Lucía López Corral

Combination of the Hematopoietic Cell Transplantation Comorbidity Index and the European Group for Blood and Marrow Transplantation Score Allows a Better Stratification of High-Risk Patients Undergoing Reduced-Toxicity Allogeneic Hematopoietic Cell Transplantation

This study was conducted to determine whether the integration of the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) and the European Group for Blood and Marrow Transplantation (EBMT) score would improve individual capacity for stratification of high-risk HCT candidates. A total of 442 consecutive patients receiving an allogeneic HCT after reduced-toxicity conditioning was included. Final HCT-CI and EBMT scores were calculated and validated. Then, patients were grouped into a 6-category new combination model according to the HCT-CI (0, 1 to 2, ≥ 3) and EBMT scores (0 to 3, 4 to 7), and the models predictive capacity was also evaluated. Median HCT-CI and EBMT scores were 3 and 4, respectively. Increased HCT-CI was associated with higher 4-year nonrelapse mortality (NRM) and lower 4-year overall survival (OS), whereas a high EBMT score was associated with higher 4-year NRM. The HCT-CI showed a trend for a better predictive capacity than the EBMT score (c-statistic .6 versus .54, P = .1). According to the new model, patients within HCT-CI of 0 and HCT-CI of 1 to 2 groups had similar risk of NRM independently of their EBMT score. Within the HCT-CI ≥ 3 group, patients with low EBMT score showed lower NRM (25% versus 40%, P = .04) and a trend to higher OS (52% versus 36%, P = .06) than patients with a high EBMT score. Moreover, patients with HCT-CI ≥ 3 and EBMT score 0 to 3 had similar outcomes than those with HCT-CI of 1 to 2. In conclusion, the combination of HCT-CI and the EBMT score is feasible and might contribute to a better identification of high-risk patients, improving selection of best allogeneic HCT candidates.

Pretransplantation Liver Function Impacts on the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation: A Study of 455 Patients

Liver dysfunction is frequent before allogeneic stem cell transplantation (allo-SCT). However, its characteristics and impact on transplantation outcomes are uncertain, especially in the reduced-intensity conditioning (RIC) setting. We analyzed 455 patients receiving an allo-SCT in 3 Spanish centers. Pretransplantation aspartate aminotransferase (AST), alanine aminotransaminase (ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (AP), total bilirubin, and international normalized ratio were analyzed. Pretransplantation liver function test abnormalities were found in 94 (22%) patients. The most frequent cause of pretransplantation liver dysfunction was isolated elevation of GGT/AP (n = 49, 53%). Patients with high bilirubin levels before allo-SCT showed higher 4-year nonrelapse mortality (4y-NRM) (hazard ratio [HR] 2 [95% confidence interval [CI] 1.1-3.8] P = .02) and patients with high GGT levels showed higher 100-day NRM and lower 4-year overall survival (OS) (HR 3.4 [95% CI 1.8-6.7] P < .001, and HR 2 [95% CI 1.4-3], P = .001), respectively. High levels of transaminases did not influence on survival or mortality. In conclusion, hepatic dysfunction before allo-SCT is frequent and has an impact on transplantation outcomes. The best indicator of liver dysfunction still has to be determined.

Outcomes of Advanced Hodgkin Lymphoma after Umbilical Cord Blood Transplantation: A Eurocord and EBMT Lymphoma and Cellular Therapy & Immunobiology Working Party Study

Allogeneic stem cell transplantation is an alternative for patients with relapsed or refractory Hodgkin lymphoma (HL), but only limited data on unrelated umbilical cord blood transplantation (UCBT) are available. We analyzed 131 adults with HL who underwent UCBT in European Society for Blood and Marrow Transplantation centers from 2003 to 2015. Disease status at UCBT was complete remission (CR) in 59 patients (47%), and almost all patients had received a previous autologous stem cell transplantation. The 4-year progression-free survival (PFS) and overall survival (OS) were 26% (95% confidence interval [CI], 19% to 34%) and 46% (95% CI, 37% to 55%), respectively. Relapse incidence was 44% (95% CI, 36% to 54%), and nonrelapse mortality (NRM) was 31% (95% CI, 23% to 40%) at 4 years. In multivariate analysis refractory/relapsed disease status at UCBT was associated with increased relapse incidence (hazard ratio [HR], 3.14 [95% CI, 1.41 to 7.00], P = .005) and NRM (HR, 3.61 [95% CI, 1.58 to 8.27], P = .002) and lower PFS (HR, 3.45 [95% CI, 1.95 to 6.10], P < .001) and OS (HR, 3.10 [95% CI, 1.60 to 5.99], P = .001). Conditioning regimen with cyclophosphamide + fludarabine + 2 Gy total body irradiation (Cy+Flu+2GyTBI) was associated with decreased risk of NRM (HR, .26 [95% CI, .10 to .64], P = .004). Moreover, Cy+Flu+2GyTBI conditioning regimen was associated with a better OS (HR, .25 [95% CI, .12 to .50], P < .001) and PFS (HR, .51 [95% CI, .27 to .96], P = .04). UCBT is feasible in heavily pretreated patients with HL. The reduced-intensity conditioning regimen with Cy+Flu+2GyTBI is associated with a better OS and NRM. However, outcomes are poor in patients not in CR at UCBT.

T-cell replete haploidentical stem cell transplantation attenuates the prognostic impact of FLT3-ITD in acute myeloid leukemia: A report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Acute myeloid leukemia (AML) patients harboring the FLT3‐ITD mutation are considered a high risk patient subset preferentially allocated for allogeneic stem cell transplantation in first remission. Whether FLT3‐ITD retains a prognostic role in haploidentical stem cell transplantation (haplo‐SCT) is unknown. To analyze the prognostic impact of FLT3‐ITD in haplo‐SCT, we performed a retrospective analysis of the multicenter registry of the acute leukemia working party of the European Society for Blood and Marrow Transplantation. We included all adult AML patients with known FLT3 status who underwent a first T‐cell replete related haplo‐HCT in first complete remission from 2005 to 2016. We evaluated 293 patients of whom 202 were FLT3wt and 91 were FLT3‐ITD mutated. FLT3‐ITD patients were more likely to be NPM1 mutated as well as be in the intermediate risk cytogenetic risk category. In multivariate analysis, patients with FLT3‐ITD had comparable rates of relapse incidence [Hazard ratio (HR) = 1.34, confidence interval (CI) 95%, 0.67‐2.7; P = .9] and leukemia‐free survival (HR = 0.99, CI 95%, 0.62‐1.57; P = .9) to those of FLT3wt patients. Overall survival, the incidence of nonrelapse mortality, and graft versus host disease‐free/relapse‐free survival were not significantly impacted by FLT3‐ITD status. Furthermore, relapse and overall survival were comparable between FLT3‐ITD patients transplanted from various donor pools, namely matched siblings, unrelated donors, haplo‐SCT). Finally, subset analysis of patients with intermediate risk cytogenetics confirmed the absence of a prognostic impact of FLT3‐ITD also for this patient segment. In AML patients undergoing T‐cell replete haplo‐SCT, the FLT3‐ITD mutation possibly does not retain its prognostic significance.