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1.
Haematologica ; 108(1): 150-160, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-35443559

RESUMEN

Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28- 77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of intermediate-2 (HR=1.46, P=0.049) or high (HR=3.22, P=0.0004) correlated significantly with overall survival. When the molecularly informed CPSS-Mol prognostic model was applied, a high CPSS-Mol score (HR=2 P=0.0079) correlated significantly with overall survival. The most common somatic mutations were in ASXL1 (62%), TET2 (35%), KRAS/NRAS (33% combined), and SRSF2 (31%). DNMT3A and TP53 mutations were associated with decreased overall survival (HR=1.70 [95% CI: 1.11-2.60], P=0.0147 and HR=2.72 [95% CI: 1.37-5.39], P=0.0042, respectively) while DNMT3A, JAK2, and TP53 mutations were associated with decreased disease-free survival (HR=1.66 [95% CI: 1.11-2.49], P=0.0138, HR=1.79 [95% CI: 1.06-3.03], P=0.0293, and HR=2.94 [95% CI: 1.50-5.79], P=0.0018, respectively). The only mutation associated with increased relapse was TP53 (HR=2.94, P=0.0201). Nonetheless, the impact of TP53 mutations specifically should be interpreted cautiously given their rarity in CMML. We calculated the goodness of fit measured by Harrell's C-index for both the CPSS and CPSS-Mol, which were very similar. In summary, via registry data we have determined the mutational landscape in patients with CMML who underwent allogeneic HCT, and demonstrated an association between CPSS-Mol and transplant outcomes although without major improvement in the risk prediction beyond that provided by the CPSS.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mielomonocítica Crónica , Adulto , Humanos , Persona de Mediana Edad , Médula Ósea , Leucemia Mielomonocítica Crónica/genética , Leucemia Mielomonocítica Crónica/terapia , Mutación , Pronóstico , Anciano
2.
Blood Adv ; 8(13): 3497-3506, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38661372

RESUMEN

ABSTRACT: There has been an increase in volume as well as an improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for hematologic disorders. It is unknown if these changes have affected racial/ethnic minorities equally. In this observational study from the Center for International Blood and Marrow Transplant Research of 79 904 autologous (auto) and 65 662 allogeneic (allo) HCTs, we examined the volume and rates of change of autoHCT and alloHCT over time and trends in OS in 4 racial/ethnic groups: non-Hispanic Whites (NHWs), non-Hispanic African Americans (NHAAs), and Hispanics across 5 2-year cohorts from 2009 to 2018. Rates of change were compared using Poisson model. Adjusted and unadjusted Cox proportional hazards models examined trends in mortality in the 4 racial/ethnic groups over 5 study time periods. The rates of increase in volume were significantly higher for Hispanics and NHAAs vs NHW for both autoHCT and alloHCT. Adjusted overall mortality after autoHCT was comparable across all racial/ethnic groups. NHAA adults (hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.04-1.22; P = .004) and pediatric patients (HR 1.62; 95% CI 1.3-2.03; P < .001) had a higher risk of mortality after alloHCT than NHWs. Improvement in OS over time was seen in all 4 groups after both autoHCT and alloHCT. Our study shows the rate of change for the use of autoHCT and alloHCT is higher in NHAAs and Hispanics than in NHWs. Survival after autoHCT and alloHCT improved over time; however, NHAAs have worse OS after alloHCT, which has persisted. Continued efforts are needed to mitigate disparities for patients requiring alloHCT.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Minorías Étnicas y Raciales , Adolescente , Niño , Anciano , Adulto Joven , Preescolar
3.
Cytotherapy ; 15(1): 132-7, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23260093

RESUMEN

The definition of poor mobilizers is not clear in pediatric patients undergoing autologous peripheral blood hematopoietic progenitor cell (HPC) mobilization. Most studies conducted in children define those variables related to the collection of HPC after leukapheresis, but the information regarding exclusively the mobilization process is scarce. In our experience, most children (92.2%) reach the target CD34(+) cell dose for autologous peripheral blood progenitor cell transplantation if CD34(+) cell count was higher than 10/µL. No differences were observed between those with >20 CD34(+) cells/µL and 11-20 CD34(+) cells/µL. In this study, we analyzed the variables that influence CD34(+) cell count; we found that prior use of radiotherapy was the main variable related to poor mobilization. Patients diagnosed with Ewing sarcoma, treated with radiotherapy and mobilized with standard doses of granulocyte colony-stimulating factor (G-CSF) were also at a high risk of mobilization failure. In these patients, we should consider mobilization with high dose G-CSF and be prepared with new mobilization agents to avoid delay on their course of chemotherapy.


Asunto(s)
Movilización de Célula Madre Hematopoyética , Trasplante de Células Madre de Sangre Periférica/métodos , Adolescente , Antígenos CD34/metabolismo , Niño , Femenino , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Masculino , Estudios Retrospectivos
4.
Blood Adv ; 7(22): 7007-7016, 2023 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-37792849

RESUMEN

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Trastornos Mieloproliferativos , Humanos , Persona de Mediana Edad , Trasplante Homólogo , Recurrencia Local de Neoplasia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Aguda , Trastornos Mieloproliferativos/patología , Enfermedad Crónica , Recurrencia , Células Dendríticas/patología
5.
Transplant Cell Ther ; 28(10): 696.e1-696.e7, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35798233

RESUMEN

Adult hematopoietic stem cell transplantation (HSCT) recipients are at a high risk of adverse outcomes after COVID-19. Although children have had better outcomes after COVID-19 compared to adults, data on risk factors and outcomes of COVID-19 among pediatric HSCT recipients are lacking. We describe outcomes of HSCT recipients who were ≤21 years of age at COVID-19 diagnosis and were reported to the Center for International Blood and Marrow Transplant Research between March 27, 2020, and May 7, 2021. The primary outcome was overall survival after COVID-19 diagnosis. We determined risk factors of COVID-19 as a secondary outcome in a subset of allogeneic HSCT recipients. A total of 167 pediatric HSCT recipients (135 allogeneic; 32 autologous HSCT recipients) were included. Median time from HSCT to COVID-19 was 15 months (interquartile range [IQR] 7-45) for allogeneic HSCT recipients and 16 months (IQR 6-59) for autologous HSCT recipients. Median follow-up from COVID-19 diagnosis was 53 days (range 1-270) and 37 days (1-179) for allogeneic and autologous HSCT recipients, respectively. Although COVID-19 was mild in 87% (n = 146/167), 10% (n = 16/167) of patients required supplemental oxygen or mechanical ventilation. The 45-day overall survival was 95% (95% confidence interval [CI], 90-99) and 90% (74-99) for allogeneic and autologous HSCT recipients, respectively. Cox regression analysis showed that patients with a hematopoietic cell transplant comorbidity index (HCT-CI) score of 1-2 were more likely to be diagnosed with COVID-19 (hazard ratio 1.95; 95% CI, 1.03-3.69, P = .042) compared to those with an HCT-CI of 0. Pediatric and early adolescent and young adult HSCT recipients with pre-HSCT comorbidities were more likely to be diagnosed with COVID-19. Overall mortality, albeit higher than the reported general population estimates, was lower when compared with previously published data focusing on adult HSCT recipients.


Asunto(s)
COVID-19 , Trasplante de Células Madre Hematopoyéticas , Adolescente , COVID-19/epidemiología , Prueba de COVID-19 , Niño , Estudios de Cohortes , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Oxígeno , Adulto Joven
6.
JAMA Oncol ; 8(3): 404-411, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-35024768

RESUMEN

IMPORTANCE: Matched sibling donors (MSDs) are preferred for allogeneic hematopoietic cell transplantation (allo-HCT) in myelodysplastic syndrome even if they are older. However, whether older MSDs or younger human leukocyte antigen-matched unrelated donors (MUDs) are associated with better outcomes remains unclear. OBJECTIVE: To investigate whether allo-HCT for myelodysplastic syndrome using younger MUDs would be associated with improved disease-free survival and less relapse compared with older MSDs. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study assessed data reported to the Center for International Blood and Marrow Transplant Research database from 1761 adults 50 years or older with myelodysplastic syndrome who underwent allo-HCT using an older MSD or younger MUD between January 1, 2011, and December 31, 2017, with a median follow-up of 48 months. Data analysis was performed from January 8, 2019, to December 30, 2020. INTERVENTIONS/EXPOSURES: Allo-HCT from an older MSD (donor age ≥50 years) or a younger MUD (donor age ≤35 years). MAIN OUTCOMES AND MEASURES: The primary outcome was disease-free survival. Secondary outcomes were overall survival, relapse, nonrelapse mortality, acute graft-vs-host disease (GVHD), chronic GVHD, and GVHD-free relapse-free survival. RESULTS: Of 1761 patients (1162 [66%] male; median [range] age, 64.9 [50.2-77.6] years in the MSD cohort and 66.5 [50.4-80.9] years in MUD cohort), 646 underwent allo-HCT with an older MSD and 1115 with a younger MUD. In multivariable analysis, the rate of disease-free survival was significantly lower in allo-HCTs with older MSDs compared with younger MUDs (hazard ratio [HR], 1.17; 95% CI, 1.02-1.34; P = .02), whereas the difference in overall survival rate of allo-HCT with younger MUDs vs older MSDs was not statistically significant (HR, 1.13; 95% CI, 0.98-1.29; P = .07). Allo-HCT with older MSDs was associated with significantly higher relapse (HR, 1.62; 95% CI, 1.32-1.97; P < .001), lower nonrelapse mortality (HR, 0.76; 95% CI, 0.59-0.96; P = .02), lower acute GVHD (HR, 0.52; 95% CI, 0.42-0.65; P < .001), chronic GVHD (HR, 0.77; 95% CI, 0.64-0.92; P = .005), and a lower rate of GVHD-free relapse-free survival beyond 12 months after allo-HCT (HR, 1.42; 95% CI, 1.02-1.98; P = .04). CONCLUSIONS AND RELEVANCE: This cohort study found higher disease-free survival and lower relapse for allo-HCT in myelodysplastic syndrome using younger MUDs compared with older MSDs. The risk of nonrelapse mortality and GVHD was lower with older MSDs. These results suggest that the use of younger MUDs should be considered in the donor selection algorithm for myelodysplastic syndrome, in which it is pivotal to minimize relapse given limited treatment options for managing relapsed disease.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Síndromes Mielodisplásicos , Adulto , Anciano , Estudios de Cohortes , Supervivencia sin Enfermedad , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/terapia , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Hermanos , Acondicionamiento Pretrasplante/métodos , Donante no Emparentado
7.
Blood Adv ; 6(1): 339-357, 2022 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-34547770

RESUMEN

The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLA-matched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P ≤ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P ≤ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (≤18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Sangre Fetal , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudios Retrospectivos , Hermanos , Donante no Emparentado
8.
Transplant Cell Ther ; 27(3): 274.e1-274.e5, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33781541

RESUMEN

Data on stem cell transplantation (SCT) for Diamond-Blackfan Anemia (DBA) is limited. We studied patients transplanted for DBA and registered in the EBMT database. Between 1985 and 2016, 106 DBA patients (median age, 6.8 years) underwent hematopoietic stem cell transplantation from matched-sibling donors (57%), unrelated donors (36%), or other related donors (7%), using marrow (68%), peripheral blood stem cells (20%), both marrow and peripheral blood stem cells (1%), or cord blood (11%). The cumulative incidence of engraftment was 86% (80% to 93%), and neutrophil recovery and platelet recovery were achieved on day +18 (range, 16 to 20) and +36 (range, 32 to 43), respectively. Three-year overall survival and event-free survival were 84% (77% to 91%) and 81% (74% to 89%), respectively. Older patients were significantly more likely to die (hazard ratio, 1.4; 95% confidence interval, 1.06 to 1.23; P < .001). Outcomes were similar between sibling compared to unrelated-donor transplants. The incidence of acute grades II to IV of graft-versus-host disease (GVHD) was 30% (21% to 39%), and the incidence of extensive chronic GVHD was 15% (7% to 22%). This study shows that SCT may represent an alternative therapeutic option for transfusion-dependent younger patients.


Asunto(s)
Anemia Aplásica , Anemia de Diamond-Blackfan , Trasplante de Células Madre Hematopoyéticas , Anemia Aplásica/terapia , Anemia de Diamond-Blackfan/terapia , Médula Ósea , Niño , Humanos , Estudios Retrospectivos
9.
Pediatr Blood Cancer ; 53(1): 120-4, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19215002

RESUMEN

Killer immunoglobulin-like receptors (KIRs) on natural killer cells (NKs) recognize groups of human leukocyte antigen (HLA) class I alleles. Cells without an inhibitory HLA ligand may trigger NK activation. Reduced risk of relapse has been reported in malignant hematologic diseases after haploidentical transplantation when HLA ligands against the inhibitory KIRs present in the donor were absent in the recipient. We performed haploidentical transplant in three children with refractory solid tumors. Our results showed that beneficial antitumor effects could be observed in the presence of inhibitory KIR-HLA mismatch. These preliminary results suggest a possible association between disease control and NK cell alloreactivity.


Asunto(s)
Neoplasias Óseas/terapia , Rechazo de Injerto/inmunología , Trasplante de Células Madre Hematopoyéticas , Neuroblastoma/terapia , Receptores KIR/genética , Rabdomiosarcoma/terapia , Sarcoma de Ewing/terapia , Adolescente , Neoplasias Óseas/genética , Neoplasias Óseas/inmunología , Neoplasias Óseas/secundario , Preescolar , Terapia Combinada , Resultado Fatal , Femenino , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Humanos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/trasplante , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/secundario , Masculino , Neuroblastoma/genética , Neuroblastoma/inmunología , Neuroblastoma/secundario , Inducción de Remisión , Rabdomiosarcoma/genética , Rabdomiosarcoma/inmunología , Rabdomiosarcoma/secundario , Sarcoma de Ewing/genética , Sarcoma de Ewing/inmunología , Neoplasias Testiculares/genética , Neoplasias Testiculares/inmunología , Neoplasias Testiculares/terapia
10.
Open Forum Infect Dis ; 5(10): ofy235, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30349846

RESUMEN

We report the first case, to our knowledge, of a child who presented with severe zonal hepatic necrosis after allogeneic hematopoietic stem cell transplantation secondary to infection with the rubella virus RA27/3 vaccine strain.

12.
Leuk Lymphoma ; 56(3): 656-62, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24913510

RESUMEN

Strategies for reversing graft failure (GF) after allogeneic stem cell transplant (SCT) depend on the options available in each situation. GF was reported in 16 Spanish institutions from January 2006 to July 2011. Primary GF was defined as an absolute neutrophil count (ANC) > 0.5 × 10(9)/L not reached by day + 28 after SCT from peripheral blood (PB) or bone marrow (BM) progenitors and by day + 42 after SCT from unrelated cord blood (UCB) progenitors. Secondary GF was defined as a recurrent ANC < 0.5 × 10(9)/L. Eighty-nine patients with GF were reported, and 80 patients received a second SCT. The 5-year survival probability was 31% (95% confidence interval [CI]: 18-44%), and the incidences of non-relapse mortality and relapse estimated by competing risks were 47% (95% CI: 36-58%) and 21% (95% CI: 4-28%). The strategy adopted to treat GF was heterogeneous, and no approach could be unequivocally recommended for this situation. The prognosis of patients with GF was poor even after successful recovery from GF.


Asunto(s)
Rechazo de Injerto/prevención & control , Trasplante de Células Madre , Adolescente , Adulto , Anciano , Niño , Femenino , Rechazo de Injerto/etiología , Rechazo de Injerto/mortalidad , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Neutrófilos/citología , Tasa de Supervivencia , Trasplante Homólogo , Resultado del Tratamiento , Adulto Joven
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