1.
The Simplified Comorbidity Index predicts non-relapse mortality in reduced-intensity conditioning allogeneic haematopoietic cell transplantation
Elias, S., Brown, S., Devlin, S. M., Barker, J. N., Cho, C., Chung, D. J., Dahi, P. B., Giralt, S., Gyurkocza, B., Jakubowski, A. A., et al
British journal of haematology. 2023
Abstract
Comorbidity assessment before allogeneic haematopoietic cell transplantation (allo-HCT) is essential for estimating non-relapse mortality (NRM) risk. We previously developed the Simplified Comorbidity Index (SCI), which captures a small number of 'high-yield' comorbidities and older age. The SCI was predictive of NRM in myeloablative CD34-selected allo-HCT. Here, we evaluated the SCI in a single-centre cohort of 327 patients receiving reduced-intensity conditioning followed by unmanipulated allografts from HLA-matched donors. Among the SCI factors, age above 60, mild renal impairment, moderate pulmonary disease and cardiac disease were most frequent. SCI scores ranged from 0 to 8, with 39%, 20%, 20% and 21% having scores of 0-1, 2, 3 and ≥4 respectively. Corresponding cumulative incidences of 3-year NRM were 11%, 16%, 22% and 27%; p = 0.03. In multivariable models, higher SCI scores were associated with incremental risks of all-cause mortality and NRM. The SCI had an area under the receiver operating characteristic curve of 65.9%, 64.1% and 62.9% for predicting 1-, 2- and 3-year NRM versus 58.4%, 60.4% and 59.3% with the haematopoietic cell transplantation comorbidity index. These results demonstrate for the first time that the SCI is predictive of NRM in patients receiving allo-HCT from HLA-matched donors after reduced-intensity conditioning.
2.
Reduced Intensity Compared to Non-myeloablative Conditioning in Patients with Non-Hodgkin Lymphoma undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Nath, K., Peterson, K., Brown, S., Devlin, S., Rodriguez, N., Barker, J., Giralt, S., Gyurkocza, B., Jakubowski, A., Papadopoulos, E., et al
Transplantation and cellular therapy. 2023
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Editor's Choice
Abstract
BACKGROUND . Reduced intensity (RIC) and non-myeloablative (NMA) conditioning are preferred for patients with non-Hodgkin lymphoma (NHL) receiving allogeneic hematopoietic stem cell transplantation (allo-HCT). Although prior studies have suggested that higher-intensity regimens within RIC-NMA conditioning are associated with inferior outcomes in patients with NHL, the optimal conditioning regimen remains unknown. OBJECTIVES AND STUDY DESIGN . We performed a retrospective single-center analysis to determine outcomes of adult patients with B- and T-cell NHL who underwent allo-HCT and received either RIC or NMA conditioning between March 2008 - December 2019. RIC regimens included fludarabine-cyclophosphamide-thiotepa-4Gy-total body irradiation (Flu-Cy-TT-4Gy-TBI), fludarabine-melphalan (Flu-Mel), fludarabine-cyclophosphamide-4Gy-total body irradiation (Flu-Cy-4Gy-TBI) and fludarabine-busulfan-4 (Flu-Bu-4). The NMA regimen included fludarabine-cyclophosphamide-2Gy-total body irradiation (Flu-Cy-2Gy-TBI). The primary outcome was overall survival. Secondary outcomes included progression-free survival, non-relapse mortality and the incidence of acute and chronic graft-vs-host-disease (GvHD). RESULTS . Of 279 transplanted patients (median age, 58 years), 110 received RIC (55% Flu-Mel, 38% Flu-Cy-TT-4Gy-TBI, 6% Flu-Bu-4, 1% Flu-Cy-4Gy-TBI) and 169 received NMA conditioning with Flu-Cy-2Gy-TBI. With a median of 64 months of follow-up from allo-HCT, there was no significant difference in overall survival between the NMA and RIC groups (median not reached [NR] vs 103 months, respectively. P = 0.1), and this was maintained on multivariable analysis. Similarly, after adjustment for all independently significant covariates (age, Karnofsky performance status, HCT-CI, disease histology), the regression analysis showed no significant difference in progression-free survival with RIC compared to NMA conditioning (hazard ratio [HR] 1.38; 95% CI 0.92 - 2.09, P = 0.24). On univariable analysis, there was no significant difference in non-relapse mortality between RIC and NMA conditioning (100-day estimates: 10.0% vs. 1.8%, respectively, P = 0.5). After adjustment for age, ethnicity, Karnofsky performance score, HCT-CI, GvHD prophylaxis and donor source, RIC conditioning was associated with a significantly higher incidence of non-relapse mortality compared to NMA conditioning (HR 2.61, 95% CI 1.04 - 6.52, P = 0.039). On multivariable analysis, compared with the Flu-Cy-2Gy-TBI regimen, the RIC cohort had higher rates of grade II-IV (HR, 2.25; 95% CI, 1.31 - 3.86; P = 0.002) and grade III-IV acute GvHD (HR, 5.62; 95% CI, 2.03 - 15.6; P < 0.001). CONCLUSION . The findings of this study suggest that NMA conditioning with Flu-Cy-TBI-2Gy may be considered over more intensive RIC regimens for patients with NHL undergoing allo-HCT.
PICO Summary
Population
Adults with B- or T-cell non-Hodgkin lymphoma who underwent allogeneic stem cell transplant (allo-HSCT) at a single centre in USA (n=279)
Intervention
Reduced intensity conditioning (RIC) with or without total body irradiation (n=110)
Comparison
Non-myeloablative (NMA) conditioning (n=169)
Outcome
With a median of 64 months of follow-up from allo-HCT, there was no significant difference in overall survival between the NMA and RIC groups (median not reached [NR] vs 103 months, respectively), and this was maintained on multivariable analysis. Similarly, after adjustment for all independently significant covariates (age, Karnofsky performance status, HCT-CI, disease histology), the regression analysis showed no significant difference in progression-free survival with RIC compared to NMA conditioning (hazard ratio [HR] 1.38; 95% CI 0.92 - 2.09). On univariable analysis, there was no significant difference in non-relapse mortality between RIC and NMA conditioning (100-day estimates: 10.0% vs. 1.8%, respectively). After adjustment for age, ethnicity, Karnofsky performance score, HCT-CI, GvHD prophylaxis and donor source, RIC conditioning was associated with a significantly higher incidence of non-relapse mortality compared to NMA conditioning (HR 2.61, 95% CI 1.04 - 6.52). On multivariable analysis, compared with the Flu-Cy-2Gy-TBI regimen, the RIC cohort had higher rates of grade II-IV (HR, 2.25; 95% CI, 1.31 - 3.86) and grade III-IV acute GvHD (HR, 5.62; 95% CI, 2.03 - 15.6).