1,25-dihydroxyvitamin-D3 but not the clinically applied marker 25-hydroxyvitamin-D3 predicts survival after stem cell transplantation

Abstract

The serum level of 25-hydroxyvitamin-D3 is accepted as marker for a person’s vitamin D status but its role for the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) is controversially discussed. The impact of 1,25-dihydroxyvitamin-D3 on HSCT outcome, however, has never been studied. In a discovery cohort of 143 HSCT patients we repeatedly (day −16 to 100) measured 1,25-dihydroxyvitamin-D3 and in comparison the well-established marker for serum vitamin D status 25-hydroxyvitamin-D3. Only lower 1,25-dihydroxyvitamin-D3 levels around HSCT (day −2 to 7, peritransplant) were significantly associated with higher 1-year treatment-related mortality (TRM) risk (Mann–Whitney U test, P = 0.001). This was confirmed by Cox-model regression without and with adjustment for baseline risk factors and severe acute Graft-versus-Host disease (aGvHD; unadjusted P = 0.001, adjusted P = 0.005). The optimal threshold for 1,25-dihydroxyvitamin-D3 to identify patients at high risk was 139.5 pM. Also in three replication cohorts consisting of altogether 365 patients 1,25-dihydroxyvitamin-D3 levels below 139.5 pM had a 3.3-fold increased risk of TRM independent of severe aGvHD compared to patients above 139.5 pM (Cox-model unadjusted P < 0.0005, adjusted P = 0.001). Our data highlight peritransplant 1,25-dihydroxyvitamin-D3 levels but not the commonly monitored 25-hydroxyvitamin-D3 levels as potent predictor of 1-year TRM and suggest to monitor both vitamin D metabolites in HSCT patients.

Anti-Thymocyte Globulin Treatment Augments 1,25-Dihydroxyvitamin D3 Serum Levels in Patients Undergoing Hematopoietic Stem Cell Transplantation

“…Analysing a discovery cohort consisting of 143 HSCT patients, our data highlight peri-transplant (day −2 to 7), 1,25-dihydroxyvitamin D3 levels, but not the commonly monitored 25-hydroxyvitamin D3 levels, as potent predictor of 1-year transplant-related mortality (TRM). This finding was further confirmed by analysing three additional cohorts, consisting altogether of 365 patients and suggest to monitor both vitamin D3 metabolites in HSCT patients ( 10 ).…”

“…Although several studies addressed the importance of 25hydroxyvitamin D3 serum levels in the context of HSCT, little is known about the active 1,25-dihydroxyvitamin D3 metabolite. We previously demonstrated that peri-transplant 1,25-dihydroxyvitamin D3 levels were the only significant independent predictor for oneyear-survival besides severe aGvHD (10). Nevertheless, why patients with high 1,25-dihydroxyvitamin-D3 levels are at less risk for TRM than those with low levels remains unknown.…”

“…Eligibility and exclusion criteria for all three replication groups were the same as in the discovery cohort, yielding n=115, n=107 and n=143 patients in replication cohort I, II, and III, respectively. All cohorts analysed in the present study were already described in detail in ( 10 ).…”

“…Although no impact of ATG administration was observed, basal and ATG-stimulated 25-hydroxyvitamin D3 levels differed between the cohorts and only the exploration cohort and the replication cohort I presented 25-hydroxyvitamin D3 levels higher than 50 nM, a concentration usually considered adequate. In contrast to 25hydroxyvitamin D3, patients receiving ATG therapy revealed higher 1,25-dihydroxyvitamin D3 compared with patients that did not receive ATG (Figure 1D) in the exploration cohort and the replication cohort I, where basal 25-hydroxyvitamin D3 levels met the criteria for vitamin D sufficiency [see Peter et al (10)].…”

Vitamin D has no impact on outcomes after HSCT in children—A retrospective study

“…The conflicting data about effect of vitamin D on transplant outcomes shown in several studies quoted above are hard to explain. However, Peter et al studied the effect of 1,25 dihydroxyvitamin D3 and 25 OH vitamin D3 in 143 adults patients undergoing allogenic HSCT and showed that only lower 1,25‐dihydroxyvitamin‐D3 levels around HSCT (days −2 to 7, peri‐transplant) were significantly associated with higher 1‐year TRM risk (Mann‐Whitney U test, p = .001) 17 . This was confirmed by Cox‐model regression without and with adjustment for baseline risk factors and severe acute GvHD (unadjusted p = .001 and adjusted p = .005).…”