HLA informs risk predictions after haploidentical stem cell transplantation with posttransplantation cyclophosphamide

Fuchs, Ephraim J.; McCurdy, Shannon R.; Solomon, Scott R.; Wang, Tao; Herr, Megan M.; Modi, Dipenkumar; Grunwald, Michael R.; Nishihori, Taiga; Kuxhausen, Michelle; Fingerson, Stephanie; McKallor, Caroline; Bashey, Asad; Kasamon, Yvette L.; Bolon, Yung–Tsi; Saad, Ayman; McGuirk, Joseph P.; Paczesny, Sophie; Gadalla, Shahinaz M.; Marsh, Steven G.E.; Shaw, Bronwen E.; Spellman, Stephen R.; Lee, Stephanie J.; Petersdorf, Effie W.

doi:10.1182/blood.2021013443

Cited by 80 publications

(62 citation statements)

References 49 publications

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“…In the present study, we found that a high CF-iKIR score was associated with improved OS and PFS, this could not be merely attributed to either lower NRM (HR, 0.69; P = .079) or relapse protection (HR, 0.94; P = .79) yet the combined effects on both could explain this finding. A registry study showed that higher donor age is associated with inferior mortality in haplo-HSCT (14), and our exploratory classification and regression tree analysis, which integrated donor characteristics and CF-iKIR scores, showed that donor age <58 years combined with a CMVnonreactive recipient was associated with the best OS, whereas donor age ≥58 years was associated with the worst OS. In the rest of the cases (80% of our cohort), a high CF-iKIR score was associated with superior survival in CMV-reactive recipients whose donor was <58 years old, indicating that an interaction between donor CF-iKIR and recipient ligands may be protective against CMV reactivation.…”

Section: Discussionmentioning

confidence: 70%

Donor selection for KIR alloreactivity is associated with superior survival in haploidentical transplant with PTCy

et al. 2022

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With the continuous increase in the use of haploidentical donors for transplantation, the selection of donors becomes increasingly important. Haploidentical donors have been selected primarily based on clinical characteristics, while the effects of killer cell immunoglobulin-like receptors (KIRs) on outcomes of haploidentical-hematopoietic stem cell transplantation (haplo-HSCT) with post-transplant cyclophosphamide (PTCy) remain inconclusive. The present study aimed to thoroughly evaluate the effect of KIRs and binding ligands assessed by various models, in addition to other patient/donor variables, on clinical outcomes in haplo-HSCT. In a cohort of 354 patients undergoing their first haplo-HSCT, we found that a higher Count Functional inhibitory KIR score (CF-iKIR) was associated with improved progression-free survival (adjusted hazard ratio [HR], 0.71; P = .029) and overall survival (OS) (HR, 0.66; P = .016), while none of the other models predicted for survival in these patients. Moreover, using exploratory classification and regression tree analysis, we found that donor age <58 years combined with cytomegalovirus-nonreactive recipient was associated with the best OS, whereas donor age >58 years was associated with the worst OS. In the rest of our cohort (80%), cytomegalovirus-reactive recipients with a donor <58 years old, a higher CF-iKIR was associated with superior OS. The 3-year OS rates were 73.9%, 54.1% (HR, 1.84; P = .044), 44.5% (HR, 2.01; P = .003), and 18.5% (HR, 5.44; P <.001) in the best, better, poor, and worse donor groups, respectively. Our results suggest that KIR alloreactivity assessed by CF-iKIR score can help optimize donor selection in haplo-HSCT.

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Section: Discussionmentioning

confidence: 70%

Donor selection for KIR alloreactivity is associated with superior survival in haploidentical transplant with PTCy

et al. 2022

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“…Post-HSCT cyclophosphamide is now the most widely used GVHDprevention strategy in haploidentical transplantation. However, it is less commonly used in patients with matched donors (33).…”

Section: Discussionmentioning

confidence: 99%

Ocular surface disease index questionnaire as a sensitive test for primary screening of chronic ocular graft-versus-host disease

Yang¹,

Zhao²,

Liao³

et al. 2022

Ann Transl Med

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Background: After allogeneic hematopoietic stem cell transplantation (allo-HSCT), patients are followed up by transplant clinicians. Finding an effective primary screening method that transplant clinicians or patients can master is essential in the early referral of suspected chronic ocular graft-versus-host disease (coGVHD) to an ophthalmologist. This study investigated if the ocular surface disease index (OSDI) questionnaire could be used for coGVHD primary screening.Methods: This case-controlled, cross-sectional study enrolled 161 allo-HSCT patients. All participants completed an OSDI questionnaire and underwent a silt-lamp examination. Bulbar conjunctival injection (BCI) was assessed using torchlight, while tear volume was measured via the Schirmer test (ST). The receiver operating characteristic curve was used to evaluate the sensitivity, specificity, and cutoff values of OSDI, ST, and BCI grading. Performance comparisons of the 3 tests applied in isolation, parallel, and series were made.Results: There were 84 patients with and 77 patients without coGVHD. Compared to those without coGVHD, patients with coGVHD had significantly higher median values of OSDI, corneal fluorescein staining, conjunctival injection, conjunctival fibrosis, and meibum quality, but lower ST scores (All P values <0.001). The cutoff values for OSDI, ST, and BCI grade in the diagnosis of coGVHD were 19.4 points, 7 mm, and grade 0, respectively. The sensitivity and specificity of the tests based on the cutoff values were, respectively, 89.3% and 89.6% for OSDI, 91.7% and 59.7% for ST, and 78.6% and 70.1% for BCI. The area under the curve (AUC) value of OSDI was significantly higher than that of ST (0.931 vs. 0.826; P=0.010) and BCI grade (0.931 vs. 0.781; P<0.001). The AUC values of the combinations were lower than that of OSDI alone. Conclusions:The OSDI questionnaire can be used as a simple screening test for coGVHD as demonstrated by its high sensitivity and specificity in the transplant clinic and patients' self-monitoring. An OSDI greater than 19.4 could be considered an ophthalmology referral criterion.

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“…Moving forward, the availability of potential donors that produce similar outcomes may even allow the selection of personalized donors based on other factors that may limit relapse (eg, specific HLAs) or disease predispositions. 40 …”

Section: Discussionmentioning

confidence: 99%

HLA-matching with PTCy: a reanalysis of a CIBMTR dataset with propensity score matching and donor age

et al. 2022

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Blood or marrow transplantation (BMT) outcomes using haploidentical donors (Haplo) and post-transplant cyclophosphamide (PTCy)-based graft versus host disease (GVHD) prophylaxis compare favorably to using HLA-matched donors with calcineurin inhibitor-based GVHD prophylaxis. A recent CIBMTR analysis of patients receiving homogenous PTCy-based prophylaxis found that, with reduced intensity conditioning, Haplo BMTs had worse outcomes than matched unrelated donor (MUD) BMTs. Due to significant differences in characteristics between the groups, we reanalyzed the dataset using propensity score matching and, additionally, added a donor age variable. MUD BMTs were matched to Haplo BMTs in a 1:5 ratio. After matching, no significant differences were found between groups across all measured baseline characteristics. Outcomes analyses demonstrated no significant differences in overall survival (HR of mortality with MUD vs Haplo [95% CI], 0.95[0.65-1.16], P=0.75), disease free survival (HR of relapse or death, 0.98[0.73-1.18], P=0.89), relapse rate (HR, 1.06[0.77-1.38], P=0.69), or non-relapse mortality (HR, 0.85[0.42-1.13], P=0.49) between the two groups. After stratification by conditioning intensity, MUD BMTs in the RIC cohort had a lower risk of NRM (HR, 0.56 [0.14-0.99], P=0.05), with no significant difference in other clinical outcomes. These results suggest that the effect of HLA matching on BMT outcomes with PTCy is less meaningful than previously reported and observed differences resulted in part from differences in donor age. Timely identification of a young, at least half-matched (related or unrelated) donor may be more important than finding a matched donor, if the latter leads to a substantial delay in BMT or use of an older donor.

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HLA informs risk predictions after haploidentical stem cell transplantation with posttransplantation cyclophosphamide

Cited by 80 publications

References 49 publications

Donor selection for KIR alloreactivity is associated with superior survival in haploidentical transplant with PTCy

Donor selection for KIR alloreactivity is associated with superior survival in haploidentical transplant with PTCy

Ocular surface disease index questionnaire as a sensitive test for primary screening of chronic ocular graft-versus-host disease

HLA-matching with PTCy: a reanalysis of a CIBMTR dataset with propensity score matching and donor age

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