow-derived cells to the endometrium and the endometrial SP population of women who received BMT from male donors. Five fe…