A comparison of GvHD characteristics in recipients of haploidentical vs matched unrelated donor transplantation

The limited availability of human leukocyte antigen (HLA)- matched donors for allogeneic hematopoietic stem cell transplantation (HSCT) can prevent patients from receiving potentially life-saving therapy. T-replete HLA-mismatched haploidentical (haplo) HSCT may offer an alternative donor source where matched donors are unavailable. Previous studies indicate that haplo HSCT combined with posttransplant cyclophosphamide (PTCy) can induce survival rates similar to matched related donor (MRD) and matched unrelated donor (MUD) HSCT, with reduced incidence of acute and chronic graft-versus-host disease (a/cGvHD). However, there is limited data on risk factors, as well as aGvHD and cGvHD characteristics, in patients receiving haplo HSCT.

Sohl et al. evaluated the characteristics of a/cGvHD, including organ distribution, severity, and response to treatment, in patients who received haplo HSCT with PTCy versus those who received MUD HSCT with calcineurin inhibitors (CIs). The results were published in the Biology of Blood and Marrow Transplant,¹ and the GvHD Hub is happy to provide a summary.

Study design

• The analysis included patients aged ≥ 18 years who received initial HSCT between 2005 and 2017 (N = 394) from
  • 10/10 allele MUD (n = 179) + CI GvHD prophylaxis, or
  • haplo (n = 215) + PTCy GvHD prophylaxis.
• Primary endpoints: Cumulative incidence of GvHD, time to GvHD onset, and organ involvement.
• Secondary endpoints: Overall survival, disease free survival, non-relapse mortality, and relapse.

Results

• Median follow-up: 52.2 months.
• Patient characteristics are presented in Table 1.

Table 1. Baseline patient characteristics¹

Incidence and onset of GvHD in patients receiving haplo vs MUD HSCT

• No differences in cumulative incidence and time to onset of aGvHD was observed between patients who received haplo vs MUD HSCT (Table 2).
• Higher incidences and earlier onset of cGvHD were observed in patients who received haplo vs MUD HSCT (Table 2).

Table 2. Incidences and time to onset of a/cGvHD in patients who received haplo vs MUD HSCT¹

aGvHD

• Of the patients who received haplo or MUD HSCT, 97 and 94 developed Grade 2–4 aGVHD, respectively.
• There was no statistical difference in the distribution of most affected organs in patients who developed Grade 2–4 aGVHD. The most affected organs in both groups (haplo vs MUD HSCT) were skin (75% vs 71%), gastrointestinal tract (71% vs 68%), and liver (14% vs 17%).
• There was no difference in all-cause mortality between groups (23% after haplo HSCT vs 19% after MUD HSCT; p = 0.34).
• Among patients who received haplo HSCT, a number of risk factors were associated with increased risk for developing Grade 2–4 aGVHD:
  • Myeloablative conditioning regimen (p = 0.0169)
  • Donor age ≥ 38 years (p = 0.05)
  • Child as donor (vs parent as donor; p = 0.0253).
• Among patients who received MUD HSCT, myeloablative conditioning was associated with increased development of Grade 2–4 aGVHD (HR, 1.48; p = 0.043).

cGvHD

• In patients who developed cGVHD:
  • Moderate–severe cGvHD was seen after haplo and MUD HSCT in 65% and 77% of patients, respectively
  • Two of the most affected organs, eyes and fasciae, differed significantly with eyes being more affected after MUD HSCT, while involvement of fasciae was more frequently seen after haplo HSCT (Table 3)
  • A greater proportion of haplo vs MUD recipients were off immunosuppressants at 2 years (63% vs 43%, p = 0.03)
  • Onset of cGvHD was later in MUD vs haplo recipients (274 days vs 217 days, p = 0.012)
  • No difference in 2-year all-cause mortality was observed between donor types.
• Risk factors associated with increased development of cGvHD after haplo HSCT:
  • White race (HR, 1.43; p = 0.029)
  • History of grade 2–4 aGvHD (HR, 2.34; p = 0.002)
  • Year of transplant (2012–2017 vs 2005–2011; HR, 1.68; p = 0.002)
  • Graft source (PBSC vs BM; HR, 1.41; p = 0.03).
• Risk factors associated with increased development of cGvHD after MUD HSCT:
  • Recipient age (≥ 55 vs < 55; HR, 1.55; p = 0.03)
  • Graft source PBSC (HR, 1.69; p = 0.002)
  • Year of transplant 2012–2017 (HR, 1.48; p = 0.003).

Table 3. Organs with moderate–severe (stage II–III) cGvHD in ≥ 10% of patients¹

Patient survival outcomes

• Multivariable analysis identified factors associated with significantly poorer survival outcomes (Table 4).

Table 4. Risk factors for poorer OS, DFS, NRM and relapse rates¹

Conclusion

Overall, the data suggest that haplo HSCT with PTCy leads to superior outcomes compared to MUD HSCT in patients undergoing their first transplantation. GvHD prophylaxis with PTCy resulted in lower incidences of cGvHD, faster cGvHD onset, and improved responses to immunosuppressive therapy in patients who received haplo HSCT. cGvHD organ distribution differed significantly between the two treatment groups, and the study highlighted a number of risk factors for patient survival outcomes following HSCT, such as development of severe aGvHD or cGvHD, higher age, White race, and high DRI, which were irrespective of donor type.

Limitations:

• The transplanting physician had the final decision on certain factors, including donor type, regimen intensity, and graft source.
• MUD HSCT was accompanied by CI-based GvHD prophylaxis as the most commonly used regimen (rather than PTCy, which accompanied haplo HSCT), so differences between arms may also be due to GvHD prophylaxis.