RESUMEN
ABSTRACT: In the setting of a learning collaborative, we conducted an international multicenter phase 2 clinical trial testing the hypothesis that nonmyeloablative-related haploidentical bone marrow transplant (BMT) with thiotepa and posttransplant cyclophosphamide (PTCy) will result in 2-year event-free survival (no graft failure or death) of at least 80%. A total of 70 participants were evaluable based on the conditioning protocol. Graft failure occurred in 8 of 70 (11.4%) and only in participants aged <18 years; all had autologous reconstitution. After a median follow-up of 2.4 years, the 2-year Kaplan-Meier-based probability of event-free survival was 82.6%. The 2-year overall survival was 94.1%, with no difference between children and adult participants. After excluding participants with graft failure (n = 8), participants with engraftment had median whole blood donor chimerism values at days +180 and +365 after transplant of 100% (n = 58), respectively, and 96.6% (57/59) were off immunosuppression 1 year after transplant. The 1-year grade 3 to 4 acute graft-versus-host disease (GVHD) rate was 10%, and the 2-year moderate-severe chronic GVHD rate was 10%. Five participants (7.1%) died from infectious complications. We demonstrate that nonmyeloablative haploidentical BMT with thiotepa and PTCy is a readily available curative therapy for most adults, even those with organ damage, compared to the more expensive myeloablative gene therapy and gene editing. Additional strategies are required for children to decrease graft failure rates. The trial was registered at www.clinicaltrials.gov as #NCT01850108.
Asunto(s)
Anemia de Células Falciformes , Trasplante de Médula Ósea , Enfermedad Injerto contra Huésped , Trasplante Haploidéntico , Humanos , Trasplante de Médula Ósea/métodos , Trasplante de Médula Ósea/efectos adversos , Masculino , Femenino , Niño , Adolescente , Adulto , Anemia de Células Falciformes/terapia , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante Haploidéntico/métodos , Preescolar , Adulto Joven , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Acondicionamiento Pretrasplante/métodos , Persona de Mediana Edad , Tiotepa/administración & dosificación , Tiotepa/uso terapéuticoRESUMEN
Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by life-threatening infections and inflammatory conditions. Hematopoietic cell transplantation (HCT) is the definitive treatment for CGD, but questions remain regarding patient selection and impact of active disease on transplant outcomes. We performed a multi-institutional retrospective and prospective study of 391 patients with CGD treated either conventionally (non-HCT) enrolled from 2004 to 2018 or with HCT from 1996 to 2018. Median follow-up after HCT was 3.7 years with a 3-year overall survival of 82% and event-free survival of 69%. In a multivariate analysis, a Lansky/Karnofsky score <90 and use of HLA-mismatched donors negatively affected survival. Age, genotype, and oxidase status did not affect outcomes. Before HCT, patients had higher infection density, higher frequency of noninfectious lung and liver diseases, and more steroid use than conventionally treated patients; however, these issues did not adversely affect HCT survival. Presence of pre-HCT inflammatory conditions was associated with chronic graft-versus-host disease. Graft failure or receipt of a second HCT occurred in 17.6% of the patients and was associated with melphalan-based conditioning and/or early mixed chimerism. At 3 to 5 years after HCT, patients had improved growth and nutrition, resolved infections and inflammatory disease, and lower rates of antimicrobial prophylaxis or corticosteroid use compared with both their baseline and those of conventionally treated patients. HCT leads to durable resolution of CGD symptoms and lowers the burden of the disease. Patients with active infection or inflammation are candidates for transplants; HCT should be considered before the development of comorbidities that could affect performance status. This trial was registered at www.clinicaltrials.gov as #NCT02082353.
Asunto(s)
Enfermedad Injerto contra Huésped , Enfermedad Granulomatosa Crónica , Trasplante de Células Madre Hematopoyéticas , Humanos , Enfermedad Granulomatosa Crónica/genética , Enfermedad Granulomatosa Crónica/terapia , Estudios Retrospectivos , Estudios Prospectivos , Trasplante Homólogo , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Genotipo , Acondicionamiento Pretrasplante/efectos adversos , Enfermedad Injerto contra Huésped/prevención & controlRESUMEN
Isolated optic nerve (ON) relapse is a rare occurrence in lymphoblastic leukemia (LBL). A 10-year-old boy with T-LBL presented 8 months after diagnosis with blurred vision and thickening of right ON on magnetic resonance imaging consistent with relapse. Cerebrospinal fluid and bone marrow were negative for leukemia. He received reinduction chemotherapy (including nelarabine and craniospinal radiation) followed by a myeloablative matched sibling donor bone marrow transplant. He remains in remission 2 years post-transplant with normal vision. We also review the literature for reports of isolated ON relapse in patients with LBL. Our patient's clinical course demonstrates that disease control can be achieved with early detection of ON relapse before disease progression.
Asunto(s)
Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Masculino , Niño , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Trasplante de Médula Ósea , Nervio Óptico/patología , Nervio Óptico/diagnóstico por imagen , Recurrencia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/diagnósticoRESUMEN
Sickle cell disease is a debilitating hemoglobinopathy with high morbidity and mortality. Hematopoietic stem cell transplantation (HCT) is curative, but the presence of mixed donor/recipient chimerism post-HCT raises concerns about disease control long-term. Mixed donor/recipient chimerism is reported in significant numbers even after aggressive HCT conditioning regimens. Post-HCT, adequacy of donor erythropoiesis is crucial for disease control. This review explores the relationship between mixed donor/recipient chimerism and outcomes post-HCT. Serial chimerism analysis in lineage specific manner in erythroid or myeloid cells post-HCT predicts for disease control and HCT success. Adequate and stable donor-derived erythropoiesis is essential for reversing SCD manifestations. Myeloid lineage chimerism mirrors erythropoiesis is commercially available, and a reliable indicator of adequacy. Using this tool, the minimum threshold of donor chimerism is required to prevent SCD-related complications and maintain sickle hemoglobin less than 50% is approximately 20-25% even when a donor has Hb S trait. Curative interventions should, at a minimum, meet this goal long-term. Achieving a balance between successful engraftment while minimizing toxicity is important in patients vulnerable because of age or preexisting morbidity and is the objective of recent clinical trials. As HCT and gene therapies evolve, efficient long-term follow-up that includes durability assessment of mixed donor/recipient chimerism will be crucial.
Asunto(s)
Anemia de Células Falciformes , Trasplante de Células Madre Hematopoyéticas , Humanos , Quimerismo , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Anemia de Células Falciformes/terapia , Anemia de Células Falciformes/etiología , Trasplante de Células Madre , Donantes de Tejidos , Acondicionamiento Pretrasplante , Quimera por TrasplanteRESUMEN
In the context of an evolving understanding of early T-cell precursor (ETP) lymphoma and leukemia, we present a case of concurrent T-cell lymphoblastic lymphoma and ETP lymphoma in an adolescent female. To our knowledge, this represents the first reported case of both lymphoblastic lymphoma and ETP lymphoma as distinct and conjoined components of the same neoplasm. As an exception to current literature, our patient had a strictly lymphomatous ETP component with no leukemic manifestation. Her ETP component remained viable following induction, supporting ETP resistance to chemotherapy. The patient remains in remission 4 years postallogeneic matched sibling donor bone marrow transplant.
Asunto(s)
Linfoma no Hodgkin , Leucemia-Linfoma Linfoblástico de Células Precursoras , Células Precursoras de Linfocitos T , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Adolescente , Femenino , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamiento farmacológicoRESUMEN
BACKGROUND: Pleraxifor for peripheral blood stem cell (PBSC) mobilization in children with malignancies is often given following failure of standard mobilization (SM) rather than as a primary mobilizing agent. STUDY DESIGN AND METHODS: In this retrospective multicenter study, we report the safety of plerixafor-based PBSC mobilization in children with malignancies and compare outcomes between patients who received plerixafor upfront with SM (Group A) with those who received plerixafor following failure of SM (Group B). In the latter pleraxifor was given either following a low peripheral blood (PB) CD34 (<20 cells/cu.mm) (Group B1) or as a second collection process due to an unsuccessful yield (CD34 + < 2 × 106 /kg) (Group B2) following failed SM and first apheresis attempts. RESULTS: The study cohort (n = 47) with a median age of 8 (range 0.6-21) year, comprised 19 (40%) Group A and 28 (60%) Group B patients (B1 = 12 and B2 = 16). Pleraxifor mobilization was successful in 87.2% of patients, similar between Groups A and B (84.2% vs 89.2%) and resulted in a median 4-fold increase in PB CD34. Median number of apheresis attempts was 2 in Groups A and B1 but 4 in Group B2. In Group B2, median total CD34+ yield post-plerixafor was 9-fold higher than after SM (P = .0013). Mild to moderate transient adverse events affected 8.5% of patients. Among patients who proceeded to autologous transplant (n = 39), all but one engrafted. CONCLUSION: Plerixafor-based PBSC collection was safe and effective in our cohort and supports consideration as a primary mobilizing agent in children with malignancies.
Asunto(s)
Bencilaminas/uso terapéutico , Ciclamas/uso terapéutico , Movilización de Célula Madre Hematopoyética/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Células Madre de Sangre Periférica/efectos de los fármacos , Adolescente , Antígenos CD34/sangre , Eliminación de Componentes Sanguíneos , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Linfoma/tratamiento farmacológico , Linfoma/terapia , Masculino , Meduloblastoma/tratamiento farmacológico , Meduloblastoma/radioterapia , Meduloblastoma/terapia , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/radioterapia , Neuroblastoma/terapia , Células Madre de Sangre Periférica/metabolismo , Estudios Retrospectivos , Sarcoma/tratamiento farmacológico , Sarcoma/terapia , Adulto JovenRESUMEN
In this commentary, we discuss the reasons why umbilical cord blood (UCB) allogeneic stem cell transplants are more expensive than matched related and matched unrelated peripheral blood and bone marrow transplants in patients treated at pediatric centers. We compare results of our previously published study with the recently published study from the Center for International Bone Marrow Transplant and Research/Pediatric Health Information System and also highlight the factors that contribute to increased costs of UCB transplants.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Sistemas de Información en Salud , Trasplante de Células Madre Hematopoyéticas , Síndromes Mielodisplásicos , Médula Ósea , Niño , Humanos , Síndromes Mielodisplásicos/terapiaRESUMEN
We compared the incidence of refractory thrombocytopenia (RT) and platelet transfusion requirements (PTR) in 35 children who developed veno-occlusive disease (VOD) with 35 matched control subjects who underwent hematopoietic stem cell transplant but did not develop VOD. RT developed in 100% of the VOD patients, at a median of 8 days before VOD diagnosis, as compared with 71.5% of the control group. VOD patients required more platelet transfusions than control subjects (median PTR, 6.9 mL/kg [range, .57 to 17.59] versus 3.57 mL/kg [range, 0 to 14.63], respectively) with a statistically significant difference (P < .0001). The number of days with platelet requirements was significantly higher for VOD patients as compared with control subjects (median 68% versus 39%, P =< .0001). The PTR peaked at ~12 mL/kg/day, 2 days before VOD diagnosis, whereas the PTR in the control population was 5 mL/kg/day. The positive predictive value of developing VOD was 88.9% (95% confidence interval, 66.5% to 97%) in patients who were given >7 mL/kg/day of platelets during the at-risk period of days +3 to +13 after transplant. For patients who received >8 mL/kg/day of platelets, the positive predictive value of developing VOD was 86.7% (95% confidence interval, 61.2% to 96.4%). There was no difference in the PTR in patients with mild to moderate VOD as compared with severe VOD; however, the PTR was higher in patients whose VOD did not resolve. The median daily PTR after the diagnosis of VOD in 17 patients who got defibrotide as compared with those who did not get defibrotide was 6.04 mL/kg and 5.72 mL/kg, respectively, but the difference was not statistically significant (P = .56). On univariate and multivariate analysis use of intravenous immunoglobulin was significantly associated with VOD (P = .0088) but was not significantly associated with fatal VOD. In conclusion, RT occurs in 100% of patients at a median of 8 days before VOD diagnosis. VOD should be suspected in any patient with RT after the exclusion of other causes of consumptive thrombocytopenia, especially if they require >7 mL/kg/day of platelets.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Enfermedad Veno-Oclusiva Hepática , Trombocitopenia , Niño , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Veno-Oclusiva Hepática/diagnóstico , Enfermedad Veno-Oclusiva Hepática/etiología , Humanos , Polidesoxirribonucleótidos , Trombocitopenia/diagnóstico , Trombocitopenia/etiología , Acondicionamiento PretrasplanteRESUMEN
Allogeneic hematopoietic cell transplantation (HCT) is a curative option for patients with acute leukemia and myelodysplastic syndromes (MDS) but is associated with significant cost. Compared with children (age <15 years), adolescents and young adults (AYA; age 15 to 39 years) undergoing HCT have an increased risk for transplantation-related complications. However, whether such complications translate into increased resource utilization and costs during HCT remains unknown. Therefore, we conducted a multicenter database study using the Pediatric Health Information System database, an administrative database containing resource utilization data from 49 US tertiary children's hospitals to compare inpatient costs and resource utilization in children and AYA undergoing HCT for acute leukemia and MDS. The International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify HCT recipients and transplantation-related complications occurring up to 1 year post-HCT. We identified 1693 HCT recipients at pediatric centers between January 2010 and September 2014. Eighty percent of the total costs (from admission for HCT up to 1 year post-HCT) occurred during the initial transplantation admission. During initial admission, although AYA and children had a similar median length of stay (LOS) of 43 days, AYA incurred significantly greater adjusted costs ($338,458 versus $275,723; P < .001) and costs per hospital day ($7122 versus $5838; P < .001). Median total costs and costs per day during subsequent time periods post-HCT were also significantly greater in the AYA group. In multivariable analysis, increasing age at HCT, LOS, use of cord blood or an unrelated donor, occurrence of any graft-versus-host disease, infection, and use of dialysis or mechanical ventilation were significant drivers of increased cost at initial admission. In conclusion, allogeneic HCT for acute leukemia and MDS is associated with higher costs in AYA recipients than in children. Therefore, directing efforts and resources aimed at reducing HCT-related costs may be advantageous in this high-risk group.
Asunto(s)
Costos de la Atención en Salud , Trasplante de Células Madre Hematopoyéticas/economía , Leucemia/terapia , Síndromes Mielodisplásicos/terapia , Aceptación de la Atención de Salud , Enfermedad Aguda , Adolescente , Adulto , Factores de Edad , Niño , Bases de Datos Factuales , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Tiempo de Internación/economía , Leucemia/complicaciones , Síndromes Mielodisplásicos/complicaciones , Trasplante Homólogo , Adulto JovenRESUMEN
Data on whether the T cell dose of allogeneic peripheral blood stem cell (PBSC) products influences transplantation outcomes are conflicting. Using the Center for International Blood and Marrow Transplant Research database, we identified 2736 adult patients who underwent first allogeneic PBSC transplantation for acute leukemia or myelodysplastic syndrome between 2008 and 2014 using an HLA-matched sibling donor (MSD) or an 8/8-matched unrelated donor (MUD). We excluded ex vivo and in vivo T cell-depleted transplantations. Correlative analysis was performed between CD3+ T cell dose and the risk of graft-versus-host-disease (GVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS). Using maximum likelihood estimation, we identified CD3+ T cell dose cutoff that separated the risk of acute GVHD (aGVHD) grade II-IV in both the MSD and MUD groups. A CD3+ T cell dose cutoff of 14â¯×â¯107 cells/kg identified MSD/low CD3+ (nâ¯=â¯223) and MSD/high CD3+ (nâ¯=â¯1214), and a dose of 15â¯×â¯107 cells/kg identified MUD/low CD3+ (nâ¯=â¯197) and MUD/high CD3+ (nâ¯=â¯1102). On univariate analysis, the MSD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MSD/low CD3+ group (33% versus 25%; Pâ¯=â¯.009). There were no differences between the 2 groups in engraftment rate, risk of aGVHD grade III-IV or chronic GVHD (cGVHD), NRM, relapse, DFS, or OS. The MUD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MUD/low CD3+ group (49% versus 41%; Pâ¯=â¯.04). There were no differences between the 2 groups in engraftment rate, risk of severe aGVHD or cGVHD, NRM, relapse, DFS, or OS. Multivariate analysis of the MSD and MUD groups failed to show an association between CD3+ T cell dose and the risk of either aGVHD grade II-IV (Pâ¯=â¯.10 and .07, respectively) or cGVHD (Pâ¯=â¯.80 and .30, respectively). Subanalysis of CD4+ T cells, CD8+ T cells, and CD4+/CD8+ ratio failed to identify cutoff values predictive of transplantation outcomes; however, using the log-rank test, the sample size was suboptimal for identifying a difference at this cutoff cell dose. In this registry study, the CD3+ T cell dose of PBSC products did not influence the risk of aGVHD or cGVHD or other transplantation outcomes when using an MSD or an 8/8-matched MUD. Subset analyses of CD4+ and CD8+ T cell doses were not possible given our small sample size.
Asunto(s)
Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Enfermedad Injerto contra Huésped , Leucemia , Síndromes Mielodisplásicos , Trasplante de Células Madre de Sangre Periférica , Enfermedad Aguda , Adolescente , Adulto , Aloinjertos , Relación CD4-CD8 , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/prevención & control , Antígenos HLA , Humanos , Leucemia/sangre , Leucemia/mortalidad , Leucemia/terapia , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/terapia , Recurrencia , Tasa de SupervivenciaRESUMEN
Preexisting endothelial dysfunction and vascular injury sustained during allogeneic hematopoietic cell transplantation (HCT) increases risk for endothelial injury-related complications such as posterior reversible encephalopathy syndrome (PRES) and transplant-associated thrombotic microangiopathy (TA-TMA) in patients with sickle cell disease (SCD). We report two patients with SCD who developed PRES following allogeneic HCT. In both patients, PRES-related symptoms resolved only after a diagnosis of TA-TMA was established and eculizumab therapy was initiated. Renal manifestations at diagnosis included non-nephrotic range proteinuria and hypertension. This report highlights the importance of screening PRES-affected SCD HCT recipients for TA-TMA as usual treatment strategies may be inadequate.
Asunto(s)
Anemia de Células Falciformes/terapia , Anticuerpos Monoclonales Humanizados/uso terapéutico , Inactivadores del Complemento/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Síndrome de Leucoencefalopatía Posterior/etiología , Microangiopatías Trombóticas/tratamiento farmacológico , Adulto , Niño , Femenino , Humanos , Masculino , Microangiopatías Trombóticas/etiologíaRESUMEN
Unrelated donor (URD) hematopoietic cell transplantation (HCT) in children with sickle cell disease (SCD) is associated with a high incidence of rejection and graft-versus-host disease (GVHD). We report on the first 4 patients with severe SCD who underwent URD HCT using a novel myeloablative and immunosuppressive regimen composed of busulfan, fludarabine, and antithymocyte globulin with a single dose of post-transplant cyclophosphamide along with tacrolimus and mycophenolate mofetil for GVHD prophylaxis. Three patients engrafted and remain disease-free after a median follow-up period of 2.5 years. One patient had primary graft failure attributed to low stem cell content of the graft. Of interest, none of the engrafted patients developed acute or chronic GVHD. This preparative regimen along with the use of post-transplant cyclophosphamide offers a promising approach for unrelated donor transplants in patients with SCD and needs further corroboration in larger number of patients.
Asunto(s)
Anemia de Células Falciformes/terapia , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/métodos , Adolescente , Suero Antilinfocítico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Busulfano , Niño , Preescolar , Femenino , Humanos , Masculino , Ácido Micofenólico , Premedicación/métodos , Tacrolimus , Donantes de Tejidos , Trasplante Homólogo , Resultado del Tratamiento , Vidarabina/análogos & derivados , Adulto JovenRESUMEN
Hematopoietic cell transplant (HCT) is associated with a proinflammatory, procoagulant environment that places recipients at increased risk of venous thromboembolism (VTE). Although the incidence of VTE in adult HCT recipients has been extensively studied, similar data for children are lacking. We conducted a multicenter retrospective study to analyze the prevalence of VTE and associated risk factors in a large cohort of patients who underwent HCT at tertiary care US children's hospitals. The Pediatric Health Information System database, a large administrative database that contains clinical and resource utilization data from 49 freestanding children's hospitals in the United States, was used to extract data. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify HCT recipients, VTE events, post-HCT complications, and associated risk factors up to 1 year post-transplant. Data on patients who received HCT from January 2010 through September 2014 were collected. A total of 4158 unique patients mean ± standard deviation age at transplant admit, 8.8 ± 6.5 years; range, birth to 33.4 years) were identified. After HCT 290 subjects (6.9%) developed VTE. VTE prevalence was greater in patients aged ≥ 13 versus <13 years (8.54% versus 6.33%; P = .01) and in recipients of allogeneic versus autologous grafts (7.7% versus 5%; P ≤ .01). VTE was associated with prolonged median duration of hospitalization (81 versus 54 days; P ≤.01) and increased 1-year mortality (13.9% versus 5.9%; P ≤ .01). Infections and presence of any graft-versus-host disease (GVHD) were significantly associated with VTE occurrence in recipients of allogenic grafts. Prevalence of VTE in patients who underwent HCT at pediatric tertiary care hospitals is about 7%. Age ≥ 13 years and allogeneic grafts were significant pre-HCT VTE risk factors, with GVHD and infections seen more frequently in patients with VTE.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Tromboembolia Venosa/etiología , Adolescente , Adulto , Niño , Preescolar , Trasplante de Células Madre Hematopoyéticas/métodos , Hospitales Pediátricos , Humanos , Lactante , Recién Nacido , Prevalencia , Estudios Retrospectivos , Centros de Atención Terciaria , Adulto JovenAsunto(s)
Anemia Hemolítica Autoinmune , Trasplante de Células Madre Hematopoyéticas , Síndromes de Inmunodeficiencia , Humanos , Anemia Hemolítica Autoinmune/etiología , Anemia Hemolítica Autoinmune/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Proteínas de Homeodominio , Linfocitos T , Trasplante HomólogoRESUMEN
BACKGROUND: Tacrolimus, commonly used for graft versus host disease prophylaxis is usually administered via a dedicated central venous line (CVL) and trough levels drawn from the unexposed lumen. Being an oil-based medication, it may be adsorbed to the inner lumen of the CVL and result in falsely high levels drawn from an inadvertently exposed lumen. There is no treatment for decontamination of such CVLs, and natural decay occurs over months before the CVL can be used to draw reliable trough levels. OBJECTIVE: The primary objective of the study was to estimate the effectiveness of 70% ethanol locks for decontaminating CVLs exposed to tacrolimus. METHODS: We studied the efficacy of 70% ethanol lock in decontaminating CVLs exposed to tacrolimus in patients during transplant. Trough tacrolimus levels were drawn from the exposed and unexposed (control) lumens at 8:00 am, followed by a 2-mL 70% ethanol lock instilled for a 2-hour dwell into the exposed (intervention) lumen. Trough tacrolimus levels were again drawn from both lumens at 8:00 pm and levels compared for efficacy. RESULTS: All 20 sets showed a high 8 am trough level in the exposed intervention arm (median = 30 ng/mL), significantly greater ( P < 0.0001) than that in the control arm (median = 9.05 ng/mL), and were contaminated. After the 2-hour ethanol lock, 65% of the lumens were decontaminated. The difference between the control and intervention arms was no longer found to be statistically significant ( P = 0.0826). CONCLUSION: A 2-hour 70% ethanol lock is effective for decontamination of CVLs exposed to tacrolimus.
Asunto(s)
Inhibidores de la Calcineurina/uso terapéutico , Descontaminación/métodos , Etanol/administración & dosificación , Inmunosupresores/uso terapéutico , Adolescente , Adulto , Catéteres Venosos Centrales , Niño , Preescolar , Femenino , Humanos , Masculino , Estudios Prospectivos , Tacrolimus/administración & dosificación , Adulto JovenRESUMEN
AML with the RAM immunophenotype is associated with extremely poor prognosis. We report a rare case of monozygotic twins presenting simultaneously at the age of 2 years with RAM AML. Each twin underwent a myeloablative 7/10 unrelated umbilical cord blood transplant. Pretransplant Twin A's bone marrow was negative for MRD by flow cytometry (<0.01%) unlike Twin B's bone marrow (0.07%). Twin A is alive in remission 3 years from transplant. Twin B developed primary graft failure, but subsequently rescued with a haploidentical stem cell transplant. However, she relapsed and died 13 months from diagnosis. The twins' clinical courses demonstrate that upfront intensive chemotherapy to achieve negative MRD, followed by allogeneic hematopoietic stem cell transplant as postremission intensification strategy, should be considered in this high-risk AML.
Asunto(s)
Inmunofenotipificación , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/inmunología , Médula Ósea/patología , Preescolar , Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedades en Gemelos , Resultado Fatal , Femenino , Sangre Fetal/metabolismo , Citometría de Flujo , Humanos , Leucemia Mieloide Aguda/genética , Neoplasia Residual , Pronóstico , Inducción de Remisión , Trasplante Homólogo , Gemelos MonocigóticosRESUMEN
Advances in allogeneic hematopoietic cell transplantation for sickle cell disease have improved outcomes, but there is limited analysis of healthcare utilization in this setting. We hypothesized that, compared to late transplantation, early transplantation (at age <10 years) improves outcomes and decreases healthcare utilization. We performed a retrospective study of children transplanted for sickle cell disease in the USA during 2000-2013 using two large databases. Univariate and Cox models were used to estimate associations of demographics, sickle cell disease severity, and transplant-related variables with mortality and chronic graft-versus-host disease, while Wilcoxon, Kruskal-Wallis, or linear trend tests were applied for the estimates of healthcare utilization. Among 161 patients with a 2-year overall survival rate of 90% (95% confidence interval [CI] 85-95%) mortality was significantly higher in those who underwent late transplantation versus early (hazard ratio (HR) 21, 95% CI 2.8-160.8, P=0.003) and unrelated compared to matched sibling donor transplantation (HR 5.9, 95% CI 1.7-20.2, P=0.005). Chronic graftversus host disease was significantly more frequent among those translanted late (HR 1.9, 95% CI 1.0-3.5, P=0.034) and those who received an unrelated graft (HR 2.5, 95% CI 1.2-5.4; P=0.017). Merged data for 176 patients showed that the median total adjusted transplant cost per patient was $467,747 (range: $344,029-$799,219). Healthcare utilization was lower among recipients of matched sibling donor grafts and those with low severity disease compared to those with other types of donor and disease severity types (P<0.001 and P=0.022, respectively); no association was demonstrated with late transplantation (P=0.775). Among patients with 2-year pre- and post-transplant data (n=41), early transplantation was associated with significant reductions in admissions (P<0.001), length of stay (P<0.001), and cost (P=0.008). Early transplant outcomes need to be studied prospectively in young children without severe disease and an available matched sibling to provide conclusive evidence for the superiority of this approach. Reduced post-transplant healthcare utilization inpatient care indicates that transplantation may provide a sustained decrease in healthcare costs over time.
Asunto(s)
Anemia de Células Falciformes/terapia , Trasplante de Células Madre Hematopoyéticas , Aceptación de la Atención de Salud , Adolescente , Anemia de Células Falciformes/diagnóstico , Anemia de Células Falciformes/epidemiología , Trasplante de Médula Ósea/efectos adversos , Trasplante de Médula Ósea/métodos , Niño , Preescolar , Toma de Decisiones Clínicas , Comorbilidad , Bases de Datos Factuales , Femenino , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Costos de la Atención en Salud , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Mortalidad , Medición de Riesgo , Índice de Severidad de la Enfermedad , Donantes de Tejidos , Trasplante Homólogo , Insuficiencia del Tratamiento , Resultado del Tratamiento , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Incidence and severity of transplant-associated thrombotic microangiopathy (TA-TMA) in patients with hemoglobinopathies receiving hematopoietic cell transplant is unknown. We report the outcomes for two patients with TA-TMA who received eculizumab. A 2.5-year-old male with sickle cell disease developed TA-TMA-associated pericardial tamponade, severe hypertension, and acute kidney injury 2 months after transplant. A 7-year-old female with ß-thalassemia major developed TA-TMA-related acute kidney injury, severe hypertension, and seizures at 6 months after transplant. Both patients progressed to chronic kidney disease (CKD). In patients with hemoglobinopathies, preexisting endothelial dysfunction may place them at a greater risk for TA-TMA and subsequent CKD.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Microangiopatías Trombóticas/etiología , Anemia de Células Falciformes/terapia , Niño , Preescolar , Femenino , Humanos , Masculino , Insuficiencia Renal Crónica/etiología , Talasemia beta/terapiaAsunto(s)
Anemia de Células Falciformes/terapia , Anticuerpos Monoclonales Humanizados/administración & dosificación , Enfermedades Gastrointestinales/tratamiento farmacológico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas , Aloinjertos , Quimioterapia Adyuvante , Niño , Femenino , Enfermedades Gastrointestinales/etiología , HumanosRESUMEN
Socioeconomic status (SES) and race/ethnicity have been associated with outcomes of allogeneic hematopoietic cell transplantation (allo-HCT). Certain aspects of GVHD management such as the need for long term care, prolonged immunosuppressive treatment, and need for close follow up for complications may exacerbate disparities. Adults (≥ 18 years) reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) who underwent a first alloHCT for acute leukemia, myelodysplastic syndrome, or myeloproliferative neoplasm between 2008 - 2018 were included. Endpoints for those developing GVHD included overall survival (OS), transplant related mortality (TRM), and disease relapse. Models were adjusted for patient and transplant related variables. A two-sided p-value < 0.01 was considered significant. Among the 14,825 allo-HCT recipients, 6,259 (42.2%) and 6,675 (45.0%) patients developed aGVHD and cGVHD, respectively. In patients with aGVHD, non-Hispanic Blacks had increased TRM (HR 1.50, 95% CI 1.24-1.83, p=0.0001) and overall mortality (HR 1.31, 1.14-1.50, p=0.0002) compared with non-Hispanic Whites, an association that disappeared when severity of aGVHD was included in the model. Lower SES was associated with increased risk of disease relapse (p=0.0016) but not OS or TRM. In patients who developed cGVHD, race and ethnicity were not associated with OS, TRM and disease relapse. However, the highest quartile of annual household income (≥ $80,000) had improved OS (HR 0.77, 0.69-0.85, p<0.0001) and reduced TRM (HR 0.86, 0.67-0.87, p<0.0001) compared with lowest quartile, adjusting for race and ethnicity. Race/ethnicity and SES are associated with outcomes after GVHD. Optimizing health care resources available to low SES patients and strategies to minimize the risk of severe GVHD in non-Hispanic Blacks may improve long-term outcomes.