Impact of comorbidity on health-related quality of life in newly diagnosed patients with lymphoma or multiple myeloma: results from the PROFILES-registry.

With the increasing prevalence of comorbidity in an ageing population, it is crucial to better understand the impact of comorbidity on health-related quality of life (HRQoL) after lymphoma or multiple myeloma (MM) diagnosis. We included 261 newly diagnosed patients (67% response rate) diagnosed with lymphoma or MM between October 2020 and March 2023 in a longitudinal survey. The European Organisation for Research and Treatment of Cancer (EORTC) questionnaires were used to measure generic and disease-specific HRQoL. Evidence-based guidelines for interpretation of the EORTC questionnaires were used to identify clinical importance. Patients were classified as having 'no comorbidity', 'mild comorbidity' (e.g. arthrosis or rheumatism), or 'moderate-severe comorbidity' (e.g. heart or lung disease), using the adapted self-administered comorbidity questionnaire. At diagnosis, the mean age was 64 years, 63% were male and 38% reported no comorbidity, 33% mild comorbidity, and 29% moderate-severe comorbidity. Patients with mild or moderate-severe comorbidity reported clinically relevant worse HRQoL at diagnosis than patients without comorbidity. One year post-diagnosis most outcomes showed clinically relevant improvement, irrespective of comorbidity. However, outcomes of physical functioning (ß=-7.9, p < 0.05), global health status (ß=-7.6, p < 0.05), bone pain (ß = 8.1 to 9.1, p < 0.05), muscle/joint pain (ß = 14.5 to 18.8, p < 0.01) and muscle weakness (ß = 10.4 to 15.6, p < 0.05) improved less among those with comorbidity, and clinically relevant differences between comorbidity groups persisted over time. With clinically relevant worse HRQoL at diagnosis and less recovery of HRQoL during the first year after diagnosis in patients with comorbidity, consideration of both prognosis and HRQoL is important when making treatment decisions.

Baseline Renal Function and Albumin are Powerful Predictors for Allogeneic Transplantation-Related Mortality.

Biomarkers measured in blood chemistry before allogeneic hematopoietic stem cell transplantation (HSCT) may reflect patients' physiological status. We hypothesized that selected markers are predictive for nonrelapse mortality (NRM) following transplantation and could contribute to risk assessment. We investigated the value of pre-HSCT albumin, estimated glomerular filtration rate (eGFR), and alkaline phosphatase (AlkP) in predicting NRM. We retrospectively analyzed clinical and laboratory data from 1217 patients receiving a first HSCT in 2 European centers between 2003 and 2015. Transplantation indications and conditioning regimens were diverse. Patients had a median age of 55 years and hematopoietic cell transplantation comorbidity index (HCT-CI) scores of 0 (24%), 1 to 2 (39%), and ≥3 (37%). Cutoffs of eGFR <60 mL/min, albumin <3.5 g/dL, and AlkP >180 IU/L corresponded with 8.8%, 8.3%, and 6.5% of the patients, respectively. eGFR and albumin were associated with increased risk and higher cumulative incidence of day-100, 1-year, and 2-year NRM, both as continuous or categorized variables. A similar pattern was observed for AlkP, except for day-100 NRM. In multivariable analyses, eGFR and albumin were consistently among the top risk factors for early and late-term NRM, abrogating the role of age. Prediction models for day-100, 1-year, and 2-year NRM based only on HCT-CI resulted in c-statistics of .565, .575, and .577, respectively. Addition of both biomarkers increased c-statistics for day-100, 1-year, and 2-year NRM to .651, .633, and .624, respectively. Albumin and eGFR are prognostic biomarkers for NRM after HSCT and improve the discriminative power of the HCT-CI.

Posttransplant cyclophosphamide for prevention of graft-versus-host disease: results of the prospective randomized HOVON-96 trial.

Graft-versus-host disease (GVHD) is the most important complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). We performed a prospective randomized, multicenter, phase 3 trial to study whether posttransplant cyclophosphamide (PT-Cy) combined with a short course of cyclosporine A (CsA) would result in a reduction of severe GVHD and improvement of GVHD-free, relapse-free survival (GRFS) as compared with the combination of CsA and mycophenolic acid (MPA) after nonmyeloablative (NMA) matched related and unrelated peripheral blood alloHSCT. Between October 2013 and June 2018, 160 patients diagnosed with a high-risk hematological malignancy and having a matched related or at least 8 out of 8 HLA-matched unrelated donor were randomized and allocated in a 1:2 ratio to CsA/MPA or PT-Cy/CsA; a total of 151 patients were transplanted (52 vs 99 patients, respectively). The cumulative incidence of grade 2 to 4 acute GVHD at 6 months was 48% in recipients of CsA/MPA vs 30% following PT-Cy/CsA (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29-0.82; P = .007). The 2-year cumulative incidence of extensive chronic GVHD was 48% vs 16% (HR, 0.36; 95% CI, 0.21-0.64; P < .001). The 1-year estimate of GRFS was 21% (11% to 32%) vs 45% (35% to 55%), P < .001. With a median follow-up of 56.4 months, relapse incidence, progression-free survival, and overall survival were not significantly different between the 2 treatment arms. PT-Cy combined with a short course of CsA after NMA matched alloHSCT significantly improves GRFS due to a significant reduction in severe acute and chronic GVHD.

Etanercept for steroid-refractory acute graft-versus-host disease: A single center experience.

BACKGROUND: Acute graft-versus-host disease (aGVHD) is an important complication of allogeneic stem cell transplantation (alloSCT). High dose glucocorticosteroids, are currently recommended as first-line treatment for grade II-IV aGVHD resulting in overall complete responses (CR) in 40%-50% of patients. No standard second-line regimen has been established. Different options have been reported, including anti-TNFα antibodies. METHODS: We retrospectively reviewed the outcome of 15 patients with steroid-refractory (SR) aGVHD treated with etanercept at our institution. Patients were transplanted for a hematological malignancy and received either a myeloablative or a non-myeloablative conditioning regimen. Prophylaxis of GVHD consisted of cyclosporin A and mycophenolic acid. RESULTS: Acute GVHD was diagnosed at a median of 61 days post-transplantation. All patients had grade III aGVHD of the gut. Second-line treatment with etanercept was started at a median of 13 days after initiation of first-line therapy. Overall response rate was 53%, with CR in 3 patients and PR in 5 patients. Median overall survival after initiation of treatment with etanercept was 66 days (range 5-267) for the entire group. Median overall survival was 99 days (range 47-267 days) for responders and 17 days (range 5-66 days) for non-responders (p<0.01). Nevertheless, all patients died. Causes of death were progressive GVHD in 7 patients (47%), infection in 6 patients (40%), cardiac death in 1 patient (6.7%) and relapse in 1 patient (6,7%). CONCLUSION: Second-line treatment with etanercept does induce responses in SR-aGVHD of the gut but appears to be associated with poor long-term survival even in responding patients.