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BACKGROUND: There is paucity of data regarding outcomes of children, adolescents and young adults (CAYA) patients with non-Hodgkin lymphoma (NHL) undergoing autologous stem cell transplantation (ASCT). METHODS: Patients aged 0-39 years undergoing first ASCT for NHL at MD Anderson Cancer Center between 2000 and 2020 were analyzed. RESULTS: Two hundred twenty-one patients were included in the analysis, 129 (58%) were male and the median age was 32 (range 6-39) years. The most common histological subtypes were diffuse large B cell lymphoma (DLBCL) (44%), T-NHL (19%) and primary mediastinal B-Cell lymphoma (PMBCL) (19%). Younger patients (age ≤ 25) had lower incidence of DLBCL and higher incidence of PMBCL and T-NHL compared to older patients (age > 25) (P = 0.02). None of the younger patients had double hit (DH)/double expressor (DE) DLBCL, compared to 14 patients in the older age group (18%, P = 0.07). Considering the three main aggressive NHL subtypes (DLBCL, PMBCL and T-NHL), younger patients had numerically better 15-year post-transplant progression free survival (PFS) (67% vs. 54%) and overall survival (OS) (71% vs. 62%) compared to older patients, yet these differences did not reach statistical significance (P = 0.19 and P = 0.24, respectively). In multivariate analysis, not achieving a CR prior to ASCT was independently predictive of worse PFS [partial remission (PR) (HR, 3.9); stable disease (SD) (HR, 18.0), P = 0.03] and of worse OS [PR (HR, 4.2), SD (HR, 6.5) and progressive disease (HR, 4.7), P < 0.0001]. DH/DE status was an independent adverse predictor of PFS in multivariate analysis (HR 5.8, p = 0.03). Ten patients (4.5%) (all aged > 25 years) developed second primary malignancies (SPM), at a median of 34.4 (range, 1.0-196.6) months after ASCT, and SPM was the cause of death in five (50%) of them. CONCLUSIONS: CAYA NHL patients aged ≤ 25 years who received ASCT presented a distinct NHL histology as compared to older CAYA patients, and none in this younger age group had DH/DE DLBCL. We observed a trend towards improved PFS and OS in younger patients. Disease status at ASCT was predictive of both PFS and OS. DH/DE status was an adverse predictor of PFS.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Trasplante de Células Madre , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Adulto Joven , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/terapia , Linfoma no Hodgkin/terapia , Trasplante de Células Madre/efectos adversos , Trasplante Autólogo , Resultado del TratamientoRESUMEN
Background: Sinusoidal obstruction syndrome is a potentially fatal complication following hematopoietic cell transplantation, high-intensity chemotherapies and increasingly seen with calicheamicin based leukemia therapies. Paediatric specific European Society for Blood and Marrow Transplantation (pEBMT) diagnostic criteria have demonstrated benefit in single center studies compared to historic criteria. Yet, the extent to which they have been universally implemented remains unclear. Methods: We conducted a retrospective multi-centre study to examine the potential impact of the Baltimore, modified Seattle and pEBMT criteria on the incidence, severity, and outcomes of sinusoidal obstruction syndrome among paediatric hematopoietic cell transplantation patients. Findings: The incidence of sinusoidal obstruction syndrome in this cohort (n = 488) was higher by pEBMT (21.5%) vs historic modified Seattle (15.6%) and Baltimore (7.0%) criteria (p < 0.001). Application of pEBMT criteria identified 44 patients who were not previously diagnosed with sinusoidal obstruction syndrome. Overall, 70.5% of all patients diagnosed with sinusoidal obstruction syndrome ultimately developed very severe disease and almost half of diagnosed patients required critical care support. Overall survival was significantly lower in patients who were diagnosed with sinusoidal obstruction syndrome vs those who were not. Interpretation: Taken together, pEBMT criteria may be a sensitive method for prompter diagnosis of patients who subsequently develop severe/very severe sinusoidal obstruction syndrome. To our knowledge, this is the first multi-centre study in the United States (US) to demonstrate that pEBMT guidelines are associated with earlier detection of sinusoidal obstruction syndrome. Since early initiation of definitive treatment for sinusoidal obstruction syndrome has been associated with improved survival in paediatric patients and implementation of pEBMT criteria appears feasible in the US, universal adoption should facilitate prompter diagnosis and lead to improved outcomes of children with sinusoidal obstruction syndrome. Funding: None.
RESUMEN
ABSTRACT: Veno-occlusive disease (VOD) is a rare but potentially life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Although increasing awareness and modern transplant techniques have mitigated risk, the interaction of historic risk factors in the current era with posttransplant cyclophosphamide (PTCy) is unknown. We performed a retrospective single-center analysis of adult patients aged ≥18 years undergoing allo-SCT (N = 1561) using predominately PTCy as graft-versus-host disease (GVHD) prophylaxis (72%). We found a higher rate of VOD at 16.8% (20 of 119) in those aged ≤25 years compared with 3.8% (55 of 1442) in those aged >25 years, with unique predictors of VOD within each cohort. Multivariate classification and regression tree (CART) analysis confirmed age as the primary independent determinant of the rate of VOD. Among patients aged 18 to 25 years, disease risk index (DRI; 31% with high/very high DRI vs 12% low/intermediate DRI; P = .03) and prior lines of chemotherapy (24% with >1 vs 6% with ≤1; P = .03) were the strongest predictors of VOD. Incidence of VOD in patients aged >25 years of age consistently ranged between 3% and 5% across most risk factors evaluated, with only hepatic factors (baseline elevation of bilirubin, aspartate transferase, alanine aminotransferase) or gemtuzumab exposure associated with increased rates of VOD. There was no significant difference in rates of VOD in those receiving PTCy compared with those receiving alternate GVHD prophylaxis. Our data highlight the differences in incidence and predictors of VOD between younger (≤25) and older (>25) adults undergoing allo-SCT.