Tacrolimus compared with cyclosporine A after haploidentical T-cell replete transplantation with post-infusion cyclophosphamide

Castagna, Luca; Bramanti, Stéfania; Fürst, Sabine; Giordano, Laura; Sarina, Barbara; Crocchiolo, Roberto; El-Cheikh, Jean; Granata, Angela; Morabito, Lucio; Mauro, Elisa; Faucher, Catherine; Mohty, Bilal; Harbi, Samia; Devillier, Raynier; Chabannon, Christian; Carlo‐Stella, Carmelo; Santoro, Armando; Blaise, Didier

doi:10.1038/bmt.2015.289

Cited by 8 publications

(6 citation statements)

References 14 publications

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“…Our strategy was associated with day +180 cumulative incidences of grade II‐IV and grade III‐IV aGvHD of 39% and 18%, respectively. These findings are comparable with the incidences found by Ruggeri et al (38% and 14%, respectively) and Castagna et al (38% and 12%, respectively) in patients receiving PBSC Haplo‐HCT with PTCy and calcineurin inhibitor initiation at day +5. Therefore, early introduction of CsA is not detrimental .…”

Section: Discussionsupporting

confidence: 90%

“…These findings are comparable with the incidences found by Ruggeri et al (38% and 14%, respectively) and Castagna et al (38% and 12%, respectively) in patients receiving PBSC Haplo‐HCT with PTCy and calcineurin inhibitor initiation at day +5. Therefore, early introduction of CsA is not detrimental . On the contrary, we observed that achievement of a high concentration of CsA at time of engraftment, before PTCy administration, was associated with a lower incidence of aGVHD, being 18% for grade II‐IV and 0% for grade III‐IV, at day +180.…”

Section: Discussionsupporting

confidence: 90%

“…Therefore, early introduction of CsA is not detrimental. 21 On the contrary, [8][9][10][11] we observed that achievement of a high concentration of CsA at time of engraftment, before PTCy administration, was associated with a lower incidence of aGVHD, being 18% for grade II-IV and 0% for grade III-IV, at day +180. These findings were also observed in the setting of allogeneic hematopoietic stem cell transplantation using a well-matched related or well-matched unrelated donors.…”

Section: Engraftment and Clinical Outcomesmentioning

confidence: 84%

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

Stocker

Duléry

Battipaglia

et al. 2019

European J of Haematology

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Objectives 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. Methods Sixty‐one consecutives patients who underwent Haplo‐HCT were analyzed. Results 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. Conclusions 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.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Section: Engraftment and Clinical Outcomesmentioning

confidence: 84%

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

Stocker

Duléry

Battipaglia

et al. 2019

European J of Haematology

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“…Therefore, we performed this retrospective analysis comparing the 3 most commonly used PTCY schedules in European centers according to an EBMT survey. Similar to a previous study, we found no differences in the outcomes of patients receiving either CSA or tacrolimus administered on day +5 after 2 consecutive days of PTCY [22].…”

Section: Discussionsupporting

confidence: 90%

Timing of Post-Transplantation Cyclophosphamide Administration in Haploidentical Transplantation: A Comparative Study on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Ruggeri

Labopin

Battipaglia

et al. 2020

Biology of Blood and Marrow Transplantation

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The timing of immunosuppressive therapy used in combination with post-transplantation cyclophosphamide (PTCY) in haploidentical hematopoietic stem cell transplant (haplo-HSCT) is not standardized. We evaluated the schedules of immunosuppression therapy after haplo-HSCT in 509 patients with acute leukemia receiving PTCY on days +3 and +4 along with tacrolimus (group 1; n = 215), with cyclosporine A (CSA) and mycophenolate mofetil (MMF) from day +5 (group 2; n = 170), or CSA + MMF from day 0 or 1 with PTCY on days +3 and +5 (group 3; n = 124). Compared with the other 2 groups, patients in group 3 were younger (median age, 46 years; P = .02) and more often received bone marrow (77%; P < .01) and a regimen containing thiotepa, fludarabine, and busulfan (84%; P< .01). At 2 years, overall survival was 44% was in group 1, 48% in group 2, and 59% in group 3 (P= .15); leukemia-free survival (LFS) was 43%, 46%, and 53% (P= .05); and refined graft-versus-host disease-free, relapse-free survival (rGRFS) was 33%, 39%, and 36% (P = .02). The incidence of grade II-IV acute GVHD was 25% in group 1, 39% in group 2, and 18% in group 3 (P< .01); incidence of chronic GVHD was 25%, 21%, and 24% (P= .50); relapse incidence was 36%, 37%, and 26% (P= .02); and nonrelapse mortality was 26%, 20%, and 21% (P= .35). On multivariate analysis, early start of immunosuppression therapy at day +1 followed by PTCY was associated with a better LFS (hazard ratio [HR], .58; P= .02) and improved rGRFS (HR, .62; P = .02). In this study, the timing of immunosuppression influenced the outcomes of haplo-HSCT with PTCY. An early start of CSA + MMF with PTCY administered on days +3 and +5 improves LFS and rGRFS.

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“…The standard GVHD prophylaxis in PTCy-haploSCT consisted of cyclophosphamide (50 mg/kg/day on days 3 and 4) and tacrolimus plus mycophenolate mofetil (MMF) starting on day 5 [7,8,[22][23][24][26][27][28], several groups reported modified GVHD prophylaxes for PTCy-haploSCT (Table 2) [25, [31][32][33][34]. Castagna et al [31] retrospectively analyzed patients who received tacrolimus and those who received cyclosporine. There were no major differences between tacrolimus and cyclosporine in PTCy-haploSCT.…”

Section: Gvhd Prophylaxis For Ptcy-haplosctmentioning

confidence: 99%

HLA-haploidentical stem cell transplantation using posttransplant cyclophosphamide

Sato

2019

Int J Hematol

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HLA-haploidentical stem cell transplantation using posttransplant cyclophosphamide has spread rapidly worldwide. This strategy was initially developed in the setting of bone marrow transplantation following nonmyeloablative conditioning. Recently, peripheral blood stem cell grafts and/or myeloablative conditioning regimen have been widely used. In Japan, prospective, multicenter, phase II studies have been conducted by the Japan Study Group for Cell Therapy and Transplantation to evaluate the safety and efficacy of HLA-haploidentical peripheral blood stem cell transplantation using posttransplant cyclophosphamide (PTCy-haploPBSCT). In the first such study (JSCT Haplo 13 study), we demonstrated that PTCy-haploPBSCT after busulfan-based reduced-intensity conditioning (RIC) enables stable donor engraftment and low incidences of both acute and chronic graft-versus-host disease (GVHD). In the second (JSCT Haplo 14 study), we showed that both myeloablative conditioning (MAC) and RIC are valid options for PTCy-haploPBSCT. Emerging evidence, including our findings, suggests that donor type (HLA-haploidentical donor versus HLA-matched related or unrelated donor) may no longer be a significant predictor of transplant outcome.

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Tacrolimus compared with cyclosporine A after haploidentical T-cell replete transplantation with post-infusion cyclophosphamide

Cited by 8 publications

References 14 publications

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

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

Timing of Post-Transplantation Cyclophosphamide Administration in Haploidentical Transplantation: A Comparative Study on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

HLA-haploidentical stem cell transplantation using posttransplant cyclophosphamide

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