Impact of cyclosporine-A concentration in T-cell replete haploidentical allogeneic stem cell transplantation.

This paper aims to study whether cyclosporine-A (CSA) levels have an impact on the clinical outcome of patients with T-cell replete haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT). We analyzed 140 consecutive patients who had been given T-cell replete haploidentical allo-HSCT in our institute to assess the effect of CSA concentration in the early stages of allo-HSCT on clinical outcomes, such as hematopoietic recovery, acute graft vs host disease (aGVHD), infection, disease-free survival (DFS), and overall survival (OS). The median concentrations of CSA in the blood in the 1st, 2nd, 3rd, and 4th week after allo-HSCT were 218, 235, 263, and 270 ng/mL, respectively. Additionally, 46%, 40%, 27%, and 18% of the patients had CSA blood levels below 200 ng/mL during those weeks. In total, 39 patients developed aGVHD (grade II-IV), for a cumulative incidence of 27.8%, at a median of 32 days. Patients having a low CSA concentration (below 200 ng/mL) in the 3rd week had a higher cumulative incidence of grade II-IV aGVHD (P = .02). In addition, multivariate logistic regression analysis showed that low CSA concentration (below 200 ng/mL) in the 3rd week was an independent risk factor of grade II-IV aGVHD (P = .02; odds ratio = 2.66; 95% CI, 1.15-6.17). However, CSA levels during the first 4 weeks did not have a significant impact on the patients' hematopoietic recovery, infection, DFS, and OS. Our data indicated that adequate management of CSA levels during the peri-engraftment period might improve clinical outcomes for those with T-cell replete haploidentical allo-HSCT.

Yang X ，Yang S ，Sun A ，Qiu H ，Tang X ，Han Y ，Wu D ... -  《-》

Impact of cyclosporine A concentration on acute graft-vs-host disease incidence after haploidentical hematopoietic cell transplantation.

This retrospective study analyzed the impact of early cyclosporine A (CsA) initiation (day -3) on the risk of acute graft-vs-host disease (aGvHD) after haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplant cyclophosphamide. Sixty-one consecutives patients who underwent Haplo-HCT were analyzed. At day +180, the cumulative incidences of grade II-IV and grade III-IV aGvHD were 39% and 18%, respectively. Patients having a lowest CsA concentration (<301 ng/mL; the cutoff value used to segregate the patients between low and high CsA concentrations) in the first week after Haplo-HCT had a significantly higher risk of grade II-IV aGvHD (P = 0.02), severe grade III-IV aGvHD (P = 0.03), cGvHD (P = 0.02), and extensive cGvHD (P = 0.04). In multivariate analysis, a higher CsA concentration (≥301 ng/mL) during the first week following Haplo-HCT was the only parameter significantly associated with a reduced risk of grade II-IV and grade III-IV aGvHD (RR = 0.21; P = 0.049 and RR < 0.001; P < 0.0001, respectively). We find no correlation between CsA concentration and relapse, non-relapse mortality, progression-free survival, GvHD-free and progression-free survival, or overall survival. CsA could be initiated early before Haplo-HCT with achievement of high CsA concentration to reduce the risk of aGvHD without any detrimental effect on relapse.

Stocker N ，Duléry R ，Battipaglia G ，Brissot E ，Médiavilla C ，Sestili S ，Paviglianiti A ，Ledraa T ，Mohty R ，Bazarbachi A ，Belhocine R ，Vekhoff A ，Ruggeri A ，Mohty M ，Malard F ... -  《-》

Impact of cyclosporine-A concentration on the incidence of severe acute graft-versus-host disease after allogeneic stem cell transplantation.

This single-center retrospective study analyzed 85 consecutive patients who underwent allogeneic stem cell transplantation (allo-SCT) with the aim to assess whether there is a correlation between exposure to cyclosporine-A (CsA; as measured by CsA concentrations during the first month after allo-SCT) and the risk for developing severe grade III-IV acute graft-versus-host disease (aGVHD). The median concentrations of CsA in the blood at 1, 2, 3, and 4 weeks after allo-SCT were 348 (range: 172-733), 284 (range: 137-535), 274 (range: 107-649), and 247 (range: 37-695) ng/mL, respectively. Overall, grade II-IV aGVHD occurred in 36 patients (42%) at a median of 29 (range: 6-100) days after allo-SCT. The incidence of grade III-IV aGVHD (n = 20) was 23% (95% confidence interval [CI], 14%-32%). In univariate analysis, patients receiving allo-SCT from an HLA-matched unrelated donor had a higher risk of grade III-IV aGVHD, and patients having the lowest CsA concentration in the first and second weeks after allo-SCT had a significantly higher risk of grade III-IV aGVHD. In a multivariate logistic regression analysis, a higher CsA concentration measured during the first week following graft infusion was the strongest parameter significantly associated with a reduced risk of severe grade II-IV aGVHD (P = .012; relative risk [RR] = 0.24; 95% CI, 0.08-0.73). Of note, when adjusted by donor type, CsA concentration in week 1 remained significantly associated with risk of severe grade II-IV aGVHD (P = .014). We conclude that precise monitoring of CsA concentrations and adjustment of CsA dose early after allo-SCT may be effective to prevent onset of severe aGVHD.

Malard F ，Szydlo RM ，Brissot E ，Chevallier P ，Guillaume T ，Delaunay J ，Ayari S ，Dubruille V ，Le Gouill S ，Mahe B ，Gastinne T ，Blin N ，Saulquin B ，Harousseau JL ，Moreau P ，Mohty M ... -  《-》

Low-dose methotrexate may preserve a stronger antileukemic effect than that of cyclosporine after modified donor lymphocyte infusion in unmanipulated haploidentical HSCT.

To compare the impacts of low-dose methotrexate (MTX) with cyclosporine (CSA) on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after haploidentical modified donor lymphocyte infusion (DLI). Fifty-five consecutive patients who had relapsed acute leukemia after haploidentical hematopoietic stem cell transplantation (HSCT) and received modified DLI were retrospectively studied. Forty-one patients received CSA and 14 received low-dose MTX after DLI to prevent DLI-associated GVHD. The incidence of acute GVHD and grade 2-4 acute GVHD in MTX group showed a trend toward being higher than in CSA group (61.0% vs. 37.3%, p = 0.198 and 61.0% vs. 35.5%, p = 0.155). However, no significant difference in the incidence of grade 3-4 acute GVHD between two groups (p = 0.982) was observed. Moreover, compared with CSA, patients treated with MTX had lower re-relapse rate (38.1% vs. 80.8%, p = 0.029), better disease-free survival (DFS) (51.9% vs. 15.6%, p = 0.06), and higher absolute lymphocyte counts at 30, 45, 60, and 90 d after modified DLI (p < 0.05). This study suggested that after haploidentical modified DLI, low-dose MTX is at least as effective as CSA in the prevention of DLI-associated GVHD and probably allowed stronger GVL effect than CSA. This phenomenon was probably due to a direct antitumor effect and a better reconstitution of lymphocytes after modified DLI induced by low-dose MTX.

Yan CH ，Xu LP ，Liu DH ，Chen H ，Wang Y ，Wang JZ ，Wang FR ，Han W ，Liu KY ，Huang XJ ... -  《-》

Impact of cyclosporine levels on the development of acute graft versus host disease after reduced intensity conditioning allogeneic stem cell transplantation.

García Cadenas I ，Valcarcel D ，Martino R ，Piñana JL ，Barba P ，Novelli S ，Esquirol A ，Garrido A ，Saavedra S ，Granell M ，Moreno C ，Briones J ，Brunet S ，Sierra J ... -  《-》