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The Swiss Blood Stem Cell Transplantation and Cellular Therapy Group (SBST) leads a mandatory national registry for all hematopoietic stem cell transplants (HCT) and cellular therapies. After 25 years, information was available for 11,226 patients receiving an HCT (4031 allogeneic and 7195 autologous), including 925 pediatric patients. We compared patient characteristics and outcome by quinquennia 1997-2001, 2002-2006, 2007-2011, 2012-2016, and 2017-2021. There were numerous changes over time. Allogeneic transplant recipients became older (median age 33.7 vs. 54.3) and had more frequently unrelated donors and reduced intensity conditioning in later quinquennia. Similarly, age increased for recipients of autologous HCT (median 48.3 vs. 59.9). We did not see a significant drop in transplant activity during the SARS-CoV-2 pandemic. Analysis of outcome showed overall survival (relative risk (RR) of death 0.664 (0.529-0.832) and progression free survival (RR 0.708 (0.577-0.870) being improved over time comparing the latest to the first quinquennium adjusting for risk factors. Non-relapse mortality decreased in recipients of allogeneic HCT (RR: 0.371 (0.270-0.509)) over time but relapse risks did not. Outcome of autologous HCT improved as well across quinquennia, this improvement was mainly due to decreased relapse risks (RR 0.681 (0.597-0.777)), possibly related to maintenance treatment or rescue treatment for relapse mainly in myeloma patients. Cellular therapies other than allogeneic or autologous HCT, particularly chimeric antigen receptor T-cells (CAR-T) treatment have started to increase after 2019, year of approval of the first commercial CAR-T product in Switzerland. Data on chimeric antigen receptor T-cell treatment are too early for comparative analyses. Detailed analyses of changes over time are presented. This study includes all HCTs, and cellular therapies, data useful for quality assurance programs, health care cost estimation and benchmarking. Between 50% and 60% of patients are long-term survivors after both types of HCT, indicating growing populations of surviving patients requiring long-term care.
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Trasplante de Células Madre Hematopoyéticas , Receptores Quiméricos de Antígenos , Adulto , Niño , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Recurrencia Local de Neoplasia/etiología , Recurrencia , Suiza , Acondicionamiento Pretrasplante , Trasplante Homólogo , Persona de Mediana EdadRESUMEN
BACKGROUND AND OBJECTIVES: Antibodies (Ab) against HLA and HPA antigens play an important role in HCT. In this prospective study we evaluated prevalence and kinetics of HLA- and HPA-Ab after HCT, including a possible donor-recipient transfer and their clinical relevance in respect to platelet transfusion refractoriness (PTR). MATERIALS AND METHODS: Patients were consecutively recruited. Ab were determined by microbead assay technique and a mean fluorescence intensity cut-off of 1,000. RESULTS: At baseline, 21 donors (42 %) and 27 patients (54 %) had HLA-Ab with a mean panel reactivity (cPRA) of 34.9 ± 29.4 % and 46.1 ± 36.5 %, respectively. We observed a significant higher number of HLA-Ab specificities in female donors and patients and a predominance of HLA-class I Ab. At day 0 we detected an increase of HLA-Ab (from 526 to 673) and cPRA (55.2 ± 31.9 %). Thirty-six patients (72 %) developed new HLA-Ab, mainly 3 weeks after HCT. In 7 patients an HLA-Ab with the same specificity as detected in the corresponding donor emerged, suggesting a possible transfer from the donor to the recipient. Overall, MFI showed a high variation. Type and number of transfusions were not associated with number and intensity of HLA-Ab (ρ: -0.05 - 0.02). Number of HLA-Ab, cPRA and intensity were not associated with PTR, which occurred in 9 patients (18 %) and none had bleeding WHO > 2. CONCLUSIONS: Although a considerable number of patients have and develop HLA-Ab before and early after HCT, we found no association with PTR and bleeding and management should be individualized.
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Antígenos de Plaqueta Humana , Antígenos HLA , Trasplante de Células Madre Hematopoyéticas , Trombocitopenia , Femenino , Humanos , Isoanticuerpos , Transfusión de Plaquetas/métodos , Estudios ProspectivosRESUMEN
Adverse event (AE) and adverse reaction (AR) reporting are key components of patient safety and surveillance systems. Review and analysis of this data yields opportunities for process improvement, product information and interventions, and can lead to improved patient outcomes and donor safety overall. AE and AR reporting for cellular therapy products is fragmented and not well characterized in a central reference. This review article, authored by experts from various organizations, serves to summarize the current state of reporting and offers opportunities for streamlining and coordination, as well as key reference for professionals in this field.
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Tratamiento Basado en Trasplante de Células y Tejidos/efectos adversos , Bases de Datos Factuales , Autoinforme , Humanos , Estados Unidos , United States Food and Drug AdministrationRESUMEN
BACKGROUND: CD34+ cell count correlates with engraftment potency after autologous stem cell transplantation. Assessment of CD34+ mainly occurs after apheresis and before cryopreservation with dimethyl sulfoxide (DMSO). The influence of postthaw CD34+ cell numbers over time to engraftment is not well studied, and determination of postthaw CD34+ cell counts is challenging for a variety of reasons. The aim of this retrospective study was to systematically assess the value of postthaw CD34+ cell counts in autologous grafts with and without DMSO removal. STUDY DESIGN AND METHODS: Between January 2008 and December 2015, 236 adult patients underwent a total of 292 autologous stem cell transplantations. Median age at transplantation was 56 years, and the main indication was multiple myeloma (60%). DMSO removal was done in 96 grafts (33%), either by centrifugation or by Sepax method. RESULTS: Patients receiving grafts containing DMSO showed a significantly faster platelet (p = 0.02) and RBC (p = 0.001) engraftment. DMSO removal was not associated with fewer infusion-related adverse events. We observed a good correlation between CD34+ cell count after apheresis and CD34+ cell count after thawing/washing (r = 0.931). Ninety grafts (31%) showed a significant loss of viable CD34+ cells, which translated into a delayed engraftment. CONCLUSION: DMSO removal was associated with delayed platelet and RBC engraftment without preventing adverse events. CD34+ cell enumeration after thawing remains difficult to perform, but grafts showing higher cell loss during cryopreservation and thawing are associated with slower engraftment. Prospective studies on the role of DMSO removal and postthaw CD34+ enumeration using defined protocols are needed.
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Antígenos CD34/análisis , Dimetilsulfóxido/aislamiento & purificación , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante Autólogo/métodos , Adolescente , Adulto , Anciano , Criopreservación , Crioprotectores/aislamiento & purificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
Post-transplantation cyclophosphamide (PTCy) demonstrated effectiveness to prevent GVHD after haploidentical hematopoietic cell transplantation (HCT). Reducing toxicities with a maximized efficacy is still challenging in HCT. In this retrospective study, we analyzed the safety and efficacy of transplantation from a 1-antigen HLA-mismatched unrelated donor (9/10 MMUD) in 80 patients with hematological disorders between 2010 and 2018; 22 patients received PTCy with a reduced dose of 40 mg/kg, cyclosporine A, and mycophenolate mofetil (MMF); 58 patients received anti-thymocyte globulin (ATG), cyclosporine A, and either methotrexate or MMF for GVHD prophylaxis. Cumulative incidence (CI) of acute GVHD grades II-IV in the PTCy group was significantly lower (15% vs. 50%, p = 0.006); however, CI of chronic GVHD was (not significantly) lower in the PTCy group (26% vs. 35%, p = 0.137). One-year OS was significantly longer (p = 0.008) in the PTCy group with a similar 1-year PFS (p = 0.114) in both groups. Rates of 1-year relapse and non-relapse mortality were similar. Median time to neutrophil engraftment was comparable in both GVHD prophylaxis groups (14 days vs. 16 days, respectively, p = 0.107). Our results show that a lower dose of PTCy-based prophylaxis is an effective and safe strategy to prevent acute GVHD in HCT with 9/10 MMUD compared to ATG.
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Suero Antilinfocítico/uso terapéutico , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas , Adulto , Anciano , Anemia Aplásica/terapia , Enfermedades de la Médula Ósea/terapia , Trastornos de Fallo de la Médula Ósea , Ciclofosfamida/administración & dosificación , Ciclosporina/uso terapéutico , Evaluación de Medicamentos , Femenino , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Antígenos HLA/análisis , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hemoglobinuria Paroxística/terapia , Histocompatibilidad , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Masculino , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Neoplasias/terapia , Estudios Retrospectivos , Linfocitos T/inmunología , Donantes de TejidosRESUMEN
Diagnosis and Therapy of Acute Myeloid Leukemia Abstract. Acute myeloid leukemia (AML) is a biologically complex and molecularly and clinically heterogeneous disease, and its incidence is increasing as the population ages. Cytogenetic anomalies and mutation testing remain important prognostic tools for tailoring treatment after induction therapy. Despite major advances in understanding the genetic landscape of AML and its impact on the pathophysiology and biology of the disease, as well as the rapid development of new drugs, standard treatment options have not experienced major changes during the past three decades. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the best chance for cure. Here we review diagnosis and therapy of AML.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Mutación , PronósticoRESUMEN
Acute lymphoblastic leukemia - diagnosis and therapy Abstract. Acute lymphoblastic leukemia (ALL) is a rare malignant hematological disease. The incidence of the disease peaks in the childhood and thus is rare in adults, making assessment and care at qualified centers highly desirable. Clinically, ALL presents with the proliferation and accumulation of malignant, immature lymphatic blasts in the bone marrow, peripheral blood, and lymphatic and non-lymphatic tissue. Untreated, ALL results in death within few months. ALL is a heterogeneously disease. Prognosis is determined by immunophenotype, cytogenetics and molecular markers which influences therapeutic strategies. The aim of therapy in younger patients is curative. Patients should be treated in international study group protocols. Overall survival has improved over the last decade; also with the introduction of new targeted therapies. In addition, there have been recent developments in minimal / measurable residual disease (MRD) determination, which has a strong impact on the decision for an allogeneic hematopoietic stem cell transplantation.
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Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Niño , Humanos , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pronóstico , Trasplante HomólogoRESUMEN
Hematopoietic cell transplantation - essentials on indication, patient referral and long term follow up Abstract. Both, autologous and allogeneic hematopoietic cell transplantation (HCT) are established treatment components for a large number of predominantly hemato- and lymphopoietic disorders. Diagnosis and disease status, the timing for referral to a transplant center and comorbidities are crucial factors for the patients' outcome. Survivorship care plans are an important contribution to improve intermediate and long-term outcome. Although these are mainly guided by the transplant center, family and referring physicians play an important role in prevention, early detection and treatment of late effects. This review discusses «HCT-essentials¼ for non-transplant physicians for referral and follow up of transplant patients.
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Trasplante de Células Madre Hematopoyéticas , Atención a la Salud , Estudios de Seguimiento , Humanos , Derivación y Consulta , Trasplante HomólogoRESUMEN
Cellular therapies Abstract. Transfusion medicine and allogeneic stem cell transplantation are well known and established cellular therapies in hematology. Since decades many efforts have been made, in order to re-program the patient's own immune system in order to clear malignancies. A breakthrough was achieved with the manufacturing and optimizing of so-called chimeric antigen receptor (CAR) T-cells, genetically engineered cells, specifically directed against tumor antigens. In this review we discuss the structure of CAR T-cells, their manufacturing and the different steps of a CAR T-cell treatment according to the current licensing. Furthermore, we give an outlook on future prospects of cellular therapies including the major issues in the field.
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Trasplante de Células Madre Hematopoyéticas , Neoplasias , Humanos , Neoplasias/terapia , Linfocitos TRESUMEN
Hematopoietic cell transplantation (HCT) is an increasingly used treatment for hematologic malignancies as well as for nonmalignant diseases. Kidney impairment remains an important early and late post-transplantation complication. Although numerous histopathological changes have been reported, the pathophysiology remains incompletely understood. Furthermore, correlations between clinical findings and morphological changes have not been well studied. Between 2000 and 2016, 17 recipients of allogeneic (n = 12) or autologous (n = 5) HCT underwent kidney biopsy for either proteinuria or deterioration of kidney function at our center. The most common biopsy findings were therapy-related changes with thrombotic microangiopathy (n = 5), calcineurin inhibitor toxicity (n = 4), and membranous glomerulonephritis (n = 3), representing the majority of cases in this category. In addition, kidney findings from 137 autopsies performed between 1995 and March 2017 were analyzed. The most common changes were acute kidney injury (n = 55), most likely due to the patients' premortal deteriorated state, and thrombotic microangiopathy (n = 14). Several cases demonstrated involvement by either infectious agents (n = 6) or tumors (n = 9). Distinct kidney diseases, such as glomerulonephritis, were rare (3% of cases). Uncommon and yet rarely described diagnoses for this patient cohort were IgG4-related tubulointerstitial nephritis and fibrillary nephritis. This study provides a comprehensive overview of the histomorphological findings in kidney biopsy specimens from HCT recipients. Along with treatment-related complications, one putative correlate of chronic GVHD of the kidney could be documented: membranous glomerulonephritis. In contrast, no morphological correlate of acute GVHD of the kidney was identified. Findings at the time of autopsy varied greatly, spanning a wider range than those of indication biopsies.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Riñón , Insuficiencia Renal Crónica , Adulto , Anciano , Aloinjertos , Autoinjertos , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/metabolismo , Enfermedad Injerto contra Huésped/patología , Humanos , Riñón/metabolismo , Riñón/patología , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Estudios RetrospectivosRESUMEN
The 2006 National Institutes of Health (NIH) Consensus paper presented recommendations by the Ancillary Therapy and Supportive Care Working Group to support clinical research trials in chronic graft-versus-host disease (GVHD). Topics covered in that inaugural effort included the prevention and management of infections and common complications of chronic GVHD, as well as recommendations for patient education and appropriate follow-up. Given the new literature that has emerged during the past 8 years, we made further organ-specific refinements to these guidelines. Minimum frequencies are suggested for monitoring key parameters relevant to chronic GVHD during systemic immunosuppressive therapy and, thereafter, referral to existing late effects consensus guidelines is advised. Using the framework of the prior consensus, the 2014 NIH recommendations are organized by organ or other relevant systems and graded according to the strength and quality of supporting evidence.
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Antineoplásicos/uso terapéutico , Enfermedad Injerto contra Huésped/terapia , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Inmunosupresores/uso terapéutico , Trasplante de Médula Ósea , Enfermedad Crónica , Consenso , Contraindicaciones , Manejo de la Enfermedad , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/patología , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/patología , Humanos , Fármacos Fotosensibilizantes , Guías de Práctica Clínica como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Trasplante HomólogoRESUMEN
The number of allogeneic hematopoietic stem cell (HSC) transplants performed globally each year continues to increase. Advances in HLA typing, better supportive care, and administration of reduced-intensity conditioning regimens allow treatment of older patients with older sibling donors. Pretransplant donor assessment and testing are very important processes affecting the quality and safety of donation. For unrelated HSC donors detailed recommendations for health assessment have been published, allowing donation only if they are unrestrictedly healthy. Eligibility criteria for related donors are less strict and vary significantly between centers. In situations where a family donor does not meet the suitability criteria for unrelated donors, involved physicians often struggle with the decision whether the matched relative is suitable for donation or not. On behalf of the Worldwide Network for Blood and Marrow Transplantation Standing Committee on Donor Issues, we intended to develop a consensus document with recommendations for donor workup and final clearance of family donors who would not be able to serve as unrelated donors because of their age or pre-existing diseases. This article covers different topics intending to support decision-making, with the goal of minimizing medical risk to the donor and protection of the recipient from transmissible diseases.
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Trasplante de Médula Ósea/métodos , Toma de Decisiones Clínicas/ética , Estado de Salud , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Donante no Emparentado , Comités Consultivos , Factores de Edad , Consenso , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/patología , Prueba de Histocompatibilidad , Humanos , Consentimiento Informado , Cooperación Internacional , Riesgo , Hermanos , Acondicionamiento Pretrasplante , Trasplante HomólogoRESUMEN
Health-related quality of life (HRQoL) is often substantially reduced among individuals who have undergone hematopoietic stem cell transplantation (HSCT), and incidences of depression, fatigue, and anxiety are elevated. We examined effects of a mindfulness-based intervention (MBI) compared to psycho-oncological telephone consultation upon HRQoL, depression, anxiety, and fatigue among HSCT survivors. Sixty-two medically stable patients participated in the study; they had completed HSCT ≥6 months previously. Thirty-two were randomly assigned to intervention arms, and 30 were offered their treatment preference. MBI consisted of a structured 8-week program of mindfulness training. Assessments were made at baseline, post-intervention and 3 months follow-up. Primary outcome was HRQoL. Depression, fatigue, anxiety, and personal goal attainment were secondary measures. Non-completion of interventions was low in both groups (9 %, MBI; 7 % control). Employing intention-to-treat analysis, MBI, compared with comparison procedure, improved HRQoL and reduced depression and anxiety at post-intervention (p's < 0.05); Cohen's d effect sizes, 0.6-0.7; 3-month follow-up benefits were modest. These findings demonstrate broad feasibility and acceptance of, as well as satisfaction and adherence with, a program of mindfulness training for HSCT survivors; findings also suggest improved HRQoL and well-being as a consequence of MBI. Nevertheless, this is a preliminary study; a larger trial with more prolonged intervention phase is warranted.
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Trasplante de Células Madre Hematopoyéticas/efectos adversos , Terapias Mente-Cuerpo/métodos , Atención Plena/métodos , Calidad de Vida , Sobrevivientes/psicología , Adolescente , Adulto , Anciano , Ansiedad/etiología , Ansiedad/terapia , Depresión/etiología , Depresión/terapia , Fatiga/etiología , Fatiga/terapia , Femenino , Trasplante de Células Madre Hematopoyéticas/psicología , Humanos , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud/psicología , Proyectos Piloto , Resultado del TratamientoRESUMEN
Bronchiolitis obliterans is a complication after allogeneic haematopoietic stem cell transplantation (HSCT). Management of bronchiolitis obliterans comprises intensive immunosuppression, but treatment response is poor. We investigated the effect of cyclosporine A (CsA), tacrolimus (FK506), methylprednisolone (mPRED), mycophenolate mofetil (MMF) and everolimus on the proliferation of primary lung myofibroblasts from HSCT patients with bronchiolitis obliterans syndrome (BOS). Cells were isolated from surgical lung biopsies of eight HSCT patients with BOS. Proliferation was assessed by [(3)H]-thymidine incorporation. Biopsies revealed constrictive bronchiolitis obliterans in three patients and lymphocytic bronchiolitis in five patients. CsA and FK506 significantly induced proliferation of myofibroblasts. mPRED and MMF caused a significant inhibition of proliferation, whereas everolimus had no effect. Costimulation with FK506, mPRED and MMF significantly inhibited proliferation. Serial pulmonary function tests over 12 months after lung biopsy and under triple therapy demonstrated that patients with lymphocytic bronchiolitis had a significant improvement in forced expiratory volume in 1 s (FEV1), whereas FEV1 of patients with bronchiolitis obliterans was unchanged. Our data demonstrate a pro-proliferative effect of calcineurin inhibitors on primary human lung myofibroblasts obtained from patients with BOS after HSCT. In contrast, based on the observed antiproliferative capacity of MMF in vitro, MMF-based calcineurin inhibitor-free treatment strategies should be further evaluated in patients with bronchiolitis obliterans after HSCT.
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Bronquiolitis Obliterante/tratamiento farmacológico , Inhibidores de la Calcineurina , Proliferación Celular/efectos de los fármacos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Inmunosupresores/farmacología , Pulmón/citología , Miofibroblastos/efectos de los fármacos , Adulto , Bronquiolitis Obliterante/etiología , Células Cultivadas , Ciclosporina/farmacología , Ciclosporina/uso terapéutico , Quimioterapia Combinada , Everolimus , Femenino , Volumen Espiratorio Forzado , Humanos , Inmunosupresores/uso terapéutico , Masculino , Metilprednisolona/farmacología , Metilprednisolona/uso terapéutico , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/farmacología , Ácido Micofenólico/uso terapéutico , Sirolimus/análogos & derivados , Sirolimus/farmacología , Sirolimus/uso terapéutico , Tacrolimus/farmacología , Tacrolimus/uso terapéuticoRESUMEN
Introduction: Myelofibrosis (MF) is a rare hematopoietic stem cell disorder progressing to bone marrow (BM) failure or blast phase. Allogeneic hematopoietic cell transplantation (HCT) represents a potentially curative therapy for a limited subset of patients with advanced MF, who are eligible, but engraftment in MF vs. AML is delayed which promotes complications. As determinants of engraftment in MF are incompletely characterized, we studied engraftment dynamics at our center. Methods: A longitudinal cohort of 71 allogeneic HCT performed 2000-2019 with >50% after 2015 was evaluated. Results: Median time to neutrophil engraftment ≥0.5x109/l was +20 days post-transplant and associated with BM fibrosis, splenomegaly and infused CD34+ cell number. Engraftment dynamics were similar in primary vs. secondary MF and were independent of MF driver mutations in JAK2, CALR and MPL. Neutrophil engraftment occurred later upon haploidentical HCT with thiotepa-busulfan-fludarabine conditioning, post-transplant cyclophosphamide and G-CSF (TBF-PTCy/G-CSF) administered to 9.9% and 15.6% of patients in 2000-2019 and after 2015, respectively. Engraftment of platelets was similarly delayed, while reconstitution of reticulocytes was not affected. Conclusions: Since MF is a rare hematologic malignancy, this data from a large number of HCT for MF is essential to substantiate that later neutrophil and platelet engraftment in MF relates both to host and treatment-related factors. Observations from this longitudinal cohort support that novel conditioning schemes administered also to rare entities such as MF, require detailed evaluation in larger, multi-center cohorts to assess also indicators of long-term graft function and overall outcome in patients with this infrequent hematopoietic neoplasm undergoing allogeneic transplantation.
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Introduction: Vaccine-induced myocarditis is a rare complication of messenger RNA (mRNA) COVID-19 vaccines. Case presentation: We report a case of acute myopericarditis in a recipient of allogeneic hematopoietic cells following the first dose of the mRNA-1273 vaccine and the successful administration of a second and third dose while on prophylactic treatment with colchicine to successfully complete the vaccination. Conclusion: Treatment and prevention of mRNA-vaccine-induced myopericarditis represent a clinical challenge. The use of colchicine is feasible and safe to potentially reduce the risk of this rare but severe complication and allows re-exposure to an mRNA vaccine.
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Hepatic sinusoidal obstruction syndrome (SOS)/veno-occlusive disease (VOD) is a complication after allogenic hematopoietic stem-cell transplantation (allo-HSCT) with high mortality. The purpose of this study was to assess the incidence and outcome of SOS in patients after allo-HSCT with the impact of ursodeoxycholic acid (UDCA) and low-dose heparin as SOS prophylaxis. Out of 1016 patients, 23 developed SOS, with a cumulative incidence of 2.3% (95% CI 1.3-3.3) 6 months after HSCT. Approximately one quarter of these patients (26.1%) had late-onset SOS. A high proportion were very severe SOS cases (74%), and 83% of the patients were treated with defibrotide (DF). In multivariate analysis, advanced disease (p = 0.003), previous HSCT (p = 0.025) and graft versus host disease (GvHD) prophylaxis by post-transplant cyclophosphamide (PTCy) (p = 0.055) were associated with the development of SOS. The 1-year overall survival (OS) was significantly lower in the SOS group compared to patients without SOS (13% versus 70%, p = 0.0001). In conclusion, we found a low incidence of SOS in patients receiving low-dose heparin and UDCA prophylactically, but among SOS patients, a high mortality. Low-dose heparin and UDCA might be a prophylactic approach for SOS.
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Trasplante de Células Madre Hematopoyéticas , Enfermedad Veno-Oclusiva Hepática , Adulto , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Heparina/uso terapéutico , Enfermedad Veno-Oclusiva Hepática/epidemiología , Enfermedad Veno-Oclusiva Hepática/etiología , Enfermedad Veno-Oclusiva Hepática/prevención & control , Humanos , Incidencia , Polidesoxirribonucleótidos/uso terapéutico , Ácido Ursodesoxicólico/uso terapéuticoRESUMEN
Pretransplant risk scores such as the revised Pretransplant Assessment of Mortality (rPAM) score help to predict outcome of patients receiving allogeneic hematopoietic cell transplantation (allo-HCT). Since the rPAM has not been validated externally in a heterogeneous patient population with different diseases, we aimed to validate the rPAM score in a real-world cohort of allo-HCT patients. A total of 429 patients were included receiving their first allo-HCT from 2008 to 2015. The predictive capacity of the rPAM score for 4-year overall survival (OS), nonrelapse mortality (NRM), and cumulative incidence of relapse (CIR) after allo-HCT was evaluated. Moreover, we evaluated the impact of the rPAM score for OS and used uni- and multivariable analyses to identify patient- and transplant-related predictors for OS. In rPAM score categories of <17, 17-23, 24-30, and >30, the OS probability at 4 years differed significantly with 61%, 36%, 26%, and 10%, respectively (P < 0.0001). In contrast to CIR, the NRM increased significantly in patients with higher rPAM scores (P < 0.001). Regarding the OS, the rPAM score had an area under the receiver operating characteristics curve of 0.676 (95% confidence interval [CI], 0.625-0.727) at 4 years. In the multivariable analysis, the rPAM score was associated with OS-independently of conditioning regimens (adjusted hazard ratio per 1-unit increase, 1.10; 95% CI, 1.06-1.10; P < 0.001). Additionally, forced expiratory volume in 1 second and the disease risk index were the components of the rPAM significantly associated with outcome. In our large real-world cohort with extended follow-up, the rPAM score was validated as an independent predictor of OS in patients with hematologic disorders undergoing allo-HCT.