Clinical outcomes of cGvHD following allogeneic HSCT: A Swedish population-based real-world registry study

• Among patients surviving ≥6 months post-HSCT, cGvHD incidence was 71.9%
• At 1-year post-HSCT, non-cGvHD patients had 4.72 times higher mortality risk compared to those with moderate-severe cGvHD (P <0.0001)
• Patients with moderate-severe cGvHD had higher rates of morbidities (P <0.05) and healthcare utilization (~1.6-fold) vs non- and mild cGvHD
• The study findings emphasize the need for novel treatments and real-time methods to monitor effective immunosuppression following HSCT

cGvHD is a serious immune-mediated complication of HSCT but is associated with superior survival in patients with hematological malignancies.

• Hence, a major challenge in managing cGvHD is to optimize prevention of severe disease while maximizing the graft-versus-leukemia effect

There is limited data on cGvHD burden from real-world studies

• cGvHD disease burden and associated clinical outcomes have not been adequately assessed in Sweden
• Hence, this study evaluated cGvHD disease burden (mortality and morbidities) and associated healthcare resource utilization in Sweden

• Retrospective, population-based longitudinal study using 4 national registers^*
• All patients with a record of allogeneic HSCT from 2006 to 2015 were identified in the Patient Register
• Exclusion criteria: Absence of hematological malignancy prior HSCT; reused proxy identification numbers; age <18 or >75; death ≤6 months post-HSCT
• The 0–6-month follow-up period for patients who survived ≥6 months (index date) was 6–12 months post-HSCT
• Based on the timing and extent of commonly used cGvHD treatments, patients were classified as having non-, mild, or moderate-severe cGvHD^†
• Statistical analysis^‡: OS rates by Kaplan-Meier method and difference among groups by log-rank/Mantel–Haenszel test; time-dependent HRs by multi-variate Cox-regression model; adjusted morbidity incidence rate ratios (IRR) by multivariate negative binomial model
  • For each follow-up year, rate of healthcare resource utilization was calculated as the total number of days in inpatient/outpatient care reported in the Patient Register for all causes divided by the total days contributed to follow-up time for that follow-up year

Patient characteristics

• Of 1,246 included patients, 28.1% were classified as non-cGvHD and 71.9% as cGvHD (mild cGvHD, 27.7%; moderate-severe cGvHD, 44.2%).
• Sex (58% men), age (median, 52 [40–61] years), year of HSCT (2011–2015, 65%; 2006–2010, 35%), and source for HSCT (peripheral blood stem cells, 76%; bone marrow/cord blood, 24%) were comparable across cohorts.
• Diagnosis of acute leukemia was more common in non-cGvHD patients (63%) vs those with moderate-severe cGvHD (51%) and mild cGvHD (52%).

Overall survival

• At 1-year post-HSCT:
  • OS decreased with decreasing cGvHD severity status
  • Best OS was in patients with moderate-severe cGvHD
  • Lowest OS rate was in non-cGvHD patients, mainly due to relapse-related mortality (RRM)
• At 5-year follow-up:
  • OS was similar among the 3 groups
  • During the entire follow-up period, OS did not significantly differ among the groups (P = 0.73)
• More patients died from RRM than transplant-related mortality in all groups.

Mortality

• During the follow-up period, the risk of mortality was significantly higher in non- and mild cGvHD patients than in those with moderate-severe cGvHD.
• Factors such as HSCT treatment period, sex, or donor relationship did not have an impact on the risk of mortality (P >0.05).
• Patients aged 60–75 years who underwent HSCT had increased risk of mortality vs those aged 18–39 years.
• Patients who received peripheral blood stem cells had reduced risk of mortality vs those who received bone marrow or cord blood as donor source.

Morbidities

• During the follow-up period, the risk of mortality was significantly hIncidence of most morbidities was significantly higher (P <0.05) among patients with moderate-severe cGvHD vs those with non- (21–83% higher IRRs) and mild cGvHD (10–77% higher IRRs).

Healthcare resource utilization^‡
 

• During the 10-year study period, number of transplants more than doubled, but the proportion of patients with cGvHD remained approximately constant.
• In the follow-up period, more moderate-severe cGvHD patients received inpatient or outpatient healthcare after HSCT vs non- or mild cGvHD patients.
• At 1-year follow-up, the proportion of patients with moderate-severe cGvHD using healthcare was ~1.6-fold higher vs those with non- or mild cGvHD.
• Compared to non- and mild cGvHD patients, those with moderate-severe cGvHD spent larger proportion of follow-up time in:
  • Inpatient healthcare (59% and 31% more, respectively)
  • Outpatient healthcare (54% and 36% more, respectively)