Role of primacy of birth in HLA-identical sibling transplantation

Bucher, Christoph; Stangel, Martin; Buser, Andreas; Heim, Dominik; Paulussen, Michael; Tsakiris, Dimitrios Α.; Droll, Armin; Meyer-Monard, Sandrine; Thewis, André; Passweg, Jakob; Gratwohl, Aloïs

doi:10.1182/blood-2007-02-076257

Cited by 18 publications

(17 citation statements)

References 7 publications

(6 reference statements)

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“…One might expect that maternal exposure to IPAs in previous pregnancies might also contribute to controlling relapse through sensitization to other IPAs or a booster effect with repeated pregnancies. Indeed, our observation that higher birth order of the CB donor was independently associated with a reduced relapse risk fits with this concept and is in agreement with previous studies of HLA identical sibling bone marrow transplantation (20,21). Most importantly, we demonstrated that the IPA effect was In the no-shared-IPA transplants, at a given locus, there is no match between the CB IPA and/or no IPA target for the mother's cells (i.e., the mother and CB donor match for their HLA antigens or the donor is homozygous).…”

Section: Discussionsupporting

confidence: 81%

Indirect evidence that maternal microchimerism in cord blood mediates a graft-versus-leukemia effect in cord blood transplantation

Rood

Scaradavou

Stevens

2012

Proc. Natl. Acad. Sci. U.S.A.

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During pregnancy women can develop B-and T-cell immunity against the inherited paternal antigens (IPAs) of the fetus, such as HLA, peptides of minor histocompatibilty antigens, and possibly oncofetal antigens. The biological and pathological role of these pregnancy-induced immunological events is only understood in part. However, anti-IPA immunity in the mother persists for many decades after delivery and may reduce relapse in offspring with leukemia after HLA-haploidentical transplantation of maternal hematopoietic stem cells (HSC). We hypothesized that maternal anti-IPA immune elements cross the placenta and might confer a potent graft-versusleukemia effect when cord blood (CB) is used in unrelated HSC transplantation. In a retrospective study of single-unit CB recipients with all grafts provided by the New York Blood Center, we show that patients with acute myeloid or lymphoblastic leukemia (n = 845) who shared one or more HLA-A, -B, or -DRB1 antigens with their CB donor's IPAs had a significant decrease in leukemic relapse posttransplantation [hazard ratio (HR) = 0.38, P < 0.001] compared with those that did not. Remarkably, relapse reduction in patients receiving CB with one HLA mismatch (HR = 0.15, P < 0.001) was not associated with an increased risk of severe acute graft-versus-host disease (HR = 1.43, P = 0.730). Our findings may explain the unexpected low relapse rate after CB transplantation, open new avenues in the study of leukemic relapse after HSC transplantation (possibly of malignancies in general), and have practical implications for CB unit selection.cord blood stem cell transplantation | birth order

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Section: Discussionsupporting

confidence: 81%

Indirect evidence that maternal microchimerism in cord blood mediates a graft-versus-leukemia effect in cord blood transplantation

Rood

Scaradavou

Stevens

2012

Proc. Natl. Acad. Sci. U.S.A.

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“…24 Donor recipient birth order may influence the state of tolerance in HLA-identical sibling transplants and add to or decrease TRM. 25 Last, comorbidity increases the likelihood of TRM, as recently shown in 2 independent series. 26 Information on cytokine polymorphisms, birth order, and comorbidity was not available in the data set.…”

Section: Discussionmentioning

confidence: 95%

Risk score for outcome after allogeneic hematopoietic stem cell transplantation

Gratwohl

Stangel

Brand

et al. 2009

Cancer

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343

285

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BACKGROUND: It was investigated whether the European Group for Blood and Marrow Transplantation risk score, previously established for chronic myeloid leukemia, could be used to predict outcome after allogeneic hematopoietic stem cell transplantation (HSCT) for hematological disease in general. METHODS: Age of patient, disease stage, time interval from diagnosis to transplant, donor type, and donor‐recipient sex combination were used to establish a score from 0 to 7 points. Its validity was tested in 56,505 patients, 33,113 (58%) male, 23,392 female, median age 33 years (range, 0.5‐77 years), with an allogeneic HSCT for a hematological disorder between 1980 and 2005. RESULTS: Survival probability at 5 years decreased from 71% (95% confidence interval [CI], 69%‐73%) for risk score 0 for the whole cohort (75%, 95% CI, 72%‐78% for the most recent time cohort) to 24% (95% CI, 21%‐27% for risk score 6 and 7; 25%, 95% CI, 22%‐29% most recent cohort). Transplant‐related mortality increased from 15% (95% CI, 14%‐17%) for risk score 0 (11%, 95% CI, 9%‐13%, most recent cohort) to 47% with risk score 6 and 7 (95% CI, 44%‐50%) for the whole cohort (45%, 95% CI, 42%‐48%, most recent cohort). The risk score was predictive in all disease categories, over all time periods, and was not altered by transplant techniques. CONCLUSIONS: Five well‐defined pretransplant patient and donor characteristics give a reasonable risk estimate of allogeneic HSCT. This risk score can provide a basis for the decision between transplant and nontransplant strategies. Cancer 2009. © 2009 American Cancer Society.

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“…27 Our data also subscribe the need for routine collection of detailed information on the parity 4 and family history of female donors, in particular regarding the sex of the donors' offspring and older siblings. 28 Such information may help to explain the differences in reported data sets wherein the effect of donor sex and parity on outcome variables such as GvHD and overall survival after allogeneic HSCT is addressed.…”

Section: Resultsmentioning

confidence: 99%