Landmark studies for MMUD transplant (HCT)
| Study . | Population . | Study design . | Comparison . | Key findings . |
|---|---|---|---|---|
| Flomenberg et al (2004)11 | 1874 patients in NMDP who underwent HCT for HMs and nonmalignant disorders | Retrospective | 1. Mismatches at loci HLA-A (n = 374), -B (n = 477), -C (n = 749), or -DRB1 (n = 311), -DQ (n = 415), and -DP (n = 1648) 2. Study included 108 patients with 8/8 match | 1. Reduced OS after MMUD HCT with mismatches at loci HLA-A, -B, -C, or -DRB1 2. Survival was worse with increasing number of mismatches. 3. Mismatches at loci HLA-A, -B, -C, or -DRB1 all showed more frequent aGVHD 4. The incidence of grade III/IV aGVHD was much higher with mismatch at HLA-A as compared to mismatch at HLA-B, -C, or -DRB1. 5. Mismatches at HLA-DQ and -DP had little effect on HCT outcomes. 6. Class I HLA mismatches with or without HLA-DQ mismatch had similar outcomes. |
| Lee et al (2007)6 | 3857 patients with HMs (early stage, intermediate stage, and advanced/higher stage) who underwent MAC HCT • 94% received BMSCs • 78% received T-cell replete grafts • GVHD prophylaxis included calcineurin inhibitor | Retrospective (CIBMTR) | 1. 8/8 MUD (n = 1840) 2. Single (n = 985) or multiple (n = 1032) MMUD | 1. Higher-risk disease at the time of HCT had a higher association with poor survival as compared to increased number of HLA mismatches. 2. No statistically significant difference in survival outcomes between single-antigen mismatch vs allele mismatch on the same locus. No statistically significant difference between 8/8 and 7/8 with respect to engraftment, relapse, and chronic GVHD. 3. A single mismatch at HLA-A, -C, or -DRB1 was associated with significantly reduced OS compared to 8/8 matches. 4. Multiple mismatches were associated with poorer survival outcomes. 5. Single mismatch at HLA-DQ was not associated with any effect on survival. 6. HLA-DP mismatch did not affect survival but was associated with increased risk of aGVHD. |
| Saber et al (2012)4 | 2223 adult patients with AML who underwent alloHCT between 2002 and 2006 | Retrospective (CIBMTR) | 1. MSD (n = 624) 2. 8/8 MUD (n = 1193) 3. 7/8 MUD (MMUD) (n = 406) | 1. Significantly lower 100-day cumulative incidence of grade II to IV aGVHD in MSD HCT recipients than in 8/8 MUD and 7/8 MUD HCT recipients (33%, 51%, and 53%, respectively; P < .001). 2. 8/8 MUD HCT recipients had a similar survival rate compared with MSD HCT recipients (RR, 1.03; P = .62). 3. 7/8 MUD HCT recipients had higher early mortality than MSD HCT recipients (RR, 1.40; P < .001), but beyond 6 months after HCT, their survival rates were similar (RR, 0.88; P = .30). |
| Pidala et al (2014)12 | 8003 patients with HMs (early stage, intermediate stage, and advanced/higher stage) who underwent MUD HCT with MAC between 1999 and 2011 | Retrospective (CIBMTR) | 1. 8/8 MUD (n = 5449) 2. 7/8 MMUD (n = 2071) 3. 6/8 MMUD (n = 483) | 1. 6/8-7/8 led to significantly increased risk of grade II to IV and III to IV aGVHD, chronic GVHD, TRM, and reduced OS as compared to 8/8 matched pairs. 2. For 8/8 HCTs, mismatch at both HLA-DQB1 and HLA-DPB1 loci led to an increased incidence of aGVHD and mismatch at HLA-DPB1 resulted in reduced relapse. Both PR and no-PR HLA-DPB1 allele mismatches led to significantly increased incidence of grade II to IV and grade III to IV aGVHD and reduced risk of relapse. 3. Significantly increased risk of TRM in no-PR pairs as compared to matched pairs or pairs with PR DPB1 allele mismatches. 4. Adjusted OS for 8/8 matched HCT was best among the HLA-DPB1 allele mismatched pairs followed by fully matched HLA-DPB1, with worst adjusted OS for nonpermissive mismatches (P = .015). 5. No difference in outcomes for 1 or double allele mismatches at HLA-DPB1 for permissive or nonpermissive mismatches. |
| Malki et al (2020)14 | 310 patients RIC HCT | Retrospective | 1. 12/12 MUD 2. 11/12 MUD (DPB1-mismatched) 3. 10/12 MUD (DPB1-mismatched) | 1. Better OS and relapse in 11/12 when compared to 12/12 and better OS as compared to 10/12. 2. Among the 11/12 pairs, when compared with permissive DP mismatch (PR), nonpermissive DP mismatch (no-PR) is associated with increased risk of grade II to IV aGVHD and NRM. 3. When DP expression was considered, using high DP expressors as donors for low-expressor recipients was associated with increased risk of mortality. DP PR 11/12 mismatch was associated with higher OS when both donor and patient were DP low expressors when compared with other combinations. |
| Study . | Population . | Study design . | Comparison . | Key findings . |
|---|---|---|---|---|
| Flomenberg et al (2004)11 | 1874 patients in NMDP who underwent HCT for HMs and nonmalignant disorders | Retrospective | 1. Mismatches at loci HLA-A (n = 374), -B (n = 477), -C (n = 749), or -DRB1 (n = 311), -DQ (n = 415), and -DP (n = 1648) 2. Study included 108 patients with 8/8 match | 1. Reduced OS after MMUD HCT with mismatches at loci HLA-A, -B, -C, or -DRB1 2. Survival was worse with increasing number of mismatches. 3. Mismatches at loci HLA-A, -B, -C, or -DRB1 all showed more frequent aGVHD 4. The incidence of grade III/IV aGVHD was much higher with mismatch at HLA-A as compared to mismatch at HLA-B, -C, or -DRB1. 5. Mismatches at HLA-DQ and -DP had little effect on HCT outcomes. 6. Class I HLA mismatches with or without HLA-DQ mismatch had similar outcomes. |
| Lee et al (2007)6 | 3857 patients with HMs (early stage, intermediate stage, and advanced/higher stage) who underwent MAC HCT • 94% received BMSCs • 78% received T-cell replete grafts • GVHD prophylaxis included calcineurin inhibitor | Retrospective (CIBMTR) | 1. 8/8 MUD (n = 1840) 2. Single (n = 985) or multiple (n = 1032) MMUD | 1. Higher-risk disease at the time of HCT had a higher association with poor survival as compared to increased number of HLA mismatches. 2. No statistically significant difference in survival outcomes between single-antigen mismatch vs allele mismatch on the same locus. No statistically significant difference between 8/8 and 7/8 with respect to engraftment, relapse, and chronic GVHD. 3. A single mismatch at HLA-A, -C, or -DRB1 was associated with significantly reduced OS compared to 8/8 matches. 4. Multiple mismatches were associated with poorer survival outcomes. 5. Single mismatch at HLA-DQ was not associated with any effect on survival. 6. HLA-DP mismatch did not affect survival but was associated with increased risk of aGVHD. |
| Saber et al (2012)4 | 2223 adult patients with AML who underwent alloHCT between 2002 and 2006 | Retrospective (CIBMTR) | 1. MSD (n = 624) 2. 8/8 MUD (n = 1193) 3. 7/8 MUD (MMUD) (n = 406) | 1. Significantly lower 100-day cumulative incidence of grade II to IV aGVHD in MSD HCT recipients than in 8/8 MUD and 7/8 MUD HCT recipients (33%, 51%, and 53%, respectively; P < .001). 2. 8/8 MUD HCT recipients had a similar survival rate compared with MSD HCT recipients (RR, 1.03; P = .62). 3. 7/8 MUD HCT recipients had higher early mortality than MSD HCT recipients (RR, 1.40; P < .001), but beyond 6 months after HCT, their survival rates were similar (RR, 0.88; P = .30). |
| Pidala et al (2014)12 | 8003 patients with HMs (early stage, intermediate stage, and advanced/higher stage) who underwent MUD HCT with MAC between 1999 and 2011 | Retrospective (CIBMTR) | 1. 8/8 MUD (n = 5449) 2. 7/8 MMUD (n = 2071) 3. 6/8 MMUD (n = 483) | 1. 6/8-7/8 led to significantly increased risk of grade II to IV and III to IV aGVHD, chronic GVHD, TRM, and reduced OS as compared to 8/8 matched pairs. 2. For 8/8 HCTs, mismatch at both HLA-DQB1 and HLA-DPB1 loci led to an increased incidence of aGVHD and mismatch at HLA-DPB1 resulted in reduced relapse. Both PR and no-PR HLA-DPB1 allele mismatches led to significantly increased incidence of grade II to IV and grade III to IV aGVHD and reduced risk of relapse. 3. Significantly increased risk of TRM in no-PR pairs as compared to matched pairs or pairs with PR DPB1 allele mismatches. 4. Adjusted OS for 8/8 matched HCT was best among the HLA-DPB1 allele mismatched pairs followed by fully matched HLA-DPB1, with worst adjusted OS for nonpermissive mismatches (P = .015). 5. No difference in outcomes for 1 or double allele mismatches at HLA-DPB1 for permissive or nonpermissive mismatches. |
| Malki et al (2020)14 | 310 patients RIC HCT | Retrospective | 1. 12/12 MUD 2. 11/12 MUD (DPB1-mismatched) 3. 10/12 MUD (DPB1-mismatched) | 1. Better OS and relapse in 11/12 when compared to 12/12 and better OS as compared to 10/12. 2. Among the 11/12 pairs, when compared with permissive DP mismatch (PR), nonpermissive DP mismatch (no-PR) is associated with increased risk of grade II to IV aGVHD and NRM. 3. When DP expression was considered, using high DP expressors as donors for low-expressor recipients was associated with increased risk of mortality. DP PR 11/12 mismatch was associated with higher OS when both donor and patient were DP low expressors when compared with other combinations. |
BMSC, bone marrow stem cell; HM, hematological malignancies; NMDP, National Marrow Donor Program; PR, permissive match; no-PR, nonpermissive match; TRM, transplant-related mortality.