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…

Spanish Society of Hematology and Hemotherapy expert consensus opinion for SARS-CoV-2 vaccination in onco-hematological patients.

Abstract In the midst of the COVID-19 pandemic, different vaccines in front of SARS-CoV-2 have been approved and administered in different vulnerable populations. As patients with cancer were excluded from pivotal trials of vaccination, little is known on their immunogenic response to these vaccines, particularly in patients with severely impaired immune system. In response to that uncertainty, the Spanish Society of Hematology and Hemotherapy launched an initiative aimed to provide recommendations for vaccination of the main hematological conditions. This document is based on the available information on COVID-19 outcomes, prior knowledge on vaccination in hematological patients, recent pu…

SARS-CoV-2 vaccine response and rate of breakthrough infection in patients with hematological disorders

Abstract Background The clinical efficacy of SARS-CoV-2 vaccines according to antibody response in immunosuppressed patients such as hematological patients has not yet been established. Patients and methods A prospective multicenter registry-based cohort study conducted from December 2020 to December 2021 by the Spanish transplant and cell therapy group was used to analyze the relationship of antibody response at 3–6 weeks after full vaccination (2 doses) with breakthrough SARS-CoV-2 infection in 1394 patients with hematological disorders. Results At a median follow-up of 165 days after complete immunization, 37 out of 1394 (2.6%) developed breakthrough SARS-CoV-2 infection at median of 77 …

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,…

Epstein-Barr virus DNA load kinetics analysis in allogeneic hematopoietic stem cell transplant recipients: Is it of any clinical usefulness?

Abstract Background There is a lack of clinical information regarding the usefulness of plasma Epstein-Barr virus (EBV) DNA load kinetics analyses in the management of EBV infections in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Namely, it remains unknown whether this type of analysis can help physicians to anticipate the development of high-level EBV DNAemia episodes requiring rituximab treatment or predict the risk of recurrent EBV DNAemia or post-transplant lymphoproliferative disorders (PTLDs). Study design Unicentric, retrospective, observational study including 142 consecutive patients undergoing T-cell replete allo-HSCT. The plasma EBV DNA load was mon…

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…

CD34+ Cell Selection versus Reduced-Intensity Conditioning and Unmodified Grafts for Allogeneic Hematopoietic Cell Transplantation in Patients Age >50 Years with Acute Myelogenous Leukemia and Myelodysplastic Syndrome .

Reduced-intensity conditioning (RIC) and T cell depletion (TCD) through CD34+ cell selection without the use of post-transplantation immunosuppression are 2 strategies used to reduce nonrelapse mortality (NRM) in older patients after allogeneic hematopoietic cell transplantation (allo-HCT). To compare the efficacy of the RIC and TCD approaches, we evaluated the outcomes of patients age >50 years with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) who underwent allo-HCT from an HLA-matched donor with one of these strategies. Baseline characteristics were comparable in the patients receiving TCD (n = 204) and those receiving RIC (n = 151), except for a higher proportion o…

Efficacy and Safety of a Preemptive Antiviral Therapy Strategy Based on Combined Virological and Immunological Monitoring for Active Cytomegalovirus Infection in Allogeneic Stem Cell Transplant Recipients.

Preemptive antiviral therapy for active CMV infection in allogeneic stem cell transplant recipients guided by immunological and virological parameters minimizes the risk of recurrent viremia in a subset of patients.

Spontaneously‐resolving episodes of cytomegalovirus DNAemia in allogeneic hematopoietic stem cell transplant recipients: Virological features and clinical outcomes

It has been reported that low-plasma cytomegalovirus (CMV) DNA loads are associated with an increased risk of overall mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Utilizing a conservative strategy for initiation of preemptive antiviral therapy (>1500 IU/mL), we characterized the virological features of spontaneously-resolving episodes of CMV DNAemia and assessed their impact on mortality through the first year after transplantation. We reviewed the CMV DNA polymerase chain reaction results and clinical charts of 230 consecutive adult patients who underwent T-cell replete allo-HSCT at our center. A total of 280 episodes of CMV DNAemia were registered in 164 pa…

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…

Evolving patterns of care and outcomes in relapsed/refractory FLT3 mutated acute myeloid leukemia adult patients.

We have analyzed treatment patterns and outcomes of relapsed/refractory(R/R) FLT3mut AML adult patients registered in our institutional data base between 1998 and 2018. Overall, 147 patients were evaluable: 34 from 1998 to 2009, 113 from 2010 to 2018. Salvage treatments were intensive chemotherapy ( n = 25, 74%), and supportive care ( n = 9, 26%) in the 1998-2009 period, and intensive chemotherapy ( n = 63, 56%), hypomethylating agent ( n = 7, 6%), low-dose cytarabine-based ( n = 8, 7%), clinical trial ( n = 16, 14%) and supportive care ( n = 19, 17%) in the 2010-2018 period. Complete remission (CR) or with incomplete recovery (CRi) rate was 44%, 49% among patients treated intensively (vs 3…

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…

Effect of Sirolimus Exposure on the Need for Preemptive Antiviral Therapy for Cytomeglovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation

The current study evaluates the clinical effect of sirolimus exposure on the occurrence of cytomegalovirus (CMV) DNAemia necessitating preemptive antiviral therapy. A total of 167 consecutive recipients of reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT) who received sirolimus- and tacrolimus-based graft-versus-host disease (GVHD) prophylaxis and whose CMV serostatus was positive for donors and/or recipients were included in this multicenter retrospective study. A parametric model with consecutive sirolimus blood levels describing the time to CMV DNAemia-RAT was developed using NONMEM version 7.4. Overall, 122 of 167 patients (73%) were all…

Epidemiologic and Clinical Characteristics of Coronavirus and Bocavirus Respiratory Infections after Allogeneic Stem Cell Transplantation: A Prospective Single-Center Study

Highlights • Human coronavirus are common after allogeneic stem cell transplantation and can progress to LRTDs, and in some cases this leads to hospitalization and requires supportive care. • Human bocavirus are quite rare after allogeneic stem cell transplantation and are commonly detected in conjunction with other viral co-pathogens.

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…

Evolutionary and phenotypic characterization of spike mutations in a new SARS-CoV-2 Lineage reveals two Variants of Interest

Molecular epidemiology of SARS-CoV-2 aims to monitor the appearance of new variants with the potential to change the virulence or transmissibility of the virus. During the first year of SARS-CoV-2 evolution, numerous variants with possible public health impact have emerged. We have detected two mutations in the Spike protein at amino acid positions 1163 and 1167 that have appeared independently multiple times in different genetic backgrounds, indicating they may increase viral fitness. Interestingly, the majority of these sequences appear in transmission clusters, with the genotype encoding mutations at both positions increasing in frequency more than single-site mutants. This genetic outco…

Assessment of the association between cytomegalovirus DNAemia and subsequent acute graft-versus-host disease in allogeneic peripheral blood stem cell transplantation: A multicenter study from the Spanish hematopoietic transplantation and cell therapy group.

The potential role of active CMV infection in promoting acute Graft-versus-Host Disease (aGvHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. We further addressed this issue conducting a retrospective, observational, multicenter study of 632 patients subjected to allogeneic peripheral blood HSCT at 20 Spanish centers. Monitoring of CMV DNA load in plasma or whole blood was performed by real-time PCR assays. Cumulative incidence of CMV DNAemia was 48.9% (95% CI, 45%-52.9%), of any grade aGvHD, 45.6; 95% (CI, 41.3%-50.1%), and of grade II-IV aGvHD, 30.7 (95% CI, 24.9%-36.4%). Overall, development of CMV DNAemia at any level resulted in an increa…

The kinetics of torque teno virus plasma DNA load shortly after engraftment predicts the risk of high-level CMV DNAemia in allogeneic hematopoietic stem cell transplant recipients

Monitoring Torque teno virus (TTV) DNA load helps to estimate the risk of opportunistic infections in solid organ transplant recipients. We investigated whether the early kinetic pattern of plasma TTV DNA load after allogeneic hematopoietic stem cell transplantation (allo-HSCT) associates with subsequent CMV and EBV DNAemia. This study included 71 allo-HSCT patients. We found that the area under the curve (AUC) for log10 TTV DNA loads quantified by days 20 and 30 after transplantation (TTV DNA load AUC20-30), was significantly lower (P=0.036) in patients who subsequently developed CMV DNAemia requiring preemptive antiviral therapy (n=17) than in those who did not (n=8) or had no CMV DNAemia…

Booster effect after SARS-CoV-2 vaccination in immunocompromised hematology patients with prior COVID-19

Patients with hematological malignancies have been excluded from the new zoonotic coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) vaccine trials despite being at higher risk for SARS-CoV-2 disease (COVID-19)-related mortality. However, most health authorities worldwide have designated these patients as a priority for COVID-19 vaccination, even in the absence of efficacy data in these highly immunosuppressed patients. In addition, on 12 August 2021, the US Food and Drug Administration amended the emergency use authorizations for the Pfizer-BioNTech and Moderna COVID-19 vaccines to allow for the use of an additional dose in immunocompromised individuals, such as sol…

Clinical Validation of the Myelofibrosis Transplant Scoring System in an Independent Series of Myelofibrosis Patients Undergoing Allogeneic Hematopoietic Transplantation

Introduction: Allogeneic hematopoietic cell transplantation (allo-HCT) constitutes the only curative treatment for myelofibrosis (MF), but its associated toxicity remains high. Prognostic risk models are widely used in clinical practice to select those MF patients who are more likely to benefit from transplantation. Recently, a new prognostic model, the Myelofibrosis Transplant Scoring System (MTSS), has been developed to predict the outcome of MF patients undergoing allo-HCT (Gagelmann N et al, Blood 2019). We aimed to evaluate the performance of such model in an independent series of patients. Methods: This is a retrospective study that included all adult patients who underwent first allo…

Multi-body-site colonization screening cultures for predicting multi-drug resistant Gram-negative and Gram-positive bacteremia in hematological patients

Abstract Background To investigate the multi-drug resistant bacteria (MDRB) colonization rate in hematological patients hospitalized for any cause using a multi-body-site surveillance approach, and determine the extent to which this screening strategy helped anticipate MDRB bloodstream infections (BSI). Methods Single-center retrospective observational study including 361 admissions documented in 250 adult patients. Surveillance cultures of nasal, pharyngeal, axillary and rectal specimens (the latter two combined) were performed at admission and subsequently on a weekly basis. Blood culture samples were incubated in an automated continuous monitoring blood culturing instrument (BACTEC FX). …

Cytomegalovirus DNAemia and risk of mortality in allogeneic hematopoietic stem cell transplantation: Analysis from the Spanish Hematopoietic Transplantation and Cell Therapy Group

The net impact of cytomegalovirus (CMV) DNAemia on overall mortality (OM) and nonrelapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. This was a retrospective, multicenter, noninterventional study finally including 749 patients. CMV DNA monitoring was conducted by real-time polymerase chain reaction (PCR) assays. Clinical outcomes of interest were OM and NRM through day 365 after allo-HSCT. The cumulative incidence of CMV DNAemia in this cohort was 52.6%. A total of 306 out of 382 patients with CMV DNAemia received preemptive antiviral therapy (PET). PET use for CMV DNAemia, but not the occurrence of CMV DNAemia, taken …

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…

A Time-to-Event Model for Acute Kidney Injury after Reduced-Intensity Conditioning Stem Cell Transplantation Using a Tacrolimus- and Sirolimus-based Graft-versus-Host Disease Prophylaxis.

There is a paucity of data evaluating acute kidney injury (AKI) incidence and its relationship with the tacrolimus-sirolimus (Tac-Sir) concentrations in the setting of reduced-intensity conditioning (RIC) after allogeneic stem cell transplantation (allo-HSCT). This multicenter retrospective study evaluated risk factors of AKI defined by 2 classification systems, Kidney Disease Improving Global Outcome (KDIGO) score and "Grade 0-3 staging," in 186 consecutive RIC allo-HSCT recipients with Tac-Sir as graft-versus-host disease prophylaxis. Conditioning regimens consisted of fludarabine and busulfan (n = 53); melphalan (n = 83); or a combination of thiotepa, fludarabine, and busulfan (n = 50). …

Cytomegalovirus DNAemia Burden and Mortality Following Allogeneic Hematopoietic Stem Cell Transplantation: An Area Under a Curve-Based Investigational Approach.

Diversity and dynamic changes of anelloviruses in plasma following allogeneic hematopoietic stem cell transplantation.

Monitoring of alphatorquevirus (torque teno virus [TTV]) DNA in plasma may prove to be useful to assess the net state of immune competence following allogeneic hematopoietic stem cell transplantation (allo-HSCT). There are scarce data published on the prevalence of beta (torque teno mini virus [TTMV]) and gammatorqueviruses (torque teno midi virus [TTMDV]) and, in particular, on the dynamics of anelloviruses in allo-HSCT patients. Twenty-five allo-HSCT recipients with available plasma specimens obtained before conditioning and after engraftment were included. Degenerated primers targeting a highly conserved genomic sequence across all anelloviruses were designed for genomic amplification an…

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.

SARS‐CoV ‐2‐reactive antibody detection after SARS‐CoV ‐2 vaccination in hematopoietic stem cell transplant recipients: Prospective survey from the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group

This is a multicenter prospective observational study which included a large cohort (n = 397) of allogeneic (allo-HSCT) (n = 311) and autologous (ASCT) hematopoietic stem cell transplant (n = 86) recipients who were monitored for antibody detection within 3 to 6 weeks after complete SARS-CoV-2 vaccination from February 1st 2021 to July 20th 2021. Most patients (n = 387, 97.4%) received mRNA-based vaccines. Most of recipients (93%) were vaccinated more than 1 year after transplant. Detectable SARS-CoV-2-reactive antibodies were observed in 242 (78%) of allo-HSCT and in 73 (85%) of ASCT recipients. Multivariate analysis in allo-HSCT recipients identified lymphopenia <1x109 /mL [Odds ratio (OR…

Allogeneic Stem Cell Transplantation in Mantle Cell Lymphoma; Insights into Its Potential Role in the Era of New Immunotherapeutic and Targeted Therapies : The GETH/GELTAMO Experience

Simple Summary We present the long-term results of patients receiving allogeneic stem cell transplantation (allo-SCT) for relapsed/refractory mantle cell lymphoma (R/R MCL) in the last 25 years in Spain. We conclude that allo-SCT may be a curative option in R/R MCL with a low cumulative incidence (CI) of relapse, although non-relapse mortality (NRM) is still high, which is mainly secondary to acute graft-versus-host disease (aGVHD). Results are better for fit patients, using HLA-identical (related or unrelated) or haploidentical related donors and without previous ASCT. However, the arrival of new highly effective and low toxic immunotherapeutic or targeted therapies inevitably will relegat…

Additional file 1 of SARS-CoV-2 vaccine response and rate of breakthrough infection in patients with hematological disorders

Additional file 1: Table S1. Characteristics of serological assays used in the study. Table S2. Commercial PCR test available in participating centers.

Kinetics of torque teno virus DNA load in saliva and plasma following allogeneic hematopoietic stem cell transplantation

Plasma torque teno virus (TTV) DNA load directly correlates with the degree of T-cell immune reconstitution early after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, the kinetics of oral TTV DNA shedding was examined to assess whether quantitation of TTV DNA load in saliva may either replace or complement that in plasma for predicting lymphocyte (ALC) reconstitution after engraftment. This prospective observational study enrolled 38 nonconsecutive allo-HSCT recipients. Saliva and plasma specimens were collected at baseline (pretransplant) and at around days +30, +50, and +90 after allo-HSCT. TTV DNA was quantitated in both specimen types by real-time PCR. ALCs were m…

SARS-CoV-2 Immunity in Hematopoietic Stem Cell Transplant and Cell Therapy Recipients : What Do We Know, and What Remains to Be Determined?

Hematopoietic stem cell transplantation (HSCT) results in profound immunosuppression for the first few months after the procedure, requiring patients to be revaccinated against childhood vaccine-preventable infectious diseases. Patients who undergo allo-HSCT are at high risk of bacterial, fungal, and viral infections, with infectious complications responsible for at least one third of deaths. Even before the COVID-19 pandemic, respiratory virus infections were known to be more severe in HSCT recipients. The pandemic has highlighted the vulnerability of HSCT recipients, who experience an increased risk of morbidity and mortality after COVID-19 compared with healthy populations due to their s…

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)…

A risk-adapted approach to treating respiratory syncytial virus and human parainfluenza virus in allogeneic stem cell transplantation recipients with oral ribavirin therapy: A pilot study.

Here we report the applicability of a protocol based on clinical conditions and risk factors (RFs) for managing 35 allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients who developed a total of 52 episodes of respiratory viral infections (RVIs) caused by respiratory syncytial virus (RSV; n=19), human parainfluenza virus (HPIV; n=29), or both (n=4) over a 2-year study period. Risk categories were classified as high risk (cat-1) when the immunodeficiency scoring index was >= 3 and/or >= 3 RFs and/or >= 1 co-infective virus(es) were present; the remaining cases were classified as low risk (cat-0). The presence of two or more signs or symptoms including fever (T>38 degrees C…

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…

Incidence, features, and outcomes of cytomegalovirus DNAemia in unmanipulated haploidentical allogeneic hematopoietic stem cell transplantation with post‐transplantation cyclophosphamide

Background Conflicting data have been published as to the risk of cytomegalovirus (CMV) DNAemia and CMV disease in patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplantation cyclophosphamide. Methods We conducted a multicenter retrospective study including 118 patients subjected to unmanipulated haplo-HSCT to further clarify this issue. An historic cohort comprising 165 patients undergoing other transplant modalities (HLA-matched related, matched unrelated or mismatched) was built for comparison purposes. Plasma CMV DNA monitoring was performed using two highly sensitive real-time PCR assays. Results Overall, the cumulative incidence of…

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…

Cambios en el estado nutricional, composición corporal y sintomatología asociada en pacientes hospitalizados sometidos a trasplante de médula ósea: estudio longitudinal prospectivo

Introducción: Los pacientes sometidos a Trasplante de Células Madre Hematopoyéticas o trasplante de médula padecen varias complicaciones nutricionales. El objetivo del estudio fue realizar una descripción prospectiva en estos pacientes.Material y métodos: Se reclutaron 14 pacientes con una edad media de 48,0±9,8 años. Resultados: El 28,6% padecía sobrepeso, el 14,3% obesidad y el 57,1% tenía un peso normal, con una evoluciónentre -0,3±0,3 kg/m2 (normopeso) hasta -3,1±0,2 kg/m2 (obesidad). Se observó una pérdida de peso variable, de hasta 7,3±0,7% en pacientes con mayor Índice de Masa Corporal (IMC). La composición corporal también empeoró al alta, con una evolución de la circunferencia braq…

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%) …

Single-agent GvHD prophylaxis with tacrolimus after post-transplant high-dose cyclophosphamide is a valid option for haploidentical transplantation in adults with hematological malignancies.

Eighty-one patients with high-risk hematological malignancies received unmanipulated haploidentical stem cell transplants (haploSCT) using the same protocol at four Spanish institutions. The conditioning regimen was thiotepa, busulfan and fludarabine; following bone marrow or peripheral blood infusion. GvHD prophylaxis with high-dose cyclophosphamide on days +3 and +4, and IV tacrolimus from day +5 was administered. 62% were in complete remission, 17% had received previous allogeneic SCT and 44% had a high-very high refined disease risk index. One patient had primary graft failure and three more died before +21. The median days to neutrophil and platelet recoveries were +18 and +23, respect…

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 < …

CAR-T therapy in solid transplant recipients with post-transplant lymphoproliferative disease: case report and literature review

Patients with postransplant lymphoproliferative disease (PTLD) who are refractory to rituximab-based regimens have extremely poor prognosis. Data is lacking in the setting of solid organ transplantation (SOT)-related PTLD treated with chimeric antigen receptor T-cell (CAR-T) therapy. Moreover, limited information is available on the influence of concomitant immunosuppressive drugs on CAR-T function. Here, we describe the clinical outcome in one PTLD patient and propose a strategy for tailoring immunosuppressive treatment and organ monitoring in patients with kidney allografts after CAR-T infusion. This report also reviews the limited published data in the setting of SOT-related PTLD treated…

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…

Re-examining the relationship between active cytomegalovirus (CMV) infection and acute graft-versus-host disease in allogeneic stem cell transplant recipients in the era of real-time PCR CMV assays.

Factors influencing cytomegalovirus DNA load measurements in whole blood and plasma specimens from allogeneic hematopoietic stem cell transplant recipients

We assessed the impact of several parameters, including the nature of the episode of Cytomegalovirus (CMV) DNAemia, the use of preemptive antiviral therapy, and the blood cell content in CMV DNA loads measured in whole blood (WB) and plasma (PL). CMV DNA load was quantified in 245 paired specimens collected within 43 postengraftment episodes of CMV DNAemia by using the CMV RealTime CMV PCR (Abbott Molecular). Concordant categorical results were obtained for 78.4% of paired specimens (Kappa index, 0.385; P = 0.001). Overall, CMV DNA loads in PL were higher than those in WB (mean bias, +0.115 log IU/mL) in both initial and recurrent episodes; this was so in post-antiviral treatment but not in…

Validation of a plasma metabolomics model that allows anticipation of the occurrence of cytomegalovirus DNAaemia in allogeneic stem cell transplant recipients.

A plasma metabolomic model obtained by means of untargeted 1H nuclear magnetic resonance, to which taurine, choline, methylamine, total glutathione, trimethylamine N-oxide, lactate, lysine, isoleucine, total fatty acids and unsaturated fatty acids contributed, was validated for the prediction of first episodes of cytomegalovirus (CMV) DNAaemia in a cohort of 79 allogeneic stem haematopoietic stem cell transplant (allo-HSCT) recipients. The predictive success rate was nearly 65 % for patients at both low and high risk of CMV-related complications according to their baseline characteristics. Plasma metabolomics profiling shortly after engraftment (day 21 after transplantation) allowed the ant…

Reduced intensity conditioning HLA identical sibling donor allogeneic stem cell transplantation for patients with follicular lymphoma: long-term follow-up from two prospective multicenter trials

Background Allogeneic hematopoietic stem cell transplantation is an effective treatment for patients with poor risk lymphoma, at least in part because of the graft-versus-lymphoma effect. Over the past decade, reduced intensity conditioning regimens have been shown to offer results similar to those of conventional high-dose conditioning regimens but with lower toxicity early after transplantation, especially in patients with chemosensitive disease at transplant. Design and Methods The aim of this study was to analyze the long-term outcome of patients with follicular lymphoma who received an HLA identical sibling allogeneic stem cell transplant with a reduced intensity conditioning regimen w…

Failure of Cytomegalovirus-Specific CD8+ T Cell Levels at Viral DNAemia Onset to Predict the Eventual Need for Preemptive Antiviral Therapy in Allogeneic Hematopoietic Stem Cell Transplant Recipients

When should preemptive antiviral therapy for active CMV infection be withdrawn from allogeneic stem cell transplant recipients?

When should preemptive antiviral therapy for active CMV infection be withdrawn from allogeneic stem cell transplant recipients?

Lack of evidence for a reciprocal interaction between bacterial and cytomegalovirus infection in the allogeneic stem cell transplantation setting

Summary Pathogenic interactions between bacteria and cytomegalovirus (CMV) may potentially occur early after allogeneic stem cell transplantation (Allo-SCT). This possibility nevertheless has not been investigated in depth. This was a retrospective study that included 170 consecutive patients who underwent 173 Allo-SCTs. Both bacterial infection (most of which were bacteremic) and CMV DNAemia were detected in 78 Allo-SCTs (62.9%). In total, 51 and 32 episodes of bacterial infection preceded or occurred after CMV DNAemia detection, respectively. Both events were diagnosed concurrently in four Allo-SCTs. The cumulative incidence of bacterial infection (of any type) over the study period was c…

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…

Features of Cytomegalovirus DNAemia Blips in Allogeneic Hematopoietic Stem Cell Transplant Recipients: Implications for Optimization of Preemptive Antiviral Therapy Strategies.

Cytomegalovirus (CMV) DNAemia occurs frequently in allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). There is limited information about the incidence, features, and clinical impact of CMV DNAemia blips (episodes defined by an isolated positive PCR result) in this setting. In this retrospective study, 225 consecutive adult patients undergoing any modality of allo-HSCT at our center between May 2012 and July 2019 were included. Plasma CMV DNA load was monitored using a highly sensitive real-time PCR assay. In all, 187 of 225 patients had CMV DNAemia through day 365 after allo-HSCT (total number of episodes, n = 379). Eighty-three of the 187 patients had 1 or more blips (n …

Impact of cytomegalovirus DNAemia on overall and non-relapse mortality in allogeneic stem cell transplant recipients.

Background We conducted a retrospective single-center study to investigate the potential impact of cytomegalovirus (CMV) DNAemia on mortality in allogeneic stem cell transplant recipients (allo-SCT). Methods A total of 151 consecutive patients who underwent T-cell replete allo-SCT were included in the study. Patients with CMV DNAemia were treated pre-emptively with antivirals upon detection of plasma CMV DNA loads >1500 IU/mL. Results At least one episode of CMV DNAemia occurred in 109 (72.2%), and 67 of these patients (61.5%) required one or more courses of antiviral therapy. The cumulative incidence of 1-year overall and non-relapse mortality (NRM) was 28.5% (95% confidence interval [CI],…

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…

Sirolimus exposure and the occurrence of cytomegalovirus DNAemia after allogeneic hematopoietic stem cell transplantation

Sirolimus appears to protect against cytomegalovirus (CMV) in organ transplant recipients. The effect of this drug in allogeneic hematopoietic stem cell transplantation recipients remains unexplored. By means of multivariate continuous-time Markov model analyses, we identified 3 independent covariates that significantly impacted the risk of CMV DNAemia: recipient/donor CMV serostatus, tacrolimus exposure, and sirolimus exposure. CMV-seropositive recipients with CMV-seronegative donors had a significantly higher probability of having detectable CMV DNAemia. Increasing the tacrolimus trough concentration from 0 to 16 ng/mL increased the probability of patients having detectable CMV DNAemia by…

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…

Preemptive antiviral therapy for CMV infection in allogeneic stem cell transplant recipients guided by the viral doubling time in the blood

Preemptive antiviral therapy for CMV infection in allogeneic stem cell transplant recipients guided by the viral doubling time in the blood

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,